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:"6765",leadTitle:null,fullTitle:"Flexible Electronics",title:"Flexible Electronics",subtitle:null,reviewType:"peer-reviewed",abstract:"The interest in flexible electronics is on the rise as it brings an added functionality and esthetic value in the unconventional interfaces, such as biomonitoring systems, wearables, flexible textiles, paper-based technologies, and many other curves of soft schemes, for which traditional electronics are not suitable. The demand in new flexible platforms turns to a pursuit for functional materials and technologies commonly compatible with a low temperature, high-throughput processing, and novel methods for device integration. A wide range of functional materials involving nanoparticles, composites, semiconductor and metallic nanowires, carbon nanomaterials, polymers, conductive inks, and different hybrid structures are particularly interesting. This book brings a comprehensive overview on the most important technology development in the field of flexible electronics.",isbn:"978-1-78923-457-2",printIsbn:"978-1-78923-456-5",pdfIsbn:"978-1-83881-697-1",doi:"10.5772/intechopen.72522",price:119,priceEur:129,priceUsd:155,slug:"flexible-electronics",numberOfPages:122,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"cff79f8bf37b0651dec3f20a936fd498",bookSignature:"Simas Rackauskas",publishedDate:"July 25th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6765.jpg",numberOfDownloads:8944,numberOfWosCitations:52,numberOfCrossrefCitations:64,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:93,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:209,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 5th 2017",dateEndSecondStepPublish:"January 4th 2018",dateEndThirdStepPublish:"February 24th 2018",dateEndFourthStepPublish:"May 15th 2018",dateEndFifthStepPublish:"July 14th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"195783",title:"Dr.",name:"Simas",middleName:null,surname:"Rackauskas",slug:"simas-rackauskas",fullName:"Simas Rackauskas",profilePictureURL:"https://mts.intechopen.com/storage/users/195783/images/system/195783.jpg",biography:"Simas Rackauskas defended his PhD in Physics at Aalto University, Finland in 2011. He was a Marie Curie Fellow in University of Turin (Italy). He also held post-doctoral positions in Aalto University (Finland) and State University of Campinas (Brazil). He had fellowships in Swiss Federal Institute of Technology in Lausanne (EPFL, Switzerland), Technical University of Denmark (DTU) and University of Nagoya (Japan). His research interests are mainly focused on non-catalytic growth of metal oxide nanowires, application in sensing, carbon nanomaterials and flexible electronics.",institutionString:"Kaunas University of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Turin",institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"741",title:"Electronic Engineering",slug:"electronic-engineering"}],chapters:[{id:"61049",title:"Surface Modification of Polyimide Films for Inkjet-Printing of Flexible Electronic Devices",doi:"10.5772/intechopen.76450",slug:"surface-modification-of-polyimide-films-for-inkjet-printing-of-flexible-electronic-devices",totalDownloads:1419,totalCrossrefCites:6,totalDimensionsCites:9,hasAltmetrics:1,abstract:"Kapton polyimide films are one of the most commonly used flexible and robust substrates for flexible electronic devices due to their excellent thermal, chemical, mechanical, and electrical properties. However, such films feature an inert and highly hydrophobic surface that inhibits the deposition of functional materials with water-based fluids (solutions, suspensions, inkjet inks, etc.), which raise the need for their surface modification to reduce their inherent surface inertness and/or hydrophobicity in order to allow for the fabrication of electronic devices on the substrates. Traditional Kapton surface modification approaches use harsh conditions that not only cause environmental and safety problems but also compromise the structural integrity and the properties of the substrates. This chapter focuses on two recently-developed mild and environmentally friendly wet chemical approaches for surface modification of Kapton HN films. Unlike the traditional methods that target the polyimide matrix of Kapton films, these two methods target the slip additive embedded in the polyimide matrix. The surface modified Kapton films resulted from these two methods allowed for not only great printability of both water- and organic solvent-based inks (thus facilitating the full-inkjet-printing of entire flexible electronic devices) but also strong adhesion between the inkjet-printed traces and the substrate films.",signatures:"Yunnan Fang and Manos M. Tentzeris",downloadPdfUrl:"/chapter/pdf-download/61049",previewPdfUrl:"/chapter/pdf-preview/61049",authors:[{id:"83617",title:"Dr.",name:"Manos",surname:"Tentzeris",slug:"manos-tentzeris",fullName:"Manos Tentzeris"},{id:"240624",title:"Dr.",name:"Yunnan",surname:"Fang",slug:"yunnan-fang",fullName:"Yunnan Fang"}],corrections:null},{id:"61708",title:"Fabrication and Applications of Flexible Transparent Electrodes Based on Silver Nanowires",doi:"10.5772/intechopen.77506",slug:"fabrication-and-applications-of-flexible-transparent-electrodes-based-on-silver-nanowires",totalDownloads:1802,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:0,abstract:"There has been an explosion of interests in using flexible transparent electrodes for next-generation flexible electronics, such as touch panels, flexible lighting, flexible solar cells, and wearable sensors. Silver nanowires (AgNWs) are a promising material for flexible transparent electrodes due to high electrical conductivity, optical transparency and mechanical flexibility. Despite many efforts in this field, the optoelectronic performance of AgNW networks is still not sufficient to replace the present material, indium tin oxide (ITO), due to the high junction resistance. Also, the environmental stability and the mechanical properties need enhancement for future commercialization. Many studies have attempted to overcome such problems by tuning the AgNW synthesis and optimizing the film-forming process. In this chapter, we survey recent progresses of AgNWs in flexible electronics by describing both fabrication and applications of flexible transparent AgNW electrodes. The synthesis of AgNWs and the fabrication of AgNW electrodes will be demonstrated, and the performance enhanced by various methods to suit different applications will be also discussed. Finally, technical challenges and future trends are presented for the application of transparent electrodes in flexible electronics.",signatures:"Peiyun Yi, Yuwen Zhu and Yujun Deng",downloadPdfUrl:"/chapter/pdf-download/61708",previewPdfUrl:"/chapter/pdf-preview/61708",authors:[{id:"240672",title:"Prof.",name:"Peiyun",surname:"Yi",slug:"peiyun-yi",fullName:"Peiyun Yi"},{id:"252593",title:"Dr.",name:"Yuwen",surname:"Zhu",slug:"yuwen-zhu",fullName:"Yuwen Zhu"},{id:"252594",title:"Dr.",name:"Yujun",surname:"Deng",slug:"yujun-deng",fullName:"Yujun Deng"}],corrections:null},{id:"61428",title:"Printing Technologies on Flexible Substrates for Printed Electronics",doi:"10.5772/intechopen.76161",slug:"printing-technologies-on-flexible-substrates-for-printed-electronics",totalDownloads:3271,totalCrossrefCites:42,totalDimensionsCites:62,hasAltmetrics:0,abstract:"Printing technologies have been demonstrated to be