Mineral and chemical composition of POMSW.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"7218",leadTitle:null,fullTitle:"OCT - Applications in Ophthalmology",title:"OCT",subtitle:"Applications in Ophthalmology",reviewType:"peer-reviewed",abstract:"I am very proud and excited to introduce to you this book, which provides many interesting indications on how to better understand and handle the world of optical coherence tomography (OCT). Reading the chapters, you will be aware that this device is extremely important not just in the clinical practice of retinal diseases, but is also very useful as a surgical tool. Moreover, application of OCT has crossed the borders of the retina and is currently being applied to corneal diseases and glaucoma. I am confident you will find enough useful information to improve your practice using OCT and to provide a better quality of care for your patients.",isbn:"978-1-78923-755-9",printIsbn:"978-1-78923-754-2",pdfIsbn:"978-1-83881-774-9",doi:"10.5772/intechopen.74129",price:119,priceEur:129,priceUsd:155,slug:"oct-applications-in-ophthalmology",numberOfPages:200,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"e3a3430cdfd6999caccac933e4613885",bookSignature:"Michele Lanza",publishedDate:"September 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",numberOfDownloads:12797,numberOfWosCitations:5,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:17,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 1st 2018",dateEndSecondStepPublish:"February 22nd 2018",dateEndThirdStepPublish:"April 23rd 2018",dateEndFourthStepPublish:"July 12th 2018",dateEndFifthStepPublish:"September 10th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1094",title:"Ophthalmic Pathology",slug:"ophthalmic-pathology"}],chapters:[{id:"62724",title:"Novel Insight into Morphological Features and Vascular Profile of Selected Macular Dystrophies Using Swept-Source Optical Coherence Tomography and Optical Coherence Tomography Angiography",doi:"10.5772/intechopen.78679",slug:"novel-insight-into-morphological-features-and-vascular-profile-of-selected-macular-dystrophies-using",totalDownloads:1156,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Our perception of macular dystrophies has evolved overtime from collective grouping into hereditary disorders of unclear etiology and no effective treatment to avid search for the underlying pathogenic mechanism that would provide base for future therapy. A causal conjunction between abnormalities in the photoreceptors layer and the RPE—Bruch’s membrane complex and abnormal profile of the retinal vascular plexuses and the choriocapillaris—stands out as a plausible theory of pathogenesis. The recently introduced swept-source optical coherence tomography (SS-OCT) technology incorporates long-wavelength (1050-nm) scanning light, less susceptibility to sensitivity roll-off, and ultrahigh-speed image acquisition. These features enabled in vivo noninvasive visualization of different strata of the outer retina and the choriocapillaris with unprecedented finesse. Furthermore, the SS-OCT technology incorporated a blood flow detection algorithm; OCTARA that in tandem with the deeper penetration and superior axial resolution of SS-OCT enabled detailed assessment of the retinal capillary plexuses and the choriocapillaris in terms of structure and density. This novel technology could help explore yet undiscovered frontiers in the pathophysiology of macular dystrophies and guide future therapeutic approaches. This chapter includes a review of literature along with the authors’ experience in imaging selected macular dystrophies using SS-OCT and SS-OCT angiography (SS-OCTA).",signatures:"Magdy Moussa and Mahmoud Leila",downloadPdfUrl:"/chapter/pdf-download/62724",previewPdfUrl:"/chapter/pdf-preview/62724",authors:[{id:"242399",title:"Prof.",name:"Magdy",surname:"Moussa",slug:"magdy-moussa",fullName:"Magdy Moussa"},{id:"257712",title:"Dr.",name:"Mahmoud",surname:"Leila",slug:"mahmoud-leila",fullName:"Mahmoud Leila"}],corrections:null},{id:"61732",title:"Retinal Vasculature Identification and Characterization Using OCT Imaging",doi:"10.5772/intechopen.78292",slug:"retinal-vasculature-identification-and-characterization-using-oct-imaging",totalDownloads:1045,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The eye fundus is the part of the human body where the blood vessels can be directly observed and studied. For this reason, the analysis and diagnosis of many relevant diseases that affect the circulatory system, for example, reference, hypertension, diabetes or arteriosclerosis can be supported by the use of this source of information, analyzing their degree of severity and impact by the study of the properties of the retinal microcirculation. The development of computer aided-diagnosis tools became relevant over the recent years as they support and facilitate the work of specialists, helping to accurately identify the target structures in many processes of analysis and diagnosis. In that sense, the automatic identification of the retinal vasculature is crucial as its manual identification is an exhaustive and tedious work when it is manually performed by the experts. This chapter presents an analysis of the characteristics of the optical coherence tomography imaging and its potential for the retinal vascular identification and characterization. In that sense, we also analyze computational approaches to automatically obtain and characterize the retinal vasculature and provide an intuitive visualization that facilitates the posterior clinical analysis of relevant diseases such as hypertension or diabetes.",signatures:"Joaquim de Moura, Jorge Novo, José Rouco, Noelia Barreira,\nManuel Penedo and Marcos Ortega",downloadPdfUrl:"/chapter/pdf-download/61732",previewPdfUrl:"/chapter/pdf-preview/61732",authors:[{id:"30409",title:"Dr.",name:"Marcos",surname:"Ortega",slug:"marcos-ortega",fullName:"Marcos Ortega"},{id:"30410",title:"Prof.",name:"Manuel",surname:"González Penedo",slug:"manuel-gonzalez-penedo",fullName:"Manuel González Penedo"},{id:"123553",title:"Prof.",name:"Jorge",surname:"Novo",slug:"jorge-novo",fullName:"Jorge Novo"},{id:"123554",title:"Dr.",name:"Noelia",surname:"Barreira",slug:"noelia-barreira",fullName:"Noelia Barreira"},{id:"242893",title:"Ph.D. Student",name:"Joaquim",surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura"},{id:"242894",title:"Dr.",name:"José",surname:"Rouco",slug:"jose-rouco",fullName:"José Rouco"}],corrections:null},{id:"62034",title:"Spectral Domain Optical Coherence Tomography in the Diagnosis and Monitoring of Diabetic Macular Edema",doi:"10.5772/intechopen.78681",slug:"spectral-domain-optical-coherence-tomography-in-the-diagnosis-and-monitoring-of-diabetic-macular-ede",totalDownloads:1224,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Currently, spectral domain optical coherence tomography (SD-OCT) is a basic tool in diagnosing and monitoring diabetic macular edema (DME), which is the most frequent cause of visual impairment in the diabetic patients. OCT technology has changed the classification of DME from the traditional criteria. Macular thickness measured on OCT is considered an outcome measure to evaluate the structural and functional outcome of various therapeutic means used in DME. SD-OCT evaluates ultrastructural retinal parameters, such as the ellipsoid zone, photoreceptor outer segment length and quantifies the individual layers according to various algorithms. The aim is to present the way in which SD-OCT technology has changed our clinical practice during the last years, in diagnosing, classifying and treating DME and to illustrate its impact with practical cases.",signatures:"Simona Delia Nicoară",downloadPdfUrl:"/chapter/pdf-download/62034",previewPdfUrl:"/chapter/pdf-preview/62034",authors:[{id:"87785",title:"Prof.",name:"Simona-Delia",surname:"Nicoara",slug:"simona-delia-nicoara",fullName:"Simona-Delia Nicoara"}],corrections:null},{id:"62203",title:"iOCT in PVR Surgical Management",doi:"10.5772/intechopen.78774",slug:"ioct-in-pvr-surgical-management",totalDownloads:918,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Recent advances in optical coherence tomography (OCT) technology have allowed the introduction of OCT into the operating room. Intraoperative OCT (iOCT) has been utilized to visualize the retinal architecture prior, during, and following several retinal surgical technics. The identification of epiretinal, subretinal, and intraretinal changes is one of the crucial points in PVR management. The iOCT can identify intraretinal changes and/or subretinal PVR membranes which cannot be easily peeled as epiretinal membranes. Intraretinal forms are especially difficult to identify preoperatively but their presence may be crucial in surgical management because the attempt to remove the presumed membrane may result in severe retinal tissue damage and iatrogenic tears. Therefore, surgical technique and even tamponade choice may be seriously affected by OCT imaging results.",signatures:"Salvatore Di Lauro, Salvador Pastor Idoate and Jose Carlos Pastor",downloadPdfUrl:"/chapter/pdf-download/62203",previewPdfUrl:"/chapter/pdf-preview/62203",authors:[{id:"81828",title:"Prof.",name:"Jose-Carlos",surname:"Pastor Jimeno",slug:"jose-carlos-pastor-jimeno",fullName:"Jose-Carlos Pastor Jimeno"},{id:"241897",title:"Ph.D.",name:"Salvador",surname:"Pastor Idoate",slug:"salvador-pastor-idoate",fullName:"Salvador Pastor Idoate"},{id:"244950",title:"Dr.",name:"Salvatore",surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro"}],corrections:null},{id:"62880",title:"Clinical Use of OCT in the Management of Epiretinal Membranes",doi:"10.5772/intechopen.79770",slug:"clinical-use-of-oct-in-the-management-of-epiretinal-membranes",totalDownloads:1192,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Epiretinal membranes (ERM) are frequently seen in an aging eye, especially after posterior vitreous detachment, and can cause decreased vision, and/or metamorphopsia. Not all of the ERMs detected in routine ophthalmological examination are indicated to be removed with surgery. Optical coherence tomography (OCT) examination reveals the microanatomy of all the retinal layers and enables the vitreoretinal surgeon to make decision to follow-up or to perform a vitrectomy to peel the ERM. OCT imaging clearly shows all the tractions on the retina and the intraretinal layers; and can have a prognostic value for the surgery. OCT imaging is also very valuable in the differential diagnosis of pseudoholes with macular and lameller holes; much better than the clinical examination. It is a routine part of the detailed retinal examination of an eye with an ERM. This chapter covers OCT findings in ERMs, and examples of cases with ERMs indicated for surgery of follow-up will be shown, explaining the clinical results of the cases.",signatures:"Nur Acar",downloadPdfUrl:"/chapter/pdf-download/62880",previewPdfUrl:"/chapter/pdf-preview/62880",authors:[{id:"244973",title:"Prof.",name:"Nur",surname:"Acar",slug:"nur-acar",fullName:"Nur Acar"}],corrections:null},{id:"63008",title:"Optical Coherence Tomography: Essential Tool in Macular Hole Management",doi:"10.5772/intechopen.79279",slug:"optical-coherence-tomography-essential-tool-in-macular-hole-management",totalDownloads:1271,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Optical coherence tomography (OCT) is a noninvasive, diagnostic technique for accurately identifying and quantitatively characterizing macular holes. OCT is crucial in assessing fellow eyes of patients with a macular hole to detect preclinical changes leading to subsequent hole formation. The tomographic information provided by OCT, akin to an in vivo biopsy, has led to a better understanding of the pathogenesis of hole formation. The cross-sectional view produced by OCT effectively distinguishes full-thickness macular holes from mimicking conditions like lamellar holes, macular pseudoholes, and cysts, which may sometimes be difficult to differentiate clinically. This information enables early diagnosis and can guide the intervention of choice when treatment is deemed necessary. OCT is useful to prognosticate cases, thereby facilitating discussions with patients and managing visual expectations preoperatively. Intraoperative OCT (iOCT) can identify intraoperative changes in the macular anatomy during surgery that can influence functional outcomes. Postoperatively, OCT is extremely useful for documenting serial changes in the foveal architecture and is helpful in correlating functional and anatomic outcomes. As the technology continues to improve, OCT has become indispensable for all aspects of patient care for macular holes.",signatures:"Sana I. Tinwala",downloadPdfUrl:"/chapter/pdf-download/63008",previewPdfUrl:"/chapter/pdf-preview/63008",authors:[{id:"247275",title:"Dr.",name:"Sana",surname:"Tinwala",slug:"sana-tinwala",fullName:"Sana Tinwala"},{id:"248157",title:"Prof.",name:"Atul",surname:"Kumar",slug:"atul-kumar",fullName:"Atul Kumar"}],corrections:null},{id:"62419",title:"Intraoperative OCT in Lamellar Corneal Transplants (DALK, DSAEK, DMEK)",doi:"10.5772/intechopen.79322",slug:"intraoperative-oct-in-lamellar-corneal-transplants-dalk-dsaek-dmek-",totalDownloads:972,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"An explanation of this new technology, consisting of optical coherence tomography integrated to the microscope in both anterior and posterior lamellar corneal transplants (DALK, DSAEK, DMEK). The advantages of visualizing the different