French-American-British (FAB) Classification of Acute Myelogenous Leukemia.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"10469",leadTitle:null,fullTitle:"Nanofibers - Synthesis, Properties and Applications",title:"Nanofibers",subtitle:"Synthesis, Properties and Applications",reviewType:"peer-reviewed",abstract:"Nanofibers are well known for their vast range of applications in sensors, catalysts, conductors, tissue engineering, and so on, owing to their high surface-area-to-volume ratio, high porosity, and the ease of tuning their structures, functionalities, and properties This book is a comprehensive overview of the synthesis, characterization, and application of nanofibers. Written by experts in the field, chapters cover such topics as green synthesis of nanofibers, electrospinning of carbon nanofibers, applications of ceramic nanofibers, transparent electrodes for flexible and stretchable electronics, nanoribbons, and much more.",isbn:"978-1-83968-426-5",printIsbn:"978-1-83968-425-8",pdfIsbn:"978-1-83968-427-2",doi:"10.5772/intechopen.92484",price:139,priceEur:155,priceUsd:179,slug:"nanofibers-synthesis-properties-and-applications",numberOfPages:330,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"28dc655dde01b94399cab954663f8bff",bookSignature:"Brajesh Kumar",publishedDate:"September 15th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10469.jpg",numberOfDownloads:6113,numberOfWosCitations:1,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:11,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:17,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 10th 2020",dateEndSecondStepPublish:"October 2nd 2020",dateEndThirdStepPublish:"December 1st 2020",dateEndFourthStepPublish:"February 19th 2021",dateEndFifthStepPublish:"April 20th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"176093",title:"Dr.",name:"Brajesh",middleName:null,surname:"Kumar",slug:"brajesh-kumar",fullName:"Brajesh Kumar",profilePictureURL:"https://mts.intechopen.com/storage/users/176093/images/system/176093.JPG",biography:"Dr. Brajesh Kumar is currently working as an Assistant Professor and Head in the Post Graduate Department of Chemistry, TATA College, Chaibasa, India. He received a Ph.D. in Chemistry from the University of Delhi, India. His research interest is in the development of sustainable and eco-friendly techniques for (a) nanoparticles synthesis and their applications for environmental remediation, (b) active films of organic solar cells, (c) nanomedicine, (d) sensors, (e) natural product extraction, purification, and analysis,(f) natural polymers, (g) peptide chemistry, (h) microwave and ultrasound-assisted organic synthesis and (i) organic synthesis. Dr. Brajesh Kumar has been credited for different national and international fellowships and he has also worked as a faculty member in various universities of India, Ecuador, and South Korea. He has also published numerous SCI/ SCIE/ Scopus research articles (h index = 29, Citations 2917) and is also an active reviewer of more than 50 Journals. He is also included in the top 2% of the scientist list prepared by experts at Stanford University, USA.",institutionString:"TATA College, Kolhan University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"208",title:"Material Science",slug:"nanotechnology-and-nanomaterials-material-science"}],chapters:[{id:"76386",title:"New Perspective of Nano Fibers: Synthesis and Applications",doi:"10.5772/intechopen.97460",slug:"new-perspective-of-nano-fibers-synthesis-and-applications",totalDownloads:433,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Nano fibers are most attractive materials in the scientific world due to their enormous applications in various fields. Their applications start with generation of energy, solution to environmental problems and continues with medical field and many more. Nano materials got much importance from their peculiar electrical, optical, mechanical and thermal properties. Fibrous materials are obtained from several sources and by different mechanisms these materials are converted into nano materials. As of bulk fibers include specific properties compared to other materials, the generation of nano fibers enhance all the properties. The synthesis of nano fibers from natural and synthetic polymers, metals, semiconductors, composite materials, carbon based materials lead to new perspective in science and engineering fields. Most pronouncing techniques that include conventional and modern methods are available to fabricate nano fibers from these materials. Of them some are being used from a long time and some are emerging techniques to generate flexible substrates. Electrospinning, template based synthesis, polymerization, self-assembly, sonochemical synthesis are the conventional methods for the production of nano fibers. New technologies include electro hydrodynamic writing, plasma induced synthesis, centrifugal jet spinning, CO2 laser supersonic marks a trend in development of nano fibrous materials. This chapter give details about fabrication materials and provides synthetic routes to generate them along with applications. Also this chapter focuses on the challenges in development of nano fiber technology in commercial perspective.",signatures:"Deepthi Sista",downloadPdfUrl:"/chapter/pdf-download/76386",previewPdfUrl:"/chapter/pdf-preview/76386",authors:[{id:"333738",title:"Dr.",name:"Deepthi",surname:"Sista",slug:"deepthi-sista",fullName:"Deepthi Sista"}],corrections:null},{id:"73914",title:"Green Synthesis of Nanofiber and Its Affecting Parameters",doi:"10.5772/intechopen.94539",slug:"green-synthesis-of-nanofiber-and-its-affecting-parameters",totalDownloads:378,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nanofibers, the widely applied in various field of science research, is one of the important area in nanotechnology research. Nanofibers can be classified into polymeric, ceramic and composite nanofibers depending upon the material used. A variety of nanofibers are applied in field of energy storage, biotechnology and healthcare industry, environmental engineering, as well as security and defense. The wide uses of nanofibers are mainly due to low density, high porosity, tight pore size and large surface area per unit mass. Synthesis of nanofibers depends upon various parameters of solution like molecular weight of polymer, concentration, electrical conductivity, surface tension and viscosity. The process parameters affecting nanofibers synthesis are distance between needle tip and collector, feeding rate of polymer material and electric field.",signatures:"Dan Bahadur Pal and Deen Dayal Giri",downloadPdfUrl:"/chapter/pdf-download/73914",previewPdfUrl:"/chapter/pdf-preview/73914",authors:[{id:"240067",title:"Dr.",name:"Dan Bahadur",surname:"Pal",slug:"dan-bahadur-pal",fullName:"Dan Bahadur Pal"},{id:"327200",title:"Dr.",name:"Deen Dayal",surname:"Giri",slug:"deen-dayal-giri",fullName:"Deen Dayal Giri"}],corrections:null},{id:"75317",title:"Fabrication of PVA/Carbon-Based Nanofibers Using Electrospinning",doi:"10.5772/intechopen.96175",slug:"fabrication-of-pva-carbon-based-nanofibers-using-electrospinning",totalDownloads:218,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nanofibers are widely used in various fields, including water filtration. In the development of nanofibers as water filtration, a mixture of carbon in a polymer solution is often used. Nanofibers can be made by several methods such as multicomponent fiber spinning techniques, melt blowing, electrospinning. Electrospinning is currently a simple development method but can produce nanofibers with a small fiber diameter, it is easy to develop and many parameters can be controlled. Parameters that affect the results of the nanofibers that are formed include flow rate or syringe pump flow rate and high voltage dc high voltage. Various types of nanofibers can be produced from various types of polymers, both natural polymers and synthetic polymers. Generally, because they have properties and characteristics such as high surface area, small pore size, and the possibility to be developed in various applications. Therefore, this chapter discusses the electrospinning of carbon nanofibers using PVA polymer.",signatures:"Gatut Yudoyono, Diky Anggoro, Lutfi Fitria Ningsih and Rizki Romadoni",downloadPdfUrl:"/chapter/pdf-download/75317",previewPdfUrl:"/chapter/pdf-preview/75317",authors:[{id:"333866",title:"Dr.",name:"Gatut",surname:"Yudoyono",slug:"gatut-yudoyono",fullName:"Gatut Yudoyono"},{id:"334524",title:"MSc.",name:"Diky",surname:"Anggoro",slug:"diky-anggoro",fullName:"Diky Anggoro"},{id:"336625",title:"Mrs.",name:"Lutfi",surname:"Fitria Ningsih",slug:"lutfi-fitria-ningsih",fullName:"Lutfi Fitria Ningsih"},{id:"336627",title:"Mr.",name:"Rizki",surname:"Romadoni",slug:"rizki-romadoni",fullName:"Rizki Romadoni"}],corrections:null},{id:"76007",title:"Recent Advances in Applications of Ceramic Nanofibers",doi:"10.5772/intechopen.97118",slug:"recent-advances-in-applications-of-ceramic-nanofibers",totalDownloads:387,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Ceramic materials are well known for their hardness, inertness, superior mechanical and thermal properties, resistance against chemical erosion and corrosion. Ceramic nanofibers were first manufactured through a combination of electrospinning with sol–gel method in 2002. The electrospun ceramic nanofibers display unprecedented properties such as high surface area, length, thermo-mechanical properties, and hierarchically porous structure which make them candidates for a wide range of applications such as tissue engineering, sensors, water remediation, energy storage, electromagnetic shielding, thermal insulation materials, etc. This chapter focuses on the most recent advances in the applications of ceramic nanofibers.",signatures:"Nuray Kizildag",downloadPdfUrl:"/chapter/pdf-download/76007",previewPdfUrl:"/chapter/pdf-preview/76007",authors:[{id:"189995",title:"Ph.D.",name:"Nuray",surname:"Kizildag",slug:"nuray-kizildag",fullName:"Nuray Kizildag"}],corrections:null},{id:"76526",title:"Electrospun Nanofibers: Characteristic Agents and Their Applications",doi:"10.5772/intechopen.97494",slug:"electrospun-nanofibers-characteristic-agents-and-their-applications",totalDownloads:311,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This study aimed to introduce antibacterial nanofibers, produced by electrospinning as a novel technique in constructing nanostructured materials. The large size and less bioavailability due to impenetrable (or partial/improper penetration) membrane has resulted in production of nanofibers. These nano sized Fibers were successful in delivering the active ingredients and served the purpose of using plants for its cause. Some of the active ingredients include antimicrobial compounds that are incorporated into various products to prevent unwanted microbial growth. As higher bioavailability is one of the most crucial parameters when it comes to medical solutions, electro spun nanofibers are highly preferred. This method is preferable for organic polymers as they have high flexibility, high specific surface area and surface functionalization. Electrospinning technology has been used for the fabrication and assembly of nanofibers into membranes, which have extended the range of potential applications in the biomedical, environmental protection, nanosensor, electronic/optical, protective clothing fields and various other fields.",signatures:"Lingayya Hiremath, O. Sruti, B.M. Aishwarya, N.G. Kala and E. Keshamma",downloadPdfUrl:"/chapter/pdf-download/76526",previewPdfUrl:"/chapter/pdf-preview/76526",authors:[{id:"288954",title:"Dr.",name:"Lingayya",surname:"Hiremath",slug:"lingayya-hiremath",fullName:"Lingayya Hiremath"},{id:"342611",title:"Ms.",name:"O.",surname:"Sruti",slug:"o.