\r\n\tDiagnosis (clinical, radiological, cytogenetic, and molecular criteria), pathogenesis (risk factors, pre-myeloma conditions, and bone marrow microenvironment), cytogenetic abnormalities and molecular profiles disease staging and risk stratification, novel therapies such as proteasome inhibitors, immunomodulatory agents as well as monoclonal antibodies, drug resistance (primary and secondary resistance as well as evolution of new genetic mutations that may be disease or therapy-related), hematopoietic stem cell transplantation (HSCT) (autologous HSCT, allogeneic HSCT, and tandem transplantation), relapsed and refractory multiple myeloma, minimal residual disease (evaluation by flow cytometry or various sequencing techniques, importance of MRD in prognosis and prediction of disease relapse), chimeric antigen receptor (CAR) T-cell therapy, infectious complications in multiple myeloma (viral infections, bacterial infections, fungal infections, disease-related infections and therapy-related infections).
\r\n\r\n\tThe book chapters will intend to be written by scientists and experts in the field from various institutions around the world.
",isbn:"978-1-80356-093-9",printIsbn:"978-1-80356-092-2",pdfIsbn:"978-1-80356-094-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"c8e2b12df4fc2d313aced448fe08a63e",bookSignature:"Dr. Khalid Ahmed Al-Anazi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11600.jpg",keywords:"Risk Factors, Angiogenesis, Signaling Pathways, Therapeutic Targets, Drug Resistance, Genetic Mutations, Disease-Related Infections, Therapy-Related Infections, Complete Remission, Overall Survival, Immunomodulatory Agents, Bone Marrow Microenvironment",numberOfDownloads:13,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 26th 2022",dateEndSecondStepPublish:"March 29th 2022",dateEndThirdStepPublish:"May 28th 2022",dateEndFourthStepPublish:"August 16th 2022",dateEndFifthStepPublish:"October 15th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Khalid Al-Anazi established the Hematopoietic Stem Cell Transplantation Services in Saudi Arabia. He is a distinguished researcher in the fields of stem cell therapies & infections in immunocompromised individuals.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"37255",title:"Dr.",name:"Khalid",middleName:"Ahmed",surname:"Al-Anazi",slug:"khalid-al-anazi",fullName:"Khalid Al-Anazi",profilePictureURL:"https://mts.intechopen.com/storage/users/37255/images/system/37255.jpg",biography:"Dr. Khalid Ahmed Al-Anazi is a consultant Hemato-Oncologist and the Chairman of the Department of Adult Hematology and Hematopoietic Stem Cell Transplantation (HSCT) at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia. \r\nHe graduated from the college of medicine, King Saud University (KSU) in Riyadh in 1986. After having his Boards in Internal Medicine, he trained in clinical hematology and HSCT at King’s College Hospital, University of London, U.K. He has 4 year experience in internal medicine and 28 year experience in adult clinical hematology and HSCT at: Riyadh Armed Forces Hospital; King Faisal Specialist Hospital and Research Centre (KFSH&RC) in Riyadh; King Khalid University Hospital (KKUH) and the College of Medicine, KSU in Riyadh; and KFSH in Dammam, Saudi Arabia. \r\nHe established the adult HSCT program at KFSH in Dammam in the year 2010. He received the award of the best teacher in the Department of Medicine, at the College of Medicine and KKUH in Riyadh in the year 2014. \r\n\r\nHe has more than 95 publications including retrospective studies, review articles, book chapters, and electronic books and he is a reviewer for 25 international medical journals. \r\nHe is the Editor-in-Chief of the Journal of Stem Cell Biology and Transplantation and the Journal of Molecular Genetics and Medicine in addition to being Associate Editor for 26 other medical journals in HSCT, hematology, cancer and infectious diseases. \r\nHe is a member of several international organizations including ECIL (European Conference of Infections in Leukemia).",institutionString:"King Fahad Specialist Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"King Fahad Specialist Hospital",institutionURL:null,country:{name:"Saudi Arabia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:[{id:"82492",title:"Treatment of Patients with Newly-Diagnosed Multiple Myeloma",slug:"treatment-of-patients-with-newly-diagnosed-multiple-myeloma",totalDownloads:3,totalCrossrefCites:0,authors:[null]},{id:"82258",title:"Management of Renal Failure in Multiple Myeloma",slug:"management-of-renal-failure-in-multiple-myeloma",totalDownloads:11,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429341",firstName:"Paula",lastName:"Gavran",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"paula@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"8026",title:"Update on Mesenchymal and Induced Pluripotent Stem Cells",subtitle:null,isOpenForSubmission:!1,hash:"48115afa72bcce1bde1e5b0e6c45f1b8",slug:"update-on-mesenchymal-and-induced-pluripotent-stem-cells",bookSignature:"Khalid Ahmed Al-Anazi",coverURL:"https://cdn.intechopen.com/books/images_new/8026.jpg",editedByType:"Edited by",editors:[{id:"37255",title:"Dr.",name:"Khalid",surname:"Al-Anazi",slug:"khalid-al-anazi",fullName:"Khalid Al-Anazi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6710",title:"Update on Multiple Myeloma",subtitle:null,isOpenForSubmission:!1,hash:"229a96a2de131b3ac67f9f41b91de8f8",slug:"update-on-multiple-myeloma",bookSignature:"Khalid Ahmed Al-Anazi",coverURL:"https://cdn.intechopen.com/books/images_new/6710.jpg",editedByType:"Edited by",editors:[{id:"37255",title:"Dr.",name:"Khalid",surname:"Al-Anazi",slug:"khalid-al-anazi",fullName:"Khalid Al-Anazi"}],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. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"50663",title:"High-Risk Human Papillomavirus and Colorectal Carcinogenesis",doi:"10.5772/63295",slug:"high-risk-human-papillomavirus-and-colorectal-carcinogenesis",body:'\nColorectal cancers (CRCs) colon and rectal, are the most common malignancies, accounting for approximately 1.36 million new cases worldwide every year [1]. These cancers are characterized by a marked propensity for local invasion and lymph node metastases. Thus, the overall 5-year-survival rate for patients diagnosed with colorectal cancers is approximately 60% worldwide and has not significantly improved over the past decade [2]. Colorectal carcinogenesis is a complex, multistep process involving environmental, demographic, and lifestyle factors in addition to gene alterations and viral infections. The highest incidence of CRCs is observed in Western Europe, North America, Australia as well as in some Middle-Eastern countries [3, 4]. It is notable also that although the rate of this disease is relatively lower in sub-Saharan African communities, South America, and Asia; however, CRCs are gradually increasing due to assimilating life style and dietary habits of Western countries [3–5]. Additionally, around two-thirds of CRC patients will develop distant metastases during the course of their illness, which is the main cause of cancer-related death of this disease [6].