layers of the host and donor cornea, with specific emphasis in the Descemet-stroma interphase, are explained in the written work and captured in the intraoperative images. This technology makes the procedure safer, increases the surgery success rate and consequently improves the postoperative results in the patient. The surgical technique of the lamellar transplants and its benefits are explained. The advantages of this new technology are analyzed, including visualizing the corneal planes, checking the tissue orientation and ensuring the correct execution of critical surgical steps; all of these help in reducing the technical difficulty of the procedure. Likewise, it is explained that by providing direct transurgical visualization in a screen, there is a potential teaching and academic advantage.",signatures:"Jorge Luis Domene Hinojosa, Jorge L. Domene-Hickman and Nuria\nJudith Alemán Hurtado",downloadPdfUrl:"/chapter/pdf-download/62419",previewPdfUrl:"/chapter/pdf-preview/62419",authors:[{id:"244037",title:"Dr.",name:"Jorge Luis",surname:"Domene",slug:"jorge-luis-domene",fullName:"Jorge Luis Domene"},{id:"248007",title:"Dr.",name:"Jorge Luis",surname:"Domene Hickman",slug:"jorge-luis-domene-hickman",fullName:"Jorge Luis Domene Hickman"},{id:"258512",title:"Dr.",name:"Nuria Judith",surname:"Aleman Hurtado",slug:"nuria-judith-aleman-hurtado",fullName:"Nuria Judith Aleman Hurtado"}],corrections:null},{id:"62289",title:"OCT in Lamellar Corneal Transplantation",doi:"10.5772/intechopen.78294",slug:"oct-in-lamellar-corneal-transplantation",totalDownloads:1024,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Anterior segment optical coherence tomography (AS-OCT) is a valuable tool in corneal transplantation surgery. In deep anterior lamellar keratoplasty (DALK), AS-OCT gives valuable information on preoperative decision process. AS-OCT image of the recipient cornea helps the surgeon to decide whether to proceed with a big bubble DALK or a manual dissection. Preoperative AS-OCT imaging of recipient stroma can also predict Descemet membrane perforation during big bubble induction. Intraoperative AS-OCT assures reaching the proper depth in order, and postoperatively, a surgeon can objectively assess the Descemet membrane and donor association and define complications such as a double anterior chamber. Before deciding for a Descemet membrane endothelial keratoplasty (DMEK), preoperative stromal scars can be identified with an AS-OCT and might affect the decision of the surgical procedure (DMEK or penetrating keratoplasty). After DMEK, graft detachment can be visualized by AS-OCT and treated accordingly.",signatures:"Mehmet Cüneyt Özmen and Hüseyin Baran Özdemir",downloadPdfUrl:"/chapter/pdf-download/62289",previewPdfUrl:"/chapter/pdf-preview/62289",authors:[{id:"89721",title:"Dr.",name:"Mehmet",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen"},{id:"256970",title:"Dr.",name:"Hüseyin Baran",surname:"Özdemir",slug:"huseyin-baran-ozdemir",fullName:"Hüseyin Baran Özdemir"}],corrections:null},{id:"61907",title:"Imaging the Cornea, Anterior Chamber, and Lens in Corneal and Refractive Surgery",doi:"10.5772/intechopen.78293",slug:"imaging-the-cornea-anterior-chamber-and-lens-in-corneal-and-refractive-surgery",totalDownloads:1272,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Anterior segment OCT (AS-OCT) is an optical and noncontact imaging technology, which has numerous fields of application in the imaging of the cornea, anterior chamber, and the lens. In this chapter, we will present some of the application fields of AS-OCT in corneal, cataract, and refractive surgery. We will emphasize the potential of AS-OCT by several clinical examples including corneal imaging (keratoconus, keratoplasty, and refractive surgery) and intraocular lens imaging after refractive surgery. AS-OCT shows special potential for corneal imaging in case of corneal edema and for postoperative control after Descemet’s membrane endothelial keratoplasty (DMEK). The postoperative follow-up of a posterior chamber Collamer lens’ses vault and measuring the anterior chamber angle could be identified as another promising field of application for AS-OCT.",signatures:"Timo Eppig, Stephanie Mäurer, Loay Daas, Berthold Seitz and\nAchim Langenbucher",downloadPdfUrl:"/chapter/pdf-download/61907",previewPdfUrl:"/chapter/pdf-preview/61907",authors:[{id:"244421",title:"Associate Prof.",name:"Timo",surname:"Eppig",slug:"timo-eppig",fullName:"Timo Eppig"},{id:"244423",title:"Prof.",name:"Achim",surname:"Langenbucher",slug:"achim-langenbucher",fullName:"Achim Langenbucher"},{id:"244424",title:"MSc.",name:"Stephanie",surname:"Mäurer",slug:"stephanie-maurer",fullName:"Stephanie Mäurer"},{id:"255046",title:"Mr.",name:"Loay",surname:"Daas",slug:"loay-daas",fullName:"Loay Daas"},{id:"255953",title:"Prof.",name:"Berthold",surname:"Seitz",slug:"berthold-seitz",fullName:"Berthold Seitz"}],corrections:null},{id:"62200",title:"OCT in Glaucoma Diagnosis, Detection and Screening",doi:"10.5772/intechopen.78683",slug:"oct-in-glaucoma-diagnosis-detection-and-screening",totalDownloads:1590,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Glaucoma is a chronic and progressive optic neuropathy in which increased intraocular pressure is the most important risk factor in the etiopathogenesis. The basic pathology is the progressive loss of retinal ganglion cells (RGCs) especially the death of the axons of ganglion cells initially (apoptosis), followed by peripapillary retinal nerve fiber layer (RNFL) defects. Since optical coherence tomography (OCT)’s first demonstration in 1991 by Huang et al. and introduction commercially in 1996, it began gaining popularity in 2000s for retinal evaluation and the detection, diagnosis, and follow-up of glaucoma. Previously available OCT instruments used a technique referred to as time-domain (TD-) OCT, followed by spectral-domain (SD-) OCT, which has an increased scan acquisition rate, allowing for a more detailed sampling of the area of interest. Recently, swept-source OCT (SS-OCT), a newer generation of OCT, has been introduced. Clinical assessment using multiple parameters, including peripapillary RNFL, ganglion cells, optic nerve head, and macular parameters, has proven useful for managing and diagnosing glaucoma as well as for evaluating risk in glaucoma suspects. In this chapter, we aim to evaluate the use of OCT and its modalities in diagnosis, screening, and progression of glaucoma.",signatures:"Aydin Yildiz",downloadPdfUrl:"/chapter/pdf-download/62200",previewPdfUrl:"/chapter/pdf-preview/62200",authors:[{id:"255594",title:"M.D.",name:"Aydin",surname:"Yildiz",slug:"aydin-yildiz",fullName:"Aydin Yildiz"}],corrections:null},{id:"61354",title:"OCT Application Before and After Cataract Surgery",doi:"10.5772/intechopen.77281",slug:"oct-application-before-and-after-cataract-surgery",totalDownloads:1133,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Optical coherence tomography (OCT), especially anterior segment OCT (AS-OCT), plays an important role in ophthalmology. With the technology evolving from time-domain to spectral-domain, more and more detailed ocular information has become available. Anterior segment OCT provides particularly useful information for cataract surgeons. This chapter focuses mainly on AS-OCT evaluation of eyes before and after cataract surgery. Four aspects including: (1) anterior lens capsule and lens epithelium evaluation using spectral-domain OCT (SD-OCT); (2) investigation of clear corneal incision in femtosecond laser assisted cataract surgery using SD-OCT; (3) capsular block syndrome evaluation before and after treatment using SD-OCT; (4) IOL power calculation in post-myopic excimer laser eyes using SD-OCT, will be discussed in this chapter.",signatures:"Xiaogang Wang, Jing Dong, Suhua Zhang and Bin Sun",downloadPdfUrl:"/chapter/pdf-download/61354",previewPdfUrl:"/chapter/pdf-preview/61354",authors:[{id:"243698",title:"M.D.",name:"Xiaogang",surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang"},{id:"253583",title:"Ms.",name:"Jing",surname:"Dong",slug:"jing-dong",fullName:"Jing Dong"},{id:"253584",title:"Prof.",name:"Suhua",surname:"Zhang",slug:"suhua-zhang",fullName:"Suhua Zhang"},{id:"253585",title:"Prof.",name:"Bin",surname:"Sun",slug:"bin-sun",fullName:"Bin Sun"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"7",series:{id:"7",title:"Biomedical Engineering",issn:"2631-5343",editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}}},tags:null},relatedBooks:[{type:"book",id:"7858",title:"A Practical Guide to Clinical Application of OCT in Ophthalmology",subtitle:null,isOpenForSubmission:!1,hash:"8e2d479cc9258dee430f8ba4c353c468",slug:"a-practical-guide-to-clinical-application-of-oct-in-ophthalmology",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/7858.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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Within these last decades, with the population growth and food security, both developed and developing countries face many environmental challenges as waste management [1, 2]. Nowadays, the sustainable management of waste is a global issue, because of their permanent increase and their harmful effects on the environment. According to Sotamenou and Kamgnia [3], wastes are produced during household, agricultural, industrial, and commercial activities. In Benin Republic, a new national waste strategy adopted in 2008, concerns mainly solid household wastes and market wastes [4]. Despite population bury and burn household wastes, the solid waste disposal rate is very low in cities and villages. The systems of collection, evacuation, and treatment being little operational and garbage are evacuated in the side streets and empty plots. The situation is worse in rural areas. The survey demographic and health, conducted in Benin in 2001, evaluated the garbage evacuation rate at 39% in urban and 3% in rural areas [5]. There is no specific national strategy to manage agricultural and industrial wastes in Benin. For agricultural wastes, farmers had to burnt them or return them to the field. Almost all research studies on waste management concern household wastes in urban areas [4, 6–8]. Industrial wastes are mostly come from food processing. Small‐scale food industries are important in the rural areas because they generate employment; reduce rural‐urban migration, and associated social problems. They are vital to reducing postharvest food losses and increasing food availability [9]. Food processing has traditionally been the domain of women. They had to produce little quantities and manage all wastes quantities. Nowadays, food processing had been improving by introduction of new technologies and engines. This is the case of palm oil production in Benin Republic. Oil palm is an oleaginous crop. It provides 39% of vegetable oil world production with 7% of oleaginous plantation areas compared with soybean (61%), colza (18%), and sunflower (14%) [10]. Benin Republic is a small oil palm producing country, where oil palm plays social, cultural, and economic roles for farmers. In 1848, palm oil gradually replaced slave trade. Oil palm through its products, the palm oil and “sodabi” (local palm wine), highly contributes to the income and social capital accumulation; this also discriminates operators and their households socially and economically. In Southern Benin, the more the oil palm acreage is wide, the more farmers are wealthy [11]. Oil palm is cultivated by many farmers and retailed to secure a decent retirement. They used this crop to affirm and secure their land. In addition, incomes from palm kernel sales help households to pay their children school fees. The local wine is used in festivities and ceremonies (weeding, mourning, receptions, etc.). This made the oil palm a serious component in populations’ culture where it is grown [12]. Moreover, during revitalization of this sector by the government and NGO, oil palm become as a cash crop that means “money symbol” and palm oil become a great interest for people in this production chain, who began to produce palm oil by themselves. These people improved the extraction method by introducing engines [13, 14]. According to the type of machine used for palm oil production in a partial or total process, they are categorized into four palm oil mill processes: traditional palm oil process (no machine use), small mechanized or improved palm oil process (integration of digester engine in the process), motorized or modern palm oil process (integration of digester and press engines in the process), and semi‐industrial or mechanized palm oil processing (integration of large cookers, presses, digesters, sterilizers, clarifiers, and other facilities in the process) [15] (\nFigure 1\n). Despite of that, only 40% of national needs in vegetable oils were covered [16]. These improvements consequently increase palm oil mill wastes to an extent that some mills struggle to recycle all quantities produced. These wastes cause environmental nuisances. According to Ojonoma and Nnennaya [17], the sustainability of the palm oil sector is questioned in the majority of oil palm producing countries because of environmental harm due to the mismanagement of palm oil mill wastes. In Benin Republic, traditional palm oil mills had to use these wastes for many purposes. The present study analyzes the linkage between the improvement of palm oil process extraction and palm oil mill solid waste (POMSW) management for sustainable palm oil production in Benin Republic.