-sruti",fullName:"O. Sruti"},{id:"342612",title:"Ms.",name:"B.M.",surname:"Aishwarya",slug:"b.m.-aishwarya",fullName:"B.M. Aishwarya"},{id:"342613",title:"Ms.",name:"N.G.",surname:"Kala",slug:"n.g.-kala",fullName:"N.G. Kala"},{id:"342614",title:"Dr.",name:"E.",surname:"Keshamma",slug:"e.-keshamma",fullName:"E. Keshamma"}],corrections:null},{id:"75951",title:"An Insight into Biofunctional Curcumin/Gelatin Nanofibers",doi:"10.5772/intechopen.97113",slug:"an-insight-into-biofunctional-curcumin-gelatin-nanofibers",totalDownloads:257,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Electrospinning (ESPNG) was used to synthesize ultrathin (UT) and uniform nanofibers (from 5 nm to a few hundred nanometers) of various materials which have biomedical applications (BAs) such as dressing of wounds, drug discharge, and so on and so forth. In the first half of the report, there is an audit on the nanofibers having low diameter so that it could have larger surface area to volume proportion, likewise with that it would have sufficient porosity and improved mechanical properties required for wound healing. Nanofibrous mats (NMs) with high biocompatibility could be utilized during healing of wounds by sustained release of curcumin (Cc) and oxygen. The ESPNG was understood through in-depth numerical investigation in the present report. Furthermore, the process parameters (PMs) were reviewed in depth for their contributions in synthesizing UT - Curcumin/Gelatin (Cc/G) nanofibers (NFs) of optimum diameter. The aim of the discussion was to demonstrate that simply optimizing biofunctional (BF) - Cc/G NFs might not be enough to satisfy experts until they are also given access details about the complete ESPNG method (mathematical mechanism) to improve hold over the synthesis of NMs (suitable for BAs) for the release profile of Cc throughout critical periods of healing process.",signatures:"Nand Jee Kanu, Eva Gupta, Venkateshwara Sutar, Gyanendra Kumar Singh and Umesh Kumar Vates",downloadPdfUrl:"/chapter/pdf-download/75951",previewPdfUrl:"/chapter/pdf-preview/75951",authors:[{id:"328085",title:"Assistant Prof.",name:"Nand Jee",surname:"Kanu",slug:"nand-jee-kanu",fullName:"Nand Jee Kanu"},{id:"328086",title:"Mrs.",name:"Eva",surname:"Gupta",slug:"eva-gupta",fullName:"Eva Gupta"},{id:"349972",title:null,name:"Venkateshwara",surname:"Sutar",slug:"venkateshwara-sutar",fullName:"Venkateshwara Sutar"},{id:"349973",title:"Associate Prof.",name:"Gyanendra Kumar",surname:"Singh",slug:"gyanendra-kumar-singh",fullName:"Gyanendra Kumar Singh"},{id:"349974",title:"Associate Prof.",name:"Umesh Kumar",surname:"Vates",slug:"umesh-kumar-vates",fullName:"Umesh Kumar Vates"}],corrections:null},{id:"75273",title:"Electrochemical Behavior of Cellulose Nanofibrils Functionalized with Dicyanovinyl Groups",doi:"10.5772/intechopen.96181",slug:"electrochemical-behavior-of-cellulose-nanofibrils-functionalized-with-dicyanovinyl-groups",totalDownloads:272,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cellulose is considered one of the most important renewable sources of biopolymers on Earth. It has attracted widespread attention due to its physical–chemical characteristics, such as biocompatibility, low toxicity, biodegradability, low density, high strength, stability in organic solvents, in addition to having hydroxyl groups, which enable its chemical modification. In this study, cellulose nanofibrils (CNFs) were functionalized with dicyanovinyl groups through nucleophilic vinylic substitution (SNV) and used as electrocatalyst in electrochemical of carbon dioxide (CO2) reduction. Results indicate that introducing dicyanovinyl groups into the structure of nanocellulose increases electrocatalytic activity as compared to that of pure nanocellulose, shifting the onset potential of the electrochemical CO2 reduction reaction to more positive values as compared to those for the reaction with argon. The atomic force microscopy (AFM) images show no changes in the morphology of CNFs after chemical modification.",signatures:"Robson V. Pereira, Thais E. Gallina, Marcelo A. Pereira-da-Silva, Kênia S. Freitas and Aparecido J. de Menezes",downloadPdfUrl:"/chapter/pdf-download/75273",previewPdfUrl:"/chapter/pdf-preview/75273",authors:[{id:"105654",title:"Dr.",name:"Marcelo A.",surname:"Pereira-da-Silva",slug:"marcelo-a.-pereira-da-silva",fullName:"Marcelo A. Pereira-da-Silva"},{id:"331764",title:"Associate Prof.",name:"Aparecido Junior",surname:"de Menezes",slug:"aparecido-junior-de-menezes",fullName:"Aparecido Junior de Menezes"},{id:"332146",title:"Prof.",name:"Kênia",surname:"Da Silva Freitas",slug:"kenia-da-silva-freitas",fullName:"Kênia Da Silva Freitas"},{id:"332147",title:"Mrs.",name:"Thais Eugênio",surname:"Gallina",slug:"thais-eugenio-gallina",fullName:"Thais Eugênio Gallina"},{id:"332149",title:"Prof.",name:"Robson",surname:"Valentim Pereira",slug:"robson-valentim-pereira",fullName:"Robson Valentim Pereira"}],corrections:null},{id:"75357",title:"The Nanocellulose Fibers from Symbiotic Culture of Bacteria and Yeast (SCOBY) Kombucha: Preparation and Characterization",doi:"10.5772/intechopen.96310",slug:"the-nanocellulose-fibers-from-symbiotic-culture-of-bacteria-and-yeast-scoby-kombucha-preparation-and",totalDownloads:321,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Symbiotic Culture of Bacteria and Yeast (SCOBY) is a by-product in the form of cellulose polymers produced by bacteria in the kombucha fermentation process. Until now, SCOBY products still have application limitations. Several world designers have succeeded in making works using fabrics based on SCOBY. The resulting fabric has a flexible texture and is brown like synthetic leather. Fabrics based on SCOBY are also considered cheap and more environmentally friendly with short production time. The use of SCOBY as a fabric base material still has problems, where the fabric produced from SCOBY kombucha, directly through the drying process, has the characteristic of being very easy to absorb water. Another problem is that SCOBY production in the kombucha fermentation process is difficult to achieve a uniform thickness and SCOBY production in a large surface area is also difficult to stabilize. The development of SCOBY into cellulose fibers can be done by first changing the structure of SCOBY into nanocellulose. This nanocellulose production can then be developed into nanocellulose fibers in the form of threads and then spun to become a complete fabric. The production of nanocellulose is carried out using cellulase enzymes. It is known that cellulase enzymes can be obtained through the growth of bacteria or specific fungi. One of the groups of fungi and bacteria commonly used to produce cellulase enzymes are Trichoderma and Bacillus.",signatures:"Pingkan Aditiawati, Rudi Dungani, Salsabila Muharam, Aminudin Sulaeman, Sri Hartati, Mustika Dewi and Enih Rosamah",downloadPdfUrl:"/chapter/pdf-download/75357",previewPdfUrl:"/chapter/pdf-preview/75357",authors:[{id:"220081",title:"Dr.",name:"Pingkan",surname:"Aditiawati",slug:"pingkan-aditiawati",fullName:"Pingkan Aditiawati"},{id:"256251",title:"Dr.",name:"Sri",surname:"Hartati",slug:"sri-hartati",fullName:"Sri Hartati"},{id:"313317",title:"Dr.",name:"Enih",surname:"Rosamah",slug:"enih-rosamah",fullName:"Enih Rosamah"},{id:"327831",title:"Associate Prof.",name:"Rudi",surname:"Dungani",slug:"rudi-dungani",fullName:"Rudi Dungani"},{id:"327832",title:"Dr.",name:"Mustika",surname:"Dewi",slug:"mustika-dewi",fullName:"Mustika Dewi"},{id:"337483",title:"MSc.",name:"Salsabila Mutiara",surname:"Muharam",slug:"salsabila-mutiara-muharam",fullName:"Salsabila Mutiara Muharam"},{id:"346766",title:"Dr.",name:"Aminudin",surname:"Sulaeman",slug:"aminudin-sulaeman",fullName:"Aminudin Sulaeman"}],corrections:null},{id:"74289",title:"Electrodeposition of Nanoporous Gold Thin Films",doi:"10.5772/intechopen.94604",slug:"electrodeposition-of-nanoporous-gold-thin-films",totalDownloads:446,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Nanoporous gold (NPG) films have attracted increasing interest over the last ten years due to their unique properties of high surface area, high selectivity, and electrochemical activity along with enhanced electrical conductivity, and chemical stability. A variety of fabrication techniques to synthesize NPG thin films have been explored so far including dealloying, templating, sputtering, self-assembling, and electrodeposition. In this review, the progress in the synthetic techniques over the last ten years to prepare porous gold films has been discussed with emphasis given on the technique of electrodeposition. Such films have wide-ranging applications in the fields of drug delivery, energy storage, heterogeneous catalysis, and optical sensing.",signatures:"Palak Sondhi and Keith J. Stine",downloadPdfUrl:"/chapter/pdf-download/74289",previewPdfUrl:"/chapter/pdf-preview/74289",authors:[{id:"192643",title:"Prof.",name:"Keith J.",surname:"Stine",slug:"keith-j.-stine",fullName:"Keith J. Stine"},{id:"327846",title:"Ms.",name:"Palak",surname:"Sondhi",slug:"palak-sondhi",fullName:"Palak Sondhi"}],corrections:null},{id:"74267",title:"Micro Nano Manufacturing Methods for Chemical, Gas and Bio Sensors, Water Purification and Energy Technologies",doi:"10.5772/intechopen.94962",slug:"micro-nano-manufacturing-methods-for-chemical-gas-and-bio-sensors-water-purification-and-energy-tech",totalDownloads:367,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter reports on the various methods of fabricating and manufacturing micro and nano sensor, membrane and energy devices. Firstly, the characteristic often sought after by scientists and engineers for effective and efficient performance of these technologies were thoroughly discussed in details together with the characterization techniques for evaluating them. Several state-of-the-art fabricating techniques for sensor devices, water and medical based-membranes, solar cells and batteries were also discussed.",signatures:"Amos Adeleke Akande, Aderemi Timothy Adeleye, Abraham Abdul Adenle and Bonex Wakufwa Mwakikunga",downloadPdfUrl:"/chapter/pdf-download/74267",previewPdfUrl:"/chapter/pdf-preview/74267",authors:[{id:"49771",title:"Dr.",name:"Bonex",surname:"Wakufwa Mwakikunga",slug:"bonex-wakufwa-mwakikunga",fullName:"Bonex Wakufwa Mwakikunga"},{id:"328359",title:"Dr.",name:"Amos Adeleke",surname:"Akande",slug:"amos-adeleke-akande",fullName:"Amos Adeleke Akande"},{id:"336200",title:"Mr.",name:"Abraham Abdul",surname:"Adenle",slug:"abraham-abdul-adenle",fullName:"Abraham Abdul Adenle"},{id:"336201",title:"Mr.",name:"Aderemi Timothy",surname:"Adeleye",slug:"aderemi-timothy-adeleye",fullName:"Aderemi Timothy Adeleye"}],corrections:null},{id:"77027",title:"Microwave Assisted Synthesis of Organic Compounds and Nanomaterials",doi:"10.5772/intechopen.98224",slug:"microwave-assisted-synthesis-of-organic-compounds-and-nanomaterials",totalDownloads:448,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"In the Conventional laboratory or industry heating technique involve Bunsen burner, heating mental/hot plates