highly efficient and compatible with polymeric materials (both inks and substrates) enabling a new generation of flexible electronics applications. Conductive flexible polymers are a new class of materials that are prepared for a wide range of applications, such as photovoltaic solar cells, transistors molecular devices, and sensors and actuators. There are many possible printing techniques. This chapter provides an opportunity to review the most common printing techniques used at the industrial level, the most commonly used substrates and electronic materials, giving an overall vision for a better understanding and evaluation of their different features. Several technological solutions (contact/noncontact) and its critical challenges are also presented. Inkjet Printing Technology (IPT) has been receiving a great attention and therefore higher focus is given to this technology. An overview of IPT is presented to evidence its importance and potential as a key-technology on the research field for printed electronics development, as well as on large scale industrial manufacturing. A background and a review on prior work are presented along with used materials, developed applications and potential of IPT technology. The main features of the different printing technologies, advantages and main challenges are also compared.",signatures:"Sílvia Manuela Ferreira Cruz, Luís A. Rocha and Júlio C. Viana",downloadPdfUrl:"/chapter/pdf-download/61428",previewPdfUrl:"/chapter/pdf-preview/61428",authors:[{id:"15565",title:"Prof.",name:"Julio",surname:"Viana",slug:"julio-viana",fullName:"Julio Viana"},{id:"238389",title:"Ph.D.",name:"Sílvia",surname:"Cruz",slug:"silvia-cruz",fullName:"Sílvia Cruz"},{id:"247716",title:"Prof.",name:"Luís",surname:"Rocha",slug:"luis-rocha",fullName:"Luís Rocha"}],corrections:null},{id:"58992",title:"Direct Growth of Graphene on Flexible Substrates toward Flexible Electronics: A Promising Perspective",doi:"10.5772/intechopen.73171",slug:"direct-growth-of-graphene-on-flexible-substrates-toward-flexible-electronics-a-promising-perspective",totalDownloads:1117,totalCrossrefCites:7,totalDimensionsCites:8,hasAltmetrics:1,abstract:"Graphene has recently been attracting considerable interest because of its exceptional conductivity, mechanical strength, thermal stability, etc. Graphene-based devices exhibit high potential for applications in flexible electronics, optoelectronics, and energy harvesting. In this paper, we review various growth strategies including metal-catalyzed transfer-free growth and direct-growth of graphene on flexible insulating substrates which are “major issues” for avoiding the complicated transfer process that cause graphene defects, residues, tears and performance degradation of its functional devices. Recent advances in practical applications based on “direct-grown graphene” are discussed. Finally, several important directions, challenges and perspectives in the commercialization of ‘direct growth of graphene’ are also discussed and addressed.",signatures:"Viet Phuong Pham",downloadPdfUrl:"/chapter/pdf-download/58992",previewPdfUrl:"/chapter/pdf-preview/58992",authors:[{id:"236073",title:"Dr.",name:"Phuong",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham"}],corrections:null},{id:"60921",title:"Technological Integration in Printed Electronics",doi:"10.5772/intechopen.76520",slug:"technological-integration-in-printed-electronics",totalDownloads:1335,totalCrossrefCites:5,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Conventional electronics requires the use of numerous deposition techniques (e.g. chemical vapor deposition, physical vapor deposition, and photolithography) with demanding conditions like ultra-high vacuum, elevated temperature and clean room facilities. In the last decades, printed electronics (PE) has proved the use of standard printing techniques to develop electronic devices with new features such as, large area fabrication, mechanical flexibility, environmental friendliness and—potentially—cost effectiveness. This kind of devices is especially interesting for the popular concept of the Internet of Things (IoT), in which the number of employed electronic devices increases massively. Because of this trend, the cost and environmental impact are gradually becoming a substantial issue. One of the main technological barriers to overcome for PE to be a real competitor in this context, however, is the integration of these non-conventional techniques between each other and the embedding of these devices in standard electronics. This chapter summarizes the advances made in this direction, focusing on the use of different techniques in one process flow and the integration of printed electronics with conventional systems.",signatures:"Almudena Rivadeneyra, Florin C. Loghin and Aniello Falco",downloadPdfUrl:"/chapter/pdf-download/60921",previewPdfUrl:"/chapter/pdf-preview/60921",authors:[{id:"237781",title:"Dr.",name:"Almudena",surname:"Rivadeneyra",slug:"almudena-rivadeneyra",fullName:"Almudena Rivadeneyra"},{id:"237782",title:"Dr.",name:"Aniello",surname:"Falco",slug:"aniello-falco",fullName:"Aniello Falco"},{id:"237783",title:"MSc.",name:"Florin",surname:"Loghin",slug:"florin-loghin",fullName:"Florin Loghin"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7432",title:"Nanowires",subtitle:"Synthesis, Properties and Applications",isOpenForSubmission:!1,hash:"459e88b91c31f4788eadbeb0ebe36b0b",slug:"nanowires-synthesis-properties-and-applications",bookSignature:"Simas Rackauskas",coverURL:"https://cdn.intechopen.com/books/images_new/7432.jpg",editedByType:"Edited 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As well as this, school climate is one of the main aspects of the teaching and learning process. The deliberate cultivation of a culture of learning and participation in an organization requires the systematic collection, processing, and distribution of knowledge aimed at the organization’s optimal performance [3].
However, school climate is not always positive or creative, and teachers and students alike may not feel good at school, while school objectives may not be achieved. It is a fact that conditions in education are becoming increasingly difficult, as a result of the broader, rapidly changing, and increasingly complex environment. Teachers are often faced with violent, even criminal, acts, which may cause them to consider changing careers or have low self-confidence regarding their chosen profession [4]. Critical situations can disrupt school climate [5, 6, 7]. Ways of dealing with such problematic situations can be sought by competent bodies, but they can also come from within the school, from educators themselves, probably with more successful and long-lasting outcomes. This is because when the school community itself is involved in resolving a problem, there is increased likelihood of the solutions being viable. In contrast, when the solution is imposed by external agencies, it is often rejected by the school. The school setting is a microcosm of society. Here, participants are not production units of an industrial or business organization, but partakers in the learning process which is, first and foremost, an act of communication [8, 9].
At this point, the questions arise: How can a school become a space where teachers and students wish to belong to? What factors can foster a positive feeling and creativity? How can effective communication within the school unit act as a catalyst for enhancing school climate?