\nTypes of palm oil processing [
The data were collected from (i) literature review on the characterization and uses of palm oil mill solid wastes in the world and (ii) research project fieldwork. An approach used for the research project fieldwork was based on the survey in the six departments of the Southern part of the Republic of Benin (\nFigure 2\n). This part of Benin Republic extends from the coast at 6°25’ to 7°30’ N latitude. It belongs to the Guinea‐Congolese zone and submits to subequatorial with two rainy seasons (March–June and September–mid‐November) and two dry seasons (July–September and November–March). The annual rainfall of this area, which varies between 1100 and 1400 mm, makes this part of the country adequate for oil palm production. The average daily temperature ranges from 25 to 29°C. The soils are in 66% (700,000 ha) deep lateritic soils of low fertility, and the rest are more fertile alluvial soils and heavy clay soils (360,000 ha) located in the river valleys of Mono, Couffo, Oueme, and in the Lama depression [19]. The survey was carried out from November 2011 to March 2012 and 335 palm oil mills were randomly surveyed using a semi‐structure questionnaire. The collected data concerned the method of palm oil production, management of wastes produced, and management practices of waste quantities use (Did he use it? Did he sell it? Did he dump it? How did he use it?). The percentage usage (Pu) or proportion of interviewees who used palm oil mill wastes, the commercial value (CV) or proportion of mills who sell the wastes and rejection rate (RR) or proportion of mills who discard the wastes were calculated as follows:
\nStudy area.
where Nusers is the number of informants who use a waste;
\nwhere Nw is the number of informants who sell wastes;
\nwhere
All these parameters vary between 0 and 1.
\nConcerning POMSW nutrient composition analyses, samples were collected in one semi‐industrial palm oil mill. The palm oil extraction process was followed three times and at each time, sample of 1 kg of each kind of wastes was randomly selected. All the samples were mixed and a sample of 500 g was taken. The analyses were performed with ion chromatography system Dionex ICS 1000. Nitrogen was determined by the Kjeldahl method.
\nDouble principal component analysis (PCA) was performed using SAS software to explain the relation between palm oil mill categories and POMSW uses.
\nPalm oil mills generate two kind of solid wastes during palm oil fruits transformation: empty fruit bunches (EFBs) and palm mesocarp fiber (PMF) (\nFigure 3\n). EFB is obtained after the removal of oil seeds from fruit bunches. It is the supporting structures of the oil‐bearing fruits in a bunch and comprises spikelet (68–80% dry matter) and stalks (20–32% dry matter) [20, 21]. PMF is the fibrous residues separated from the mesocarp and kernel during palm oil extraction [22]. POMSW is mainly composed of fibers. Spikelet contains more fibers than stalk. Fibers of spikelet are stronger than those of stalk. PMFs are richer in cellulose and lignin than EFB (\nTable 1\n).
\nPalm oil mill solid wastes (POMSW).
Main fraction/Parameters | \nEFB (literature) [20, 23–30] | \nSpikelet (study) | \nSpikelet (literature) [20, 32] | \nStalk (study) | \nStalk (literature) [31, 32] | \nPMF (study) | \nPMF (literature) [33] | \n
---|---|---|---|---|---|---|---|
C (%) | \n44.1–54.5 | \nna | \n50.23–51.67 | \nna | \n43.62–48.6 | \n\n | 45.61 | \n
N (%) | \n0.44–1 | \n0.95 | \n0.5–0.96 | \n1.2 | \n0.7–071 | \n1.4 | \n1.36 | \n
C/N | \n58.9, 77.7 | \nna | \n– | \nna | \n– | \n50.3 | \n33.54 | \n
Lignin (%) | \n10.5–36.6 | \nna | \n23.5–29.10 | \nna | \n– | \nna | \n11–20.5 | \n
Cellulose (%) | \n33.7–63 | \nna | \n20.6–20.7 | \nna | \n26.9–28.8 | \nna | \n14–39.9 | \n
Hemicellulose (%) | \n20.1–35.3 | \nna | \n23.9–28.9 | \nna | \n24–28.8 | \nna | \n20.8–28.9 | \n
P (%) | \n0.03–0.7 | \n0.001 | \n0.05–0.19 | \n0.001 | \n0.07–0.3 | \n0.17 | \n– | \n
K (%) | \n1.4–2.8 | \n16.9 | \n1.75–1.78 | \n16.2 | \n3.31–4.03 | \n4.6 | \n– | \n
Ca (%) | \n0.16–0.9 | \n0.9 | \n2–2.41 | \n0.6 | \n0.09–0.31 | \n1.5 | \n– | \n
Mg (%) | \n0.008–0.8 | \n0.003 | \n0.12–0.17 | \nTraces | \n0.13–0.15 | \n0.9 | \n– | \n
Na (%) | \n– | \n0.6 | \n0.001–0.03 | \n0.5 | \n0.004–0.05 | \n1.4 | \n– | \n
Cl− (mg/g) | \n– | \n4.7 | \n– | \n21.4 | \n– | \n20.68 | \n– | \n
SO4\n2− (mg/g) | \n0.1–1.4 | \n0.7 | \n– | \n0.19 | \n– | \n0.27 | \n– | \n
Mineral and chemical composition of POMSW.
The chemical and mechanical proprieties of these fibers vary with the type of waste. Fibers are the wastes that contain the most ammonium and nitrates. Stalks and spikelet contain low amount of phosphorus. All these wastes contained large amount of calcium (0.6–1.6%) and sulfur (0.2–0.7 mg/g). Fibers and stalks contain large amount of chloride (21.4 and 20.7 mg/g, respectively). The high amount of potassium and chloride can be explained by the fertilizer of oil palm in plantation with KCl.
\nIn Benin Republic, from 1 ton of fresh fruit bunch (FFB), any mill obtains 152.3 l of crude palm oil and generates an average 254.7 kg of EFB and 114.9 kg of PMF [15, 18]. Compare to the other oil palm producer countries (\nTable 2\n), there are no great differences on EFB obtained. However, mills from Benin produce more EFB than those from Indonesia and less PMF than those from Nigeria, Malaysia, and Thailand. These differences can be explained by the variety of fruits used to produce oil. “Dura” variety possesses more shell than the kernel, while “Tenera” possesses more kernel than the shell [34] and the quantities of PMF produce by Dura are less than those from Tenera [35]. In Benin Republic, POMSW quantities vary with the oil extraction process (\nFigure 4\n).
\nQuantities of POMSW generate by each category of mills. a; b and c: figures followed by different letters are significantly different (Tukey HSD test, p<0.05) (adapted from Ref. [
Country | \nBenin | \nIndonesia | \nIndonesia | \nMwalaysia | \nNigeria | \n\n | Thailand | \nThailand | \n
---|---|---|---|---|---|---|---|---|
\n | \n[15] | \n[36] | \n[37] | \n[38] | \n[35] | \n[39] | \n[40] | \n|
\n | \n– | \nTenera | \nTenera | \nTenera | \nDura | \nTenera | \nTenera | \nTenera | \n
\n | \n254.7 | \n225 | \n210 | \n230–250 | \n237–324 | \n257–282 | \n240 | \n214–316 | \n
\n | \n114.9 | \n143 | \n144 | \n130–150 | \n232–281 | \n191–203 | \n140 | \n120–130 | \n
\n | \n152.3 | \n218 | \n235 | \n160–200 | \n94–128 | \n260–282 | \n– | \n250–280 | \n
Palm oil wastes and crude palm oil quantities generated from 1 t of full fruit bunch in different country.
The semi‐industrialized process produced significantly more EFB and PFM than the traditional process. In fact, mills that extracted palm oil by semi‐industrialized process used only Tenera fruit variety. Mills that use traditional method transform more Dura variety [18]. The other mills use the two seed varieties. POMSW quantity trends were similar to palm oil produced (\nFigure 5\n). From 1961 to 1968, 1980 to 1985 and 1991 to 1999, POMSW was relatively stable. After 1968 and 1985, POMSW drop in 1971 and 1997. A pic evolution of POMSW was obtained in 176 (78,600.8 tons of EFB and 35458,3 of PMF. After 1999, POMSW increased quickly from 60,204.86 and 27,159.6 tons in 2000 to 93,652 and 42,248 tons in 2013 for EFB and PMF, respectively. This period corresponds to the entrance of men in palm oil chain value. These men possess large areas of exploitable selected oil palm plantation and have a high financial capacity to buy modern engine or build big palm oil extraction engine and to employ a large number of laborers [13, 14, 18]. In 2022, POMSW quantities generated by mills are projected to reach 155,821.3 tons of EFB and 70,294 tons of PMF. Koura et al. [18] identified four classes of oil mills based on the quantity of waste produced: small, medium, large, and very large producers of waste. The analysis of POMSW quantities generated by mills of regional union of oil palm producers (RUOPPs) union régionale des producteurs de palmier à huilie (URPPH) during the last years reveals that EFB and PMF increased only in mills that used the modern and semi‐industrialized process (\nFigure 6\n).
\nEvolution of POMSW biomass generated in Benin Republic [
Evolution of POMSW biomass according to extraction palm oil process [
In Benin Republic, some mills do not use all of their generated POMSW. Consequently, they sell and/or discard the excess (\nTable 3\n). The PMFs are more used and sold than EFB. When traditional mill owners decide to upgrade their mills by using the improved extraction method, most of them used these wastes. However, fewer mill owners who practice the modern extraction method use POMSW. Compared to other mill categories, most semi‐industrialized mills sell and reject PMF. The problem of fiber and empty fruit bunches management is not related to the amount of waste generated. In fact, palm oil mills are facing problems of management of fiber and empty fruit bunches even if they are produced in small quantities.
\n\n | % users (Up) | \nCommercial value (CV) | \nRejection rate (RR) | \n|||
---|---|---|---|---|---|---|
Mills categories | \nEFB | \nPMF | \nEFB | \nPMF | \nEFB | \nPMF | \n
\n | \n72 | \n98ab | \n0.02b | \n0.1b | \n0.4 | \n0.1b | \n
\n | \n83.6 | \n100a | \n0b | \n0.3a | \n0.5 | \n0.1ab | \n
\n | \n87.3 | \n94.4b | \n0.03b | \n0.1b | \n0.4 | \n0.01c | \n
\n | \n88.9 | \n88.9ab | \n0.1a | \n0.6 a | \n0.4 | \n0.6a | \n
\n | \n0.09 | \n0.02 | \n<2.2e−16\n | \n3.2 e−6\n | \n0.37 | \n3.9e−10\n | \n
Management of palm oil mill waste quantity generated according to each mill category.
\n
Parameters | \nAxis 1 | \nAxis 2 | \n
---|---|---|
Traditional | \n−0.021 | \n0.159 | \n
Improved | \n0.04 | \n−0.06 | \n
Modern | \n−0.059 | \n−0.005 | \n
Semi‐industries | \n0.509 | \n−0.102 | \n
EFB uses for soap | \n0.017 | \n−0.015 | \n
EFB uses as boiler fuel | \n0.008 | \n−0.046 | \n
EFB uses for fertilization | \n−0.073 | \n0.174 | \n
EFB uses for mushroom production | \n0.034 | \n0.297 | \n
Fiber uses for fertilization | \n1.084 | \n0.367 | \n
Fiber uses as boiler fuel | \n0.021 | \n−0.034 | \n
Fiber uses for fire starting cake production | \n−0.134 | \n0.06 | \n
Correlation between the POMSW uses and mill categories and the first two PCA axes (in brackets is the proportion of variation explained by each axis, expressed in percentage).
