Tip values in Damon’s system.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"9415",leadTitle:null,fullTitle:"Advanced Oxidation Processes - Applications, Trends, and Prospects",title:"Advanced Oxidation Processes",subtitle:"Applications, Trends, and Prospects",reviewType:"peer-reviewed",abstract:"Advanced Oxidation Processes – Applications, Trends, and Prospects constitutes a comprehensive resource for civil, chemical, and environmental engineers researching in the field of water and wastewater treatment. The book covers the fundamentals, applications, and future work in Advanced Oxidation Processes (AOPs) as an attractive alternative and a complementary treatment option to conventional methods. This book also presents state-of-the-art research on AOPs and heterogeneous catalysis while covering recent progress and trends, including the application of AOPs at the laboratory, pilot, or industrial scale, the combination of AOPs with other technologies, hybrid processes, process intensification, reactor design, scale-up, and optimization. The book is divided into four sections: Introduction to Advanced Oxidation Processes, General Concepts of Heterogeneous Catalysis, Fenton and Ferrate in Wastewater Treatment, and Industrial Applications, Trends, and Prospects.",isbn:"978-1-78984-891-5",printIsbn:"978-1-78984-890-8",pdfIsbn:"978-1-83880-971-3",doi:"10.5772/intechopen.85681",price:119,priceEur:129,priceUsd:155,slug:"advanced-oxidation-processes-applications-trends-and-prospects",numberOfPages:182,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"60d177837fbb691b82c80922cd9bb295",bookSignature:"Ciro Bustillo-Lecompte",publishedDate:"June 10th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9415.jpg",numberOfDownloads:8703,numberOfWosCitations:32,numberOfCrossrefCitations:20,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:58,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:110,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 6th 2019",dateEndSecondStepPublish:"June 27th 2019",dateEndThirdStepPublish:"August 26th 2019",dateEndFourthStepPublish:"November 14th 2019",dateEndFifthStepPublish:"January 13th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!0,featuredMarkup:null,editors:[{id:"189304",title:"Dr.",name:"Ciro",middleName:"Fernando",surname:"Bustillo-Lecompte",slug:"ciro-bustillo-lecompte",fullName:"Ciro Bustillo-Lecompte",profilePictureURL:"https://mts.intechopen.com/storage/users/189304/images/system/189304.jpeg",biography:"Dr. Ciro Bustillo LeCompte has a multidisciplinary background\nin the areas of civil, environmental, and chemical engineering.\nHe completed his Bachelor of Engineering (2008) at the University of Cartagena, Colombia, and obtained his MASc (2012)\nand PhD (2016) at Ryerson University, Canada. Dr. LeCompte\nis a certified Professional Engineer (PEng), Environmental\nProfessional (EP), a Fraternal Member of the Canadian Institute\nof Public Health Inspectors (CIPHI), and a 2017-2018 Queen Elizabeth Scholar\n(QES). He is currently an Associate Member in the Environmental Applied Science\nand Management Graduate Programs, and a Lecturer in the School of Occupational\nand Public Health at Ryerson University. He has co-authored over twenty peer-reviewed scientific papers, several conference proceedings, chapters, and books. His\nresearch interests include advanced oxidation processes, advanced treatment of\nwater and wastewater, waste minimization, water, soil and air quality, energy and\nresource recovery, water reuse, and heterogeneous catalysis.",institutionString:"Ryerson University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ryerson University",institutionURL:null,country:{name:"Canada"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1354",title:"Wastewater Engineering",slug:"technology-environmental-engineering-wastewater-engineering"}],chapters:[{id:"70086",title:"Advanced Oxidation Processes: A Powerful Treatment Option for the Removal of Recalcitrant Organic Compounds",doi:"10.5772/intechopen.90192",slug:"advanced-oxidation-processes-a-powerful-treatment-option-for-the-removal-of-recalcitrant-organic-com",totalDownloads:1624,totalCrossrefCites:6,totalDimensionsCites:20,hasAltmetrics:0,abstract:"Advanced oxidation processes (AOPs) are the technologies that generally use the hydroxyl radicals, the ultimate oxidant for the remediation of organic contaminants in wastewater. These are highly effective novel methods speeding up the oxidation process. AOP can combine with ozone (O3), catalyst, or ultraviolet (UV) irradiation to offer a powerful treatment of wastewater. Future research should be focused on enhancing the properties of heterogeneous catalysts in AOPs. This chapter reports general review of different AOPs utilized for the removal of various phenolic compounds and textile dyes in wastewater. The chapter also aimed at an investigation of efficiency for different photochemical AOPs. The authors have carried out the experimental runs at a laboratory scale for the removal of malachite green oxalate (MGO) dye with photochemical AOPs. The influence of ferrous ions and oxidant dosage on percentage decolorization of MGO in wastewater has been reported. The discussion extends to the utilization of different modified photocatalysts for the photocatalysis process. The future challenges, such as the adoption of strategies for the integration of processes and the decrement in operational cost of AOPs, are discussed. The discussion covers the utilization of different heterogeneous catalysts, the reduction of input demands of chemicals and energy for the processes.",signatures:"Damodhar Ghime and Prabir Ghosh",downloadPdfUrl:"/chapter/pdf-download/70086",previewPdfUrl:"/chapter/pdf-preview/70086",authors:[{id:"251470",title:"Dr.",name:"Prabir",surname:"Ghosh",slug:"prabir-ghosh",fullName:"Prabir Ghosh"},{id:"312650",title:"Mr.",name:"Damodhar",surname:"Ghime",slug:"damodhar-ghime",fullName:"Damodhar Ghime"}],corrections:null},{id:"70440",title:"Heterogeneous Catalytic Process for Wastewater Treatment",doi:"10.5772/intechopen.90393",slug:"heterogeneous-catalytic-process-for-wastewater-treatment",totalDownloads:983,totalCrossrefCites:1,totalDimensionsCites:6,hasAltmetrics:0,abstract:"This chapter introduced heterogeneous catalysis and described diverse heterogeneous catalytic processes for wastewater treatment. The main advantages of heterogeneous catalysis were explained compared with homogeneous catalysis. The methods of synthesis and characterization of heterogeneous catalysts with some examples were then elaborated. The principle of heterogeneous catalytic treatment process of refractory wastewater was analyzed, and several different types of heterogeneous catalytic oxidation processes, technical progresses, and application examples were presented. The mechanisms of heterogeneous catalytic oxidation degradation of pollutants in wastewater were also discussed. According to the review, the heterogeneous catalytic oxidation technology was considered having a good application prospect, and the further research directions of heterogeneous catalysis were proposed.",signatures:"Ting Zhang",downloadPdfUrl:"/chapter/pdf-download/70440",previewPdfUrl:"/chapter/pdf-preview/70440",authors:[{id:"308235",title:"Dr.",name:"Ting",surname:"Zhang",slug:"ting-zhang",fullName:"Ting Zhang"}],corrections:null},{id:"71660",title:"Applications of Chemical Kinetics in Heterogeneous Catalysis",doi:"10.5772/intechopen.91939",slug:"applications-of-chemical-kinetics-in-heterogeneous-catalysis",totalDownloads:1112,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Chemical kinetics is a key subdiscipline of physical chemistry that studies the reaction rate in every elemental step and corresponding catalytic mechanism. It mainly concludes molecular reaction dynamics, catalytic dynamics, elemental reaction dynamics, macrodynamics, and microdynamics. Such a research field has wide applications in heterogeneous catalysis. Based on the Arrhenius plot fitted by the catalytic conversions below 15% without the mass transfer effect and heat transfer effect, the apparent activation energy echoing with the intrinsically catalytic sites and the pre-exponential factor echoing with the relative number of active sites can be, respectively, derived from the slope and intercept of the Arrhenius plots, which can be used to compare the intrinsically catalytic activity of different catalysts and the relative amount of active sites. Reaction orders of both reactants and products are derived from the reaction rate equation and also fitted by the catalytic conversions below 15% without the mass transfer effect and heat transfer effect. According to the acquired reaction orders, the reaction mechanism can be proposed and even defined in some simple reactions. Therefore, investigations of chemical kinetics are of extreme importance and meaning in heterogeneous catalysis.",signatures:"Zhenhua Zhang, Li-Ping Fan and Yue-Juan Wang",downloadPdfUrl:"/chapter/pdf-download/71660",previewPdfUrl:"/chapter/pdf-preview/71660",authors:[{id:"312555",title:"Prof.",name:"Zhenhua",surname:"Zhang",slug:"zhenhua-zhang",fullName:"Zhenhua Zhang"},{id:"316868",title:"Ms.",name:"Li-Ping",surname:"Fan",slug:"li-ping-fan",fullName:"Li-Ping Fan"},{id:"316869",title:"Prof.",name:"Yue-Juan",surname:"Wang",slug:"yue-juan-wang",fullName:"Yue-Juan Wang"}],corrections:null},{id:"70242",title:"Advancements in the Fenton Process for Wastewater Treatment",doi:"10.5772/intechopen.90256",slug:"advancements-in-the-fenton-process-for-wastewater-treatment",totalDownloads:1894,totalCrossrefCites:10,totalDimensionsCites:23,hasAltmetrics:0,abstract:"Fenton is considered to be one of the most effective advanced treatment processes in the removal of many hazardous organic pollutants from refractory/toxic wastewater. It has many advantages, but drawbacks are significant such as a strong acid environment, the cost of reagents consumption, and the large production of ferric sludge, which limits Fenton’s further application. The development of Fenton applications is mainly achieved by improving oxidation efficiency and reducing sludge production. This chapter presents a review on fundamentals and applications of conventional Fenton, leading advanced technologies in the Fenton process, and reuse methods of iron containing sludge to synthetic and real wastewaters are discussed. Finally, future trends and some guidelines for Fenton processes are given.",signatures:"Min Xu, Changyong Wu and Yuexi Zhou",downloadPdfUrl:"/chapter/pdf-download/70242",previewPdfUrl:"/chapter/pdf-preview/70242",authors:[{id:"307479",title:"Dr.",name:"Changyong",surname:"Wu",slug:"changyong-wu",fullName:"Changyong Wu"},{id:"307546",title:"Prof.",name:"Yuexi",surname:"Zhou",slug:"yuexi-zhou",fullName:"Yuexi Zhou"},{id:"311139",title:"Dr.",name:"Min",surname:"Xu",slug:"min-xu",fullName:"Min Xu"}],corrections:null},{id:"70285",title:"Application of Ferrate for Advanced Water and Wastewater Treatment",doi:"10.5772/intechopen.90231",slug:"application-of-ferrate-for-advanced-water-and-wastewater-treatment",totalDownloads:871,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Treatment of recalcitrant organics and inorganics present in wastewater is a major challenge. Conventional biological treatments alone are not capable of removing these toxic compounds from wastewater. To overcome these problems, advanced oxidation processes (AOPs) have been used to completely mineralize or transform the organics into simpler compounds, which can then be treated through biological processes. However, conventional AOPs result in the generation of byproducts, which are known to have higher toxicity. Among various AOPs, ferrate has been gaining popularity because of its advantages such as high oxidation potential, no byproduct formation and also non-toxic end products. The end product generated also acts as a coagulant, which thereby enhances the removal efficiency. In the present chapter, the chemical properties, preparation methods and the factors affecting the stability of ferrate were evaluated based on literature. Further, ferrate oxidation as a potential method for the treatment of both organic and inorganic pollutants in drinking and real