The problem set forth in this study is based upon the changes in educational context as caused by current social, financial, and technological factors, and their impact on school climate. The importance of this study lies in its effort to seek effective interventions in school that can create appropriate conditions for the development of teachers’ and students’ creativity. We argue that both effective interpersonal communication among all members of the school community and the principal’s communication skills are crucial.
The aim of the present analysis is to examine the variables of school climate and communication in order to find the extent to which their relationship can work in favor of an open, safe, and creative educational organization where a positive school climate exists and to which teachers and students will wish to belong. In particular, the following questions will be considered:
What does the concept of school climate entail and what is its importance?
How can school communication contribute to its improvement?
What is the role of school principals in this process?
Gorton and Alston note that through communication, the organization’s culture is shaped, while the workforce is encouraged to develop, obtain, and process information, to take decisions and to plan ([10], pp. 96–97). The principal’s role as pedagomanager acts as a catalyst both in the formation of cooperative relationships and in the performance of the educational work of the school unit. The principal is the central regulator of school climate. The term
Over the last two decades, there has been a growing appreciation that school climate, the quality and character of school life, fosters teachers’ professional effectiveness, dedication to the profession, and continuing professional development. Research confirms what teachers and parents have claimed for decades: a safe and supportive school environment, in which teachers and students have positive social relationships and are respected, engaged in their work, and feel competent, matters.
But what is meant by
The school experience is recorded as a process whereby participants interact based on the operation of principles, rules and values pertaining to teaching, learning, administration, and the school’s relationship with the family and the broader environment. Relevant and alternative terms applied to the concept of school climate are “psychological climate,” “pedagogical climate,” and “pedagogical atmosphere”. At the same time, Peterson & Deal write of school culture: “culture is the underground stream of norms, values, beliefs, traditions, and rituals that has built up over time as people work together, solve problems, and confront challenges” ([15], p. 28). Culture influences everything that goes on in schools: staff collaboration, abilities, and their willingness to change, the practice of instruction, and the relations among parents.
In this paper, we have adopted the term “school climate”, which we define as the way in which the interactions of participants in pedagogical events and phenomena are experienced. The vast majority of researchers and scientists indicate that school climate, in essence, reflects the individual experience at school. School climate is described as pleasant, unpleasant, positive, negative, boring, fertile, shifting, open, closed, constructive, interesting, engaged, cold, etc. As an umbrella term, “positive” is more frequently encountered in the relevant literature to cover those terms that denote the above desirable qualities. Positive school climate exists when participants feel safe and at ease in a setting where interaction is favored through the care and support provided by principals and colleagues. A positive school climate is characterized by:
A sense of warmth, an active interest in students, and adult participation;
Setting limits to unacceptable behavior;
Absence of corporal punishment when rules are violated or otherwise undesirable behavior exhibited;
Adults acting as positive role models [16].
Such an environment has an impact on all those related to the school: educators, students, parents, and the broader community. Positive school climate favors the teachers’ professionalization and students’ development and progress at a socio-political, emotional, moral, and academic level. It constitutes a constructive experiential process preparing students for adult life within a democratic society. To create a positive school climate, the educator supports students, expresses high expectations, opts for student-centered approaches, provides immediate feedback, creates a family-like atmosphere, encourages interpersonal communication, evaluates success positively, formulates clear rules, gives work and academic orientation, and expresses his/her confidence in students ([17, 18], p. 125).
It has been acknowledged that there are various elements that shape school climate although there is no universal agreement on its key features. What is certain is that “strong positive cultures are places with a shared sense of what is important, a shared ethos of caring and concern, and a shared commitment to helping students learn” ([15] p. 29). Researchers have divided climate into variables, subsystems, or dimensions in order to define the components of organizational climate. Owens and Valesky [19] explain that organizational climate is the product of four variables or subsystems: ecology, milieu, organization, and culture. A review of relevant research shows that there are 10 fundamental dimensions that shape individual experience in school, which are grouped in four categories:
Safety (physical, social, and emotional);
Teaching and learning (quality of teaching, social, emotional, and ethical skills for learning, professional development of educators, and leadership);
Interpersonal relationships (respect for diversity, a sense of community, cooperation, and cohesion);
As far as the teaching and learning process is concerned, positive school climate activates motivation and the willingness to learn. Learning is not possible outside a suitable school climate, both in terms of the learning outcomes and in terms of the process. It is worth noting that the school climate that the child experiences at the start of his/her learning route is the foundation upon which he/she builds learning ability and experience.
School climate can be disrupted by a range of external factors, such as certain natural phenomena (e.g. severe weather conditions) or social events (conflict, transition, loss, etc.) or by internal factors, such as the educators’ and the staff’s behavior, the number of students, the composition of groups, third parties entering the classroom, an accident in the classroom, and so on. In cases when the disruption is threatening to participants, we speak of a state of crisis. According to Freiberg, “a healthy school climate contributes to effective teaching and learning. These instruments for assessing climate can help schools make informed and meaningful changes for the better” ([21], p. 22). To manage states of crisis in schools, it is necessary to take measures, including school readiness, the cognitive and emotional competence of educators in matters of mental health, information on the students’ family background and health, good cooperation with educational institutions, parents, school administrators and educators, and clearly defined and predetermined rules of action. Hoy et al. note that “A healthy school climate is imbued with positive student, teacher, and administrator interrelationships. Teachers like their colleagues, their school, their job, and their students are driven by a quest for academic excellence” (2002:39) [22]. According to Marshall [23], school climate is influenced by the following factors:
The number and quality of interactions between adults and students;
The school environment, including buildings, classrooms, available materials, but also the educators’ and students’ perception of this environment;
Students’ academic performance;
A sense of security at the school for all members of the school community;
A feeling of trust and respect for students and educators.
School atmosphere can have an impact on many areas of the school experience. Positive school climate has been associated with fewer emotional and behavioral problems [24]. Commitment to compliance with school operational rules and positive feedback by educators are two aspects of the pedagogical climate that affect the school experience and students’ self-esteem [25]. In addition, a special research project into school climate in high-risk urban settings has shown that a positive and supportive school climate can affect students’ academic performance to a great extent [26]. According to another research project, positive interpersonal relationships and an increase in learning opportunities for students in all demographic settings can increase levels of achievement and decrease dangerous behavior [27].