\nAlthough, human papillomaviruses (HPVs) have been established as etiological agents of invasive cervical cancer, as generally 96% of these cancers are positive for high-risk HPVs [7–9]. However, persistent infection with high-risk HPVs is necessary but not sufficient for the development of malignant lesions [10, 11]. Furthermore, it was pointed-out that high-risk HPVs have carcinogenic effects at several other anatomical sites in women and men such as head and neck (HN) as well as colorectal [12–15]. These studies and others showed that high-risk HPVs are present in roughly 30% and 70% of HN and colorectal cancers, respectively, especially in their invasive form [14, 15]. Accordingly, we recently investigated the incidence of high-risk HPVs in CRCs in the Syrian population; our data revealed that 54% of human CRCs in Syria are positive for high-risk-HPVs; this was accompanied by an expression/overexpression of Fascin, Id-1, and P-cadherin genes [16], which are major regulators of cell invasion and metastasis [17–19]. Meanwhile, we revealed that E5 and E6/E7 oncoproteins of high-risk HPVs could cooperate together to enhance cancer progression through the deregulation of several key controller genes of the epithelial–mesenchymal transition (EMT) event [7, 20, 21]. It is clear that CRCs and especially their invasive forms are major health problems wherein high-risk HPVs infection can play important roles in the development of these malignancies as well as their metastasis via EMT. In this chapter, we will overview the presence and contributions of high-risk HPVs in CRC initiation and progression.
\nCRCs are the most prevalent cancers worldwide, along with lung and breast cancers, they are one of the deadliest diseases today [22]. For instance, in the United States, CRCs are the third leading cause of cancer death in both sexes and the second overall in men and women combined [23, 24]. At current rates, approximately 5–6% of individuals will develop colon or rectum cancer within their lifetime [23]. These malignances are most common in Europe with 432,000 new cases reported annually in men and women combined, and the second most common cause of cancer deaths in Europe [22, 25]. In general, it is the second leading cause of cancer-related mortality worldwide and the third most commonly diagnosed malignant disease [26].
\nThe prognosis of patients with colorectal cancer has slowly but steadily improved during the past decades in many countries. A 5-year relative survival has reached almost 65% in high-income countries, such as Australia, Canada, the USA, and several European countries, but has remained less than 50% in low-income countries [27–29]. Relative survival decreases with age, and at young ages, it is slightly higher for women than for men [30]; taking into consideration that the stage at diagnosis is the most important prognostic factor.
\nColorectal carcinogenesis is common in the elderly; as approximately 90% of new colorectal cancers are diagnosed in patients over 50 years with the median age of diagnosis being 69 years. Furthermore, the incidence of CRCs dramatically rises as one ages, regardless of sex and racial background [26]. Although, it is well-known that patients with colorectal cancer may have a range of symptoms that include occult blood loss, rectal bleeding, change in stool caliber, unintentional weight loss, or have signs of bowel obstruction or perforation.
\nThere are many risk factors for the development of colorectal cancer, one of which is colonic polyps. Pathologic entities include tubular adenoma, tubulovillous adenoma, villous adenoma, hyperplastic polyp, sessile serrated adenoma, sessile serrated polyp, and traditional serrated adenoma. In addition, some hamartomatous polyps are considered premalignant lesions [31]. Among precancerous polyps adenomatous and advanced adenomatous polyps that have polyp size >10 mm, in addition to villous/tubulovillous histological features, or having high-grade dysplasia (HGD), are found to have an increased prevalence and incidence in the elderly [26], and have a potential to progress to invasive adenocarcinomas [26, 32]. HGD is associated with larger size, villous morphology,
For the most part, colorectal cancer arises sporadically, however, few cases are associated with inherited syndromes such as familial adenomatous polyposis (FAP; <1% of CRC) where patients exhibit germline mutations in one allele of the adenomatous polyposis (
The usual malignant tumor of the large bowel is a well-to-moderately differentiated adenocarcinoma secreting variable amounts of mucin [34]. In World Health Organization (WHO) classification, a number of histologic variants of this tumor are listed, such as mucinous adenocarcinoma, signet ring cell, medullary, micropapillary, serrated, cribriform comedo-type, adenosquamous, spindle cell, and undifferentiated. The most widely used immunohistochemical markers for colorectal adenocarcinoma are cytokeratin (CK) 20, CK7, and CDX2. The most common immunophenotype of colorectal adenocarcinoma is positivity for CK20 and negativity for CK7 [35]. The CRCs are divided in to four grades. G1 are well-differentiated tumors (usually adenocarcinomas) that have more than 95% glandular structures. Further, G2 are designated as moderately differentiated tumors with 50–95% gland formation. G3 are poorly differentiated tumors with 5–50% gland formation; whereas G4 are highly aggressive and undifferentiated tumors with less than 5% gland formation. Recently, WHO also suggests dividing CRCs into low grade (G1 and G2) and high grade (G3 and G4) categories. The diagnosis of G3 and G4 is relatively consistent, but differentiation between G1 and G2 is associated with a significant degree of inter-observer variability [36, 37] .
\nAs we mentioned above, CRCs are characterized by a marked propensity for invasion and metastasis. About 20% of patients with newly diagnosed colorectal cancer present with distant metastases [38, 39]. The most common location is the liver [38, 40]; however, investigators identified lung metastases in 2·1% of patients newly diagnosed with CRC in a large cancer registry in France [41]. Frequency was nearly three times higher for patients with rectal cancer than for patients with colon cancer. Smaller studies [42–44] have shown isolated lung metastases in 9–18% of patients with rectal cancer; although distant metastases can be identified in other organs including the bone and the brain [38].
\nAs we cited above, lifetime risk of CRCs is estimated to be 5–6% in the general population of Western countries [45, 46]. Although hereditary forms of CRC have been well established; however, most cases are sporadic [47]. Numerous epidemiological studies have identified lifestyle and environmental factors contributing to the occurrence of CRCs [48, 49]. In the past decades,
Papillomaviruses were first identified in rabbits in 1933, and they were found to be involved in transmissible growth of benign papillomas [54]. HPVs were first identified in 1956, and they were associated with a variety of benign growths in humans [55]. However, it was later observed that HPVs, a highly prevalent sexually transmitted infection, have potentially serious health consequences in males and females. HPV infections have received considerable attention in recent years. So far, more than 150 HPV types have been isolated and characterized. While the involvement of HPV in causing benign warts was already known, the first evidence of the association between human cancer and certain HPV types was proposed more than thirty years ago by zur Hausen and his colleagues [56].