wastewater is discussed.",signatures:"Ansaf V. Karim, Sukanya Krishnan, Lakshmi Pisharody and Milan Malhotra",downloadPdfUrl:"/chapter/pdf-download/70285",previewPdfUrl:"/chapter/pdf-preview/70285",authors:[{id:"310802",title:"Ph.D.",name:"Milan",surname:"Malhotra",slug:"milan-malhotra",fullName:"Milan Malhotra"},{id:"312701",title:"Mr.",name:"Ansaf V",surname:"Karim",slug:"ansaf-v-karim",fullName:"Ansaf V Karim"},{id:"312732",title:"Ms.",name:"Lakshmi",surname:"Pisharody",slug:"lakshmi-pisharody",fullName:"Lakshmi Pisharody"},{id:"312733",title:"Ms.",name:"Sukanya",surname:"Krishnan",slug:"sukanya-krishnan",fullName:"Sukanya Krishnan"}],corrections:null},{id:"72151",title:"Application of Advanced Oxidation Process in the Food Industry",doi:"10.5772/intechopen.92355",slug:"application-of-advanced-oxidation-process-in-the-food-industry",totalDownloads:645,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Wastewater in the food industry contains recalcitrant organic compounds and a certain degree of toxicity. Present wastewater treatment plants are insufficient in dealing with the increasing complexity of effluents from modern food industries. Improperly treaded wastewaters can lead to spoil soil and are threads to aquatic life. The reaction of these recalcitrant chemicals with reactive radicals is an efficient treatment strategy. Researchers have proposed advanced oxidation processes (AOPs) that generate reactive radicals including ozonation, UV irradiation, (photo-) Fenton process, etc. This chapter reviews laboratory-scale and pilot-scale AOPs to incorporate with conventional pre-treatment methods and to evaluate their effectiveness and factors including operation condition and catalysts to optimize the process. Further research related to novel catalyst synthesis and cost evaluation of pilot-scale study is suggested.",signatures:"Zhaoran Xin and Lars Rehmann",downloadPdfUrl:"/chapter/pdf-download/72151",previewPdfUrl:"/chapter/pdf-preview/72151",authors:[{id:"316358",title:"Dr.",name:"Lars",surname:"Rehmann",slug:"lars-rehmann",fullName:"Lars Rehmann"},{id:"322088",title:"Dr.",name:"Zhaoran",surname:"Xin",slug:"zhaoran-xin",fullName:"Zhaoran Xin"}],corrections:null},{id:"70153",title:"Catalytic Ozone Oxidation of Petrochemical Secondary Effluent: Mechanism, Application and Future Development",doi:"10.5772/intechopen.90170",slug:"catalytic-ozone-oxidation-of-petrochemical-secondary-effluent-mechanism-application-and-future-devel",totalDownloads:678,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Petrochemical secondary effluent contains toxic and refractory organic compounds, which are difficult to be further treated by traditional biological process. In China, most of the advanced treatment units have been built recently by catalytic ozone oxidation process to achieve the high-quality effluent. In this chapter, the mechanism and reaction process of catalytic ozone oxidation of petrochemical secondary effluent will be introduced in detail. With the operation of the catalytic ozone oxidation tank, a series of problems which are not taken into account at the beginning of the design have arisen. The chapter will talk about the problems concerning the biological flocs, colloidal macromolecule organic compounds, ozone mass transfer, and catalysts based on practical applications. In the last part of the chapter, the development trends of catalytic ozone oxidation of petrochemical secondary effluent will also be discussed.",signatures:"Yu Tan, Liya Fu, Changyong Wu, Yanan Li, Xiumei Sun and Yuexi Zhou",downloadPdfUrl:"/chapter/pdf-download/70153",previewPdfUrl:"/chapter/pdf-preview/70153",authors:[{id:"307479",title:"Dr.",name:"Changyong",surname:"Wu",slug:"changyong-wu",fullName:"Changyong Wu"},{id:"307546",title:"Prof.",name:"Yuexi",surname:"Zhou",slug:"yuexi-zhou",fullName:"Yuexi Zhou"},{id:"307543",title:"Dr.",name:"Yu",surname:"Tan",slug:"yu-tan",fullName:"Yu Tan"},{id:"307544",title:"Dr.",name:"Xiumei",surname:"Sun",slug:"xiumei-sun",fullName:"Xiumei Sun"},{id:"307545",title:"MSc.",name:"Yanan",surname:"Li",slug:"yanan-li",fullName:"Yanan Li"},{id:"322089",title:"Dr.",name:"Liya",surname:"Fu",slug:"liya-fu",fullName:"Liya Fu"}],corrections:null},{id:"71672",title:"Scale-Up and Optimization for Slurry Photoreactors",doi:"10.5772/intechopen.91920",slug:"scale-up-and-optimization-for-slurry-photoreactors",totalDownloads:898,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Several aspects of scale-up and optimization of heterogeneous photocatalytic reactors are detailed in the following chapter. The relevance of the dimensionless numbers, the critical factors of the photoreactor design, and the optimization methods are explored from an engineering point of view. The apparent optical thickness is the most crucial dimensionless parameter for photoreactor design and optimization; therefore, the study will be more focused on this topic. Moreover, a real case for a commercial application of the solar photocatalysis will be presented in this chapter. This full-scale plant is currently operating as an industrial wastewater treatment plant in a flexographic company located in Cali, Colombia.",signatures:"Gianluca Li Puma, Fiderman Machuca-Martínez, Miguel Mueses, José Colina-Márquez and Ciro Bustillo-Lecompte",downloadPdfUrl:"/chapter/pdf-download/71672",previewPdfUrl:"/chapter/pdf-preview/71672",authors:[{id:"189304",title:"Dr.",name:"Ciro",surname:"Bustillo-Lecompte",slug:"ciro-bustillo-lecompte",fullName:"Ciro Bustillo-Lecompte"},{id:"309822",title:"Prof.",name:"Gianluca",surname:"Li Puma",slug:"gianluca-li-puma",fullName:"Gianluca Li Puma"},{id:"309823",title:"Prof.",name:"Fiderman",surname:"Machuca-Martínez",slug:"fiderman-machuca-martinez",fullName:"Fiderman Machuca-Martínez"},{id:"309826",title:"Prof.",name:"Miguel",surname:"Mueses",slug:"miguel-mueses",fullName:"Miguel Mueses"},{id:"309827",title:"Prof.",name:"José",surname:"Colina-Márquez",slug:"jose-colina-marquez",fullName:"José 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It accounts for approximately 1.35% of all malignant neoplasm and 29.5% of cancer-related death [1]. Brain and CNS tumors include tumors of the brain, cranial nerves, spinal nerves, spinal cord, and the meninges. The tumor can be broadly classified as malignant and non-malignant (or benign) tumors. The world health organization (WHO) classification specifies a grading system ranging from grade, whereas, grade III/IV are malignant or high grade [2]. A brain tumor is a diverse group of neoplasm with different types of primary brain tumor (or) metastatic cancer. The most common malignant brain tumors are glioblastoma that originates from glial cells [3]. Metastatic brain tumors (MBTs) account for the majority of an intra-axial brain tumors in adult patients. It is estimated that up to one-third of patients diagnosed with a primary malignancy will develop central nervous system metastatic lesions during their disease course [4]. Pediatric central nervous system (CNS) tumors are the second most common childhood malignancy and the most common solid tumor in children [5]. Early diagnosis and treatment of brain tumors are imperative to prevent permanent damage to the brain (or) death of the patient. At the level of medical data analysis, the features election and classification process are the ones intensively used to identify the patient data whether it is normal (or) abnormal [6]. Once the tumor is detected under the microscope. It is often too late for effective treatment prognosis in patients is correlated with the stage of disease at the time of detection and therefore, it is important to find markers that allow the early detection of the tumor. The treatment options for patients with brain metastases include corticosteroids, surgery, chemotherapy, whole-brain radiation therapy, and stereotactic radiosurgery [7]. A patient with a brain tumor suffers from a significant problem called neurocognitive dysfunction. To diagnose the neurocognitive dysfunction in the brain tumor needs new strategies for the early initiation of appropriate neurocognitive rehabilitation. Raman spectroscopy technique is used for the differentiation of brain tumors. This leads to accurate identification of two essential factors such as brain tumor boundary and the complete resection of the tumor which is important for removal of glioma tumor in brain surgery [8].
In the 19th century, Stephen Paget postulated the “seed and soil” hypothesis, which considers that metastatic growth depends on cancer cells (the seed) interactions with and affinity for specific distant organ tissues (the soil). Paget’s assertion that a nutritional microenvironment is imperative for metastatic cells to grow in distant tissues is supported by conceptual frameworks of contemporary cancer research [9]. A more advanced understanding of the complex and multifactorial mechanisms of metastasis formation consists of three premises: first, the existence of tumor heterogeneity, including morphologically- and phenotypically-distinct profiles of cancer cells with different proliferative, angiogenic, invasive, and metastatic characteristics; second, a metastatic process that is selective for tumor cells that accomplish all the key steps of the metastatic cascade; and third, the metastatic potential of a tumor, which depends on multiple, reciprocal interactions between the primary tumor and the tumor microenvironment, as well as homeostatic mechanisms [10]. This reciprocal cross-talk determines tumor progression and the potential for metastatic growth. As in the periphery, a brain tumor’s microenvironment plays a critical role in metastatic colonization of the brain; but the outgrowth of tumor cells to the brain depend on specific behaviors of the tumor cells and conditions in the brain tumor microenvironment. In the literature, at least three microenvironments have been considered involved in brain metastasis formation: the perivascular niche, the brain parenchyma, and the cerebrospinal fluid also termed the leptomeningeal niche [11]. As the brain tumor grows it creates pressure on and changes the function of surrounding cells and it leads to symptoms. Most cases of Brain Tumor travel by hematogenous spread and occur most often at the gray-white matter junction [4]. The markers involved in the brain tumor are as follows:
Circulating tumor cells
O-6 methylguanine-DNA mutations
Epidermal growth factor receptor
Isocitrate dehydrogenase
Circulating free DNA
Circulating proteins
Tumor protein39.
Tumor protein 53.
Circulating tumor cells
Circulating tumor cells (CTCs) are cells that are shed from primary or metastatic tumors in the body fluids, including blond, cerebrospinal fluid, and urine. CTCs determine the ability of epithelial tumor cells to metastasize [12]. These different types of potential biomarkers in the blood can be present in cell-free forms, attached to lipid or protein structures, or delivered by circulating extracellular vesicles or platelets [13]. CTCs are also used in the monitoring of glioblastoma patients. The level of CTCs detected after chemotherapy is significantly lower compared to their level before the treatment, which may provide invaluable insight in differentiating tumor progression from radiation necrosis [14, 15].
O-6 methylguanine-DNA methyltransferase mutations (MGMT)
The gene encoding O-6-methylguanine DNA methyltransferase (MGMT) is found on chromosome 10q26 [4]. By methylating DNA base pairs, alkylating chemotherapeutic drugs such as temozolomide impair DNA replication. Active MGMT reverses the effect of temozolomide, enabling normal DNA replication to occur within a tumor [16]. O-6-methyl transferase DNA methyltransferase contributes to DNA repair by reversing DNA alkylation and eliminating the guanine-alkyl group, therefore preventing apoptosis. MGMT has recently been established as a biomarker for tumor diagnosis [17]. Methylation promotes the gene code for MGMT in glioblastoma and is the genetic fingerprint with the greatest influence on clinical practice. The presence of O-6-methylguanine-DNA methyltransferase (MGMT) suggests that the current standard of treatment, adjuvant chemoradiotherapy with the alkylating drug temozolomide, is more effective [18, 19, 20].