Regarding the roles of the teaching and administrative staff, Taylor and Tashakkori [28] found that the existence of a positive climate in school is connected to an increased sense of job satisfaction for school staff. Finally, the transition from one educational level to the next is also influenced by school climate. Entering a new school can cause stress in teachers and students, and this can have a negative impact on the teaching and learning process. Research has found that a positive and supportive school climate is important for a smooth transition to a new school [21]. Establishing a positive climate in a school unit is a collective, coordinated, and, to a certain degree, disciplined endeavor by the whole staff. When teachers and students feel that they are in an environment that is truly and actually interested in them, they view their everyday teaching and learning experience as a positive process ([29], p. xi). These are schools where staff exhibit a passionate professionalism and enjoy extensible opportunities for collegial dialog, problem solving, and community building and where the culture encourages student involvement in community service and teacher commitment to continual instructional development ([15], p. 29).
Evaluating school climate is one of the best ways to ensure its positive characteristics. An environment of cooperation and learning is founded on the social and emotional environment of the school, which is reflected in school climate [9, 30]. The evaluation process is aimed at assessing the level of school climate and designing its further improvement so that schools with a positive school culture can be created. Although traditionally the assessment of student performance has used reading, mathematics, and scientific knowledge as its criteria, an increasing number of education agencies are realizing that these indicators cannot convey educational outcomes in their totality. Data from the assessment of school climate are now used as a complementary form of evaluation. Important information is derived from the reviews of students in their final year. As Freiberg stresses, “the feedback process allows students to be citizens rather than tourists in their school, as they realize that they have an opportunity to participate in shaping the education process” ([21], p. 26).
The school community determines policies that promote the holistic development of all participants in the school community—the social, emotional, moral, political, and intellectual. Also, it promotes an integrated system for overcoming hindrances during teaching and learning. We could say that the school community creates an environment in which all members feel safe and creative. School climate and relationships within the school are one of the main areas of evaluation in the assessment programs for schools. Specifically, during the evaluation process, attention is paid to the following criteria of quality:
The process of evaluating and improving school climate is a demanding one. It is understood as a circular process consisting of five stages, including preparation and planning, assessment-evaluation of strengths, weaknesses, and needs, understanding evaluation outcomes, designing and application of the action plan, and reassessing what has been achieved and developing the next stage for improving school climate. The evaluation of indicators is based on data collected through the use of qualitative and quantitative methods and observation and recording tools [32]. The quality of education is, to a great extent, a function of school climate quality, which can be improved substantially, especially when it is understood and evaluated internally by the individuals actually involved in the education process. Internal evaluation requires additional competences on the educator’s part, but experience has shown that educators avoid recording data of their pedagogical action. The collection of data with the use of various methods identifies the educator as an education researcher, a quality inherent in pedagogical action. A combination of methods and techniques for observation and recording is the most effective way to cross-check and interpret data, and to define goals for each of the stages of evaluation [33].
School climate is expressed by tangible means, it is greatly influenced by leadership, and it responds to change rapidly. It becomes evident through collectivity, communication, decision-making, trust, expectations, recognition, support, and experimentation. School climate should reflect directly the school’s mission statement through its focus and actions. External factors, such as increased funding and provision of resources and staff can play a key role in shaping positive school climate. We are aware, however, that when planning and interventions are carried out by those involved in the internal environment of the school, they tend to be more viable. Could internal school communication be efficient in this respect? This question is analyzed in the following section.
Communication is the main parameter in the creation and development of civilization. For ancient Greeks and Romans, it was an area of great importance. The Athenian society called for greater competence in oral speech. When in court, citizens could not hire advocates but, rather, they had to defend themselves publicly. Those who stood for public office had to learn how to voice their ideas clearly and convincingly. In an attempt to understand the variables affecting persuasion, modern scholars have tried to transfer the classical persuasion practice into modern reality.
A multitude of definitions can be found in the literature with regard to communication. It has been defined as the delivery, reception, processing, and interpretation of information. This information can be transmitted orally, in writing, and in an active, passive, formal, informal, conscious, or unconscious manner ([34], p. 290). Robbins, Coulter and DeCenzo note that communication is the transfer of understanding and meaning ([35], p. 446). According to Schermerhorn [36], communication is an interpersonal process of sending and receiving symbols with attached messages. Communication is an interpersonal, that is, a social process, which can only be considered complete when some kind of understanding has been reached. It never is a simple case of a stimulus and a response in the way that these terms are used in psychology. Communication is the mechanism by means of which human relationships exist and develop. Irrespective of its conceptual definition, it must involve not only the transfer of meaning but also an understanding of it. Only when the sender’s message is fully understood by its recipient(s) can communication be considered effective ([34], p. 294; [36], p. 491).
Communication is a social activity, a social phenomenon that is present both at the interpersonal level and at the organization level. Communication is about transmitting and receiving information and messages between individuals and between groups through a system of symbols. Educators, just like doctors, social workers, psychologists, vocational guidance and business counselors, etc., are what is called “interpersonal professionals”, meaning that a great part of their work is dedicated to face-to-face interactions with other people. Such professionals must possess certain skills:
Cognitive skills: the fundamental knowledge pertaining to their profession that characterizes it and distinguishes it from other professions;
Technical skills: skills involving the use of tools and instruments relevant to the profession;
Social and communication skills: an individual’s ability to interact effectively with others at a professional level [37].
It is a fact that the ways used to communicate today have increased significantly compared to the past [38, 39]. Although educators have several new possibilities and media at their disposal that enable them to send their message to multiple audiences, they still seem to be lacking in key communication skills. It is also true that educators are not concerned about the way and the outcomes of their communication with students on the micro-scale of the classroom. However, experience has shown that this is not the case when they need to collaborate and communicate with other groups, such as staff associations, parents’ associations, and education agencies. On such occasions, the necessary communication skills are situated on the macro-level of the social and political sphere, where argumentation and persuasion require more complex knowledge and skills [40].
Conversation analysis in the school context aims to highlight the kinds of conversation that are most effective in students’ understanding of the material taught. Most research focuses on teacher-student dialogs [41, 42, 43], while studies into student-to-student talk within the education process are rather limited in number. The orality movement has helped to emphasize the significance of oral discourse in the school context. Regarding the systematic research of talk, two models of communication have been proposed. The
According to contemporary educational research, communication is one of the main factors in the development of a sustainable system for improving school climate ([29, 48], p. xv). Within a school unit the whole of the educational workforce communicates with one another, with colleagues from other school units, with the community of parents, but also with various agencies from outside the school [49]. The communication process occurs on a daily basis with all educators within school orgnanizations. For cooperational relationships to be developed in the school, effective communication among members of the school community is considered essential ([35], pp. 428–36). Sergiovanni notes that “School climate and relationships are obviously affected by the organization and communication in the school; school climate lies at the center” ([50], pp. 100–101).
