The key ECM components in each layer of the leaflet and their major functions
\r\n\t
",isbn:"978-1-80355-841-7",printIsbn:"978-1-80355-840-0",pdfIsbn:"978-1-80355-842-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"c8bc6f25678ec6a696adb8003e937432",bookSignature:"Dr. Wei Wu, Ms. Qiuqin Tang, Prof. Panagiotis Tsikouras, Prof. Werner Rath and Prof. Georg-Friedrich Von Tempelhoff",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11280.jpg",keywords:"Ultrasound, Biochemical Screening, Amniocentesis, Fetoscopy, Karyotype, Molecular DNA Testing, Congenital Malformation, Birth Defects, Biomarker, Protein, Prenatal Diagnosis, Prenatal Screening",numberOfDownloads:268,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 2nd 2021",dateEndSecondStepPublish:"February 23rd 2022",dateEndThirdStepPublish:"April 24th 2022",dateEndFourthStepPublish:"July 13th 2022",dateEndFifthStepPublish:"September 11th 2022",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A pioneering researcher in reproductive medicine, appointed associate department chair of Department of Toxicology, Nanjing Medical University, Society of Toxicology full member and holder of eleven registered patents. Dr. Wei Wu has received awards from many national societies for the originality and quality of his projects. He has authored 70 peer-reviewed papers in international journals.",coeditorOneBiosketch:"A pioneering researcher in obstetrics and holder of three registered patents. Dr. Qiuqin Tang's research interests include genetic and epigenetic risk factors of reproductive and developmental health. She has authored over 20 papers in international journals.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"178661",title:"Dr.",name:"Wei",middleName:null,surname:"Wu",slug:"wei-wu",fullName:"Wei Wu",profilePictureURL:"https://mts.intechopen.com/storage/users/178661/images/system/178661.jpeg",biography:"Dr. Wei Wu is an associate professor and associate department\nchair in the Department of Toxicology, Nanjing Medical University, China, where he received his Ph.D. in Toxicology in 2012.\nHe was a guest researcher at the National Institute of Environmental Health Sciences (NIEHS) between 2017 and 2018. Dr.\nWu is a member of different national and international societies\nin the fields of human reproduction and toxicology and has\nreceived awards from many national societies for the originality and quality of his\nprojects. Dr. Wu has authored seventy-three peer-reviewed papers in international\njournals. He has edited four books and collaborated on ten others as well as seventeen patents and in the organization of three international conferences. He is a\nreviewer for ninety-eight journals.",institutionString:"Nanjing Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Nanjing Medical University",institutionURL:null,country:{name:"China"}}}],coeditorOne:{id:"184798",title:"Ms.",name:"Qiuqin",middleName:null,surname:"Tang",slug:"qiuqin-tang",fullName:"Qiuqin Tang",profilePictureURL:"https://mts.intechopen.com/storage/users/184798/images/13334_n.jpg",biography:"Qiuqin Tang is an attending doctor of The Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital). Her research interests include genetic and epigenetic risk factors of reproductive and developmental health. She has authored over 20 papers in international journals such as EBioMedicine, Clinical Epigenetics, Molecular Human Reproduction, Scientific Reports, and European Journal of Endocrinology. She has collaborated in four books and three patents. She is the Editor-in-Chief of Journal of Woman\\'s Reproductive Health, and editor of many other journals including Journal of Gynecology and Obstetrics, and Journal of Gynecology and Obstetrics Forecast.",institutionString:"Nanjing Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Nanjing Medical University",institutionURL:null,country:{name:"China"}}},coeditorTwo:{id:"48837",title:"Prof.",name:"Panagiotis",middleName:null,surname:"Tsikouras",slug:"panagiotis-tsikouras",fullName:"Panagiotis Tsikouras",profilePictureURL:"https://mts.intechopen.com/storage/users/48837/images/system/48837.jpg",biography:"Dr. Panagiotis Tsikouras is a specialist in obstetrics-gynecology,\nperinatal medicine, and contraception at the School of Medicine,\nDemocritus University of Thrace, Greece. He is also the headmaster of the Family Planning Centre and Gynecological Cytology\nLaboratory at the same university. Dr. Tsikouras is a fellow of the\nInternational Academy of Clinical and Applied Thrombosis/Hemostasis. His scientific activities focus on paediatric and adolescence medicine, gynecological oncology, high-risk pregnancies. He is a reviewer for several international journals and has numerous scientific publications to his credit, including papers and book chapters. He has also contributed to international and national guidelines on coagulation and thrombosis in obstetrics-gynecology.",institutionString:"Democritus University of Thrace, Komotini",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"11",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Democritus University of Thrace",institutionURL:null,country:{name:"Greece"}}},coeditorThree:{id:"290374",title:"Prof.",name:"Werner",middleName:null,surname:"Rath",slug:"werner-rath",fullName:"Werner Rath",profilePictureURL:"https://mts.intechopen.com/storage/users/290374/images/system/290374.jpg",biography:"Dr. Werner Rath is a specialist in obstetrics and gynecology, gynecologic oncology, perinatal medicine, and hemostaseology. He\nis currently a professor in the Gynecology and Obstetrics Faculty\nof Medicine, University of Kiel, Germany, and honorary doctor\nat the Democritus University of Thrace, Alexandroupoli University Hospital He previously served as chief of the Department\nof Gynecology and Obstetrics at University Hospital RWTH Aachen,\nGermany. Dr. Rath is a reviewer for numerous journals and chief editor of Geburtshilfe und Frauenheilkunde (GebFra). He has several publications, including thirteen\nbook chapters, to his credit.",institutionString:"Kiel University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Kiel University",institutionURL:null,country:{name:"Germany"}}},coeditorFour:{id:"299669",title:"Prof.",name:"Georg-Friedrich",middleName:null,surname:"Von Tempelhoff",slug:"georg-friedrich-von-tempelhoff",fullName:"Georg-Friedrich Von Tempelhoff",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:"St. Vinzenz Krankenhaus",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:[{id:"79159",title:"Open Fetal Surgery and Fetoscopic Repair in Spina Bifida and Myelomeningocele in Romania",slug:"open-fetal-surgery-and-fetoscopic-repair-in-spina-bifida-and-myelomeningocele-in-romania",totalDownloads:61,totalCrossrefCites:0,authors:[null]},{id:"79947",title:"Endoscopic Approach to Ectopic Pregnancy",slug:"endoscopic-approach-to-ectopic-pregnancy",totalDownloads:59,totalCrossrefCites:0,authors:[null]},{id:"80212",title:"Diagnosis of Ectopic Pregnancy",slug:"diagnosis-of-ectopic-pregnancy",totalDownloads:74,totalCrossrefCites:0,authors:[null]},{id:"80756",title:"Medical Management of Ectopic Pregnancy",slug:"medical-management-of-ectopic-pregnancy",totalDownloads:32,totalCrossrefCites:0,authors:[null]},{id:"81269",title:"Fetal Craniospinal Malformations: Aetiology and Diagnosis",slug:"fetal-craniospinal-malformations-aetiology-and-diagnosis",totalDownloads:13,totalCrossrefCites:0,authors:[null]},{id:"81570",title:"Prenatal Diagnosis of Diaphragmatic Hernia",slug:"prenatal-diagnosis-of-diaphragmatic-hernia",totalDownloads:15,totalCrossrefCites:0,authors:[null]},{id:"81868",title:"Prenatal Diagnosis: The Main Advances in the Application of Identification of Biomarkers Based on Multi-Omics",slug:"prenatal-diagnosis-the-main-advances-in-the-application-of-identification-of-biomarkers-based-on-mul",totalDownloads:1,totalCrossrefCites:0,authors:[null]},{id:"81273",title:"Ectopic Pregnancy after Ipsilateral Salpingectomy",slug:"ectopic-pregnancy-after-ipsilateral-salpingectomy",totalDownloads:13,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6295",title:"Pregnancy and Birth Outcomes",subtitle:null,isOpenForSubmission:!1,hash:"fc1274517f5c0c09b0a923b3027f3d8a",slug:"pregnancy-and-birth-outcomes",bookSignature:"Wei Wu",coverURL:"https://cdn.intechopen.com/books/images_new/6295.jpg",editedByType:"Edited by",editors:[{id:"178661",title:"Dr.",name:"Wei",surname:"Wu",slug:"wei-wu",fullName:"Wei Wu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10724",title:"Male Reproductive Anatomy",subtitle:null,isOpenForSubmission:!1,hash:"a3fdda3194735da4287e9ea193beb07e",slug:"male-reproductive-anatomy",bookSignature:"Wei Wu",coverURL:"https://cdn.intechopen.com/books/images_new/10724.jpg",editedByType:"Edited by",editors:[{id:"178661",title:"Dr.",name:"Wei",surname:"Wu",slug:"wei-wu",fullName:"Wei Wu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10464",title:"Oxytocin and Health",subtitle:null,isOpenForSubmission:!1,hash:"77ae1cfbfdab58a8d50b657502c9fc11",slug:"oxytocin-and-health",bookSignature:"Wei Wu and Ifigenia Kostoglou-Athanassiou",coverURL:"https://cdn.intechopen.com/books/images_new/10464.jpg",editedByType:"Edited by",editors:[{id:"178661",title:"Dr.",name:"Wei",surname:"Wu",slug:"wei-wu",fullName:"Wei Wu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7931",title:"Male Reproductive Health",subtitle:null,isOpenForSubmission:!1,hash:"5754baea5de6a634c66bae12a33d52d9",slug:"male-reproductive-health",bookSignature:"Wei Wu, Francesco Ziglioli and Umberto Maestroni",coverURL:"https://cdn.intechopen.com/books/images_new/7931.jpg",editedByType:"Edited by",editors:[{id:"178661",title:"Dr.",name:"Wei",surname:"Wu",slug:"wei-wu",fullName:"Wei Wu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9500",title:"Recent Advances in Bone Tumours and Osteoarthritis",subtitle:null,isOpenForSubmission:!1,hash:"ea4ec0d6ee01b88e264178886e3210ed",slug:"recent-advances-in-bone-tumours-and-osteoarthritis",bookSignature:"Hiran Amarasekera",coverURL:"https://cdn.intechopen.com/books/images_new/9500.jpg",editedByType:"Edited by",editors:[{id:"67634",title:"Dr.",name:"Hiran",surname:"Amarasekera",slug:"hiran-amarasekera",fullName:"Hiran Amarasekera"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"44726",title:"Extracellular Matrix Organization, Structure, and Function",doi:"10.5772/52842",slug:"extracellular-matrix-organization-structure-and-function",body:'Heart valves are thin, complex, layered connective tissues that direct blood flow in one direction through the heart. There are four valves in the heart, located at the entrance to and exit from the ventricular chambers. The normal function of the heart valves is essential to cardiovascular and cardiopulmonary physiology. The opening and closing of valve leaflets at precise times during the cardiac cycles contributes to the generation of sufficiently high pressure to eject blood from the ventricles, and also prevents blood from flowing backwards into the heart instead of forward towards the systemic circulation and the lungs.
The ability of heart valves to open and close repeatedly, as well as the maintenance of the phenotypes of valvular cells, is made possible by their tissue microstructure, specifically the composition and orientation of extracellular matrix (ECM). The ECM within heart valves is primarily comprised of collagen, elastic fibers, and proteoglycans and glycosaminoglycans, although other ECM components are present as well. Taken together, the ECM performs several roles in heart valves. First, the ECM plays a biomechanical role: it is responsible for the unique mechanical behavior of the valve tissue and thus the overall valve function. Second, the valvular cells are bound to and surrounded by the ECM that is located within the immediate vicinity of the cell; this ECM is specifically known as the pericellular matrix (PCM). The PCM influences cell function by serving as a source of ligands for cell surface receptors, which transfers mechanical strains (experienced by the leaflet tissues) to the cells and initiates intracellular signaling pathways. Third, the various types of ECM have different innate mechanical behaviors, for example with collagen being stiffer than elastic fibers, and a growing body of research has demonstrated that the phenotype and function of cells, including valve cells, are influenced by the stiffness of the substrate to which they are adhered [1]. These two latter functions of the ECM are considered to be mechanobiological as opposed to merely biomechanical since they affect cell behavior. Fourth, ECM has binding sites for growth factors and other soluble molecules found in the extracellular space, and thus the ECM serves as a reservoir for numerous bioactive factors than can affect cell behavior if they are released (such as when the ECM is degraded) or if a cell migrates close to this ECM reservoir.
Overall, the heart valve field is beginning to appreciate that there are numerous interactions between the ECM, valve cells, and valve mechanics. Given the complicated relationships that are being demonstrated, it is not surprising that alterations to the normal arrangement or composition of ECM, which frequently occur in valve disease, significantly and detrimentally impact valve function in a rather vicious cycle. For this reason, there has been an increasing effort to characterize the ECM within normal heart valves not only to elucidate valve biomechanics and mechanobiology, but also to obtain a solid basis for comparison with diseased valves.
This chapter will provide an overview of the ECM within heart valves, focusing on the aortic valve. After detailing the layered structure of the valve leaflets, each type of ECM component will be described and discussed in relation to its role in valve function and, in some instances, valve dysfunction.
Aortic valve leaflets consist of three main layers: the fibrosa, spongiosa, and ventricularis. Each layer has a distinct composition that aids in the normal mechanical and biochemical behavior of the valve. In diseased states, however, the composition of the layered structures can be altered compared to healthy tissues.
The fibrosa layer, close to the outflow surface, is mainly composed of collagen fibers with a small amount of elastic fibers, which are the major stress-bearing components and provide strength to maintain coaptation during diastole [2]. The circumferential alignment and orientation of collagen fibers contribute to the biological stress-strain relationship for aortic valve leaflets (Figure 1). This bilinear stress-strain curve represents the high extension with a low load and high elastic modulus with a high load applied [3]. Moreover, the particular architecture of collagen fibers contributes to the anisotropic mechanical behavior of the fibrosa layer. It has been found that the fibrosa is 4-6 times stiffer in the circumferential direction than in the radial direction [4].
The middle spongiosa layer of the leaflet predominantly consists of glycosaminoglycans and proteoglycans, particularly hyaluronan, which form a foam-like structure and bind a large amount of water. The spongiosa layer absorbs energy during compression, and facilitates the arrangement of collagen fibrils in the fibrosa and elastin in the ventricularis during the cardiac cycles [5].
Schematic drawing of stress-strain relationships for collagen and elastin fibers during valve motion, reproduced with permission [
The ventricularis layer, close to the inflow surface, is rich in elastin with a moderate amount of collagen, which extends in diastole and recoils during systole [6]. The recoil of elastin restores the crimp of collagen fibrils and decreases the surface area of the stretched tissue from the closing phase [5]. The thickness of the three layers varies from the base to the free edge of the cusp [7].
It is worth noting that elastic fibers were found to span the whole leaflet, and connect or anchor three discrete layers together [6,8]. In addition, elastin provides intrafibrillar connections between collagen bundles in the fibrosa layer, whereas it forms a three-dimensional interconnected network in the spongiosa layer [8]. During unloading, the intrafiber elastin, which has high extensibility, helps the collagen fibers return to their wavy and crimped state [6]. These interconnected structures of elastic fibers anchor the discrete layers together, and prevent delamination, which therefore improves the continuity of material behavior of the whole leaflet. Table 1 summarizes the key ECM components in the layers and their major functions.
