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.
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By 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:
All 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.
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"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
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"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
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In 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\\n
We 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\\n
Feel free to share this news on social media and help us mark this memorable moment!
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\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\n
By 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:
All 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\n
In 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\n
We 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\n
Feel 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:"5789",leadTitle:null,fullTitle:"Nanoscaled Films and Layers",title:"Nanoscaled Films and Layers",subtitle:null,reviewType:"peer-reviewed",abstract:"In recent years, scientific investigations and technological developments have resulted in many new results. Direct applications of quantum mechanical laws to system with length scales lower than 100 nm (nano) had opened a way to construction of new equipment in the field f.e. of nano- and optoelectronics. This book fits into this trend summarizing the results related to discoveries and technological applications of nanolayer in different fields of material science and even life science. The chapters are organized into three subfields:\n -Preparation and fabrications of nanolayers with different methods.\n -Description of recent achievements related to very important III-V heterostructures.\n -Descriptions of mechanical, thermal, optoelectronic, photocatalytic, and tribological properties of nanolayered structures.\n Some environmentally friendly applications are also treated in this book.\nThe presented book provides a description of specific and original results obtained by authors. We hope that the volume will be of interest for a wide range of readers working in the field of material science.",isbn:"978-953-51-3144-1",printIsbn:"978-953-51-3143-4",pdfIsbn:"978-953-51-4829-6",doi:"10.5772/65465",price:119,priceEur:129,priceUsd:155,slug:"nanoscaled-films-and-layers",numberOfPages:298,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"f43ea8f3894ee0c3e44b2351bf3447d5",bookSignature:"Laszlo Nanai",publishedDate:"May 24th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5789.jpg",numberOfDownloads:19241,numberOfWosCitations:13,numberOfCrossrefCitations:15,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:60,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 26th 2016",dateEndSecondStepPublish:"October 17th 2016",dateEndThirdStepPublish:"January 13th 2017",dateEndFourthStepPublish:"April 13th 2017",dateEndFifthStepPublish:"June 12th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"61978",title:"Prof.",name:"Laszlo",middleName:null,surname:"Nanai",slug:"laszlo-nanai",fullName:"Laszlo Nanai",profilePictureURL:"https://mts.intechopen.com/storage/users/61978/images/system/61978.png",biography:"Prof. Nanai was born on April 19, 1948, in Csopak (Hungary). He studied physics (MSc) at Saint Petersburg State University (RU), and his PhD degree and habilitation in the field of quantum electronics were obtained at Lebedev Physical Institute, Moscow (RU), and Szeged University (H). \r\n\r\nHe is a specialist in the fields of solid-state physics, laser-matter interaction fabrication and characterization of nanostructures. He has written over 170 scientific publications including about 10 books and chapters in books and conference proceedings.",institutionString:"University of Szeged",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Szeged",institutionURL:null,country:{name:"Hungary"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1169",title:"Condensed Matter Physics",slug:"nanotechnology-and-nanomaterials-material-science-condensed-matter-physics"}],chapters:[{id:"54288",title:"Formation of Nanolayer on Surface of EPD Coatings Based on Poly-Ether-Ether-Ketone",doi:"10.5772/67570",slug:"formation-of-nanolayer-on-surface-of-epd-coatings-based-on-poly-ether-ether-ketone",totalDownloads:1435,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Poly-ether-ether-ketone (PEEK) is a high performance polymer with many intrinsic properties. When it is used in the form of coating, an improvement of some of its functional properties was achieved by forming a surface nanolayer. In this chapter, it will be described how it was possible to obtain this result. Firstly, three kinds of PEEK composite coatings were deposited by electrophoretic deposition, adding alumina particles, polytetrafluoroethylene (PTFE) and lignin to PEEK. Then, the composite coatings were thermal treated in a furnace. Therefore, surface nanostructure and chemical composition of these PEEK composite coatings were modified with respect to bulk coatings, due to interaction between PEEK chain and secondary phase, emphasised by the thermal treatment conditions. Experimental evidence of the formation of surface nanolayer was provided by SEM, TEM, GIXRD, ATR-FTIR and XPS characterisations. Functional characterisations demonstrated that wear resistance—in the presence of alumina particles—hydrophobicity—in the presence of PTFE—and corrosion resistance—in the presence of Lignin—were increased with respect to pure PEEK.",signatures:"Maria Federica De Riccardis",downloadPdfUrl:"/chapter/pdf-download/54288",previewPdfUrl:"/chapter/pdf-preview/54288",authors:[{id:"77857",title:"Dr.",name:"M. Federica",surname:"De Riccardis",slug:"m.-federica-de-riccardis",fullName:"M. Federica De Riccardis"}],corrections:null},{id:"54678",title:"Electroless Deposition of Nanolayered Metallic Coatings",doi:"10.5772/intechopen.68220",slug:"electroless-deposition-of-nanolayered-metallic-coatings",totalDownloads:3438,totalCrossrefCites:5,totalDimensionsCites:8,hasAltmetrics:1,abstract:"Electroless metallic coating is referred as the deposition of a substrate material by the process of chemical or autocatalytic reduction of aqueous metal ions deposited to a substrate material without any external supply of power. Electroless nickel alloys are generally considered synonymous to the word “electroless coating” as ~90% of productions in industries are of this alloy coating. Rest of the electroless metallic coatings includes gold, copper, palladium, cobalt, silver, etc. These electroless metallic coatings (other than electroless nickel coatings) are also one of the vibrant areas in the field of materials properties and surface engineering research. From the year 2000 to till date, nearly 1000 SCI indexed research papers were published on this topic. However, no comprehensive studies about the recent progress on this topic were reported elsewhere so far. In this context, the present chapter aims to give a complete overview on various aspects of the rest of the electroless metallic nanocoatings/layer as a whole. More importance will be on the recent developments of the nanocharacteristics and future scopes.",signatures:"Jothi Sudagar, Rajendraprasad Tamilarasan, Udaykumar Sanjith, Raj\nRajendran and Ravi Kumar",downloadPdfUrl:"/chapter/pdf-download/54678",previewPdfUrl:"/chapter/pdf-preview/54678",authors:[{id:"202302",title:"Dr.",name:"Jothi",surname:"Sudagar",slug:"jothi-sudagar",fullName:"Jothi Sudagar"},{id:"203599",title:"Dr.",name:"Tamilarasan",surname:"Tr",slug:"tamilarasan-tr",fullName:"Tamilarasan Tr"},{id:"203600",title:"MSc.",name:"Sanjith",surname:"U",slug:"sanjith-u",fullName:"Sanjith U"},{id:"203601",title:"Prof.",name:"Rajendran",surname:"R",slug:"rajendran-r",fullName:"Rajendran R"},{id:"203602",title:"Prof.",name:"Ravi Kumar",surname:"Nv",slug:"ravi-kumar-nv",fullName:"Ravi Kumar Nv"}],corrections:null},{id:"54328",title:"Laser Prepared Thin Films for Optoelectronic Applications",doi:"10.5772/67659",slug:"laser-prepared-thin-films-for-optoelectronic-applications",totalDownloads:1502,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Laser techniques such as pulsed laser deposition, combinatorial pulsed laser deposition, and matrix-assisted pulsed laser evaporation were used to deposit thin films for optoelectronic applications. High-quality transparent conductor oxide films ITO, AZO, and IZO were deposited on polyethylene terephthalate by PLD, an important experimental parameter being the target-substrate distance. The TCO films present a high transparency (>95%) and a reduced electrical resistivity (5 × 10−4 Ωcm) characteristics very useful for their integration in the flexible electronics. InxZn1−xO films with a compositional library were obtained by CPLD. These films are featured by a high optical transmission (>95%), the lowest resistivity (8.6 × 10−4 Ωcm) being observed for an indium content of about 44–49 at.%. Organic heterostructures based on arylenevinylene oligomers (P78 and P13) or arylene polymers (AMC16 and AMC22) were obtained by MAPLE. In the case of ITO/P78/Alq3/Al heterostructures, a higher current value is obtained when the film thickness increases. Also, a photovoltaic effect was observed for heterostructures based on AMC16 or AMC22 deposited on ITO covered by a thin layer of PEDOT:PSS. Due to their optical and electrical properties, such organic heterostructures can be interesting for the organic photovoltaic cells (OPV) applications.",signatures:"Marcela Socol, Gabriel Socol, Nicoleta Preda, Anca Stanculescu and\nFlorin Stanculescu",downloadPdfUrl:"/chapter/pdf-download/54328",previewPdfUrl:"/chapter/pdf-preview/54328",authors:[{id:"21373",title:"Dr.",name:"Anca",surname:"Stanculescu",slug:"anca-stanculescu",fullName:"Anca Stanculescu"},{id:"21611",title:"Dr.",name:"Florin",surname:"Stanculescu",slug:"florin-stanculescu",fullName:"Florin Stanculescu"},{id:"178419",title:"Dr.",name:"Gabriel",surname:"Socol",slug:"gabriel-socol",fullName:"Gabriel Socol"},{id:"184343",title:"Dr.",name:"Nicoleta",surname:"Preda",slug:"nicoleta-preda",fullName:"Nicoleta Preda"},{id:"198589",title:"Dr.",name:"Marcela",surname:"Socol",slug:"marcela-socol",fullName:"Marcela Socol"}],corrections:null},{id:"54765",title:"Heteroepitaxy of III–V Zinc Blende Semiconductors on Nanopatterned Substrates",doi:"10.5772/67572",slug:"heteroepitaxy-of-iii-v-zinc-blende-semiconductors-on-nanopatterned-substrates",totalDownloads:1557,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"In the last decade, zinc blende structure III–V semiconductors have been increasingly utilized for the realization of high‐performance optoelectronic applications because of their tunable bandgaps, high carrier mobility and the absence of piezoelectric fields. However, the integration of III–V devices on the Si platform commonly used for CMOS electronic circuits still poses a challenge, due to the large densities of mismatch‐related defects in heteroepitaxial III–V layers grown on planar Si substrates. A promising method to obtain thin III–V layers of high crystalline quality is the growth on nanopatterned substrates. In this approach, defects can be effectively eliminated by elastic lattice relaxation in three dimensions or confined close to the substrate interface by using aspect‐ratio trapping masks. As a result, an etch pit density as low as 3.3 × 105 cm−2 and a flat surface of submicron GaAs layers have been accomplished by growth onto a SiO2 nanohole film patterned Si(001) substrate, where the threading defects are trapped at the SiO2 mask sidewalls. An open issue that remains to be resolved is to gain a better understanding of the interplay between mask shape, growth conditions and formation of coalescence defects during mask overgrowth in order to achieve thin device quality III–V layers.",signatures:"Thomas Riedl and Jörg K.N. Lindner",downloadPdfUrl:"/chapter/pdf-download/54765",previewPdfUrl:"/chapter/pdf-preview/54765",authors:[{id:"196852",title:"Dr.",name:"Thomas",surname:"Riedl",slug:"thomas-riedl",fullName:"Thomas Riedl"},{id:"197870",title:"Prof.",name:"Jörg K.N.",surname:"Lindner",slug:"jorg-k.n.-lindner",fullName:"Jörg K.N. Lindner"}],corrections:null},{id:"54687",title:"Surface Modification of III-V Compounds Substrates for Processing Technology",doi:"10.5772/67916",slug:"surface-modification-of-iii-v-compounds-substrates-for-processing-technology",totalDownloads:1969,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Semiconductor materials became a part of nowadays life due to useful applications caused by characteristic properties as variable conductivity and sensitivity to light or heat. Electrical properties of a semiconductor can be modified by doping or by the application of electric fields or light; and from this view, devices made from semiconductors can be used for amplification or energy conversion. The compound semiconductor materials from III-V class experienced a qualitative leap from promising potential to nowadays technologic environment. The III-V semiconductor compounds are the material bases for electronic and optoelectronic devices such as high-electron-mobility transistors (HEMT), bipolar heterostructure transistors, IR light-emitting diodes, heterostructure lasers, Gunn diodes, Schottky devices, photodetectors, and heterostructure solar cells for terrestrial and spatial operating conditions. Among III-V semiconductor compounds, gallium arsenide (GaAs) and gallium antimonide (GaSb) are of special interest as a substrate material due to the lattice parameter match to solid solutions (ternary and quaternary) whose band gaps cover a wide spectral range from 0.8 to 4.3 μm in the case of GaSb. The solid/solid interfaces could play a key part in the development of microelectronic device technology. In most of the cases, the initial surface of III-V compounds exposed to laboratory conditions is covered usually with native oxide layers. Various techniques for performing the surface cleaning process are used, e.g., controlled chemical etching, in situ ion sputtering, coupled with controlled annealing in vacuum and often these classic techniques are combined in order to prepare an eligible semiconductor surface to be exposed to a technological device chain. The evolution of surface native oxides in different cleaning procedures and the characteristics of as-prepared semiconductor surface were investigated by modern surface investigation techniques, i.e., X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Rutherford backscattering spectrometry (RBS) combined with electrical characterization. Surface preparation of semiconductors in particular for III-V compounds is a necessary requirement in device technology due to the existence of surface impurities and the presence of native oxides. The impurities can affect the adherence of ohmic and Schottky contacts and due to thermal decomposition of native oxides (e.g., GaSb) it also affect the interface metal/semiconductor. The practical experience reveals that the simple preparation of a surface is a nonrealistic expectation, i.e., surface preparation is a result of combined treatments, namely chemical etching and thermal treatment, ion beam sputtering and thermal reconstruction procedure.",signatures:"Rodica V. Ghita, Constantin Logofatu, Constantin-Catalin Negrila,\nLucian Trupina and Costel Cotirlan-Simioniuc",downloadPdfUrl:"/chapter/pdf-download/54687",previewPdfUrl:"/chapter/pdf-preview/54687",authors:[{id:"50919",title:"Dr.",name:"Rodica V.",surname:"Ghita",slug:"rodica-v.