School principals’ communication skills can determine, to a large extent, school efficacy and the achievement of goals. Research has shown that school principals devote a great amount of time to communicating with students, other educators, parents, education authorities, and with other individuals relevant to the school environment ([51], p. 53). According to certain findings, their communication is not rigidly planned, but, rather, spontaneous and relaxed, while they do not seem to make a systematic effort to receive or provide feedback or evaluate the effectiveness of communication. In addition, the communication roles assumed by school principals have increased, mainly because of the possibilities provided by new technologies. Gordon and Alston [10], 97–99) talk about four communication roles of principals: a) communication agent, b) message recipient, c) supervisor, and d) communication seeker.
In a critical analysis of these roles, we could suggest that the roles of the agent and recipient are somewhat inherent in the principal’s responsibilities, while the roles of supervisor and seeker require the development of communication skills and practices by the principals themselves. The role of a communication agent requires, first and foremost, that the principal understands the main objective of the message they wish to transfer [52]. When they understand the purpose of the message, they will be able to determine precisely both its content (message encoding) and the appropriate means of transmission (communication channel) ([36], pp. 491–493). At the same time, they must be aware of potential obstacles that may arise in the process of decoding by the person or persons that the message addresses (recipients). Such obstacles can be lack of interest on the recipients’ part, their poor cognitive background, prejudice, a problematic situation, etc. An important factor in this process is the existence or nonexistence of mutual trust between the agent and the recipient. Trust, i.e., confidence in the integrity, personality, and competences of a manager, constitutes a key parameter of communicative efficacy, as it is through this trust that the principal can convince recipients of the legitimacy of the objectives involved in the message ([35], p. 413). The role of recipient requires that principals be active listeners who try to decodify the sender’s messages without making judgments or resorting to spontaneous interpretations. Instead, they should engage in close observation of nonverbal clues, avoiding distractions and, above all, strengthening empathy for the sender. But how capable are school principals of understanding the emotions of others, including educators? With a certain degree of emotional intelligence, school principals can “read” other people’s feelings by focusing communication on actual behaviors, such as verbal, nonverbal, and paralinguistic clues. Communication is of great importance when it comes to understanding and interpreting the feelings of others, that is, their emotional intelligence. Donaldson [53] researched his own high school principalship by surveying staff members regarding communication. He analyzed both direct and indirect forms of communication finding a discrepancy between how he saw himself and how his staff members saw him.
Teachers are in a state of ongoing interaction and communication. The quality of this interaction is mainly dependent on the form of communication they use. An authoritarian attitude and administration turn workers into passive and submissive individuals and can ruin any possibility for meaningful communication and interaction. By contrast, a democratic attitude can contribute to the creation of a better emotional climate of cooperation, optimism, sincerity and responsibility and provides better possibilities for working efficiently and developing the personalities of those involved. A democratic principal can help create a positive school climate and, by doing so, a climate that is also productive. A principal who is demanding, pressing, and authoritarian cannot foster the improvement of interpersonal relationships. By contrast, a friendly, democratic principal can contribute substantially to the development of good relationships among the staff, which is a necessary condition for the progress of the whole organization. “School leaders—principals, teachers, and parents—are the key to eliminating toxic culture and building positive culture” ([15], p. 28).
To conclude, it can be argued that school principals should not restrict their communication roles to sending and receiving messages. Supervising and seeking communication within, from and to the school unit are quality features for establishing an appropriate process of communication than can make a difference in the lives of all stakeholders—educators, students, and parents. These roles call for a principal who is constantly active and has a profound insight, a principal whose vision will be the enhancement of communication at all levels so that a climate of trust can be created and communication can be promoted.
The problem set forth in this study is based upon the changes in educational context as caused by current social, financial, and technological factors, and their impact on school climate. This analysis explores the variables of school climate and communication in order to find the extent to which their relationship can work in favor of an open, safe, and creative educational organization where a positive school climate exists, and to which teachers and students will wish to belong.
The conceptual framework of this study is based on research related to organizational culture and educational communication. The material analyzed consists of contemporary articles and books, which highlight the importance of positive school climate in achieving school objectives, and interpersonal communication as a determining factor in terms of the research questions posed.
The examination of literature developed on a general-to-specific basis. By constructing the specific research question, we narrowed the focus of the research. We decided on the specific preliminary research question and identified key concepts and preliminary search terms. We selected appropriate databases in library catalogs and on the World Wide Web open access journals.
This study is a critical meta-analysis of literature on the research hypothesis, that communication is a key factor in promoting positive school climate. Meta-analysis is a recent trend in research. It refers to analyzing published studies to examine trends in the literature or in the results of research studies, such as the impact of a certain independent variable on another [54, 55]. By combining results found in scholarly journals and chapters, researchers can tell how much of an effect a particular variable has had over time.
The availability of electronic databases containing the results of published studies was a substantial benefit for the researcher conducting this meta-analysis. Databases such as https://eric.ed.gov/, www.ascd.org, https://www.hepg.org/, http://education.gsu.edu/, and databases of libraries were used. Sixty articles and books on the subject were selected that cover the key aspects of the topic and the new directions. A thorough study and analysis of their content was performed.
These results are presented and discussed under subthemes, which addressed the questions posed for this study. Thus, the subthemes: “The concept and the importance of school climate”, “The Rivals of school climate”, and “Evaluation of school climate” emerged for, for the theme “School Climate” and “
We have discussed the concept and the importance of school climate for ensuring the effectiveness of educators’ work and achieving school objectives. The conditions of school life are increasingly harsh, with incidents of violence and aggressiveness becoming part of the daily life in schools [6]. As a microcosm of society, school is influenced by the broader environment, in which rapid change, uncertainty, violence, and insecurity prevail. Furthermore, verbal and physical abuse often occurs in settings of grinding poverty. There are two sides to school climate: for those directly involved it can be understood as a subjective experience, while for outsiders it can be seen as a set of objective characteristics. Such characteristics include violent and aggressive acts, negative behavior, higher dropout rates, and educators abandoning the field of education.
We have analyzed the parameters that can contribute to the improvement of school climate as lived experience. In the workplace, educators observe and record aspects of the broader society. Their profession becomes harder not so much because of the demands concerning teaching and the promotion of knowledge as the social and psychological problems they are required to address. They have to work in an environment of increasing cultural and technological complexity, at a time when availability of resources is being restricted. Studies on educators’ work-related stress indicate that their profession is becoming increasingly demanding and their role is being redefined. In the context of this redefinition, many are those who take a decision to leave their jobs [4]. We have seen how school climate as lived experience can be a crucial factor affecting educators’ performance and a sense that they are effective and competent. When there is tension, violence, and uncertainty in school, it is not only the performance of educators that is reduced but also, as a consequence, that of students as well. By contrast, in a school climate which is positive, job satisfaction increases, while work-related stress tends to decrease. This finding has provided an answer to the first research question.
