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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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Neutrophils are the most abundant circulating leukocytes. They are short-lived, terminally differentiated myeloid cells produced in the bone marrow. They contain intracellular granules and vesicles and a multi-lobed nucleus. The condensed nuclear chromatin is considered to indicate a limited transcriptional activity in the cells. Neutrophils are an important part of innate and adaptive immunity, and the first line of defense against invading pathogens. There are multiple types of proteins expressed on neutrophil surfaces, including Fc-receptors, adhesion molecules, integrins, multiple cytokine receptors, innate immune receptors such as Toll-like receptors, and C-type lectins. Some receptors directly recognize and bind to pathogens and play their role in the defensive functions, some other receptors, such as Fc-receptors, bind the Fc fragment of the antibody molecules to neutrophils, which enable the neutrophils to recognize the targets of the antibodies and then perform their functions in adaptive immunity. Some other receptors recognize the inflammatory signals. The extracellular structures from neutrophil surface proteins are involved in signal transduction, cell-cell interactions, neutrophil migration, and substance releases such as cytokines, reactive oxygen species, exocytosis of intracellular granules, and neutrophil extracellular trap (NET) formation, the structure that traps and kills the invading bacteria. Some of the glycoproteins expressed on the neutrophil surface carry the Neutrophil-Specific Antigens. The protective effects of neutrophils are also contributed by their ability to receive signals through their receptors that stimulate them to rapidly generate pseudopods, move and invade their targets. They phagocytize the microorganisms and digest them by proteolytic enzymes present in their intracellular granules. Eli Metchnikoff (1845–1916) of Pasteur Institute in Paris was the first investigator who identified neutrophil immunogenicity. He reported that guinea pigs injected with rabbit blood produce antibodies against rabbit leukocytes and called the antibodies leukoagglutinins and leukolysins [1]. In 1926, Charles Doan recognized that leukocyte incompatibility causes transfusion reaction and suggested that leukocytes have their own “groups” [2]. Jean Dausset later reported that the presence of leukoagglutinins in blood could be associated with chronic autoimmune neutropenia [3]. In 1957, Tom Brittingham, of the hematology team of Washington University in St. Louis, produced leukoagglutinins experimentally [4]. He volunteered to receive weekly 100 mL blood for nine consecutive weeks from a patient who had chronic myelogenous leukemia, the last four causing chills and fever. He could prevent the reaction by minimizing the number of injected leukocytes. To study the effects of antibodies in donors’ blood, he received 50 mL blood from a patient who had received numerous transfusions. This injection caused high fever, vomiting, dyspnea, cyanosis and hypotension. A chest X-ray on the following day revealed bilateral lung infiltrations, a reaction that is now recognized as transfusion-related acute lung injury (TRALI). Dausset [5] and others [6, 7] in subsequent years demonstrated inheritance of leukocyte antigens.
Neutrophil-specific antigens were identified during the investigation on alloimmune neonatal neutropenia (ANN), proven to be due to fetal-maternal incompatibility [8]. In that study, the first child had died from neutropenia and sepsis, and the three subsequent infants also had neutropenia at birth. The diagnosis of ANN was based on the detection of a strong leukoagglutinin in the maternal serum that reacted with the paternal neutrophils but not with the maternal own cells. The blood smear from the last infant showed the absence of mature neutrophils but lymphocytes, monocytes, eosinophils, basophils and platelets were normal. Neutrophil-specificity of the antibody was established by demonstrating that the antibody could be absorbed only by isolated neutrophils and not by any other blood cells or tissue cells [9]. An anti-5b antibody [10], known to react with all blood leukocytes and many other tissue cells tested, was used as a control and showed that the ANN antibody reacted only with neutrophils. This first neutrophil-specific antigen identified was named NA1, “N” for Neutrophil, “A” for the first locus, and 1 for the first allele. Further investigation on ANN led to the identification of other antigens including NA2, NC1 [9, 11], SH [12, 13] and HNA-1d [14]. ANN could be identified