Epidermal growth factor receptor
Most signaling pathways and physiological responses, including migration, proliferation, survival, and tumor development, are activated by the epidermal growth factor receptor (EGFR). EGF, TGF-, heparin-binding epidermal growth factor-like factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), neuregulins (NRGs), also known as neuregulin; neu differentiation factors; glial growth factors; acetylcholine receptor inducing activity; and epiregulin are all members of the EGF superfamily (EPR) [21, 22].
Isocitrate dehydrogenase
Isocitrate dehydrogenase (IDH) is a protein enzyme that encodes genes on chromosome 2, the main function of IDH in the Krebs cycle is to catalyze oxidative decarboxylation [4]. IDH has been grouped into two classes (IDH 1 and IDH 2). Mutation of isocitrate dehydrogenase 1 (IDH-1) in glioblastoma was first noted by following an integrated genomic analysis of human glioblastoma samples [16]. The IDH-1 protein protects the cytoplasm against oxidative damage. In 12% of glioblastoma samples, a heterozygous point mutation at R132 was discovered. Glioblastomas that were known to have developed from lower-grade tumors had a considerably greater prevalence of IDH-1 mutation (83%) [23]. Grade II/III astrocytomas, oligoastrocytomas, and oligodendrogliomas all have isocitrate dehydrogenase, which can be utilized to distinguish primary from secondary glioblastomas [24, 25].
Circulating free DNA
Cell-free DNA (cfDNA) as a double-stranded, DNA fragments released for the breakdown of cancer tissue by bloodstream that is approximately 150 to 200 base pairs in length, corresponding to nucleosome-associated DNA, can be released by cells under physiological and pathological conditions as well. It is suggested that cfDNA could be derived from apoptotic or necrotic cells, rapidly dividing cells, or CTCs [4]. Blood cfDNA is mostly derived from genomic DNA released during inflammation or cell death in people without cancer. Due to phagocyte clearance, the concentration of cfDNA in the blood is low in physiological settings. Circulating protein markers may be used to track the efficacy of therapy in patients with brain tumors. Current MR imaging techniques cannot effectively detect the unique biological tumor characteristics and complicated tissue changes produced by various cancer treatments [26, 27].
The incidence of detectable ctDNA varies significantly across patients with various tumor types. The concentration of cancer cell-generated ctDNA in plasma in glioblastoma is low when compared to other cancer types, which might be due to the existence of the blood–brain barrier. In glioblastoma, ctDNA analysis presents a number of difficulties. Aside from the common issues of short half-lives (1.5 h) of ctDNA fragments, distinguishing mutant from wild-type alleles, and developing mutation thresholds, the primary issue is the low amount of ctDNA in the samples [28].
Circulating proteins
Several tumor-derived circulating nucleic acids (e.g., ctDNA, cmtDNA, mRNA, non-coding RNAs including miRNAs, long non-coding RNAs) that can be detected from blood or other types of body fluids like urine, cerebrospinal fluid (CSF), saliva, pleural fluid, and ascites. In brain tumor patients, the secretion of the proteins may lead to an increase in the level of circulating proteins (CPs) in the blood and urine and/or CSF [4]. Angiogenesis-related protein markers were discovered in malignancies. The amount of vascular endothelial growth factor was shown to be substantially greater in brain tumor patients than in healthy persons, and even higher in patients with brain metastases [29]. There are two types of prognostic CP indicators: tumor-associated markers and related markers with endogenous systemic stress responses. Overall survival was adversely associated with the tumor-related plasma markers YKL-40, the extracellular domain of EGFR, and osteopontin [30, 31].
Tumor protein 39 (TP39)
Tumor protein 39A (TP39A) belongs to the Transmembrane protein 39 families (TMEM39), consisting of TMEM39A and TMEM39B. The two TMEM39 isoforms are produced via alternative splicing. The TMEM39A-encoding gene may be a susceptibility causes the brain tumor [4]. Transmembrane proteins across the plasma membrane from one side to the other. The movement of materials across biological membranes is regulated by several transmembrane proteins. Multiple sclerosis susceptibility may be linked to the TMEM39A-encoding gene. TMEM39A has also been linked to systemic lupus erythematosus [32, 33].
Tumor protein 53 (TP53)
TP53 is a typical tumor suppressor gene located in 17p13.1. This encodes the nuclear protein p53. To regulate the expression of its target genes the p53 protein responds to diverse cellular stresses, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or metabolic changes. Several human malignancies, including Li-Fraumeni syndrome and numerous hereditary gliomas, are linked to mutated TP53 genes and overexpressed aberrant p53 protein, which has a longer half-life than wild type p53 [4]. If p53 mutations are important in the start of malignant transformation of glial cells, i.e., if they play the function of “mutator” mutations, families with hereditary mutations of one of the p53 alleles would be expected to develop CNS malignancies. Furthermore, the histological kind of glioma that was found should match the usual histology of gliomas with a p53 mutation [34].
The well-known tumor suppressor protein p53 is encoded by the TP53 gene. It is known as the genome’s guardian, and it has a variety of tasks in preventing tumor development. Secondary brain cancers (90 percent) have considerably more TP53 point mutations than initial brain tumor (30%), and in rare cases, primary lesions had none at all [35, 36].
Population-based studies are generally considered more accurate and less biased than the more limited clinical (or) autopsy-based series [37]. The exact incidence of brain metastases is unknown. The epidemiological study is done by using the hospital records, tumor registers, and death certificates. Finally from this study, the incidence of brain metastases seems equal to the incidence of gliomas [38]. The survival rate by histology is summarized in Figure 1.
Meningiomas
Meningiomas are the most common brain tumors in adults accounts about 36% of all brain tumors in the central brain tumor registry of the united states (CBTRUS). In 2015 CBTRUS estimates that there will be approximately 24,000 new meningiomas diagnosed in the united states [37]. The incidence of meningioma steadily increases with age being twice as common in women as in men and 20% more common in blacks than in whites. A majority of meningiomas are benign (grade I), with 5–20% atypical (grade II) and 1–3% malignant in type (grade III) [38, 39].
Although benign meningiomas are a minor cause of death, skull-based tumors can cause considerable morbidity. Atypical and malignant meningiomas, on the other hand, are linked to high rates of recurrence and substantial morbidity and death [40, 41]. Meningioma is shown in Figure 2. Because telomerase activity is detected in all anaplastic/malignant (WHO grade III) and the majority of atypical (WHO grade II) meningiomas, there is a link between telomerase activity and tumor grading in meningiomas [42, 43].
Glioma
Glioma is the second most common brain tumor in adults. In 2015 the CBTRUS estimates approximately 20,000 newly diagnosed gliomas in the united states. Approximately one-half of gliomas is glioblastoma, the commonest malignant primary brain tumor in adults. Glioma occurs almost in all four lobes in the brain: frontal (23.6%), temporal (17.4%), parietal (10.6%), occipital (2.8%), a small percentage in the brain stem, cerebellum and spinal cord [20].
Glioma is shown in Figure 3. Secondary glioblastomas are considered to develop as a result of progression from pre-existing astrocytomas, thus this finding is fascinating [44].
Pituitary tumor
The third most common brain tumor in adults is the pituitary tumor and it accounts for 15%. A majority of brain tumors are benign adenomas [45]. Even people who do not produce hormones might have symptoms as a result of the intracranial mass effect. Hormones that control normal pituitary function, as well as growth factors implicated in normal fetal pituitary development, appear to stimulate tumor growth [46, 47]. Pituitary tumor is shown in Figure 4.
Pediatric brain tumor
CNS tumors in children are the second most frequent malignancy in children and the most common solid tumor in children. According to CBTRUS, about 2000 children in the United States are diagnosed with a brain tumor before the age of 14. The most frequent solid tumor in babies and toddlers is a brain tumor. More than 8% of children and adolescent cancers are caused by genetic predisposition syndromes, and this percentage is anticipated to climb as research continues [3].
CNS tumor epidemiology -the incidence of brain tssumor in different regions of brain.
Brain meningioma.
Glioma.
Pituitary tumor.
Non–posterior fossa embryonal tumors, also known as CNS-primitive neuroectodermal tumors (PNETs), are a kind of uncommon juvenile brain tumor that accounts for less than 3% of all cases and has a dismal prognosis [46]. All CNS embryonal tumors are very malignant and are classified as WHO grade IV tumors by the World Health Organization. Many tumors classified as supratentorial embryonal tumors histologically cluster with other tumor types, such as high-grade gliomas and ependymomas, according to molecular studies; this has major therapeutic implications in terms of the amount of radiotherapy required for tumor control and the choice of adjuvant chemotherapy or biologic therapy [47, 48].
Headache
Headache occurs commonly in all brain tumor patients. The headache is said to develop in the temporal and the spatial, relation to the neoplasm and resolves 7 days of surgical removal or treatment with corticosteroids [48].
Headache in pituitary brain tumor
The presence of headache has been shown to be more highly associated with family history than the tumor size [47].
Headache in pediatric brain tumor
Headache appears to be the most common presenting symptom (41% of patients in some studies). It tends to occur with other symptoms such as vomiting, unsteadiness, behavioral problems, and cranial nerve palsies, and most commonly nocturnally (or) in the early morning [49].
Mechanism of headache in brain tumor
The mechanism of headache in brain tumors may include the traction on vascular structure, cranial or central sensitization through neurogenic inflammation as well as the component of central sensitization through trigeminovascular afferents on the meninges and the cranial nerves [50].
Nausea and vomiting
Nausea and vomiting occur when the chemo trigger zone in the area postrema, located on the floor of the fourth ventricle is stimulated. Raised intracranial pressure leads to vomiting. It can also occur in the absence of elevated intracranial pressure in brain stem tumors involving the nucleus solitarius [51].
Mechanism of vomiting
Nausea and vomiting are highly conserved responses and the survival advantages in survival vertebrates. Vomiting is primitive, low-threshold, brain stem response that allows the human to purge the gastrointestinal tract of orally consumed noxious substances. Vomiting is multidimensional having a higher cognitive brain center, emotions, and interoceptive domains is more common disabling, and more difficult to control than vomiting [52].
Altered mental status
Mental and cognitive abnormalities may be specific, or nonspecific. Specific findings include aphasia, agnosia, abulia, alexia, or apraxia. In about 16–34% of patients, the symptoms for brain tumor patients include irritability, change in personality, emotional liability, forgetfulness, lack of enthusiasm or spontaneity, and slowed response progressing apathy and lathery [53].
Papilledema
Papilledema is an indicator of increased intracranial pressure it is now rarely seen in patients at the time of presentation of the tumor. Like headache, papilledema is seen mostly seen in young adults and children, this is probably because older adults have tumor expansion due to tumor atrophy [53].
Mechanism of papilledema
The mechanism of papilledema is due to axoplasmic flow stasis. High intracranial pressure produces raise in cerebrospinal fluid pressure surrounding the optic nerve, which disturbs the normal gradient between intraocular pressure retro lamellar pressure leading to high pressure within the nerves and this leads to papilledema [54].