POMSW was used as energy, in agriculture and cosmetic (\nFigures 7\n and \n8\n). EFB was burned and the ash was used as potassium in preparation of local soap called “Koto”. According to FAO [43], this ash is also used as a fertilizer by some mills. Analyses of the physicochemical parameters of this ash by Udoetok [44] in Nigeria reveal that it contains appreciable amount of plant nutrients such as calcium (146.15 mg/kg), potassium (139.35 mg/kg), nitrate (97.6 mg/kg), phosphate (47.5 mg/kg), sodium (0.63 mg/kg), magnesium (1.68 mg/kg),and zinc (0.38 mg/kg) and that it justifies its use as an organic manure. POMSW was used directly or indirectly in agriculture as the fertilizer. Fresh POMSW was applied in palm plantation (33.1% of informants) by using two methods. The most common method is local application and the second is mulching [15]. Schuchardt et al. [45] stated that EFBs need to be applied in fresh state to reduced erosion, decreased nitrogen losses, controlled weed growth, improved soils nutrients, and avoided the danger of
Uses of POMSW as energy and in cosmetic in Benin Republic.
Uses of POMSW in agriculture in Benin Republic.
However, POMSW use as a boiler fuel was prohibited in some countries [59] to preserve human and ecological health [60–62]. The double PCA shows that two axes explain 82% of different POMSW uses according to mill categories. Table 4 shows the coefficients of correlation between the POMSW uses and mill categories and the first two PCA axes. This table shows that axis 1 explains modern (modern) and semi‐mechanized (minimech) mills and uses of PMF for fertilization (ffert) and fire starting cake production (ffire). The axis 2 explains traditional (traditio) and improved (improved) mills and EFB uses as a boiler fuel (eboil) or mushroom production (emush) and PMF uses as a boiler fuel (fboil). \nFigure 9\n shows the projection of the POMSW uses by palm oil mill category in the system axes 1 and 2.
\nProjection of POMSW uses by mill categories in the system axes 1 and 2.
The results show that modern mills use more PMF for fire starting production and EFB as a boiler fuel. Mini industrial mills use fibers for fertilization and boiler fuel and EFB for soap production. Traditional mills use EFB for fertilization, mushroom production, and PMF for fertilization and fire starting production. Improved mills use more POMSW as the boiler fuel and sometime EFB for soap production. These wastes can be used for other purposes. According to Abdullah and Sulaiman [63], EFB and PMF are clean, noncarcinogenic, free from pesticides, and soft parenchyma cells. Consequently, they can be used in erosion control, mattress cushion production, soil stabilization, horticulture and landscaping, ceramic and brick manufacturing, paper production, and acoustics control [63]. In great oil palm countries, such as Malaysia, Indonesia, and Thailand, others potentialities of oil palm wastes had been studied [64]. These results demonstrate the possibility of employing hydro thermal for producing solid fuel as well as nutrient recovery from EFB. POMSW can also use as a source of renewable energy [64, 65]. In fact, they can produce steam for processing activities and for generating electricity [64].
\nThe wastes management choice must be influencing by many factors. In Garissa municipality, a study shows that understaffing, lack of education, poor supervision, lack of appropriate facilities, and lack of resident’s support are among reasons leading to poor solid waste management [66]. In Benin Republic, the use of POMSW by a mill does not depend on waste quantities [18] but on the knowledge of producers on this waste uses, the importance and economical input of these wastes. In fact, it had been shown by Koura et al. [67] that the use values of these wastes depend on their importance for mill owners and by Koura et al. [15] that the uses of POMSW for new purposes as composting depends on farmers’ knowledge on what is compost, composting method and possibilities to compost POMSW. Contrary to traditional mills, all others mills use POMSW as the boiler fuel. These mills reduce the quantities of wood use to cook palm fruits with POMSW.
\nPOMSW is useful for farmers in Benin Republic. However, because of the large quantity of wastes produced, some palm oil mills face waste management problem. The choice of one use of these wastes depends on its importance and economic input. By improving oil extraction process, mills are confronted to wood necessity as fuel for stoves and boilers. Consequently, these wastes are priority use as the boiler fuel. This use must be prohibited for environment protection. POMSW is mainly composed of fibers that can be used as renewable energy and solve electricity problems in rural areas. \nTable 5\n presents the estimation of energy content on POMSW in different oil palm countries. Energy content of these wastes is very lower in Benin Republic than the others palm oil producer’s countries. However, this is an opportunity for palm oil mill owners’ country, where there is a predominance of wood energy (fuel wood and charcoal) in the national energy balance. Fuel wood represents 59.4% in the final energy total consumption in 2005, while petroleum products accounted for 38.4%. Electricity represents only 2.2% of these intakes [14].
\nPOMSW | \nBenin Republic [68] | \nNigeria (Rivers state) [69] | \nNigeria (Imo state) [70] | \nMalaysia [71] | \n
---|---|---|---|---|
\n | \n4.4 | \n17.75 | \n– | \n18.84 | \n
\n | \n9.6 | \n18.75 | \n19.67 | \n19.07 | \n
Energy content of POMSW.
On the other hand, POMSW is agricultural waste, rich in unit fertilizers in particular nitrogen and potassium. The best manner to valorize agricultural wastes is their use as fertilizers to improve soil fertility and increase crop yields, hence enhance food security since waste generation had increased with population expansion and industrialization [72]. The present study reveals that the use of POMSW as fertilizer was practiced in traditional mills and was abandon with the upgrade of traditional mill to improve and modern palm oil mills. This use was practiced in semi‐industrial mills that produce big quantities of POMSW. Further research must conduct on the possibilities of using biogas derive from composting to produce electricity for the mill and compost for soils fertilization. It is important to integrate raw materials rich in phosphorus such as poultry manure for POMSW composting because they are poor in this nutrient. These two kinds of POMSW uses will ensure environmental protection, contribute to food security, restore degraded soils, and increase earning money of producers of rural areas.
\nMainly formed of fibers, EFBs composed of spikelet and stalk, and PMFs are the solid wastes generated during palm oil fruit transformation. These wastes contained large amount of nitrogen, calcium, potassium, sulfur, and chloride and less phosphorus. In Benin Republic, POMSW had increased only in mills that used modern and semi‐industrialized process during the 5 last years. Some mills sold and/or discarded these wastes.
\nThe present study reveals that as mini industrial mill that produces big POMSW quantities, traditional mills are confronted to waste management. POMSW was used as energy, in agriculture and cosmetic. The upgrade of traditional mill to improve or modern mills creates the need of wood to feed boiler and stoves. However, this use must be avoided preserving environment. Since the use of POMSW depends on its importance and economic input, furthers studies must be made on its use for electricity generation and cropping soil fertilization through composting.
\nCancer is described as one of the challenging diseases globally, which accounts for 19 million newly diagnosed cases and over 10 million deaths annually making it the leading cause of death [1]. The burden of cancer incidence and mortality is rapidly growing worldwide [1]. Cancer development in humans is a multistep process, which involves various genetic or epigenetic changes and results in the malignant transformation of the normal cells [2]. Recently the use of proteomics, genomics and bioinformatic techniques has unraveled the intricate interplay of numerous cellular genes and regulatory genetic elements that account for the cancerous phenotypes. Higher mortalities associated with cancers are as a result of the absence of very reliable cancer biomarkers, which could be used to diagnose early cancers, predict prognostics and treatment response as well as detection of biomarkers for drug resistance [3]. The unavailability of good biomarkers is a major hindrance for cancer treatment. Cancer biomarkers are not only important for diagnostic purposes but can also be of great prognostic value. With the identification of the right biomarker the cancer progression and effect of chemotherapeutic drugs can be evaluated in great detail [4]. Again, the presence of resistance to therapy, disease relapse, and individual differences continue to reduce the survival chances of cancer patients and makes the disease impossible to cure [5]. It is predicted that therapeutic response assessment, especially treatment response prediction, is valuable to guide treatment strategy determinations and provide responsive therapy for better survival [6]. The identification of reliable cancer biomarkers in the management of cancers may play a crucial role in reducing cancer-related mortality.
Cancer biomarkers are biological molecules that suggest the presence of cancer in a patient. They are either produced by the cancer cells or by other non-cancer cells in response to cancer [7]. Cancer biomarkers may be used to identify the presence of cancer and also help determine its stage, subtype, and whether they will respond to therapy [8]. Cancer biomarkers identified from serum are the most desirable form of the biomarkers that can be used for regular personalized screening, diagnosis, establishing prognosis, monitoring treatment, and detecting relapse. Cancer biomarkers can be classified into three main categories: prognostic biomarkers, which allow prediction of the disease course and survival chances; predictive biomarkers; to assess if a patient benefits from a certain treatment; and pharmacodynamic biomarkers, which are used in the clinics to guide personalized drug dosing and response assessment. In recent years, a group of biological molecules receiving research attention due to their potential utility as circulating biomarkers for cancer are the extracellular vesicles.
Extracellular vesicles (EVs) are small, lipid-bound particles containing nucleic acid and protein cargo which are excreted from cells under a variety of normal and pathological conditions [9]. Recent studies indicated that cancer-associated EVs play pivotal roles in constructing favorable microenvironments for cancer cells. They are therefore considered as new and promising biomarkers for many cancer types. EVs secreted from a variety of cancer types, including pancreatic cancer, ovarian cancer, prostate cancer, breast cancer, colorectal cancer, glioblastoma multiforme (GBM) are reported to contain cancer-associated protein markers [10]. The EVs play important roles in the regulation of intercellular communication and cell microenvironment homeostasis and again as important biomarkers of various cancers. As EVs are increasingly revealed to play important roles in cancer development and to carry specific information related to cancer state. In cancer research, growing evidence indicates that EVs possess the ability to promote tumor growth, metastasis, and angiogenesis [11] mediate tumor immune responses [12]; and stimulate chemotherapeutic resistance, Identification and modification of cancer cell-derived extracellular vesicles may allow for the development of novel diagnostic, preventive and therapeutic approaches in cancers. This chapter summarizes the functions of EV’s in cancers, their potential as biomarkers and therapeutic targets. It further emphasizes the roles of EV’s in cancer prognosis, treatment response and drug resistance.
As membranous vesicles, many cell types in the human body release EVs and cancer cells actively secrete EVs even during the early phase of the disease. Another interesting characteristic of EVs is that its contents are protected from degradative enzymes in body fluids [13]. Based on various characteristics, ranging from size, biogenesis, content, cell of origin, morphology, EV are categorized into four main classes: endosomal-derived small exosomes (Exo) (30–150 nm), plasma membrane-derived middle-sized microvesicles (MV) (100–1000 nm), and large oncosomes (LO) (1000–10,000 nm), as well as apoptotic bodies (500–4000 nm) that are released from dying cells [14].
Typically, exosomes are about 30–150 nm in diameter and are generated via an endosomal route [15, 16, 17]. Exosomes are generated through the endosomal network. This is a compartment, which is membranous in nature and aids in the sorting and direction of intraluminal vesicles such as cell surface membranes and lysosomes to their specific destinations. It is known that exosomal vesicles are formed during an inward budding of early endosomal limiting membrane, which develops into multivesicular bodies in the process [17, 18, 19]. When late endosomal membranes invaginate, intraluminal vesicles (ILVs) are formed within the larger multivesicular bodies [20]. It is during this process that the molecules carried by exosomes including proteins, lipids and nucleic acids are incorporated into the invaginating membrane whiles the components of the cytosol are engulfed by the ILVs [21]. They are liberated into the surrounding body fluids when the multivesicular bodies fuse with plasma membrane. The general function of these early endosomes and multivesicular bodies are endocytic and transportation of the cell’s material. These include storage, recycling, transport, protein sorting and release of these materials [16].
Apoptotic cell-derived extracellular vesicles (ApoEVs) are subcellular and membrane bound in nature. They are produced when cells are undergoing senescence. Further they can be derived from various cell types including endothelial cells, osteoblasts, precursor cells, stem cells and immunocytes [22]. Basically, three major steps are involved in ApoEVs formation. Firstly, there is a prerequisite step which involves cell surface membrane blebbing [23], which is then followed by projections of apoptotic membrane such as apoptopodia, beaded apoptopodia and microtubule spikes which releases 10–20 ApoEVs [24] and lastly the final formation of ApoEVs. Several factors have been shown to present the regulatory function on the generation of ApoEVs, these includes Rho-associated kinase (ROCK1) [25, 26] and Myosin-Light Chain Kinase (MLCK) [27]. Specifically, MLCK is known to enhance nuclear material packaging into ApoEVs, thus molecules that could inhibit caspases, MLCK and ROCK1 are also able to downregulate the production of ApoEVs [28]. Orlando et al., report that formation of blebs which is the first stage in ApoEVs formation are mediated by the presence of actomyosin which increases cell contraction leading to elevated hydrostatic pressure [29]. Researchers have unraveled that ApoEVs are key messengers released by dying cells to regulate processes including cell clearance, tissue homeostasis, pathogen dissemination and immunity thereby implicating them as therapeutic targets and diagnostic purposes.