because the tests were directly performed on the blood from the affected infants and their parents, and not on blood samples from multiparous female donors who develop multiple forms of antibodies against the HLA, red blood cells and platelets. This may explain the reason for some other investigators inability to recognize ANN, and even conclude that neonatal neutropenia was the result of infection and not alloimmunization [15]. Neutrophil specificity causes ANN because the total neutrophil mass in fetus blood is small, and there are no other cell types in the body that express the same antigens and can absorb the maternal antibodies. The more common HLA antibodies in maternal blood do not cause ANN because HLA antigens are widely distributed in blood cells and other tissues, and also, as soluble antigens, can absorb the maternal-derived antibodies [16]. In one ANN example, both neutrophil-specific and HLA antibodies were detected in the maternal plasma, but only the neutrophil-specific antibody was detected in the affected newborn’s blood. ANN is a self-limited disorder and lasts as long as the maternal antibodies remain in the infant’s circulation, a period of a few weeks to a few months. The recovery can be predicted when the antibody can no longer be detected in the infant’s plasma. In ANN, the absolute neutrophil counts are below 500 and the common symptoms are omphalitis, and infections in the skin and in other locations. It has been estimated that ANN occurs in 0.1–0.2% of pregnancies. This may be an underestimation; because now most birth deliveries are performed under sterile conditions and the newborns are not exposed to bacteria, and consequently, neutropenic infants may remain asymptomatic and undiagnosed. Also, blood counts and differentials are not routinely tested on asymptomatic newborns. ANN, in contrast to erythroblastosis fetalis, known as Rh disease, can occur in the first pregnancies. This information should warn the blood banks that blood donors with single pregnancy and asymptomatic children or undiagnosed ANN infants may be carriers of the hazardous neutrophil-specific antibodies, and transfusion of their blood may result in severe reactions and even fatalities.
The second clinical disorder that increased interest in neutrophil-specific antigens was autoimmune neutropenia of infancy (AINI). In 1975, a strong anti-NA2 antibody was identified in the blood of a six months old infant. The antibody was not present in the mother’s blood and the child was too old to have ANN [17]. Additional studies [18] demonstrated autoantibodies on 119 of 121 severely neutropenic children. The disorder, called AINI, was shown to be very common and the autoantibodies were directed against neutrophil-specific antigens found in ANN. Thus far, the antigens NA, NB, ND1 [19] NE1 [20] and 9a [18] are associated with AINI, and some of these antibodies are also found in a few cases of autoimmune neutropenia in adults [16]. Before detection of autoantibodies and establishing the autoimmune nature of this disorder, AINI was recognized as “chronic benign neutropenia,” benign because it was a self-limited neutropenia disorder, lasting several months to a few years. The neutrophil count in blood of AINI patients is between zero to 500, and there is an elevation of monocytes and eosinophils, which may represent a protective defense mechanism. Pathogenesis of AINI has not yet been determined, but it has been suggested that a delay in maturation of the regulatory T-cells (T-regs) causes a lack of tolerance to neutrophil-specific antigens, and that the autoimmunity becomes corrected when T-regs become functional [21, 22].
The NA and NB antigen systems are the most investigated neutrophil-specific antigens and are discussed here, with their information summarized in Tables 1 and 2. The genetics and biological functions of these two systems are different and are described separately. However, their clinical impacts, such as their roles in ANN, AINI, blood transfusion, and bone marrow transplantation are similar. Also, in this report, the nomenclature used is based on the original and not the HNA that will be discussed separately.
System | Allele | Frequency | Location | Amino acids | MW (kDa)* | Chromosome | Exons | Nucleotide, base pairs |
---|---|---|---|---|---|---|---|---|
NA (CD16b) | NA1 | 0.560 | Membrane, intracellular | 233 | 58–65 | 1q23.3 | 5 | 699 |
NA2 | 0.885 | 233 | 65–80 | |||||
NA3 (SH) | 0.05 | 233 | 65–80 | |||||
NA4 (HNA1d) | Unknown | 233 | 65–80 | |||||
NAnull | Rare | |||||||
NB (CD177) | NB1 | 0.97 | Membrane, secondary granules, vesicles | 437 | 55–64 | 19q13.2 | 9; 6 in the pseudo-gene | 1614 |
Neutrophil-specific antigens, the NA and NB system.