-ghita",fullName:"Rodica V. Ghita"},{id:"197743",title:"Dr.",name:"Lucian",surname:"Trupina",slug:"lucian-trupina",fullName:"Lucian Trupina"},{id:"198134",title:"Dr.",name:"Constantin",surname:"Logofatu",slug:"constantin-logofatu",fullName:"Constantin Logofatu"},{id:"198135",title:"Dr.",name:"Constantin-Catalin",surname:"Negrila",slug:"constantin-catalin-negrila",fullName:"Constantin-Catalin Negrila"},{id:"198140",title:"Dr.",name:"Costel",surname:"Cotirlan-Simioniuc",slug:"costel-cotirlan-simioniuc",fullName:"Costel Cotirlan-Simioniuc"}],corrections:null},{id:"54581",title:"Nanoscaled Fluorescent Films and Layers for Detection of Environmental Pollutants",doi:"10.5772/67869",slug:"nanoscaled-fluorescent-films-and-layers-for-detection-of-environmental-pollutants",totalDownloads:1797,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Hazardous gas and ion pollutants are the most serious environmental problems around the world. It is of great importance to develop devices for easy detection of these hazardous substances. Fluorescence technology with high resolution and operational simplicity has attracted a lot of attention in recent years. Organic fluorescent dyes absorb/emit lights within a broad wavelength range, which is suitable for various demands. Chromophores, such as perylene, cyanine dyes, spiropyran, and so on, are widely studied as fluorescent probes for gases and ions. The dyes could respond to external stimuli through structural changes of the conjugated chromophore itself or the attached functional groups, leading to detectable spectral changes. Organic dyes are incorporated into nanoscaled films and layers, which are portable and durable for effective sensing in complex environments. In this chapter, preparation and application of fluorescent films and layers (FFL) for gaseous/ionic detection are reviewed. We discuss the response mechanism of fluorescent dyes, the fabrication of nanoscaled FFL, and some examples of FFL for the detection of gas and ion pollutants.",signatures:"Meizhen Yin and Chendong Ji",downloadPdfUrl:"/chapter/pdf-download/54581",previewPdfUrl:"/chapter/pdf-preview/54581",authors:[{id:"197509",title:"Prof.",name:"Meizhen",surname:"Yin",slug:"meizhen-yin",fullName:"Meizhen Yin"},{id:"200372",title:"Mr.",name:"Chendong",surname:"Ji",slug:"chendong-ji",fullName:"Chendong Ji"}],corrections:null},{id:"54290",title:"Mechanical Nanoprocessing and Nanoviscoelasticity of Surface- Modified Polycarbonate",doi:"10.5772/67512",slug:"mechanical-nanoprocessing-and-nanoviscoelasticity-of-surface-modified-polycarbonate",totalDownloads:1280,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"To clarify their potential as atomic force microscope (AFM) memory media, the nanometer‐scale mechanical processing properties of untreated and fluorocarbon plasma‐treated polycarbonate samples were determined via the sliding of an AFM tip. The surface energy of the polycarbonate was reduced by the fluorocarbon plasma treatment, as well as the force necessary for processing. Nanometer‐scale precise processing of the polycarbonate was realized after the fluorocarbon plasma treatment, and the interval pitch in the formation of lines, spaces, and nanometer‐scale fine dots was minimized to 60 nm with these samples. The viscoelastic properties of the fluorinated polycarbonate were evaluated using an AFM in force modulation mode. The fluorocarbon plasma treatment reduced the friction force of the polycarbonate sample and improved its wear resistance, which caused the friction durability corresponding to the reliability of data reproduction to be markedly improved. These results show that high‐density recording can be realized by nanometer‐scale processing of fluorocarbon plasma‐treated polycarbonate samples.",signatures:"Shojiro Miyake and Mei Wang",downloadPdfUrl:"/chapter/pdf-download/54290",previewPdfUrl:"/chapter/pdf-preview/54290",authors:[{id:"22097",title:"Dr.",name:"Mei",surname:"Wang",slug:"mei-wang",fullName:"Mei Wang"}],corrections:null},{id:"54966",title:"Green Intelligent Nanomaterials by Design (Using Nanoparticulate/2D-Materials Building Blocks) Current Developments and Future Trends",doi:"10.5772/intechopen.68434",slug:"green-intelligent-nanomaterials-by-design-using-nanoparticulate-2d-materials-building-blocks-current",totalDownloads:1501,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Feasibility of designing and synthesizing ‘smart’ and ‘intelligent’ materials using nanostructured building blocks has been examined here based on the current status of the progress made in this context. The added advantages of using 2D layered/nonlayered materials along with phytosomal species derived from natural plants are highlighted with special reference to their better programmability along with minimum toxicity in biomedical applications. The current developments taking place in their upscaled productions are also included while assessing their upcoming industrial usages in diverse fields.",signatures:"Dinesh Kumar and Shamim Ahmad",downloadPdfUrl:"/chapter/pdf-download/54966",previewPdfUrl:"/chapter/pdf-preview/54966",authors:[{id:"196523",title:"Dr.",name:"Shamim",surname:"Ahmad",slug:"shamim-ahmad",fullName:"Shamim Ahmad"},{id:"205981",title:"Prof.",name:"Dinesh",surname:"Kumar",slug:"dinesh-kumar",fullName:"Dinesh Kumar"}],corrections:null},{id:"54751",title:"Molybdenum Disulfide-Based Photocatalysis:Bulk-to-Single Layer Structure and Related Photomechansim for Environmental Applications",doi:"10.5772/67825",slug:"molybdenum-disulfide-based-photocatalysis-bulk-to-single-layer-structure-and-related-photomechansim-",totalDownloads:2002,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Bulk-to-single layer molybdenum disulfide (MoS2) is widely used as a robust candidate for photodegradation of organic pollutants, hydrogen production, and CO2 reduction. This material features active edge sites and narrow band gap features, which are useful for generating reactive species in aqueous suspensions. However, the high-charge carrier recombination, photocorrosion, unstable sulfide state, and formation of Mo-S-O links during photocatalytic reactions limit its applicability. Thus, research has focused on improving the performance of MoS2 by tailoring its bulk-to-single layer structure and combining it with other semiconductor materials to improve the photocatalytic performance. Different strategies have been successfully applied to enhance the photocatalytic activity of MoS2, including tailoring of the surface morphology, formation of heterojunctions with other semiconductors, doping, and modification with excess sulfur or carbon nanostructures. This review describes the influence of starting precursors, sulfur sources, and synthetic methods to obtain heterostructured morphologies and study their impact on the photocatalytic efficiency. Finally, the relevance of crystal facets and defects in photocatalysis is outlined. Future applications of MoS2 with tailoring and tuning physicochemical properties are highlighted.",signatures:"Surya Veerendra Prabhakar Vattikuti and Chan Byon",downloadPdfUrl:"/chapter/pdf-download/54751",previewPdfUrl:"/chapter/pdf-preview/54751",authors:[{id:"196995",title:"Prof.",name:"S V Prabhakar",surname:"Vattikuti",slug:"s-v-prabhakar-vattikuti",fullName:"S V Prabhakar Vattikuti"},{id:"199682",title:"Prof.",name:"Chan",surname:"Byon",slug:"chan-byon",fullName:"Chan Byon"}],corrections:null},{id:"54449",title:"Advance in Tribology Study of Polyelectrolyte Multilayers",doi:"10.5772/67571",slug:"advance-in-tribology-study-of-polyelectrolyte-multilayers",totalDownloads:1393,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This review introduced the preparation and structural characterization of polyelectrolyte multilayers in recent years and also summarized the tribology research progress of the polyelectrolyte multilayers, including tribological properties, surface adhesion characteristics, and wear resistance properties. Statistics analysis indicated that nanoparticles‐doped polyelectrolyte multilayers present better friction and wear performance than pristine polyelectrolyte multilayers. Furthermore, the in situ growth method resulted in improved structural order of nanoparticles composite molecular deposition film. In situ nanoparticles not only reduced the molecular deposition film surface adhesion force and friction force but also significantly improved the life of wear resistance. That was due to the nanoparticles that possessed a good load‐carrying capacity and reduced the mobility of the polymer‐chain segments, which can undergo reversible shear deformation. 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\n
1. Introduction
\n
Breast cancer remains the most frequently diagnosed cancer in women worldwide. In the United States (US), the American Cancer Society estimates that in 2018, the highest frequency of cancer diagnosed and the second highest cancer-related death in women will be breast cancer, at 30 and 14%, respectively [1]. Breast cancer survival statistics have improved tremendously over the years with a decrease of 39% mortality from 1989 to 2015 [1, 2]. This is mainly due to mammogram screening resulting in early detection and intervention [3, 4]. When diagnosed at a localized stage, the 5-year survival rate is 99% [5]. However, metastasis remains the major cause of mortality in breast cancer patients. Five-year survival rate decreases dramatically according to spread of cancer, with regional and distant metastasis spreads at 85 and 27%, respectively [1]. Ten-year survival rate for stage IV metastatic breast cancer female patients is only approximately 13% [6]. These statistics indicate that metastasis is the major barrier against breast cancer eradication.
\n
Breast cancer can be categorized largely into two types, in situ and invasive breast cancer [2]. In situ represents the subset in which the cancer is still confined within the transformed origin. Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are the two main types of frequently diagnosed in situ breast cancer at 83 and 13%, respectively [2]. DCIS, as its name suggests, refers to cancer originating from the epithelial cells of the breast ducts, whereas LCIS arises from the lobules of the breast. On the other hand, majority (80%) of breast cancer will become invasive, i.e., that they will outgrow into surrounding breast tissue [2].
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The primary treatment for in situ breast cancer is surgery. This includes lumpectomy where only the tumor and surrounding tissues are removed or mastectomy in which the entire breast is removed [2]. Very often, radiation and adjuvant therapy are recommended after surgery to prevent recurrence and to eliminate breast tumor cells which might have spread [2]. Examples of adjuvant therapy are cytotoxic chemotherapy, hormone therapy, and targeted therapy [2, 3]. These will be discussed in more detail in the later sections.
\n
Although adjuvant therapy has been shown to be beneficial in preventing metastatic recurrence, the patient’s quality of life is severely affected in many cases. Side effects include fatigue, osteoporosis, increased thromboembolic events, premature menopause, weight gain, and mild memory loss [7, 8]. Although as many as 80% of patients receive adjuvant treatment, only 40% of them relapse and die from metastatic breast cancer indicating that majority of patients are over-treated and suffer unnecessary side effects [3]. In addition, only 15% of patients treated with tamoxifen after surgery will have distant recurrence, indicating that 85% of patients will be overtreated if chemotherapy is mandatory [9].
\n
One solution to overcome unnecessary treatment is through identifying patients with high and low risk of metastasis using prognostic biomarkers. Current established metastasis biomarkers are available but have poor predictive power [10]. With new concepts such as gene expression profiling and circulating tumor cells, new prognostic markers with greater accuracy could be identified. The following sections will describe established markers as well as new upcoming markers for the prediction of survival, metastasis risk, and recurrence risk for metastatic breast cancer. Current and potential use of these markers in the clinic as predictive biomarkers for treatment and as potential targets is also discussed.
\n
\n
\n
2. Established biomarkers
\n
\n
2.1. Tumor size and lymph node status
\n
The tumor-node-metastasis (TNM) staging system is commonly used to stage breast cancer progression during initial diagnosis [11]. It constitutes a manner to measure the aggressiveness of the cancer. The abbreviations represent different characteristics of the cancer. “T” represents tumor size, “N” indicates the number of lymph nodes that the cancer has spread to, and “M” conveys the presence of distant metastasis [11]. In the absence of distant metastasis (“M”), tumor size and lymph node status are established prognostic markers for likelihood of metastasis. Specifically, primary tumors that are less than 2 cm have low prognosis for developing into metastatic breast cancer. Tumor sizes of 2–5 cm and more than 5 cm have a high and very high likelihood of progressing into metastatic cancer respectively [12, 13, 14, 15]. Likewise, breast cancer patients with no detectable lymph node metastases are at low risk of distant metastasis. Patients with presence of lymph node metastasis have high risk of metastasis, and more than four lymph node metastases represent a high probability progressing to distant metastasis [12, 13, 14, 15].
\n
\n
\n
2.2. Histological grade
\n
Histological grade is the determination of how differentiated a tumor is. As the histological grade increases, the tumor appears more poorly differentiated [16]. The determination of histological grade is performed by a trained pathologist using certain characteristics of the cancer tissue section such as mitotic count, extent of tubule or gland formation, and nuclear pleomorphism [16]. Histological grade 1 tumors have low risk of metastasis, while grade 2 and 3 tumors have intermediate- and high-risk tumors [12, 14, 17]. Integrating histological grade with the aforementioned tumor size and lymph node status, several prognostic indices such as the Nottingham Prognostic Index, the Kalmar Prognostic Index, and the St. Gallen guidelines have been established and used in clinics to aid in adjuvant treatment decision [16].