and electric heating ovens. To produce a variety of useful compounds for betterment of mankind, the Microwave Chemistry was introduced in year 1955 and finds a place in one of the Green chemistry method. In Microwave chemistry is the science of applying microwave radiation to chemical reactions. Microwaves act as high frequency electric fields and will generally heat any material containing mobile electric charges, such as polar molecules in a solvent or conducting ions in a solid. Polar solvents are heated as their component molecules are forced to rotate with the field and lose energy in collisions i.e. the dipole moments of molecules are important in order to proceed with the chemical reactions in this method. It can be termed as microwave-assisted organic synthesis (MAOS), Microwave-Enhanced Chemistry (MEC) or Microwave-organic Reaction Enhancement synthesis (MORE). Microwave-Assisted Syntheses is a promising area of modern Green Chemistry could be adopted to save the earth.",signatures:"Anjali Jha",downloadPdfUrl:"/chapter/pdf-download/77027",previewPdfUrl:"/chapter/pdf-preview/77027",authors:[{id:"327522",title:"Prof.",name:"Anjali",surname:"Jha",slug:"anjali-jha",fullName:"Anjali Jha"}],corrections:null},{id:"75297",title:"Polarization of Electrospun PVDF Fiber Mats and Fiber Yarns",doi:"10.5772/intechopen.96305",slug:"polarization-of-electrospun-pvdf-fiber-mats-and-fiber-yarns",totalDownloads:293,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Electrospun fibers are of interest in a number of applications due to their small size, simplicity of fabrication, and ease of modification of properties. Piezoelectric polymers such as Polyvinylidene Fluoride (PVDF) can be charged when formed in the electrospinning process. This chapter discusses fabrication of PVDF fiber mats and fiber yarns and the measurement of their charge using a custom-made Faraday bucket. The results show the measured charge per mass of fiber mats was greater than the values measured for the yarns of the same mass. The measured charges may be related to both mass and external surface areas of the mats and yarn samples. It was observed the area/mass ratios of the fiber yarns were more than 30% less than the fiber mats.",signatures:"Harshal Gade, Sreevalli Bokka and George G. Chase",downloadPdfUrl:"/chapter/pdf-download/75297",previewPdfUrl:"/chapter/pdf-preview/75297",authors:[{id:"60647",title:"Prof.",name:"George",surname:"Chase",slug:"george-chase",fullName:"George Chase"},{id:"240152",title:"Mr.",name:"Harshal",surname:"Gade",slug:"harshal-gade",fullName:"Harshal Gade"},{id:"328945",title:"Ms.",name:"Sreevalli",surname:"Bokka",slug:"sreevalli-bokka",fullName:"Sreevalli Bokka"}],corrections:null},{id:"73960",title:"Recent Developments in All-Solid-State Micro-Supercapacitors Based on Two-Dimensional Materials",doi:"10.5772/intechopen.94535",slug:"recent-developments-in-all-solid-state-micro-supercapacitors-based-on-two-dimensional-materials",totalDownloads:417,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Owing to their unique features such as high surface area, rich electroactive sites, ultrathin thickness, excellent flexibility and mechanical stability and multiple surface functionalities enables outstanding electrochemical response which provides high energy and power density supercapacitors based on them. Also, the Van der Waals gap between layered 2D materials encourages the fast ion transport with shorter ion diffusion path. 2D materials such as MXenes, graphene, TMDs, and 2D metal–organic frame work, TMOs/TMHs materials, have been described with regard to their electrochemical properties for MSCs. We have summarized the recent progress in MSC based on well-developed 2D materials-based electrodes and its potential outcomes with different architectures including interdigitated pattern, stacked MSC and 3D geometries for on-chip electronics. This chapter provides a brief overview of the recent developments in the field of 2D material based all-solid-state microsupercapacitors (MSCs). A brief note on the MSC device configuration and microfabrication methods for the microelectrodes have been discussed. Taking advantage of certain 2D materials such as 2D MXenes, TMDs, TMOs/TMHs that provide good surface chemistry, tunable chemical and physical properties, intercalation, surface modification (functionalization), heterostructures, phase transformations, defect engineering etc. are beneficial for enhancement in pseudocapacitance as it promotes the redox activity.",signatures:"Minu Mathew, Sithara Radhakrishnan and Chandra Sekhar Rout",downloadPdfUrl:"/chapter/pdf-download/73960",previewPdfUrl:"/chapter/pdf-preview/73960",authors:[{id:"327311",title:"Prof.",name:"Chandra Sekhar",surname:"Rout",slug:"chandra-sekhar-rout",fullName:"Chandra Sekhar Rout"},{id:"332396",title:"Ms.",name:"Sithara",surname:"Radhakrishnan",slug:"sithara-radhakrishnan",fullName:"Sithara Radhakrishnan"},{id:"332397",title:"Ms.",name:"Minu",surname:"Mathew",slug:"minu-mathew",fullName:"Minu Mathew"}],corrections:null},{id:"73308",title:"Pulsed Electrochemical Micromachining in Stainless Steel",doi:"10.5772/intechopen.93750",slug:"pulsed-electrochemical-micromachining-in-stainless-steel",totalDownloads:392,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter presents research on pulsed electrochemical micromachining of stainless steel. Suitable equipment to study the process is described as well as a fitting procedure to machine and measure the variables involved. The pulse on-time must be maintained in the order of ns to achieve a good current confinement since the tool is active. Some experiments were carried out to assess the most important variables of the process: current confinement, surface roughness, material removal rate and efficiency. The current confinement has been observed to worsen when the pulse on-time increases, as well as the surface roughness. The material removal rate and efficiency increase with the voltage amplitude and the pulse on-time. The voltage amplitude must be higher than 12 V so that the phenomenon of passivation does not affect the process. There is a compromise in the choice of the variables, so a suitable combination of parameters is determined in order to achieve a good material removal rate with an acceptable result.",signatures:"Pablo Rodríguez, Daniel Hidalgo and Julio Eduardo Labarga",downloadPdfUrl:"/chapter/pdf-download/73308",previewPdfUrl:"/chapter/pdf-preview/73308",authors:[{id:"328423",title:"Dr.",name:"Pablo",surname:"Rodriguez",slug:"pablo-rodriguez",fullName:"Pablo Rodriguez"},{id:"328425",title:"Dr.",name:"Julio",surname:"Labarga",slug:"julio-labarga",fullName:"Julio Labarga"},{id:"328427",title:"Mr.",name:"Daniel",surname:"Hidalgo",slug:"daniel-hidalgo",fullName:"Daniel Hidalgo"}],corrections:null},{id:"74310",title:"RF MEMS Switch Fabrication and Packaging",doi:"10.5772/intechopen.95003",slug:"rf-mems-switch-fabrication-and-packaging",totalDownloads:485,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"RF (Radio Frequency) MEMS (Micro Electro Mechanical Systems) technology is the application of micromachined mechanical structures, controlled by electrical signals and interacting with signals in the RF range. The applications of these devices range from switching networks for satellite communication systems to high performance resonators and tuners. RF MEMS switches are the first and foremost MEMS devices designed for RF technology. A specialized method for fabricating microsturctures called surface micromachining process is used for fabricating the RF MEMS switches. Die level packaging using available surface mount style RF packages. The packaging process involved the design of RF feed throughs on the Alumina substrates to the die attachment, wire bonding and hermetic sealing using low temperature processes.",signatures:"Lakshmi Swaminathan",downloadPdfUrl:"/chapter/pdf-download/74310",previewPdfUrl:"/chapter/pdf-preview/74310",authors:[{id:"327053",title:"Associate Prof.",name:"Lakshmi",surname:"Swaminathan",slug:"lakshmi-swaminathan",fullName:"Lakshmi Swaminathan"}],corrections:null},{id:"75368",title:"Vacuum-Free Fabrication of Transparent Electrodes for Soft Electronics",doi:"10.5772/intechopen.96311",slug:"vacuum-free-fabrication-of-transparent-electrodes-for-soft-electronics",totalDownloads:430,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Optoelectronic devices are advancing from existing rigid configurations to deformable configurations. These developing devices need transparent electrodes (TEs) having high mechanical deformability while preserving the high electrical conductivity and optical transparency. In agreement with these requirements, vacuum-fabricated conventional TEs based on transparent conducting oxides (TCOs) are receiving difficulties due to its low abundance, film brittleness, and low optical transmittance. Novel solution-processed TE materials including regular metal meshes, metal nanowire (NW) grids, carbon materials, and conducting polymers have been studied and confirmed their capabilities to address the limitations of the TCO-based TEs. This chapter presents a comprehensive review of the latest advances of these vacuum-free TEs, comprising the electrode material classes, the optical, electrical, mechanical and surface feature properties of the soft TEs, and the vacuum-free practices for their fabrication.",signatures:"Arshad Khan, Shawkat Ali, Saleem Khan, Moaaz Ahmed, Bo Wang and Amine Bermak",downloadPdfUrl:"/chapter/pdf-download/75368",previewPdfUrl:"/chapter/pdf-preview/75368",authors:[{id:"308939",title:"Dr.",name:"Saleem",surname:"Khan",slug:"saleem-khan",fullName:"Saleem Khan"},{id:"310184",title:"Dr.",name:"Shawkat",surname:"Ali",slug:"shawkat-ali",fullName:"Shawkat Ali"},{id:"310185",title:"Prof.",name:"Amine",surname:"Bermak",slug:"amine-bermak",fullName:"Amine Bermak"},{id:"327293",title:"Dr.",name:"Arshad",surname:"Khan",slug:"arshad-khan",fullName:"Arshad Khan"},{id:"332999",title:"Dr.",name:"Moaaz",surname:"Ahmed",slug:"moaaz-ahmed",fullName:"Moaaz Ahmed"},{id:"333000",title:"Dr.",name:"Bo",surname:"Wang",slug:"bo-wang",fullName:"Bo Wang"}],corrections:null},{id:"74229",title:"Calculation of the Electronic Properties and Reactivity of Nanoribbons",doi:"10.5772/intechopen.94541",slug:"calculation-of-the-electronic-properties-and-reactivity-of-nanoribbons",totalDownloads:266,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"It has been demonstrated that matter at low dimensionality exhibits novel properties, which could be used in promising applications. An effort to understand their behavior is being through the application of computational methods providing strategies to study structures, which present greater experimental challenges. It is proven that thin and narrow carbon-based nanostructures, such as, nanoribbons show promising tunable electronic properties, particularly when they are substitutionally functionalized. This chapter is proposed as a guidance to help the readers to apply conceptual density functional theory to calculate helpful intrinsic properties, e. g., energetic, electronic and reactivity of one-dimension nanomaterial’s, such as, carbon nanoribbons. As a case of study, it is discussed the effect of boron atoms on the properties of pristine carbon nanoribbons concerning the main aspect and considerations must take into account in their computational calculations.",signatures:"Pedro Navarro-Santos, Rafael Herrera-Bucio, Judit Aviña-Verduzco and Jose Luis Rivera",downloadPdfUrl:"/chapter/pdf-download/74229",previewPdfUrl:"/chapter/pdf-preview/74229",authors:[{id:"209394",title:"Dr.",name:"Pedro",surname:"Navarro Santos",slug:"pedro-navarro-santos",fullName:"Pedro Navarro Santos"},{id:"328881",title:"Dr.",name:"Rafael",surname:"Herrera-Bucio",slug:"rafael-herrera-bucio",fullName:"Rafael Herrera-Bucio"},{id:"329262",title:"Dr.",name:"Jose Luis",surname:"Rivera",slug:"jose-luis-rivera",fullName:"Jose Luis Rivera"},{id:"329263",title:"Dr.",name:"Judit",surname:"Aviña-Verduzco",slug:"judit-avina-verduzco",fullName:"Judit Aviña-Verduzco"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10489",title:"Biocomposites",subtitle:null,isOpenForSubmission:!1,hash:"c794533fcae9dcea38672f814ae182db",slug:"biocomposites",bookSignature:"Brajesh Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/10489.jpg",editedByType:"Edited by",editors:[{id:"176093",title:"Dr.",name:"Brajesh",surname:"Kumar",slug:"brajesh-kumar",fullName:"Brajesh Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7640",title:"Perspective of Carbon Nanotubes",subtitle:null,isOpenForSubmission:!1,hash:"8b85a9957fad5206369eadf0c1ffa27d",slug:"perspective-of-carbon-nanotubes",bookSignature:"Hosam El-Din Saleh and Said Moawad Mohamed El-Sheikh",coverURL:"https://cdn.intechopen.com/books/images_new/7640.