\nThe common mode of transmission and acquisition of HPV is by horizontal transmission consequent to sexual activity. Occasionally, HPV may be transmitted through modes other than sexual activity [57–61]. Thus, prevalence sites of HPVs include the epithelium of the vagina, vulva, penis, anal canal, cervix, perianal region, crypts of the tonsils, and oropharynx. Persistent HPV infection is essential for the development of cervical precancerous lesions and cancer. However, this may take a long time, usually a decade or more after the initial infection [62].
\nHPVs are small, double-stranded DNA viruses that generally infect cutaneous and mucosal epithelial tissues of the anogenital tract. The HPV DNA genome encodes approximately eight open reading frames (ORFs) [52, 62]. It is divided into three functional parts: the early (E) region, the late (L) region, and a long control region (LCR). The E region is important for replication, cellular transformation, and for the control of viral transcription, whereas the L region encodes the structural proteins (L1-L2) that take part in assembly [12]. The LCR is necessary for viral DNA replication and transcription. The seven proteins of the E region are E1, E2, E3, E4, E5, E6, and E7. E1 is necessary for viral DNA replication, while E2 has a role in viral gene transcription and replication. The function of E3 is still not understood. On the other hand, E4 protein interacts with the keratin cytoskeleton and intermediate filaments. Moreover, it facilitates virus assembly and release. The E5 protein interacts with the receptors of growth factors and stimulates cellular proliferation and inhibits apoptosis. E6 induces DNA synthesis, prevents cell differentiation, and interacts with tumor suppressor proteins and repair factors. In fact, E7 induces cell proliferation and interacts with negative regulators of cell cycle and tumor suppressor proteins. E5, E6, and E7 proteins act as oncogenes which are associated with carcinogenesis [12, 20, 63–66] (please see below).
\nAs we mentioned above, over 150 different viral types have been identified, and about one-third of these infect epithelial cells in the genital tract [67]. HPVs are classified as either high risk or low risk. Infections with low-risk types are generally self-limiting and do not lead to malignancy. However, infections with high-risk HPVs (type 16, 18, 31, 33, 35, 39, 45, 51, 52, 55, 56, 58, 59, 68, 73, 82, and 83) are associated with the development of cervical cancers since more than 96% of these cancers are positive for high-risk HPVs [7, 9, 68–70].
\nIt is well known that high-risk HPV early proteins, including E5, E6, and E7 oncoproteins, increase cellular alteration and probably lead to HPV induced carcinogenesis [20, 71–73]. More specifically, the E5 oncoprotein interacts with EGF-R1 signaling pathways (MAP Kinase and P13K-Akt) and proapoptotic proteins [74–76]; and therefore, it can play an important role in cell transformation and tumor formation. On the other hand, E6 and E7 of the high-risk HPV types, such as HPV16, are thought to work together in lesions caused by this virus, since, the two proteins are expressed from bicistronic mRNA [77] and initiated from the viral early promoter (p97). These proteins have functions that stimulate cell cycle progression and both can associate with regulators of the cell cycle [70, 72, 78].
\nSeveral studies have shown that the viral E6 protein complements the role of E7 and is thought to prevent the induction of apoptosis in response to unscheduled S-phase entry mediated by E7 [70, 79]. The E6 protein is also involved in the inactivation of p53-mediated growth suppression and/or apoptosis and can also associate with other proapoptotic proteins including Bak [80] and Bax [81]. In addition, E6 stimulates cell proliferation independently from E7 through its C-terminal PDZ-ligand domain [70, 82]. E6-PDZ binding is sufficient to mediate suprabasal cell proliferation [83, 84] and may contribute to the development of metastatic tumours by disrupting normal cell adhesion. On the other hand, the E7 viral is involved with members of the pocket protein family such as pRb, which is well documented. E7 binding to pRb displaces E2F, irrespective of the presence of external growth factors and leads to the expression of proteins necessary for DNA replication [70, 71, 78, 85].
\nTo address the role of E6/E7 genes in high-risk HPV-associated carcinogenesis
High-risk HPVs have been established as etiological agents of invasive cervical cancer, as more than 96% of these cancers are positive for high-risk HPVs which are the most common viral sexually transmitted infection worldwide [7–9]. Infection with high-risk HPVs is important for the development of premalignant lesions and/or progression of the disease [10, 11]. Additionally, it was revealed that high-risk HPVs have carcinogenic effects at several other anatomical regions in women and men such as HN as well as colorectal [12–15]. These studies showed that high-risk HPVs are present in roughly 30 and 70% of HN and colorectal cancers, respectively, especially in their invasive form [14, 15]. Therefore, several recent studies including one from our group pointed-out that high-risk HPVs are present in human CRCs, specifically types 16, 18, 31, 33, and 35 [7, 12, 15, 16, 52]. Moreover, six recent meta-analysis studies confirmed the presence of high-risk HPVs in human CRCs [70, 91–95]; however, the prevalence of high-risk HPVs varied from one geographic location to another [7, 52]. Meanwhile, it was stated that high-risk HPVs are present especially in the invasive form of these malignancies worldwide [15].
\nNevertheless, it is important to mention that high-risk HPV infection alone is not sufficient to induce neoplastic transformation of human normal epithelial cells; the infected cells must undergo additional genetic changes and/or coinfection with another oncovirus to reach full transformation and consequently tumor formation. Based on this fact, we have developed a new model to study the cooperation effect between high-risk HPVs and other oncogenes in human carcinogenesis using human normal epithelial (HNE) cells. In this model, we established that E6/E7 oncoproteins of high-risk type 16 cooperate with the ErbB-2 receptor to induce cellular transformation of HNE cells; this was accompanied by a delocalization of β-catenin from the undercoat membrane to the nucleus in HNE cells. Furthermore, we reported that cyclin D1 is the target of E6/E7/ErbB-2 cooperation via the conversion of β-catenin’s role from a cell–cell adhesion molecule to a transcriptional regulator [96]. In parallel, we revealed that D-type cyclins (D1, D2, and D3) are essential for cell transformation induced by E6/E7/ErbB-2 cooperation in human HNE and mouse normal embryonic fibroblast (NEF) cells [96, 97]. Finally, we were able to show that the cooperation effect of E6/E7 with ErbB-2, in human normal epithelial and cancer cells, occurs via β-catenin tyrosine phosphorylation through pp60 (c-Src) kinase activation [98, 99]. Thus, the cooperation between E6/E7 oncoproteins of high-risk HPVs and other oncogenes could occur in colorectal carcinogenesis.
\nE6/E7 oncoproteins of high-risk HPV type 16 induce cellular transformation in human primary normal colorectal “mesenchymal” cell lines, NCE1, and NCE5 cells [103]. We note that NCE1 and NCE5 cells are unable to grow in soft agar. In contrast, NCE1 and NCE5 cells expressing E6/E7 oncoproteins form colonies in soft agar assay, which is an important characteristic of cancer cells.