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\n
\n
2.3. Angioinvasion
\n
Angioinvasion is the presence of blood vessel invasion by cancer cells. In lymph node negative patients, angioinvasion has some prognostic value in predicting metastasis [18, 19]. In particular, tumor emboli in more than three blood vessels suggest a high risk of metastasis [18, 19]. Although these tumor characteristics (tumor size, lymph node status, histological grade, and angioinvasion) represent a simple and cheap method to predict metastasis, statistics show that these prognostic factors only accurately predict metastatic outcome in 30% of patients [3, 16]. As such, better prognostic markers are required for the remaining 70%.
\n
\n
\n
2.4. Molecular subtype
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Invasive breast cancer can be divided into four main molecular subtypes based on the presence of hormone receptors (estrogen or progesterone) (HR) and human epidermal growth factor receptor 2 (HER2) [2]. The four subtypes are luminal A (HR+/HER2−), luminal B (HR+/HER2+), HER2 enriched (HR−/HER2+), and triple negative (HR−/HER2−) at frequencies of 71, 12, 5, and 12% of all invasive breast cancer, respectively [2].
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In general, luminal A and B subtypes are associated with the most favorable prognosis and least aggressive, followed by HER2 enriched and triple negative sequentially [2, 20, 21, 22, 23]. In a 6.9-year follow-up study on patients who were initially diagnosed with localized breast cancer, the frequency of distant metastasis increases progressively in the following order, luminal A (6.4%), luminal B (12.1%), HER2-enriched (19.2%), and triple negative (27.4%) [24]. Another study involving metastatic breast cancer found that luminal A exhibited the longest survival rate (34.4 months), followed by luminal B (24.8 months), HER2 enriched (19.8 months), and triple negative (8.8 months) [25]. Similarly, follow-up on patients with early stage breast cancer found that survival with distant metastasis showed similar patterns [26]. Luminal A survived the longest duration (2.2 years), followed by luminal B (1.6 years), HER2 enriched (0.7 years), and triple negative (0.5 years) [26]. These findings strongly suggest that molecular subtype correlates with metastasis rate and survival and can be used as a prognostic marker for metastasis.
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In fact, molecular subtypes are already routinely used in clinics as prognostic and predictive biomarkers for overall survival and stratification of patients to targeted therapy [2]. As a predictive biomarker, patients who are either HR+ or HER2+ benefit majorly due to targeted therapy options. The estrogen receptor (ER) in breast cancer plays an important tumor promoting role by activating downstream intracellular signals for proliferation and survival [27]. As such, patients with ER+ breast cancer are routinely treated with selective estrogen receptor modulators (SERMs) [8]. Tamoxifen is the first approved SERM to be used for the treatment of ER+ metastatic breast cancer [8]. Five-year use of tamoxifen as an adjuvant significantly reduced local and distant recurrences by 40–50% making ER status both a prognostic and predictive biomarker [28].
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Apart from using SERMs, aromatase inhibitors (AIs) are an alternative targeted treatment for ER+ breast cancer patients. These inhibitors function to block estrogen production by inhibiting the aromatase enzyme [8]. Studies have found that there is no difference in efficacy and time to distant recurrence when compared to tamoxifen treatment [29]. In addition, both tamoxifen and AI treatment are associated with increased overall survival and distant metastasis-free survival [30]. Since ovaries are the main source of estrogen, ovarian surgery, ovarian irradiation, or ovarian suppression by drugs have been shown to improve therapeutic outcomes [2, 31]. Particularly, in a clinical study, 5-year disease free survival was as high as 91.1%, when ER+ premenopausal women were treated with adjuvant ovarian suppression combined with AI treatment [31]. Additionally, use of AI with ovarian suppression significantly decreased recurrence as compared to tamoxifen with ovarian suppression [31]. These evidences strongly illustrate the use of ER status for metastatic survival prognosis and for tamoxifen or AI adjuvant therapy decision.
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Historically, HER2-enriched metastatic breast cancer is associated with high aggressiveness and has a poor prognosis [2, 32, 33, 34]. That is until the first anti-HER2 targeted therapy Trastuzumab clinical trial emerged, which showed improved clinical outcomes by including Trastuzumab into adjuvant treatment with chemotherapy for HER2-enriched metastatic breast cancer [35]. Trastuzumab is a monoclonal antibody which binds and targets the extracellular portion of the HER2 receptor protein [8]. Specifically, combining Trastuzumab with standard chemotherapy for HER2-enriched metastatic breast cancer resulted in increased time to progression, overall survival, and duration of response [35, 36].
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In recent years, many new biologics targeting HER2 have been approved for advanced metastatic HER2-enriched breast cancer [37]. Pertuzumab, another monoclonal antibody which inhibits HER2 dimerization, is approved for use in combination with trastuzumab in metastatic HER2+ breast cancer [38]. Treatment of HER2-enriched metastatic breast cancer patients using a combination of Pertuzumab, Trastuzumab, and Docetaxel resulted in a significant increase in median overall survival of 15.7 months as compared to just treating with Trastuzumab and Docetaxel [38]. Increase in progression free survival and duration of response by 6.3 months and 7.7 months, respectively, were also noted when Pertuzumab was used in combination [38].
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Another recently approved biologic for HER2+ advanced breast cancer is the antibody-drug conjugate T-DM1 [39, 40]. It involves the ingenious exploitation of Trastuzumab’s specificity to HER2+ breast cancer cells to deliver the linked cytotoxic microtubule-inhibitory drug DM1 directly to HER2+ cancer cells [39, 40]. It is particularly effective in slowing disease progression for HER2+ advanced breast cancer patients who were initially treated with first line Trastuzumab/Taxane combination [39]. Progression free survival when treated with T-DM1 was significantly longer (9.6 months) as compared to the standard second line treatment (6.4 months) [39]. Overall survival improved significantly from 25.1 to 30.9 months [39]. Additionally, patients treated with T-DM1 experienced less toxicity as compared to the standard second line treatment [39]. Taken together, it is recommended that the Docetaxel/Trastuzumab/Pertuzumab combination be used as a first line choice and T-DM1 as a second line therapy [37].
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The importance of HER2-targeted therapy for metastatic breast cancer is further emphasized by the finding that as many as 16% of initially HER2 negative breast cancer exhibits HER2 expression upon metastasis [37]. This indicates that HER2-targeted therapies could be extended to treat metastasis in this select group of patients, and it is recommended in clinics that HER2 status in metastatic cells be tested by fluorescence in situ hybridization or immunohistochemistry staining to evaluate eligibility for HER2-targeted therapy regardless of initial subtype of the primary tumor [37]. Overall, these findings highlight the importance of using HER2 status as both a prognostic and predictive biomarker in clinics for metastatic breast cancer.
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As for triple negative cancers which do not currently have their own targeted therapy, neoadjuvant anthracycline-based chemotherapy has been found to benefit this group [41]. Clinical response in triple negative was 85% as compared to luminal (47%) or HER2 positive (70%), and all subtypes had equally good prognosis after treatment [41]. However, this only applies to triple negative patients who exhibited pathologic complete response from treatment, which constitutes only 27% [41]. As such, for majority of triple negative patients who do not display complete pathologic response after chemotherapy, more studies need to be done to discover targets specific against triple negative breast cancer.
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In addition to metastasis frequency and survival, molecular subtypes could potentially predict distant metastasis tumor sites and distant relapse sites. With the exception of triple negative basal subtype, bone metastasis is the most common metastasized site among all subtypes, with the luminal subtypes displaying the highest frequency [26, 42]. Correspondingly, bone is the most frequent metastatic relapse site, with luminal subtypes exhibiting the highest frequency [43, 44]. The subtypes with the highest brain and lung metastasis rates are HER2 enriched and triple negative [26]. Among all subtypes, metastatic lung and brain relapse are highest for triple negative [43, 44]. HER2-enriched subtype has the highest liver metastasis rate, whereas triple negative has more distant lymph node metastasis as compared to other subtypes [26, 42]. The importance of determining site of metastasis is covered in the next section.
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2.5. Site of distant metastasis
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The significance of predicting site of metastasis for metastatic breast cancer patients is highlighted by the intrinsic correlation with overall survival and survival after distant recurrence. In the following order, breast cancer patients with single site brain, lung or liver, and bone metastasis have the worst to best prognosis [42, 45]. Median overall survival rates for patients with brain, lung, liver, and bone metastasis are 11 months, 30 months, 31 months, and 41 months, respectively [42]. In addition, the survival trend holds true when patients are stratified based on HR indicating that it is independent of HR status [45].
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Postmetastasis distant recurrence is also associated with the site of recurrence. In particular, first visceral (including brain) site recurrence is associated with a poorer prognosis as compared to first bone recurrence with 3-year breast cancer specific survival (BCSS) rate at 13 (visceral) and 23% (bone), respectively [46]. When compared to recurrences closer to the primary tumor, first local and first lymph node recurrences 3-year BCSS are significantly higher at 83 and 33%, respectively, indicating that metastatic site proximity to primary tumor origin site is also strongly linked to prognosis [46].
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Apart from the site of distant metastasis, the number of initial metastatic sites is also prognostic of survival. Patients with multiple metastatic sites have significantly poorer overall survival than patients with single metastatic site in both HR+ (9 months) and HR− (5 months) patients [45]. Multiple metastatic sites are also more prone to occur in HR− patients, which are in line with the poorer prognosis of HR− patients [45].
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2.6. Age of diagnosis
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Indubitably, as with many diseases, age is a major determinant of prognosis in metastatic breast cancer. Survival rate in stage IV invasive breast cancer patients significantly decreases with age [6]. Ten-year breast cancer specific survival rates for three groups of stage IV patients namely, below the age of 40 years, between 41 and 50 years, and between 51 and 70 years, drops from 15.7 to 14.9% to 11.7%, respectively [6]. Likewise, another study found similar trends in metastatic breast cancer patients, where overall survival decreases significantly with age, from 32 months (age < 50 years) to 25 months (50–69 years) to 16 months (>69 years) [47]. One plausible explanation is that younger patients are more physically fit to endure treatment than elder patients, and this is supported by a significantly higher rate of surgery and radiation therapy underwent by patients below 69 years [47].
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Age is also a determinant in the prediction of distant metastasis site. In accordance with the age-related survival trend, frequency of the deadlier lung metastasis increases significantly with age from 5.9% (age < 50 years) to 7.6% (50–69 years) to 14.2% (> 69 years), respectively [47]. Correspondingly, a significantly lower rate of the less lethal distant lymphatic metastasis is observed as age increases with rates at 7.3, 5.4, and 4.0% for patient age of less than 50 years, 50–69 years, and more than 69 years, respectively [47]. Metastasis to the brain, liver or bone is not dependent on age [47]. Interestingly, multiple metastatic sites, which are associated with poorer prognoses, occurred more frequently in younger patients (<69 years) than in older patients (>69 years) at approximately 34.9 (age < 50 years) and 36.2% (50–69 years), and 28.3% (>69 years), respectively [47]. This discrepancy could be explained by the higher rate of treatment in younger patients, suggesting that patients with multiple metastatic sites could benefit from surgery and radiation therapy [47]. Overall, age at diagnosis is a strong independent prognostic factor for metastatic breast cancer patient survival and for predicting the site of metastasis [47].
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2.7. Urokinase-type plasminogen activator (uPA) and plasminogen activator type 1 inhibitor (PAI-1)
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The urokinase-type plasminogen activator (uPA), which is a serine protease, and its inhibitor plasminogen activator type 1 inhibitor (PAI-1) are involved in the degradation of extracellular matrix, which is a crucial process in the initial stages of metastasis [48]. Although PAI-1 inhibits uPA activity, it has been found to promote tumor invasion and angiogenesis through other means [49]. As such, both uPA and PAI-1 could potentially be used as metastasis prognostic markers. Supporting this, high uPA and PAI-1 levels are correlated with lower metastasis-free survival and overall survival in breast cancer patients [50, 51, 52, 53, 54]. In addition to being a prognostic marker, both uPA and PAI-1 could be used as predictive biomarkers for adjuvant therapy. In a study, patients with high uPA and PAI-1 levels benefited significantly from adjuvant chemotherapy compared to patients with low uPA and PAI-1 levels [55]. This indicates that patients with high uPA and PAI-1 levels could be treated with chemotherapy after surgery.
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Furthermore, since uPA functions by binding to its receptor, urokinase plasminogen activator receptor (uPAR), the interaction could be exploited for metastasis targeted therapy. Indeed, one of the developments in this area is the use of an antibody to target uPAR [56, 57]. Remarkably, the antibody is shown to inhibit invasion of cancer cells and induce apoptosis, indicating its potential use for metastatic breast cancer [57].
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2.8. Gene expression profiling
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With the advent of gene expression profiling, treatment options are expected to shift toward a more personalized approach [58]. Although the idea of sequencing every cancer patient for individualized prognosis and treatment remains elusive, using multigene signatures to stratify patients into groups with different prognosis and therapeutic options has been very well established and routinely used in clinics. The first report of using high throughput methods for stratification of patients started in diffuse large B-cell lymphoma (DLBCL) patients [59, 60]. Based on their gene signatures from microarray, two subtypes of DLBCL, namely germinal center B-like DLBCL and activated B-like DLBCL, were characterized and were prognostic of overall survival [59]. In fact, molecular subtypes of breast cancer (mentioned in previous sections) were also identified using microarray-based gene expression profiling and are routinely used in clinical settings for prognosis [20, 21, 22, 23].
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Following the clinical success of using multigene signatures to identify and stratify patients with different clinical outcomes, two different gene expression profiling panels have emerged and are currently used in clinical settings. Each platform relies on different gene panel and is routinely used for predicting metastasis risk, local and distant metastasis recurrence, and for treatment decisions [61]. These are Oncotype DX and MammaPrint. Other gene expression profiling panels such as the PAM50 [62], two-gene expression ratio [63], and MapQuant DX [64] are not covered here [65].