Fibrosa | \n\t\t\tCollagen | \n\t\t\tStress bearing | \n\t\t
Spongiosa | \n\t\t\tGlycosaminoglycans and proteoglycans | \n\t\t\tConferring flexibility, dampening vibrations from closing, and resisting delamination | \n\t\t
Ventricularis | \n\t\t\tElastin | \n\t\t\tRestoration of the wavy and crimped state of collagen fibers | \n\t\t
The key ECM components in each layer of the leaflet and their major functions
The structures of the leaflets described above provide the following critical functions [6,9–11]: 1) anisotropic mechanical behavior withstanding circumferential stress and extending radially; 2) bilinear biological stress-strain behavior allowing the leaflet to extend before bearing load in the closed phase; 3) elastic recoil to fully open the valve and restore the layer structures for the next cycle. The particular shape of the leaflets and their unique macro- and micro-structures cause the anisotropic mechanical behavior along the circumferential and radial directions of the leaflets [9–11].
During the closed phase (diastole), the leaflets experience the maximum load. Collagen bundles in the fibrosa layer are the major stress-bearing component withstanding approximately 80 mm Hg pressure while the valve is closed and bulging back towards the ventricle [3]. Collagen fibrils are assembled into parallel collagen fiber bundles oriented along the circumferential direction in the leaflet, which are able to withstand such high tensile forces. However, collagen fibers cannot be compressed, making the alignment of collagen (waviness and crimping) important for decreasing the area of the stretched fibrosa layer. Although the collagen fibrils have limited extensibility (approximately 1-2% yield strain), the waviness and crimping allows the fibrosa to withstand roughly 40% strain under loading. Straightening of wavy fibers provides approximately 17% strain, whereas the crimping allows additional approximately 23% strain [6]. In addition, the strains of the cusps in the closed phase are anisotropic, i.e., the strains differ in the radial and circumferential directions [11].
During valve opening, cusps become relaxed through recoil of the elongated, taut elastin. This restores the wavy and crimped state of collagen fibers while decreasing the surface area of the cusps. The GAG-rich spongiosa layer facilitates the rearrangements of the collagen and elastic fibers during the cardiac cycle, dampens vibration from closing, and resists delamination between layers [6,8].
It is evident that normal aortic valve function is maintained, in part, by not only the composition but also the arrangement and orientation of ECM components, particularly collagen, elastin, and GAGs, in the leaflets. Furthermore, it is important to note that alteration of the composition [12] and mechanics [13] of ECM in the aortic valve leaflets was found in diseased conditions. In calcific aortic valve disease (CAVD), collagen bundles and elastin fibers in the fibrosa layer were disrupted and disorganized [14]; meanwhile, there was increased proteoglycan deposition [12]. Matrix metalloproteinases (MMPs) [14,15] and the potent elastase cathepsin S [16], which are produced by macrophages, contribute to this ECM remodeling. Moreover, ECM proteins related to bone, i.e., osteocalcin and osteonectin, were present in the calcified fibrosa layer [17]. These proteins promote mineralization, and their presence suggests the osteoblastic differentiation of valve interstitial cells (VICs).
In addition, excessive myofibroblast differentiation from VICs, leading to ECM accumulation and fibrosis, was influenced by remodeling of ECM in the fibrosa and facilitated by elastin degradation [18]. Furthermore, myofibroblast differentiation from VICs and calcification
Taken together, the macroscopic layered structure and the microscopic structure in each layer of the leaflets impart pronounced anisotropic mechanical behavior that allows the valve to open and close during a great number of cardiac cycles throughout life. These structures are tailored to fulfill the normal functions and maintain the homeostasis of the leaflets in a healthy condition. However, abnormal alteration of composition and mechanics of ECM in these structures may lead to calcific heart valve disease.
Collagen is an essential component of the aortic valve’s layered structure and is vital for maintaining the tissue’s mechanical integrity. Mainly responsible for tensile strength, collagen is a strong load-bearing protein created and regulated by VICs. Although present throughout the entire valve, collagen is largely located in the fibrosa where it reduces high tensile stresses. In addition to its central role in valve mechanics, collagen acts as a regulator of VIC phenotype and calcification. Insight into the structure of collagen reveals its unique mechanical properties that support aortic valve function.
Fibrillar collagens are high strength fibers that comprise nearly all of the valve’s collagen content. Fibrillar collagens are groups of 3 coiled polypeptide chains that assemble together in tightly packed parallel arrangements. These coils are approximately 300 nm long and join together in a staggered banding pattern with a periodicity of 67 nm [20]. The aortic valve is mainly composed of fibrillar collagen types I, III, and V. Each of these collagens is constructed from different types of alpha chains that govern the overall function of the collagen molecule. Together, these three collagen types work to provide the aortic valve with unique mechanical properties suited for maintaining unidirectional blood flow.
Synthesis of fibrillar collagen is an essential mechanism for maintaining the valve’s mechanical integrity. This complex process originates within VICs and is completed in the valve ECM. Production of collagen begins with the intracellular creation of polypeptide alpha chains. There exist ten distinct polypeptide chains that consist of approximately 300 consecutive Gly-X-Y amino acid sequences flanked by small terminal domains. The secondary structure of collagen is created by folding alpha chains into a right-handed alpha helix with the peptide bonds localized at the backbone of the helix and the amino acid side chains facing outward. With slightly less than three residues per turn and a pitch of approximately 8.6 nm, glycine residues are positioned in such a way that the side chains of these residues allow for the formation of the helix. The single hydrogen side chains of these glycine residues allows for the formation of a triple helix structure [21].
The tertiary structure of collagen involves the formation of a left-handed triple helix constructed in the C to N direction. These triple helices exist as both homotrimers and heterotrimers of alpha chains. Collagen type III is a homotrimer of α1(III) while collagen type I is a heterotrimer of α1(I) and α2(I). Additionally, collagen type V is a heterotrimer of α1(V) and α2(V). Known as procollagen, the tertiary structure molecule is approximately 1.5 nm wide and longer than 300 nm. For creation of the final supramolecular structure, the procollagen molecule is transported into the ECM for crosslinking and fibril formation. After modification in the extracellular space, procollagen is converted into tropocollagen, which undergoes fibrillogenesis where the triple helices are packed together into bundles. Crosslinking of the fibrils ensures the stability of the complex [21].
The arrangement of collagen fiber bundles is crucial to the proper functioning of the aortic valve. Collagen fibers are organized into multilayer structures linked by thin membranes containing variably aligned collagen. Ranging from 10 to 50 μm in size, these membranes are believed to be much more extensible than the collagen fiber bundles they connect. These multilayer structures can easily slide past one another during valve movement, providing the combination of flexibility and tensile strength necessary for the required mechanics during valve opening and closing [22].
Collagen constitutes approximately 90% of the protein content of the valve insoluble matrix [23]. The vast majority of the valve’s content is composed of collagens type I, III, and V. Together, these fibrillar collagens account for 60% of the valve’s dry weight [24]. There is approximately 74% collagen type I, 24% collagen type III, and 2% collagen type V distributed throughout the valve [25–27]. Whereas collagen type I mainly exists in the fibrosa, collagen type III is expressed ubiquitously throughout all three layers [25].
Collagen fibers mainly function to reduce stress on the leaflets during systole and diastole. While elastin controls initial valve opening and closing, collagen fibers reduce peak stresses in the leaflet matrix by an estimated 60%. These fibers have an important role in stabilizing leaflet motion [28]. Throughout leaflet movement, collagen fibers adjust position to resist tensile forces. As transvalvular pressure increases, the ventricularis expands in the circumferential direction, causing collagen fibers to become highly aligned. This is believed to increase the cuspal stiffness of the valve during diastole and prevent overextension of the valve [29].
The heterogeneous distribution of collagen throughout the aortic valve provides high strength in areas of greater stress while also allowing the valve to achieve a large degree of flexibility. Within the fibrosa, the primary tensile load-bearing layer, collagen fibers are highly aligned in the circumferential direction, resulting in tissue anisotropy. The arrangement of these fibers corresponds to the direction of highest tensile stress. In contrast, the ventricularis endures smaller tensile forces involved with initial opening and closing of the valve [30]. In addition to circumferentially oriented collagen, the largest and strongest collagen fiber bundles are localized in the areas of greatest tensile stress along the lower part of the commissure and coapting regions [22]. This unique arrangement and positioning of collagen reduces high tensile loads on the valve while allowing flexibility to open and close.
Comparisons between the fibrosa and ventricularis indicate that the fibrosa has a greater elastic modulus in the circumferential direction but a similar elastic modulus in the radial direction. These mechanical differences are largely the result of the number of aligned collagen fibers in each direction. With fewer collagen fibers, the ventricularis is approximately half as stiff as the fibrosa in the circumferential direction. In the radial direction, however, each layer contains approximately the same amount of collagen fibers and has similar elastic moduli [31]. Taken together, the multilayer valve structure causes aortic valves to be less stiff and more extensible radially than circumferentially [32].
Collagen achieves high strength and extensibility with the aid of additional mechanisms that contribute to the valve’s mechanical properties. These include collagen cross-links, collagen crimp, and layer corrugations. Collagen cross-links function to increase the strength of aligned collagen. In the circumferential direction, the number of collagen cross-links per collagen molecule directly corresponds to the elastic modulus. However, this relationship does not apply to the radial direction, possibly due to the presence of elastin [31]. When there is no mechanical stress on the leaflet, the fibrosa exists as a number of folds in the radial direction known as corrugations. Large extensibility is achieved through these collagen corrugations in combination with collagen crimp. When stress is applied to the leaflet, initial extension is accomplished by straightening of the collagen crimp. Further stress causes the corrugations to unfold in the radial direction [30]. Together, collagen crimp and corrugations allow the fibrosa to extend further in the radial direction when compared to the circumferential direction.
Throughout the lifetime of the aortic valve, collagen synthesis and degradation are responsible for maintaining adequate valve strength and extensibility. Constant turnover of collagen allows the valve to adapt to regional changes in tensile strength.
Aside from its mechanical functions, collagen has been shown to regulate VIC phenotype and calcification potential.
Elastic fibers are macromolecular assemblies of several different molecules. The majority of the elastic fiber consists of elastin, an insoluble protein generated by lysyl oxidase crosslinking of soluble tropoelastin monomers (approximately 70 kDa). The elastin tends to be located in the inner core of the elastic fiber and is surrounded by a fine mesh of microfibrils. These microfibrils are predominantly fibrillin-1, but to a lesser extent Fibrillin-2. Microfibril associated glycoproteins (MAGPs), fibulins, and other proteins are also present in the microfibrillar sheath [38]. At the light microscope level, one can observe the fine elastic fibers by histological staining with Voerhoff’s stain or related methods, but when tissue sections are viewed with transmission electron microscopy, there is a clear distinction between the electron-dense elastin core and the microfibrillar sheath [39].
The unique mechanical behavior of the elastic fiber is conferred primarily by the mechanical function of elastin and fibrillin. Crosslinked elastin is remarkable for its ability to undergo high amounts of deformation when subjected to small amounts of load, as well as to recoil back to its original dimensions, when the load is removed, with very little loss of energy. Fibrillin-1, the most widely studied of the microfibrillar components, is also highly extensible. Fibrillin and the other microfibrillar components also coordinate, in a complicated manner still under investigation [38], to aid in the cross-linking of tropoelastin and assemble the final elastic fiber. Interestingly, fibrillin is not always associated with elastic fibers. Fibrillin can often be found by itself, in which it may independently function as a mechanical, load-bearing but highly extensible scaffold [40]. Numerous domains in fibrillin exist for binding integrins, heparan sulafate proteoglycans, and growth factors, which point to substantial roles for alone fibrillin and mature elastic fibers in mediating cell signaling and adhesion [41].
In semilunar heart valves, elastin is found primarily within the ventricularis layer on the inflow side of the leaflet, but is also abundant in the middle spongiosa layer. A thin, frequently imperceptible layer of elastic fibers, the aterialis, is found atop the collagen-rich fibrosa layer. These elastic fibers merge with the intima of the adjacent arterial well, but the overall function of the arterialis has not been well characterized [42].
In the ventricularis, elastic fibers are present in dense and continuous sheets across the whole of the leaflet. These fiber sheets are the most significant contributor to the mechanical properties of the ventricularis [6,30], which can be demonstrated when all ECM components but elastin are removed when using NaOH digestion. After this treatment, the digested ventricularis matches the mechanical behavior of the undigested ventricularis radially, indicating a strong presence of elastin in the radial direction [30]. The elastic fibers within the ventricularis undergo considerable, continual stretch from the initial stage of closure, when blood flow vortices are starting to push the leaflets towards the valve orifice, to the final coapted position of the leaflets. The extension of these elastic fibers accommodates the unfolding of the fibrosa layer, which is normally corrugated in the unloaded position. During this unfolding process, the elastic fibers are bearing the loading of the entire leaflet [43]. Even at high strains, when the collagen in the fibrosa is considered to dominate mechanical properties, the elastin in the ventricularis still plays a significant role. This effect was shown when separated ventricularis was preloaded to mimic its intact configuration; the separated ventricularis was shown to bear load before the separated fibrosa [44]. It has been speculated that this response acts as a safety mechanism to prevent radial overextension of the aortic valve leaflet. Then, when the pressure across the valve is reduced, the elastic fiber sheet in the ventricularis recoils and retracts the leaflets back toward the annular attachment to the arterial wall, a process that involves the re-folding of the corrugations in of the fibrosa. This action restores the original shape and orientation of collagen quickly and consistently to prepare for the next cycle of valve closing. Although the elastic sheet in the ventricularis has fibers that are also oriented circumferentially as well as radially, elastin does not appear to play an important role in the mechanical behavior of the leaflet in the circumferential direction. Valve leaflets exposed to cyclic circumferential stretch and cultured under flow for 48 hours maintained a constant concentration of elastic, suggesting that elastogenesis was not activated during the duration of stretch [45]. However, it is speculated that connections between the elastic fiber and collagen networks facilitate the radial extensibility of the ventricularis layer and the overall leaflet [43]. There are also some elastic fibers in the fibrosa, which surround and connect the collagen fibers, thus preserving collagen crimp and the characteristic corrugated nature of the fibrosa [6,46,47].
The elastic fiber structure in the spongiosa has been characterized much less than in the ventricularis, partly due to the difficulty in isolating its structure from the rest of the leaflet [30]. This elastic structure, however, has been observed during microdissection separating the leaflet [30,48], with scanning electron microscopy (SEM) [6,46], micro-computed tomography (micro-CT) [6], immunohistochemistry (IHC) [25], and autofluorescence imaging [49,50], which all have shown a fine elastic fiber network emanating from the ventricularis and connecting to the fibrosa. We have recently reported that the thickness of this elastic fiber network in the spongiosa is significantly thicker in the hinge and coaptation region than in the belly region of the aortic valve leaflet [8]. We also found two distinct patterns of spongiosa elastic fibers within the leaflet: (i) a rectilinear pattern in the hinge and coaptation region; and (ii) a radially oriented stripe pattern in the belly. Overall, it is believed that the elastic fibers in the spongiosa contribute to valve function in three ways. First, they connect the elastic fibers in the ventricularis to collagen in the fibrosa, which allows coupling of the mechanics of the two layers and matrix components, while using elastic recoil to exert preload on the fibrosa. Second, they distribute stress between collagen and elastic fibers, particularly at low strains. Third, they passively allow relative movement and shear between the outer layers [5,6,48].