Seizures
Seizure is the most frequent symptom in patients with brain tumors. The incidence of brain tumors varies 30–100% depending on the tumor type and location with a slow-growing tumor that is being epileptogenic [53]. Brain tumor patients with epilepsy will have a high risk of seizure-related morbidities, mortality as well as experience a low quality of life [55].
Mechanism of seizure
The mechanism of seizure in brain tumor patients involves changes in aminoacid neurotransmission is the most important mechanism underlying tumor-related seizures and changes in extracellular ions also play an important role. Hypoxia, acidosis, metabolic, immunological, and inflammatory changes may also be involved in seizure occurrence [56].
Diagnostic tests to detect these changes using biomarkers show significant potential for early detection [57]. Development of neurologic deficits and new-onset seizures are commonly followed by neurologic workup that includes magnetic resonance imaging (MRI). Computer tomography (CT) with contrast enhancement is less sensitive in detecting the typical features of glioblastoma [58].
WCFS-IBMDNT
Many recent studies have attempted to define the characteristics of brain tumors to diagnose the illnesses. However, with a large dataset, the correlations across brain tumor characteristics limit the illness diagnosis performance. Furthermore, when using standard approaches for categorization, misclassification outcomes might arise. The WCFS-IBMDNL approach employs the IBMDNN classifier after selecting a subset of characteristics for efficient brain tumor diagnosis with low time complexity. The most significant diagnostic approach used to diagnose brain tumors is Weighted Co-relation Feature Selection Based Iterative Bayesian Multivariate Deep Neural Learning (WCFS-IBMDNT). The WCFS-IBMDNT approach was created to enhance brain tumor diagnosis by requiring the least amount of time [59]. The major importance of WCFS-IBMDNT are as follows:
The WCFS-IBMDNT technique was designed to enhance the prediction of brain tumors based on classification. Weighed correlation-based feature selection is the traditional method and performs WC-FS for highlighting the characterization of brain tumors by the subset of medicinal hights [59]
First it is proposed to enhance the performance of brain tumor prediction via a classification technique. The proposed WCFS-IBMDNL technique is designed with the implementation of WC-FS and IBMDNN classifier [59].
The feature selection procedure for providing effective brain tumor detection diagnostic is carried out using WC-FS. The Pearson correlation coefficient is used in WCFS-IBMDNL, which is a first. The Pearson correlation coefficient is used to determine the relationship between two medical variables to choose a group of medical parameters that are most important to the categorization of brain tumors [59].
The IBMDNN classifier is used in the proposed WCFSIBMDNL method to improve brain tumor diagnostic classification performance. BMLR is also utilized in the IBMDNN classifier to analyze medical characteristics to categorize patients as normal or abnormal. The least absolute error is calculated after the categorization. Finally, to reduce the error rate, the IRLS technique is utilized. This contributes to a higher illness detection rate while lowering the FAR [59].
Magnetic resonance imaging (MRI)
MRI is the most important technique for the diagnosis of brain tumors. MRI is used in the biomedical to detect and visualize finer details in the internal structure of the body. This technique is used to detect the differences in the tissues. MRI is fundamentally better than CT scanning [60]. This study proposes the computer-assisted computed organization feature extraction with abnormal MRI images of brain tumors to develop the accuracy of classification results according to the original feature classification. The initial input database images are fed for pre-processing and the images are transferred as 3 × 3 blocks. Then for each image of 3 × 3 blocks, 22 number of texture feature was extracted. Then the extracted feature was used to classify the brain tumor as normal as unusual [61].
The most prevalent metabolites of the brain, such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate, may be quantified using MR spectroscopy (MRS) [57]. Choline is considered to correspond with cell turnover, therefore variations in Cho might be linked to the stage of radio-necrosis. Cho rises in the first few months following radiation therapy, according to two studies, but it declines as radionecrosis develops, according to Rock et al. Rapid Cho, on the other hand, is a common characteristic of tumor recurrence due to high cell turnover [62].
CT Scanning (computer tomography)
Computer tomography has a high accuracy than magnetic resonance imaging MRI. CT uses ionizing radiation for the diagnosis of brain tumors. This is used for the diagnosis of primary glaucoma and lymphoma of the Central Nervous System (CNS) was performed [59]. A CT scan may reveal hypodensity in the white matter, as well as a mass effect on surrounding structures. In vascular metastases, localized bleeding may be observed [63].
Fused MRI and CT Analysis
Tumor identification is done using a combination of computed tomography CT and MRI scans. Multiple modalities such as CT and MRI are utilized to create the merged pictures (MRI). CT pictures, which are utilized to determine the difference in tissue density, and MRI images, which give a good contrast between distinct bodily tissues, play a vital role in medical image processing [64]. CT pictures show differences in tissue density based on the tissues’ capacity to respond to X-rays, whereas MRI images show the contrast between soft tissues. When compared to the source pictures, the fused image retains the complementary and redundant information from both source images, including tumor size and position, allowing for better tumor detection [65].
Positron emission tomography [PET]
The brain’s major energy source is aerobic glucose metabolism. The most commonly used PET radiotracer, F18-FDG, is actively transported across the BBB and accumulates in areas where aerobic glucose metabolism is enhanced. FDG accumulation is proportional to glucose metabolism in the cell, and higher accumulation correlates to higher cellular metabolism. The brain’s typical strong metabolic activity causes high uptake in the normal brain parenchyma, resulting in poor tumor-to-brain contrast. Another possible stumbling block is the nonspecific nature of FDG absorption, which may be seen in inflammatory and infectious processes [66].
PET radiolabelled amino acids increase proportionately to cellular proliferation due to enhanced transport. Tumors increase transporter activity, metabolic enzyme activity, and demand, resulting in increased radiotracer accumulation proportionate to protein synthesis and food demand [67].
Single-photon emission computed tomography [SPECT]
SPECT is a low-cost imaging technique that is readily available and may be used in conjunction with CT and MRI to evaluate tumors and RN. In the post-treatment context, a variety of SPECT radiotracers are available for brain tumor imaging. Thallium201 is very accurate for post-treatment evaluation of tumor burden because it concentrates on living tumors; nevertheless, Thallium201 has nonspecific absorption in non-neoplastic processes such as granulomatous or fungal etiologies [66].
Thallium201 absorption is unaffected by the BBB and is primarily determined by the pace of cell growth, making it highly selective for brain tumors. Thallium201-SPECT had a sensitivity of 71.7 percent and a specificity of 80.9 percent for supratentorial brain tumors, according to a retrospective analysis of 90 patients. Because tumor growth rates are substantially greater than normal brain parenchyma, thalllium201 accumulates in brain malignancies without considerable absorption in the normal brain parenchyma, producing good tumor-to-background contrast [68, 69].
The brain plays an important role in the body by controlling voluntary and involuntary processes. It is highly necessary to maintain a healthy brain to live longer. But some factors like environmental and genetic factors tumors in the brain can be developed [70]. These tumor causes the damage in healthy tissues and increases the pressure in the brain. Thus, some tissues may get pushed against the skull.
The tumors are classified according to the place they occur and the type of cell as follows:
The type and grade
Primary or secondary tumor
Malignant or benign tumor
Tumor location [71].
According to WHO (World Health Organization) brain tumors are classified as:
Astrocytoma
Glioblastoma
Oligodendroglioma [71].
Astrocytoma
Astrocytoma tumors arise from the supportive glial cells of the brain. About 7% of the primary brain tumor are astrocytoma. A star-shaped tumor that begins in the brain is called astrocytoma. In adults, the astrocytoma most often arises in the cerebrum, wherein in children it occurs in the brain stem [63]. Astrocytoma is shown in Figure 5. The basal ganglia and thalamus are the two most likely locations where the long-term prognosis is poorer than for hemisphere injuries [72]. Post-operative radiation is a treatment option for low-grade gliomas. However, one disadvantage of radiation is that it causes neurocognitive damage and does not result in considerable improvement. As a result, radiation is often reserved for individuals with tumors that are at high risk of malignant transformation [73].
Glioblastoma
Glioblastomas (GBMs) is the most common and primary aggressive brain tumor. Glioblastoma is shown the Figure 6. Glioblastoma accounts for 45.6% of primary malignant brain tumors. Typical molecular changes in glioblastoma include mutation in gene-regulating receptor tyrosine kinase (RTK) /phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signaling [71]. Secondary glioblastoma is a kind of glioblastoma that develops in younger people when a previous malignancy, such as grade II astrocytoma or anaplastic astrocytoma, somatically mutates into a glioblastoma [74].
Oligodendroglioma
Oligodendroglioma is a rare form of brain tumor. The brain is made up of many supporting cells that are called glial cells. Any tumor of these glial cells is called glioma. A tumor that arises from the glial cells (oligodendrocyte cells) is called oligodendroglioma [72]. Oligodendrogliomas vary from other glial tumors in their molecular genetic makeup. On chromosome 1p and chromosome 19q, LOH is seen often in oligodendrogliomas of all grades [75]. Oligodendroglioma is shown in Figure 7.
Astrocytoma.
Glioblastoma.
Oligodendroglioma.
The pediatric brain tumor is the second most childhood malignant brain tumor and the most common solid tumor in children. The genetic syndromes that cause brain tumors are due to NF-1, tuberous sclerosis, Li-Fraumeni syndrome, and other less common inherited conditions, such as Gorlin syndrome or Turcot syndrome [76].
low-grade glioma
Low-grade gliomas (LGGs) is the most common pediatric central nervous system (CNS) tumor and it comprises for 30–40% of all CNS tumor. LGGs are infiltrative and incurable primary brain tumors with a typical slow evolution. Treatment of this low-grade glioma includes chemotherapy, radiation therapy, and targeted therapy [77].
High-grade glioma
High grade comprises up to 12% of pediatric CNS tumors and it includes anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). The symptoms depend on tumor location. The treatment method includes chemotherapy regimens that have been studied in the patients with high-grade gliomas, including temozolomide, lomustine, and thalidomide but have unfortunately not resulted in significant improvement in survival rates [78].
Medulloblastoma
Medulloblastoma is the most common CNS embryonal tumor. It represents about 10% of all pediatric brain tumors [79]. Medulloblastoma is the most common malignant brain tumor in children accounting for approximately 25% of pediatric brain tumors, with many reports indicating an increase in medulloblastoma in recent years [80].
Ependymoma
Ependymomas are tumors of the central nervous system that derive from the ependymal cells that line the ventricles of the brain and the central canal of the spinal cord [81]. Ependymoma can occur throughout the neuroaxis-supratentorial, posterior fossa, and spinal cord; however, 90% of pediatric ependymomas occur intracranially with 2/3 in the posterior fossa and 1/3 supratentorially [82].
The molecular genetics of brain tumors is due to the mutation in enzymatic activity. The mutation rate that commonly occurs in various gene to cause brain tumor are:
Astrocytoma a grade II, III type of brain tumor is due to IDH mutation, P53 mutation, ATRX mutation.
Glioblastoma a grade IV type is due to amplification of EGFR, PDGFRA amplification mutation of EGFRvIII, deletion of PTEN homozygous, CDKN2A homozygous deletion, BRAF V600E mutation, (epithelioid GBM) TP53 mutation.
Oligodendroglioma a grade II, III is due to IDH mutation, 1p/19q codeletion, CIC/FUBP1 mutation, TERTp mutation [83].
