Compounds manifesting activity against human adenoviruses.
\r\n\tHomeostasis is brought about by a natural resistance to change when already in the optimal conditions, and equilibrium is maintained by many regulatory mechanisms. All homeostatic control mechanisms have at least three interdependent components for the variable to be regulated: a receptor, a control center, and an effector. The receptor is the sensing component that monitors and responds to changes in the environment, either external or internal. Receptors include thermoreceptors and mechanoreceptors. Control centers include the respiratory center and the renin-angiotensin system. An effector is a target acted on to bring about the change back to the normal state. At the cellular level, receptors include nuclear receptors that bring about changes in gene expression through up-regulation or down-regulation and act in negative feedback mechanisms. An example of this is in the control of bile acids in the liver.
\r\n\tSome centers, such as the renin-angiotensin system, control more than one variable. When the receptor senses a stimulus, it reacts by sending action potentials to a control center. The control center sets the maintenance range—the acceptable upper and lower limits—for the particular variable, such as temperature. The control center responds to the signal by determining an appropriate response and sending signals to an effector, which can be one or more muscles, an organ, or a gland. When the signal is received and acted on, negative feedback is provided to the receptor that stops the need for further signaling.
\r\n\tThe cannabinoid receptor type 1 (CB1), located at the presynaptic neuron, is a receptor that can stop stressful neurotransmitter release to the postsynaptic neuron; it is activated by endocannabinoids (ECs) such as anandamide (N-arachidonoylethanolamide; AEA) and 2-arachidonoylglycerol (2-AG) via a retrograde signaling process in which these compounds are synthesized by and released from postsynaptic neurons, and travel back to the presynaptic terminal to bind to the CB1 receptor for modulation of neurotransmitter release to obtain homeostasis.
\r\n\tThe polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) and are synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs) mediate significant effects in the fine-tuning adjustment of body homeostasis.
\r\n\t
\r\n\tThe aim of this book is to discuss further various aspects of homeostasis, information that we hope to be useful to scientists, clinicians, and the wider public alike.
Adenoviruses (AdVs) [1] occupy a significant place in the human pathology [2]. It was established that 30–70% of the human population in Europe and North America shows a seroprevalence to AdVs (cit. in [3]). These viruses are causative agents of wide range of human diseases, showing varying tissue tropism. They are generally middle and self-limiting. Among them, large place is occupied by acute respiratory tract diseases, especially in children [4]. Conjunctivitis is very often registered in these infections. More severe course manifests viral gastroenteritis, especially in infants, as well as hemorrhagic cystitis, and in rare cases, hepatitis, myocarditis, meningoencephalitis or nephritis [5, 6]. AdVs are characteristic with their severe course in persons with hereditary decreased or impaired immune system: (1) hereditary immunodeficiency; (2) in persons transplant recipients treated with immunosuppressive agents; (3) AIDS. In such patients, the abovementioned clinical manifestations are particularly prone to disseminated disease frequently show a fatal outcome, in children mortality rate attains 83% [7, 8, 9]. EKC is another serious and very frequent AdV induced disease, extremely often with social importance [10, 11, 12, 13, 14].
The major problem of AdVs infections is the absence of chemotherapeutic agents not only for the clinical practice, but even the absence at strong anti-adenovirals in experimental research. This is pointed in all manuals of virology considering AdVs and AdV-induced infections, in the review articles and even in all encyclopedic sources. Evidently, development of an effective antiviral treatment is a principal task.
This chapter presents a concentrated view on the investigations of experimental chemotherapy of AdV infections and results of their clinical application (Table 1).
Compounds manifesting activity against human adenoviruses.
The antiviral effect of cidofovir is based on its transformation in the infected cells in di- and triphosphate and such way becoming an alternative substrate of the AdV DNA polymerase possessing higher affinity compared to cellular DNA polymerases (I, II and III) [15]. Sequence changes in a conserved region of the AdV DNA polymerase were established at cidofovir-resistant AdV mutants [16].