Given the presence of a thick, rectilinearly-arranged structure of elastic fibers in the spongiosa of the hinge and coaptation regions, it is speculated that this elastin structure plays a role in leaflet flexure [5,30]. Flexure of the leaflet towards the outflow direction compresses the fibrosa and applies tension to the ventricularis. Rather than undergoing compression, however, the fibrosa may attempt to buckle separately from the leaflet, thereby exaggerating its corrugated configuration. The leaflet would subsequently bend at the troughs of this corrugation, where the second moment of inertia would be locally reduced, albeit temporarily. Buckling would only occur with shearing between the fibrosa and ventricularis, which is allowed by both the compliant elastic fibers in the spongiosa connecting the two outer layers as well as by GAGs in the spongiosa lubricating the outer layer movement [5,30,51,52]. Recoil from the elastic fibers in the spongiosa would then return the fibrosa to its original configuration so it could undergo the next cycle of loading [5,30]. At the hinge, where bending occurs in the opposite direction, it is speculated that the elastic fiber-rich ventricularis compresses readily without buckling, most likely due to the tensile preload already exerted on the ventricularis, but that leaflet deflection may be limited by the stiff fibrosa, which would not allow the leaflet to bend [4,53]. Limited flexure at the hinge would allow the leaflet to absorb pressure from reverse blood flow in diastole, but prevents distention of the leaflet. Thus, our finding of a thicker spongiosa and elastic fiber structure in flexural regions provides evidence of a significant role for elastin in flexure [8]. In addition, the thick network of elastic fibers that we have observed in the spongiosa of the coaptation region may play a role in dampening vibrations that result from valve closing [5].
Glycosaminoglycans and proteoglycans (GAGs and PGs, respectively) comprise a significant part of the aortic valve leaflets. PGs and GAGs are mainly found in the spongiosa layer of the valve, located between the ventricularis and fibrosa, where they play a vital role in maintaining normal valve function. Previous work has shown that GAGs and PGs serve to not only provide mechanical support to the tissue but also aid in the normal biological functions of the valve [54]. Therefore, it is crucial to fully understand the function of GAGs and PGs in both the normal and possible diseased states of tissues.
GAGs are composed of long and unbranched chains of repeating disaccharides, which consist of a hexosamine and either, depending on the GAG type, uronic acid or galactose. There exist the following families of GAGs with each group being defined by its composition: hyaluronan (HA), heparin, heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), and keratan sulfate (KS) (Table 2) [55–58].
GAGs are primarily formed in the lumen of the Golgi apparatus. The formation process occurs, except in the case of HA, with glycosyltransferases alternatively adding a uronic acid or galactose with a hexosamine to a protein core. The attachment to the protein core varies based on the GAG type. Heparin, HS, CS, and DS are attached to a serine residue, connected to the protein core, via xylose. KS can attach to the protein core either by an asparagine residue at the N-terminus or linked to serine or threonine at the O-terminus. HA does not attach to a protein core. It is synthesized by the addition of sugars to the non-reducing termini of the forming polysaccharide by HA synthase, without a protein backbone. In all cases, modifications can be made to the resulting polysaccharides. Two noteworthy changes include sulfation of the chains and epimerization of the uronic acid. These changes do not occur, however, with HA. Sulfation and epimerization modifications can give a more distinct characteristic to the GAG chains. The epimerization of the uronic acid of CS leads to the production of DS. Epimerization also occurs on heparin and HS. Sulfation can occur in CS, DS, heparin, HS, and KS. N-sulfation takes place in heparin and HS; whereas, O-sulfation can take place in heparin, HS, CS, and DS. In addition to epimerization and sulfation, phosphorylation of the xylose linkage—occurring among CS, DS, heparin, and HS to their respective protein cores—can take place [54,58,59]. Through gel electrophoresis, it has been found that HA comprises approximately half of the total GAG content in aortic valves [60]. It is important to note that all GAGs, with the exception of HA, exist
Hyaluronan | \n\t\t\tGlucuronic | \n\t\t\t- | \n\t\t\tN-acetylglucosamine | \n\t\t
Heparin | \n\t\t\tGlucuronic Iduronic | \n\t\t\t- | \n\t\t\tN-acetylglucosamine | \n\t\t
Heparan sulfate | \n\t\t\tGlucuronic Iduronic | \n\t\t\t- | \n\t\t\tN-acetylglucosamine | \n\t\t
Chondroitin sulfate | \n\t\t\tGlucuronic | \n\t\t\t- | \n\t\t\tN-acetylgalactosamine | \n\t\t
Dermatan sulfate | \n\t\t\tGlucuronic Iduronic | \n\t\t\t- | \n\t\t\tN-acetylgalactosamine | \n\t\t
Keratan sulfate | \n\t\t\t- | \n\t\t\t+ | \n\t\t\tN-acetylglucosamine | \n\t\t
List of glycosaminoglycans and their composition [59]
Proteoglycan structure
PGs are formed when GAGs are added to a protein core through a covalent linkage (Figure 2). During PG synthesis, a protein core moves from the endoplasmic reticulum of a cell to the Golgi apparatus, where GAGs are then added to the protein core [55]. PGs can be found in intracellular organelles, on the cell surface, and in the extracellular matrix (ECM) [59]. PGs found in the ECM can be divided into three categories: PGs found within the basement membrane, hyalectans or PGs that interact with HA and lectins, and small leucine-rich PGs (SLRPs) or PGs that contain a leucine motif and have considerably low molecular weights. These PGs can be further classified by the type of protein backbone they contain, as well as the amount, type, and sulfation pattern of the GAGs that are attached to the backbone. More than thirty PGs have been characterized [61]. For example, well-characterized PGs that exist in cardiovascular tissue include decorin, biglycan, and versican. Decorin and biglycan have a core protein size of 40 kDa and are a part of the SLRP family of PGs. They contain CS and DS GAG chains [61]. Versican is a large, chondroitin sulfate proteoglycan. It interacts with HA, and therefore is a hyalectan PG [62]. Other significant PGs in mammalian tissues include perlecan—a basement membrane protein that contains HS and CS, aggrecan—a hyalectan containing CS, and syndecans—a family of cell surface heparan sulfate proteoglycans containing HS and CS [61].
GAGs, and in turn PGs, have a significant role in aortic valve tissue behavior. GAGs have been shown to enhance the viscoelastic properties of the valve leaflets through binding of water molecules [63]. The sulfation and carboxylation on the GAGs make them highly negatively-charged polysaccharides. This negative charge draws in water molecules. Once the tissue becomes hydrated, it acts like a sponge for the valve leaflets. As noted previously, GAGs and PGs are highly abundant in the middle layer of the aortic valve leaflet. One of the main functions of this cushioned layer, the spongiosa, is to provide a barrier between two other layers, the ventricularis and fibrosa, of the valve. This barrier allows for proper shearing between the layers as well as compressibility of the leaflet without compromising the leaflet’s overall structural or biological integrity when mechanical stimuli are applied to aortic valve leaflets [63,64]. The mechanical competency that GAGs provide is crucial to the aortic valve leaflets. The aortic valve leaflets serve to ensure unidirectional blood flow from the left ventricle to the aorta. In order to guarantee normal blood flow, the leaflets must open and close properly. Therefore, the flexibility that GAGs provide to the leaflet is crucial to the normal valve’s function. In addition, the space that GAGs occupy and form in the matrix serve to organize other molecules within the structure. The structure and hydration that GAGs provide also allow for biological cues to occur within the valve. Moreover, GAGs are known to aid in cell migration, proliferation, act as receptors for signaling molecules, bind growth factors, and serve in the recruitment of various cell types [54].
It is believed that GAGs/PGs likely play an active role in aortic valve tissue disease. Research has shown regional variation of decorin, biglycan, versican and HA in, near, and distal to regions of calcification in diseased aortic valves, suggesting the occurrence of remodeling in the tissue during an unhealthy state [65]. In addition, although the exact causation of calcific aortic valve disease is unknown, it is speculated that it may be due, at least in part, to an inflammatory process [17]. Interestingly, GAGs are thought to play an active role, quite often in the case of cellular injury, in many inflammatory processes for a variety of cell types and have shown to alter in structure and localization in these processes [66]. In addition, some researchers believe that lipid binding due to the unique structure of GAGs may be critical to the accumulation of lipids in calcified aortic valves, a characteristic that is hypothesized to aid in valvular calcification [67]. Although the specific mechanisms underlying calcific aortic valve disease are not quite understood, the complex nature and distinguishable differences of GAGs in both healthy and diseased tissue give rise to the possibility of GAGs being a key factor in valve calcification.
GAGs are very complex disaccharides that highly dictate the behavior of PGs. These polysaccharides are vital in maintaining mechanical, structural, and biological integrity of the aortic valve. Although there is growing interest in further elucidating the role of GAGs in healthy tissues, the exact role of GAGs in diseased aortic valves needs further investigation, as well.
The extracellular matrix of heart valves contain a number of minor components that perform a variety of functions. They are important in valve development, function, and pathology. The study and further characterization of these minor ECM components not only facilitates the development of targeted therapies but would also aid in the microenvironmental mimicry needed for potential tissue engineering applications.
Vitronectin is a glycoprotein that is approximately 75 kDa in size and is present in both serum and the ECM as an adhesive substrate [68]. It is involved in the inhibition of the complement system [68] and is associated with the regulation of hemostasis [69]. Vitronectin also promotes cellular attachment to ECM and is involved in cellular migration [68]. This glycoprotein, along with fibronectin, is found in moderate amounts in aortic, pulmonary, and mitral valves, localizing around valve endothelial cells (VEC) on the inflow layer [25]. In addition, both fibronectin and vitronectin have been shown to associate with collagen fibers in chordae tendinae [70].
Fibronectin is a dimer glycoprotein which consists of two ~250 kDa subunits and is a component of the extracellular matrix [71]. There are many various isoforms of fibronectin, which is the result of alternative mRNA splicing [71]. In addition to being an insoluble ECM component secreted primarily by fibroblasts, soluble fibronectin is also found in the plasma [71]. Fibronectin acts by binding to integrins, collagens, fibrin, and heparin sulfate proteoglycans [71], which allows it to participate in wound healing [72,73] and act as a critical player in embryogenesis [74]. Although not a major ECM component in heart valves, valve interstitial cells (VIC) secrete fibronectin in response to valve damage, providing a means for cell migration [75].
Additionally, fibronectin, along with osteonectin and periostin, confers stiffness to the fibrosa layer [76]. Periostin is a component of the ECM that acts as a ligand for α-V/β-3 and α-V/β-5 integrins and is known to support adhesion and epithelial migration [77]. It is present in the extracellular matrix of several types of tissues and is upregulated in several types of cancers [78]. Recombinant periostin has been shown to promote cardiomyocyte proliferation and angiogenesis after a myocardial infarction [79]. It has been shown previously that periostin plays a role in murine embryonic valve development and remains present in the valves throughout the lifespan even when there is no pathological calcification [80]. A recent study involving chick cardiac development suggests that the presence of periostin in the developing heart may provide a means of organizing other ECM molecules in order to facilitate early epithelial-mesenchymal transition (EMT) [81]. However, the overexpression of periostin and osteopontin can lead to valve calcification.
Osteopontin is a phosphoprotein, meaning that it contains chemically bound phosphoric acid. Originally found in bone, it also contains the arginine-glycine-aspartate (RGD) motif more commonly attributed to fibronectin and is also a constituent of ECM in other tissues [82]. It is secreted by various tissues such as fibroblasts [82] and immune cells, including dendritic cells, macrophages, and neutrophils [83]. Osteopontin is known to interact with various surface receptors that make it a crucial player in bone remodeling [84], wound healing, inflammation, and immune responses [83]. It is also known to be involved in vascular remodeling during endothelial injury [82]. Osteopontin is present in valves calcified as a result of disease as well as in calcified bioprosthetic heart valves [85]. The calcification process of aortic valves closely resembles osteoblast differentiation in regards to expression of genes characteristic of bone formation, such as osteopontin and osteocalcin [86].
Osteocalcin is a small, non-collagenous protein that is considered a late-stage marker for bone formation and is one of a small group of proteins that are osteoblast-specific [87,88]. It is present in general circulation [87] and its capacity for binding hydroxyapatite and calcium suggests that it is largely involved in mineral deposition [88], but it also has recently been shown to act in a hormone-like manner by enhancing insulin secretion [87]. Its traditional role as a product of bone indicates that valve calcification may actually be a result of active bone formation in the valve tissue [86]. This bone formation may be the result of VEGF secretion by endothelial cells during neoangiogenesis occurring in response to inflammation, as seen in rheumatic valve calcification [89]. Additionally, increased serum levels of osteocalcin were shown to be indicative of aortic valve disease in patients [90].
In addition to the matrix proteins, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are also found in heart valves. They assist in tissue development and remodeling and can be used as indicators of disease. It is also believed that the ECM degradation resulting from MMP activity serves to release growth factors bound to ECM components and thus alter the microenvironment chemically, as well as structurally [91]. Calcified leaflets from stenotic valves have been shown to express levels of MMP-2 that are similar to those of normal valves but express higher levels of MMP-3, MMP-9, and TIMP-1 [14]. MMP-1, produced by activated myofibroblasts and macrophages, is also prevalent in calcific aortic valve stenosis and may be related to high TNF-α levels resulting from inflammation [92].
The basement membrane is a myriad of proteins, proteoglycans, and glycoproteins that not only supply a substrate to anchor the valve endothelial cells, but also has a large array of biological activities that regulate spatial organization, sequester growth factors, modulate angiogenesis and migration, and regulate the diffusion of nutrients through it towards the underlying valve interstitial cells [93]. The major constituents of the basement membrane are laminin, perlecan, collagen type IV and VIII, nidogen, and the glycoprotein SPARC (secreted protein, acidic and rich in cysteine). Each of these constituents play a role in the overall function of the basement membrane. In addition, MMPs contribute to the biological activity that occurs within the basement membrane. Understanding basement membrane composition and behavior, during both healthy and diseased states of the aortic valve, may lead to a better understanding of calcific aortic valve disease.
Laminins belong to a family of heterotrimeric glycoproteins composed of combinations of α, β, and γ chains that form a cross-like structure averaging between 400-900 kDa in size [94,95]. Laminins play an integral role in the formation of the supportive ECM network. The unique cross-like shape allows laminin molecules to bind with neighboring laminins and ECM via the three short chains, and use the long alpha chain as a cell anchoring site [96]. In addition to their structural contributions to the basement membrane, laminins are essential for proper biological activity. These glycoproteins have been shown to promote cell adhesion, migration, differentiation, and maintenance of cellular phenotype [94,97,98]. Dysfunction in laminin expression has been linked to diseases with improper tissue formation such as muscular dystrophy, epidermolysis bullosa, and various nephritic syndromes [94,99].
Although laminin is not as ubiquitous as collagen, this basement membrane component has been highly investigated as an ECM substrate for
Perlecan (Pln) is one of the more abundant heparan sulfate proteoglycans and is found in several tissues including in the endochondral barrier in bones [105]; however, it is primarily localized in vascular basement membranes. It has a major role in regulating the development of blood vessels, the heart, cartilage, and the nervous system. Physiologically, perlecan plays a prominent role in regulating cellular proliferation, differentiation, organization, and mediating inflammation [106]. Perlecan derives its functionality from five protein subdomains which share their sequence homology with several other proteins [107]. Domain 1 contains an SEA (Sperm protein, Enteokinase, Agrin) module and three SGD (Ser-Gly-Asp) tripeptide sequences to which three heparan sulfate (HS) glycosaminoglycans attach. These HS can bind and sequester several important growth factors for determining endothelial quiescence in a process known as matricrine signaling. The SEA section is unique to perlecan, and it has no known function other than to influence the O-linked glycosylation of the SGD domain. Interestingly, it has been shown that several factors that determine the activity of these sugar chains vary greatly by the cell source that is producing them [108]. These factors can include the ratio of heparan sulfate to chondroitin sulfate, the length of the chains, and the sulfation level of the chains which all affect how the chains modulate the bioactivity of nearby growth factors. Domain II contains 4 low-density lipoprotein receptor sequences and one immunoglobulin-like repeat. Domain III contains three laminin-like domain modules and eight epidermal growth factor-like repeats. Domain IV, the largest domain, contains many N-CAM-like Ig repeats. Domain V has been demonstrated to be the major cell- binding domain of perlecan due to the laminin and agrin homologies that it contains. Domain V can also be glyocosylated, which can contribute along with domain I to the matricrine signaling capabilities of perlecan, which could potentially contribute to the development of CAVD [109].