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Oncotype DX is the most widely used multigene panel tool for the prediction of distant recurrence risk in the United States [2]. It is a reverse-transcription-polymerase-chain-reaction (RT-PCR) based assay which measures the expression of 16 cancer-related genes and 5 reference genes in tumor tissue [9]. Based on the expression level of the 21 genes, an algorithm computes a recurrence score which quantifies the probability of distant recurrence [9]. Using the recurrence score, a patient with higher score is considered high risk and would likely benefit from chemotherapy as compared to a patient with lower score who could avoid chemotherapy altogether [2, 9].
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Oncotype DX is currently utilized in clinics to predict distant recurrence for ER+, lymph node negative breast cancer patients who had prior tamoxifen treatment [9]. In the original paper, 51% of ER+, lymph node negative, tamoxifen-treated patients were classified under low-risk, and indeed, only 6.8% of this group had distant recurrence within 10 years [9]. This is in comparison with the high-risk group consisting of 27% of patients who had a 30.5% distant recurrence rate within 10 years [9]. In addition, recurrence score could also predict overall survival and relapse-free survival [9]. In support, a recent prospective validation study showed that Oncotype DX could potentially select low recurrence patients with high probability to forgo chemotherapy [66]. Five-year recurrence free rate from all sites and distant site, for patients with low recurrence score and only underwent tamoxifen treatment, were a high 98.7 and 99.3%, respectively [66]. Overall survival and invasive disease-free rates were up to 98 and 93.8%, respectively [66]. These findings show the clinical applicability of Oncotype DX to select for patients who could forgo chemotherapy and its unnecessary side effects.
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The second most commonly used multigene panel for prognosis and treatment decision is MammaPrint [65, 67]. It utilizes an oligonucleotide microarray to measure the expression of 70 genes to identify gene signatures that stratify patients into a “good” or “poor” prognosis that predicts metastasis risk in lymph node negative early breast cancer patients [68, 69, 70, 71, 72]. Sensitivity and specificity of MammaPrint are 91 and 73%, respectively [3]. Genes involved in “poor” prognosis signature include angiogenesis, cell cycle, invasion, and metastasis [69].
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In one of the earlier studies depicting the prognostic value of MammaPrint patient stratification, 10-year distant metastasis free probabilities were lower for “poor” prognosis group at 50.0% than in “good” prognosis group at 85.2% [68]. Overall survival rates were also significantly different between groups at 50.6 and 85.2% for “poor” and “good” prognosis groups correspondingly [68].
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In a follow-up study with longer term survival statistics, 25-year distant metastasis free survival was significantly lower for “poor” prognosis group (41.6%) as compared to “good” prognosis group (60.4%) [72]. Overall survival at 25 years also showed the same trend at 44.5 and 57.3% for “poor” and “good” prognosis groups, respectively [72]. These statistics show the relevance of using MammaPrint in clinical settings as a prognostic biomarker for metastasis risk and overall survival. It could also be applied as a predictive biomarker for selecting patients with “poor” prognosis for adjuvant treatment.
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Overall, the importance of multigene expression profiling tools for prognosis and treatment decision in the clinic is apparent when compared to classical clinicopathological parameters which are determined by a trained pathologist. It is found that low agreement exists among pathologists in breast cancer grading as tumor grading includes a degree of subjectivity [9]. A study comparing the different gene expression profiling tools found that although different gene sets were used among different panels, 4 out of 5 (including Oncotype DX and MammaPrint) achieved high concordance in relation to predicting outcomes [73]. As such, tools like Oncotype DX and MammaPrint stand out in this aspect.
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3. New biomarkers
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3.1. Improved gene expression profiling
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Although the first generation gene expression profiling tools, Oncotype DX, and MammaPrint have greatly advanced the prognosis of breast cancer patients for metastasis risk and distant recurrence, a major drawback is that they are unable to accurately predict late distant recurrence of more than 5 years [74]. Two newer gene expression profiling tools, EndoPredict and The Breast Cancer Index, have emerged successful in this aspect [74].
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EndoPredict is a RT-PCR-based assay, which measures the expression of eight cancer genes and three housekeeping genes to stratify patients into high- and low-risk distant recurrence groups [75, 76, 77]. A newer version of it combines the 11 gene expression with tumor size and nodal status to calculate a risk score termed the EPclin [76]. Patients with an EPclin score of less than 3.3 are classified as low-distant recurrence risk, while more than or equals to 3.3 are classified as high-distant recurrence risk [76]. The EPclin score is the best predictor of late relapse (>5 years), when compared to the earlier version of EndoPredict or to nodal status and tumor size alone [76]. Metastasis free survival for short term (less than 5) and long term (5–12 years) are also significantly different between the EPclin-stratified high- and low-risk groups, validating its applicability to predict metastasis [76]. In addition, distant recurrence free rates at 10 years in EPclin low-risk group is higher than in EPclin high-risk group, at 98.20 and 87.69%, respectively, depicting its ability to predict distant recurrence for longer time frames [76].
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The breast cancer index (BCI) is another RT-PCR-based assay, which combines two independent biomarkers namely a set of five cell cycle genes and the HOXB13 and IL17BR gene ratio to determine the recurrence probability of early stage ER+, lymph node negative breast cancer patients [63, 78, 79]. Independently, both the five gene panel and the two gene ratio are associated with distant metastasis free survival rates [78]. However, when combined, three groups could be formed, low-, intermediate-, and high-risk groups, which are significantly predictive of metastasis occurrence [78]. Ten-year distant metastasis free survival for low-, intermediate-, and high-risk groups are 98, 87, and 60%, respectively [78]. Additionally, in a study comparing the prognostic ability of BCI with Oncotype DX and another gene panel, BCI emerged as the only test capable of significantly predicting both early and late distant metastasis recurrence, whereas the other two were only able to predict early recurrence [80].
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In general, both EndoPredict and BCI seem to be superior as compared to the first-generation counterparts. This is particularly in terms of predicting longer term distant recurrence while also predictive of early recurrence [74].
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3.2. Circulating tumor cells
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An essential part of distant metastasis requires cells from the primary tumor to migrate into the bloodstream to spread throughout the body till it finds a secondary site to establish a secondary tumor [3]. As such, it is not surprising that circulating tumor cells (CTCs) in peripheral blood could be utilized as a prognostic indicator. The peripheral blood also represents an easily accessible region, which is an added advantage of using CTCs for prognosis [81].
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The history of CTCs dates back as far as the nineteenth century when researchers have just begun to study the concept of tumor cells shedding from primary tumor [82, 83]. Today, there are multiple platforms for the isolation and detection of CTCs in the peripheral blood in clinical use [84]. Termed the ”golden standard”, the CellSearch system is the only FDA-approved platform for such purpose in breast, prostate, and colorectal cancer [84]. The problems associated with detection of CTCs are its rare amount in the peripheral blood and the absence of a universal surface marker for different cancer cell types [84]. The CellSearch system overcomes these sensitivity and specificity issues through the use of an antibody to capture CTCs and poststaining the captured CTCs for identification [84]. Specifically, an avidin-biotin anti-EpCAM antibody complex is used to bind CTCs followed by a magnetic capture to isolate CTCs [84, 85, 86]. Following which, the captured pool of cells is stained with DAPI and cytokeratins CK8, CK18, and CK19 to select for nucleated and epithelial cells, respectively [84, 85, 86]. Additionally, to differentiate from circulating white blood cells, anti-CD45 is used to further isolate CTCs [84, 85, 86]. Other systems using size [87, 88, 89], density [90], and microfluidic [91] characteristics of CTCs for isolation exist but are not covered in this chapter [81].
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Enumerating CTCs in peripheral blood holds immense potential in clinics. The early paper using the CellSearch system to study progression of metastatic breast cancer provided many useful information [86]. The first thing noted was that CTCs were only present in metastatic breast cancer patients. Two or more CTCs per 7.5 mL of blood were present in metastatic breast cancer patients, while CTCs were rare (less than or equal to 1) in both healthy and benign breast cancer women [86]. Next, CTCs were independent prognostic marker of overall survival and progression-free survival [86]. After new treatment, patients with high level of CTCs (CTCs ≥5) had a significantly lower median progression-free survival and overall survival than patients with low level of CTCs (CTCs <5), at 2.1 months versus 7.0 months for progression-free survival and 8.2 months versus >18 months for overall survival, respectively [86]. Additionally, the prognostic value of CTCs for overall survival and progression-free survival is also validated in two other studies, wherein one of it is a prospective study with metastatic breast cancer patients who were not treated previously [92, 93].
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In terms of treatment, median progression-free and overall survival differed significantly between patients with CTCs ≥5 before treatment and CTCs <5 after treatment (1st group) and patients with decrease in CTCs after treatment but still ≥5 after treatment (2nd group) [86]. Median overall survival and progression free survival for 1st group are 7.6 months and 14.6 months, and for the 2nd group, 2.1 months and 9.2 months, respectively [86]. This suggests that CTCs could potentially be used to measure treatment efficiency, although the authors cautioned against this interpretation [86]. Following this, two other studies have also observed CTCs as a predictor of therapy efficiency for metastatic breast cancer [94, 95].
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3.3. TIP60
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Tat-interactive protein 60 kDa (TIP60) is a haploinsufficient tumor suppressor involved in both early and late stage breast cancer [96, 97, 98, 99]. In particular for late stage progression, TIP60 is known to regulate epithelial to mesenchymal transition, an important pathway for cellular metastasis [96, 97]. Both in vitro and mouse models have shown that loss of TIP60 results in increased metastatic breast cancer cell migration and invasion, indicating that therapies to increase TIP60 in breast cancer could be a potential therapeutic approach for metastatic breast cancer [96, 97]. Additionally, the microRNA miR-22 inhibits the expression of TIP60, thereby making it a promoter of metastasis and a potential therapeutic target for metastatic breast cancer [97]. More importantly, both miR-22 and TIP60 are prognostic of overall survival and metastasis free survival [96, 97]. As such, both miR-22 and TIP60 expression levels would be invaluable tools in clinics to predict metastatic probability and prognosis of overall survival.
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4. Future directions/conclusions
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Using only clinicopathological characteristics for assessing metastasis risk, the St Gallen criteria and National Institutes of Health criteria each classified a low 15 and 7% of lymph node negative breast cancer as low metastasis risk, respectively [3, 68]. However, after 10 years, up to 25% of the low-risk group developed distant recurrence [3, 68]. In addition, only slightly less than half (45%) of high-risk patients developed metastasis, indicating that the remaining 55% of “high-risk” patients had adjuvant treatment and tolerated its unnecessary effects [3, 68]. In contrast, using MammaPrint in the same cohort, a high 60% of total patients were categorized as low risk, out of which only 13% of these low-risk patients developed metastasis after 10 years, showing that as many as 52.2% of overall patients were safely spared from adjuvant therapy, as compared to 5.25 to 11.25% of overall patients stratified using clinicopathological characteristics [3, 68]. These findings clearly delineate the superiority of gene expression panels for prognosis as compared to just clinicopathological characteristics.
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A more beneficial solution would be to combine both clinicopathological markers and multigene expression profiling to have an additive or synergistic effect in prediction for the betterment of patient prognosis and prediction of treatment outcomes. An example is the multigene expression EPclin risk score which combines its predecessor, the EndoPredict with tumor size, and nodal status to better predict distant metastatic recurrence as compared to if the markers were used individually [76].
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However, a significant problem still exists in the field of prognosis for metastatic breast cancer. Many of the gene expression profiling tools, such as Oncotype DX and BCI, are suitable only for prediction of distant metastasis recurrence in ER+, lymph node negative metastatic breast cancers [74, 100]. As such, it represents a gap in the identification of prognostic markers for other subtypes. For this, newer markers like the detection of CTCs which does not discriminate between subtypes may be used. TIP60 which also does not discriminate between subtypes in risk-free survival rates [98] may be explored and could potential be used as a prognostic biomarker for breast cancer metastasis. Other upcoming biomarkers which are not discussed here such as blood-based biomarkers [101] and long noncoding RNA [102] also holds immense potential as prognostic markers in breast cancer metastasis.
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Overall, the field of metastatic breast cancer prognosis has come a long way, beginning with clinicopathological markers to molecular subtypes to multigene expression profiling and eventually CTCs. Continuing on, it is likely that future direction for this field will entail combining existing biomarkers together or with newly identified biomarkers, leading to tremendous improvements in metastatic breast cancer prognosis and in predicting metastasis.