On the other hand, and to determine the role of high-risk HPVs infection in human cancer cells, we examined the effect of E6/E7 of HPV type 16 in two noninvasive human breast cancer cell lines. We reported that E6/E7 of HPV type 16 induce cell invasive and metastatic abilities of the two cell lines
In order to investigate the role of high-risk HPV infection in human colorectal carcinogenesis, we examined the effect of E6/E7 of HPV type 16 in two human primary normal colorectal “mesenchymal” cell lines, NCM1 and NCM5, which were established in our laboratory [20]. We found that the expression of E6/E7 oncoproteins stimulate cell proliferation and induce cellular transformation (Figure 1) and migration of NCM1 and NCM5 cell lines. Moreover, our data revealed that E6/E7 of HPV type 16 provoke the upregulation of D-type cyclins and Cyclin E as well as Id-1 in these cell lines [103]. It is important to highlight that there are no other studies regarding the role of E6/E7 oncoproteins of high-risk HPVs in human colorectal cancers. Meanwhile, the function of E5 oncoprotein, in these malignancies, has not been investigated yet.
\n\nAdditionally, we have recently investigated the incidence of high-risk HPVs in human CRCs in the Syrian population in a cohort of 78 cancer samples using PCR and tissue microarray analyses. We reported, for the first time, that high-risk HPVs are present in 42 samples (53.84%), which represent the majority of invasive colorectal cases; more significantly, our data pointed-out that the most frequent high-risk HPV types in the Syrian population are 16, 33, 18, 35, and 31, respectively. Furthermore, the expression of E6 oncoprotein of high-risk HPVs was found to be correlated with Fascin, Id-1, and P-cadherin expression/overexpression in the majority of cancer tissue samples, which are major regulators of cell invasion and metastasis [17–19, 52]. Our data imply that high-risk HPVs are present in human CRCs, and their presence is associated with invasive and metastatic phenotype [16, 52, 104]. Collectively, these data suggest that high-risk HPVs are present in CRCs and therefore could play an important role in the initiation and progression of these cancers. Thus, we believe that high-risk HPVs can be associated with a subset of colorectal cancers. However, future large-scale multicenter case–control studies with data on risk factors such as lifestyle and sexual behavior are needed; meanwhile, molecular and cellular studies are necessary to determine the role of E5 and E6/E7 oncoproteins in human colorectal cancer and normal cells since it was proposed that E5 can cooperate with E6/E7 oncoproteins to enhance cancer progression of other human malignancies via the EMT event [20, 52]. Thus, we believe that E5 and E6/E7 of high-risk HPVs can cooperate with other oncogenes and/or risk factors such as smoking or alcohol to initiate colorectal cancer; in addition, E5 could cooperate with E6/E7 to enhance cancer progression of this malignancy via the EMT event (Figure 2).
\nE5 and E6/E7 of high-risk HPVs cooperation and colorectal carcinogenesis. We believe that E5 and E6/E7 of high-risk HPVs can cooperate with other oncogene overexpressions that are linked to lifestyle or/and environmental factors to induce cellular transformation and consequently tumor formation. On the other hand, E5 and E6/E7 together can enhance cancer progression of colorectal cancer via the initiation of the epithelial-mesenchymal transition (EMT) event .
Finally, we think it is important to talk about the prevention strategy of HPV infections and their related cancers, which is essentially based on HPV vaccines. These vaccines are made of virus-like particles (VLPs) that contain inactive L1 HPV proteins—proteins from and specific to each type of HPV viruses [105, 106]. Thus, the quadrivalent vaccine Gardasil (Merck and Co) was developed and approved by the FDA in 2006 for protection against low-risk HPV types 6 and 11, which cause genital warts—and rarely, nongenital warts [107] and high-risk HPV types 16 and 18 [108]. The quadrivalent vaccine will not protect against anogenital disease other than HPV types 6, 11, 16, and 18 [109, 110]. In 2010, the FDA approved the quadrivalent vaccine for the prevention of CRC [106]. The efficacy of prevention of rectal intraepithelial neoplasia in some group of patients is 77.5% [111]. In 2009, a bivalent vaccine (Cervarix; GlaxoSmithKline) was approved for the prevention of HPV infections from high-risk types 16 and 18 [112]. On December 10, 2014, the FDA approved a 9-valent HPV vaccine (Gardasil-9; Merck and Co) that was approved to be given in three intramuscular doses to males 9–15 years of age and females 9–26 years of age [106, 113]. The 9-valent HPV vaccine targets high-risk HPV type 16 (responsible for 50% of cervical carcinogenesis) [114], high-risk HPV type 18 (detected in 20% of cervical cancers) [115], and types 31, 33, 45, 52, and 58, which are responsible for 25% of cervical cancers. Immunizations against low-risk HPV types 6 and 11, which cause genital warts, are also included in the 9-valent vaccine [106, 116]. Approval of the 9-valent vaccine was based on a randomized control study with 14,000 females 16–26 years of age; it noted efficacy of 97% [106]. Therefore, this vaccine will have an important role in preventing HPV infections and their related cancers including colorectal malignancies and their metastasis.
\nThis chapter presented substantial evidence that high-risk HPVs are present in human CRCs, thereby these viruses, through their E5 and E6/E7 oncoproteins, could play an important role in the initiation and progression of these malignances (Figure 2) [20, 100]. However, we believe that further studies are required to determine the function of E5 and E6/E7 oncogenes in human colorectal normal and cancer cells. Thus, developing new
Alternatively, and with regards to colorectal malignancies as well as other human carcinomas prevention, we assume that the elimination of a number of known risk factors especially unprotected sexual activity, physical inactivity, smoking, alcohol, high consumption of red meat, and oncovirus infections such as high-risk HPVs could diminish the development of these malignancies and their metastases [20, 23, 26]. Additionally, prevention methodologies of high-risk HPVs using presently available vaccines could greatly reduce high-risk HPVs-associated cancers, including colorectal, and their progression to invasive form, which is responsible for the majority of cancer-related deaths.
\nWe are grateful to Mrs. A. Kassab for her critical reading of the chapter. The research works from Dr. Al Moustafa’s laboratory is supported by the College of Medicine of Qatar University.
\nTerpenes are chemical molecules synthesized from isoprene, 2-methyl-1,3 butadiene which are polymerized, thus obtaining one of nature’s most diversified families of secondary metabolites.
The chemical diversity of terpenes is determined by the polymerization capacity of isoprene; because of this their classification is linked to the addition of five carbons to the basic molecular unit. The biosynthesis of the chemical precursors of isoprene, dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) is produced by two diversified metabolic routes, the mevalonate route (MEV) and the 2C-Methyl-D-erythirol-4-phosphate (MEP) route [1].