Microvascular vesicles are derived from myriad cell types surfaces [19]. Unlike ApoEVs, which are generated via indiscriminate surface blebbing or exosomes, which are derived intracellularly within MVBs, microvesicles are formed through active interaction between cytoskeletal protein contraction and the redistribution of phospholipids. Aminophospholipid translocases closely regulate an uneven distribution of the phospholipids in the plasma membrane leading to the formation of micro-domains [30, 31, 32]. Specifically, the plasma membrane budding process is induced by translocation of phosphatidylserine to the outer-membrane leaflet [33, 34]. The process is completed via actin–myosin interactions which cause cytoskeletal structures to contract. This ensures the release of nascent microvesicles into the extracellular space via the direct outward blebbing and breaking off of the plasma membrane [35, 36]. After blebbing, there is a distinct localization of plasma membrane lipids and proteins which informs the rigidity and curvature of the membrane [37, 38]. In addition to the redistribution of membrane lipids and proteins, there is a selective redistribution of the components of microvesicles’ cargo for specific microvesicles enrichment [39]. MVs carry proteins, such as enzymes, growth factors, growth factor receptors, cytokines and chemokines. They also carry lipids, and nucleic acids, including mRNA, miRNA, ncRNA, and genomic DNA [40]. MVs have been detected in the circulation of patients with several cancers, such as lung, breast, prostate ovarian, gastric cancer and colorectal cancer [41, 42]. They have been identified to contribute to tumorigenesis, progression of cancer cells, evasion of apoptosis by tumor cells, and induction of angiogenesis. The tumor-promoting role of MV in tumor mediated exosome communication largely depends on their bioactive cargo. It is believed that the shuttling of tumor-specific proteins to the surrounding cells influence tumor growth. This is achieved through the transfer of oncogenic traits between tumor cells, which result in enhanced tumor growth, and progression [43]. MVs are recently receiving research attention as potential biomarkers because tumor cells are able to constitutively release large amounts of MVs bearing tumor-specific antigens into the bloodstream and other bodily fluids [35]. Researchers have proposed many uses of MV in cancers. Others believe that MVs can be useful for disease staging as well as evaluate the response to therapy by permitting an accurate assessment of a patient’s responsiveness and personalization of treatment [44].
Large oncosomes (LO) are atypically large (1–10 μm diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease [45]. They contain proteins and nucleic acids [46]. Proteins such as caveolin-1 and metalloproteinases 2–9 (MMP2, 9) and GTPase ADP-ribosylation factor 6 (ARF6) are reported to be contained in LO [45]. LO contain miRNA, mRNA and DNA, which transmit signaling complexes between cell and tissue compartments. They can propagate oncogenic information, including transfer of signal transduction complexes, across tissue spaces. Compared to other EVs such as exosomes and MV, LO remains a poorly characterized EV type. LO exerts some functional effects varying on different cells from a direct proteolytic activity to the activation of pro-tumorigenic signals into different types of target cells including other tumor cells or cells of tumor microenvironment [47]. LO has been identified in highly migratory and invasive prostate cancer cells [48]. Recent studies have found that LO can contribute to tumor progression because they are able to degrade directly ECM in vitro [45]. Other researchers again have revealed that they have the ability to establish a tumor growth-supporting environment. This they believe is through the export of specific oncogenic cargo to other tumor or stromal cells [49]. Prostate cancer cell–derived oncosomes contain bioactive MMP9 and MMP2 and exhibit proteolytic activity on gelatin. This suggests that they could be a means to focally concentrate proteases that facilitate migration of tumor cells, thus promoting metastasis [50]. Considering their atypical size and their specific release from cancer cells, LO are promising source of both diagnostic and prognostic markers in cancers.
The importance and the role played by the tumor microenvironment on tumor development and progression has been established in recent years [51]. EVs are known to influence the tumor microenvironment either through a direct impact on the tumor or from a distant site which promote future metastasis of circulating cancer cells [51]. Due to these characteristics, key processes involved in cancer developments such as angiogenesis, thrombosis, oncogenic transfer, immune modulation and pre-metastatic niche formation have seen an up-regulation of EVs [52, 53, 54, 55, 56, 57]. Compared to non-malignant cells, tumor cells are known to release higher amounts of EVs. In this regard increased levels ESCRT components as well as heparanase and syntenin have been expressed in various cancers [58, 59, 60]. Specifically, in colorectal cancer and pancreatic carcinoma, hyperactivity of RalB has been observed and in non-small-cell lung cancer YKT6 overexpression coupled with elevated Rho-ROCK signaling expressed in various type of cancers may contribute to EVs generation in tumor cells [61, 62, 63, 64]. On the basis that tumorigenesis occurs due to accumulation of genetic alterations, the metastatic traits of EVs are expressed through the transfer of their oncogenic cargo. Tumor derived EVs through the co-transfer of protein crosslinking enzymes (tissue transglutaminase) and fibronectin, are able to import transformed characteristics of cancer cells on to recipients endothelial cells and fibroblast [57]. Both the cell-intrinsic and environmental signals may influence EV release in tumor cells. EVs production in tumor cells may be induced by the activation of H-RASv12 and EGFRvIII oncogenic signal pathways [65, 66, 67]. Again, the level (de)regulation of the machinery, which aid in plasma membrane fusion could also influence the release of EVs in tumor cells. For example, it has been demonstrated that EV secretion could be enhanced when PKM2 (a glycolytic enzyme associated with the Warburg effect) is over expressed leading to phosphorylating tSNARE SNAP23 [68]. Also SRC, a proto-oncogene, through the phosphorylation of the cytosolic domains of syntenin and syndecan is able to stimulate the syntenin exosome biogenesis pathway [69]. On the other hand, in some cancers such as colon cancer cells, mutant proto-oncogene, KRAS could be transferred via EVs to increase the population of recipients colon cancer cells expressing the wild-type KRAS [70]. Further an increase in levels of tissue factor (TF) bearing EVs are known to mediate thrombosis occurrence in cancer patients. Available evidence indicates a possible role of tumor-derived EVs in thrombosis occurrence among cancer subjects [54]. Specifically, P-selectin glycoprotein ligand-1 (PSGL-1) and TF have been implicated in cancer associated thrombosis [71]. In mice with induced pancreatic tumor, formation of thrombosis was high compared to cancer free mice [72]. A major hallmark of tumor growth and development is increased angiogenesis. That is to say for the development of the tumor beyond its minute size an adequate supply of oxygen and nutrients is essential for its survival. Thus, numerous studies have established that besides the cell’s intrinsic mechanisms, the release and regulation of exosomes and microvesicles could be due to enhanced prevailing hypoxic microenvironmental conditions [73, 74, 75]. In hypoxic glioma cells, an induction of a pro-angiogenic process mediated by derived EVs was able to influence the vasculature surrounding cell [55]. Another specific example where EVs promotes angiogenesis is reported in squamous carcinoma. It was reported that in A431 squamous carcinoma cells, angiogenesis was induced as a results of a direct transfer oncogenic epidermal growth factor receptor (EGFR) from the derived EVs to endothelial cells [76].
RNAs are a major important cargo incorporated into EVs. Cancer cells promote an increase in the release of EVs containing varying amount and types of proteins and RNAs compared to normal cells [77, 78]. There exist an EV-RNA mediated crosstalk within tumors and also between tumors and stroma which could modify the malignant behavior of cancer cells [79]. EV-RNAs derived from tumor may be implicated in the devolvement of oncogenic, pro-angiogenic, and pro-metastatic processes as well as stromal cell differentiation in the tumor microenvironment. Also it is known that normal and tumor cells subpopulations are likely to be driven towards malignant phenotypes aided by tumor derived EVs [79]. Some EV-RNAs are known to actively mediate proliferation, migration, invasion, apoptosis, dormancy and therapy resistance of cancer cells. There seems to be a dual function of EV-RNAs in cancer pathology. Whiles some are known to promote the malignant characteristics of cancer cells, it also possible for some EV-RNAs to inhibit the malignant characteristics of cancer cells. In this regard various studies have reported the ability of EV-RNAs to inhibit mechanisms that favor tumor growth. In order to establish homeostasis, various non tumor cells can produce miRNAs which could suppress the malignant phenotypes of adjacent cancerous cells [80]. This is due to the fact that a natural competition exists between cancerous and adjacent non-cancerous cells during the development of cancer [81, 82]. In hepatocellular carcinoma, EV-miRNAs released from liver stem cells were able to promote apoptosis whiles inhibiting cell proliferation
Tumor cells release EV-RNAs. These EV-RNAs mediate many functions including sustaining proliferation, migration, invasion and metastasis, evading growth suppression, dormancy and therapy resistance of tumor cells, which promote growth.
The release and (de)regulation of cancer EVs and their cargo critically influence the crosstalk between tumor and stromal in the tumor microenvironment, adjacent normal cells and even distant (pre-) metastatic areas. Various stages of cancer metastasis especially the epithelial-mesenchymal transition (EMT) stage are influenced by cancer stromal cell derived EVs [91]. Mesenchymal stromal cells (MSC) are very important in the cancer stromal EMT induction [92]. There is ample evidence to show that certain components of the cargo carried by MSC-derived EVs could promote cancer metastasis by stimulating, inducing and promoting EMT. Specifically, it was shown that in breast cancer cells, EVs generated from adipose-tissue MSCs could activate the Wnt signaling pathway thus promoting cancer cell migration [93]. Again it has been demonstrated that EVs generated from human umbilical cord MSCs promoted EMT through Extracellular signal-regulated kinase (1/2) (ERK) signaling pathway with subsequent promotion of invasion and migration of breast cancer cells [94]. Also in lung cancer, EVs derived human umbilical cord MSCs promoted EMT and when TGF-β in the MSCs were knocked down EMT was inhibited [95].
EVs have gained extensive attention as promising biomarkers for cancer diagnostics. Characteristics of EV include their relatively short-lived or highly labile in the cytoplasm of donor cells make them a stable biomarker cargo, be it protein, lipid, nucleic acid. In cancer these molecules can be reflective of both the tumors presence and also of cancer staging. Some studies have demonstrated that biomolecules in serum or plasma exosomes are of great value for tumor diagnosis including long non-coding RNAs (lncRNAs), miRNAs, and proteins [96]. Some other important properties of EVs which make researchers believe they represent cancer biomarkers are: (a) most of EVs populations are shed from all cell types in the organism; (b) molecular determinants contained in EVs are dependent on cells/tissues of origin; (c) however the specific EVs cargo (i.e. proteins, miRNAs) is not always coupled to the overexpression in the cells of origin; (d) molecular cargos in EVs can be affected by microenvironment conditions such as inflammation, oxygen deprivation, and metabolic balance; (e) EVs size may affect their content. In several cancers, including ovarian cancer, it has been demonstrated that the expression of a specific subset of miRNAs may potentially be used in clinical practice, for example, for screening or early diagnosis to evaluate the response to therapeutic treatments. EVs in blood and urine of prostate cancer patients contain unique prostate-cancer specific contents that are biomarkers of prostate cancer [97, 98]. EVs are proving to be valuable diagnostic biomarker in pancreatic cancer; flow cytometry coupled with mass spectrometry analysis of exosome glypican-1 can distinguish benign disease from early and late stage cancer [99]. Again, the detection of DEL-1 on circulating EVs facilitated early-stage breast cancer diagnosis and discrimination of breast cancer from benign breast disease [100]. EV-survivin is proposed to be useful in breast cancer diagnosis [101]. Kibria et al. also suggested that EV-CD47 may be a possible breast cancer biomarker [102].