They are several ways to create a positive and creative climate in schools in order to enable educators and students to express themselves, create and experience the joy of achievement. It is true that external agencies and competent bodies cannot sense school experience. To them, school reality is an abstraction, an object to be observed, a set of quantitative data to be statistically analyzed. It is hard for outsiders to perceive the lived school reality and thus to fully understand the meaning of school conditions. Given this fact, factors that can contribute to forming positive school climate which come from within the school community were identified in the literature. We have found that interpersonal communication in school is an invaluable tool that can be used to this end. Communication is a social activity
In our study, we found that school principals have a very important role to play regarding school climate. School principals should possess considerable communication skills, be democratic, and promote cooperation. Understanding the attitude and behavior of educators is one of the desiderata of school leadership. But for this to happen, principals should be emotionally intelligent; in other words, they should be capable of “reading” the emotions of those they work with. Individuals with high emotional intelligence are capable of the following:
Characteristics of Principals personality | Principals’ emotional intelligence actions |
---|---|
Self-awareness | Understand the way in which they experience their own emotions |
Empathy | Be sensitive to and understand other people’s feelings |
Socially responsible | Offer assistance voluntarily and willingly |
Reality-oriented | See things as they are |
Sociable | Develop interpersonal relationships, approach others, and care about other people’s interests |
Impulse control | Manage situations that may cause them to be upset or angry |
Positive school climate is an essential attribute of a school in which each individual experiences positive emotions, a school that everyone involved wants to belong to. This study has attempted an examination of the importance of school climate for achieving school objectives and identifying the factors that can ensure its improvement. School climate is defined as the way in which interactions between those participating in the school community are experienced. In short, it is an experience during which emotions are formed and participants’ motivation enhanced, thus promoting educational work and meeting expectations.
Creating a pleasant school climate, however, is not an easy task. External factors, such as the broader social environment, provision of funding and resources, and collaboration with educational and social institutions, can be crucial in shaping positive school climate. On the other hand, internal factors have proved to be more effective. It is mainly educators’, principals’ and students’ action and behavior that create a school’s atmosphere. This is because these are the ones who experience school reality and the effects of its quality. They are directly involved in the school’s problems and achievements. For this reason, they are more aware than external actors that a positive and efficient school environment can facilitate the fulfillment of goals and expectations.
Educational work, being a social process, requires effective communication and cooperation. A listening culture, empathy and a collective spirit are conducive to resolving problems and conflicts. Central to the management of school climate is the role of school principals. A principal who employs a democratic system of administration and has high communication skills can be vital to the creation of positive school climate. The communication skills of teachers and school administration can be a stepping stone or an obstacle to the formation of a pleasant, desirable, and productive school. Every teacher should be aware of their students’ needs and potential. With increased emotional intelligence, a teacher can know how to make the best of these needs and potential for their students’ benefit. Similarly, the school principal should be aware of the teachers’ needs and potential and support them so that the best possible result can be achieved from their work.
Positive school climate is based on respect for singularity and freedom of expression, and on cooperative understanding. It requires work carried out through democratic processes for all participants in the school community. Positive school climate cannot be created in a definitive manner. Instead, it is an ongoing process of observation, planning and evaluation. Each and every member of the school community has an influence on and is responsible for its creation. In conclusion, positive school climate should satisfy the following requirements:
Covering the biological, emotional, and exploratory needs of participants;
A surrounding space which is pleasant and provides stimuli for action;
The ability of neutralizing negative factors;
Possibilities for verbal, nonverbal and symbolic communication;
Teacher-centered leadership;
Educators’ ability to communicate and self-regulate emotions;
Collaboration between school workforce and external agents;
Effective communication and positive school climate in the school context can be viewed as a challenge and an achievement, but also as the core and source of students’ and teachers’ well-being and development. After all, what both students and teachers later remember from the school experience is how they felt and whether there were conditions encouraging personal expression and creativity, rather than what they were taught or taught to others. For seeing school climate as a fertile soil where knowledge can be cultivated and diffuse, communication is an essential requirement.
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.
In our mission to support the dissemination of knowledge, we travel throughout the world to present our publications and support our Authors and Academic Editors. We attend international symposia, conferences, workshops and book fairs as well as business meetings with science, academic and publishing professionals. Take a look at the current events.
",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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03 - 12 June 2022
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24 - 27 August 2022, Beijing, China
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19 - 23 October 2022, Frankfurt, Germany
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Guadalajara International Book Fair
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May 18, 2022 | 1:00 PM - 2:00 PM CEST
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24 - 27 August 2022, Beijing, China
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19 - 23 October 2022, Frankfurt, Germany
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Guadalajara International Book Fair