Matricrine signaling occurs when the ECM modulates cell behavior by controlling the local levels of growth factor concentrations by sequestering or releasing them when the underlying matrix is intact or degraded, respectively [109]. Proteoglycans, like perlecan, and their GAG chains are the major sites for matricrine signaling due to their heparan sulfate and chondroitin sulfate chains electrostatically binding free growth factors. Their role in the pathology of CAVD is widely unexplored despite their presence in normal valves and their increased production in diseased valves [67]. It is known that PGs and GAGs play an integral role in the progression of atherosclerosis via sequestering of inflammatory molecules and lipids [110–113] and mediating angiogenesis into the vessel supplying an entry way for additional inflammatory entities. Both of these factors are seen histologically in CAVD, but their role is merely speculative at this moment.
Collagens in the basement membrane can form lateral, axial, and linear connections with surrounding ECM. Of the basement membrane collagens, collagen IV (COL IV) is the most abundant and essential for network formation. Only found in basement membrane tissues, COL IV molecules are approximately 400 kDa, and composed of two α1, and one α2 [115–117]. COL IV proteins have many biologically active domains that can influence specific cellular responses, as well as have specific affinities to other molecules such as BMP-4, fibronectin, Von Hippel Lindau protein, and factor IX [115,117]. Mapping of COL IV protein reveals 3 major integrin motifs that are located in strategic regions to promote cell activity or protein degradation when activated [115]. During angiogenesis and tumor invasion, COL IV is degraded by MMP-2 and MMP-9 enzymes to allow for cell migration and infiltration into the matrix. Studies have found that the cleavage sites also overlap with many integrin binding domains such as α1β1, resulting in the availability of αvβ3 integrin binding sites known to promote neutrophil binding [115,118]. Collagen IV networks are highly adhesive to all cells types except erythrocytes [115,119]. Furthermore, cell binding has been found to be enhanced in the presence of various ECM molecules such as perlecan, SPARC, and von Willebrand factor (vWF) [115,118,119]. Interestingly, COL IV also has numerous anti-angiogenic domains that are activated after MMP degradation at the non-collagenous (NC) 1 domain, thereby limiting angiogenesis or migration of endothelial and tumor cells [115]. The changes in COL IV bioactivity depending on the domain region and cleavage state can greatly affect the functionality of surrounding cells. Dysfunctional COL IV expression or mutations in the heterotrimer formation have been found to be extremely detrimental and cause matrix disorders such as Goodpasture’s syndrome or Alport syndrome [94,115]. Therefore, additional studies should be done to investigate how the highly bioactive COL IV meshworks may promote the onset of calcification in valve tissues.
COL VIII has also been found to play a network forming role, maintaining the sheet-like structure ECM, while sequestering various integrin binding sites and growth factors. COL VIII is smaller than COL IV, and can form tetrahedral and hexagonal assemblies [117,118]. Though work on COL VIII in regards to valve tissues has been limited, vascular basement membrane studies have found that COL VIII plays a large role in interacting with subendothelial cells such as smooth muscle cells and fibroblasts. In vitro, COL VIII promotes fibroblast proliferation and migration [114]. Furthermore, COL VIII may be linked to atherogenesis, a pathology similar to CAVD, as its expression in cells is upregulated during vessel injury [114,120]. This collagen has even been found to interact with elastic fibers in liver tissues, suggesting it may have a bridging function between the basement membrane components and subendothelial ECM [118]. Therefore, COL VIII could play an integral role in mediating valve interstitial and endothelial cell communication. Recent studies have found after enzyme cleavage at the NC1 domain, the resulting C-terminal fragment known as vastatin will prevent endothelial cell proliferation and induce cell apoptosis [120]. While some work has investigated using vastatin as an anti-angiogenic agent, further studies are needed to elucidate how it may affect the functionality of surrounding cells and ECM, especially in older valve tissue.
Similar to perlecan, nidogen is a 150 kDa glycoprotein that has sequence homologies with other basement membrane proteins. It consists of two amino (G1, G2) and one carboxyl (G3) terminal globular domains that are connected by a rod domain composed primarily of endothelial growth factor repeats [121]. Nidogen binds collagen type IV, perlecan, and laminin. This binding contributes to the hypothesis that nidogen is important in basement membrane assembly; although some recent animal studies have demonstrated that nidogen may not be necessary for basement membrane formation [121]. The role of nidogen in CAVD is unexplored, but it may play a role in maintaining valvular basement membrane functionality by regulating infiltration of inflammatory agents [93].
SPARC positive neovascularisation is a documented histological change in CAVD [122]. Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, is a small basement membrane protein. It interacts with cells, binds to other members of the basement membrane, growth factors, various proteases, and is found in newly developing neovessels. Intact SPARC protein inhibits cellular proliferation and has anti-angiogenic activity in vitro [123]. However, enzymatic degradation of SPARC can release matricryptic fragments with the KGHK motif that may induce angiogenic activity both
In conclusion, the last several years have witnessed significant acceleration in the number of studies characterizing specific types of extracellular matrix in heart valves, although there is still much to be learned. The basement membrane of heart valves, and its role in regulating valvular endothelial cell function, are particularly understudied. The broad scope of cell-matrix and matrix-matrix interactions within heart valves, and how these are regulated by the local, dynamic signaling environment, is another subject that merits further investigation. We expect that insights gained from these research endeavors will lead to novel treatments for valve diseases in the future.
As already mentioned in other chapters, milk whey is a liquid by-product generated after obtaining cottage cheese or curd (proteins coagulated by acid and heat), also known as cheese whey, that for many years has been considered a waste product, and sent to bodies of water, soil, and sewage systems. However, currently it is used due to its multiple nutritional and functional properties [1].
In Mexico, the production of whey in 2016 was estimated at 1,010,000 tons, 47% of which was discharged to soil, drains, and bodies of water. Despite the fact that multiple uses have been found to cheese whey, this has become a serious environmental problem [2]. This by-product is composed of water, lactose, proteins, peptides, fat, and mineral salts [3]. One of the peptides of interest is glycomacropeptide (GMP), which is obtained after the coagulation of milk κ-casein during cheese production and represents 15–20% (w/w) of the total proteins contained in milk whey [4].
GMP is the C-terminal fragment released by the proteolytic action of the endopeptidase chymosin (renin) on κ-casein during the initial stages of cheese making, or by the action of pepsin during the gastric digestion. κ-casein is hydrolyzed at phenylalanine105-methionine106 bond, forming two very different polypeptides. One is called para-κ-casein (residues 1–105), and it is slightly cationic at pH 6.6, hydrophobic and poorly soluble, which remains in cheese curd; and the other is GMP (residues 106–169), that is strongly polar so diffuses into the aqueous phase, being eliminated during the draining with the cheese whey (as reviewed in [5]).
GMP has 64 amino acid residues, with an isoelectric point (pI) between 4 and 5. Fifty percent of GMP is deglycosylated and is known as caseinomacropeptide (CMP) [5]. However, milk GMP can present different types of carbohydrates, such as: sialic acid, galactosyl, and N-acetylgalactosamine, which generate different glycosylated forms of the molecule. GMP is rich in amino acids such as proline, glutamine, serine, and threonine, but deficient in tryptophan, tyrosine, phenylalanine, and cysteine. The absence of aromatic amino acids in its primary structure causes that GMP does not present absorption at the wavelength of 280 nm. However, GMP can be detected at wavelengths between 205 and 226 nm and absorption differences between 210 and 280 nm are used for the characterization of GMP (as reviewed in [5]). The composition of GMP can be variable and depends on the source of serum and the fractionation technology used in its isolation [3] (Figure 1).
Primary structure of bovine GMP variant A and B, where ● indicates its three phosphorylation sites and ▲ the most important glycosylation sites. Modified from Thomä-Worringer et al. [
As reviewed by Neelima [7], the three-dimensional structure of GMP cannot be evaluated due to its crystallization which is not possible, so it can only be seen from a purely theoretical approach. GMP is a peptide that does not possess defined secondary and tertiary structure. However, three-dimensional structure of GMP has been predicted by means of protein modeling and shows that a large part of the peptide has a strong negative charge, whereas there are three small domains with a positive charge at the N-terminal end. At pH 7.0, its mean value of the hydropathy is −0.322, and GMP is more hydrophilic than hydrophobic. The hydropathy value decreases when glycosylation of GMP increases, due to the greater amount of sialic acid residues.
The use of GMP is growing, since it is a bioactive peptide with unique nutritional and nutraceutical properties. Many biological activities of GMP have been reported, highlighting antimicrobial, anticariogenic, gastric acid inhibitory, cholecystokinin (CCK) releasing, prebiotic, and immune modulatory. Of particular interest is GMP’s capacity to modulate the immune response, due to its potential use in treatment or prevention of different immunopathologies.
One of the first antimicrobial effects observed in GMP was due to its ability to bind cholera toxin and
There are several
In association with this antimicrobial effect, an anticariogenic activity to GMP has been demonstrated. Firstly,
Several studies have related GMP with the inhibition of gastric secretion. First ones were mostly developed using dogs by a group of Russian researchers. The first evidence that GMP inhibits gastric secretion was showed by Shlygin and co-workers [18] using gastrin to evoke it. Subsequent works demonstrated similar effect using different gastric secretion stimulants [19]. Some years later, it was proposed that this inhibitory effect was caused by a GMP fragment rather than the whole molecule [20, 21]. Later, injecting dogs with a protein fraction obtained from the gastric content of unweaned rats, it was observed an inhibition in dog gastric secretion to a food stimulus [22]. This inhibitory action was similar to that induced by GMP in dogs. GMP was also demonstrated to inhibit gastric motility after its intravenous injection in dogs [23]. All these experiments point out that at physiological conditions GMP may be playing a crucial role in the preservation of active milk proteins in newborn animal during natural breast feeding. In addition to dogs, other experimental models such as rats, pigs, and calves and also isolated organs were used to demonstrate that GMP induces gastric secretion inhibition in association with a decrease in blood of some regulatory digestive hormones, as gastrin and CCK (as reviewed in [24]). However, variations in used gastric stimuli, GMP dose, and origin, via of administration and experimental approach may be the cause of the differences in the reported intensity to this GMP activity.
Related with the effect of this bioactive peptide on digestive hormones, GMP has also been associated with appetite control. Several
For many years, the prebiotic properties of GMP have been discussed. The first evidence that GMP might possess prebiotic activity arose with the bifidobacterial growth promoting effect of human’s colostrums and milk by
In the last years, several research groups have demonstrated that oral treatment with GMP modifies
GMP has been shown to modulate the immune response in a number of different ways. First, we summarize literature reports about regulatory activity of GMP on immune cells demonstrated by
In relation to the immunomodulatory effects of GMP on immune cells, different
On the other hand, GMP is also able to downregulate dendritic cell response to LPS by inducing a slight but significant decrease in the production of IL-6, IL-1β, and TNF-α, but without changing the production of IL-12 and IL-10 [49]. Strikingly, the regulatory effect of GMP on neutrophils is the opposite, as it improves proliferation and phagocytic activity of the human macrophage like cells U937 [52]. However, the observation that both polypeptide and carbohydrate portions are essential for GMP biological effects is reinforced in this study, as peptides of pepsin-digested GMP and sialic acid-rich GMP fractions significantly enhanced cell proliferation and phagocytic activities stimulated by non-digested or asialo-GMP on U937 cell. Also, an upregulatory effect of GMP on production of IgA by LPS-stimulated splenocytes has been reported, being correlated with an increase in the population of IgA positive cells [53].
There are several studies that analyze the immunomodulatory activity of GMP on immune response when it is orally administered to experimental animals. In the context of splenocytes response to mitogens, two
The effect of orally administered GMP on humoral immunity has also been studied. Mice fed with GMP have shown suppressed levels of specific IgG to dietary and injected antigens, with no change in IgM, IgA, and IgE antibody response [54]. In this regard, a recent study showed that oral administration of GMP to mice resulted in a greater number of IgA positive plasma cells in the intestinal lamina propria [56]. All these results [54, 56] plus
Martínez-Augustin and co-workers [57, 58] have studied the immunomodulatory action of GMP in experimental models of intestinal inflammation. They have demonstrated that GMP administered orally to rats exerts an anti-inflammatory effect in ileitis and colitis induced with trinitrobenzenesulfonic acid (TNBS); said anti-inflammatory effect shows a degree of efficacy similar to that of sulfasalazine, a drug widely used in the treatment of inflammatory bowel disease. GMP was shown to protect rats from TNBS-induced colonic and ileal inflammatory damage, by reducing the damage score and the extent of necrosis, and also by diminishing the increased alkaline phosphatase colonic activity and inducible oxide nitric synthase expression. IL-1β and IL-1ra messenger RNA levels were significantly decreased in colon as a consequence of GMP administration; and myeloperoxidase activity and levels of IL-1β and IL-17 were decreased in ileum. Initially, the authors assumed that the action mechanism of GMP was not related to anti-oxidative activity or to regulatory cell induction, as glutathione or TGF-β levels in colon and Foxp-3 in ileum were not affected [57, 58]. However, when GMP was orally administered to rats, an increase on Foxp3 expression in spleen cells was observed, although secretion of cytokines by
In recent years, a Mexican laboratory led by Salinas [55, 59, 60, 61] has focused on the study of the immunomodulatory activity of GMP in experimental allergy models. They found that oral administration of GMP to rats before and during sensitization with allergen significantly reduces the level of allergen-specific IgE in serum, and also decreases the proliferative response and the production of IL-13 by splenocytes stimulated by the allergen [55]. Treatment of animals with GMP also protected them from systemic anaphylaxis as GMP administration increased survival rates and lessened signs of severity of anaphylactic shock. Moreover, GMP reduced the intensity of urticarial inflammatory reaction when sensitized animals were intradermically challenged with the allergen [55]. With these results, it was demonstrated the immunomodulatory properties of GMP on allergic sensitization and its beneficial effect on clinical signs associated to early-phase allergic reaction. Then, they investigated whether GMP may impact on late-phase and chronic inflammatory allergic reactions, using two experimental models that after repetitive exposure to allergens displayed local recruitment and activation of immune cells with persistent production of inflammatory mediators in affected tissues, together with substantial changes in the extracellular matrix and alterations in structural cells [62]. Specifically, they used experimental models of asthma and atopic dermatitis prophylactically administered with GMP, that is to say, prior to and during pathology establishment. As expected, GMP intake resulted in reduction of IgE titers in serum. In addition to this, in asthma model, GMP substantially decreased blood eosinophilia and suppressed the recruitment of inflammatory cells to the bronchoalveolar compartment. GMP also inhibited eosinophils infiltration, goblet cells hyperplasia, and collagen deposit in lung tissue [59]. Equivalent results were obtained in allergen-induced atopic dermatitis model, where GMP reduced the intensity of cutaneous inflammatory process and edema, abolished pruritus, and reduced eosinophils recruitment and mast cells hyperplasia in dermis [60]. In both models, expression of IL-5 and IL-13 was markedly inhibited in lung and skin, while expression of IL-10 was increased. Their research then turned to the mechanism by which GMP modulates the allergic response. They demonstrated that GMP administration increases the amount of
Finally, there are few studies that analyze the role of GMP on cancer. In a rat model of pharmacological-induced colorectal cancer, oral administration of 100 mg/kg of GMP decreased the number of aberrant crypt foci although no effect was observed at doses of 10 and 50 mg/kg. On the other hand, there was no change in methylation and expression level of p16 and MUC2, two tumor suppressor genes [63]. Additionally, through an
Although more studies are needed in relation to some biological activities, current results propose GMP as a good candidate to be used as a functional ingredient in food industry.