Communication between cells in a tumor microorganism is largely via chemokines, cytokines, or growth factors [10]. These notwithstanding, EVs from cells in the tumor microenvironment are also noted to facilitate such communications owing to their role in tumor progression [103]. EVs are endogenous vesicles whose composition and function makes them attractive vehicles for the delivery of therapeutic agents to target cells. They have experienced increasing attention in recent years since studies into their roles demonstrated their importance as therapeutic nanomaterials. Compared to some existing synthetic or traditional carriers, EVs are considered more suitable for use as nanovesicles due to their characteristic properties of being intrinsically biocompatible, low immunogenicity and toxicity and their ability to cross-physiological barriers such as the blood-brain barrier. In addition, they have biodegradable and modification abilities and have the capability to escape clearing actions of the immune system [104, 105]. The first report of a successful therapeutic application of EVs was reported by Alvarez-Erviti et al. [106] in 2011. In that study, modified exosomes were exploited and a transfer of siRNAs was made into the brain of mice, which resulted in a knock down of the targeted gene. Supporting this hypothesis, a study by Saari et al. observed the delivery of chemotherapeutics to recipient cells and these were subsequently released into intracellular milieu to give rise to an increased cytotoxic bioactivity. The chemotherapeutics were noted to have been loaded by tumor-cell derived EVs [107]. There are three main approaches that are utilized by EVs in their role as therapeutic agents that include elimination of EVs in circulation, inhibition of secretion and disruption of the absorption of EVs.
The elimination of EVs secreted by cancer cells has been one of EV-targeting therapeutic strategies. The first report of the use of this target therapeutic approach was by Marleau et al., [108] In the study, a hemofiltration system that was capable of targeting EVs from cancer cells by specifically aiming at human epidermal growth factor receptor 2 (HER-2) on the surface of EVs was proven [108]. This targeting of HER-2 which results in the selective elimination of cancer derived-EVs could be very valuable for cancer treatment [109].
A number of studies have focused on other strategies that block EV secretion. Inhibition of intraluminal vesicles formation and release of EVs by the fusion of MVBs to the plasma membrane have been achieve by the use of a sphingomyelinase inhibitor drug, GW4869 [110, 111]. Again, the inhibition of EV production and the transfer of miR-210-3p have reportedly been achieved by the attenuation of neutral sphingomyelinase 2 (nSMase2). nSMase2 is known to control the synthesis of ceramide and suppresses angiogenesis and metastasis in breast cancer xenograft model [112]. Conversely, EV secretion from prostate cancer cells was not inhibited by the downregulation of nSMase2. Meanwhile, nSMases have been revealed in normal neural cells [113, 114]. Their presence in these normal cells indicates the inhibition of some other fundamental pathways. Cancer specific mechanisms of EV secretion are therefore very crucial in the establishment of the role of EVs as cancer therapeutic targets. Quite recently, a group of researchers have identified a number of activators and inhibitors of EV production from prostate cancer cells [115]. This implies a clear understanding of cancer specific mechanism of EV production is required in identifying cancer-specific therapies mediated by targeted EVs.
Reports into the role of EVs have shown that the process of anti-melanoma is facilitated by EVs released by natural killer cells [116]. Similarly, the abundance of histocompatibility complex classes I and II from dendritic cells are capable of triggering other immune system cell types and also activate antitumour immune responses [117]. The use of these traditional methods in obtaining EVs for direct use as cancer therapeutic targets are not without challenges. Indistinct production mechanisms, low product yield, and the high probability of obtaining EV contents that stand the chance of mutation are a few of such challenges faced by these methods. The intrinsic properties of EVs, however, makes the engineering of these nanoparticles for the purpose of drug delivery to target cells a more favorable approach for cancer management. Engineering parental cells to shed EVs with a particular cargo or loading it directly can achieve encapsulating of therapeutic cargoes into EVs. This has been utilized in breast cancer and leukemia cell studies by Usman et al., [118] in the delivery of RNA drugs by RBC-derived EVs (RBCEVs) which showed an improved miRNA inhibition and CRISPR-Cas9 genome editing with no known cytotoxicity. Other studies on the engineering of EVs include research using mesenchymal stem cells in the overexpression of MiR-379 to obtain MiR-379-rich EVs which functions to subdue metastatic breast cancer development [119].
An increasing amount of research has established that EVs are present in every human biological fluid including lymphatic and seminal fluids, bile, urine, breast milk, ascites, cerebrospinal fluid, saliva and blood, making these fluids a good source for many liquid biopsy approaches [120, 121, 122]. An increase in the rate of release of EVs on the account of cellular activation and/or during pathologic conditions may be considered an indication of a possible pathologic condition [123, 124, 125]. Real-time cancer treatment response and monitoring can be done using cancer-derived components obtained from these body fluids. The components include EVs, microRNA, circulating tumor cells (CTC), circulating cell-free tumor DNA, long non-coding RNA and EVs [126]. During the development and treatment of cancer conditions, the state of the cell is revealed by the level of active secretion of EVs, which provide timely information on the changing dynamics of the cell [18, 127]. Cancer-derived components like miRNAs obtained through liquid biopsy inhibits mRNA degradation by binding to coding sequences, 5’untranslated region (UTR), or 3’UTR of target mRNAs leading to the inhibition of mRNA degradation or translation [128]. When miRNAs bind to target mRNAs, the mRNA level as well as protein expression are essentially regulated. This means, circulating EVs are latent tools that are utilized in the quest to find a way of monitoring changes in tumor cells during treatment.
A number of studies have reported the relationship between EVs and cancer treatment response. The presence of immune checkpoints and the application of the blocking of these points by some drugs have been exploited in novel anti-cancer treatment regimens [129]. Research into the capacity of EVs as a regulating tool for checkpoint therapy has contributed immensely to the growing need of the essence of monitoring immunotherapy. Anti-tumor immunity and related expressions can be suppressed by programmed cell death 1 ligand (PDL-1) and the identification of these ligands on EVs has shown the potential for use as biomarkers in tumor patients [130]. In a syngeneic mouse melanoma model in C57BL/6 mice and B16-F10 cells experiment by Chen et al. [131]. Analysis of PDL-1 expression proved the application of EVs as a potential monitoring tool in PDL-1 therapy in melanoma patients. PDL-1 expression was either present or knocked down in these models and the levels of tumor-infiltrating CD8+ T-lymphocytes was significantly reduced in the PDL-1 expressing group compared those knocked down. A positive correlation which varied all through anti-PDL-1 therapy was observed of interferon-γ and the level of EV associated PDL-1 during the analysis of patients with metastatic melanoma [131].
In some specific cancer studies, König et al., [132] analyzed EV concentration and circulating tumor cells in breast cancer patients as a marker for the close observation, monitoring and prediction of prognosis in primary and locally advanced breast cancer. Analysis of the cells and EVs were done before and after the administration of neoadjuvant chemotherapy (NACT) prior to a surgical procedure. Patients’ response to NAC is an early indication of the efficacy of subsequent systemic therapy. The overall after-NACT response is a strong prognostic factor for the risk of reoccurrence [133]. Patients with a pathologic complete response (pCR) after NACT have a significant higher overall as well as disease-free survival (OS, DFS) than their counterpart patients with residual invasive disease [134]. Studies have shown that before the administration of NACT during therapy, there is an overall an increase in EV concentration, which is linked to lymph node infiltration, while the after-NACT elevation of EV concentration is associated with reduced three-year progression-free and overall survival. This means, the analysis of EVs together with CTC analysis is a promising tool in the assessment of residual disease and the monitoring of therapy and disease outcome [132]. Other studies have used EVs in diverse ways with respect to their role in treatment response and prognosis. The first exosome-based liquid biopsy test, ExoDx™ Prostate IntelliScore (Exosome Diagnostics, Inc., Waltham, MA, USA), was approved by the Food and Administration Authority (FDA) in 2019 to analyze the exosomal RNA for the biomarkers PCA3, TMPRSS2:ERG, and SPDEF on urine specimen [135]. The prostate specific antigen available in this approach is an effective diagnostic and prognostic tool and the monitoring of this antigen together with digital rectal examination is utilized in men who have gone through a definitive therapy for localized cancer of the prostate. Again, in non-metastatic prostate cancer patients undergoing radiotherapy, a higher concentration of circulating EVs have been detected by Nano tracking analysis as a means of monitoring treatment response [136]. The study proposed a possible radiation specific induction resulting from the upregulation of hsa-miR-21-5p and hsa-let-7a-5p, both of which are specific miRNAs related to prostate cancer and radiotherapy [137]. This is further supported by the observation of altered expression of blood extracted EVs and their miRNA cargoes in the monitoring of prostate cancer radiotherapy response [138]. A high expression of some specific miRNAs before radiotherapy were noted to be an indication of better therapeutic outcomes [138]. More applications of the role of EVs in the cancer are recorded for cancer conditions such as glioblastoma [139], colorectal [140], liver [141], and non-solid cancers [142].
Due to an improved effectiveness of cancer therapies lately, there have been an increase in the survival rate of diagnosed cases [143]. Some tumors however, remain non-responsive to available treatment regimen resulting in patients going through relapse. Many cancer drugs work by causing damage in the DNA of dividing cells, which eventually result in their apoptotic death. Research has shown that some cells gain the ability to effectively repair the damage caused to them or lose the capacity to recognize apoptotic signals which renders them less capable of submitting to programmed cell death [144, 145]. Such cells become more likely to grow resistant. The failure of treatment in general and for that matter cancer treatment could occur through various ways. It could happen through drug metabolism alterations, or changes in the efflux and/or absorption of drugs from target cells. In addition to this, the ability of drugs to induce mutations and the inhibition of cellular apoptotic pathways are all ways by which drug resistance could occur. Once acquired, the multidrug resistance of cancer drugs can lead to resistance to other drugs of different structural make-up or target.
Cancer cells have specific characteristic genetic make-up together with varying expressions of tumor suppressor genes and oncogenes. This makes them respond distinctively to various drugs. Interactions exist between host and tumor microenvironment together with changes in these genetic factors which contribute to drug resistance [146, 147]. Drug resistance represents a daunting challenge in the treatment of cancer patients. There are two types of drug resistance: de novo drug resistance, which refers to the insensitivity of cancer cells to chemotherapy before receiving drug treatment, and acquired resistance, which refers to the acquired drug resistance of cancer cells after being treated [148]. Understanding drug resistance has not been an easy task because of how complex and challenging their supporting molecular mechanisms are [149, 150, 151, 152]. In fact, the source of resistance of a drug in a person may be very different from that of another individual because of the variations in fundamentals of different cellular processes. Playing an important role in drug resistance are extracellular vesicles. They mediate cancer drug resistance such that cells that secrete more of these vesicles show higher level of resistance than those that secrete less [153].
Recently, there are many studies concerning the role and effects of EVs in disease control and drug resistance. They have been identified to show a profound role in the development of chemo-insensitivity and drug resistance [148]. The study into their characteristics increased after they were discovered to be involved aspects of cancer progression including in proliferation, tumorigenesis, angiogenesis, and invasiveness [154, 155, 156]. In cancer drug resistance analysis, therapeutic targets are very much implicated in the development of resistance. The mediation of drug resistance by EVs takes place through a number of mechanisms. One is by the reduction of the effective concentration of cytotoxic drugs at target sites through the behavior of EVs acting as a pathway for the sequestration of such drugs. That is, resistance can arise when there is an up-regulation of vesicles that export drugs from cells or a reduction in those carriers that import drugs into the cells [157, 158, 159, 160, 161]. The results of such changes are the alteration in the concentrations of chemotherapeutics at the active sites. These vesicles may also act as decoys, carrying membrane proteins and capturing monoclonal antibodies intended to target receptors at the cell surface. They can also mediate cross-talk between cancer cells and stromal cells in the tumor microenvironment, leading to tumor progression and acquisition of therapeutic resistance. Apart from their role in drug resistance within a cell, EVs can transfer the resistance from a cell to another cell [162].
Although cargoes of EVs are passively packaged into EVs, evidence have shown the existence of selective packaging as well [163]. Major components of EVs include protein that contribute to determining the destination of EVs and also influence the phenotype of recipient cells [163]. Vesicular protein transfers between cells constitute a potential mechanism of action of these effects. An example is the transfer of an ATP binding cassette called P-glycoprotein (P-gp), which has been reported to mediate resistance in recipient cells during their transfer between cells. In other instances, it is the expression of P-gp that becomes induced in receiver cells after a different kind of protein is delivered [164]. For example, the transfer of TrpC5 protein to recipient cells by adriamycin resistant MCF7 cells through EVs is known to stimulate the translocation of NFATc3 protein resulting in the transcriptional activation of MDR1 (ABCB1) promoter [165]. The characteristics and pathways by which drug-sensitive cells acquire resistance from EVs containing P-gp have been investigated quite extensively. The process of transfer of cancer traits from drug resistant cells to drug sensitive cells is dependent on characteristics of donor cell. While EVs from cells of leukemia transfer P-gp to malignant and non-malignant cells, those from drug resistant breast cancer cells transfer P-gp to malignant recipient cells only [166]. These findings demonstrated that P-gp transfer by EVs are potentially tissue selective and are likely associated with the cell of origin of EVs rather than their possible relation to a particular feature of recipient cell membrane [166]. In another study, de-Souza et al., [167] explored the selectivity of P-gp transfer and found no discrimination in relation to cell-type. In their study, EVs from drug-resistant leukemia cells could transfer P-gp to drug-sensitive lung and breast cancer cells. Altogether, these findings indicate the debatable issue of the selectivity of EV cargo and therefore require further investigation.