DMAPP and IPP are hemiterpenes and are responsible of forming the various subclasses of compounds that make up the terpenes. Additionally, these isoprene polymers can be linear or can form rings and adhere to their structure oxygen and nitrogen atoms. The approximate number of known terpenes is close to 55,000 compounds [2].
Traditionally they are classified as [3]:
Hemiterpenes. These are constituted by five carbon atoms and are the basic units of the terpenes, the best-known example is 2-methyl-1,3 butadiene or isoprene.
Monoterpenes. These are constituted by 10 carbon atoms, resulting from the union of two units of isoprene, which are abundant in essential oils. Some important substances are: pinene, myrcene, limonene, thujene, etc.
Sesquiterpenes. These are formed by 15 carbon atoms, which are the result of the junction of three units of isoprene, some examples are: bisabolene, zingiberene, germacrene, caryophyllene, etc.
Diterpenes. These are formed by 20 carbon atoms or four units of isoprene; some important compounds are retinol, taxol and phytol.
Triterpenes. Squalene and several phytosterols such as sitosterol stand out among the terpenes containing 30 carbon atoms or six units of isoprene.
Tetraterpenes. These are constituted by 40 carbon atoms and eight units of isoprene, many of them are dyes like carotenes, among these the most important are carotene, lycopene and bixin.
Polyterpenes. These are composed of more than 40 carbon atoms; they are often found in gums and latex of various plant species.
Essential oils are common secondary metabolites in vegetables. From 10 to 200 compounds can be found in an essential oil, and their main characteristic is their ability to evaporate at room temperature. The chemical variability in an oil is significant; however, its components can be classified into three large groups (Figure 1).
Main molecules of essential oils.
Terpenes are the majority group, being monoterpenes and sesquiterpenes the most abundant. These can be present as hydrocarbons, consisting of carbon and hydrogen, or can have various functional groups such as alcohols, thiols, aldehydes, ketones, and ethers.
The second group of importance is aromatic compounds, many of them with an important biological activity such as derivatives of cinnamaldehyde, thymol, anethole or carvacrol.
There is a third miscellaneous group in a lower proportion that groups various molecules such as hydrocarbons, aldehydes, ketones, esters, etc. Examples of these substances are isovaleraldehyde or dodecanal.
Essential oils are usually found in low concentrations in plant organisms, ranging from 0.1 to 1%. They can exceed this value as is the case of clove oil with up to 10%, and are present in all plant organs and leaves:
The extraction processes are diverse, depending on the part of the plant used; the simplest and most widespread is the extraction by distillation with steam current, which does not require expensive equipment. Other methods are mechanical extraction used mainly to obtain oil from citrus pericarps, extraction using solvents which is useful when components can be affected by high temperatures and extraction using a supercritical CO2 current, which does not need high temperatures while maintaining the chemistry of molecules, but it is very expensive to implement.
About 4000 species have been investigated by their ability to produce essential oils, but only about 30 are marketed massively globally; their main use is intended for the cosmetic industry and aromatherapy, although several of the compounds from essences could be valuable to the pharmaceutical industry. There are certainly still species whose essential oils have not been analyzed in their chemical composition or in their bioactivity, which could be interesting as a source of new secondary metabolites.
Since they are volatile metabolites, their low boiling points make it possible to have them as steam in a remarkably simple way; for this reason the ideal analysis is gas chromatography with GC/MS mass spectrometry.
The use of capillary columns has made it possible to have defined separations in essential oils that exceed 100 compounds, usually chromatographic separation is made in nonpolar columns with 95% dimethylpolysiloxane, due to the fact that several components of an essential oil contain polar groups such as hydroxyl (OH); the realization of these components using columns of intermediate polarity has been made. Both assays result in a complete chemical inquiry of molecules and are complementary. The correct structural elucidation is performed by combining several analyses such as comparison with spectrum databases and the theoretical and experimental determination of the retention rates of the compounds. For this purpose, there are databases, being the most used the “Identification of essential oil components by gas chomatography/mass spectrometry,” with approximately 4000 compounds from essential oils [4].
The GC/MS technique is limited in the fact that it is ineffective in evaluating stereoisomers, in such cases it is necessary to use chiral columns or techniques such as nuclear magnetic resonance imaging.
A more thorough investigation of the chemical identity of the molecules of an essential oil can be done with an equipment that couples gas chromatography with spectrophotometric techniques, such as nuclear magnetic resonance imaging and infrared spectroscopy. It is also possible to analyze NMR or IR spectra in previously isolated molecules by column or thin layer chromatography [5].
Several monoterpenes have a diverse and useful biological activity for treating diseases and ailments; some have valuable aromatic characteristics in cosmetics and perfumery. Those molecules that have relevant information and studies are analyzed to verify their use as phytotherapeutic elements (Figure 2).
Monoterpene molecules with therapeutic importance.
Pinenes. These have alpha and beta isomers; their formula is C10H10 and they are common in essential oils from conifers, although they can be found in many other species such as rosemary and lavender [6, 7, 8]; oils with high concentrations of pinenes generally have antimicrobial activity [8, 9]. Traditionally many plants containing pinene-rich essential oils are used in respiratory system disease [9].
1–8 cineol (Eucalyptol). Oxygenated monoterpene has a C10H18O formula whose functional group is an ether that is present in many varieties of eucalyptus. Among its most noteworthy properties are analgesic, anti-inflammatory and antimicrobial [10]. Plants with eucalyptol-rich essential oils are used for expectorant and decongestant properties of the respiratory system [11].
Limonene. It is a monoterpene whose formula is C10H16; it has two optical isomers R-limonene or D- limonene and S-limonene or L-limonene, which stand out by the insecticide [12, 13] and antimicrobial properties [14].
Myrcene. It is a monoterpene whose formula is C10H16; it is the main component of
Linalool. It is a hydroxylated monoterpene with C10H18O formula, its pleasant aroma makes it widely used in perfumery. Its action on the central nervous system is evidenced by its sedative, anxiolytic, analgesic and anti-inflammatory properties [19, 20]. Its antimicrobial and antioxidant properties have been evaluated with good results [21, 22].
Citral. It is an oxygenated monoterpene containing a group of aldehyde; its formula is C10H16O. There are two isomers known as neral (cis isomer) and geranial (trans isomer) [23], which are abundant in species such as
Camphor. It is an oxygenated monoterpene whose functional group is a ketone; its formula is C10H16O and it is present in two optical isomers R and S, which are abundant in the species
Menthol. It is a hydroxylated monoterpene, with a C10H20O formula, which has seven isomers that are very common in mint varieties such as Peppermint. It is one of the most used compounds in the food, cosmetic, pharmaceutical industries, and pesticides, among others. Its aromatic properties are very well known [30]; however, its most noticeable and known effect is that of analgesia at the topical level [31, 32].