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. 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D in Physics in 2012 from Indian Institute of Technology Guwahati, India. Presently, he is associated with the Faculty of Science, Sri Sri University, India as an Assistant Professor in Physics. Prior to joining the current\naffiliation, he was a postdoctoral fellow at different renowned institutions, Kobe University Japan, S. N. Bose National Centre for Basic Sciences, India and Cardiff University, United Kingdom. He was awarded prestigious JSPS postdoctoral fellowship based on his research contribution on semiconducting nanowires. He has published more than 32 research articles including 1 review article in high profile international journals and 3 book chapters to his credit. 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Encoder",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/74512.pdf",downloadPdfUrl:"/chapter/pdf-download/74512",previewPdfUrl:"/chapter/pdf-preview/74512",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/74512",risUrl:"/chapter/ris/74512",chapter:{id:"70013",slug:"many-core-algorithm-of-the-embedded-zerotree-wavelet-encoder",signatures:"Jesús Antonio Alvarez-Cedillo, Teodoro Alvarez-Sanchez, Mario Aguilar-Fernandez and Jacobo Sandoval-Gutierrez",dateSubmitted:"May 18th 2019",dateReviewed:"August 22nd 2019",datePrePublished:"December 7th 2019",datePublished:"March 11th 2020",book:{id:"7623",title:"Coding Theory",subtitle:null,fullTitle:"Coding Theory",slug:"coding-theory",publishedDate:"March 11th 2020",bookSignature:"Sudhakar Radhakrishnan and Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/7623.jpg",licenceType:"CC BY 3.0",editedByType:"Edited 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Sandoval-Gutierrez",slug:"jacobo-sandoval-gutierrez",email:"jacobosandoval@hotmail.com",position:null,institution:{name:"Universidad Autónoma Metropolitana",institutionURL:null,country:{name:"Mexico"}}},{id:"305587",title:"Dr.",name:"Mario",middleName:null,surname:"Aguilar-Fernandez",fullName:"Mario Aguilar-Fernandez",slug:"mario-aguilar-fernandez",email:"maguilarf@ipn.mx",position:null,institution:{name:"Instituto Politécnico Nacional",institutionURL:null,country:{name:"Mexico"}}}]}},chapter:{id:"70013",slug:"many-core-algorithm-of-the-embedded-zerotree-wavelet-encoder",signatures:"Jesús Antonio Alvarez-Cedillo, Teodoro Alvarez-Sanchez, Mario Aguilar-Fernandez and Jacobo Sandoval-Gutierrez",dateSubmitted:"May 18th 2019",dateReviewed:"August 22nd 2019",datePrePublished:"December 7th 2019",datePublished:"March 11th 2020",book:{id:"7623",title:"Coding Theory",subtitle:null,fullTitle:"Coding Theory",slug:"coding-theory",publishedDate:"March 11th 2020",bookSignature:"Sudhakar Radhakrishnan and Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/7623.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"26327",title:"Dr.",name:"Sudhakar",middleName:null,surname:"Radhakrishnan",slug:"sudhakar-radhakrishnan",fullName:"Sudhakar Radhakrishnan"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"118717",title:"Ph.D.",name:"Jesús Antonio",middleName:null,surname:"Álvarez-Cedillo",fullName:"Jesús Antonio Álvarez-Cedillo",slug:"jesus-antonio-alvarez-cedillo",email:"jaalvarez@ipn.mx",position:null,institution:{name:"Instituto Politécnico Nacional",institutionURL:null,country:{name:"Mexico"}}},{id:"305584",title:"Dr.",name:"Teodoro",middleName:null,surname:"Alvarez-Sanchez",fullName:"Teodoro Alvarez-Sanchez",slug:"teodoro-alvarez-sanchez",email:"talvares@citedi.mx",position:null,institution:{name:"Instituto Politécnico Nacional",institutionURL:null,country:{name:"Mexico"}}},{id:"305586",title:"Dr.",name:"Jacobo",middleName:null,surname:"Sandoval-Gutierrez",fullName:"Jacobo Sandoval-Gutierrez",slug:"jacobo-sandoval-gutierrez",email:"jacobosandoval@hotmail.com",position:null,institution:{name:"Universidad Autónoma Metropolitana",institutionURL:null,country:{name:"Mexico"}}},{id:"305587",title:"Dr.",name:"Mario",middleName:null,surname:"Aguilar-Fernandez",fullName:"Mario Aguilar-Fernandez",slug:"mario-aguilar-fernandez",email:"maguilarf@ipn.mx",position:null,institution:{name:"Instituto Politécnico Nacional",institutionURL:null,country:{name:"Mexico"}}}]},book:{id:"7623",title:"Coding Theory",subtitle:null,fullTitle:"Coding Theory",slug:"coding-theory",publishedDate:"March 11th 2020",bookSignature:"Sudhakar Radhakrishnan and Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/7623.jpg",licenceType:"CC BY 3.0",editedByType:"Edited 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\r\n\tSchiff base (imine -N=CH-) is one of a popular group of organic compounds prepared from primary amines and aldehyde. Not only as organic compounds but also as ligands for metal complexes, a number of studies have been carried out so far. In this context, this book aims to record a wider range of interdisciplinary content on Schiff base compounds, with an emphasis on the latest advances. This book will aim to compile research results, commentary, reviews, etc., that have dealt with preparation, spectroscopy, crystallography, (asymmetric) synthetic roles, physical properties (magnets, optics, and so on), computational chemistry, and/or theoretical chemistry and their discussions. The book will also intend to focus on Schiff base and its strong connection from organic chemistry to biochemistry or polymer materials chemistry.
",isbn:"978-1-80355-679-6",printIsbn:"978-1-80355-678-9",pdfIsbn:"978-1-80355-680-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"ce51efbe2cae97ca3199350ef6c498ec",bookSignature:"Dr. Takashiro Akitsu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12078.jpg",keywords:"Schiff Base, Imine, Azomethine, Synthesis, Characterization, Crystal Structure, Chirality, Liquid Crystals, Polymers or Biopolymers, Metal Complex, Salen-Type Ligand, Computational Chemistry",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 20th 2022",dateEndSecondStepPublish:"July 21st 2022",dateEndThirdStepPublish:"September 19th 2022",dateEndFourthStepPublish:"December 8th 2022",dateEndFifthStepPublish:"February 6th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A professor from the University of Science, Japan, has published 220 articles and book chapters. Dr. Akitsu studied at the Institute for Protein Research (metalloproteins), Keio University (photo and magnetic functional organic/inorganic hybrid compounds), and Stanford University (physical and bioinorganic chemistry) before moving to Tokyo University of Science.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"147861",title:"Dr.",name:"Takashiro",middleName:null,surname:"Akitsu",slug:"takashiro-akitsu",fullName:"Takashiro Akitsu",profilePictureURL:"https://mts.intechopen.com/storage/users/147861/images/system/147861.jpg",biography:"Takashiro Akitsu, Ph.D., is now a professor in the Department of Chemistry, Faculty of Science Division II, Tokyo University of Science, Japan. Studying crystal and electronic structures of chiral copper complexes, he graduated from Osaka University and obtained his Ph.D. in Physical and Inorganic Chemistry in 2000. Dr. Akitsu studied at the Institute for Protein Research (metalloproteins), Keio University (photo and magnetic functional organic/inorganic hybrid compounds), and Stanford University (physical and bioinorganic chemistry) before moving to Tokyo University of Science. He has published 220 articles and book chapters. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"25114",title:"Classification of Acute Leukemia",doi:"10.5772/19848",slug:"classification-of-acute-leukemia",body:'\n\t\tAcute leukemia is a proliferation of immature bone marrow-derived cells (blasts) that may also involve peripheral blood or solid organs. The percentage of bone marrow blast cells required for a diagnosis of acute leukemia has traditionally been set arbitrarily at 30% or more. However, more recently proposed classification systems have lowered the blast cell count to 20% for many leukemia types, and do not require any minimum blast cell percentage when certain morphologic and cytogenetic features are present.
\n\t\t(1) by morphology and cytochemistry supplemented by immunophenotyping, as proposed by French-American-British (FAB) group (Bennet et al 1976); (2) Proposed World Health Organization Classification of Acute Leukemia (Harris et al 1999); (3) by immunophenotyping alone, as proposed by the European Group for the immunological classification of leukemias (EGIL) (Bene et al 1995& Hayhoe FG 1988).
\n\t\t\tThe traditional classification of acute leukemia used criteria proposed by the French–American–British Cooperative Group (FAB), using the 30% bone marrow blast cell cutoff (Bennett et al, 1985). This classification system originally distinguished different leukemia types by morphologic features and cytochemical studies, particularly myeloperoxidase (or Sudan black B) and non-specific esterase staining. It was revised to include leukemia types that could only be accurately identified with the addition of immunophenotyping or electron microscopic studies (Bennett et al., 1991). Although the FAB classification failed to distinguish immunophenotypic groups of acute lymphoblastic leukemias, did not recognize the significance of myelodysplastic changes in acute myeloid leukemias or cytogenetic abnormalities in either leukemia type, and resulted in some subcategories of little clinical significance, this system provided very clear guidelines for classification. In addition, some distinct leukemia subtypes, particularly acute promyelocytic leukemia and acute myeloid leukemia with abnormal eosinophils, were found to correlate with specific cytogenetic aberrations and had unique clinical features, and those remain in recently proposed classification systems.
\n\t\t\tAcute myelogenous leukemia (AML) was based on how leukemic blasts, the predominant cell in the disease process, recapitulate normal hematopoiesis. Are blasts in a given case myeloblasts, monoblasts, megakaryoblasts, etc., and are they un-, minimally, or moderately differentiated.