Mutation IDH1/2
IDH catalyzes the oxidative decarboxylation of isocitrate to generate (-KG) and CO2, however, mutant IDH1/2 preferentially binds -KG rather than isocitrate outside of the citric acid cycle, resulting in the formation and accumulation of the oncometabolite 2-hydroxyglutarate (2HG) [84].
HIF1 (Hypoxia Inducible Factor) levels and alterations in the HIF1 downstream pathway are modulated by -KG–dependent prolyl hydroxylases, resulting in an increase in reactive oxygen species levels and potentially contributing to the risk of cancer [85].
TP53 mutation
TP53 is a tumor suppressor gene that encodes the nuclear protein p53 and is found on the 17p13.1 chromosome [86]. Several human malignancies, including Li-Fraumeni syndrome and numerous hereditary gliomas, are linked to mutated TP53 genes and over-expressed aberrant p53 protein, which has a longer half-life than wild type p53 [87].
ATRX is an X-linked gene of α- Thalassemia and mental retardation syndrome
ATRX is a 280-kDa nuclear protein that has been implicated in a variety of biological activities including DNA recombination, repair, and transcription control. It is found on chromosome 21.1 and encodes a 280-kDa nuclear protein [88]. When ATRX and DAXX connect, the resulting complex acts as a histone chaperone, allowing histone variation H3.3 to be deposited into heterochromatic repeats such as pericentric, telomeric, and ribosomal DNA repeat regions [89].
EGFR amplification and EGFRvIII truncation mutation
EGFR, also known as Erb1 or HER1, is an ErbB family receptor tyrosine kinase that is found on chromosome 7q12. EGFR over-expression is linked to EGFR amplification. The EGFRvIII mutation is a frame deletion of 801 bytes from exons 2 to 7 of the EGFR gene, which is linked to EGFR amplification, antibody response, and poor prognosis [90, 91].
BRAF mutation
Pilocytic astrocytoma is defined by BRAF V600E mutations and BRAF fusions with KIAA1549 or FAM131B. A tandem duplication at 7q34 was verified, and a novel fusion gene was discovered in pilocytic astrocytoma, which was previously uncharacterized by a fusion between the KIAA1549 and BRAF genes [92].
Immunotherapy
When it comes to treating brain tumors, immunotherapy is a potential treatment option. Chemotherapy, radiation treatment, and surgery have all been used to treat it in the past. An immune-based cancer therapy uses the body’s immune system to destroy cancer cells [93]. If the cells are no longer required or pose a hazard, apoptosis, or programmed cell death, will occur to halt cell growth [94]. Cancer progresses and develops through eight processes, which are as follows:
Stained proliferation
Evasion of growth suppressor
Cell death resistance
Replicative immortality
Angiogenesis
Metastasis
Reprogrammed metabolism
Evasion of immune destruction [95].
The evasion of immune destruction has been studied for decades. Because EphA2 is abundantly expressed in glioblastoma but only at low levels in normal brain tissue, CAR T cell treatment targeting the glioblastoma antigen EphA2 is an appealing strategy to enhance outcomes [93].
Since brain tumor immunotherapy has been extensively studied [94, 95, 96], we will focus in this work on the most recent and late-stage clinical trial treatments, as well as the engineering problems these immunotherapies confront in the brain tumor environment [96].
Vaccines
Traditional vaccinations against viral illnesses (for example, influenza) employ attenuated or live viruses in combination with a danger signal (as an adjuvant) to activate DCs. DCS then takes up the viral antigen, digests it, moves to lymph nodes through lymphatic channels, and activates T-cells via the presentation of various peptide antigens/antigenic epitopes on MHC molecules [93].
Peptide vaccines
Immunization using peptide vaccine when released at the tumor site, peptide vaccinations stimulate T-cell responses by releasing antigen-specific peptides. APCs take up peptides, which are often associated with carrier proteins and adjuvants, and display them on the cell surface by way of MHC [97]. The treatment method by peptide vaccine is explained in Figure 8. APCs take up peptides, which are often associated with carrier proteins and adjuvants, and display them on the cell surface by way of MHC. Molecules of human leukocyte antigens (HLA) MHC I (HLA) [98].
Dendric cell vaccines
If you are looking for an alternative to peptide vaccines in situ, you may also use direct activation of DCs ex vivo to create a cancer vaccine. Autologous dendritic cells derived from peripheral blood monocytes primed with tumor-related antigens have been utilized in cancer immunotherapy instead of injecting a peptide that is given to an APC [99]. If there are inflammatory signals, immature CD4+ T cells can deliver antigen to T-cells that recognize it in an MHC-restricted way as a result of immature DC maturation. T-cells activated with CD8+ antigens and MHC I complexes may now identify tumor cells and seek to lyse them [100]. Dendritic vaccine therapy is explained in Figure 8.
Adaptive cell therapy (ACT)
T-cells, x-cells, and other tumor infiltrating lymphocytes (TILs) can be activated directly via Adoptive Cell Therapy (ACT) instead of DC activation [101].
Adaptive cell therapy is shown in Figure 9. It is most usual to utilize cytokine-induced killer (CIK) and CAR T-cells in the ACT process. IFN, IL2, and CD3 monoclonal antibodies are used to induce peripheral blood lymphocytes into CIK cells in vitro. Cells that have been modified to express a single or many costimulatory tumor antigens are called CAR T-cells [102].
Monoclonal antibodies
Using monoclonal antibodies is a passive method of immunotherapy that does not need the body’s immune system. Figure 10 shows the monoclonal antibodies treatment method [93]. Antibodies that target abnormally expressed surface receptors in malignancies or receptors implicated in carcinogenesis are generally selected. However, Nimotuzumab, another monoclonal antibody widely used in brain tumors, is an anti-EGFR inhibitor that has only slightly improved overall survival when administered in children with high-grade gliomas [103].
To some extent, monoclonal antibody treatment in the brain has suboptimal survival benefits because monoclonal antibodies are unable to penetrate the BBB without causing considerable barrier disruption and because patient-specific antigen mutations affect antibody binding efficiency [104].
Virotherapy
Non-pathogenic viruses are used in oncolytic virotherapy to selectively infiltrate or express proteins in brain tumor cells that can directly destroy cancer cells or else activate an immune response. Many virotherapy techniques have been investigated, but their broad use in the brain remains a problem [105]. The virotherapy method for brain tumor treatment is shown in Figure 11.
Furthermore, the targeting of non-neuronal lineage cells may make a method like PVSRIPO appealing; nevertheless, other component cells in the CNS may be misidentified for cancer cells, resulting in negative side effects. The BBB can also limit viral migration to the tumor site, which is important in virotherapy for brain cancers [106].
Radiation therapy
Patients with primary brain tumors benefit from radiation therapy because it helps them maintain local control or prolong their progression-free life. In the treatment of primary brain tumors, radiation therapy (RT) plays a crucial role, with the majority of patients experiencing local control or prolonged progression-free survival. On the other hand, RT can have a negative influence on cognitive performance, which can have a detrimental effect on the quality of life. When one or more cognitive processes, such as attention, memory, language, and executive function are impaired [107, 108].
Primary brain tumors, both benign and malignant, are commonly treated with radiation therapy (RT). Post-treatment neurocognitive deterioration has been documented with RT in verbal and visuospatial memory most commonly (i.e., difficulty encoding, retaining, and retrieving visual information) [109, 110].
Surgery
The majority of therapy is surgical resection. Patients with persistent hydrocephalus despite tumor excision require a third ventriculostomy or CSF diversion to cure the condition. A cardiac examination should be performed on neonates suspected of having tuberous sclerosis before an intraventricular tumor is surgically removed [111].
Chemotherapy
The discovery of chromosomal markers that indicate greater chemosensitivity in patients with low-grade astrocytoma and other histopathologies has sparked renewed interest in using chemotherapy in the treatment of low-grade astrocytoma patients with other histopathologies. Temozolomide is the most widely used chemotherapy regimen in adult low-grade astrocytoma patients, followed by procarbazine, CCNU, and vincristine (PCV) if temozolomide fails [112].
Dendritic vaccine therapy and treatment method by peptide vaccine.
Adaptive cell therapy.
Monoclonal antibodies treatment method.
Virotherapy method for brain tumor treatment.
The Southwest Oncology Group conducted an early randomized trial to see if treating low-grade astrocytoma patients with single-agent CCNU after radiation was beneficial. In this research, adding CCNU to the therapy schedule had no further benefits. Furthermore, individuals in the CCNU arm experienced a high rate of hematologic adverse effects after chemotherapy [113].
The effectiveness of temozolomide, an oral alkylating drug, in treating patients with low-grade astrocytoma is now a staple of adjuvant treatment, although it is also being investigated in several trials [114]. Response rates range from 31 to 61 percent when minor replies are considered. Despite the short duration of follow-up, the median time to advancement ranged from 31 months to >36 months. It was concluded by Brada and co-workers (2003, in a phase 2 study) that the drug temozolomide has single-agent action against low-grade astrocytoma and may also assist control seizures in this patient group and that it is safe and effective in this patient population [115].
In 2020, A new improved WOA is used to propose a comprehensive method for brain tumor detection based on optimal feature extraction and feature selection. On a set of benchmark cases, IWOA’s experimental results are compared to those of other common optimizers, and the results are verified [116].
Z.U. Rehman, M.S. Zia, G.R. Bojja, and F. Jinchao explained Two recent and useful trends for brain tumor localization: (1) using the texton-map to create the image in texture form (2) extracting the features from the superpixels The three contributions were used in this paper. First, superpixel segmentation is performed on texton-map images, which reduces the computational cost of image segmentation in small regions, improves spatial smoothness of superpixels, and improves low-level feature accuracy. Second, we covered the concept of data balancing, which aids in the development of vision-based classifiers. Third, we created a quick comparison of four different classifiers and examined their performance in terms of model training accuracy. Initially, our image denoising method is shown to effectively remove false-positive regions [117].
Ratan et al. developed watershed segmentation and used edge detection, contrast, and greyscale on 2D and 3D images to detect brain tumors. Somasundaram and Kalaiselvi used ten data sets with normal and abnormal subjects to detect brain tumors. Muscles, scalp, skull, and fats the unwanted brain areas are removed first in their proposed framework, followed by fuzzy segmentation. Finally, for tumor region detection, and intensity-based extended maxima transform is used [18]. proposes a systematic model that starts with a diagnosis of the brain tumor and then extracts the brain tumor region. A classifier called Naive Bayes is used to diagnose the tumor from brain MR images. After a diagnosis, the brain tumor region is extracted using K-mean clustering and boundary detection techniques. It had an accuracy rate of over 80%. To detect the brain tumor region, researchers propose a segmentation method based on color and edge detection. Edge detection is done with the Prewitt, Canny, Sobel, and Laplacian of Gaussian operators, while color-based segmentation is done with the K-mean clustering technique [118].