Today, one of the objectives of the food industry is the development of novel food products with beneficial properties for health. For its different health benefits, GMP can be used in therapeutic and dietary foods, or as a functional ingredient in various special products, like oral care products.
It is crucial to demonstrate that GMP is hypoallergenic to be used in food compositions. In this regard, Takahashi and collaborators patented a food composition that contained GMP and a mixture of free amino acids (leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, tryptophan, arginine, histidine, and glycine) [65]. The composition presented good taste, good absorption and digestion properties, and a high nutritional value. They demonstrated that this composition was hypoallergenic, as after repeated injections of the GMP composition together with an adjuvant used to induce experimental allergy in mice, no antibody against GMP was detected in serum by Ouchterlony. Although this method is not very accurate, GMP hypoallergenicity was later corroborated by Milkkelsen and collaborators using ELISA test to show absence of specific antibodies in mice after being sensitized both systemically or orally with GMP [66].
Due to the particular amino acid composition of GMP, devoid of aromatics amino acids (phenylalanine, tryptophan, and tyrosine), it can be used for special diets of people suffering from phenylketonuria (PKU), being an adequate choice as a source of proteins [67]. On the other hand, GMP has low amount of methionine but high amount of branched chain amino acids (valine and isoleucine), which makes this peptide an excellent candidate to be used for the control of liver diseases, as this type of amino acids are good as caloric sources [68]. There is a patent to use of GMP to improve female’s health [69]. The inventors claim that administration of a composition comprising GMP can improve the health of the females. They used murine models fed with GMP composition and showed that females decreased final fat mass and percent body fat, when comparing with females that received a diet based on caseins or free amino acids as source of proteins. In relation to bone characteristics, femur length was larger in GMP administered mice, although only females showed less femoral weakness and greater bone mineral content and density as compared to those fed with amino acids or casein diets, respectively.
As previously mentioned, research results suggest that GMP has an effect on the feeling of fullness but this does not translate into a lower food intake [27, 28]. For an application in food intake regulation and in potentially body weight management, more work is required. Understanding dose, timing, and delivery mode, including food form and composition, in relation to the pattern of release of CCK, is needed for the use of GMP as appetite suppressant [70].
GMP has physicochemical properties that make it attractive for use as an additive in food products. According to studies on the functional properties of GMP, it can act as an emulsifier, foaming, and gelling agent.
GMP as an emulsifier presents stability to pH variations, which is attractive for foods that undergo pH changes during their process, such as the case of fermented milk products [71]. The best emulsifying capacity was obtained at alkaline pH. However, it has been observed that emulsions with GMP as emulsifying agent are not stable during storage when they have received thermal treatment [72]. Besides, GMP modified covalently with disaccharides or fatty acids can present an improved function and even increase its biological activity [73, 74]. Therefore, in order to modify the emulsification activity of GMP, this peptide has been conjugated with other molecules such as lactose [73] and fatty acids [74]. The conjugation of GMP with lactose was carried out through the reaction of Maillard, and this conjugate showed a better emulsifying capacity without significantly reducing the solubility of GMP [73].
Currently, foams have many industrial uses of great importance in the production of beer, soaps, whipped cream, shaving cream, aerosols, etc. The formation of a foam requires the participation of a surfactant capable of diffusing to the air/water interface to lower the surface tension. GMP complies with this property, although the foams formed with GMP are stronger or more stable when combined with other foaming proteins [75, 76]. In order to improve the foam properties of the proteins, synergistic mixtures of biopolymers and pH variations have been made that can modify their charge and, consequently, their foam ability. In relation to this, by combining sodium caseinate with GMP, synergistic interactions take place between these molecules on foaming and on stability at pH 5.5 [77]. Non-glycosylated GMP has better foaming properties than glycosylated GMP [78]. This is due to the glycosidic structures favor a combination of hydrophilic and electrostatic effects, which prevents an orderly adsorption of the glycosylated GMP molecules at the air/water interface; whereas, non-glycosylated GMP forms a very stable network at the interface.
On the other hand, gels are semi-solid systems that consist of a network of solids (three-dimensional network of polymers) with an inside trapped-liquid. They are of great importance in food and pharmaceutical industry as many gelled products are manufactured throughout the world (gummies, gelatins, jelly jams, bakery fillings, and therapeutic or cleaning agents). Generally, gelling agents are proteins and polysaccharides. Gelling properties of GMP has been studied and it is known that its gelation depends on pH and temperature, reporting that even aqueous solutions with low GMP amounts can be gelled at pH below 4 [79]. Besides, GMP can potentiate gellying capacity of other substances. Thus, by fermenting goat milk to which GMP was added, a more ordered and structured gel was obtained, in addition to obtaining a better elasticity in it, as compared to that obtained when whey protein concentrate was added [80]. The influence of GMP on the gelation made by gelatin has also been studied and when these two compounds are mixed, lower concentration of both substances are need to get a gel as compared with the ones need when they are used separately [81]. This synergistic effect in gelation is very important in the food industry for the preparation of desserts and foods based on gels.
Dental caries is one of the chronic diseases that most often affect humans. Due to the anticariogenic and remineralization properties demonstrated to GMP and previously reviewed in biological activities section, nowadays GMP is being incorporated to some oral care products [15, 16, 17].
One of the problems presented by the dairy industry is the adulteration of milk with whey cheese, which is very cheap and not detected by sensorial tests. Cheese whey does not cause harm to health, however, it affects milk-derived products manufacturers financially and can affect the consumers nutritionally, so the addition of cheese whey is considered a fraud. Due to GMP present in cheese whey, the detection of this peptide may indicate the addition of cheese whey to milk. Some of the methods that detect GMP as an indicator of the presence of cheese whey are described below.
High performance liquid chromatography (HPLC) has been widely used to identify GMP as indicative of milk adulteration with cheese whey. In order to carry out the analysis, it is necessary to pre-treat the samples with TCA to precipitate proteins that can interfere (k-casein) and to concentrate GMP [86]. Similarly, a rapid and sensitive HPLC method on a gel permeation column was developed to detect GMP to follow the hydrolysis of k-casein by chymosin in milk [87]. The only pretreatment given to samples was addition of TCA (final concentration 8%) to precipitate the interfering caseins and whey proteins. This method was widely used by several researchers to analyze different samples, such as skimmed milk powder [88]. Cation-exchange chromatography has also been used to detect GMP, previously removing caseins from whey samples by precipitation with HCl at pH 4.6, neutralizing with TCA at 2–8% and analyzing supernatants [89]. On the other hand, a Reversed-Phase HPLC (RP-HPLC) method was developed and validated to separate and quantify GMP and was demonstrated to be precise, sensitive, and reliable [90]. The determinations were performed in the linear range of 15–200 μg/mL and the detection limit was 2 μg/mL. The method was applied to the analysis of rennet and acid whey, whey protein concentrates produced by the dairy industry, and also for the detection of rennet whey in powdered milks.
The European Commission uses two methods to detect the presence of cheese whey in milk: a gel permeation chromatography and subsequently a RP-HPLC as a confirmatory test [91]. However, it has been shown that the sensitivity of this method is affected by the presence of acidified rennet whey, which makes it difficult to detect the addition of whey [92]. Besides, the HPLC methodology used to analyze compounds like GMP in dairy products usually includes extractions with solvents, sample’s preparation require a lot of time and reactives, the equipment is very sophisticated and demands trained personal.
Spectroscopy has also been used to detect GMP. The medium infrared spectroscopy (MIR) was used to analyze milk powder in order to detect GMP as adulteration parameter. Although this method is fast, it is not widely used because derived spectra are not very easy to interpret, in addition to its high cost [93]. On the other hand, by liquid chromatography/electrospray coupled to mass spectrometry, milk products were analyzed and it was able to quantify GMP from concentration of 10 pmol, although the method was not used to detect milk adulteration [94].
Immunoassays are analytical methods of great application in the food area, and have the advantages that they are quick, sensitive, and that the sample to be analyzed requires little or no treatment. Several immunochemical methods have been developed in order to identify and quantify GMP in milk. Firstly, it is necessary to produce antibodies against GMP and later, these antibodies can be used for the development of the different immunochemical methods that detect it. Some of these assays are described below:
In summary, different techniques and methods have been developed and used to detect GMP as an index of adulteration of milk with cheese whey. Some of them can also be used to quantify GMP in food products. The aim of this area of research is to achieve one that bring together being cheap, fast, easy to develop, and to interpret the results, with high sensitivity and a limited sample processing. These characteristics will allow people to use them at the time and place of milk reception.
GMP possesses several nutritional and health promoting properties. Among them, it exerts important modulatory effects on the immune system that are beneficial in a number of different inflammatory conditions. GMP immune response mechanism of action might be mediated by increasing healthy intestinal microbiota, by inhibiting splenocyte proliferation, by promoting both local and systemic regulatory environment, and also by directly modulating immune cell functions. More research is needed to support these findings, as we cannot exclude a possible effect of products derived from GMP digestion on
We appreciate the support given to the Autonomous University of Aguascalientes for the publication of this chapter.
Authors declare that there is no conflict of interest between the authors of the chapter entitled: “Glycomacropeptide: Biological activities and uses.”
As an Open Access publisher, IntechOpen is dedicated to maintaining the highest ethical standards and principles in publishing. In addition, IntechOpen promotes the highest standards of integrity and ethical behavior in scientific research and peer-review. To maintain these principles IntechOpen has developed basic guidelines to facilitate the avoidance of Conflicts of Interest.
",metaTitle:"Conflicts of Interest Policy",metaDescription:"As an Open Access publisher, IntechOpen is dedicated to maintaining the highest ethical standards and principles in publishing. In addition, IntechOpen promotes the highest standards of integrity and ethical behavior in scientific research and peer-review.",metaKeywords:null,canonicalURL:"/page/conflicts-of-interest-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"In each instance of a possible Conflict of Interest, IntechOpen aims to disclose the situation in as transparent a way as possible in order to allow readers to judge whether a particular potential Conflict of Interest has influenced the Work of any individual Author, Editor, or Reviewer. IntechOpen takes all possible Conflicts of Interest into account during the review process and ensures maximum transparency in implementing its policies.
\\n\\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
\\n\\nA Conflict of Interest can be identified at different phases of the publishing process.
\\n\\nIntechOpen requires:
\\n\\nCONFLICT OF INTEREST - AUTHOR
\\n\\nAll Authors are obliged to declare every existing or potential Conflict of Interest, including financial or personal factors, as well as any relationship which could influence their scientific work. Authors must declare Conflicts of Interest at the time of manuscript submission, although they may exceptionally do so at any point during manuscript review. For jointly prepared manuscripts, the corresponding Author is obliged to declare potential Conflicts of Interest of any other Authors who have contributed to the manuscript.
\\n\\nCONFLICT OF INTEREST – ACADEMIC EDITOR
\\n\\nEditors can also have Conflicts of Interest. Editors are expected to maintain the highest standards of conduct, which are outlined in our Best Practice Guidelines (templates for Best Practice Guidelines). Among other obligations, it is essential that Editors make transparent declarations of any possible Conflicts of Interest that they might have.
\\n\\nAvoidance Measures for Academic Editors of Conflicts of Interest:
\\n\\nFor manuscripts submitted by the Academic Editor (or a scientific advisor), an appropriate person will be appointed to handle and evaluate the manuscript. The appointed handling Editor's identity will not be disclosed to the Author in order to maintain impartiality and anonymity of the review.
\\n\\nIf a manuscript is submitted by an Author who is a member of an Academic Editor's family or is personally or professionally related to the Academic Editor in any way, either as a friend, colleague, student or mentor, the work will be handled by a different Academic Editor who is not in any way connected to the Author.
\\n\\nCONFLICT OF INTEREST - REVIEWER
\\n\\nAll Reviewers are required to declare possible Conflicts of Interest at the beginning of the evaluation process. If a Reviewer feels he or she might have any material, financial or any other conflict of interest with regards to the manuscript being reviewed, he or she is required to declare such concern and, if necessary, request exclusion from any further involvement in the evaluation process. A Reviewer's potential Conflicts of Interest are declared in the review report and presented to the Academic Editor, who then assesses whether or not the declared potential or actual Conflicts of Interest had, or could be perceived to have had, any significant impact on the review itself.
\\n\\nEXAMPLES OF CONFLICTS OF INTEREST:
\\n\\nFINANCIAL AND MATERIAL
\\n\\nNON-FINANCIAL
\\n\\nAuthors are required to declare all potentially relevant non-financial, financial and material Conflicts of Interest that may have had an influence on their scientific work.
\\n\\nAcademic Editors and Reviewers are required to declare any non-financial, financial and material Conflicts of Interest that could influence their fair and balanced evaluation of manuscripts. If such conflict exists with regards to a submitted manuscript, Academic Editors and Reviewers should exclude themselves from handling it.
\\n\\nAll Authors, Academic Editors, and Reviewers are required to declare all possible financial and material Conflicts of Interest in the last five years, although it is advisable to declare less recent Conflicts of Interest as well.
\\n\\nEXAMPLES:
\\n\\nAuthors should declare if they were or they still are Academic Editors of the publications in which they wish to publish their work.
\\n\\nAuthors should declare if they are board members of an organization that could benefit financially or materially from the publication of their work.
\\n\\nAcademic Editors should declare if they were coauthors or they have worked on the research project with the Author who has submitted a manuscript.
\\n\\nAcademic Editors should declare if the Author of a submitted manuscript is affiliated with the same department, faculty, institute, or company as they are.
\\n\\nPolicy last updated: 2016-06-09
\\n"}]'},components:[{type:"htmlEditorComponent",content:"In each instance of a possible Conflict of Interest, IntechOpen aims to disclose the situation in as transparent a way as possible in order to allow readers to judge whether a particular potential Conflict of Interest has influenced the Work of any individual Author, Editor, or Reviewer. IntechOpen takes all possible Conflicts of Interest into account during the review process and ensures maximum transparency in implementing its policies.
\n\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
\n\nA Conflict of Interest can be identified at different phases of the publishing process.
\n\nIntechOpen requires:
\n\nCONFLICT OF INTEREST - AUTHOR
\n\nAll Authors are obliged to declare every existing or potential Conflict of Interest, including financial or personal factors, as well as any relationship which could influence their scientific work. Authors must declare Conflicts of Interest at the time of manuscript submission, although they may exceptionally do so at any point during manuscript review. For jointly prepared manuscripts, the corresponding Author is obliged to declare potential Conflicts of Interest of any other Authors who have contributed to the manuscript.
\n\nCONFLICT OF INTEREST – ACADEMIC EDITOR
\n\nEditors can also have Conflicts of Interest. Editors are expected to maintain the highest standards of conduct, which are outlined in our Best Practice Guidelines (templates for Best Practice Guidelines). Among other obligations, it is essential that Editors make transparent declarations of any possible Conflicts of Interest that they might have.
\n\nAvoidance Measures for Academic Editors of Conflicts of Interest:
\n\nFor manuscripts submitted by the Academic Editor (or a scientific advisor), an appropriate person will be appointed to handle and evaluate the manuscript. The appointed handling Editor's identity will not be disclosed to the Author in order to maintain impartiality and anonymity of the review.