Difference in molecular weight (MW) is due to differences in glycosylation.
System | Gene | Protein | Antigen name | Nucleotide | Amino acids |
---|---|---|---|---|---|
FcγRIIIb (CD16) | CD16 | NA1 | 108G, 114C, 194A, 233C, 244G, 316G | 36R, 38 L, 65 N, 78A, 82D, 106 V | |
NA2 | 108C, 114 T, 194G, 233A/C, 244A, 316A | 36S, 38 L, 65S, 78D/A, 82 N, 106I | |||
NA3 (SH) | 108C, 114 T, 194G, 233A, 244A, 316A | 36S, 38 L, 65S, 78D, 82 N, 106I | |||
NA4 (HNA1-d) | 108C,114 T,194G, 233A, 244A, 316A | 36S, 38 L, 655S, 78A, 82 N,106I | |||
NAnull | — | — | |||
CD177 | CD177 | NB1 | 787A | Full length | |
CD177 negative | NB2(?)* | NB2(?)* NB1-neg | 787 T | 264 (Truncated length) | |
CD177 | NB1 soluble in plasma | NB1 | 1291G > A | Truncated at the GPI-binding site |
Neutrophil-specific antigens alleles; nucleotide and amino acid differences.
NB2 is suggested to be a truncated protein, but needs to be confirmed.
Four expressing alleles, NA1, NA2, NA3 (SH), and NA4 are currently known in this system (Table 1). NA1 was the first, described with neonatal neutropenia. The antigen SH, here referred to as NA3, was first described in one case of ANN, and subsequently in three other cases [12, 13]. The antigen referred to as NA4, was originally described in two cases of ANN [14]. In rare individuals, the NA antigens are not expressed. This abnormality, caused by gene alteration, is called NAnull [12, 23, 24]. The NA antigens appear at the metamyelocytic phase of neutrophil maturation and are anchored on the cell membranes by the Glycosylphosphatydylinositol (GPI) at the density of 100,000 to 300,000 copies per cell [25, 26]. Some NA molecules are also stored inside the cells and translocate to the membrane and are released during cell activation. NA antigens are the low-affinity Fc-receptors, FcγRIII [27]. Fc-receptors are glycoproteins that bind the Fc fragment of immunoglobulins and connect the humoral to the cellular components of the immune system. In this process, the effector cell, via its Fc-receptor, is connected to the F(ab)2, the antigen-binding part of the antibodies. This connection leads to phagocytosis and antibody-mediated cell cytotoxicity (ADC) [28]. The genetic polymorphisms in the coding genes for Fc-receptors influence their effectiveness. Three Fc gamma receptor (FcγR) subclasses have been identified thus far: FcγRI, FcγRII, and FcγRIII [29]. The NA epitopes are located on FcγRIIIb (CD16b), exclusively expressed on neutrophils, bind Fc fragments of IgG1 and IgG3 immunoglobulin subclasses [30, 31]. The
NB1 [44, 45, 46], also known as CD177, is a cysteine-rich glycoprotein that expresses at the promyelocytic phase of neutrophil maturation [47]. This early expression on immature neutrophils causes the bone marrow of the newborns affected with NB1 alloimmune neonatal neutropenia, to show a “maturation arrest” profile, and even be misdiagnosed as acute leukemia. NB1 is anchored on the neutrophil membrane, and also mediates the expression of proteinase 3 (PR3), a serine protease enzyme, on the neutrophil membrane [48]. NB1 is also present in neutrophil secondary granules and intracellular vesicles. Stroncek and Skubitz determined that NB1 is a 58–65 KDa, GPI anchored glycoprotein [49, 50]. Not all circulating neutrophils in NB1-positive individuals carry the NB1 antigen on their surfaces [19, 51, 52]. This bimodal expression divides the neutrophils into NB1-positive and NB1-negative subpopulations in NB1-positive blood. Although, the percentage of NB1-positive neutrophils remains stable, infection, pregnancy, treatment with granulocyte-colony stimulating factor (G-CSF), and Polycythemia Rubra Vera (PRV) upregulate, CD177 expression [49, 53, 54]. CD177 is not detectable on neutrophils of 3–5% of normal populations. These individuals are defined as CD177-null. Kissel [55] sequenced the gene and determined it to be composed of 1614 base pair nucleotides, belonging to the urokinase-type Plasminogen Activator Receptor Superfamily (uPAR, CD59, Ly6), located on chromosome 19q13.3 [53]. The gene has 9 exons and a pseudogene composed of 6 exons derived from the original gene and is reversely