Alexander Winkler-Schwartz and his colleagues have created a comprehensive research framework for studying oncological neurosurgery’s technical performance and resection extent. This platform works by incorporating a low-cost alginate-based artificial brain tumor into an ex-vivo calf brain in a controlled operative environment. To our knowledge, this is the first time an artificial tumor has been created using the biomechanical properties of human specimens obtained through resection. Given that its components are relatively inexpensive and combined in small quantities, the overall cost of the artificial tumor is well under 2 cents/mL. To put this into perspective, 1 kg of alginate and 5800 mL of calcium sulphate, respectively, can yield 40,000 and 5800 mL of final tumor. Gadobutrol (Bayer AG) or its analogues, arguably the most expensive compound in the mix, can often be obtained for a low price from clinical units’ expired stockpiles. Even if one were to pay the full cost for an average 30-mL vial, this would yield 27,000 mL of tumor. A 10e100-mL pipette and a laboratory-grade scale are required, but they are both one-time purchases. The recordings from the surgical microscope and ceiling-mounted camera, as well as the movements generated by the instrument-mounted fiducial markers, can be used to evaluate operative “performance” [119].
Medical imaging is still the gold standard for detecting, diagnosing, and examining gliomas and other diseases. Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI, computed tomography, and positron emission tomography is the most commonly used imaging techniques in clinical practice [120].
The brain is responsible to control all activities of the human body. It is well-known that a disease occurred in the brain may affect human life negatively. A brain tumor is one of the critical diseases that originate from the abnormal growth of cells in the brain. Automatic brain tumor classification plays an important role in the early stage of tumor detection and this system allows patients to be diagnosed in time and chance of survival. Also, this system may help radiologists in decision-making and treatment plans. In this paper, we proposed a new scheme to classify three types of brain tumors, namely, Meningioma, Glioma, and Pituitary tumors from MRI images. First, pre-processed is applied to images [70].
Recent laboratory advances in primary brain tumors have shown that specific molecular signatures can predict the biological behavior of tumors. Current brain tumor classification systems based on histology and morphology may soon be supplemented by a system based on molecular markers of tumor differentiation and progression [74].
The quantitative, domain-specific data acquired through these studies will improve our understanding of brain toxicity and cognitive decline associated with radiation dosage to non-targeted tissue and can provide the basis for evidence-based cognition-sparing brain radiotherapy. Interestingly, this study introduces an association between certain WM diffusion changes and radiation-induced memory decline, which may indicate that there are other ROIs not studied in this paper that should be investigated as potentially vulnerable areas contributing to post-RT cognitive decline. Further research is needed to investigate the dynamic trajectories of tissue response to radiation to better understand how MRI changes can be used to predict important neurocognitive trajectories post-treatment [60].
Treatments and better outcomes for primary brain tumors have long lagged behind those of other tumors. However, a new era in neuro-oncology has emerged, with major advances in both cancer and CNS immunology, and progress in genomics [55].
Alpha- Thalassemia X- linked mental Retardation
Blood Brain Barrier
Chimeric Antigen Receptor
Cyclin-Dependent Kinase inhibitor 2A
Cluster of Differentiation 4
Cluster of differentiation 3
Interferon
Interleukin-2
Monoclonal antibody-1
Quantitative Real-Time Polymerase Chain Reaction
Natural Killer
Major histocompatibility complex
Orthodontics and orthodontists have always worked towards delivering better care for patients. This has led to the invention of various bracket systems along with the changes in the protocol of management of extraction cases.
The Self Ligating Brackets (SLB) has come into orthodontic practice since 1930’s with the invention of Boydband bracket. These bracket systems along with the thermally activated NiTi wires have reduced the treatment duration, chair-side time, and improved the treatment efficacy and patient co-operation. This led to the invention of Damon’s system by Dr. Dwight Damon in the year 1996. It is called as “System” rather than “Brackets” because it utilizes the benefits of both the brackets and copper NiTi wires, thus delivering a “low force- low friction” mechanics for the management of dental malocclusion [1].
There has been lot of evidence in literature which states that “atraumatic” remodeling of periodontal tissues was rarely achieved using conventional orthodontic bracket system. This is mainly because the tooth was always moved in group. In Damon’s system, the tooth is allowed to move individually, yet stay in the group. The bracket system allows for easy sliding of the tooth along the path of least or no resistance thus leading to faster leveling and alignment and reduced treatment duration [2]. The aim of this chapter is to describe the bracket prescription, efficiency of the appliance, the possible outcomes and its influence on orthodontic therapy.
Damon philosophy uses the concept of passive self-ligation technique which claims to have the lowest frictional resistance of any ligation system. Reduction in friction helps the force to transmit directly from the arch wires to the teeth and its supporting structures without any force dissipation by the ligature system [3].
Comparing the other prescriptions, Damon system has lots of benefits:
Limitations in the use of intraoral expansion appliances such as quad-helix or jack-screw as the optimal forces from the arch wires completely allows the connective tissue and alveolar bone to follow tooth movement with uninterrupted vascular supply to the tooth and its surrounding system thereby providing the necessary expansion [3, 4, 5].
In a study stated that Damon System produced a significant transversal increase in the posterior region of the arches with differences in teeth buccolingual inclinations at post-treatment [6].
Faster alignment of teeth as passive self-ligation produces lower resistance thus allowing a wire to slide.
Reduced amount of pain experienced by patients, and higher treatment efficiency as this friction-free system produces less forces on the teeth [4, 5].
Reduction in the need for extraction as the force applied is minimal that the pressure from lips can control unwanted tipping of incisors during alignment stage [5].
Decreased demand for the use of anchorage devices comparing the conventional appliances as there is reduced friction between the ligation for better tooth control [7].
Reduction in the overall duration of orthodontic treatment up to 7 months and also reduced number of appointments have been found in few researches [8, 9].
Control of tooth position because there is an edgewise slot of adequate width and depth [3].
Decreased discomfort experienced by the patients with the Damon prescription as the forces applied to the teeth are kept minimal throughout the treatment [4].
More efficient chair-side due to reduced ligation time [10].
Promotes periodontal health with better infection control [11].
In orthodontics achieving ideal inclination of anterior using the edgewise system is challenging. In an attempt to overcome this drawback, Damon’s system has different torque prescription. This includes:
These brackets can be used in cases where the incisors or cuspids are severely retroclined or palatally placed. Examples are:
Class I extraction cases with proclined of anterior.
Class II division 1 malocclusion.
Class II division 2 malocclusion with retroclined incisors.
Palatally placed incisors or cuspids.
These brackets can be used in cases where the inclination of anterior is satisfactory and when there will not be any obvious change in the inclination during the course of the treatment.
Examples of the cases include:
Anterior open bite cases with severe proclination of anteriors.
Moderate and severe crowding.
Treatment mechanics which may result in proclination of anteriors.
Incisors with palatally positioned roots.
In class II fixed functional cases or class II elastics cases where control of lower incisor proclination is necessary.
Lingually placed lower incisors [3].
The tip and torque values of Damon’s system are as in Tables 1 and 2.
Upper arch | ||||||
---|---|---|---|---|---|---|
U1 | U2 | U3 | U4 | U5 | U6 | U7 |
+5° | +9° | +6° | +2° | +2° | ||
Lower arch | ||||||
L1 | L2 | L3 | L4 | L5 | L6 | L7 |
+2° | +2° | +5° | +2° | +2° |
Tip values in Damon’s system.
Upper arch | |||||||
---|---|---|---|---|---|---|---|
U1 | U2 | U3 | U4 | U5 | U6 | U7 | |
High torque | +17° | +10° | +7° | ||||
Standard torque | +12° | +8° | 0° | −7° | −7° | −18° | −27° |
Low torque | +7° | +3° | |||||
Lower arch | |||||||
L1 | L2 | L3 | L4 | L5 | L6 | L7 | |
High torque | +7° | ||||||
Standard torque | −1° | −1° | 0° | −12° | −17° | −28° | −10° |
Low torque | −6° | −6° |
Torque values in Damon’s system.
Clinically proven
Enhances facial esthetics
More comfortable than traditional braces
Reduced friction and faster tooth movement
Shorter treatment duration
Lesser visits
Expensive than traditional braces
“Metal Mouth” look
The phases of tooth movement are generally.
Initial leveling and aligning – where initial round wires made of multistranded steel or NiTi are used, starting from the smaller dimensions then proceeded with the larger dimensions.
Retraction and space closure – where rigid rectangular wires are used for major mechanics like torque expression and space closure.
Finishing and detailing – round steel wires are usually used.
There are two sequences which are generally followed in pre-adjusted edgewise prescription.
An older concept of a sequence which initially uses round steel wires from sizes.014, .016, .018 and .020 followed by rectangular steel wires from dimensions.018 × .025, .019 × .025 and.021 × .025 in.022 slots.
Multi-stranded wires of dimensions .015 and .0175 were used for initial aligning before .014 round Steel wire came into practice and finishing and detailing was done with.014 steel wires.
Later with the introduction of MBT prescription, arch wire sequencing started with initial .016 CuNiTi wire followed by .019 × .025 CuNiTi and then .019 × .025 Steel wire was used for major biomechanics and detailing was done with .014 round steel wire [12, 13].
A clinical research by Mandall, in which three wire sequences were randomly allocated to patients to compare are as follows:
Group A - 0.016 NiTi, 0.018 × 0.025nNiTi, and .019 × 0.025 Steel wires.
Group B- 0.016 Niti, 0.016 SS and finally 0.020-inch Steel wires.
Group C - 0.016 × 0.022 CuNiTi wire, followed by 0.019 × 0.025 CuNiTi, and ending with 0.019 × 0.025 Steel wire,
And found that all sequences were equally effective. However, the CuNiTi may be preferred by the clinicians as it reduces the number of appointments [14].
In another study by Ong, the three different archwire sequences were applied are as follows:
0.014 Niti, 0.017×0.017 HANT, 0.016×0.022 Steel
0.014 Sentalloy, 0.016×0.022 Bio force, 0.016×0.022 Steel
0.014 CuNiTi, 0.014×0.025 CuNiTi, 0.016×0.022 Steel,
And found that there were no differences among the archwire sequences in terms of aligning or discomfort [15].
Phase 1: Light Round Wires
This phase of treatment uses 0.013, 0.014, or 0.016 CuNiTi arch wires. The aim of this first phase of treatment is to achieve tooth alignment including rotation correction except second molars, level the arches and initiate arch development with light forces to permit the soft tissues to desired arch shape. This phase of treatment normally extends from 10 to 20 weeks and the intervals between appointments are about 10 weeks.
Phase 2: High Rectangular Wires
Phase 2 uses two arch wires: 0.014 × 0.025 CuNiTi followed by 0.018 × 0.025 CuNiTi wires. In case of well aligned arches only 0.016 × 0.025 CuNiTi are used in this phase. If intrusion of anteriors is planned, 0.017× 0.025 or 0.019× 0.025 CuNiTi arch wires with preformed curves or reverse curves of Spee or additional torque can be applied anteriorly in this stage.
The main purposes of this phase are:
Continue arch development
achieve complete alignment of all teeth including second molars,
consolidate anterior spaces and maintain tooth contact,
Initiate torque control and bite opening,
The duration of this phase ranges from 20 to 30 weeks. The first archwire is placed from 8 to 10 weeks and the second is from 4 to 6 weeks.
Phase 3: Major Mechanics
Preposted stainless steel arch wires of size 0.019 × .025 are used. Presence of cross bite at this stage when persisted can be corrected with the use of 0.016 × 0.025 preposted stainless steel arch wire with the use of cross elastics where buccal and lingual tipping can be achieved at this stage.
The main purposes of this phase are:
Finish torque control,
Consolidate posterior space and
Maintain the arch form which developed during the initial two phases,
Completely correct the tooth position in all the three relationships.