\n\nIf a manuscript is submitted by an Author who is a member of an Academic Editor's family or is personally or professionally related to the Academic Editor in any way, either as a friend, colleague, student or mentor, the work will be handled by a different Academic Editor who is not in any way connected to the Author.
\n\nCONFLICT OF INTEREST - REVIEWER
\n\nAll Reviewers are required to declare possible Conflicts of Interest at the beginning of the evaluation process. If a Reviewer feels he or she might have any material, financial or any other conflict of interest with regards to the manuscript being reviewed, he or she is required to declare such concern and, if necessary, request exclusion from any further involvement in the evaluation process. A Reviewer's potential Conflicts of Interest are declared in the review report and presented to the Academic Editor, who then assesses whether or not the declared potential or actual Conflicts of Interest had, or could be perceived to have had, any significant impact on the review itself.
\n\nEXAMPLES OF CONFLICTS OF INTEREST:
\n\nFINANCIAL AND MATERIAL
\n\nNON-FINANCIAL
\n\nAuthors are required to declare all potentially relevant non-financial, financial and material Conflicts of Interest that may have had an influence on their scientific work.
\n\nAcademic Editors and Reviewers are required to declare any non-financial, financial and material Conflicts of Interest that could influence their fair and balanced evaluation of manuscripts. If such conflict exists with regards to a submitted manuscript, Academic Editors and Reviewers should exclude themselves from handling it.
\n\nAll Authors, Academic Editors, and Reviewers are required to declare all possible financial and material Conflicts of Interest in the last five years, although it is advisable to declare less recent Conflicts of Interest as well.
\n\nEXAMPLES:
\n\nAuthors should declare if they were or they still are Academic Editors of the publications in which they wish to publish their work.
\n\nAuthors should declare if they are board members of an organization that could benefit financially or materially from the publication of their work.
\n\nAcademic Editors should declare if they were coauthors or they have worked on the research project with the Author who has submitted a manuscript.
\n\nAcademic Editors should declare if the Author of a submitted manuscript is affiliated with the same department, faculty, institute, or company as they are.
\n\nPolicy last updated: 2016-06-09
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{id:"965887@"},profiles:[],filtersByRegion:[{group:"region",caption:"North America",value:1,count:6601},{group:"region",caption:"Middle and South America",value:2,count:5906},{group:"region",caption:"Africa",value:3,count:2400},{group:"region",caption:"Asia",value:4,count:12541},{group:"region",caption:"Australia and Oceania",value:5,count:1008},{group:"region",caption:"Europe",value:6,count:17561}],offset:0,limit:12,total:null},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"1",sort:"dateEndThirdStepPublish",src:"ECM",topicId:"8,9,10,11,14,15,17,20,22,24"},books:[{type:"book",id:"11554",title:"Information Systems Management",subtitle:null,isOpenForSubmission:!0,hash:"3134452ff2fdec020663f241c7a9a748",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11554.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11546",title:"Smart and Sustainable Transportation",subtitle:null,isOpenForSubmission:!0,hash:"e8ea27a1ff85cde00efcb6f6968c20f8",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11546.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11834",title:"Steppe Geography",subtitle:null,isOpenForSubmission:!0,hash:"363517fa6f079daf94c51ea1b91fed2a",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11834.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11836",title:"Estuary Research",subtitle:null,isOpenForSubmission:!0,hash:"ef822fc9eee5600aeb7e45492e04a6e7",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11836.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11837",title:"The Mediterranean",subtitle:null,isOpenForSubmission:!0,hash:"bbb25987a982d61da4f47fb13614ba3c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11837.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11846",title:"Seabed",subtitle:null,isOpenForSubmission:!0,hash:"1b1698a2d8d36b5ec3571c20486eb2c9",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11846.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11911",title:"Scientometrics",subtitle:null,isOpenForSubmission:!0,hash:"ed74b66a0dc7d009900af198efc6b2e1",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11911.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11913",title:"Scheduling Algorithms",subtitle:null,isOpenForSubmission:!0,hash:"da42ea7b678d715e23ffcae50ae47078",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11913.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11915",title:"Ontology in Computer Science",subtitle:null,isOpenForSubmission:!0,hash:"b52397215f6b5e05a22368f629695704",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11915.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11917",title:"Computational Semantics",subtitle:null,isOpenForSubmission:!0,hash:"bd9343348f2c50dbbc819a0b48a76591",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11917.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11938",title:"Ballistics",subtitle:null,isOpenForSubmission:!0,hash:"9c64ef67aac55216f08c65a2a179835c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11938.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11941",title:"Advances in Turbomachinery",subtitle:null,isOpenForSubmission:!0,hash:"fe2c693976d70c5d0cc5f8003e6e73c5",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11941.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:41},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:12},{group:"topic",caption:"Business, Management and Economics",value:7,count:7},{group:"topic",caption:"Chemistry",value:8,count:17},{group:"topic",caption:"Computer and Information Science",value:9,count:16},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:17},{group:"topic",caption:"Engineering",value:11,count:32},{group:"topic",caption:"Environmental Sciences",value:12,count:7},{group:"topic",caption:"Immunology and Microbiology",value:13,count:11},{group:"topic",caption:"Materials Science",value:14,count:11},{group:"topic",caption:"Mathematics",value:15,count:6},{group:"topic",caption:"Medicine",value:16,count:106},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:2},{group:"topic",caption:"Neuroscience",value:18,count:7},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:11},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:8},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:32},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:106},popularBooks:{featuredBooks:[{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11001",title:"Density Functional Theory",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"82d53383af78ab41eb982086c02fb2bb",slug:"density-functional-theory-recent-advances-new-perspectives-and-applications",bookSignature:"Daniel Glossman-Mitnik",coverURL:"https://cdn.intechopen.com/books/images_new/11001.jpg",editors:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10251",title:"Plankton Communities",subtitle:null,isOpenForSubmission:!1,hash:"e11e441ca2d2d5f631b1b4704505cfb6",slug:"plankton-communities",bookSignature:"Leonel Pereira and Ana Marta Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/10251.jpg",editors:[{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",isOpenForSubmission:!1,hash:"79944fc8fbbaa329aed6fde388154832",slug:"animal-feed-science-and-nutrition-production-health-and-environment",bookSignature:"Amlan Kumar Patra",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10356",title:"Natural Medicinal Plants",subtitle:null,isOpenForSubmission:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",slug:"natural-medicinal-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11752",title:"Natural Drugs from Plants",subtitle:null,isOpenForSubmission:!1,hash:"a0a83c0822608ef7592bf16a5ed0ada4",slug:"natural-drugs-from-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/11752.jpg",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10853",title:"Recent Advances in Polynomials",subtitle:null,isOpenForSubmission:!1,hash:"9e8671bae09ccaa8b8e276c639a737fc",slug:"recent-advances-in-polynomials",bookSignature:"Kamal Shah",coverURL:"https://cdn.intechopen.com/books/images_new/10853.jpg",editors:[{id:"231748",title:"Dr.",name:"Kamal",middleName:null,surname:"Shah",slug:"kamal-shah",fullName:"Kamal Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10676",title:"Recent Applications in Graph Theory",subtitle:null,isOpenForSubmission:!1,hash:"900c60742d224080732bd16bd25ccba8",slug:"recent-applications-in-graph-theory",bookSignature:"Harun Pirim",coverURL:"https://cdn.intechopen.com/books/images_new/10676.jpg",editors:[{id:"146092",title:"Dr.",name:"Harun",middleName:null,surname:"Pirim",slug:"harun-pirim",fullName:"Harun Pirim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10903",title:"Genetically Modified Plants and Beyond",subtitle:null,isOpenForSubmission:!1,hash:"4d7ed4faab99c92cd4d676dc86501df9",slug:"genetically-modified-plants-and-beyond",bookSignature:"Idah Sithole Niang",coverURL:"https://cdn.intechopen.com/books/images_new/10903.jpg",editors:[{id:"90172",title:"Prof.",name:"Idah",middleName:null,surname:"Sithole-Niang",slug:"idah-sithole-niang",fullName:"Idah Sithole-Niang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10904",title:"Fusarium",subtitle:"An Overview of the Genus",isOpenForSubmission:!1,hash:"49d9063e43f94bd1517d65fbc58b93c3",slug:"fusarium-an-overview-of-the-genus",bookSignature:"Seyed Mahyar Mirmajlessi",coverURL:"https://cdn.intechopen.com/books/images_new/10904.jpg",editors:[{id:"100573",title:"Dr.",name:"Seyed Mahyar",middleName:null,surname:"Mirmajlessi",slug:"seyed-mahyar-mirmajlessi",fullName:"Seyed Mahyar Mirmajlessi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10871",title:"Computed-Tomography (CT) Scan",subtitle:null,isOpenForSubmission:!1,hash:"966d8cf74fa27eea1b9cbc9a6ee94993",slug:"computed-tomography-ct-scan",bookSignature:"Reda R. Gharieb",coverURL:"https://cdn.intechopen.com/books/images_new/10871.jpg",editors:[{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",slug:"reda-r.-gharieb",fullName:"Reda R. Gharieb"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11196",title:"New Updates in E-Learning",subtitle:null,isOpenForSubmission:!1,hash:"6afaadf68e2a0a4b370ac5ceb5ca89c6",slug:"new-updates-in-e-learning",bookSignature:"Eduard Babulak",coverURL:"https://cdn.intechopen.com/books/images_new/11196.jpg",editors:[{id:"10086",title:"Prof.",name:"Eduard",middleName:null,surname:"Babulak",slug:"eduard-babulak",fullName:"Eduard Babulak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4387},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",publishedDate:"May 18th 2022",numberOfDownloads:3340,editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11001",title:"Density Functional Theory",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"82d53383af78ab41eb982086c02fb2bb",slug:"density-functional-theory-recent-advances-new-perspectives-and-applications",bookSignature:"Daniel Glossman-Mitnik",coverURL:"https://cdn.intechopen.com/books/images_new/11001.jpg",publishedDate:"May 18th 2022",numberOfDownloads:1845,editors:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10251",title:"Plankton Communities",subtitle:null,isOpenForSubmission:!1,hash:"e11e441ca2d2d5f631b1b4704505cfb6",slug:"plankton-communities",bookSignature:"Leonel Pereira and Ana Marta Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/10251.jpg",publishedDate:"May 18th 2022",numberOfDownloads:1096,editors:[{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",isOpenForSubmission:!1,hash:"79944fc8fbbaa329aed6fde388154832",slug:"animal-feed-science-and-nutrition-production-health-and-environment",bookSignature:"Amlan Kumar Patra",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",publishedDate:"May 18th 2022",numberOfDownloads:995,editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10356",title:"Natural Medicinal Plants",subtitle:null,isOpenForSubmission:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",slug:"natural-medicinal-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",publishedDate:"May 11th 2022",numberOfDownloads:3791,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11752",title:"Natural Drugs from Plants",subtitle:null,isOpenForSubmission:!1,hash:"a0a83c0822608ef7592bf16a5ed0ada4",slug:"natural-drugs-from-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/11752.jpg",publishedDate:"May 11th 2022",numberOfDownloads:2982,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10853",title:"Recent Advances in Polynomials",subtitle:null,isOpenForSubmission:!1,hash:"9e8671bae09ccaa8b8e276c639a737fc",slug:"recent-advances-in-polynomials",bookSignature:"Kamal Shah",coverURL:"https://cdn.intechopen.com/books/images_new/10853.jpg",publishedDate:"May 18th 2022",numberOfDownloads:559,editors:[{id:"231748",title:"Dr.",name:"Kamal",middleName:null,surname:"Shah",slug:"kamal-shah",fullName:"Kamal Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10676",title:"Recent Applications in Graph Theory",subtitle:null,isOpenForSubmission:!1,hash:"900c60742d224080732bd16bd25ccba8",slug:"recent-applications-in-graph-theory",bookSignature:"Harun Pirim",coverURL:"https://cdn.intechopen.com/books/images_new/10676.jpg",publishedDate:"May 18th 2022",numberOfDownloads:546,editors:[{id:"146092",title:"Dr.",name:"Harun",middleName:null,surname:"Pirim",slug:"harun-pirim",fullName:"Harun Pirim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10903",title:"Genetically Modified Plants and Beyond",subtitle:null,isOpenForSubmission:!1,hash:"4d7ed4faab99c92cd4d676dc86501df9",slug:"genetically-modified-plants-and-beyond",bookSignature:"Idah Sithole Niang",coverURL:"https://cdn.intechopen.com/books/images_new/10903.jpg",publishedDate:"May 18th 2022",numberOfDownloads:539,editors:[{id:"90172",title:"Prof.",name:"Idah",middleName:null,surname:"Sithole-Niang",slug:"idah-sithole-niang",fullName:"Idah Sithole-Niang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10904",title:"Fusarium",subtitle:"An Overview of the Genus",isOpenForSubmission:!1,hash:"49d9063e43f94bd1517d65fbc58b93c3",slug:"fusarium-an-overview-of-the-genus",bookSignature:"Seyed Mahyar Mirmajlessi",coverURL:"https://cdn.intechopen.com/books/images_new/10904.jpg",publishedDate:"May 18th 2022",numberOfDownloads:535,editors:[{id:"100573",title:"Dr.",name:"Seyed Mahyar",middleName:null,surname:"Mirmajlessi",slug:"seyed-mahyar-mirmajlessi",fullName:"Seyed Mahyar Mirmajlessi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"10251",title:"Plankton Communities",subtitle:null,isOpenForSubmission:!1,hash:"e11e441ca2d2d5f631b1b4704505cfb6",slug:"plankton-communities",bookSignature:"Leonel Pereira and Ana Marta Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/10251.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",isOpenForSubmission:!1,hash:"79944fc8fbbaa329aed6fde388154832",slug:"animal-feed-science-and-nutrition-production-health-and-environment",bookSignature:"Amlan Kumar Patra",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10853",title:"Recent Advances in Polynomials",subtitle:null,isOpenForSubmission:!1,hash:"9e8671bae09ccaa8b8e276c639a737fc",slug:"recent-advances-in-polynomials",bookSignature:"Kamal Shah",coverURL:"https://cdn.intechopen.com/books/images_new/10853.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"231748",title:"Dr.",name:"Kamal",middleName:null,surname:"Shah",slug:"kamal-shah",fullName:"Kamal Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10871",title:"Computed-Tomography (CT) Scan",subtitle:null,isOpenForSubmission:!1,hash:"966d8cf74fa27eea1b9cbc9a6ee94993",slug:"computed-tomography-ct-scan",bookSignature:"Reda R. Gharieb",coverURL:"https://cdn.intechopen.com/books/images_new/10871.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",slug:"reda-r.-gharieb",fullName:"Reda R. Gharieb"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10903",title:"Genetically Modified Plants and Beyond",subtitle:null,isOpenForSubmission:!1,hash:"4d7ed4faab99c92cd4d676dc86501df9",slug:"genetically-modified-plants-and-beyond",bookSignature:"Idah Sithole Niang",coverURL:"https://cdn.intechopen.com/books/images_new/10903.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"90172",title:"Prof.",name:"Idah",middleName:null,surname:"Sithole-Niang",slug:"idah-sithole-niang",fullName:"Idah Sithole-Niang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10904",title:"Fusarium",subtitle:"An Overview of the Genus",isOpenForSubmission:!1,hash:"49d9063e43f94bd1517d65fbc58b93c3",slug:"fusarium-an-overview-of-the-genus",bookSignature:"Seyed Mahyar Mirmajlessi",coverURL:"https://cdn.intechopen.com/books/images_new/10904.