Terpineol. It is a hydroxylated monoterpene with a C10H18O formula. It is known by having five isomers (α, β, γ, δ and 4-terpineol) [33], which are abundant in the essential oil of tea tree (
Citronellol. It is a hydroxylated monoterpene with a C10H20O formula. There are two enantiomers (+)-citronellol and (−)-citronellol [36]. The first is quite common in citronella oil, and the second is abundant in rose oil [37], which is used in perfumery. Its properties are insecticide [38], analgesic and anti-inflammatory [39], and antioxidant [40].
Several molecules with interesting properties can be found in C15 sesquiterpene (Figure 3). From a therapeutic view, there is evidence that validates its biological activity, highlighting anti-inflammatory, analgesic and anticancer trials.
Sesquiterpene molecules with therapeutic purposes.
Bisabolol. These are isomers, out of which stand (−)-α-Bisabolol, (−)-epi-α-Bisabolol, (+)-α-Bisabolol and (+)-epi-α-Bisabolol which are abundant in the species
β-Caryophyllene. It has a C15H24 formula. It is one of the most abundant sesquiterpenes in essential oils. Various bioactivity studies have been carried out in this molecule with good results, such as analgesic [45, 46], anti-inflammatory [47] and anticancer [48].
Chamazulene. With a C14H16 formula, it is a molecule derived from the sesquiterpene matricina, which is one of the few aromatic molecules that have a blue coloration. It is found in
Caryophyllene oxide. It is an oxygenated sesquiterpene with a C15H24O formula; it has properties similar to those of caryophyllene, such as analgesic and anti-inflammatory [53].
Germacrene. It belongs to the sesquiterpenes family, and it has three double links in its structure. There are five types of germacrenes: A, B, C, D, E. Recent studies mention its antioxidant potential [5, 54].
Artemisinic acid. It has a C15H22O2 formula, and it is one of the most interesting sesquiterpenes for health due to its antimalarial properties [55]. It is abundant in the species
Patchoulene. It is a sesquiterpene with a C15H24 formula. It is common to find its isomers α, β, α, and δ in essential oils. It is attributed to various types of bioactivity, the most relevant being those found in β-patchoulene as anti-inflammatory [57], antigastritis [58, 59], and cosmetic [60].
Humulene. Also known as α-caryophyllene, its formula is C15H24. It is named after the essential oil of the species
Bergamotene. It is a sesquiterpene with a C15H24 formula. It has four isomers α-cis, β-cis, α-trans and β-trans. It is found in several citric species such as
Farnesene. It has a C15H24 formula. It is a molecule found in several essential oils, and it is a precursor to many other sesquiterpenes since its open-chain structure and its 4-double bonds contribute to this action, as well as in the possibility of having a wide variety of isomers between geometrics and stereoisomers. Its cytotoxic and genotoxic [68], insecticide [69] and neuroprotective effects [70, 71] have been evaluated.
Eudesmol. Hydroxylated sesquiterpene with a C15H26O formula is a very interesting molecule by the multiple positive bioactivity assays, highlighting antimicrobial and antifungal [72], anticancer [73, 74] and antiangiogenic [75].
Most of the terpenes present in essential oils have some degree of toxicity, which is not detected when consuming aromatic species directly because in most cases the oil yield is low. Many commonly used essential oil components are potentially dermal irritating with restrictions on application concentrations [76, 77]. There are also some terpenes whose toxicity is much more dangerous, such as pulegone which causes liver damage and seizures [78], and thujone that can cause dementia by being neurotoxic [79].
This brief review has shown the chemical and biological importance of low molecular weight and volatile terpenes. For this reason, components of secondary metabolites are known as essential oils. The abundance of these molecules is much higher than the one presented in this chapter, since the information presented covers those whose scientific evidence and industrial importance are references in this family of metabolites. There is still much research to be carried out on the hundreds of molecules from which there is still little or no information. There are still aromatic species whose essential oils have not yet been described and that could be a source of new monoterpenes and sesquiterpenes that are beneficial to humans.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
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His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. 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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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The target disorder was focused on infection. In the practice of pathology diagnosis services, it is important for us diagnostic pathologists to judge whether the lesion is caused by an infection or not. When an infectious disease is highly likely, the visualization of pathogens within the inflammatory lesion is required to suggest a causative agent. Two main approaches the author would like to introduce include (1) the use of commercially available antisera showing wide cross-reactivity to a variety of bacteria and (2) the use of diluted patients’ sera. 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This revolutionary technology is providing an important visual technique for tumor examination in formalin-fixed paraffin-embedded specimens for a better understanding of tumor microenvironment, new treatment discoveries, cancer prevention, as well as translational studies. The aim of this chapter is to highlight the use of tyramide signal amplification methodology in mIF and image analysis to identify several proteins at the same time in one single tissue and their spatial distribution in different tumor specimens including whole sections, core needle biopsies, and tissue microarrays. This type of methodology associated with image analysis can perform high-quality throughput assay in translational research studies to be applied in cancer prevention and treatments.",book:{id:"7013",slug:"immunohistochemistry-the-ageless-biotechnology",title:"Immunohistochemistry",fullTitle:"Immunohistochemistry - The Ageless Biotechnology"},signatures:"Edwin Roger Parra",authors:null},{id:"64808",title:"Detection Systems in Immunohistochemistry",slug:"detection-systems-in-immunohistochemistry",totalDownloads:2033,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Immunohistochemistry (IHC) is a process of selectively imaging antigens in cells or tissue sections by exploiting antibody specificity. This technique is widely used in diagnostic pathology and research experiments for tracking specific molecular markers characteristic of a particular cell type or cellular events such as cancerous cell development, cell proliferation, or apoptosis. Visualizing the target antigen following an antibody-antigen interaction is accomplished by different detection systems. In the simplest instance, primary antibody directly conjugated to an enzyme is responsible for both specifically binding to the antigen and catalyzing a color-producing reaction. Alternatively, complex detection systems could be designed to profoundly improve minimal detection level of the antigen. During the past years, there has been a considerable improvement in designing and introduction of new and highly sensitive detection systems. The choice of an IHC detection system is a compromise of a variety of variables including desired sensitivity, cost, and the time needed for an IHC staining to be performed. This chapter covers the immunohistochemistry detection systems with emphasis on their principle, history, advantages, and limitations and delineates factors needed to be considered for choosing an appropriate detection system for IHC