This phase of treatment extends from 8 to 10 weeks with an interval about 10-weeks between appointments.
Phase 4: Finishing and Detailing
The stainless steel arch wires continued in this phase with elastics for achieving proper interdigitation. But for individual teeth position 0.019× 0.025 ß-titanium arch wires may also be used [2, 3, 16].
In a study by Handem, used the arch sequence with initial round wires 0.014 or 0.016, followed by rectangular 0.016 × 0.025, 0.018 × 0.025, and 0.019 × 0.025 CuNiTi arch wires subsequently, rectangular 0.017 × 0.025 or 0.019 × 0.025 Steel arch wires [17].
Various clinicians have put forth bracket placement methodologies of the Damon bracket system to achieve the desired smile arc protection, functional occlusion and enhancing the facial esthetics.
Standard bracket placement by Dwight Damon [18]:
According to him, the arch wire slot should be at the distances mentioned below from the incisal edge.
Maxillary
U-l 4.75 mm.
U-2 4.50 mm.
U-3 5.00 mm.
U-4 4.50 mm.
U-5 4.25 mm.
Mandibular
L-l 4.75 mm.
L-2 4.50 mm.
L-3 5.00 mm.
L-4 4.50 mm.
L-5 4.25 mm.
The upper brackets open occlusally and the lower brackets open gingivally.
The mesiodistal width of the pad and the mesiodistal edges of the teeth should be given importance.
Panorex view prior to bracket placement allows to identify root position.
The internal slot and the horizontal components should be parallel to the occlusal plane. This is of greater importance in the lower anteriors.
The scribe line of the bracket and crown long axis should be focused while placing the bracket.
Dr. Dwight Damon advises placement of the bracket within the green zone (in between the green lines). The Damon prescription has variable torque prescriptions to foster the need for different clinical cases. A clinician can place the upper and lower mid-bracket slot within the green lines without dramatically impacting torque.
Dr. Thomas. R. Pitts Protocol [19]:
Dr. Thomas. R. Pitts worked with a philosophy of “beginning with the end in mind”. He believed that developing acumen in precise bracket placement is the single most important protocol to achieve an esthetically pleasing smile and functional occlusion.
Basic principles of the Pitts placement protocol:
Detailed bonding plan before the day of bonding and to select brackets of appropriate torque based on the demand of the case.
Ensure tray setup entails all items for an efficient bonding.
Use two assistants to assist in bonding.
Recontour teeth for esthetics and bracket fit.
Follow an exacting placement protocol to achieve an ideal smile arc in the anteriors and leveling buccal cusps and marginal ridges in the posteriors.
Dr. Pitts bonds the maxillary anteriors to achieve a consonant smile arc at the end of the treatment, the mandibular anteriors for overjet and overbite and the remaining teeth for a good occlusion. He first bonds the mandibular teeth, from the second molar to canine on one side, and repeats the same on the opposite side, followed by lateral to lateral. This is followed to achieve symmetry on either side. The same sequence is repeated in the upper arch. He believed in keying off the maxillary canine to ensure that the canine-lateral and canine- premolar contacts are esthetic and functional.
In the posteriors, to achieve leveled marginal ridges and contact points, the teeth are bonded using the contact points as reference. This is done up to the canine and then the incisors are bonded based on the slot of the maxillary canine to give a sweep in the smile arc which gives a pleasing appearance Figures 1 and 2.
Standard bracket placement of damon bracket.
Picture depicting the “green zone” for bracket placement in the Damon system.
Dr. Pitt’s occluso gingival positioning of brackets is slightly more gingival to the conventional placement on both arches. He believed positioning the brackets more incisally will prevent us from achieving the ideal smile arc and hinders torque control (Figure 3). Dr. Pitts along with Dr. Mike Steffan developed a method to making the bracket positioning easier by drawing lines on the stone models from contact points for the canine, premolars and molars to prevent mistakes in bracket positioning in the transition of contact points from posteriors to anteriors (Figure 4).
Gingival bracket placement for smile arc protection by Dr. Thomas Pitts.
Marking the contact points reference for establishing occlusogingival positioning of brackets.
The position of the maxillary canine is given the prime importance for the sweep in the smile arc. Based on the positioning of this bracket, other anterior brackets were placed. In this method, the incisal edge of the canine bracket wing needs to be placed on a line drawn from mesial to distal contact at the height of contour interproximally. This line was called the mesiodistal (M-D) contact line. The level of the slot of this bracket was used as a reference for maxillary central and lateral incisor positioning. The maxillary lateral incisor bracket is placed 0.5 mm gingival to the canine bracket and central incisor bracket 0.25 mm gingival to this to achieve the ideal smile arc (Figure 5) Further to avoid the bracket positioning error, the author advises the use of a two inch large front surface mirror to avoid any error in bracket positioning (Figure 6).
Bracket positioning in the maxillary incisors and canines.
Use of a large front surface mirror to prevent errors in bracket positioning.
The maxillary premolars are positioned by aligning the scribe line with the crown long axis at the height of contour paralleling the central groove and the M-D buccal line angle. Following correct bracket placement, the bracket on the first premolar would seem too distal to the height of contour and the second premolar at times would appear mesial to the height of contour when viewed from the buccal aspect. The occlusal edge of the brackets should touch the M-D contact line (Figure 7).
Bracket positioning in the maxillary premolars.
The mesiodistal positioning of the buccal tube is done by centering the buccal tube pad over the buccal groove of the teeth and the occluso gingival positioning is done by placing the occlusal edge of the pad on the M-D contact line of the first molar. The second molars follows the same rule for mesiodistal positioning but placed 1.5 mm more occlusally to the first molar tube (Figure 8).
Bracket positioning in the maxillary molars.
The mandibular incisors are placed such that the scribe line is aligned with the long axis of the tooth. The bracket position is viewed from the incisal aspect. For deep bite, the position of the top of the slot is 3.5 mm from the incisal edge to reverse the curve of spee and for open bite; the position of the top of the slot is 5 mm from the incisal edge to open the curve of spee (Figure 9).
Bracket positioning in the mandibular anteriors.
The mesiodistal positioning is done by aligning the scribe line to the long axis of the crown at the height of contour. The position is verified by viewing from the incisal aspect. The occluso gingival positioning is placing the incisal edge of the bracket wing at the M-D contact line (Figure 10).
Bracket positioning in the mandibular canine.
The mesiodistal positioning is done by aligning the scribe line to the crown long axis and viewed from the occlusal aspect. The occluso gingival positioning is based on positioning the occlusal edge of the bracket wing 0.5 mm gingival to the M-D contact line (Figure 11).
Bracket positioning in the mandibular premolars.
The mandibular molars are placed in the same way as the maxillary molars in terms of mesiodistal positioning by orienting the center of the buccal tip of the buccal tube with that of the buccal groove of the tooth. Unlike the maxillary molars, both the mandibular molars are placed at the same height, which is 0.5 mm gingival to the M-D contact line (Figure 12).
Bracket positioning in the mandibular molars.
Another technique that was proposed was the bracket placement in Beethoven’s Orthodontic center. The bracket placement was similar to that given by Dr. Pitts except some modifications that were made in the maxillary canines. According to him, the maxillary canine bracket is placed by aligning it 1 mm mesially away from the long axis of the crown. The slot of the canine was used as a reference for placing the incisor brackets. The slots of the central and lateral incisor brackets are raised 0.5 mm consecutively (Figure 13).
Figure showing placement of brackets in the maxillary anteriors.
Dr. Damon has said that force applied to the bracket should be as light as possible to stimulate tooth movement. His philosophy was to employ the concept of biological adaptation and facially driven treatment plan that focuses on facial esthetics as a critical foundation for diagnosis.
The treatment objective in Damon cases is to
Gain maxillary and mandibular arch length.
Establish upper and lower incisor position to give lip support.
Establish maxillary and mandibular posterior arch width to support mid-face.
Establish ideal maxillary lip-to-tooth relationship.
Design treatment mechanics to eliminate need for higher force rapid palatal expansion.
With low-force mechanics to work with the orofacial muscle complex, bone, and tissue to establish a physiologic tooth position
Damon system can be used in the following cases
Class I- Non Extraction- Young patient with severe crowding and a flat profile
Class I- Non Extraction- Adult patient with severe crowding and a flat profile
Class I- Non Extraction- Young patient- Open bite with posterior crossbite and very narrow deep palate.
Class I- Non Extraction- Adult patient- Open bite with posterior crossbite and very narrow deep palate.
Class I- Extraction- Bimaxillary protrusion and crowding.
Class II division I subdivision with functional shift- Non Extraction
Class II division I- Severe crowding and deep bite
Class II division II- Severe crowding and deep bite
Class III- Severe crowding.
Using the light forces from the Copper NiTi wires and friction less passive self-ligating brackets along with Superelastic NiTi open coil springs wherever required we can achieve a desired treatment outcome with the Damon system.
In case of Class II patients with retrognathic mandibles we can go for Phase 1 therapy with functional appliances or fixed functional appliances.
The Damon self-ligating appliances have certain characteristics such as ease in ligation, wire engagement without undesirable force relaxation of elastomeric modules, which helps in maintaining a constant active status of engaged wires. This makes the Damon appliance more suitable than conventional appliances. This is in agreement with the findings by various other orthodontists, Berger [20], Harradine [9], Turnbull and Birnie [4].
Ormco, Damon Company keeps evolving over the years, coming out with different and more compatible bracket systems. Starting from Damon 3©, to Damon 3mx©, to Damon Q©, to Damon Q2© followed by the latest development, the Damon Ultima™© system. In clear ceramic braces from Damon clear© they have recently developed the Damon Clear 2© system.
They are completely esthetic passive self-ligating brackets made of polycrystalline alumina (PCA) material, which is resistant to staining from coffee, mustard, red wine and other agents. It eliminates the need for the use of elastomers (modules) which generally stain and collect bacteria during the course of the treatment.
Damon Clear 2© brackets have a sturdy base with a fortified slide, window channel and tie wings for extra strength and durability. The four solid walls enable effective torque expression and rotation control for a good and meticulous finishing (Figures 14 and 15).
Damon clear 2© bracket.
Enhanced strength for effective torque expression.
The base design of the Damon Clear 2© brackets is a patented laser etched pad that provides optimal bond strength for greater reliability (Figure 16). The contours of the brackets are smooth and rounded, which ensures patient comfort. The is an option to switch to brackets that have discrete contoured hooks for elastics and other auxiliaries (Figure 17).
Laser etched base for enhanced stability.
Discrete contoured hooks for auxiliaries.
Generally ceramic brackets are thought of as messy, while debonding as they tend to crack and splutter while using a debonding plier to remove the bracket. Whilst, for Damon Clear 2©, Ormco has a patented debonding instrument, the Damon Clear Debonding Instrument ©, which results in fast and comfortable debonding experience for patients (Figure 18). There is also no requirement for removing flash after the debonding procedure.
Debonding of the bracket with Damon clear Debonding instrument ©.
Removable positioning gauge with scaler notch is present in each of the clear brackets for easy and efficient placement of the bracket (Figure 19). There are color-coded positioning gauges on brackets (13–23) present that denote torque values.
Removable position gauge with scalar notch.