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\n\n',keywords:"metastasis, prognostic biomarker, metastatic breast cancer, relapse, recurrence, distant-free metastasis survival, overall survival",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/63870.pdf",chapterXML:"https://mts.intechopen.com/source/xml/63870.xml",downloadPdfUrl:"/chapter/pdf-download/63870",previewPdfUrl:"/chapter/pdf-preview/63870",totalDownloads:1171,totalViews:391,totalCrossrefCites:0,totalDimensionsCites:1,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:59,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"February 23rd 2018",dateReviewed:"July 29th 2018",datePrePublished:"November 5th 2018",datePublished:"December 5th 2018",dateFinished:"October 2nd 2018",readingETA:"0",abstract:"Breast cancer treatment has improved rapidly through the years, starting from surgery, to hormonal therapy, to targeted therapy. Despite this, tumor metastasis remains the highest cause of breast cancer–related death. The current regime to deter metastasis is through adjuvant therapy, but such therapy frequently yields undesirable side effects. As such, prognostic markers for metastasis are important to stratify patients for adjuvant therapy so as to ameliorate the standard of living of patients with low metastatic potential. So far, only a few well-characterized prognostic biomarkers for metastasis are used in clinics. This chapter will cover both established and novel prognostic biomarkers for breast cancer metastasis and metastatic breast cancer prognosis. The potential of using these biomarkers as predictive biomarkers or new targeted therapy will also be discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/63870",risUrl:"/chapter/ris/63870",book:{id:"7271",slug:"cancer-metastasis"},signatures:"Kwok Kin Lee, Wee Joo Chng and Sudhakar Jha",authors:[{id:"190426",title:"Dr.",name:"Sudhakar",middleName:null,surname:"Jha",fullName:"Sudhakar Jha",slug:"sudhakar-jha",email:"csi_singapore@nus.edu.sg",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"National University of Singapore",institutionURL:null,country:{name:"Singapore"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Established biomarkers",level:"1"},{id:"sec_2_2",title:"2.1. Tumor size and lymph node status",level:"2"},{id:"sec_3_2",title:"2.2. Histological grade",level:"2"},{id:"sec_4_2",title:"2.3. Angioinvasion",level:"2"},{id:"sec_5_2",title:"2.4. Molecular subtype",level:"2"},{id:"sec_6_2",title:"2.5. Site of distant metastasis",level:"2"},{id:"sec_7_2",title:"2.6. Age of diagnosis",level:"2"},{id:"sec_8_2",title:"2.7. Urokinase-type plasminogen activator (uPA) and plasminogen activator type 1 inhibitor (PAI-1)",level:"2"},{id:"sec_9_2",title:"2.8. Gene expression profiling",level:"2"},{id:"sec_11",title:"3. New biomarkers",level:"1"},{id:"sec_11_2",title:"3.1. Improved gene expression profiling",level:"2"},{id:"sec_12_2",title:"3.2. Circulating tumor cells",level:"2"},{id:"sec_13_2",title:"3.3. TIP60",level:"2"},{id:"sec_15",title:"4. Future directions/conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018;68(1):7-30\n'},{id:"B2",body:'Breast Cancer Facts & Figures 2017-2018. Atlanta: American Cancer Society, Inc.; 2017\n'},{id:"B3",body:'Weigelt B, Peterse JL, van \'t Veer LJ. Breast cancer metastasis: Markers and models. 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Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clinical Cancer Research. 2006;12(14 Pt 1):4218-4224\n'},{id:"B95",body:'Budd GT et al. Circulating tumor cells versus imaging–predicting overall survival in metastatic breast cancer. Clinical Cancer Research. 2006;12(21):6403-6409\n'},{id:"B96",body:'Gorrini C et al. Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature. 2007;448(7157):1063-1067\n'},{id:"B97",body:'Pandey AK et al. TIP60-miR-22 axis as a prognostic marker of breast cancer progression. Oncotarget. 2015;6(38):41290-41306\n'},{id:"B98",body:'Bassi C et al. The acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair. Cell Death and Differentiation. 2016;23(7):1198-1208\n'},{id:"B99",body:'Zhang Y et al. TIP60 inhibits metastasis by ablating DNMT1-SNAIL2-driven epithelial-mesenchymal transition program. Journal of Molecular Cell Biology. 2016;8(5):384-399\n'},{id:"B100",body:'Gong G et al. A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+/HER2− early breast cancer. Scientific Reports. 2017;7:45554\n'},{id:"B101",body:'Berghuis AM et al. Detecting blood-based biomarkers in metastatic breast cancer: A systematic review of their current status and clinical utility. International Journal of Molecular Sciences. 2017;18(2):363\n'},{id:"B102",body:'Zhang K et al. Long non-coding RNAs as novel biomarkers for breast cancer invasion and metastasis. Oncology Letters. 2017;14(2):1895-1904\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Kwok Kin Lee",address:null,affiliation:'
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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1. Introduction
Kisspeptins are a family of neuropeptides with diverse functions in humans. They are cleaved from a precursor peptide encoded by the KISS-1 gene, which was originally identified in melanoma cells as a metastasis suppressor gene [1]. Expression of KISS-1 has subsequently been identified in many other cell lines, including those of the placenta, ovaries, and testes [2]. It is now known that kisspeptin plays a critical role in reproduction and fertility [3]. Kisspeptin is believed to regulate the secretion of gonadotropin-releasing hormone (GnRH) by integrating central and peripheral signals [4]. During the menstrual cycle, gonadal sex steroid concentrations impact the secretion of GnRH from neurons located in the hypothalamus. It is hypothesized that kisspeptin mediates this hypothalamic feedback because 1) GnRH neurons lack gonadal sex steroid receptors but some express kisspeptin receptors [5, 6, 7] and 2) kisspeptin neurons express sex steroid receptors [8, 9]. This review will focus on the role of kisspeptins throughout the menstrual cycle and their potential use as a biomarker of viable pregnancy.
2. Kisspeptin in the follicular phase and periovulation
Kisspeptin neurons are primarily located in the preoptic area and hypothalamic arcuate nucleus and function as upstream regulators of GnRH neurons [10]. In both of these anatomic locations, serum estrogen and progesterone concentrations have been shown to regulate kisspeptin-mediated GnRH secretion [11]. During the early follicular phase of the menstrual cycle, estrogen exerts negative feedback on GnRH stimulation of luteinizing hormone (LH) secretion. As the follicular phase progresses, rising estrogen levels result in pulsatile secretion of GnRH, which then stimulates the pulsatile release of follicle-stimulating hormone (FSH) and LH [10]. This pulsatile secretion pattern is likely mediated by kisspeptin through regulation of GnRH neurons. Involvement of kisspeptin in this regulatory pathway is suspected because GnRH neurons lack estrogen and progesterone receptors, and thus cannot directly respond to serum sex steroid concentrations [12, 13]. The absence of a direct biochemical connection between the gonads and hypothalamus suggests the presence of an intermediary signal. This “missing link” is thought to be kisspeptin neurons, which express estrogen receptors and secrete a ligand that can bind to GnRH [12].
During the early follicular phase when follicles are underdeveloped, kisspeptin levels are low [4, 14]. A study by Zhai et al. showed that kisspeptin levels sharply increase when the dominant follicle reaches 1.2 cm in diameter [14]. Kisspeptin levels during the periovulatory period are then high [4, 14, 15], and may have potential in predicting development of the dominant ovarian follicle [14]. A study by Dhillo et al. demonstrated that administration of exogenous kisspeptin to healthy women results in increased gonadotropin secretion; this response is most potent during the preovulatory phase [16].
A study by Meczekalski et al. demonstrated that kisspeptin and LH are co-secreted (i.e. each kisspeptin pulse is accompanied by a pituitary LH pulse in response to a hypothalamic GnRH pulse) [11]. Another study demonstrated that blockade of the kisspeptin receptor (GPR54) resulted in blockade of pulsatile LH secretion [17]. There is also topographical evidence of the connection between GnRH and kisspeptin neurons – in several species, it has been shown that GnRH neuronal axons extend from the arcuate nucleus, where kisspeptin neurons are located, to the median eminence, where GnRH is secreted [12]. Human studies have not reproducibly demonstrated this neuroanatomy for all GnRH neurons, which may suggest that kisspeptin neuronal connections in humans are more complex [11, 18].
3. Kisspeptin in ovulation
At mid-cycle, estrogen secreted by the preovulatory follicle eventually triggers GnRH neurons to transition from pulsatile GnRH secretion to sustained secretion. The mechanism by which estrogen transforms from a negative to positive feedback signal on the hypothalamus still remains unclear. Estrogen binds to the ERα receptor on kisspeptin neurons in the arcuate nucleus, inhibiting kisspeptin secretion and subsequent GnRH secretion [15]. In the anteroventral periventricular nucleus, estrogen binds kisspeptin ERα receptors and exerts positive feedback, which ultimately initiates the LH surge associated with ovulation.
The sustained secretion of high concentrations of GnRH (GnRH surge) occurs for over 24 hours and triggers the pituitary gland to secrete high levels of LH (LH surge) [19]. The LH surge is what ultimately triggers ovulation [7]. The LH surge is also the target of at-home ovulation predictor kits [14]. This cascade of hormone surges is thought to be primarily regulated by kisspeptin; in fact, kisspeptin is the most potent activator of GnRH neurons discovered to date [5]. It is suspected that rising estrogen levels during the follicular phase stimulate kisspeptin neurons, which then activate GnRH neurons to initiate the GnRH surge [7]. In contrast, administration of a monoclonal antibody that blocks kisspeptin has been shown to prevent ovulation in rat models [20].
It is postulated that kisspeptin could be useful as a biomarker of the periovulatory/ovulatory phase [14]. This would be clinically useful because kisspeptin surges prior to LH and therefore could predict the time of ovulation before it happens (rather than as it happens). The target of most ovulation prediction kits is LH, which surges at the time of ovulation. According to Zhai et al., the probability of ovulation is increased when kisspeptin surges on the 11th day and LH surges on the 14th day [14]. In comparison, a study by Goto et al. showed that administration of a kisspeptin antagonist resulted in shrinkage of ovarian follicles and delayed ovulation [21].
4. Kisspeptin in the luteal phase and implantation
Kisspeptin is not only expressed in the central nervous system – it also performs peripheral functions. Expression of kisspeptin and its receptor KISS-1 has been demonstrated in the human ovary, fallopian tube, uterus, and placenta [22]. It is thought that kisspeptin primarily functions in the hypothalamus, but also interacts between the signaling pathways of the central and peripheral reproductive systems [23]. In fact, several studies have supported the idea that kisspeptin exerts direct effects on ovarian tissue via ovarian kisspeptin receptors [24, 25, 26].
A number of studies have demonstrated that kisspeptin is expressed at the maternal-fetal interface of many species, including humans [27]. In the human uterus, kisspeptin is expressed in the endometrial epithelial and stromal cells, but not in the myometrium [28]. In the early placenta, kisspeptin is initially produced by villous cytotrophoblast cells, then villous syncytiotrophoblast cells and the placental bed [29, 30]. As pregnancy progresses, placental production of kisspeptin declines [31, 32].
Kisspeptin expression in the endometrium is absent during the proliferative and early secretory phases but becomes abundant during the late secretory phase [27, 33]. This indicates a potential role of kisspeptin in the preparation of endometrial tissue for implantation. Kisspeptin knockout mice exhibit thin, weak uteri with almost no endometrial glands, suggesting kisspeptin is an important regulator of normal endometrial development [34]. Kisspeptin may also act as a mediator that facilitates implantation of the growing embryo to the uterine wall. It has been shown that exogenous kisspeptin administration strengthens adhesion of kisspeptin-expressing trophoblast cells to collagen present in uterine tissue [34]. Immediately after implantation, kisspeptin levels are known to rise; this suggests involvement of kisspeptin during the decidualization process [35]. A study by Wu et al. demonstrated a dose-dependent relationship between kisspeptin expression and inhibition of cell invasion/migration in human decidualized endometrial cells [29]. In contrast, a kisspeptin antagonist called kisspeptin 234 stimulates the process of decidual invasion and migration [29]. Similarly, when small interfering RNAs that antagonize kisspeptin are introduced, stromal decidualization is impaired [35]. In a study by Calder et al., ablation of the KISS-1 gene and subsequent absence of kisspeptin expression resulted in infertile mice [36]. Even in mice that received rescue gonadotropins and estradiol, which restored ovulation, the mice embryos could not implant in the mice that lacked KISS-1. These embryos were, however, able to implant in wildtype mice [36].
Kisspeptin was originally identified as a suppressor of cancer metastasis; its function in the regulation of cellular proliferation and growth is also integral to the process of placentation. The early placenta expresses high levels of kisspeptin, perhaps to tame the invasive and migratory capability of trophoblasts [32]. Kisspeptin decreases the activity of collagenases, matrix metalloproteinases, and vascular endothelial growth factor, which are all signaling proteins involved in trophoblast proliferation [31, 37]. Kisspeptin also supports the adhesion of extravillous trophoblasts to the endometrium, which inhibits migration [38]. This careful balance between invasion and the prevention of invasion is essential to the placentation process as well as the appropriate remodeling of the maternal uterine wall [34]. As the placenta develops throughout pregnancy, it exhibits a pattern of kisspeptin expression that follows a circadian rhythm [39]. The term placenta demonstrates kisspeptin surges at 0400 and 1200 daily. This rhythm correlates with circadian expression of other proteins involved in placental physiology, including TNFα, melatonin, and oxytocin [39].
5. Kisspeptin in pregnancy
Maternal kisspeptin levels rise dramatically during pregnancy, then return to normal within 15 days of delivery [28]. Unlike β-hCG, kisspeptin levels rise steadily and do not plateau [40]. It is thought that the primary source of maternal kisspeptin is placental tissue [27], and that maternal kisspeptin levels reflect the volume of viable placental tissue [41]. Kisspeptin may be useful as a biomarker of pregnancy due to its association with placental invasion and apoptosis [42]. It also has potential utility as a biomarker of miscarriage.
Spontaneous abortion (SAB) is a common experience, seen in 10–20% of clinically recognized pregnancies [43]. A study by Jayasena et al. showed that maternal plasma kisspeptin is significantly lower in women with early pregnancies who later develop SAB compared to women who have a viable intrauterine pregnancy (IUP) [44]. Maternal kisspeptin levels also had higher diagnostic performance than β-hCG in detecting SAB [44]. Wu et al. demonstrated that women with recurrent SAB have decreased decidual kisspeptin expression compared to women with IUP [45]. Kavvasoglu also showed decreased maternal kisspeptin levels in women with SAB compared to healthy IUPs [46]. Sullivan et al. validated a serum kisspeptin-54 assay as well as confirmed that maternal kisspeptin levels are positively correlated with fetal gestational age and pregnancy viability [40].