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Urban tunnels are often made in soils with very low values of overburden. Risks of collapse and large deformations at the surface are high; thus negative impact on old buildings are likely to occur if appropriate measures are not taken in advance, when designing and constructing the tunnel. For deep tunnels with high overburden and low rock mass properties, squeezing conditions and excessive loads around the excavation can jeopardize the stability of the tunnel, leading to extensive collapse. The aim of the chapter is to give details on advance computational modelling and analytical methodologies, which can be used in order to design shallow and deep tunnels and to present real case studies from around the world, from very shallow tunnels in India with only 4.5 m overburden to a deep tunnel in Venezuela with extreme squeezing conditions under 1300 m overburden.",book:{id:"7690",slug:"tunnel-engineering-selected-topics",title:"Tunnel Engineering",fullTitle:"Tunnel Engineering - Selected Topics"},signatures:"Spiros Massinas",authors:[{id:"295762",title:"Dr.",name:"Spiros",middleName:null,surname:"Massinas",slug:"spiros-massinas",fullName:"Spiros Massinas"}]},{id:"68157",title:"Introductory Chapter: Textile Manufacturing Processes",slug:"introductory-chapter-textile-manufacturing-processes",totalDownloads:4484,totalCrossrefCites:16,totalDimensionsCites:26,abstract:null,book:{id:"8892",slug:"textile-manufacturing-processes",title:"Textile Manufacturing Processes",fullTitle:"Textile Manufacturing Processes"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]},{id:"66828",title:"Breathing Monitoring and Pattern Recognition with Wearable Sensors",slug:"breathing-monitoring-and-pattern-recognition-with-wearable-sensors",totalDownloads:3113,totalCrossrefCites:12,totalDimensionsCites:16,abstract:"This chapter introduces the anatomy and physiology of the respiratory system, and the reasons for measuring breathing events, particularly, using wearable sensors. Respiratory monitoring is vital including detection of sleep apnea and measurement of respiratory rate. The automatic detection of breathing patterns is equally important in other respiratory rehabilitation therapies, for example, magnetic resonance exams for respiratory triggered imaging, and synchronized functional electrical stimulation. In this context, the goal of many research groups is to create wearable devices able to monitor breathing activity continuously, under natural physiological conditions in different environments. Therefore, wearable sensors that have been used recently as well as the main signal processing methods for breathing analysis are discussed. The following sensor technologies are presented: acoustic, resistive, inductive, humidity, acceleration, pressure, electromyography, impedance, and infrared. New technologies open the door to future methods of noninvasive breathing analysis using wearable sensors associated with machine learning techniques for pattern detection.",book:{id:"7654",slug:"wearable-devices-the-big-wave-of-innovation",title:"Wearable Devices",fullTitle:"Wearable Devices - the Big Wave of Innovation"},signatures:"Taisa Daiana da Costa, Maria de Fatima Fernandes Vara, Camila Santos Cristino, Tyene Zoraski Zanella, Guilherme Nunes Nogueira Neto and Percy Nohama",authors:[{id:"192464",title:"Ph.D.",name:"Percy",middleName:null,surname:"Nohama",slug:"percy-nohama",fullName:"Percy Nohama"},{id:"285706",title:"MSc.",name:"Taísa Daiana",middleName:null,surname:"Da Costa",slug:"taisa-daiana-da-costa",fullName:"Taísa Daiana Da Costa"},{id:"285707",title:"MSc.",name:"Maria de Fatima Fernandes",middleName:null,surname:"Vara",slug:"maria-de-fatima-fernandes-vara",fullName:"Maria de Fatima Fernandes Vara"},{id:"285708",title:"BSc.",name:"Camila Santos",middleName:null,surname:"Cristino",slug:"camila-santos-cristino",fullName:"Camila Santos Cristino"},{id:"285709",title:"Prof.",name:"Guilherme Nunes",middleName:null,surname:"Nogueira Neto",slug:"guilherme-nunes-nogueira-neto",fullName:"Guilherme Nunes Nogueira Neto"},{id:"293109",title:"BSc.",name:"Tyene",middleName:null,surname:"Zoraski Zanella",slug:"tyene-zoraski-zanella",fullName:"Tyene Zoraski Zanella"}]},{id:"41411",title:"Textile Dyes: Dyeing Process and Environmental Impact",slug:"textile-dyes-dyeing-process-and-environmental-impact",totalDownloads:20676,totalCrossrefCites:101,totalDimensionsCites:320,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Farah Maria Drumond Chequer, Gisele Augusto Rodrigues de Oliveira, Elisa Raquel Anastácio Ferraz, Juliano Carvalho Cardoso, Maria Valnice Boldrin Zanoni and Danielle Palma de Oliveira",authors:[{id:"49040",title:"Prof.",name:"Danielle",middleName:null,surname:"Palma De Oliveira",slug:"danielle-palma-de-oliveira",fullName:"Danielle Palma De Oliveira"},{id:"149074",title:"Prof.",name:"Maria Valnice",middleName:null,surname:"Zanoni",slug:"maria-valnice-zanoni",fullName:"Maria Valnice Zanoni"},{id:"153502",title:"Ph.D.",name:"Farah",middleName:null,surname:"Chequer",slug:"farah-chequer",fullName:"Farah Chequer"},{id:"153504",title:"MSc.",name:"Gisele",middleName:null,surname:"Oliveira",slug:"gisele-oliveira",fullName:"Gisele Oliveira"},{id:"163377",title:"Dr.",name:"Juliano",middleName:null,surname:"Cardoso",slug:"juliano-cardoso",fullName:"Juliano Cardoso"},{id:"163393",title:"Dr.",name:"Elisa",middleName:null,surname:"Ferraz",slug:"elisa-ferraz",fullName:"Elisa Ferraz"}]},{id:"70242",title:"Advancements in the Fenton Process for Wastewater Treatment",slug:"advancements-in-the-fenton-process-for-wastewater-treatment",totalDownloads:1985,totalCrossrefCites:13,totalDimensionsCites:26,abstract:"Fenton is considered to be one of the most effective advanced treatment processes in the removal of many hazardous organic pollutants from refractory/toxic wastewater. It has many advantages, but drawbacks are significant such as a strong acid environment, the cost of reagents consumption, and the large production of ferric sludge, which limits Fenton’s further application. The development of Fenton applications is mainly achieved by improving oxidation efficiency and reducing sludge production. This chapter presents a review on fundamentals and applications of conventional Fenton, leading advanced technologies in the Fenton process, and reuse methods of iron containing sludge to synthetic and real wastewaters are discussed. Finally, future trends and some guidelines for Fenton processes are given.",book:{id:"9415",slug:"advanced-oxidation-processes-applications-trends-and-prospects",title:"Advanced Oxidation Processes",fullTitle:"Advanced Oxidation Processes - Applications, Trends, and Prospects"},signatures:"Min Xu, Changyong Wu and Yuexi Zhou",authors:[{id:"307479",title:"Dr.",name:"Changyong",middleName:null,surname:"Wu",slug:"changyong-wu",fullName:"Changyong Wu"},{id:"307546",title:"Prof.",name:"Yuexi",middleName:null,surname:"Zhou",slug:"yuexi-zhou",fullName:"Yuexi Zhou"},{id:"311139",title:"Dr.",name:"Min",middleName:null,surname:"Xu",slug:"min-xu",fullName:"Min Xu"}]}],onlineFirstChaptersFilter:{topicId:"24",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82676",title:"Electrospinning of Fiber Matrices from Polyhydroxybutyrate for the Controlled Release Drug Delivery Systems",slug:"electrospinning-of-fiber-matrices-from-polyhydroxybutyrate-for-the-controlled-release-drug-delivery-",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.105786",abstract:"The submission provides an overview of current state of the problem and authors’ experimental data on manufacturing nonwoven fibrous matrices for the controlled release drug delivery systems (CRDDS). The choice of ultrathin fibers as effective carriers is determined by their characteristics and functional behavior, for example, such as a high specific surface area, anisotropy of some physicochemical characteristics, spatial limitations of segmental mobility that are inherent in nanosized objects, controlled biodegradation, and controlled diffusion transport. The structural-dynamic approach to the study of the morphology and diffusion properties of biopolymer fibers based on polyhydroxybutyrate (PHB) is considered from several angles. In the submission, the electrospinning (ES) application to reach specific characteristics of materials for controlled release drug delivery is discussed.",book:{id:"11127",title:"Electrospinning - Material Technology of the