For a higher efficient and quality treatment, proper wire sequencing must be employed. The initial arch wires being the Damon Optimal-Force Copper Ni-Ti® to low-friction TMA and stainless-steel arch wires. Each wire must have sufficient time to express itself before progression to the next wire. For anterior torque expression, either pre-torqued nickel titanium arch wires or TMA arch wires are to be used. For rotational bends, TMA arch wires or titanium niobium arch wires are to be used. However, care should be taken in employing finishing bends in stainless steel wires, since such bends may result in fractures.
Damon Ultima ™ © was designed and introduced for a faster and a more precise finishing. Traditional passive self-ligating brackets and wires have significant play which generally results in poor control, manual adjustments and extended treatment time. The Damon Ultima ™© system is the first system that is completely reengineered to virtually eliminate play, for a precise control of rotation, angulation and torque [3].
The enhanced features in Damon Ultima ™© are as follows:
Completely re-engineered tie-wing is said to improve the ability to engage and ligate elastomeric chains (Figure 20).
Smoother tie wings were designed for a better patient comfort and minimal occlusal interference (Figure 21).
The base of the bracket with 80 gauge mesh designed for reliable and increased bond strength throughout treatment and for a predictable debonding experience (Figure 22).
Easy to open and close the slot door design with low reciprocal forces and tactile feedback. The bracket door and wire are designed to reduce door closure interference (Figure 23).
Rhomboid shaped pad with enhanced scribe line help in guiding bracket placement (Figure 24).
Presence of vertical slot for convenient placement of drop-in hooks (Figure 25).
Reengineered tie wing in Damon Ultima ™©.
Smoother tie wings for patient comfort.
Base of the bracket of Damon Ultima ™©.
The enhanced bracket door design.
Rhomboid shaped pad in Damon Ultima ™©.
Vertical slot for placement of drop-in hooks.
The retrocline and procline bracket options were introduced for enhanced torque control. Brackets were designed from the centre point of the clot to the line-up with the FA point to express desired torque and provide easier and more precise placement (Figure 26).
Adversity of procline and retrocline brackets in the Damon Ultima ™© system, that can be used to incorporate torque whenever needed.
Additionally, extra arch wire options were included, for torque control when needed. Sizes available are: 0.019*0.0275, 0.0020*0.0275, and 0.021*0.0275 in Copper NiTi, TMA and SS (Figure 27).
Reengineered arch wire for better torque control.
Passive self-ligation offers the most direct transmission of force from the arch wire to the tooth with very low friction, a very secure ligation along with excellent control of tooth position. Every contemporary modality of orthodontic treatment achieves tooth alignment; however passive self-ligation achieves the results effectively and efficiently. With the evolution of various systems like Damon Clear2 and Damon Ultima ©, the orthodontic tooth movement is achieved at its best.
Dr. Suvetha Siva- No conflict of interest with the product (ORMCO).
Dr. Shreya Kishore- No conflict of interest with the product (ORMCO).
Dr. Suganya Dhanapal- No conflict of interest with the product (ORMCO).
Dr. Janani Ravi- No conflict of interest with the product (ORMCO).
Dr. Chandhini Suresh- No conflict of interest with the product (ORMCO).
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\\n\\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\\n\\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\\n\\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\\n\\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\\n\\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\\n\\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\\n\\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\\n\\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\\n\\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Pristupom na stranicu www.intechopen.com slažete se s ovim odredbama, sa svim primjenjivim zakonskim odredbama, te se slažete s poštovanjem svih lokalnih zakona. Korištenje i/ili pristup ovoj stranici temelji se na potpunom prihvaćanju ovih odredbi. Svi materijali na ovoj stranici zaštićeni su primjenjivim zakonima o autorskim pravima i žigu.
\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\nSve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\n\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\n\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\n\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\n\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\n\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. 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I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). 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by",editors:[{id:"196461",title:"Prof.",name:"Hideki",middleName:null,surname:"Nakano",slug:"hideki-nakano",fullName:"Hideki Nakano"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10475",title:"Smart Biofeedback",subtitle:"Perspectives and Applications",isOpenForSubmission:!1,hash:"8d2bd9997707c905959eaa41e55ba8f1",slug:"smart-biofeedback-perspectives-and-applications",bookSignature:"Edward Da-Yin Liao",coverURL:"https://cdn.intechopen.com/books/images_new/10475.jpg",editedByType:"Edited by",editors:[{id:"3875",title:"Dr.",name:"Edward Da-Yin",middleName:null,surname:"Liao",slug:"edward-da-yin-liao",fullName:"Edward Da-Yin Liao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8059",title:"Neurostimulation and Neuromodulation in Contemporary Therapeutic 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by",editors:[{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8751",title:"Somatosensory and Motor Research",subtitle:null,isOpenForSubmission:!1,hash:"86191c18f06e524e0f97a5534fdb2b4c",slug:"somatosensory-and-motor-research",bookSignature:"Toshiaki Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/8751.jpg",editedByType:"Edited by",editors:[{id:"70872",title:"Prof.",name:"Toshiaki",middleName:null,surname:"Suzuki",slug:"toshiaki-suzuki",fullName:"Toshiaki Suzuki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9347",title:"Neuroimaging",subtitle:"Neurobiology, Multimodal and Network Applications",isOpenForSubmission:!1,hash:"a3479e76c6ac538aac76409c9efb7e41",slug:"neuroimaging-neurobiology-multimodal-and-network-applications",bookSignature:"Yongxia Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/9347.jpg",editedByType:"Edited by",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8938",title:"Inhibitory Control Training",subtitle:"A Multidisciplinary Approach",isOpenForSubmission:!1,hash:"bd82354f3bba4af5421337cd42052f86",slug:"inhibitory-control-training-a-multidisciplinary-approach",bookSignature:"Sara Palermo and Massimo Bartoli",coverURL:"https://cdn.intechopen.com/books/images_new/8938.jpg",editedByType:"Edited by",editors:[{id:"233998",title:"Ph.D.",name:"Sara",middleName:null,surname:"Palermo",slug:"sara-palermo",fullName:"Sara Palermo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6998",title:"Synucleins",subtitle:"Biochemistry and Role in Diseases",isOpenForSubmission:!1,hash:"2b4b802fec508928ce8ab9deebd1375f",slug:"synucleins-biochemistry-and-role-in-diseases",bookSignature:"Andrei Surguchov",coverURL:"https://cdn.intechopen.com/books/images_new/6998.jpg",editedByType:"Edited by",editors:[{id:"266540",title:"Dr.",name:"Andrei",middleName:null,surname:"Surguchov",slug:"andrei-surguchov",fullName:"Andrei Surguchov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:65,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"46296",doi:"10.5772/57398",title:"Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity",slug:"physiological-role-of-amyloid-beta-in-neural-cells-the-cellular-trophic-activity",totalDownloads:5886,totalCrossrefCites:18,totalDimensionsCites:31,abstract:null,book:{id:"3846",slug:"neurochemistry",title:"Neurochemistry",fullTitle:"Neurochemistry"},signatures:"M. del C. Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. Gómez-Virgilio, G. Ramírez-Rodríguez, E. Vera-\nArroyo, R. Fiorentino-Pérez, U. García, J. Luna-Muñoz and M.A.\nMeraz-Ríos",authors:[{id:"42225",title:"Dr.",name:"Jose",middleName:null,surname:"Luna-Muñoz",slug:"jose-luna-munoz",fullName:"Jose Luna-Muñoz"},{id:"114746",title:"Dr.",name:"Marco",middleName:null,surname:"Meraz-Ríos",slug:"marco-meraz-rios",fullName:"Marco Meraz-Ríos"},{id:"169616",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Cardenas-Aguayo",slug:"maria-del-carmen-cardenas-aguayo",fullName:"Maria del Carmen Cardenas-Aguayo"},{id:"169857",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Silva-Lucero",slug:"maria-del-carmen-silva-lucero",fullName:"Maria del Carmen Silva-Lucero"},{id:"169858",title:"Dr.",name:"Maribel",middleName:null,surname:"Cortes-Ortiz",slug:"maribel-cortes-ortiz",fullName:"Maribel Cortes-Ortiz"},{id:"169859",title:"Dr.",name:"Berenice",middleName:null,surname:"Jimenez-Ramos",slug:"berenice-jimenez-ramos",fullName:"Berenice Jimenez-Ramos"},{id:"169860",title:"Dr.",name:"Laura",middleName:null,surname:"Gomez-Virgilio",slug:"laura-gomez-virgilio",fullName:"Laura Gomez-Virgilio"},{id:"169861",title:"Dr.",name:"Gerardo",middleName:null,surname:"Ramirez-Rodriguez",slug:"gerardo-ramirez-rodriguez",fullName:"Gerardo Ramirez-Rodriguez"},{id:"169862",title:"Dr.",name:"Eduardo",middleName:null,surname:"Vera-Arroyo",slug:"eduardo-vera-arroyo",fullName:"Eduardo Vera-Arroyo"},{id:"169863",title:"Dr.",name:"Rosana Sofia",middleName:null,surname:"Fiorentino-Perez",slug:"rosana-sofia-fiorentino-perez",fullName:"Rosana Sofia Fiorentino-Perez"},{id:"169864",title:"Dr.",name:"Ubaldo",middleName:null,surname:"Garcia",slug:"ubaldo-garcia",fullName:"Ubaldo Garcia"}]},{id:"58070",doi:"10.5772/intechopen.72427",title:"MRI Medical Image Denoising by Fundamental Filters",slug:"mri-medical-image-denoising-by-fundamental-filters",totalDownloads:2564,totalCrossrefCites:17,totalDimensionsCites:30,abstract:"Nowadays Medical imaging technique Magnetic Resonance Imaging (MRI) plays an important role in medical setting to form high standard images contained in the human brain. MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"26258",doi:"10.5772/28300",title:"Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke",slug:"excitotoxicity-and-oxidative-stress-in-acute-ischemic-stroke",totalDownloads:7157,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"931",slug:"acute-ischemic-stroke",title:"Acute Ischemic Stroke",fullTitle:"Acute Ischemic Stroke"},signatures:"Ramón Rama Bretón and Julio César García Rodríguez",authors:[{id:"73430",title:"Prof.",name:"Ramon",middleName:null,surname:"Rama",slug:"ramon-rama",fullName:"Ramon Rama"},{id:"124643",title:"Prof.",name:"Julio Cesar",middleName:null,surname:"García",slug:"julio-cesar-garcia",fullName:"Julio Cesar García"}]},{id:"62072",doi:"10.5772/intechopen.78695",title:"Brain-Computer Interface and Motor Imagery Training: The Role of Visual Feedback and Embodiment",slug:"brain-computer-interface-and-motor-imagery-training-the-role-of-visual-feedback-and-embodiment",totalDownloads:1439,totalCrossrefCites:13,totalDimensionsCites:23,abstract:"Controlling a brain-computer interface (BCI) is a difficult task that requires extensive training. Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"63258",title:"Anatomy and Function of the Hypothalamus",slug:"anatomy-and-function-of-the-hypothalamus",totalDownloads:4558,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hypothalamus is a small but important area of the brain formed by various nucleus and nervous fibers. Through its neuronal connections, it is involved in many complex functions of the organism such as vegetative system control, homeostasis of the organism, thermoregulation, and also in adjusting the emotional behavior. The hypothalamus is involved in different daily activities like eating or drinking, in the control of the body’s temperature and energy maintenance, and in the process of memorizing. It also modulates the endocrine system through its connections with the pituitary gland. Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"}],onlineFirstChaptersTotal:17},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:289,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. 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He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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