There is currently no established clinical test for early miscarriage; diagnosis relies on serial β-hCG measurements and correlation with ultrasound. This requires multiple maternal encounters with the healthcare system, a prolonged timeframe, and can involve considerable distress of the patient and partner. Jayasena et al. describes the current diagnostic pathway for establishing fetal viability as having limited clinical utility due to delay and a high degree of uncertainty [44]. Thus, there is interest in establishing a more accurate and streamlined diagnostic marker of viable IUP vs. SAB.
Kisspeptin has been shown to be massively downregulated in the case of ectopic pregnancy [47]. Ectopic pregnancy occurs when a fertilized ovum implants and develops outside the uterine cavity. Similarly to SAB, ectopic pregnancy is currently diagnosed by serial β-hCG measurements in correlation with ultrasound. Definitive diagnosis may require direct visualization via laparoscopy [48]. A study by Romero-Ruiz et al. explored the roll of kisspeptin in individuals with ectopic pregnancy. They found that maternal circulating kisspeptins gradually increased during the first trimester of pregnancy in healthy controls. However, in those with ectopic pregnancy, kisspeptin levels were suppressed. The study correlated these results to levels of microRNAs (miRNA) (small noncoding RNAs that can modulate gene and protein expression). In particular, miR-324-3p is known to inhibit kisspeptin function. Romero-Ruiz et al. found that in ectopic pregnancies, miR-324-3p was significantly increased in placental tissue (though maternal circulating levels were low). This finding suggests defective export of the miRNA from its embryonic/placental source in ectopic pregnancy, which may further contribute to the local suppression of kisspeptin. The authors suggested that correlation of maternal miR-324-3p with kisspeptin and β-hCG levels could provide a better modality for timely diagnosis of ectopic pregnancy, especially considering the stability of miRNA in maternal serum [46].
Kisspeptin could also have diagnostic utility in identifying women at risk of preeclampsia. A study by Qaio showed that the placentas of term preeclamptic pregnancies express significantly lower kisspeptin levels compared to healthy pregnancies [49]. These findings were reproduced by Farina et al., which demonstrated lower KISS-1 expression in preeclamptic patients compared to healthy pregnant patients [50]. The study also suggested KISS-1 cell-free mRNA has potential to serve as a predictive biomarker of preeclampsia [50]. Matjila et al. investigated the relationship between maternal kisspeptin levels and placental kisspeptin expression in preeclamptic pregnancies – they found that preeclamptic placentas demonstrated high kisspeptin expression but low maternal kisspeptin levels [30]. It is speculated that elevated kisspeptin expression in diseased placentas may inhibit trophoblast invasion and contribute to the development of preeclampsia [30, 34]. Kisspeptin therefore has potential to offer predictive information about the risk of preeclampsia.
6. Kisspeptin in in vitro fertilization
Because of its apparent role in reproduction and fertility, there is interest in the use of kisspeptin as a tool to aid in assisted reproductive technology. Exogenous kisspeptin has been used to trigger oocyte maturation in women undergoing in vitro fertilization (IVF) with very low rates of ovarian hyperstimulation syndrome (OHSS) [41, 51]. Oocyte maturation is the process during which an oocyte transitions from metaphase I to metaphase II; at this time, it is capable of becoming fertilized [51]. Jayasena et al. demonstrated that a single kisspeptin bolus was capable of producing an LH surge that induced oocyte maturation in women undergoing IVF [41]. This was an important study, as it was the first to label kisspeptin as an effective maturation trigger. 92% of the study participants who received kisspeptin had at least one embryo available for transfer [41]. A study by Owens et al. then demonstrated that when kisspeptin is administered as an oocyte trigger during IVF cycles, granulosa cell gene expression is altered in such a way that increases FSH and LH receptor expression [52]. This altered gene expression is postulated to augment downstream signaling, resulting in increased sex steroid synthesis [52]. In fact, kisspeptin is currently considered to be the most potent stimulator of GnRH secretion [53, 54].
OHSS is considered a serious adverse event during IVF treatment and is typically related to the use of hCG as a trigger for oocyte maturation. This syndrome is characterized by extreme vascular permeability, which can result in pleural effusions, ascites, renal impairment, and in severe cases, death [51]. This vascular permeability is a downstream effect of hCG-mediated release of vascular endothelial growth factor (VEGF) from the ovary [55]. Kisspeptin has been shown to directly inhibit ovarian VEGF production, which significantly decreases the risk of OHSS when used as a trigger for ovulation induction [56]. Moreover, kisspeptin acts to release endogenous GnRH, which triggers an LH surge dependent on the individual’s own GnRH reserves, and is unlikely to excessively or pathologically stimulate the ovaries [57].
7. Kisspeptin in puberty
In addition to its role in pregnancy and fertility, kisspeptin is also implicated in sexual development in humans. The target of the kisspeptin molecule is G-protein coupled receptor 54 (GPR54) [58]. A study by de Roux et al. demonstrated that humans with a defect in the GPR54 gene exhibit isolated hypogonadotrophic hypogonadism, suggesting that kisspeptin is an important regulator of gonadal axis development [59]. This finding was then reproduced by an independent study by Seminara et al., who evaluated a large family with idiopathic hypogonadotrophic hypogonadism and generated GPR54 knockout mice, which failed to undergo adult sexual development and had low serum gonadotropin levels [47]. In contrast, exogenous kisspeptin administration in prepubertal rodents and primates has been shown to induce precocious puberty [60]. Furthermore, Teles et al. describes a female with an activating mutation of GPR54 who exhibited idiopathic central precocious puberty [61].
Kisspeptin is thought to be imperative in all phases of sexual development, beginning in the embryonic phase. During the second trimester of pregnancy, GnRH secretion first occurs and is required for normal testicular development [62]. Aberrant gonadal pathways can result in male infants born with microphallus or cryptorchidism [63]. Kisspeptin is suspected to be crucial in the stimulation of GnRH secretion in both infancy and puberty [62].
8. Conclusion
Kisspeptins have a multitude of regulatory neuroendocrine functions that span the sexual life cycle. Though its mechanisms are not entirely characterized, there is strong evidence supporting its involvement in puberty and development, ovulation, implantation, and pregnancy. Because of their role in these reproductive processes, kisspeptins have potential to be useful as biomarkers in a variety of contexts, such as ovulation prediction and diagnosis of viable IUP. Kisspeptins may also be useful in the advancement of assisted reproductive technology. Continued exploration of kisspeptin function will help to develop and standardize practices that harness its diagnostic and therapeutic potential.
\n',keywords:"kisspeptin, reproduction, fertility, placentation, biomarker",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/77030.pdf",chapterXML:"https://mts.intechopen.com/source/xml/77030.xml",downloadPdfUrl:"/chapter/pdf-download/77030",previewPdfUrl:"/chapter/pdf-preview/77030",totalDownloads:208,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 24th 2021",dateReviewed:"May 18th 2021",datePrePublished:"June 7th 2021",datePublished:"November 17th 2021",dateFinished:"June 3rd 2021",readingETA:"0",abstract:"Kisspeptins are a group of neuropeptides with regulatory functions related to puberty, fertility, and reproduction. They are primarily produced by hypothalamic nuclei and are thought to regulate the activity of neurons that produce gonadotropin-releasing hormone. They are also expressed by placental syncytiotrophoblasts in developing pregnancies and are likely involved in the processes of trophoblast invasion and placentation. Similarly to beta-hCG, kisspeptins are found in maternal plasma during the first trimester of pregnancy and increase proportionately with gestational age. Because of their role in implantation, there is currently interest in the use of kisspeptins as minimally invasive biomarkers. It is suspected that maternal kisspeptin levels have diagnostic potential in identifying viable early pregnancies.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/77030",risUrl:"/chapter/ris/77030",signatures:"Erin Ahart, Elaine Phillips, Michael Wolfe and Courtney Marsh",book:{id:"10875",type:"book",title:"Infertility and Assisted Reproduction",subtitle:null,fullTitle:"Infertility and Assisted Reproduction",slug:"infertility-and-assisted-reproduction",publishedDate:"November 17th 2021",bookSignature:"Wei-Hua Wang",coverURL:"https://cdn.intechopen.com/books/images_new/10875.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-825-2",printIsbn:"978-1-83962-824-5",pdfIsbn:"978-1-83962-829-0",isAvailableForWebshopOrdering:!0,editors:[{id:"336024",title:"Dr.",name:"Wei-Hua",middleName:null,surname:"Wang",slug:"wei-hua-wang",fullName:"Wei-Hua Wang"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",fullName:"Courtney Marsh",slug:"courtney-marsh",email:"cmarsh2@kumc.edu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255491/images/system/255491.jpg",institution:{name:"University of Kansas Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"350310",title:"Dr.",name:"Erin",middleName:null,surname:"Ahart",fullName:"Erin Ahart",slug:"erin-ahart",email:"eahart@kumc.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Kansas Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"352233",title:"Dr.",name:"Michael",middleName:null,surname:"Wolfe",fullName:"Michael Wolfe",slug:"michael-wolfe",email:"mwolfe2@kumc.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Kansas Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"352234",title:"Ms.",name:"Elaine",middleName:null,surname:"Phillips",fullName:"Elaine Phillips",slug:"elaine-phillips",email:"ephillips8@kumc.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Kansas Medical Center",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Kisspeptin in the follicular phase and periovulation",level:"1"},{id:"sec_3",title:"3. Kisspeptin in ovulation",level:"1"},{id:"sec_4",title:"4. Kisspeptin in the luteal phase and implantation",level:"1"},{id:"sec_5",title:"5. Kisspeptin in pregnancy",level:"1"},{id:"sec_6",title:"6. Kisspeptin in in vitro fertilization",level:"1"},{id:"sec_7",title:"7. Kisspeptin in puberty",level:"1"},{id:"sec_8",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631-34636.'},{id:"B2",body:'Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S, et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. 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The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function. Hum Reprod. 2018;33(2):292-302.'},{id:"B53",body:'Roa J, Castellano JM, Navarro VM, Handelsman DJ, Pinilla L, Tena-Sempere M. Kisspeptins and the control of gonadotropin secretion in male and female rodents. Peptides. 2009;30(1):57-66.'},{id:"B54",body:'Quaas AM, Legro RS. Pharmacology of medications used for ovarian stimulation. Best Pract Res Clin Endocrinol Metab. 2019;33(1):21-33.'},{id:"B55",body:'Hunjan T, Abbara A. Clinical Translational Studies of Kisspeptin and Neurokinin B. Semin Reprod Med. 2019;37(3):119-124.'},{id:"B56",body:'Zhai J, Liu J, Zhao S, Zhao H, Chen ZJ, Du Y, et al. Kisspeptin-10 inhibits OHSS by suppressing VEGF secretion. Reproduction. 2017;154(4):355-362.'},{id:"B57",body:'Abbara A, Jayasena CN, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Nijher GM, et al. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy. J Clin Endocrinol Metab. 2015;100(9):3322-3331.'},{id:"B58",body:'Franssen D, Ioannou YS, Alvarez-real A, Gerard A, Mueller JK, Heger S, et al. Pubertal timing after neonatal diethylstilbestrol exposure in female rats: Neuroendocrine vs peripheral effects and additive role of prenatal food restriction. Reproductive Toxicology. 2014;44:63-72.'},{id:"B59",body:'de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100(19):10972-10976.'},{id:"B60",body:'Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Mayen A, Barreiro ML, et al. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol. 2004;561(Pt 2):379-386.'},{id:"B61",body:'Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, et al. A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med. 2008;358(7):709-715.'},{id:"B62",body:'Chan YM, Broder-Fingert S, Seminara SB. Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men. Peptides. 2009;30(1):42-48.'},{id:"B63",body:'Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. 2005;90(5):3122-3127.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Erin Ahart",address:"eahart@kumc.edu",affiliation:'
University of Kansas Medical Center, Kansas City, KS, USA
University of Kansas Medical Center, Kansas City, KS, USA
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Though wound healing is a multiphase process and involved multiple biomarkers that acts in stepwise manner, pathophysiology diabetic foot ulcers is still not much clear and need standardization. Matrix metalloproteinases (MMPs) are often linked with non-healing characteristic of diabetic foot ulcers. They play vital roles in various phases of healing process. Major functions are removal of damaged extracellular matrix in inflammatory phase, breakdown of capillary basement membrane prior to angiogenesis and facilitation in fibroblast migration during proliferation phase. For efficient healing, these enzymes are needed in certain amount only. Imbalance of these enzymes leads to excessive degradation which has been linked with the non-healing nature of diabetic ulcers. This chapter will shed light on the role of MMP’s in various phases of wound healing and the inhibitors of MMP’s from natural as well as synthetic origin. 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IntechOpen has always supported new and evolving ideas in scholarly publishing. We understand the community we serve, but to provide an even better service for our IntechOpen Authors and Academic Editors, we have partnered with leading companies and associations in the scientific field and beyond.
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ALPSP
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The Association of Learned and Professional Society Publishers (ALPSP) is the largest association of scholarly and professional publishers in the world. Its mission is to connect, inform, develop and represent the international scholarly and professional publishing community. IntechOpen has been a member of ALPSP since 2016 and has consequently stayed informed about industry trends through connecting with peers and developing jointly.