applications.",book:{id:"7013",slug:"immunohistochemistry-the-ageless-biotechnology",title:"Immunohistochemistry",fullTitle:"Immunohistochemistry - The Ageless Biotechnology"},signatures:"Sorour Shojaeian, Nasim Maslehat Lay and Amir-Hassan Zarnani",authors:null},{id:"65712",title:"In Situ Identification of Ectoenzymes Involved in the Hydrolysis of Extracellular Nucleotides",slug:"in-situ-identification-of-ectoenzymes-involved-in-the-hydrolysis-of-extracellular-nucleotides",totalDownloads:922,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Adenosine triphosphate (ATP) and other nucleotides and nucleosides, such as adenosine, are signaling molecules involved in many physiological and pathophysiological processes. The group of cell and tissue responses mediated by these molecules is known as purinergic signaling. Ecto-nucleotidases are ectoenzymes expressed at the cell membrane that act sequentially to efficiently hydrolyze extracellular ATP into adenosine, and they are key elements of this signaling. There is growing interest in studying these enzymes in relation to various pathologies, especially those with an inflammatory component such as cancer. This review summarizes the main protocols for the study of the expression and in situ activity of ectoenzymes in tissue slices and cultured cells.",book:{id:"7013",slug:"immunohistochemistry-the-ageless-biotechnology",title:"Immunohistochemistry",fullTitle:"Immunohistochemistry - The Ageless Biotechnology"},signatures:"Mireia Martín-Satué, Aitor Rodríguez-Martínez and Carla Trapero",authors:null},{id:"66392",title:"Low-Specificity and High-Sensitivity Immunostaining for Demonstrating Pathogens in Formalin-Fixed, Paraffin-Embedded Sections",slug:"low-specificity-and-high-sensitivity-immunostaining-for-demonstrating-pathogens-in-formalin-fixed-pa",totalDownloads:1266,totalCrossrefCites:5,totalDimensionsCites:5,abstract:"The present review describes a part of the author’s own experience in applying immunoperoxidase staining to routine histopathological diagnosis. The target disorder was focused on infection. In the practice of pathology diagnosis services, it is important for us diagnostic pathologists to judge whether the lesion is caused by an infection or not. When an infectious disease is highly likely, the visualization of pathogens within the inflammatory lesion is required to suggest a causative agent. Two main approaches the author would like to introduce include (1) the use of commercially available antisera showing wide cross-reactivity to a variety of bacteria and (2) the use of diluted patients’ sera. These immunohistochemical studies employing “low-specificity” and “high-sensitivity” probes are useful for confirming the localization of pathogen within the infectious lesion.",book:{id:"7013",slug:"immunohistochemistry-the-ageless-biotechnology",title:"Immunohistochemistry",fullTitle:"Immunohistochemistry - The Ageless Biotechnology"},signatures:"Yutaka Tsutsumi",authors:[{id:"280338",title:"Dr.",name:"Yutaka",middleName:null,surname:"Tsutsumi",slug:"yutaka-tsutsumi",fullName:"Yutaka Tsutsumi"}]},{id:"78305",title:"Anti-Microbial Peptides: The Importance of Structure-Function Analysis in the Design of New AMPs",slug:"anti-microbial-peptides-the-importance-of-structure-function-analysis-in-the-design-of-new-amps",totalDownloads:53,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In recent years the rapid emergence of drug resistant microorganisms has become a major health problem worldwide. The number of multidrug resistant (MDR) bacteria is in a rapid increase. Therefore, there is an urgent need to develop new antimicrobial agent that is active against MDR. Among the possible candidates, antimicrobial peptides (AMPs) represent a promising alternative. Many AMPs candidates were in clinical development and the Nisin was approved in many food products. Exact mechanism of AMPs action has not been fully elucidated. More comprehensive of the mechanism of action provide a path towards overcoming the toxicity limitation. This chapter is a review that provides an overview of bacterial AMPs named bacteriocin, focusing on their diverse mechanism of action. We develop here the structure–function relationship of many AMPs. A good understanding of AMPS structure–function relationship can helps the scientific in the conception of new active AMPs by the evaluation of the role of each residue and the determination of the essential amino acids for activity. This feature helps the development of the second-generation AMPs with high potential antimicrobial activity and more.",book:{id:"10874",slug:null,title:"Insights on Antimicrobial Peptides",fullTitle:"Insights on Antimicrobial Peptides"},signatures:"Awatef Ouertani, Amor Mosbah and Ameur Cherif",authors:null}],onlineFirstChaptersFilter:{topicId:"149",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"80915",title:"Molecular Pathogenesis of Inflammatory Cytokines in Insulin Resistance Diabetes Mellitus",slug:"molecular-pathogenesis-of-inflammatory-cytokines-in-insulin-resistance-diabetes-mellitus",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.100971",abstract:"Diabetes Mellitus Type 2 (T2DM) is a non-communicable and multifactorial disease. It is a leading cause of premature deaths worldwide. Inflammatory cytokines are reported that they have potential to enhance insulin resistance and hence T2DM. The current research was taken to investigate the possible role of inflammatory mediators: Tumor Necrosis Factor (TNF-α) and White blood cells (WBC’s) in mobilizing biological molecules mainly immunological nature. A total of 320 subjects were selected in this study among them 160 were T2DM cases and 160 were healthy controls. Serum concentration of Tumor Necrosis Factor-a (TNF-α) was quantified by ELISA method, WBC count was measured on Sysmax (Germany) hematology analyzer, biochemical and Immunoassay parameters were done on fully automatic analyzers. The expression of candidate pro-inflammatory cytokine (TNF-α), and (WBC’s) were elevated in T2DM. TNF-α shows association (p<0.001) with glycemic profile and insulin sensitivity in T2DM cases in comparison with healthy controls. Induction of inflammation and up regulation of pro-inflammatory cytokines has been purported to play a significant role in pathogenesis of T2DM and study confirms that the positive correlation of TNF-α with T2DM and hence to insulin sensitivity. These can act as early prediction biomarkers in diagnosis and prognosis of human disease i.e Diabetes Mellitus. Further studies are needed to help clinicians manage and treat T2DM effectively.",book:{id:"10874",title:"Insights on Antimicrobial Peptides",coverURL:"https://cdn.intechopen.com/books/images_new/10874.jpg"},signatures:"Haamid Bashir, Mohammad Hayat Bhat and Sabhiya Majid"},{id:"81299",title:"Peptides with Therapeutic Potential against Acinetobacter baumanii Infections",slug:"peptides-with-therapeutic-potential-against-em-acinetobacter-baumanii-em-infections",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.100389",abstract:"Antibiotic poly-resistance (multi drug-, extreme-, and pan-drug resistance) is a major global threat to public health. Unfortunately, in 2017, the World Health Organization (WHO) introduced the carbapenemresistant isolates in the priority pathogens list for which new effective antibiotics or new ways of treating the infections caused by them are urgently needed. Acinetobacter baumannii is one of the most critical ESKAPE pathogens for which the treatment of resistant isolates have caused severe problems; its clinically significant features include resistance to UV light, drying, disinfectants, and antibiotics. Among the various suggested options, one of the antimicrobial agents with high potential to produce new anti-Acinetobacter drugs is the antimicrobial peptides (AMPs). AMPs are naturally produced by living organisms and protect the host against pathogens as a part of innate immunity. The main mechanisms