positioned [52, 56, 57, 58]. A missense mutation in exon 7 of CD177 gene, c.787A > T replaces amino acid 263 with a stop codon and induces production of a truncated protein and consequently loss of CD177 expression on the neutrophil surface (Table 2) [57]. The stop codon responsible for the absence of CD177 protein on the neutrophil surface arises when exon 7 in the CD177 coding region is provided by the CD177 pseudogene, called CD177P1 [52]. The heritable ratio between CD177/CD177P1 determines CD177 high and low expression; individuals homozygous for the CD177 gene have higher CD177 expression whereas the existence of CD177P1 sequence in the CD177 gene leads to the presence of CD177 negative subpopulation [52]. However, in only 40% of CD177-null individuals, the presence of c.787 T homozygote is responsible for the absence of CD177 protein from the neutrophil surface [58, 59]. Later studies have added c.1291G > A SNP that affects the GPI anchor region of CD177 molecule and converts membrane-bound to the soluble form of CD177. This polymorphism has been introduced as a genetic regulator for atypical/low expression that participates in the mechanism of CD177 deficiency. The combination of SNPs, c.787 T and c.1291A is responsible to regulate the presence of CD177 on the neutrophil surface [60]. A study on the epigenetic component that regulates CD177 expression, has documented a non-classical random monoallelic expression (MAE) on neutrophil subsets of CD177 positive individuals [61]. The complete absence of gene transcription (neither complete, nor truncated) in the CD177 negative neutrophil subpopulation has been introduced as a mechanism regulating the absence of CD177 protein on the CD177 negative subpopulation. However, later study analyzing mRNA content in sorted CD177 positive and negative subpopulations has shown the presence of CD177 mRNA in both neutrophil subsets and doubted the previous observation [59]. Additional interpretation on the potential role of c.787 T and c.1291 on NB system is presented in the NB2–dilemma subsection, separately.
The role of CD177 on neutrophil function is complicated and poorly understood. Physical association of CD177 with CD11b/CD18, concentrated on lipid rafts, support transduction of signals initiated after binding of anti-PR3 antibodies (such as Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA)) on CD177/PR3 complex toward neutrophil cytoplasm and consequently leads to neutrophil activation, degranulation, and superoxide production [62]. The association of CD177 in ANCA-mediated neutrophil degranulation may explain the selective activation of CD177 positive neutrophil subsets involved in the mechanism of ANCA-associated vasculitis (AAV). Analysis has introduced an epitope formed by CD177/PR3 complex as a relevant epitope for CD177 autoantibodies but not isoantibodies. Interestingly this epitope is a signaling relevant epitope that upon binding of relevant antibodies induces neutrophil activation [63]. A previous study indicated CD177 as a heterophilic binding partner for platelet endothelial cell adhesion molecule 1 (PECAM-1). Inhibitory analysis has introduced PECAM-1 membrane-proximal domain 6 to mediate the binding of CD177. The later study however introduced PR3 as a binding partner for PECAM-1 but not CD177 alone [63]. The CD177/PECAM-1 interaction is considered to induce a signal in endothelial cells, destabilize VE-cadherin from the endothelial junction, and lead to the preferential trans-endothelial migration ability of CD177-positive neutrophils [64, 65]. The binding of monoclonal antibodies to CD177 (such as MEM166) enhances the expression of β2 integrins, activates CD177 positive neutrophils, raises neutrophil adhesion, and interrupts neutrophil’s migratory ability [66]. This effect rather than direct CD177/PECAM-1 binding, explains a neutrophil adhesion via a CD177-driven pathway [67]. In CD177 deficient mice, besides a slight decrease in neutrophil counts, no defect in neutrophil function, chemotaxis, and clearance of bacterial infection was observed [68]. Although, no distinct difference between CD177 positive and negative