EVs can also carry non-coding RNAs such as miRNAs, IncRNAs, and circRNAs which are noted to mediate cell to cell transfer of resistance [164, 168]. These RNAs have been found to be associated with cancer progression and their deregulation is noted to support drug resistance in tumors of diverse origins [169, 170, 171]. Through the transmission of active biomolecules to neighboring cells, these various RNAs induce drug resistance in recipient cells. The transmitted biomolecules regulates certain genes together with their corresponding signaling pathways [168].
miRNAs contributes to the progress of chemoresistance by influencing the genes that are involved in cell cycle, cell proliferation and survival, apoptosis and immunity [172]. They regulate the genes by inhibiting the translation of mRNA. miRNAs have been reported in several studies to play a role in EV mediated chemoresistance. For instance, several miRNAs have been identified to be involved in the transfer of gemcitabine resistance. Gemcitabine is a chelator of DNA that gets activated by deoxycytidine kinase. EVs secreted by macrophages associated with tumors and having miR-365 cargoes have been identified to induce resistance of pancreatic ductal adenocarcinoma cells in the treatment of gemcitabine. The concentration of triphosphate nucleotides (NTPs) in the recipient cells become increased by miRNAs and the result is competitive interaction between activated gemcitabine and the increased levels of NTPs which efficiently reduces the efficacy of gemcitabine [173]. In another study, abundance of miR-1246 was observed to have been present in EVs secreted by paclitaxel resistant ovarian cancer cells. The transfer of this miRNA upregulated the expression of ABCB1 and inhibited the expression of Cav1 to facilitate paclitaxel efflux and in the process promoting drug resistance phenotype in recipient cells [174]. Conversely, EVs secreted by cancer-associated fibroblasts were found to contain miR-106 when exposed to gemcitabine. Resistance of pancreatic cancer cells (AsPC-1) against the treatment of gemcitabine has been found to be associated with the uptake of miR-106 enriched EVs [175].
Several studies have also made efforts to demonstrate the link between specific EV-transferred miRNAs and drug resistance. Through the EV-mediated transfer of miR-21, drug resistance has been found to be induced in MCF7 cells after they were co-cultured with EVs from multidrug-resistant chronic myeloid leukemia cell lines [167], Again, cisplatin resistance in lung cancer cells by miR-96 [176], Adriamycin resistance in breast cancer by miR-222 [148], and EVs’ miR-155 mediated gemcitabine resistance in pancreatic cancer cells [177] have been reported. Further studies found exosomal miR-19b mediated oxaliplatin-resistance in SW480 colorectal cancer cells [178], tamoxifen-resistance in ER-positive breast cancer MCF7 cells by miR221/222 [179].
The EVs are secreted from various types of cells and are regulated by physiological conditions and other pathological conditions including cancers. EVs are considered to be attractive resources for cancer biomarker development. More research to identify potential biomarkers should be performed. This may provide more clues for elucidating the biological functions of EVs in cancer development as well as predicting the disease progression. These researches about the EVs will again offer valuable information to increase our understanding into the pathology of cancer and provide the novel ways to advance the diagnosis and prognosis of cancers.
This work was supported by China Postdoctoral Science Foundation (Grant No. 2018M642187).
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Samim Al Azad and Slimane Ed-dafali",coverURL:"https://cdn.intechopen.com/books/images_new/11392.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10400",title:"The Application of Ant Colony Optimization",subtitle:null,isOpenForSubmission:!1,hash:"f4fdfd07ee1ab99fb7c740d6d0c144c6",slug:"the-application-of-ant-colony-optimization",bookSignature:"Ali Soofastaei",coverURL:"https://cdn.intechopen.com/books/images_new/10400.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"257455",title:"Dr.",name:"Ali",middleName:null,surname:"Soofastaei",slug:"ali-soofastaei",fullName:"Ali Soofastaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10915",title:"Leadership",subtitle:"New Insights",isOpenForSubmission:!1,hash:"0d72e79892f2a020cee66a52d09de5a4",slug:"leadership-new-insights",bookSignature:"Mário Franco",coverURL:"https://cdn.intechopen.com/books/images_new/10915.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"105529",title:"Dr.",name:"Mário",middleName:null,surname:"Franco",slug:"mario-franco",fullName:"Mário Franco"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10683",title:"Technological Innovations and Advances in Hydropower Engineering",subtitle:null,isOpenForSubmission:!1,hash:"7ce7ad8768bd2cad155470fe1fd883f4",slug:"technological-innovations-and-advances-in-hydropower-engineering",bookSignature:"Yizi Shang, Ling Shang and Xiaofei Li",coverURL:"https://cdn.intechopen.com/books/images_new/10683.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7102",title:"Pneumonia",subtitle:null,isOpenForSubmission:!1,hash:"9fd70142814192dcec58a176749f1b60",slug:"pneumonia",bookSignature:"Nima Rezaei",coverURL:"https://cdn.intechopen.com/books/images_new/7102.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9670",title:"Current Trends in Wheat Research",subtitle:null,isOpenForSubmission:!1,hash:"89d795987f1747a76eee532700d2093d",slug:"current-trends-in-wheat-research",bookSignature:"Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9670.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"961",title:"Fluid Dynamics",slug:"surface-science-fluid-dynamics",parent:{id:"160",title:"Surface Science",slug:"surface-science"},numberOfBooks:5,numberOfSeries:0,numberOfAuthorsAndEditors:104,numberOfWosCitations:222,numberOfCrossrefCitations:123,numberOfDimensionsCitations:294,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"961",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7385",title:"Cavitation",subtitle:"Selected Issues",isOpenForSubmission:!1,hash:"075ee4bb432760777ffcba092d0cffae",slug:"cavitation-selected-issues",bookSignature:"Wojciech Borek, Tomasz Tański and Mariusz Król",coverURL:"https://cdn.intechopen.com/books/images_new/7385.jpg",editedByType:"Edited by",editors:[{id:"186373",title:"Dr.",name:"Wojciech",middleName:null,surname:"Borek",slug:"wojciech-borek",fullName:"Wojciech Borek"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7352",title:"Granularity in Materials Science",subtitle:null,isOpenForSubmission:!1,hash:"a451ff13b9bc3b08989979518577594a",slug:"granularity-in-materials-science",bookSignature:"George Kyzas and Athanasios C. Mitropoulos",coverURL:"https://cdn.intechopen.com/books/images_new/7352.jpg",editedByType:"Edited by",editors:[{id:"152296",title:"Prof.",name:"George",middleName:"Z.",surname:"Kyzas",slug:"george-kyzas",fullName:"George Kyzas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6512",title:"Superfluids and Superconductors",subtitle:null,isOpenForSubmission:!1,hash:"24385ec1d5de9c6597896900c80ee279",slug:"superfluids-and-superconductors",bookSignature:"Roberto Zivieri",coverURL:"https://cdn.intechopen.com/books/images_new/6512.jpg",editedByType:"Edited by",editors:[{id:"181334",title:"Prof.",name:"Roberto",middleName:null,surname:"Zivieri",slug:"roberto-zivieri",fullName:"Roberto Zivieri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5319",title:"Wetting and Wettability",subtitle:null,isOpenForSubmission:!1,hash:"49767cc09f266bd5bdf55f4a5c57792b",slug:"wetting-and-wettability",bookSignature:"Mahmood Aliofkhazraei",coverURL:"https://cdn.intechopen.com/books/images_new/5319.jpg",editedByType:"Edited by",editors:[{id:"155413",title:"Dr.",name:"Mahmood",middleName:null,surname:"Aliofkhazraei",slug:"mahmood-aliofkhazraei",fullName:"Mahmood Aliofkhazraei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2854",title:"Viscoelasticity",subtitle:"From Theory to Biological Applications",isOpenForSubmission:!1,hash:"63c4a0eddb48f02ebe48d80aa70972de",slug:"viscoelasticity-from-theory-to-biological-applications",bookSignature:"Juan de Vicente",coverURL:"https://cdn.intechopen.com/books/images_new/2854.jpg",editedByType:"Edited by",editors:[{id:"99801",title:"Dr.",name:"Juan",middleName:null,surname:"De Vicente",slug:"juan-de-vicente",fullName:"Juan De Vicente"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:5,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"48816",doi:"10.5772/60824",title:"Wettability and Other Surface Properties of Modified Polymers",slug:"wettability-and-other-surface-properties-of-modified-polymers",totalDownloads:3698,totalCrossrefCites:9,totalDimensionsCites:36,abstract:"Surface wettability is one of the crucial characteristics for determining of a material’s use in specific application. Determination of wettability is based on the measurement of the material surface contact angle. Contact angle is the main parameter that characterizes the drop shape on the solid surface and is also one of the directly measurable properties of the phase interface. In this chapter, the wettability and its related properties of pristine and modified polymer foils will be described. The wettability depends on surface roughness and chemical composition. Changes of these parameters can adjust the values of contact angle and, therefore, wettability. In the case of pristine polymer materials, their wettability is unsuitable for a wide range of applications (such as tissue engineering, printing, and coating). Polymer surfaces can easily be modified by, e.g., plasma discharge, whereas the bulk properties remain unchanged. This modification leads to oxidation of the treated layer and creation of new chemical groups that mainly contain oxygen. Immediately after plasma treatment, the values of the contact angles of the modified polymer significantly decrease. In the case of a specific polymer, the strongly hydrophilic surface is created and leads to total spreading of the water drop. Wettability is strongly dependent on time from modification.",book:{id:"5319",slug:"wetting-and-wettability",title:"Wetting and Wettability",fullTitle:"Wetting and Wettability"},signatures:"Nikola Slepickova Kasalkova, Petr Slepicka, Zdenka Kolska and\nVaclav Svorcik",authors:[{id:"144929",title:"Prof.",name:"Vaclav",middleName:null,surname:"Svorcik",slug:"vaclav-svorcik",fullName:"Vaclav Svorcik"},{id:"146297",title:"Dr.",name:"Petr",middleName:null,surname:"Slepicka",slug:"petr-slepicka",fullName:"Petr Slepicka"},{id:"147600",title:"Ph.D.",name:"Nikola",middleName:null,surname:"Slepičková Kasálková",slug:"nikola-slepickova-kasalkova",fullName:"Nikola Slepičková Kasálková"},{id:"153983",title:"Dr.",name:"Zdeňka",middleName:null,surname:"Kolská",slug:"zdenka-kolska",fullName:"Zdeňka Kolská"}]},{id:"48822",doi:"10.5772/60808",title:"Wettability of Nanostructured Surfaces",slug:"wettability-of-nanostructured-surfaces",totalDownloads:3122,totalCrossrefCites:11,totalDimensionsCites:31,abstract:"There are many studies in literature concerning contact angle measurements on different materials/substrates. It is documented that textiles can be coated with multifunctional materials in form of thin films or nanoparticles to acquire characteristics that can improve the protection and comfort of the wearer. The capacity of oxide nanostructures to inhibit fungal development and neutralize bacteria is a direct consequence of their wetting behavior [1–6]. Moreover, the radical modification of wetting behavior of nanostructures from hydrophilic to hydrophobic when changing the pulsed laser deposition (PLD) ambient will be thoroughly discussed.",book:{id:"5319",slug:"wetting-and-wettability",title:"Wetting and Wettability",fullTitle:"Wetting and Wettability"},signatures:"L. Duta, A.C. Popescu, I. Zgura, N. Preda and I.N. Mihailescu",authors:[{id:"17636",title:"Prof.",name:"Ion N.",middleName:null,surname:"Mihailescu",slug:"ion-n.