Cidofovir IC50 values in cell culture testing versus broad spectrum of AdVs are within 0.8–17 μg/ml [17]. In in vivo testing in ocular infection with AdV (type C) of New Zealand rabbits and cotton rats the compound treatment is efficacious when administered as 0.5–1% eye drops [18, 19, 20]. Romanowski and Gordon [21] found efficacy of topical 0.5% cidofovir on several human adenoviruses (AdV1, AdV5 and AdV6) in the New Zealand rabbit ocular model. AdV type B and type C-induced pneumonia registered in mice and in cotton rats [22] could be used for in vivo treatment with antivirals.
This compound is a lipidic conjugate of cidofovir. It prevents AdV induced mortality in a permissive, immunosuppressed animal model [23].
Its anti-AdV effect has the same mechanism as cidofovir—inhibition of the AdV DNA chain elongation [24].
This compound proved active against multiple AdV serotypes in vitro and was effective versus AdV-C6 in hamsters immunosuppressed by cyclophosphamide. Administered orally USC-187 prevented or significantly decreased mortality, virus titers and liver pathology up to 4 days post AdV i.v. challenge. Applied in a respiratory AdV-C6 challenge model USC-187 manifested symptoms of toxicity [25].
The compound anti-AdV activity registered was slightly inferior than that of cidofovir and HPMPA [26].
In vitro manifested a marked activity on AdV replication with selectivity index exceeding cidofovir [26].
This compound is known as a drug approved for the treatment of herpes infection (cytomegalovirus infection especially) was reported to be effective against human AdVs in vitro [27]. In cell culture GCV inhibits AdV5 replication and expression of late genes [28]. These authors established a marked effect of 3% GCV in cotton rat eyes, on replication and pathology of this virus [28] Ying et al. [29] tested the GCV administered locally for prophylactic or therapeutic effect in immunosuppressed (by cyclophosphamide) Syrian hamsters intravenously infected with human AdV5 and was established that the compound suppresses AdV5 replication in the liver and AdC5-induced pathology of infected hamsters thus mitigated the consequences of the AdV infection. It was showed that GCV inhibits AdV5 DNA synthesis and late gene expression. The slight increase in GCV phosphorylation in AdV infected cells established by Ying et al. [29] could be a result of slightly elevated cellular thymidine kinase activity, higher in testing in vivo. These authors hypothesize the direct inhibition of the AdV DNA polymerase as a possible mechanism of GCV suppressive effect on AdV DNA synthesis.
This anti-HIV compound possesses a marked anti-AdV activity, even stronger than cidofovir in ocular AdV infections in laboratory animals [30].
Alovudine (FddT) manifest in vitro (IC50 = 0.2–0.7 μg/ml) and in vivo (mouse model of AdV pneumonia) anti-AdV activity of the order of that of cidofovir [26, 31].
Anti-AdV activity of these anti-HSV compounds is moderate, and the current data on their testing are controversial [32, 33, 34].
This triazole nucleoside was described initially by Sidwell et al. [35]. Numerous studies were carried out on the mode of action of this compound manifesting activity toward large spectrum of viruses (predominantly RNA containing) belonging to different taxonomic groups. However, there are no data about the mechanism of anti-AdV effect of ribavirin. Several different mechanisms were formulated about the antiviral effects of this compound: (1) decreased levels of intracellular guanosine triphosphate pools based on inhibition of cellular inosine-5-monophosphate dehydrogenase; (2) inhibition of viral polymerases; (3) inhibition of RNA capping activity of viral transcripts; (4) lethal mutagenesis of the viral RNA genomes, also termed “error catastrophe,” based on the induction of increased viral mutation rate over the critical error rate (especially expressed on enterovirus replication) via incorporation of the compound into newly synthesized genomes; (5) immunomodulatory role particularly on adaptive immune responses—the compound is inducer of the helper-T-cell type 1 cytokine response, but also a suppressor of the type 2 cytokine phenotype. Data about anti-AdV effect in cell culture experiments are very controversial. It was established that its activity is limited to AdVs of group C and strongly cell culture-dependent [36]. However, the plasma concentrations reached by ribavirin are 10 times below the required IC50 value [36, 37].