action of AMPs are the ability to cause cell membrane and cell wall damage, the inhibition of protein synthesis, nucleic acids, and the induction of apoptosis and necrosis. AMPs would be likely among the main anti-A. baumannii drugs in the post-antibiotic era. Also, the application of computer science to increase anti-A. baumannii activity and reduce toxicity is also being developed.",book:{id:"10874",title:"Insights on Antimicrobial Peptides",coverURL:"https://cdn.intechopen.com/books/images_new/10874.jpg"},signatures:"Karyne Rangel and Salvatore Giovanni De-Simone"},{id:"78305",title:"Anti-Microbial Peptides: The Importance of Structure-Function Analysis in the Design of New AMPs",slug:"anti-microbial-peptides-the-importance-of-structure-function-analysis-in-the-design-of-new-amps",totalDownloads:59,totalDimensionsCites:0,doi:"10.5772/intechopen.99801",abstract:"In recent years the rapid emergence of drug resistant microorganisms has become a major health problem worldwide. The number of multidrug resistant (MDR) bacteria is in a rapid increase. Therefore, there is an urgent need to develop new antimicrobial agent that is active against MDR. Among the possible candidates, antimicrobial peptides (AMPs) represent a promising alternative. Many AMPs candidates were in clinical development and the Nisin was approved in many food products. Exact mechanism of AMPs action has not been fully elucidated. More comprehensive of the mechanism of action provide a path towards overcoming the toxicity limitation. This chapter is a review that provides an overview of bacterial AMPs named bacteriocin, focusing on their diverse mechanism of action. We develop here the structure–function relationship of many AMPs. A good understanding of AMPS structure–function relationship can helps the scientific in the conception of new active AMPs by the evaluation of the role of each residue and the determination of the essential amino acids for activity. This feature helps the development of the second-generation AMPs with high potential antimicrobial activity and more.",book:{id:"10874",title:"Insights on Antimicrobial Peptides",coverURL:"https://cdn.intechopen.com/books/images_new/10874.jpg"},signatures:"Awatef Ouertani, Amor Mosbah and Ameur Cherif"},{id:"79192",title:"Mass Spectrometry (Imaging) for Detection and Identification of Cyclic AMPs: Focus on Human Neutrophil Peptides (HNPs)",slug:"mass-spectrometry-imaging-for-detection-and-identification-of-cyclic-amps-focus-on-human-neutrophil-",totalDownloads:71,totalDimensionsCites:0,doi:"10.5772/intechopen.99251",abstract:"Antimicrobial peptides (AMPs) are known best for their role in innate immunity against bacteria, viruses, parasites and fungi. However, not only are they showing increasing promise as potential antimicrobial drug candidates, recently, it has been reported that certain AMPs also show a cytotoxic effect against cancer cells. Their possible antitumor effect could make AMPs interesting candidate cancer biomarkers and a possible lead for new anticancer therapy. Due to their cyclic structure, detection and identification of AMPs is challenging, however, mass spectrometry (imaging; MSI) has been shown as a powerful tool for visualization and identification of (unknown) cyclic AMPs. In this chapter, we will discuss how mass spectrometry (imaging), combined with the use of electron-transfer dissociation (ETD) as fragmentation technique, can be used as a reliable method to identify AMPs in their native cyclic state. Using this approach, we have previously detected and identified human neutrophil peptides (HNPs) as important AMPs in cancer, of which a detailed bacterial, viral and cancer-related overview will be presented.",book:{id:"10874",title:"Insights on Antimicrobial Peptides",coverURL:"https://cdn.intechopen.com/books/images_new/10874.jpg"},signatures:"Eline Berghmans and Geert Baggerman"},{id:"78302",title:"Antimicrobial Peptides Derived from Ascidians and Associated Cyanobacteria",slug:"antimicrobial-peptides-derived-from-ascidians-and-associated-cyanobacteria",totalDownloads:74,totalDimensionsCites:0,doi:"10.5772/intechopen.99183",abstract:"Ascidians belonging to Phylum Chordata are the most largest and diverse of the Sub-phylum Tunicata (Urochordata). Marine ascidians are one of the richest sources of bioactive peptides. These bioactive peptides from marine ascidians are confined to various types of structures such as cyclic peptides, acyclic peptides (depsipeptides), linear helical peptides with abundance of one amino acid (proline, trytophane, histidine), peptides forming hairpin like beta sheets or α-helical/β-sheet mixed structures stabilized by intra molecular disulfide bonding. Cyanobactins are fabricated through the proteolytic cleavage and cyclization of precursor peptides coupled with further posttranslational modifications such as hydroxylation, glycosylation, heterocyclization, oxidation, or prenylation of amino acids. Ascidians are known to be a rich source of bioactive alkaloids. β-carbolines form a large group of tryptophan derived antibiotics. Pyridoacridines from ascidians are tetra- or penta- cyclic aromatic alkaloids with broad range of bioactivities. Didemnidines derived from ascidian symbiotic microbes are inhibitors of phospholipase A2 and induce cell apoptosis. Meridianins are indulged in inhibiting various protein kinases such as, cyclindependent kinases, glycogen synthase kinase-3, cyclic nucleotide dependent kinases, casein kinase, and also implicate their activity of interfering with topoisomerase, altering the mitochondrial membrane potential and binding to the DNA minor groove to inhibit transcriptional activation. Most of these bioactive compounds from ascidians are already in different phases of the clinical and pre-clinical trials. They can be used for their nutraceutical values because of their antineoplastic, antihypertensive, antioxidant, antimicrobial, cytotoxic, antibacterial, antifungal, insecticidal, anti-HIV and anti-parasitic, anti-malarial, anti-trypanosomal, anti-cancer etc. This chapter mostly deals with antibacterial compounds from ascidian and their associate symbiotic cyanobacteria.",book:{id:"10874",title:"Insights on Antimicrobial Peptides",coverURL:"https://cdn.intechopen.com/books/images_new/10874.jpg"},signatures:"Rajaian Pushpabai Rajesh and Grace Vanathi M"}],onlineFirstChaptersTotal:5},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:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,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:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,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:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. 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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. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of 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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{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:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{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:"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:"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:"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:"Igor Victorovich Lakhno 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.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in 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 been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), 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 a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). 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: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",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:"243698",title:"Dr.",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. 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