-mihailescu",fullName:"Ion N. Mihailescu"},{id:"23532",title:"Dr.",name:"Andrei",middleName:null,surname:"Popescu",slug:"andrei-popescu",fullName:"Andrei Popescu"},{id:"174343",title:"Dr.",name:"Liviu",middleName:null,surname:"Duta",slug:"liviu-duta",fullName:"Liviu Duta"},{id:"174344",title:"Dr.",name:"Irina",middleName:null,surname:"Zgura",slug:"irina-zgura",fullName:"Irina Zgura"},{id:"174345",title:"Dr.",name:"Ligia",middleName:null,surname:"Frunza",slug:"ligia-frunza",fullName:"Ligia Frunza"}]},{id:"49090",doi:"10.5772/61205",title:"The Wetting of Leaf Surfaces and Its Ecological Significances",slug:"the-wetting-of-leaf-surfaces-and-its-ecological-significances",totalDownloads:3519,totalCrossrefCites:13,totalDimensionsCites:25,abstract:"Leaf wettability, indicating the affinity for water on leaf surfaces, is a common phenomenon for plants in a wide variety of habitats. The contact angle (θ) of water on leaves measured at the gas, solid and liquid interface is an index of surface wettability. Leaves are termed as “super-hydrophilic” if θ < 40°, “highly wettable” if θ < 90°, and “wettable” if θ < 110°. If θ > 110°, the leaves are classified as being non-wettable, while θ > 130° for highly non-wettable and θ > 150° for super-hydrophobic. Both internal and external factors can influence leaf wettability. The chemical composition and structure of leaf surfaces are internal causes, but the external environment can also influence wettability by affecting the structure and composition of the surface. The main internal factors that affecting leaf wettability include the content and microstructure of the epidermal wax, the number, size and pattern of trichomes, stomatal density, the shape of epidermal cells, and leaf water status. The leaf contact angles increased with the increasing of leaf wax content. However, studies have shown that the contact angles were more dependent on the complexity of wax structure than on the absolute amount. For trichomes, there are three types of interaction between trichomes and water droplets, including (1) low trichomes density: no apparent influence of trichomes on the location of surface moisture, droplet formation and retention ; (2) medium trichomes density: trichomes appear to circle surface moisture into patches; (3) high trichomes density: trichomes appear to hold water droplets above the trichomes. In some cases, a higher stomatal density was accompanied with a higher contact angles. While, it was also observed that there was no significant correlation between contact angle and stomatal density for some species. For the effects of epidermal cells on leaf wettability, it was generally considered that the combination of a dense layer of surface wax and the convex epidermal cells was what created a hydrophobic leaf surface. However, the influence of leaf water content on contact angle of water droplets on different leaf surfaces was complex, e.g., contact angles increased with decreasing of leaf water content, contact angle remained to be constant with different leaf water content.",book:{id:"5319",slug:"wetting-and-wettability",title:"Wetting and Wettability",fullTitle:"Wetting and Wettability"},signatures:"Huixia Wang, Hui Shi and Yanhui Wang",authors:[{id:"173921",title:"Dr.",name:"Huixia",middleName:null,surname:"Wang",slug:"huixia-wang",fullName:"Huixia Wang"}]},{id:"40738",doi:"10.5772/49979",title:"Viscoelastic Properties of Biological Materials",slug:"viscoelastic-properties-of-biological-materials",totalDownloads:5567,totalCrossrefCites:12,totalDimensionsCites:24,abstract:null,book:{id:"2854",slug:"viscoelasticity-from-theory-to-biological-applications",title:"Viscoelasticity",fullTitle:"Viscoelasticity - From Theory to Biological Applications"},signatures:"Naoki Sasaki",authors:[{id:"140935",title:"Prof.",name:"Naoki",middleName:null,surname:"Sasaki",slug:"naoki-sasaki",fullName:"Naoki Sasaki"}]},{id:"40741",doi:"10.5772/50137",title:"Die Swell of Complex Polymeric Systems",slug:"die-swell-of-complex-polymeric-systems",totalDownloads:6066,totalCrossrefCites:3,totalDimensionsCites:17,abstract:null,book:{id:"2854",slug:"viscoelasticity-from-theory-to-biological-applications",title:"Viscoelasticity",fullTitle:"Viscoelasticity - From Theory to Biological Applications"},signatures:"Kejian Wang",authors:[{id:"141238",title:"Prof.",name:"Kejian",middleName:null,surname:"Wang",slug:"kejian-wang",fullName:"Kejian Wang"}]}],mostDownloadedChaptersLast30Days:[{id:"48768",title:"TiO2 -Based Surfaces with Special Wettability – From Nature to Biomimetic Application",slug:"tio2-based-surfaces-with-special-wettability-from-nature-to-biomimetic-application",totalDownloads:5008,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Super-wetting/antiwetting surfaces with extremely high contrast of surface energy and liquid adhesion have attracted a lot of interest in both fundamental research and industry. Various types of special wetting surfaces can be constructed by adjusting the topographical structure and chemical composition. In this chapter, recent advance of the super-wetting/antiwetting surfaces with special solid/liquid adhesion has been reviewed, with a focus on the biomimetic fabrication and applications of TiO2-based surfaces. Special super-wettability examples include lotus-leaf-inspired surfaces with low adhesion, rose-petal-inspired surfaces with high adhesion, spider silk bio-inspired surfaces with directional adhesion, fish-scale-inspired underwater superoleophobic surface, and artificial surfaces with controllable or stimuli-responsive liquid adhesion. In addition, we will review some potential applications related to artificial antiwetting surface with controllable adhesion, e.g., self-cleaning, antifogging/anti-icing, micro-droplet manipulation, fog/water collection, water/oil separation, anti-bioadhesion, micro-template for patterning, and friction reduction. Finally, the difficulty and prospects of this renascent and rapidly developing field are also briefly proposed and discussed.",book:{id:"5319",slug:"wetting-and-wettability",title:"Wetting and Wettability",fullTitle:"Wetting and Wettability"},signatures:"Jian-Ying Huang and Yue-Kun Lai",authors:[{id:"175512",title:"Prof.",name:"Yuekun",middleName:null,surname:"Lai",slug:"yuekun-lai",fullName:"Yuekun Lai"}]},{id:"62882",title:"Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters",slug:"inside-the-phenomenological-aspects-of-wet-granulation-role-of-process-parameters",totalDownloads:1424,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.",book:{id:"7352",slug:"granularity-in-materials-science",title:"Granularity in Materials Science",fullTitle:"Granularity in Materials Science"},signatures:"Veronica De Simone, Diego Caccavo, Annalisa Dalmoro, Gaetano\nLamberti, Matteo d’Amore and Anna Angela Barba",authors:[{id:"140173",title:"Prof.",name:"Anna Angela",middleName:null,surname:"Barba",slug:"anna-angela-barba",fullName:"Anna Angela Barba"},{id:"143947",title:"Prof.",name:"Matteo",middleName:null,surname:"D'Amore",slug:"matteo-d'amore",fullName:"Matteo D'Amore"},{id:"176104",title:"Prof.",name:"Gaetano",middleName:null,surname:"Lamberti",slug:"gaetano-lamberti",fullName:"Gaetano Lamberti"},{id:"176239",title:"MSc.",name:"Diego",middleName:null,surname:"Caccavo",slug:"diego-caccavo",fullName:"Diego Caccavo"},{id:"181500",title:"Dr.",name:"Annalisa",middleName:null,surname:"Dalmoro",slug:"annalisa-dalmoro",fullName:"Annalisa Dalmoro"},{id:"260822",title:"MSc.",name:"Veronica",middleName:null,surname:"De Simone",slug:"veronica-de-simone",fullName:"Veronica De Simone"}]},{id:"49177",title:"Influence of Wettability and Reactivity on Refractory Degradation – Interactions of Molten Iron and Slags with Steelmaking Refractories at 1550°C",slug:"influence-of-wettability-and-reactivity-on-refractory-degradation-interactions-of-molten-iron-and-sl",totalDownloads:2067,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Refractories, materials that can withstand high temperatures, play an important role in the iron and steel sector which alone accounts for ~70% of total refractories produced. In this chapter, detailed wettability and interfacial phenomena investigations on alumina-carbon and zirconia-carbon refractories at steelmaking temperatures. The wettability between refractory substrates and molten iron/slags was investigated at 1550°C using the sessile drop approach in a horizontal tube furnace equipped with a CCD camera. Detailed experimental results were obtained on alumina-carbon/molten iron system at high temperatures. Alumina is known to be non-wetting to molten iron while carbon can be easily wetted. Observed contact angles were found to depend strongly on the substrate composition and contact time. While the refractory substrates containing 50 and 60% carbon were found to be non-wetting to molten iron, the substrates containing higher amounts of C (≥ 70%) were found to become increasingly wetting. Molten iron droplets were seen to spread on these substrates.",book:{id:"5319",slug:"wetting-and-wettability",title:"Wetting and Wettability",fullTitle:"Wetting and Wettability"},signatures:"R. Khanna, M. Ikram-ul-Haq and V. Sahajwalla",authors:[{id:"19010",title:"Associate Prof.",name:"Rita",middleName:null,surname:"Khanna",slug:"rita-khanna",fullName:"Rita Khanna"}]},{id:"48822",title:"Wettability of Nanostructured Surfaces",slug:"wettability-of-nanostructured-surfaces",totalDownloads:3122,totalCrossrefCites:11,totalDimensionsCites:31,abstract:"There are many studies in literature concerning contact angle measurements on different materials/substrates. It is documented that textiles can be coated with multifunctional materials in form of thin films or nanoparticles to acquire characteristics that can improve the protection and comfort of the wearer. The capacity of oxide nanostructures to inhibit fungal development and neutralize bacteria is a direct consequence of their wetting behavior [1–6]. Moreover, the radical modification of wetting behavior of nanostructures from hydrophilic to hydrophobic when changing the pulsed laser deposition (PLD) ambient will be thoroughly discussed.",book:{id:"5319",slug:"wetting-and-wettability",title:"Wetting and Wettability",fullTitle:"Wetting and Wettability"},signatures:"L. Duta, A.C. Popescu, I. Zgura, N. Preda and I.N. Mihailescu",authors:[{id:"17636",title:"Prof.",name:"Ion N.",middleName:null,surname:"Mihailescu",slug:"ion-n.-mihailescu",fullName:"Ion N. Mihailescu"},{id:"23532",title:"Dr.",name:"Andrei",middleName:null,surname:"Popescu",slug:"andrei-popescu",fullName:"Andrei Popescu"},{id:"174343",title:"Dr.",name:"Liviu",middleName:null,surname:"Duta",slug:"liviu-duta",fullName:"Liviu Duta"},{id:"174344",title:"Dr.",name:"Irina",middleName:null,surname:"Zgura",slug:"irina-zgura",fullName:"Irina Zgura"},{id:"174345",title:"Dr.",name:"Ligia",middleName:null,surname:"Frunza",slug:"ligia-frunza",fullName:"Ligia Frunza"}]},{id:"62615",title:"Nanolevel Surface Processing of Fine Particles by Waterjet Cavitation and Multifunction Cavitation to Improve the Photocatalytic Properties of Titanium Oxide",slug:"nanolevel-surface-processing-of-fine-particles-by-waterjet-cavitation-and-multifunction-cavitation-t",totalDownloads:1161,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Titanium oxide particles were treated by water jet cavitation (WJC) generated and multifunction cavitation (MFC) using an ejector nozzle. Generation, growth, and collapse of cavitation are repeated with the particles of titanium oxide and platinum. Because the cavitation has an extremely high collapse pressure, the surface of the titanium oxide particles is processed by the microjets of cavitation in a reactor comprising the ejector nozzle. In the multifunction cavitation, ultrasonic irradiation of a waterjet during floating cavitation was used to generate microjets with hot spots. Hot working can be performed at the nanoscale on a material surface using this MFC process, resulting in morphological changes and variations in the surface electrochemical characteristics. The fundamental characteristics of multifunction cavitation were investigated theoretically and experimentally. Furthermore, the additional nozzle was put on the ejector nozzle in order to increase the temperature and pressure of bubble and the mechanism was clarified. The quantities of hydrogen and oxygen generated from titanium dioxide particles treated by multifunction cavitation in response to UV and visible light irradiation were remarkably increased compared to the amounts produced by particles treated by WJC processing. 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A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. 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