neutrophil subsets have been described and both CD177 positive and null individuals are healthy, in multiple diseases the CD177 expression/upregulation has been introduced as a risk factor. In comparison to healthy donors, a higher proportion of CD177 positive neutrophils have been detected in patients with ANCA vasculitis [69]. The study documented a differential gene expression between CD177 negative and positive neutrophils; CD177 positive produces a lower level of pro-inflammatory cytokines and exhibits increased bactericidal activities such as ROS production and neutrophil extracellular trap (NET) [70]. A decreased percentage of CD177 positive neutrophils in Myelodysplastic Syndrome has been documented [71]. In contrast, in Kawasaki disease, an epigenetic hypomethylation and consequently increased CD177 gene transcription has been reported [72]. Beyond neutrophils, the presence of CD177 on epithelial cells, in cervical cancer, prostate cancer and ovarian cancer has been documented. Analysis of CD177 in mammary epithelial cells revealed a strong CD177 expression on epithelial cells that was significantly reduced in paired cancer specimens [73]. These data suggest CD177 molecule as a cancer cell-intrinsic tumor suppressor and introduced this molecule as a potential good prognostic factor in different cancer types [73]. A recent study documented TRALI induction in a CD177 pre-immunized recipient after transfusion with packed red blood cells (PRBC) from CD177 positive donors, but not CD177 negative donors. In vitro analysis has documented the presence of soluble CD177/PR3 complex in plasma from CD177 donors that was significantly increased after PRBC filtration. The molecular mechanism regulating the secretion of CD177 in plasma is yet to be resolved. PECAM-1 on pre-activated endothelial cells absorbs soluble CD177/PR3 complex from plasma. Binding of CD177 isoantibodies to the absorbed CD177/PR3 complex on endothelial cells, induced endothelial barrier dysfunction implicated in the mechanism of anti-CD177 mediated reverse TRALI [74]. In severe cases of COVID-19 infections, progressive respiratory failure results from immunothrombosis that is driven by activated neutrophils and platelets. As an activation marker, CD177 molecules were upregulated in severe COVID-19 cases [75]. Further studies have documented a correlation between CD177 upregulation in the serum and disease severity and mortality in COVID-19 [76].
The presence of a stop codon on the CD177 gene is shown to prevent NB1 biosynthesis [77]. Based on this observation, the NB-negative individuals are called NBnull. This interpretation also suggests that there is no allele to NB1. In contrast to this conclusion, a NB1 positive mother was reported to have a child with ANN and have a neutrophil-specific antibody that reacted only with NB1-negative neutrophils. This antibody could be absorbed only by NB1-negative neutrophils and was called anti-NB2, an allele to NB1 [78]. In this case, the maternal neutrophils were also found to be 9a-negative, which suggested a possible relationship between NB2 and 9a, an antigen previously described by van Rood. Also, examination of data from testing neutrophils from 76 members of 11 families, tested with anti-9a and anti-NB2 showed identical results in 72 of 76 donors (these results were obtained during 1967 HL-A workshop experiments in Torino, Italy). Anti-NB2 antibodies were also reported to cause febrile transfusion reaction [79] and TRALI [80]. Future studies are needed to confirm that NB2, an allele to NB1, exists or if its identification has been the result of serological errors. If confirmed, NB2 would be a truncated NB1 molecule in NB-negative individuals who carry the c.787 stop codon, which causes the absence of amino acids responsible for CD177 expression (Table 2). Therefore, NB2 will be CD177-negative but not NBnull. It should also be recognized that individuals with SNP c.1291 G > A expression have soluble NB1 antigens present in their plasma and not on their neutrophils, and thus will be classified as NB1 negative, however, this individual would not necessarily be NB2 positive.