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"100573",title:"Dr.",name:"Seyed Mahyar",middleName:null,surname:"Mirmajlessi",slug:"seyed-mahyar-mirmajlessi",fullName:"Seyed Mahyar Mirmajlessi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10654",title:"Brain-Computer Interface",subtitle:null,isOpenForSubmission:!1,hash:"a5308884068cc53ed31c6baba756857f",slug:"brain-computer-interface",bookSignature:"Vahid Asadpour",coverURL:"https://cdn.intechopen.com/books/images_new/10654.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10676",title:"Recent Applications in Graph Theory",subtitle:null,isOpenForSubmission:!1,hash:"900c60742d224080732bd16bd25ccba8",slug:"recent-applications-in-graph-theory",bookSignature:"Harun Pirim",coverURL:"https://cdn.intechopen.com/books/images_new/10676.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"146092",title:"Dr.",name:"Harun",middleName:null,surname:"Pirim",slug:"harun-pirim",fullName:"Harun Pirim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11196",title:"New Updates in E-Learning",subtitle:null,isOpenForSubmission:!1,hash:"6afaadf68e2a0a4b370ac5ceb5ca89c6",slug:"new-updates-in-e-learning",bookSignature:"Eduard Babulak",coverURL:"https://cdn.intechopen.com/books/images_new/11196.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"10086",title:"Prof.",name:"Eduard",middleName:null,surname:"Babulak",slug:"eduard-babulak",fullName:"Eduard Babulak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"233",title:"Cognitive Science",slug:"cognitive-science",parent:{id:"21",title:"Psychology",slug:"psychology"},numberOfBooks:6,numberOfSeries:0,numberOfAuthorsAndEditors:144,numberOfWosCitations:28,numberOfCrossrefCitations:33,numberOfDimensionsCitations:47,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"233",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10978",title:"Mind and Matter",subtitle:"Challenges and Opportunities in Cognitive Semiotics and Aesthetics",isOpenForSubmission:!1,hash:"938b8668018c9338fbc8992e8e03f971",slug:"mind-and-matter-challenges-and-opportunities-in-cognitive-semiotics-and-aesthetics",bookSignature:"Asun López-Varela Azcárate",coverURL:"https://cdn.intechopen.com/books/images_new/10978.jpg",editedByType:"Edited by",editors:[{id:"302731",title:null,name:"Asun",middleName:null,surname:"López-Varela Azcárate",slug:"asun-lopez-varela-azcarate",fullName:"Asun López-Varela Azcárate"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10910",title:"Learning Disabilities",subtitle:"Neurobiology, Assessment, Clinical Features and Treatments",isOpenForSubmission:!1,hash:"0999e5f759c2380ae5a4a2ee0835c98d",slug:"learning-disabilities-neurobiology-assessment-clinical-features-and-treatments",bookSignature:"Sandro Misciagna",coverURL:"https://cdn.intechopen.com/books/images_new/10910.jpg",editedByType:"Edited by",editors:[{id:"103586",title:null,name:"Sandro",middleName:null,surname:"Misciagna",slug:"sandro-misciagna",fullName:"Sandro Misciagna"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10228",title:"Dyslexia",subtitle:null,isOpenForSubmission:!1,hash:"6b4060d23ac02fcb4a11313ec1c911c6",slug:"dyslexia",bookSignature:"Jonathan Glazzard and Samuel Stones",coverURL:"https://cdn.intechopen.com/books/images_new/10228.jpg",editedByType:"Edited by",editors:[{id:"294281",title:"Prof.",name:"Jonathan",middleName:null,surname:"Glazzard",slug:"jonathan-glazzard",fullName:"Jonathan Glazzard"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6593",title:"Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"88cae11440930f7ba788d5cfedec5979",slug:"decision-making",bookSignature:"Fausto Pedro García Márquez, Alberto Pliego Marugán and Mayorkinos Papaelias",coverURL:"https://cdn.intechopen.com/books/images_new/6593.jpg",editedByType:"Edited by",editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5878",title:"Learning Disabilities",subtitle:"An International Perspective",isOpenForSubmission:!1,hash:"233671027a40a86828b81f5f6094c4df",slug:"learning-disabilities-an-international-perspective",bookSignature:"Carolyn S. Ryan",coverURL:"https://cdn.intechopen.com/books/images_new/5878.jpg",editedByType:"Edited by",editors:[{id:"28738",title:"Dr.",name:"Carolyn S",middleName:null,surname:"Ryan",slug:"carolyn-s-ryan",fullName:"Carolyn S Ryan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"715",title:"Learning Disabilities",subtitle:null,isOpenForSubmission:!1,hash:"7cf7910a2068cff1fdcdfd5ed3c25cc7",slug:"learning-disabilities",bookSignature:"Wichian Sittiprapaporn",coverURL:"https://cdn.intechopen.com/books/images_new/715.jpg",editedByType:"Edited by",editors:[{id:"73395",title:"Dr.",name:"Phakkharawat",middleName:null,surname:"Sittiprapaporn",slug:"phakkharawat-sittiprapaporn",fullName:"Phakkharawat Sittiprapaporn"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:6,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"31205",doi:"10.5772/31726",title:"Could Motor Development Be an Emergent Property of Vestibular Stimulation and Primary Reflex Inhibition? A Tentative Approach to Sensorimotor Therapy",slug:"could-motor-development-be-an-emergent-property-partly-of-vestibular-stimulation-and-primary-reflex-",totalDownloads:4252,totalCrossrefCites:4,totalDimensionsCites:5,abstract:null,book:{id:"715",slug:"learning-disabilities",title:"Learning Disabilities",fullTitle:"Learning Disabilities"},signatures:"Mats Niklasson",authors:[{id:"88435",title:"MSc.",name:"Mats",middleName:null,surname:"Niklasson",slug:"mats-niklasson",fullName:"Mats Niklasson"}]},{id:"31209",doi:"10.5772/34299",title:"Disability and Oral Health",slug:"disability-and-oral-health",totalDownloads:7129,totalCrossrefCites:5,totalDimensionsCites:5,abstract:null,book:{id:"715",slug:"learning-disabilities",title:"Learning Disabilities",fullTitle:"Learning Disabilities"},signatures:"Jenny Gallagher and Sasha Scambler",authors:[{id:"99560",title:"Dr",name:"Jenny",middleName:null,surname:"Gallagher",slug:"jenny-gallagher",fullName:"Jenny Gallagher"},{id:"151953",title:"Dr.",name:"Sasha",middleName:null,surname:"Scambler",slug:"sasha-scambler",fullName:"Sasha Scambler"}]},{id:"55805",doi:"10.5772/intechopen.69464",title:"Classification and Detection of Specific Language Impairments in Children Based on their Speech Skills",slug:"classification-and-detection-of-specific-language-impairments-in-children-based-on-their-speech-skil",totalDownloads:1679,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"The ability to use the spoken language is one of the most important characteristics in child development. Speech is difficult to replace in real life, although there are several other options for communication. Inabilities to communicate with speech skills can isolate children from society, especially children with specific language impairments. This research study focused on a specific disorder, known as specific language impairment (SLI); in the Czech language, it is specifically known as developmental dysphasia (DD). One major problem is that this disorder is detected at a relatively late age. Early diagnosis is critical for successful speech therapy in children. The current chapter presents several different approaches to solve this issue, including a simple test for detecting this disorder. One approach involves the use of an original iPad application for detecting SLI based on the number of pronunciation errors in utterances. One advantage of this method is its simplicity; anyone can use it, including parents.",book:{id:"5878",slug:"learning-disabilities-an-international-perspective",title:"Learning Disabilities",fullTitle:"Learning Disabilities - An International Perspective"},signatures:"Pavel Grill and Jana Tučková",authors:[{id:"199652",title:"Ph.D.",name:"Pavel",middleName:null,surname:"Grill",slug:"pavel-grill",fullName:"Pavel Grill"}]},{id:"57766",doi:"10.5772/intechopen.72052",title:"Developing Automaticity in Children with Learning Disabilities: A Functional Perspective Part Two: Programme Methods and Materials",slug:"developing-automaticity-in-children-with-learning-disabilities-a-functional-perspective-part-two-pro",totalDownloads:1392,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"This chapter is the second of two chapters in this book to describe an instructional programme based on Luria's theories, which can be used to develop basic skills and automaticity in reading, writing, and spelling. The first chapter focused on the programme's theory, and then described how assessment is used to develop an individual programme relating to both basic skill and fluency needs in reading, writing, and spelling. The process was illustrated with one detailed case study. The results of this case study (Child 1) are presented in the current chapter, together with the results of 13 children exposed to similar fluency-based interventions. The results of six children exposed to one or more systematic variations in programme implementation are then discussed. Case contrast analysis is used to highlight three variables affecting successful programme implementation, namely: consistent and regular exposure to phonological and phonic instruction to provide a foundation of basic skills on which the fluency interventions in the programme can be built; consistent implementation of methods designed to improve both reading fluency, and writing and spelling fluency, to produce the greatest likelihood of positive effects; and consistent support from parents in programme implementation to produce the greatest likelihood of positive effects.",book:{id:"5878",slug:"learning-disabilities-an-international-perspective",title:"Learning Disabilities",fullTitle:"Learning Disabilities - An International Perspective"},signatures:"Charles Potter",authors:[{id:"93190",title:"Dr.",name:"Charles",middleName:null,surname:"Potter",slug:"charles-potter",fullName:"Charles Potter"}]},{id:"31189",doi:"10.5772/30128",title:"Meeting the Needs of Twice-Exceptional Children in the Science Classroom",slug:"meeting-the-needs-of-twice-exceptional-children-in-the-science-classroom",totalDownloads:3020,totalCrossrefCites:2,totalDimensionsCites:3,abstract:null,book:{id:"715",slug:"learning-disabilities",title:"Learning Disabilities",fullTitle:"Learning Disabilities"},signatures:"Manabu Sumida",authors:[{id:"80976",title:"Dr.",name:"Manabu",middleName:null,surname:"Sumida",slug:"manabu-sumida",fullName:"Manabu Sumida"}]}],mostDownloadedChaptersLast30Days:[{id:"57054",title:"Specific Learning Disabilities: Response to Intervention",slug:"specific-learning-disabilities-response-to-intervention",totalDownloads:2118,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The content included in the current chapter centers around the screening and identification of students who experience learning challenges in an educational setting in the United States of America. The specific learning challenges discussed will focus on students who may have a specific learning disability (SLD). Legislation that brought about concepts such as response to intervention (RTI) is discussed in detail. The various levels of intensity of interventions, or tiers, provided to students are explained by more than one discipline. The new regulations guiding access to special education services are based on the identification, intervention, and close monitoring of student progress. The overarching goal of RTI is to provide support to students who may be experiencing difficulty, before they experience failure by falling too far behind their peers.",book:{id:"5878",slug:"learning-disabilities-an-international-perspective",title:"Learning Disabilities",fullTitle:"Learning Disabilities - An International Perspective"},signatures:"Kimberly A. Heinemann, Heather Bolanos and Jennifer S. Griffin",authors:[{id:"205622",title:"Mrs.",name:"Kimberly",middleName:null,surname:"Heinemann",slug:"kimberly-heinemann",fullName:"Kimberly Heinemann"},{id:"208681",title:"Mrs.",name:"Heather",middleName:null,surname:"Bolanos",slug:"heather-bolanos",fullName:"Heather Bolanos"},{id:"208691",title:"Mrs.",name:"Jennifer S.",middleName:null,surname:"Griffin",slug:"jennifer-s.-griffin",fullName:"Jennifer S. Griffin"}]},{id:"59913",title:"Decision-Making in Complex Dynamic and Evolutive Systems: The Need for a New Paradigm",slug:"decision-making-in-complex-dynamic-and-evolutive-systems-the-need-for-a-new-paradigm",totalDownloads:4566,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"For contemporary psychology, decision-making represents behaviours, which are very different from automatic responses. They are developed by implementing integrative cognitive functions adapted to the finalities sought and the situation to treat. Through the diversity of epistemological choices for instance, research in previous decades focused on the individual choices expressed by situations or contexts with a stable structure. The new problems of life in today’s society lead to making decisions on societal problems (climate, energy, etc.), which bring into play systems and no longer variables. This chapter has four aspects. After having characterised the decision-making process as a cognitive behaviour (1), having recalled the best known traditional models (those of Economics and Psychology) (2), this chapter deals with the properties of complex systems (globality, interactivity, dynamism, and scalability), which render decision-making difficult (3), and concludes with the necessity of a change of paradigm by pointing to paths to follow (4).",book:{id:"6593",slug:"decision-making",title:"Decision Making",fullTitle:"Decision Making"},signatures:"Bernard Cadet",authors:[{id:"232726",title:"Emeritus Prof.",name:"Bernard",middleName:null,surname:"Cadet",slug:"bernard-cadet",fullName:"Bernard Cadet"}]},{id:"63337",title:"Introductory Chapter: An Overview to the Analytic Principles with Business Practice in Decision Making",slug:"introductory-chapter-an-overview-to-the-analytic-principles-with-business-practice-in-decision-makin",totalDownloads:917,totalCrossrefCites:0,totalDimensionsCites:1,abstract:null,book:{id:"6593",slug:"decision-making",title:"Decision Making",fullTitle:"Decision Making"},signatures:"Fausto Pedro García Márquez, Alberto Pliego Marugán and\nMayorkinos Papaelias",authors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}]},{id:"80202",title:"Depression, Suicidal Tendencies, Hopelessness, and Stress among Patients with Learning Disabilities",slug:"depression-suicidal-tendencies-hopelessness-and-stress-among-patients-with-learning-disabilities",totalDownloads:96,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Self-harm and suicide are most commonly observed in adolescents specially females in Asian countries and in western. The psychosocial predictors, along with hopelessness and non-suicidal injury (NSSI), have not been studied properly before. Therefore, there is a need to address these issues. The objective of the study was to ascertain the psychosocial and clinical features predicting suicide and NSSI in adolescents with major depression. Increased number of suicidality and impaired family function at entry is autonomously connected with a suicidal attempt. NSSI are connected at base line and apply additive effect on likelihood, one keeping on through treatment period. Poor family functions, as well as family problems and social problems, were the causative agents for adolescent’s high suicidality and NSSI. A history of NSSI treatment is a clinical marker for suicidality. The previous suicidal attempts should be evaluated in depressed juvenile patients as indicators of future suicidal intent and behavior. Both suicidal and NSSI adolescents during the therapy and after treatment endure to be depressed when they are engaged in study. Major causes of suicide among our study participants were lost friend(s), drug abuse, living alone, disturbed parental marriage, sexual abuse, and other domestic problems.",book:{id:"10910",slug:"learning-disabilities-neurobiology-assessment-clinical-features-and-treatments",title:"Learning Disabilities",fullTitle:"Learning Disabilities - Neurobiology, Assessment, Clinical Features and Treatments"},signatures:"Fahad Hassan Shah, Song Ja Kim, Laiba Zakir, Aqsa Ehsan, Sohail Riaz, Muhammad Sulaiman and Saad Salman",authors:[{id:"418086",title:"Dr.",name:"Saad",middleName:null,surname:"Salman",slug:"saad-salman",fullName:"Saad Salman"},{id:"439291",title:"Dr.",name:"Fahad Hassan",middleName:null,surname:"Shah",slug:"fahad-hassan-shah",fullName:"Fahad Hassan Shah"},{id:"439292",title:"Dr.",name:"Song Ja",middleName:null,surname:"Kim",slug:"song-ja-kim",fullName:"Song Ja Kim"},{id:"439293",title:"Dr.",name:"Laiba",middleName:null,surname:"Zakir",slug:"laiba-zakir",fullName:"Laiba Zakir"},{id:"439294",title:"Dr.",name:"Aqsa",middleName:null,surname:"Ehsan",slug:"aqsa-ehsan",fullName:"Aqsa Ehsan"},{id:"451112",title:"Dr.",name:"Sohail",middleName:null,surname:"Riaz",slug:"sohail-riaz",fullName:"Sohail Riaz"},{id:"451113",title:"Dr.",name:"Muhammad",middleName:null,surname:"Sulaiman",slug:"muhammad-sulaiman",fullName:"Muhammad Sulaiman"}]},{id:"79900",title:"Dyslexia, Dysgraphia and Dyscalculia: A Response to Intervention