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OASPA
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The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
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STM
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The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
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COPE
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The Committee on Publication Ethics (COPE) provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of misconduct in research and publication. IntechOpen has been a member of COPE since 2013 and adheres to the COPE Code of Conduct and Best Practice Guidelines, ensuring that we maintain the highest ethical standards.
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Creative Commons
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Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. IntechOpen uses the CC BY 3.0 license for chapters, meaning Authors retain copyright and their work can be reused and adapted as long as the source is properly cited and Authors are acknowledged.
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Crossref
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Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
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Altmetric and Dimensions from Digital Science
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Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
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CLOCKSS
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CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
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Counter
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COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
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DORA
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DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
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iThenticate
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iThenticate is the leading provider of professional plagiarism detection and prevention technology and is used worldwide by scholarly publishers and research institutions to ensure the originality of written work before publication. IntechOpen uses the iThenticate plagiarism software to ensure content originality and the research integrity of our published work.
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Enago
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IntechOpen collaborates with Enago, through its sister brand, Ulatus, one of the world’s leading providers of book translation services. Their services are designed to convey the essence of your work to readers from across the globe in the language they understand.
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IntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit https://www.enago.com/intech
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Straive
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Straive is the market leader in technology-driven solutions for the extraction, enrichment and transformation of content assets. IntechOpen publishing services are designed to meet the unique needs of Authors. As part of our commitment to that objective, we have an ongoing partnership agreement for production solutions.
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Amazon
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Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
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DHL
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IntechOpen has partnered with DHL since 2011 to ensure the fastest delivery of Print on Demand books.
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United Nations Sustainable Development Goals Publishers Compact
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The Compact is designed to inspire action among publishers. Launched in collaboration with the International Publishers Association, the Compact aims to accelerate progress to achieve the Sustainable Development Goals (SDGs) by 2030. Signatories aspire to develop sustainable practices and act as champions of the SDGs during the Decade of Action (2020-2030), publishing books and journals that will help inform, develop, and inspire action in that direction. Learn more here
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River Valley Technology
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River Valley Technology is the world’s first XML-based publishing solution from submission to peer review to production and to final hosting, giving full control to publishers, with full transparency of data.
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Figshare
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Figshare is an online open access repository where researchers can preserve and share their research outputs, including figures, datasets, images, and videos. It is free to upload content and free to access, in adherence to the principle of open data.
The Association of Learned and Professional Society Publishers (ALPSP) is the largest association of scholarly and professional publishers in the world. Its mission is to connect, inform, develop and represent the international scholarly and professional publishing community. IntechOpen has been a member of ALPSP since 2016 and has consequently stayed informed about industry trends through connecting with peers and developing jointly.
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OASPA
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\n\t
The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
\n
\n\n
STM
\n\n
\n\t
The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
\n
\n\n
COPE
\n\n
\n\t
The Committee on Publication Ethics (COPE) provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of misconduct in research and publication. IntechOpen has been a member of COPE since 2013 and adheres to the COPE Code of Conduct and Best Practice Guidelines, ensuring that we maintain the highest ethical standards.
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Creative Commons
\n\n
\n\t
Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. IntechOpen uses the CC BY 3.0 license for chapters, meaning Authors retain copyright and their work can be reused and adapted as long as the source is properly cited and Authors are acknowledged.
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Crossref
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\n\t
Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
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Altmetric and Dimensions from Digital Science
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\n\t
Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
\n
\n\n
CLOCKSS
\n\n
\n\t
CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
\n
\n\n
Counter
\n\n
\n\t
COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
\n
\n\n
DORA
\n\n
\n\t
DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
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\n\n
iThenticate
\n\n
\n\t
iThenticate is the leading provider of professional plagiarism detection and prevention technology and is used worldwide by scholarly publishers and research institutions to ensure the originality of written work before publication. IntechOpen uses the iThenticate plagiarism software to ensure content originality and the research integrity of our published work.
\n
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Enago
\n\n
\n\t
IntechOpen collaborates with Enago, through its sister brand, Ulatus, one of the world’s leading providers of book translation services. Their services are designed to convey the essence of your work to readers from across the globe in the language they understand.
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IntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit https://www.enago.com/intech
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\n\n
Straive
\n\n
\n\t
Straive is the market leader in technology-driven solutions for the extraction, enrichment and transformation of content assets. IntechOpen publishing services are designed to meet the unique needs of Authors. As part of our commitment to that objective, we have an ongoing partnership agreement for production solutions.
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Amazon
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\n\t
Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
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DHL
\n\n
\n\t
IntechOpen has partnered with DHL since 2011 to ensure the fastest delivery of Print on Demand books.
\n
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United Nations Sustainable Development Goals Publishers Compact
\n\n
\n\t
The Compact is designed to inspire action among publishers. Launched in collaboration with the International Publishers Association, the Compact aims to accelerate progress to achieve the Sustainable Development Goals (SDGs) by 2030. Signatories aspire to develop sustainable practices and act as champions of the SDGs during the Decade of Action (2020-2030), publishing books and journals that will help inform, develop, and inspire action in that direction. Learn more here
\n
\n\n
River Valley Technology
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\n\t
River Valley Technology is the world’s first XML-based publishing solution from submission to peer review to production and to final hosting, giving full control to publishers, with full transparency of data.
\n
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Figshare
\n\n
\n\t
Figshare is an online open access repository where researchers can preserve and share their research outputs, including figures, datasets, images, and videos. It is free to upload content and free to access, in adherence to the principle of open data.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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being attacked or harmed, either physically or emotionally. In this chapter, it is defined as a possible ability of an individual or a group to face, manage, and anticipate a possible problem. This concept of vulnerability is associated with that of risk factor for social isolation, and therefore to situations that can also lead to illness and lack of mental and physical health. It can have its roots in poverty, in social exclusion, in ethnicity, in disability or simply in disease or specific developmental phases in life. All these aspects reflect very important vulnerability factors among biological, psychological, social, and behavioral variables. To date, no one has highlighted together two critical moments in life in which this brain area undergoes important variations: adolescence, in which its development occurs, and old age, in which this area goes into cognitive decline with the relative loss of many higher cognitive functions. This knowledge can help to better understand the forms of exclusion due to vulnerability in order to develop new forms of social inclusion.",book:{id:"8262",slug:"the-new-forms-of-social-exclusion",title:"The New Forms of Social Exclusion",fullTitle:"The New Forms of Social Exclusion"},signatures:"Rosalba Morese, Sara Palermo, Matteo Defedele, Juri Nervo and Alberto Borraccino",authors:[{id:"214435",title:"Dr.",name:"Rosalba",middleName:null,surname:"Morese",slug:"rosalba-morese",fullName:"Rosalba Morese"},{id:"218983",title:"BSc.",name:"Juri",middleName:null,surname:"Nervo",slug:"juri-nervo",fullName:"Juri Nervo"},{id:"218984",title:"MSc.",name:"Matteo",middleName:null,surname:"Defedele",slug:"matteo-defedele",fullName:"Matteo Defedele"},{id:"233998",title:"Ph.D.",name:"Sara",middleName:null,surname:"Palermo",slug:"sara-palermo",fullName:"Sara Palermo"},{id:"266453",title:"Prof.",name:"Alberto",middleName:null,surname:"Borraccino",slug:"alberto-borraccino",fullName:"Alberto Borraccino"}]},{id:"74550",doi:"10.5772/intechopen.95395",title:"School Conflicts: Causes and Management Strategies in Classroom Relationships",slug:"school-conflicts-causes-and-management-strategies-in-classroom-relationships",totalDownloads:2308,totalCrossrefCites:1,totalDimensionsCites:10,abstract:"Conflicts cannot cease to exist, as they are intrinsic to human beings, forming an integral part of their moral and emotional growth. Likewise, they exist in all schools. The school is inserted in a space where the conflict manifests itself daily and assumes relevance, being the result of the multiple interpersonal relationships that occur in the school context. Thus, conflict is part of school life, which implies that teachers must have the skills to manage conflict constructively. Recognizing the diversity of school conflicts, this chapter aimed to present its causes, highlighting the main ones in the classroom, in the teacher-student relationship. It is important to conflict face and resolve it with skills to manage it properly and constructively, establishing cooperative relationships, and producing integrative solutions. Harmony and appreciation should coexist in a classroom environment and conflict should not interfere, negatively, in the teaching and learning process. This bibliography review underscore the need for during the teachers’ initial training the conflict management skills development.",book:{id:"7827",slug:"interpersonal-relationships",title:"Interpersonal Relationships",fullTitle:"Interpersonal Relationships"},signatures:"Sabina Valente, Abílio Afonso Lourenço and Zsolt Németh",authors:[{id:"324514",title:"Ph.D.",name:"Sabina",middleName:"N.",surname:"Valente",slug:"sabina-valente",fullName:"Sabina Valente"},{id:"326375",title:"Prof.",name:"Abílio Afonso",middleName:"Afonso",surname:"Lourenço",slug:"abilio-afonso-lourenco",fullName:"Abílio Afonso Lourenço"},{id:"329177",title:"Dr.",name:"Zsolt",middleName:null,surname:"Németh",slug:"zsolt-nemeth",fullName:"Zsolt Németh"}]},{id:"55323",doi:"10.5772/intechopen.68873",title:"Positive Psychology: The Use of the Framework of Achievement Bests to Facilitate Personal Flourishing",slug:"positive-psychology-the-use-of-the-framework-of-achievement-bests-to-facilitate-personal-flourishing",totalDownloads:1737,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"The Framework of Achievement Bests, which was recently published in Educational Psychology Review, makes a theoretical contribution to the study of positive psychology. The Framework of Achievement Bests provides an explanatory account of a person’s optimal best practice from his/her actual best. Another aspect emphasizes on the saliency of the psychological process of optimization, which is central to our understanding of person’s optimal functioning in a subject matter. Achieving an exceptional level of best practice (e.g. achieving excellent grades in mathematics) does not exist in isolation, but rather depends on the potent impact of optimization. This chapter, theoretical in nature, focuses on an in‐depth examination of the expansion of the Framework of Achievement Bests. Our discussion of the Framework of Achievement Bests, reflecting a methodical conceptualization, is benchmarked against another notable theory for understanding, namely: Martin Seligman’s PERMA theory. For example, for consideration, one aspect that we examine entails the extent to which the Framework of Achievement Bests could explain the optimization of each of the five components of PERMA (e.g. how does the Framework of Achievement Bests explain the optimization of engagement?).",book:{id:"5761",slug:"quality-of-life-and-quality-of-working-life",title:"Quality of Life and Quality of Working Life",fullTitle:"Quality of Life and Quality of Working Life"},signatures:"Huy P. Phan and Bing H. Ngu",authors:[{id:"196435",title:"Prof.",name:"Huy",middleName:"P",surname:"Phan",slug:"huy-phan",fullName:"Huy Phan"}]},{id:"55349",doi:"10.5772/intechopen.68596",title:"The Development of a Human Well-Being Index for the United States",slug:"the-development-of-a-human-well-being-index-for-the-united-states",totalDownloads:2041,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"The US Environmental Protection Agency (EPA) has developed a human well-being index (HWBI) that assesses the over-all well-being of its population at the county level. The HWBI contains eight domains representing social, economic and environmental well-being. These domains include 25 indicators comprised of 80 metrics and 22 social, economic and environmental services. The application of the HWBI has been made for the nation as a whole at the county level and two alternative applications have been made to represent key populations within the overall US population—Native Americans and children. A number of advances have been made to estimate the values of metrics for counties where no data is available and one such estimator—MERLIN—is discussed. Finally, efforts to make the index into an interactive web site are