\n\t\t\tThe original classification scheme proposed by the French-American-British (FAB) Cooperative Group divides AML into 8 subtypes (M0 to M7) and ALL into 3 subtypes (L1 to L3). Although AML blasts evolve from common myeloid precursors, the 8 subtypes differ in degree of maturation (Table 1). As specified in the table, M0 designates AML with minimal morphologic or cytochemical differentiation, M1–2 AML with minimal or moderate granulocytic differentiation, M3 acute promyelocytic leukemia (APL), M4 AML with mixed myelomonocytic differentiation, M5a and M5b monoblastic leukemia with minimal or moderate differentiation, M6a myeloid leukemia with dysplastic background erythropoiesis, M6b acute erythroblastic leukemia, and M7 acute megakaryoblastic leukemia. The FAB classification of ALL includes 3 subtypes (L1 to L3), which are differentiated based on morphology, including cell size, prominence of nucleoli, and the amount and appearance of cytoplasm (Table 2). Approximately 75% of adult ALL cases have blasts with the B -cell phenotype, and 25% have blasts with the T-cell phenotype. The FAB classification of ALL and AML is based on morphology and cytochemical staining of blasts (Cheson et al 1990).
\n\t\t\tM0 AML with no Romanowsky or cytochemical evidence of differentiation | \n\t\t\t\t\t
M1 Myeloblastic leukemia with little maturation | \n\t\t\t\t\t
M2 Myeloblastic leukemia with maturation | \n\t\t\t\t\t
M3 Acute promyelocytic leukemia (APL) | \n\t\t\t\t\t
M3h APL, hypergranular variant | \n\t\t\t\t\t
M3v APL, microgranular variant | \n\t\t\t\t\t
M4 Acute myelomonocytic leukemia (AMML) | \n\t\t\t\t\t
M4eo AMML with dysplastic marrow eosinophils | \n\t\t\t\t\t
M5 Acute monoblastic leukemia (AMoL) | \n\t\t\t\t\t
M5a AMoL, poorly differentiated | \n\t\t\t\t\t
M5b AMoL, differentiated | \n\t\t\t\t\t
M6 “Erythroleukemia” | \n\t\t\t\t\t
M6a AML with erythroid dysplasia | \n\t\t\t\t\t
M6b Erythroleukemia | \n\t\t\t\t\t
M7 Acute megakaryoblastic leukemia (AMkL) | \n\t\t\t\t\t
Table 1. French-American-British (FAB) Classification of Acute Myelogenous Leukemia | \n\t\t\t\t\t
French-American-British (FAB) Classification of Acute Myelogenous Leukemia.
AML-M0 is most common in adult patients. Accounts for approximately 5-10% of all AML patients. WBCs show Leukocytosis in 40% and > 50% with leukocytopenia. The diagnosis is made if less than 3% of the blasts are positive for peroxidase or the Sudan black B reaction and if the Blasts are positive for the myeloid-associated markers CD13, 14, CD15 or CD33, CD34 and negative for B or T lineage marker (CD3, CD10, CD19 and CD5). Bone marrow aspirated was hypercellular in all patients and contained a large number of leukemic blasts (Bennette JM 1991). Almost no mature myeloid cells were seen. The blasts were small to medium-sized round cells with an eccentric nucleus. The nucleus often had a flattened shape and was sometimes lobulated or cleaved and contained fine chromatin with several distinct nucleoli. The cytoplasm was lightly basophilic without granules. Auer rods are not found.
\n\t\t\tAcute myeloblastic leukemia AML –M0
It is found in all aged groups with highest incidence seen in adult and in infants less than a year old. Leukocytes in about 50% of patients at the time of diagnosis was increased. The predominant cell in the peripheral blood is usually a poorly differentiated myeloblast with finely reticulated chromatin and prominent nucleoli. Auer rods are found in the blast of 50% of the M1. If no evidence of granules or Auer rods is present, the blasts may resemble L2 lymphoblast. The myeloperoxidase or Sudan black B stains are positive in more than 3% of the blasts indicating granulocytes differentiation, the diagnosis is more likely AML-M1 than ALL (Bennett et al, 1976). PAS and alpha-naphthyl acetate esterase and naphthol AS-D-esterase are negative. About 50% of the patients will have acquired clonal chromosome aberrations in the leukemic cells. CD13, 14, 15, 33 and CD34 myeloid antigens are frequently positive in M1 leukemia. The most common cytogenetic abnormalities are: t (9; 22) (q34; q11)
\n\t\t\tAcute myeloblastic leukemia AML-M1
The presenting symptoms for M2 AML are similar to those of the M1 type. Leukocytes increased in 50% of patients. Myeloblast can usually be found in the blood smears and may be the predominant cell type. Pseudopelger–Huet and hypogranular neutrophils being most common cells are seen in M2.
\n\t\t\t\tThe bone marrow is hypercellular and types I and II myeloblasts make up from 30-83% of the promyelocytes to mature segmented cells. The monocytic component is less than 20%, differentiating M2 from M4. Basophils in some patient (M2 baso) was increased. Eosinophils and their precursors may be abundant, and in some cases accounts for up to 15% of myelogram (Berger and Flandrin, 1984). The characteristic that distinguishes AML-M2 from AML-M1 is the presence of maturation at or beyond the promyelocyte stage. Abnormal neutrophil maturation appears to be an integral part of AML-M2 with t(8;21) translocation. The neutrophils may show many abnormal nuclear segmentations and Auer rods.
\n\t\t\t\tCytochemistry; Myeloperoxidase (MPO) reaction in blast cells gives the same result as in AML-M1, but the reaction is often of little practical value because the granulocytic nature of AML-M2 is usually demonstrated clearly by the presence of maturing cells in the granulocytic series. Sodium fluoride does not inhibit esterase. PAS and nonspecific esterase are negative. Positive reaction with CD13 and CD15 antigens are frequently seen in cases of M2.
\n\t\t\tAcute myeloblastic leukemia AML-M2
The median age and survival average of APL is about 18 months and occurred in younger adult. M3 is of particular interest because it results in the fusion of a truncated retinoic acid receptor alpha (RAR-alpha) gene on chromosome 17 to a transcription unit called PML (for promyelocytic leukemia) on chromosome 15. It is interesting to note that high doses of the vitamin A derivative all-trans-retinoic acid are able to overcome thus block in differentiation both in vitro and in vivo and this agent has been successfully used to induce remission in patients.
\n\t\t\t\tA "variant" form of M3 (Bennett et al, 1980) is characterized by paucity of granules within the promyelocytic blasts and should not be confused with monocytic leukemia. The blasts are large with abundant cytoplasm, and the nucleus is usually irregular. The nucleus is often bilobed or markedly indented and a nucleolus can be seen in each lobe. The cytoplasm is completely occupied by closely packed large granules, staining bright pink, red or purple. Cells containing bundles of Auer rods "faggots" randomly distributed in the cytoplasm are characteristic, but are not present in all cases.
\n\t\t\t\tIt is believed that the release of large numbers of promyelocytic granules containing a procoagulant initiate disseminated intravascular clotting (DIC). This is the most serious complication of M3 AML occurs frequently in both AML-M3 as well as AML-M3 variant (McKenna et al, 1982). Initial therapy with the differentiating agent all-trans-retinoic acid (ATRA) has improved significantly the treatment of AML-M3 in this regard; early mortality as a result of DIC is substantially reduced.
\n\t\t\t\tCytochemistry: Peroxidase (MPO) and Sudan black B are strong positive. The periodic acid Schiff (PAS) is negative and Nonspecific esterase is also weak positive. The MPO reaction is also strong positive in the AML-M3 variant.
\n\t\t\t\tImmunological studies demonstrate positivity with CD13, CD15, CD1 and CD33 myeloid antigens. Cytogenetic studies have revealed a high prevalence (almost 50%) of the chromosomal translocation t(15; 17) associated with both AML M3 and M3 variant. M3 AML with t(15;17) is usually characterized by the association of the lymphoid marker, CD2 and CD19, with myeloid markers and the negativity of HLA-DR and CD34.
\n\t\t\t\tPromyelocytic leukemia AML-M3
Acute myelomonocytic leukemia M4
It is distinguished from M1, M2, and M3 by an increased proportion of leukemia monocytic cells in the bone marrow or blood or both. Gingival hyperplasia with gingival bleeding is present. Serum and urine levels of muramidase (lysozyme) are usually elevated because of the monocytic proliferation. The leukocyte count is usually increased monocytic cells (monoblast, promoncytes, monocytes), are increased to 5000/L or more. Anemia and thrombocytopenia are present in almost all cases. The marrow differs from M1, M2 and M3 in those monocytic cells exceed 20% of the nonerythroid nucleated cells. The sum of the myelocytic cells including myeloblasts, promyelocytes and later granulocytes is >20% and <80% of nonerythroid cells. This bone marrow picture together with a peripheral blood monocyte count of 5000/L or more is compatible with a diagnosis of M4.
\n\t\t\t\tConfirmation of the monocytic component of this subgroup requires cytochemistry. The profile includes positive reactions for sudan black B or peroxidase and both specific and non-specific esterase. A few cases of M4 AML are characterized by increased marrow eosinophils and classified as M4e (Berger et al 1985). Immunological studies demonstrate positivity with CD13, CD33, CD11b and CD14. Cytogenetic: inv(16) (p13; q22) and del (16)(q22).
\n\t\t\tCommon findings are weakness, bleeding and a diffuse erythematous skin rash. There is a high frequency of extramedulary infiltration of the lungs, colon, meninges, lymphnodes, bladder and larynx and gingival hyperplasia. Serum and urinary muramidase levels are often extremely high. The one criterion for a diagnosis of M5 is that 80% or more of all nonerythroid cells in the bone marrow are monocytic cells. There are two distinct forms 5a (maturation index <4%) and 5b (maturation index > 4%).M5a: Granulocyte <20% and Monocyte >80% >80% monoblast. M5b: Granulocyte <20% and Monocyte >80% <80% monoblast (Characterized by the presence of all developmental stages of monocytes; monoblast, promonocyte, monocyte)
\n\t\t\t\tCytochemistry: Non-specific esterase stains and alpha-naphthyl esterase are positive and PAS is negative. Myeloperoxidase and Sudan black are weak diffuse activity in the monoblast. The use of alph-naphthyl butyrate esterase (ANBE) is advantageous because of its greater degree of specificity and stronger reaction, and also because sodium fluoride inhibition is not required (Shibata et al, 1985). Immunological studies demonstrate positivity with CD11b and CD14. There is a strong association between AML M5/M4 and deletion and translocations involving band 11q23.