Approach to Classification",slug:"dyslexia-dysgraphia-and-dyscalculia-a-response-to-intervention-approach-to-classification",totalDownloads:150,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter provides a model for classification of dyslexia, dysgraphia and dyscalculia through analysis of the response of children to treatment. The model is discussed with reference to the types of multivariate treatment applied in a particular programme which works interactively online using an electronic data-base for linking functional difficulties in learning to treatment, and through this to firm diagnosis and classification. In applying the model, initial diagnosis of learning disabilities is treated as provisional, based on functional indicators as well as test data. Firm classification becomes possible through longitudinal assessment, analysis of response to multivariate intervention as well as response to specific programmes. Diagnosis can then be linked both to concessions as well as ongoing treatment.",book:{id:"10910",slug:"learning-disabilities-neurobiology-assessment-clinical-features-and-treatments",title:"Learning Disabilities",fullTitle:"Learning Disabilities - Neurobiology, Assessment, Clinical Features and Treatments"},signatures:"Charles Potter",authors:[{id:"93190",title:"Dr.",name:"Charles",middleName:null,surname:"Potter",slug:"charles-potter",fullName:"Charles Potter"}]}],onlineFirstChaptersFilter:{topicId:"233",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,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:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:null,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:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{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"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:10,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,annualVolume:11415,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:0,paginationItems:[]},overviewPagePublishedBooks:{paginationCount:0,paginationItems:[]},openForSubmissionBooks:{paginationCount:3,paginationItems:[{id:"11580",title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",hash:"1806716f60b9be14fc05682c4a912b41",secondStepPassed:!0,currentStepOfPublishingProcess:4,submissionDeadline:"March 23rd 2022",isOpenForSubmission:!0,editors:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11579",title:"Animal Welfare - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11579.jpg",hash:"12e4f41264cbe99028655e5463fa941a",secondStepPassed:!1,currentStepOfPublishingProcess:2,submissionDeadline:"June 1st 2022",isOpenForSubmission:!0,editors:[{id:"51520",title:"Dr.",name:"Shao-Wen",surname:"Hung",slug:"shao-wen-hung",fullName:"Shao-Wen Hung"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11578",title:"Antibiotics and Probiotics in Animal Food - Impact and Regulation",coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",hash:"3731c009f474c6ed4293f348ca7b27ac",secondStepPassed:!1,currentStepOfPublishingProcess:2,submissionDeadline:"June 3rd 2022",isOpenForSubmission:!0,editors:[{id:"225390",title:"Dr.",name:"Asghar Ali",surname:"Kamboh",slug:"asghar-ali-kamboh",fullName:"Asghar Ali Kamboh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:17,paginationItems:[{id:"81751",title:"NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications",doi:"10.5772/intechopen.102552",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. Guerra, Marcos V. da Silva, Carlo J.F. de Oliveira, Virmondes Rodrigues Junior, Renata M. Etchebehere, Fabiane C. de Abreu, Bruno G. Lucca, Sanívia A.L. Pereira, Rodrigo C. Rosa and Noelio O. Dantas",slug:"nanobiosensors-from-electrochemical-sensors-improvement-to-theranostic-applications",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81766",title:"Evolution of Organoids in Oncology",doi:"10.5772/intechopen.104251",signatures:"Allen Thayakumar Basanthakumar, Janitha Chandrasekhar Darlybai and Jyothsna Ganesh",slug:"evolution-of-organoids-in-oncology",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81678",title:"Developmental Studies on Practical Enzymatic Phosphate Ion Biosensors and Microbial BOD Biosensors, and New Insights into the Future Perspectives of These Biosensor Fields",doi:"10.5772/intechopen.104377",signatures:"Hideaki Nakamura",slug:"developmental-studies-on-practical-enzymatic-phosphate-ion-biosensors-and-microbial-bod-biosensors-a",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hideaki",surname:"Nakamura"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81547",title:"Organoids and Commercialization",doi:"10.5772/intechopen.104706",signatures:"Anubhab Mukherjee, Aprajita Sinha, Maheshree Maibam, Bharti Bisht and Manash K. Paul",slug:"organoids-and-commercialization",totalDownloads:33,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81412",title:"Mathematical Morphology and the Heart Signals",doi:"10.5772/intechopen.104113",signatures:"Taouli Sidi Ahmed",slug:"mathematical-morphology-and-the-heart-signals",totalDownloads:18,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81360",title:"Deep Learning Algorithms for Efficient Analysis of ECG Signals to Detect Heart Disorders",doi:"10.5772/intechopen.103075",signatures:"Sumagna Dey, Rohan Pal and Saptarshi Biswas",slug:"deep-learning-algorithms-for-efficient-analysis-of-ecg-signals-to-detect-heart-disorders",totalDownloads:31,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81294",title:"Applications of Neural Organoids in Neurodevelopment and Regenerative Medicine",doi:"10.5772/intechopen.104044",signatures:"Jing Gong, Jiahui Kang, Minghui Li, Xiao Liu, Jun Yang and Haiwei Xu",slug:"applications-of-neural-organoids-in-neurodevelopment-and-regenerative-medicine",totalDownloads:25,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81318",title:"Retinal Organoids over the Decade",doi:"10.5772/intechopen.104258",signatures:"Jing Yuan and Zi-Bing Jin",slug:"retinal-organoids-over-the-decade",totalDownloads:39,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81068",title:"Characteristic Profiles of Heart Rate Variability in Depression and Anxiety",doi:"10.5772/intechopen.104205",signatures:"Toshikazu Shinba",slug:"characteristic-profiles-of-heart-rate-variability-in-depression-and-anxiety",totalDownloads:20,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"80691",title:"Applications of Quantum Mechanics, Laws of Classical Physics, and Differential Calculus to Evaluate Source Localization According to the Electroencephalogram",doi:"10.5772/intechopen.102831",signatures:"Kristin S. Williams",slug:"applications-of-quantum-mechanics-laws-of-classical-physics-and-differential-calculus-to-evaluate-so",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}}]},subseriesFiltersForOFChapters:[{caption:"Bioinformatics and Medical Informatics",value:7,count:13,group:"subseries"}],publishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"10803",title:"Reactive Oxygen Species",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",slug:"reactive-oxygen-species",publishedDate:"April 28th 2022",editedByType:"Edited by",bookSignature:"Rizwan Ahmad",hash:"176adcf090fdd1f93cb8ce3146e79ca1",volumeInSeries:28,fullTitle:"Reactive Oxygen Species",editors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9008",title:"Vitamin K",subtitle:"Recent Topics on the Biology and Chemistry",coverURL:"https://cdn.intechopen.com/books/images_new/9008.jpg",slug:"vitamin-k-recent-topics-on-the-biology-and-chemistry",publishedDate:"March 23rd 2022",editedByType:"Edited by",bookSignature:"Hiroyuki Kagechika and Hitoshi Shirakawa",hash:"8b43add5389ba85743e0a9491e4b9943",volumeInSeries:27,fullTitle:"Vitamin K - Recent Topics on the Biology and Chemistry",editors:[{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10799",title:"Phenolic Compounds",subtitle:"Chemistry, Synthesis, Diversity, Non-Conventional Industrial, Pharmaceutical and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10799.jpg",slug:"phenolic-compounds-chemistry-synthesis-diversity-non-conventional-industrial-pharmaceutical-and-therapeutic-applications",publishedDate:"February 23rd 2022",editedByType:"Edited by",bookSignature:"Farid A. Badria",hash:"339199f254d2987ef3167eef74fb8a38",volumeInSeries:26,fullTitle:"Phenolic Compounds - Chemistry, Synthesis, Diversity, Non-Conventional Industrial, Pharmaceutical and Therapeutic Applications",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",institutionString:"Mansoura University",institution:{name:"Mansoura University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9659",title:"Fibroblasts",subtitle:"Advances in Inflammation, Autoimmunity and Cancer",coverURL:"https://cdn.intechopen.com/books/images_new/9659.jpg",slug:"fibroblasts-advances-in-inflammation-autoimmunity-and-cancer",publishedDate:"December 22nd 2021",editedByType:"Edited by",bookSignature:"Mojca Frank Bertoncelj and Katja Lakota",hash:"926fa6446f6befbd363fc74971a56de2",volumeInSeries:25,fullTitle:"Fibroblasts - Advances in Inflammation, Autoimmunity and Cancer",editors:[{id:"328755",title:"Ph.D.",name:"Mojca",middleName:null,surname:"Frank Bertoncelj",slug:"mojca-frank-bertoncelj",fullName:"Mojca Frank Bertoncelj",profilePictureURL:"https://mts.intechopen.com/storage/users/328755/images/system/328755.jpg",institutionString:"BioMed X Institute",institution:{name:"University Hospital of Zurich",institutionURL:null,country:{name:"Switzerland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8977",title:"Protein Kinases",subtitle:"Promising Targets for Anticancer Drug Research",coverURL:"https://cdn.intechopen.com/books/images_new/8977.jpg",slug:"protein-kinases-promising-targets-for-anticancer-drug-research",publishedDate:"December 8th 2021",editedByType:"Edited by",bookSignature:"Rajesh Kumar Singh",hash:"6d200cc031706a565b554fdb1c478901",volumeInSeries:24,fullTitle:"Protein Kinases - Promising Targets for Anticancer Drug Research",editors:[{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9759",title:"Vitamin E in Health and Disease",subtitle:"Interactions, Diseases and Health Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/9759.jpg",slug:"vitamin-e-in-health-and-disease-interactions-diseases-and-health-aspects",publishedDate:"October 6th 2021",editedByType:"Edited by",bookSignature:"Pınar Erkekoglu and Júlia Scherer Santos",hash:"6c3ddcc13626110de289b57f2516ac8f",volumeInSeries:22,fullTitle:"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu",profilePictureURL:"https://mts.intechopen.com/storage/users/109978/images/system/109978.jpg",institutionString:"Hacettepe University",institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9753",title:"Terpenes and Terpenoids",subtitle:"Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/9753.jpg",slug:"terpenes-and-terpenoids-recent-advances",publishedDate:"July 28th 2021",editedByType:"Edited by",bookSignature:"Shagufta Perveen and Areej Mohammad Al-Taweel",hash:"575689df13c78bf0e6c1be40804cd010",volumeInSeries:21,fullTitle:"Terpenes and Terpenoids - Recent Advances",editors:[{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",institutionString:"King Saud University",institution:{name:"King Saud University",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9403",title:"Human Microbiome",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9403.jpg",slug:"human-microbiome",publishedDate:"June 16th 2021",editedByType:"Edited by",bookSignature:"Natalia V. Beloborodova and Andrey V. Grechko",hash:"c31366ba82585ba3ac91d21eb1cf0a4d",volumeInSeries:20,fullTitle:"Human Microbiome",editors:[{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",slug:"oxidoreductase",publishedDate:"February 17th 2021",editedByType:"Edited by",bookSignature:"Mahmoud Ahmed Mansour",hash:"852e6f862c85fc3adecdbaf822e64e6e",volumeInSeries:19,fullTitle:"Oxidoreductase",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour",profilePictureURL:"https://mts.intechopen.com/storage/users/224662/images/system/224662.jpg",institutionString:"King Saud bin Abdulaziz University for Health Sciences",institution:{name:"King Saud bin Abdulaziz University for Health Sciences",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9742",title:"Ubiquitin",subtitle:"Proteasome Pathway",coverURL:"https://cdn.intechopen.com/books/images_new/9742.jpg",slug:"ubiquitin-proteasome-pathway",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Xianquan Zhan",hash:"af6880d3a5571da1377ac8f6373b9e82",volumeInSeries:18,fullTitle:"Ubiquitin - Proteasome Pathway",editors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9002",title:"Glutathione System and Oxidative Stress in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9002.jpg",slug:"glutathione-system-and-oxidative-stress-in-health-and-disease",publishedDate:"August 26th 2020",editedByType:"Edited by",bookSignature:"Margarete Dulce Bagatini",hash:"127defed0a50ad5ed92338dc96e1e10e",volumeInSeries:17,fullTitle:"Glutathione System and Oxidative Stress in Health and Disease",editors:[{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:3},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:8},{group:"subseries",caption:"Chemical Biology",value:15,count:10}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:249,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,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. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"39",type:"subseries",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11967,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,series:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713"},editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",slug:"elke-jurandy-bran-nogueira-cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",slug:"sandra-ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:9,paginationItems:[{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81681",title:"Immunomodulatory Effects of a M2-Conditioned Medium (PRS® CK STORM): Theory on the Possible Complex Mechanism of Action through Anti-Inflammatory Modulation of the TLR System and the Purinergic System",doi:"10.5772/intechopen.104486",signatures:"Juan Pedro Lapuente",slug:"immunomodulatory-effects-of-a-m2-conditioned-medium-prs-ck-storm-theory-on-the-possible-complex-mech",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81580",title:"Graft-Versus-Host Disease: Pathogenesis and Treatment",doi:"10.5772/intechopen.104450",signatures:"Shin Mukai",slug:"graft-versus-host-disease-pathogenesis-and-treatment",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"80485",title:"Potential Marker for Diagnosis and Screening of Iron Deficiency Anemia in Children",doi:"10.5772/intechopen.102792",signatures:"Yulia Nadar Indrasari, Siti Nurul Hapsari and Muhamad Robiul Fuadi",slug:"potential-marker-for-diagnosis-and-screening-of-iron-deficiency-anemia-in-children",totalDownloads:42,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"79693",title:"Ferroptosis: Can Iron be the Last or Cure for a Cell?",doi:"10.5772/intechopen.101426",signatures:"Asuman Akkaya Fırat",slug:"ferroptosis-can-iron-be-the-last-or-cure-for-a-cell",totalDownloads:90,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"79616",title:"Dietary Iron",doi:"10.5772/intechopen.101265",signatures:"Kouser Firdose and Noor Firdose",slug:"dietary-iron",totalDownloads:144,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"78977",title:"FERALGINE™ a New Oral iron Compound",doi:"10.5772/intechopen.100445",signatures:"Valentina Talarico, Laura Giancotti, Giuseppe Antonio Mazza, Santina Marrazzo, Roberto Miniero and Marco Bertini",slug:"feralgine-a-new-oral-iron-compound",totalDownloads:129,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}}]},publishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"7437",title:"Nanomedicines",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7437.jpg",slug:"nanomedicines",publishedDate:"February 13th 2019",editedByType:"Edited by",bookSignature:"Muhammad Akhyar Farrukh",hash:"0e1f5f6258f074c533976c4f4d248568",volumeInSeries:5,fullTitle:"Nanomedicines",editors:[{id:"63182",title:"Dr.",name:"Muhammad Akhyar",middleName:null,surname:"Farrukh",slug:"muhammad-akhyar-farrukh",fullName:"Muhammad Akhyar Farrukh",profilePictureURL:"https://mts.intechopen.com/storage/users/63182/images/system/63182.png",institutionString:"Forman Christian College",institution:{name:"Forman Christian College",institutionURL:null,country:{name:"Pakistan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},testimonialsList:[{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}},{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}}]},submityourwork:{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:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,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:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:null,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:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/345688",hash:"",query:{},params:{id:"345688"},fullPath:"/profiles/345688",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()