described.",book:{id:"5761",slug:"quality-of-life-and-quality-of-working-life",title:"Quality of Life and Quality of Working Life",fullTitle:"Quality of Life and Quality of Working Life"},signatures:"J. Kevin Summers, Lisa M. Smith, Linda C. Harwell and Kyle D. Buck",authors:[{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers"},{id:"197486",title:"Ms.",name:"Lisa",middleName:null,surname:"Smith",slug:"lisa-smith",fullName:"Lisa Smith"},{id:"197487",title:"Ms.",name:"Linda",middleName:null,surname:"Harwell",slug:"linda-harwell",fullName:"Linda Harwell"},{id:"197488",title:"Dr.",name:"Kyle",middleName:null,surname:"Buck",slug:"kyle-buck",fullName:"Kyle Buck"}]},{id:"56529",doi:"10.5772/intechopen.70237",title:"Well-being and Quality of Working Life of University Professors in Brazil",slug:"well-being-and-quality-of-working-life-of-university-professors-in-brazil",totalDownloads:1676,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"This chapter presents a study about the perceptions on quality of working life (QWL) regarding factors and indicator in two public universities in Brazil. It aimed also to analyze their perceptions about university working conditions. This exploratory study is based on quantitative and qualitative analyses. A sample of 715 university professors participated on the research. Data collection was carried out in two steps: online survey and focus groups. There is a moderate negative correlation between psychological well-being and work-related stress. Emotional charge also presents a moderate positive correlation with work-related stress, as well as physical charge and psychological distress. Work-life balance is negatively correlated with physical charge, emotional charge, work-related stress, psychological distress, and burnout. We observed also that 43.6% of the professors reported high levels of work-related stress in their everyday work. The precariousness of university teaching is associated with three main elements, which we defined as the tripod of the precarization of university teaching work. It consists of academic productivism, excess of administrative work and bureaucratic activities, and inadequate working conditions. The operating dynamics of this tripod effect professors’ well-being, their QWL, and even the quality of the work they develop in public universities.",book:{id:"5761",slug:"quality-of-life-and-quality-of-working-life",title:"Quality of Life and Quality of Working Life",fullTitle:"Quality of Life and Quality of Working Life"},signatures:"Alessandro Vinicius de Paula and Ana Alice Vilas Boas",authors:[{id:"175373",title:"Dr.",name:"Ana Alice",middleName:null,surname:"Vilas Boas",slug:"ana-alice-vilas-boas",fullName:"Ana Alice Vilas Boas"},{id:"196534",title:"Dr.",name:"Alessandro Vinicius",middleName:null,surname:"De Paula",slug:"alessandro-vinicius-de-paula",fullName:"Alessandro Vinicius De Paula"}]}],mostDownloadedChaptersLast30Days:[{id:"74550",title:"School Conflicts: Causes and Management Strategies in Classroom Relationships",slug:"school-conflicts-causes-and-management-strategies-in-classroom-relationships",totalDownloads:2328,totalCrossrefCites:1,totalDimensionsCites:10,abstract:"Conflicts cannot cease to exist, as they are intrinsic to human beings, forming an integral part of their moral and emotional growth. Likewise, they exist in all schools. The school is inserted in a space where the conflict manifests itself daily and assumes relevance, being the result of the multiple interpersonal relationships that occur in the school context. Thus, conflict is part of school life, which implies that teachers must have the skills to manage conflict constructively. Recognizing the diversity of school conflicts, this chapter aimed to present its causes, highlighting the main ones in the classroom, in the teacher-student relationship. It is important to conflict face and resolve it with skills to manage it properly and constructively, establishing cooperative relationships, and producing integrative solutions. Harmony and appreciation should coexist in a classroom environment and conflict should not interfere, negatively, in the teaching and learning process. This bibliography review underscore the need for during the teachers’ initial training the conflict management skills development.",book:{id:"7827",slug:"interpersonal-relationships",title:"Interpersonal Relationships",fullTitle:"Interpersonal Relationships"},signatures:"Sabina Valente, Abílio Afonso Lourenço and Zsolt Németh",authors:[{id:"324514",title:"Ph.D.",name:"Sabina",middleName:"N.",surname:"Valente",slug:"sabina-valente",fullName:"Sabina Valente"},{id:"326375",title:"Prof.",name:"Abílio Afonso",middleName:"Afonso",surname:"Lourenço",slug:"abilio-afonso-lourenco",fullName:"Abílio Afonso Lourenço"},{id:"329177",title:"Dr.",name:"Zsolt",middleName:null,surname:"Németh",slug:"zsolt-nemeth",fullName:"Zsolt Németh"}]},{id:"76968",title:"In the Darkness of This Time: Wittgenstein and Freud on Uncertainty",slug:"in-the-darkness-of-this-time-wittgenstein-and-freud-on-uncertainty",totalDownloads:461,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Both Wittgenstein and Freud experienced the crisis of humanism resulting from the first and second world wars. Although they were both considered to be influential figures, they hardly investigated the ways in which people could cope with the consequences of these crises. However, Wittgenstein and Freud did suggest ways of understanding uncertainties caused by real life events, as well as by the nature of human thought processes. This article will explore the therapeutic ways of dealing with uncertainties common to both thinkers and the different concepts facilitating their methodologies. The central contention of this article is that both Wittgenstein and Freud developed a complex methodology, acknowledging the constant and unexpected changes humans have deal with, whilst also offering the possibility of defining “hinge propositions” and “language-games” which can stabilize our consciousness.",book:{id:"10814",slug:"anxiety-uncertainty-and-resilience-during-the-pandemic-period-anthropological-and-psychological-perspectives",title:"Anxiety, Uncertainty, and Resilience During the Pandemic Period",fullTitle:"Anxiety, Uncertainty, and Resilience During the Pandemic Period - Anthropological and Psychological Perspectives"},signatures:"Dorit Lemberger",authors:[{id:"325725",title:"Dr.",name:"Dorit",middleName:null,surname:"Lemberger",slug:"dorit-lemberger",fullName:"Dorit Lemberger"}]},{id:"76565",title:"Introductory Chapter: The Transition from Distress to Acceptance of Human Frailty - Anthropology and Psychology of the Pandemic Era",slug:"introductory-chapter-the-transition-from-distress-to-acceptance-of-human-frailty-anthropology-and-ps",totalDownloads:393,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"10814",slug:"anxiety-uncertainty-and-resilience-during-the-pandemic-period-anthropological-and-psychological-perspectives",title:"Anxiety, Uncertainty, and Resilience During the Pandemic Period",fullTitle:"Anxiety, Uncertainty, and Resilience During the Pandemic Period - Anthropological and Psychological Perspectives"},signatures:"Fabio Gabrielli and Floriana Irtelli",authors:[{id:"174641",title:"Dr.",name:"Floriana",middleName:null,surname:"Irtelli",slug:"floriana-irtelli",fullName:"Floriana Irtelli"},{id:"259407",title:"Prof.",name:"Fabio",middleName:null,surname:"Gabrielli",slug:"fabio-gabrielli",fullName:"Fabio Gabrielli"}]},{id:"77214",title:"The Impact of the COVID-19 Pandemic on the Mental Health of Dentists",slug:"the-impact-of-the-covid-19-pandemic-on-the-mental-health-of-dentists",totalDownloads:390,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Since March 2020, the COVID-19 disease has declared a pandemic producing a worldwide containment. For months, many people were subjected to strict social isolation away from family and loved ones to prevent disease transmission, leading to anxiety, fear, and depression. On the other hand, many had to close down their businesses and stop working, resulting in financial issues. Previous studies have reported that pandemics, epidemics, and some diseases can lead to mental disorders such as fear, anxiety, stress, and depression. Among those most affected, healthcare workers (HCWs), especially those on the front line, often develop mental health problems. Although there is data available on the management and care of HCWs, little attention has been paid to the mental health and well-being of dentists during the COVID-19 pandemic. Therefore, this chapter aims to review the impact of the COVID-19 pandemic on dentists’ mental health and mental health-related symptoms. Finally, to recommend specific measures to avoid consequent potential implications for dentists, dental students, and dental patients.",book:{id:"10814",slug:"anxiety-uncertainty-and-resilience-during-the-pandemic-period-anthropological-and-psychological-perspectives",title:"Anxiety, Uncertainty, and Resilience During the Pandemic Period",fullTitle:"Anxiety, Uncertainty, and Resilience During the Pandemic Period - Anthropological and Psychological Perspectives"},signatures:"Andrea Vergara-Buenaventura and Carmen Castro-Ruiz",authors:[{id:"346660",title:"M.Sc.",name:"Andrea",middleName:null,surname:"Vergara-Buenaventura",slug:"andrea-vergara-buenaventura",fullName:"Andrea Vergara-Buenaventura"},{id:"419814",title:"MSc.",name:"Carmen",middleName:null,surname:"Castro-Ruiz",slug:"carmen-castro-ruiz",fullName:"Carmen Castro-Ruiz"}]},{id:"55323",title:"Positive Psychology: The Use of the Framework of Achievement Bests to Facilitate Personal Flourishing",slug:"positive-psychology-the-use-of-the-framework-of-achievement-bests-to-facilitate-personal-flourishing",totalDownloads:1748,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"The Framework of Achievement Bests, which was recently published in Educational Psychology Review, makes a theoretical contribution to the study of positive psychology. The Framework of Achievement Bests provides an explanatory account of a person’s optimal best practice from his/her actual best. Another aspect emphasizes on the saliency of the psychological process of optimization, which is central to our understanding of person’s optimal functioning in a subject matter. Achieving an exceptional level of best practice (e.g. achieving excellent grades in mathematics) does not exist in isolation, but rather depends on the potent impact of optimization. This chapter, theoretical in nature, focuses on an in‐depth examination of the expansion of the Framework of Achievement Bests. Our discussion of the Framework of Achievement Bests, reflecting a methodical conceptualization, is benchmarked against another notable theory for understanding, namely: Martin Seligman’s PERMA theory. For example, for consideration, one aspect that we examine entails the extent to which the Framework of Achievement Bests could explain the optimization of each of the five components of PERMA (e.g. how does the Framework of Achievement Bests explain the optimization of engagement?).",book:{id:"5761",slug:"quality-of-life-and-quality-of-working-life",title:"Quality of Life and Quality of Working Life",fullTitle:"Quality of Life and Quality of Working Life"},signatures:"Huy P. Phan and Bing H. Ngu",authors:[{id:"196435",title:"Prof.",name:"Huy",middleName:"P",surname:"Phan",slug:"huy-phan",fullName:"Huy Phan"}]}],onlineFirstChaptersFilter:{topicId:"278",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. In 2017, Usha was awarded the Marquis Who’s Who Lifetime Achiever Award.",institutionString:null,institution:{name:"RMIT University",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo, Ph.D., is a professor in the Department of Engineering, University of Naples “Parthenope,” Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino and Southern Lazio, Italy. Her research interests include multi-criteria decision analysis, industrial plants, logistics, manufacturing, and safety. She serves as an associate editor for the International Journal of the Analytic Hierarchy Process and is an editorial board member for several other journals. She is also a member of the Analytic Hierarchy Process (AHP) Academy.",institutionString:"Parthenope University of Naples",institution:{name:"Parthenope University of Naples",institutionURL:null,country:{name:"Italy"}}},editorTwo:null,editorThree:null},{id:"92",title:"Health and Wellbeing",coverUrl:"https://cdn.intechopen.com/series_topics/covers/92.jpg",isOpenForSubmission:!0,editor:{id:"348225",title:"Prof.",name:"Ann",middleName:null,surname:"Hemingway",slug:"ann-hemingway",fullName:"Ann Hemingway",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035LZFoQAO/Profile_Picture_2022-04-11T14:55:40.jpg",biography:"Professor Hemingway is a public health researcher, Bournemouth University, undertaking international and UK research focused on reducing inequalities in health outcomes for marginalised and excluded populations and more recently focused on equine assisted interventions.",institutionString:null,institution:{name:"Bournemouth University",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"93",title:"Inclusivity and Social Equity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/93.jpg",isOpenForSubmission:!0,editor:{id:"210060",title:"Prof. Dr.",name:"Ebba",middleName:null,surname:"Ossiannilsson",slug:"ebba-ossiannilsson",fullName:"Ebba Ossiannilsson",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6LkBQAU/Profile_Picture_2022-02-28T13:31:48.png",biography:"Professor Dr. Ebba Ossiannilsson is an independent researcher, expert, consultant, quality auditor and influencer in the fields of open, flexible online and distance learning (OFDL) and the 'new normal'. Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. She holds a Ph.D. from the University of Oulu, Finland.",institutionString:"Swedish Association for Distance Education, Sweden",institution:null},editorTwo:null,editorThree:null},{id:"94",title:"Climate Change and Environmental Sustainability",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",isOpenForSubmission:!0,editor:{id:"61855",title:"Dr.",name:"Yixin",middleName:null,surname:"Zhang",slug:"yixin-zhang",fullName:"Yixin Zhang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYWJgQAO/Profile_Picture_2022-06-09T11:36:35.jpg",biography:"Professor Yixin Zhang is an aquatic ecologist with over 30 years of research and teaching experience in three continents (Asia, Europe, and North America) in Stream Ecology, Riparian Ecology, Urban Ecology, and Ecosystem Restoration and Aquatic Conservation, Human-Nature Interactions and Sustainability, Urbanization Impact on Aquatic Ecosystems. He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. Current research interests include trophic flows across ecosystems; watershed impacts of land-use change on biodiversity and ecosystem functioning; ecological civilization and water resource management; urban ecology and urban/rural sustainable development.",institutionString:null,institution:{name:"Soochow University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"95",title:"Urban Planning and Environmental Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/95.jpg",isOpenForSubmission:!0,editor:{id:"181079",title:"Dr.",name:"Christoph",middleName:null,surname:"Lüthi",slug:"christoph-luthi",fullName:"Christoph Lüthi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHSqQAO/Profile_Picture_2022-04-12T15:51:33.png",biography:"Dr. Christoph Lüthi is an urban infrastructure planner with over 25 years of experience in planning and design of urban infrastructure in middle and low-income countries. He holds a Master’s Degree in Urban Development Planning from the University College of London (UCL), and a Ph.D. in Urban Planning & Engineering from TU Berlin. He has conducted applied research on urban planning and infrastructure issues in over 20 countries in Africa and Asia. In 2005 he joined Eawag-Sandec as Leader of the Strategic Environmental Sanitation Planning Group. Since 2015 he heads the research department Sanitation, Water and Solid Waste for Development (Sandec) at the Swiss Federal Institute of Aquatic Research and Technology (Eawag).",institutionString:"Swiss Federal Institute of Aquatic Science and Technology, Switzerland",institution:{name:"Swiss Federal Institute of Aquatic Science and Technology",institutionURL:null,country:{name:"Switzerland"}}},editorTwo:{id:"290571",title:"Dr.",name:"Rui Alexandre",middleName:null,surname:"Castanho",slug:"rui-alexandre-castanho",fullName:"Rui Alexandre Castanho",profilePictureURL:"https://mts.intechopen.com/storage/users/290571/images/system/290571.jpg",biography:"Rui Alexandre Castanho has a master\\'s degree in Planning, Audit, and Control in Urban Green Spaces and an international Ph.D. in Sustainable Planning in Borderlands. Currently, he is a professor at WSB University, Poland, and a visiting professor at the University of Johannesburg, South Africa. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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