\n\t\t\tM5 Acute monoblastic leukemia (AMoL)
M6 is a rare form of leukemia that primarily affects the peripheral cells. It is nonsexist in children. The clinical manifestations are similar to other types of AML. The most frequent presentation is bleeding. The most dominant changes in the peripheral blood are anemia with sticking poikilocytosis and anisocytosis. Nucleated red cells demonstrate abnormal nuclear configuration. The leukocytes and platelets are usually decreased. The diagnosis of erythroleukemia can be made when more than 50% of all nucleated bone marrow cells are erythroid and 30% or more of all remaining nonerythroid cells are type I or type II blast cells (Bennett et al, 1985). The erythroblast is abnormal with bizarre morphologic features. Giant multilobular or multinucleated forms are common. Other features are; fragmentation, Howell-Jolly bodies, ring sideroblast, megaloblastic and dyserythropoiesis changes are common. The cytochemistry of erythroblasts are normally PAS negative but in AML-M6, erythroblasts especially pronormoblast demonstrates coarse positivity of PAS. Blast cells express a variety of myeloid associated antigens such as CD13, CD33, anti-MPO with or without expression of precursor-cell markers as CD34, HLA-Dr determinants as for blast cells from other AML subtypes. In M6-variant forms, the more differentiated cells can be detected by the expression of glycophorin A and the absence of myeloid markers.
\n\t\t\tM6 “Erythroleukemia”
M7 is rare. It occurs as a leukemia transformation of chronic granulocytic leukemia (CGL) and myelodysplastic syndrome (MDS). Pancytopenia is characteristic at initial diagnosis. Peripheral blood shows micromegakaryocytes and undifferentiated blasts. Bone marrow dry tap is common. Bone marrow biopsy show increased fibroblasts and/or increased reticulin and presence of greater than 30% blast cells. The diagnosis of M7 should be suspected when the blast cells show cytoplasmic protrusion or budding. As bone marrow smears obtained by aspiration may not be adequate to make a diagnosis, the peripheral blood films must be examined carefully for the presence of micromegakaryoblasts. Bone marrow biopsy sections are usually necessary and show a prominent reticulin fibrosis and excessive numbers of small blasts.
\n\t\t\t\tCytochemistry: Peroxidase is negative, PAS +/-, Esterase +/- and positive acid phospatase. Cytochemical positivity for -naphthyl acetate esterase reaction and negative reaction with -naphthyl butyrate esterase is unique to megakaryoblast. (Monocytes react positively with both esterase substrates).
\n\t\t\t\tThe monoclonal antibodies that reacts with platelet glycoprotein Ib, IIb/IIIa and IIIb, using immunologic technique as well as CD41, CD42 and CD61 positivity.
\n\t\t\t\tThere is no unique chromosomal abnormality associated with acute megakaryoblastic leukemia, with the exception of t(1;22)(p13;q13), which has been found almost exclusively in young children, less than 18 months old who do not have Downís syndrome.
\n\t\t\t\tM7 Acute megakaryoblastic leukemia (AMkL)
Morphologic Classification | \n\t\t\t\t\t\t|
FAB Type | \n\t\t\t\t\t\t\tFeatures of Blasts | \n\t\t\t\t\t\t
L1 | \n\t\t\t\t\t\t\tSmall cells with scant cytoplasm; nucleoli indistinct and not visible | \n\t\t\t\t\t\t
L2 | \n\t\t\t\t\t\t\tLarge, heterogeneous cells with moderately abundant cytoplasm;clefting and indentation of nucleus; large and prominent nucleoli | \n\t\t\t\t\t\t
L3 | \n\t\t\t\t\t\t\tLarge cells with moderately abundant cytoplasm; regular, oval-to-round nucleus; prominent nucleoli;prominent cytoplasmic basophilia and cytoplasmic vacuoles | \n\t\t\t\t\t\t
Morphologic Classification of Acute Lymphocytic Leukemia.
Acute lymphoblastic leukemia (ALL) is divided in FAB L1 (children), L2 (older children and adult), and L3 (patients with leukemia secondary to Burkitt\'s lymphoma. These types are defined according to two criteria (1) the occurrence of individual cytologic features and (2) the degree of heterogeneity among the leukemic cells. These features considered are cell size, chromatin, nuclear shape, nucleoli, and degree of basophilia in the cytoplasm and the presence of cytoplasmic vacuolation (Bennett et al 1976).
\n\t\t\t\tALL-L1: Homogenous cells (Small cell): One population of cells within the case. Small cells predominant, nuclear shape is regular with occasional cleft. Nuclear contents are rarely visible. Cytoplasm is moderately basophilic. L1 accounts 70% of patients. The L1 type is the acute leukemia that is common in childhood, with 74% of these cases occurring in children 15 years of age or younger.
\n\t\t\t\tALL-L2: Heterogeneous cells: Large cells with an irregular nuclear shape, cleft in the nucleus are common. One or more large nucleoli are visible. Cytoplasm varies in colour and nuclear membrane irregularities. L2 accounts 27% of ALL patients. The FAB-L2 blast may be confused with the blasts of acute myeloid leukemia. Approximately 66% of these cases of ALL in patients older than 15 years are of type 2.
\n\t\t\t\tAcute lymphoblastic leukemia L1
Acute lymphoblastic leukemia L2
ALL-L3: Burkitt\'s lymphoma type: Cells are large and homogenous in size, nuclear shape is round or oval. One to three prominent nucleoli and sometimes to 5 nuleoli are visible. Cytoplasm is deeply basophilic with vacuoles often prominent. Intense cytoplasmic basophilia is present in every cell, with prominent vacuolation in most. A high mitotic index is characteristic with presence of varying degrees of macrophage activity. Mature B-lymphoid markers are expressed by most cases.
\n\t\t\t\tAcute lymphoblastic leukemia L3
Acute Myeloid Leukemia (AML) and Related Precursor Neoplasm | \n\t\t\t\t\t\t
AML with recurrent genetic abnormalitiesAML with t(8;21)(q22;q22); RUNX1-RUNX1T1AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARAAML with t(9 ;11)(p22;q23); MLLT3-MLLAML with t(6;9)(p23;q34); DEK-NUP214AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 | \n\t\t\t\t\t\t
AML with mutated NPM1AML with mutated CEBPAAML with myelodysplasia-related changesTherapy-related myeloid neoplasmsMyeloid sarcoma Myeloid proliferations related to Down syndrome | \n\t\t\t\t\t\t
Transient abnormal myelopoiesisMyeloid leukemia associated with Down syndromeBlastic plasmacytoid denderitic cell neoplasm | \n\t\t\t\t\t\t
World Health Organization Classification of Acute Myelogenous Leukemia (2008)
AML defined as ≥20% blasts in blood or bone marrow; however, clonal, recurring cytogenetic abnormalities should be considered AML regardless of blast percentage. Ongoing clinical trials may continue to use French-American-British (FAB) criteria of ≥30% blasts until completion of trial. FAB classification identified as M0 through M7.
\n\t\t\t\tThe classification schemes by the World Health Organization (WHO) require the additional evaluation of the leukemic blasts by molecular analysis and flow cytometry (Harris NL 1997& Brunangelo Falini 2010, Sachdeva et al 2006). The results of these 4 methods of evaluation (i.e, morphology, staining, molecular analysis, flow cytometry) not only differentiate ALL from AML, but also categorize the subtypes of acute leukemia. Table 3 summarizes the new classification of AML as proposed by WHO, Knowing the subtype of a patient’s leukemia helps in predicting the clinical behavior of the disease and the prognosis, and in making treatment recommendations. This classification also improves the reproducibility of diagnoses and stresses the heterogeneity of the subtypes of AML and ALL (Vardiman 2009). Recent advances in molecular biology have shown that various subtypes of AML and ALL behave differently and should not be treated similarly. For example, the identification of M3 AML (acute promyelocytic leukemia) is crucial because it is associated with disseminated intravascular coagulation (DIC), and retinoic acid, in addition to chemotherapy, is the treatment of choice.
\n\t\t\t\tThe two most significant differences between the FAB and the WHO classifications are:
\n\t\t\t\tPatients with recurring clonal cytogenetic abnormalities should be considered to have AML regardless of the blast percentage (8;21)(q22;q22), t(16;16)(p13;q22), inv(16)(p13;q22), or t(15;17)(q22;q12) (Arber DA et al 2008a, 2008b, 2008c, Weinberg OK et al 2009).
\n\t\t\t\tThe world Health Organization (WHO) classification has changed the grouping of ALL to reflect increased understanding of the biology and molecular pathogenesis of the diseases. In addition to discarding the L1-L3 terms, the new classification characterizes these heterogenous diseases based upon immunophenotype into 3 basic categories: precursor B-cell ALL, precursor T-cell ALL, and mature B-cell ALL (Burkitt lymphoma/leukemia) (Jaffe et al 2001)
\n\t\t\t\tWHO classification | \n\t\t\t\t\t\t
Precursor B-cell ALL/LBL Cytogenetic subgroups t(9;22)(q34,q11),BCR/ABL t(v;11q23);MLL rearranged t(1;19)(q23;p13);PBX1/E2A t(12;21)(p13;q22);TEL/AML1 Hypodiploid Hyperdiploid, "/50 \n\t\t\t\t\t\t\t\t Precursor T-cell ALL/LBL \n\t\t\t\t\t\t\t\t Mature B-cell leukemia/lymphoma | \n\t\t\t\t\t\t
ALL= acute lymphoblastic leukemia; LBL= lymphoblastic lymphoma; MLL= mixed lineage leukemia | \n\t\t\t\t\t\t
World Health Organization classification of acute lymphoblastic leukemia
Abnormalities in chromosome number as well as structural rearrangements (translocations) occur commonly in ALL. Important cytogenetic abnormalities in precursor B-cell ALL that are associated with a poor prognosis include t(9;22) or Philadelphia chromosome-positive (Ph+) ALL, which increases in frequency with age; t(4;11); hypodiploidy, especially if <45% chromosomes ; and trisomy 8 in adult ALL. The t(4;11) results from a balanced translocation involving a gene on the long arm of chromosome 11 at band q23 (11q23), known as the mixed lineage leukemia (MLL) gene. MLL gene translocations occur most commonly in infancy and are associated with both acute lymphoid and myeloid leukemias.
\n\t\t\tThe European Group for the Immunological Classification of Leukemias (EGIL)(Bene MC et al 1995& Hoelzer et al 2002)) has proposed that acute leukaemia be classified on the basis of immunophenotype alone. This classification has the strength that it suggests standardized criteria for defining a leukaemia as myeloid, T lineage, B lineage, or biphenotypic. It also suggests criteria for distinguishing biphenotypic leukaemia from AML with aberrant expression of lymphoid antigens, and from ALL with aberrant expression of myeloid antigens. However, a purely immunological classification has the disadvantage that discrete entities may fall into one of two categories; for example some cases of AML of FAB M2 subtype associated with t(8;21)(q22;q22) would be classified as "AML of myelomonocytic lineage", while others would be classified as "AML with lymphoid antigen expression," depending on whether or not a case showed aberrant expression of CD19. In addition, rare cases of acute leukaemia have been described which were clearly myeloid when assessed by cytology and cytochemistry but which did not express any of the commonly investigated myeloid antigens.