In 1964, Bernard Amos of Duke University was appointed by the National Research Council to organize an international research team to identify the antigens involved in organ transplantation. Over a few years, different antigens were identified and were named ‘HL-A’ [81, 82], in which ‘H’ and ‘L’ were the terms used by different investigators for the antigens they had discovered, and ‘A’ was for the first locus identified. It was later recognized that the system was too complicated, and HL-A was changed to HLA to make place for other antigens and loci. Therefore, the HLA is not “Human Leukocytes Antigens” nor is “Human lymphocyte Antigens,” as used by the current literature. The HLA antigens are widely distributed in various tissues and not leukocyte-specific. It should also be noted that these antigens have their biological functions. and are not designed for organ transplantation that is a medical procedure. The term “HNA,” proposed to be used for neutrophil-specific antigens, is a misinterpreted copy of HLA nomenclature and creates confusing issues: In the HNA nomenclature, the letter ‘H’ for human is wrong because these antigens are not specific for humans, and are present in various other animals, ‘N’ for neutrophil is wrong, because none of the antigens, HNA3, HNA4 nor HNA5, described in NHA systems are neutrophil-specific or cause ANN, AINI or neutropenia.
Many techniques are used for investigating neutrophils antigens [83, 84]. However, leukoagglutination is one of the most essential laboratory tests for neutrophil antibody detection. Unfortunately, some facilities avoid neutrophil agglutination testing because of the lack of reproducibility due to the use of inappropriate technology. The mechanism of neutrophil agglutination was investigated by time-lapse cinematography [85] and showed that after the addition of antibodies to neutrophil suspensions, a period of 5–10 minutes incubation at 37°C was required to activate the neutrophils. After this silent period, neutrophils develop many pseudopods and begin to move toward each other (agglutinate). This suggests that neutrophil agglutination is a chemotactic response and requires a biological environment. Damage to neutrophils during isolation, storage, presence of contamination, and centrifugation cause non-specific clumping. Another technical difficulty is the mixed agglutination that occurs when there are red cells (or red cell ghosts) in the cell preparation and red cell antibodies present. This red cell incompatibility, in the presence of complement, causes neutrophil stimulation to phagocytize the red cells, and or red cell ghosts, and form massive neutrophil aggregates. EDTA In the medium can prevent this process. Maintaining a highly viable environment for neutrophils is essential for the neutrophil agglutination test.
Neutrophil-Specific antigens are biological structures on blood neutrophils, the most frequent nucleated cells in blood circulation. Fetal-maternal incompatibility on these antigens causes neonatal neutropenia, and their autoimmunity results in neutropenia in children and adults. Also, the presence of antibodies against these antigens causes serious complications in blood transfusions, and incompatibility in bone marrow transplantation can cause graft rejection. Beyond antigenicity and immunological effects, these molecules have major roles on neutrophil functions: NA antigens connect neutrophils to antibodies to perform their phagocytic and other defense functions. The NB antigen interacts with Proteinase 3, Platelet-Endothelial Cell Adhesive Molecule 1 and other molecules to perform various neutrophil functions, including protein digestion and penetration across endothelial cells. This may be part of the mechanism of the development of serious lung injuries associated with COVID-19 infection and transfusion-related acute lung injury. It is also recognized that NB antigen expression is increased in Polycythemia Vera and in several cancer tissues. More investigation is needed to understand the significance of the appearance of NB on neoplastic tissues. This information would contribute to the understanding of the development of malignancies, their progression, and lead to the development of new approaches for their treatment.
The authors are grateful to Mr. Jeffrey Rothschild for his support of the Neurological Surgery Research Laboratory at Montefiore Medical Center. The authors also thank Shirin Lalezari and Rukmani Lekhraj for their assistance in preparation of this manuscript.
The authors declare no conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. 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. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:229,paginationItems:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",biography:"Dr. Aneesa Moolla has extensive experience in the diverse fields of health care having previously worked in dental private practice, at the Red Cross Flying Doctors association, and in healthcare corporate settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. 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Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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