Future",coverURL:"https://cdn.intechopen.com/books/images_new/11127.jpg"},signatures:"Anatoly A. Olkhov, Svetlana G. Karpova, Anna V. Bychkova, Alexandre A. Vetcher and Alexey L. Iordanskii"},{id:"82600",title:"Impact of the Spreading of Sludge from Wastewater Treatment Plants on the Transfer and Bio-Availability of Trace Metal Elements in the Soil-Plant System",slug:"impact-of-the-spreading-of-sludge-from-wastewater-treatment-plants-on-the-transfer-and-bio-availabil",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.103745",abstract:"The spreading of sludge from sewage treatment plants increased the production of durum wheat and rapeseed. Their richness in nitrogen, phosphorus, and potassium gives them a beneficial effect on crops. However, the application of the sludge can induce increases in the concentration of metals in plant tissues. This increase can generate disturbances at the level of the cell and organelles, such as mitochondria and chloroplasts, which can be altered. Repeated applications of the sludge on the same site tend to increase the accumulation of heavy metals in the soil, so that an cause toxicities for soil microorganisms, animals, and humans, via the food chain. However, it is important to specify that these nuisances mainly concerned industrial sludge, but the use of this sludge is strictly prohibited. In addition, the high doses used in our field experiments are significantly higher than those authorized in agricultural practice. Finally, the risk assessment by calculating both the level of consumer exposure and the number of years for soil saturation shows that the use of urban sludge is safe, especially in the short and medium-term. Nevertheless, the quality of the sludge to be spread must be constantly monitored.",book:{id:"11173",title:"Wastewater Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/11173.jpg"},signatures:"Najla Lassoued and Bilal Essaid"},{id:"81249",title:"Electrospun Polymeric Substrates for Tissue Engineering: Viewpoints on Fabrication, Application, and Challenges",slug:"electrospun-polymeric-substrates-for-tissue-engineering-viewpoints-on-fabrication-application-and-ch",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.102596",abstract:"Electrospinning is the technique for producing nonwoven fibrous structures, to mimic the fabrication and function of the native extracellular matrix (ECM) in tissue. Prepared fibrous with this method can act as potential polymeric substrates for proliferation and differentiation of stem cells (with the cellular growth pattern similar to damaged tissue cells) and facilitation of artificial tissue remodeling. Moreover, such substrates can improve biological functions, and lead to a decrease in organ transplantation. In this chapter, we focus on the fundamental parameters and principles of the electrospinning technique to generate natural ECM-like substrates, in terms of structural and functional complexity. In the following, the application of these substrates in regenerating various tissues and the role of polymers (synthetic/natural) in the formation of such substrates is evaluated. Finally, challenges of this technique (such as cellular infiltration and inadequate mechanical strength) and solutions to overcome these limitations are studied.",book:{id:"11127",title:"Electrospinning - Material Technology of the Future",coverURL:"https://cdn.intechopen.com/books/images_new/11127.jpg"},signatures:"Azadeh Izadyari Aghmiuni, Arezoo Ghadi, Elmira Azmoun, Niloufar Kalantari, Iman Mohammadi and Hossein Hemati Kordmahaleh"},{id:"82145",title:"Slope Casting Process: A Review",slug:"slope-casting-process-a-review",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.102742",abstract:"Semi solid processing is a near net shape casting process and one of the promising techniques to obtain dendritic free structure of metals. Semi solid casting gives numerous advantages than solid processing and liquid processing. Semi solid casting process gives, Laminar flow filling of die without turbulence, Lower metal temperature, Less shrinkage, Less porosity, Higher mechanical properties. Semi solid casting process is industrially successful, producing a variety of products with good quality. Slope Casting process is a simple technique to produce semi solid feed-stoke with globular microstructure and dendrite free structure castings. Slope casting process depends on different process parameters like slope length, slope angle, pouring temperature etc. The present study mainly focuses on review of various explorations made by researchers with different process parameters of the Slope casting process and explain the mechanisms that lead to microstructural changes which leads to good mechanical properties.",book:{id:"11119",title:"Casting Processes",coverURL:"https://cdn.intechopen.com/books/images_new/11119.jpg"},signatures:"Mukkollu Sambasiva Rao and Amitesh Kumar"},{id:"81861",title:"Emerging Human Coronaviruses (SARS-CoV-2) in the Environment Associated with Outbreaks Viral Pandemics",slug:"emerging-human-coronaviruses-sars-cov-2-in-the-environment-associated-with-outbreaks-viral-pandemics",totalDownloads:21,totalDimensionsCites:0,doi:"10.5772/intechopen.103886",abstract:"In December 2019, there was a cluster of pneumonia cases in Wuhan, a city of about 11 million people in Hubei Province. The World Health Organization (WHO), qualified CoVid-19 as an emerging infectious disease on March 11, 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which spreads around the world. Coronaviruses are also included in the list of viruses likely to be found in raw sewage, as are other viruses belonging to the Picornaviridae family. SRAS-CoV-2 has been detected in wastewater worldwide such as the USA, France, Netherlands, Australia, and Italy according to the National Research Institute for Public Health and the Environment. In addition, the SARS-CoV-2 could infect many animals since it has been noticed in pigs, domestic and wild birds, bats, rodents, dogs, cats, tigers, cattle. Therefore, the SARS-CoV-2 molecular characterization in the environment, particularly in wastewater and animals, appeared to be a novel approach to monitor the outbreaks of viral pandemics. This review will be focused on the description of some virological characteristics of these emerging viruses, the different human and zoonotic coronaviruses, the sources of contamination of wastewater by coronaviruses and their potential procedures of disinfection from wastewater.",book:{id:"11173",title:"Wastewater Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/11173.jpg"},signatures:"Chourouk Ibrahim, Salah Hammami, Eya Ghanmi and Abdennaceur Hassen"},{id:"81797",title:"Study of Change Surface Aerator to Submerged Nonporous Aerator in Biological Pond in an Industrial Wastewater Treatment in Daura Refinery",slug:"study-of-change-surface-aerator-to-submerged-nonporous-aerator-in-biological-pond-in-an-industrial-w",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104860",abstract:"Daura refinery, with a capacity of 140,000 barrel per stream day as a refining capacity, wastewater discharged from refining and treatment processing units, polluted water as foul water, drainages, oil spills, blowdown of boilers and cooling towers, and many other polluted water sources, aims to remove pollutants and reject clean water to the river; wastewater treatment system takes place in this treatment process. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. 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He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. 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She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. 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