\n\t\t\tPrecursor B-lymphoblastic leukemia ( HLA-DR+, TdT+, CD19+, and/or CD79a+, and/or CD22+, and/or CD34+). This type of ALL accounts for around 75% of adult cases and is subdivided into the following groups: | \n\t\t\t\t\t
a. Pro B-ALL expresses HLA-DR, TdT, and CD19. CD10-, cytoplasmic immunoglobulin negative; represents approximately 10% of adult ALL. | \n\t\t\t\t\t
b. Common ALL is characterized by the presence of CD10, cytoplasmic immunoglobulin negative; comprises greater than 50% of adult cases of ALL. | \n\t\t\t\t\t
c. Pre B-ALL is characterised by the expression of cytoplasmic immunoglobulin and CD10; this subtype of ALL is identified in nearly 10% of adult cases. | \n\t\t\t\t\t
d. Mature B-ALL is found in approximately 4% of adult ALL patients. The blast cells express surface antigens of mature B cells, including surface membrane immunoglobulin (SmIg+). They are typically TdT and CD34 negative and have L3 morphology. This category overlaps with Burkitt lymphoma, which is included under the mature B-cell neoplasms. | \n\t\t\t\t\t
Precursor T-lymphoblastic leukemia | \n\t\t\t\t\t
Cells are TdT+ in addition to cytoplasmic CD3+ and CD34+. This type of ALL accounts for around 25% of adult cases and is subdivided into: | \n\t\t\t\t\t
a. Pro T-ALL CD2-, CD7+, CD4-, CD8- seen in around 7% of adult ALL. | \n\t\t\t\t\t
b. Pre T-ALL CD2+, CD7+, CD4-, CD8-. | \n\t\t\t\t\t
c. Cortical T-ALL or Thymic ALL (Thy ALL) is CD1a+ and accounts for 17% of adult ALL CD7+, CD2+, CD5+, CD4+, CD8+ | \n\t\t\t\t\t
d. Mature T-ALL are surface CD3+, CD2+, CD7+, CD4 or 8, and TdT/CD34/CD1a- and make up approximately 1% of adult ALL. | \n\t\t\t\t\t
European Group for the Immunological Characterization of Leukemias (EGIL) classification of acute lymphocytic leukemia (Hoelzer 2002)
The consensus considers a 20% minimum threshold to define a positive reaction of blast cells to a given monoclonal antibody. Roughly 75% of cases of adult ALL are of B-cell lineage. B-lineage markers are CD19, CD20, CD22, CD24, and CD79a (Huh 2000).
\n\t\t\tThe earliest B-lineage markers are CD19, CD22 (membrane and cytoplasm) and CD79a (Campana 1988). A positive reaction for any two of these three markers, without further differentiation markers, identifies pro-B ALL. The presence of CD10 antigen (CALLA) defines the "common" ALL subgroup. Cases with additional identification of cytoplasmatic IgM constitute the pre-B group, whereas the presence of surface immunglobulin light chains defines mature B-ALL.
\n\t\t\tT-cell ALL constitutes approximately 25% of all adult cases of ALL. T-cell markers are CD1a, CD2, CD3 (membrane and cytoplasm), CD4, CD5, CD7 and CD8. CD2, CD5 and CD7 antigens are the most immature T-cell markers, but none of them is absolutely lineage-specific, so that the unequivocal diagnosis of T-ALL rests on the demonstration of surface/cytoplasmic CD3.
\n\t\t\tALL of B or T lineage can additionally express myeloid antigens or stem-cell antigen CD34. The latter has little diagnostic relevance but can be prognostically important (De Waele 2001) The scoring system recently proposed by the EGIL group addressed the characterization of the acute leukemia as B or T lineage ALL, or AML by including the most specific markers for the lymphoid and myeloid lineages among those of earlier stages of cell differentiation, plus some non-specific but stem-cell markers. The system introduced a modified terminology specific to each \'maturation\' step within the B- or T-cell lineage (EGIL 1995) and was confirmed as adequate for both diagnosis and subclassification of ALL (Thalhammer-Scherrer 2002).
\n\t\tBiphenotypic acute leukemia (BAL), or acute leukemia with a single population of blasts coexpressing markers of two different lineages, is a rare clinical entity.
\n\t\t\tThe scoring systems proposed by Catovsky
Myeloid lineage | \n\t\t\t\t\t\tT-lineage | \n\t\t\t\t\t\tB-lineage | \n\t\t\t\t\t\t\n\t\t\t\t\t |
MPO | \n\t\t\t\t\t\tCD3 | \n\t\t\t\t\t\tCD79 | \n\t\t\t\t\t\t2 point | \n\t\t\t\t\t
Lisozyme | \n\t\t\t\t\t\tAnti TCR | \n\t\t\t\t\t\tIgM | \n\t\t\t\t\t|
\n\t\t\t\t\t\t | \n\t\t\t\t\t\t | CD22 | \n\t\t\t\t\t|
CD13 | \n\t\t\t\t\t\tCD2 | \n\t\t\t\t\t\tCD19 | \n\t\t\t\t\t\t1 point | \n\t\t\t\t\t
CD33 | \n\t\t\t\t\t\tCD5 | \n\t\t\t\t\t\tCD10 | \n\t\t\t\t\t|
CD65 | \n\t\t\t\t\t\tCD8 | \n\t\t\t\t\t\tCD20 | \n\t\t\t\t\t|
CD10 | \n\t\t\t\t\t|||
CD14 | \n\t\t\t\t\t\tTdT | \n\t\t\t\t\t\tTdT | \n\t\t\t\t\t\t0.5 point | \n\t\t\t\t\t
CD15 | \n\t\t\t\t\t\tCD17 | \n\t\t\t\t\t\tCD24 | \n\t\t\t\t\t|
CD64, CD117 | \n\t\t\t\t\t\tCD10 | \n\t\t\t\t\t
EGIL Scoring system for biphenotypic acute leukemia
Biphenotypic acute leukemia is defined when scores are >2 for the myeloid lineage and >1 for the lymphoid lineage. In some T-ALL cases, clonality of TCR alphabeta rearrangements can now be assessed cytoflourmetrically (Langerak 2001, Xu XQ et al 2009).
\n\t\t\tThe prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. Biphenotypic acute leukemia patients showed a much higher incidence of CD34 antigen expression, complex abnormal karyotype, extramedullary infiltration, relapse, and resistance to therapy after relapse (Xu XQ et al 2009).
\n\t\tAcute leukaemia can be classified in many ways. An ideal classification is one which recognizes real entities with fundamental biological differences. The FAB classification of ALL and AML is based on morphology and cytochemical staining of blasts. However, the recent classification schemes proposed by the World Health Organization (WHO) require the additional evaluation of the leukemic blasts by molecular analysis and flow cytometry. The results of these 4 methods of evaluation (ie, morphology, staining, molecular analysis, flow cytometry) not only differentiate ALL from AML, but also categorize the subtypes of acute leukemia. Recent advances in molecular biology have shown that various subtypes of AML and ALL behave differently and should not be treated similarly. For example, the identification of M3 AML (acute promyelocytic leukemia) is crucial because it is associated with disseminated intravascular coagulation (DIC), and retinoic acid, in addition to chemotherapy, is the treatment of choice.
\n\t\t\tThe European Group for the Immunological Classification of Leukemias (EGIL) has proposed that acute leukaemia be classified on the basis of immunophenotype alone. This classification has the strength that it suggests standardized criteria for defining a leukaemia as myeloid, T lineage, B lineage, or biphenotypic. It also suggests criteria for distinguishing biphenotypic leukaemia from AML with aberrant expression of lymphoid antigens, and from ALL with aberrant expression of myeloid antigens.
\n\t\tIn late 2019, cases of pneumonia from unknown origin were detected in Wuhan, China. It was concluded that the cause was a new coronavirus [1, 2]. The World Health Organization (WHO) named the virus SARS-CoV-2 and COVID-19 the associated disease [1, 2]. In the first months of 2020, this disease became a pandemic with a reported high lethality. Since then, the search for treatments has begun.
SARS-CoV-2 is a coronavirus of the beta family and is related to the previously known SARS-CoV [3]. It is transmissible from human to human. The primary transmission is via respiratory droplets. Even so, transmission by other fluids has been reported. The protein that mediates the entry to the host cells is the so-called spike protein. It uses the angiotensin-converting enzyme 2 (ACE2) as a cellular receptor. It primarily affects the lungs and the respiratory system with flu-like symptoms presentation [3]. Nevertheless, it also causes a wide spectrum of conditions from diarrhea to loss of smell and taste. The chief complication due to COVID-19 that can lead to death is pneumonia.
Once the SARS-CoV-2 enters the host cell, the viral RNA is attached to the host ribosome, translating into two large coterminal polyproteins. These proteins are then digested into components by proteolysis for packaging new virions. The papain-like protease (PLpro) and the coronavirus main protease (Mpro) are two proteases involved in this process. SARS-CoV-2 employs RNA-dependent RNA polymerase (RdRp) to replicate the genome of RNA. The four proteins: spike, Mpro, PLpro, and RdRp, are essential to virus assembly and pathogenesis. Mpro and RdRp are the targets for drugs against SARS-CoV-2 [4].
This pandemic has disrupted the global society. Besides global health, it has affected the economy and way of living since most of the interventions to stop the dissemination were non-pharmaceutical. Governments around the world exhorted people to stay at home and social distancing [5].
As a result of the global concern posed by this disease, some experiential recommendations emerged for its treatment. Social networks played a crucial role in the diffusion of these recommendations [6]. A couple of cases are hydroxychloroquine and ivermectin [7]. Much of the supposed evidence was absent or anecdotic. It generated false expectations and misinformation.
There were no previously approved therapeutics for COVID-19 since it was an emerging disease. Later in the pandemic, the WHO authorize the emergency use of some antivirals [8, 9]. The recommendations by other institutions of treatments for use outside of clinical trials were scarce. Such is the case for ivermectin [10].
This chapter aims to review the literature on therapeutics approved by the WHO for emergency use. It will also cover some of the treatments recommended and considered based on empirical results.
It was searched on the therapeutics guidelines published by the WHO [11] and the USA Federal Drug Administration (FDA) [12] for the management of infection by SARS-CoV-2. Based on these results, we searched for more literature in PubMed to obtain evidence from the drugs against SARS-CoV-2.
Besides searching for articles in Pubmed, we used the Google Scholar database to search about treatments against SARS-CoV-2 infection, including the words: Treatment, SARS-CoV-2, COVID-19, Therapeutics, WHO approved COVID-19 drugs, and FDA approved COVID-19 drugs.
The chief inclusion criteria were articles on treatments approved by WHO [11] and FDA [12]. The search also included treatments previously approved for human use but not for COVID-19 and, even so, were used.
There are reports on drugs used empirically for the treatment of COVID-19, and the WHO has made statements on these treatments.
Table 1 shows the drugs of empirical use without approval by the WHO and FDA, for their use against COVID-19 in humans, except in clinical trial settings.
Drug | Indication |
---|---|
Ivermectin | Antiparasitic |
Hydroxychloroquine | Antimalarial |
Nitazoxanide | Antiparasitic |
Azithromycin | Antibiotic |
Some drugs used empirically without approval for emergency use.
Ivermectin is a mixture of 22, 23-dihydroavermectin B1a, and 22, 23-dihydroavermectin B1b. It is macrocyclic lactose with a wide antiparasitic spectrum [10]. Its chemical structure [13], is shown in Figure 1.
Chemical structure of ivermectin. Source. Modified from: PubChem. National Library of Medicine [
It is considered that its action mechanism is by inhibiting the nuclear transport mediated by the heterodimer importin α/β1-responsible for the viral protein’s translocation (HIV-1, SV40)-, necessary for its replication [14, 15, 16]. It has been reported that ivermectin inhibits the SARS-CoV-2 in vitro without stating clearly how it happens [16]. Since then, it was considered a potential treatment.
Even as studies suggest a reduction in mortality, most have methodological deficiencies [17, 18, 19]. Hence, further and rigorous evidence on the use of ivermectin against COVID-19 is necessary. Currently, the use of ivermectin is just recommended in clinical trial settings. Also, the Food and Drug Administration does not recommend the ivermectin use against COVID-19 due to the lack of evidence [20]. The same conclusion is supported by the Sanitary Technologies Assess Department from the Clinical and Sanitary Efficacy Institute [21].
The Pan American Health Organization states that there is no certainty about the risks and benefits from the use of ivermectin [22].
Hydroxychloroquine is a 4-aminoquinoline drug aimed to treat malaria and rheumatologic conditions [22]. In Figure 2, its chemical structure is shown.
Chemical structure of hydroxychloroquine. Source: Modified from PubChem. National Library of Medicine [
Due to the inhibition of SARS-CoV-2 in vitro, it was considered a potential treatment for COVID-19 [24]. Hydroxychloroquine received much public attention even at high political levels. It caused such a phenomenon that most random trials studying it were unable to finish properly, and those that were completed did not show any benefit [25].
Currently, the WHO makes a strong recommendation against its use in its latest therapeutics guidelines [11, 26].
Nitazoxanide and its metabolite Tizoxanide could inhibit the in vitro growth of the canine coronavirus S-378 [26]. Wang M et al. [25] have reported that Nitazoxanide could also inhibit the SARS-CoV-2 growth (Figure 3).
Chemical structure of Nitazoxanide. Source: Modified from PubChem. National Library of Medicine [
Early studies suggested a beneficial effect of Nitazoxanide by reducing the disease severity of COVID-19 [28, 29]. Rocco et al [30], reported that Nitazoxanide did not show a difference in preventing admission to the intensive care unit for COVID-19 patients with pneumonia. In this study, it was showed a difference in secondary outcomes such as hospital discharge.
There are few studies analyzing Nitazoxanide. So far, there is no evidence of a significant benefit for the COVID-19 treatment. The evidence on the use of nitazoxanide is scarce. The WHO does not include this drug in its living guideline for therapeutics and COVID-19 [11].
Azithromycin is an antibiotic mainly prescribed for bacterial diseases and belongs to the family of macrolide [31]. This drug has been considered for COVID-19 treatment due to in vitro results. Its chemical structure is shown in Figure 4.
Chemical structure of azithromycin. Source: Modified from PubChem. National Library of Medicine [
Oldenburg et al. [31], reported the results of a clinical trial involving azithromycin as a candidate. The primary outcome was the resolution of symptoms. It was not found a statistically significant effect between the experimental and the control group. From 23 secondary outcomes, only 5 showed statistically significant differences [33].
Azithromycin was chiefly used with other drugs. As it was used in combination with hydroxychloroquine, its effect and possible harms could not be clearly distinguished [34]. Nevertheless, so far, it is not recommended for COVID-19 treatment. The WHO only includes this drug tangentially in its therapeutics and COVID-19 living guideline while mentioning its use accompanied by hydroxychloroquine [11].
In the following sections, we review some of the therapeutics and their recommendation status by the WHO [11] and FDA [12]. Table 2 shows the drugs and treatments against COVID-19 treated in this section.
Drug | Indication | Dose | Observations |
---|---|---|---|
Molnupiravir | For patients with mild COVID-19 with hospitalization risk. | 800 mg (four pills) twice a day for 5 days | Do not administer in children or pregnant women. There are no data about its safety. |
Casirivimab-Imdevimab | Do not recommend for variants. | Intravenous. Ranging from 1200–2400 mg the total dose | The hospitalization risk decreases by 85%. |
Ritonavir-Nirmatrelvir | Recommended as early as possible within the first 5 days since the onset of symptoms. | 300 mg (two 150 mg tablets) of nirmatrelvir and 100 mg of ritonavir every 12 hours daily for 5 days | |
Remdesivir | Recommended as early as possible within the first 7 days since the onset of symptoms. | Intravenous administration for 3 consecutive days with the following scheme: Day one: 200 mg Day two and three: 100 mg | Conditional recommendation since the existence of potentially most beneficial treatments. |
Favipiravir | Not standardized yet | In animal models, it has potentiated the effect of molnupiravir. |
Drugs for the emergency use against COVID-19.
Molnupiravir is a drug originally designed to treat viruses such as influenza. In recent months, it has been proposed for use against COVID-19 [35]. The chemical structure is shown in Figure 5.
Chemical structure of Molnupiravir. Source: Modified from PubChem. National Library of Medicine [
In the study by Jayk Bernal et al. [37], the molnupiravir group had better outcomes than the placebo one. The chief outcome was hospitalization or death. Even as the sex was imbalanced, further analysis showed that the effect remained. There were no statistically significant differences regarding adverse events among the groups.
Singh et al. [35] conclude that the current evidence suggests that molnupiravir is effective for the prevention of hospitalization and deaths in mild COVID-19 patients. Nevertheless, further evidence is needed for the case of moderate and severe COVID-19 patients. Even far, Extance [38], mentions that the existence of only one pivotal study indicates that the evidence is very limited.
The WHO recommends the use of this drug conditionally due to the absence of data about long-term harms that may cause its use [11].
Casirivimab and imdevimab are monoclonal antibodies that target sites in the receptor binding domain of the SARS-CoV-2 spike glycoprotein [39]. The administration via has been one of the chief difficulties for their extensive use—its administration is intravenous.
The RECOVERY Collaboration Group included this treatment in their analysis [39]. They noted that casirivimab-imdevimab reduced the mortality significatively among seronegative patients (those without previously mounted humoral response).
The WHO recommends it conditionally. The reasons are that other drugs have proven to be more effective and safer. Also, these drugs are easiest to administer [11].
Nirmatrelvir is a drug designed to treat covid-19 by targeting its main protease [40]. It has been administered with ritonavir. Figure 6 shows the chemical structure of nirmatrelvir and ritonavir.
Chemical structure of: (A) nirmatrelvir; and (B) ritornavir. Source: modified from PubChem. National Library of Medicine [
Hammond et al. [40] report that the incidence of hospitalization or death was lower by approximately 6% points in the treatment group than in the control group—observed in the interim and final analysis. The difference among adverse events was not statistically significant.
Its first approval for conditional use was issued in the United Kingdom on December 31, 2021. Since then, other countries have approved this drug in different modalities, such as for emergency use [43].
It is one of the few drugs strongly recommended by the WHO [11].
It is a combination of drugs that aim to inhibit the protease of SARS-CoV-2 and its use was motivated by previous experiences against SARS [44]. Figure 7 shows the chemical structure of lopinavir.
Chemical structure of Lopinavir. Source: Modified from Pubchem. National Library of Medicine [
Cao et al. [44] did not find any statistically significant difference between the control and experimental group in their trial. The primary outcome they took was the decrease of two points on a severe scale or discharge. They recommend further studies to prove or discard benefits from ritonavir–lopinavir.
The WHO makes a recommendation against the use of this combination [11].
Remdesivir is another drug that inhibits SARS-CoV-2 and was considered for its use due to previous research on its effect on SARS and MERS [46]. The chemical structure is shown in Figure 8.
Chemical structure of remdesivir. Source: Modified from Pubchem. National Library of Medicine [
According to Beigel et al. [46], remdesivir outperformed placebo in their clinical trial, which consisted of 1062 patients. They took discharge or hospitalization for monitoring as primary outcome. The patients in the remdesivir group reached the primary outcome approximately 5 days before the patients in the placebo group. In their trial, they administered remdesivir intravenously for three consecutive days with the following regime:
Day one: 200 mg
Day two and three: 100 mg (each day)
Wang Y et al. [48] did not find a statistically significant benefit from the use of remdesivir. Nevertheless, the samples consisted of 237 participants, and a numerical difference among the groups was observed—supporting the use of remdesivir.
Spinner et al. [49], conducted a clinical trial comparing 5- and10-day treatment versus standard care for patients with moderate COVID-19. The differences in the primary outcome (degree on a seven-point scale) were statistically significant between the 5-day group and the standard care group. It was not observed for the differences between the 10-day group and the standard care group. Even though some results were statistically significant different, the authors are uncertain of the clinical importance.
The WHO conditionally recommends remdesivir. They suggest using it in the first 7 days after the onset of symptoms [11].
Favipiravir is a drug with an active agent that halts viral replication of SARS-CoV-2 [50, 51]; its chemical structure is shown in Figure 9.
Chemical structure of favipiravir. Source: Modified from Pubchem. National Library of Medicine [
Manabe et al. [51] conducted a systematic review and meta-analysis on the use of favipiravir against SARS-CoV-2. They found evidence supporting the use of favipiravir to clear the virus. It was observed in various studies a viral clearance around the seventh day after the start of treatment. However, they suggest further analysis and controlled clinical trials since the evidence was heterogeneous and not straightforwardly comparable. Also, they conclude it is necessary for further research on the dose regime to have definitive conclusions.
The WHO only mentions favipiravir tangentially as a drug that might improve the outcomes by combining it with molnupiravir, observed in animal models [11].
After the approval and research on treatments, there are two chief questions to address. The first question is how to distribute the drugs with equity. The other point is how they perform in the face of new SARS-CoV-2 variants.
Regarding the distribution of the treatments, the ones administered orally present clear advantages over the ones administered intravenously. Nevertheless, as pointed out by Bajaj and Stanford [53], there are important challenges to address. So far, the inequities detected are the manufacturing and pricing obstacles, and some countries buying most of the current stock [53].
In the face of new SARS-CoV-2, some studies have addressed the question on which therapeutics remain effective for COVID-19. According to the review made by Fernandes et al. [54], the currently approved antivirals, such as molnupiravir, ritonavir-nirmatrelvir, and remdesivir remain as effective for variants of concern as for the early versions of SARS-CoV-2. Mainly due to their mechanisms of action.
Two years ahead of the COVID-19 pandemic start, plenty of treatment options have been investigated. Only a few of them have resulted in effective and safe alternatives. The WHO [11] and the FDA [12] keep updated on the sources and status of the scientific evidence of each proposal. According to the WHO, ritonavir-nirmatrelvir outperforms other proposed therapeutics.
As SARS-CoV-2 continues mutating, an open question is whether these treatments will remain effective for these new versions. The evidence shows that they are for spike-mutated versions of the virus.
Finally, even though some drugs have been approved, availability is not even in the countries. The factors behind this include the distribution systems and logistics besides costs.
The authors declare no conflict of interest.
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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}}]}},subseries:{item:{id:"3",type:"subseries",title:"Bacterial Infectious Diseases",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools",scope:"