N′N′-anhydro-bis(β-hydroxy-ethyl)biguanide-HCl (abitylguanide) suppressed markedly the replication of a large spectrum of human AdVs, both standard laboratory strains and strains isolated from epidemic keratoconjunctivitis patients. The magnitude of inhibitory effect varied from 1.5 to 3.8 logs. A marked correlation was established between the value of inhibitory effect and belonging of tested AdVs to various subgroups, the strongest activity being found toward viruses of subgroup C (Rosen’s subgroup III). The compound susceptible period of AdV 5 replication included the total growth cycle, but is especially pronounced during the exponential phase. This was established through timing-of-addition study in primary cell cultures of human embryo kidney cells. Electron microscopy study of AdV5 morphogenesis contributed substantially to the clearing-up of the mechanism of anti-AdV action of abitylguanide. It was registered that: (1) the compound decreased about 10-fold the percentage of cells in which mature or empty virions with the characteristic nuclear localization were observed; (2) a complete absence of paracrystals; (3) the number of cells with virus particles arranged in crystals in the nucleoplasm was strongly decreased [38].
The absence of crystalline inclusions established electron microscopically in our study correlated with the established pronounced decrease of infectivity and/or lower yields of viral progeny which is in line with the meaning [39] that the protein crystals might be involved in at late steps of the virus life cycle ensuring correct capsid assembly, virus maturation and infectivity. Discussing the mode of action of abitylguanide on AdV 5 replication it has to stress on the full coincidence of the data obtained electron microscopically with the results of the timing-of-addition study demonstrating the highly-pronounced compound-sensitivity of the virus growth in the exponential phase. On the basis of the mentioned data, abitylguanide can be considered a ligand of AdV capsid protein(s) [38].
This piperazinone is a result of a large screening of low-molecular substances, embracing chemical libraries of in total more than 25,000 compounds. A prospective selection of the compounds was based on protein-protein and protein-DNA interaction [40, 41]. The derivative 15D8 showed substantial anti-AdV activity (AdV 5 and AdV16 models) in dose-dependent manner at high MOI (15,000 vp/cell) with little or absent cytotoxicity at low micromolar concentration. The compound selectively inhibits AdV DNA replication in the nucleus. It is possible 15D8 to interact with viral proteins essential for DNA, including precursor of the terminal protein (pTP), AdV DNA polymerase or the DNA-binding protein (DBP). 15D8 could be considered as a potential candidate for the development of a new class of antiviral compounds to treat AdV infections [42].
Very surprising recently (2017), the cardiotonic steroids entered in the scope of the struggle with AdV infections. As a theoretic prerequisite of their effects were the data on dependents of AdV on the host pre-RNA splicing machinery for expression of its complete genome. On such base modulators of RNA splicing as digoxin and digitoxin could be considered as antivirals versus human AdVs. Grosso et al. [3] proved that both drugs reduced of a series of AdVs of four different species (A to D) by 2–3 logs. This is a result of affecting several steps needed for AdV genome replication (late proteins E4 or f6 and the major late capsid hexon protein is compromised). The authors proved that these two drugs altered EiA RNA splicing early in infection and partially blocked the translation from 12S and 13S to 9S RNA at later stages of viral replication. By blocking AdV replication at one or more steps beyond the onset of E1A expression and before genome replication, digoxin and digitoxin manifest very prospective potential as antivirals for the treatment of serious AdV infections.
Convallatoxin, a synthetic cardiotonic steroid, manifested a stronger activity versus AdV5 when compared with digoxin and digitoxin. In general, these three substances alter the cascade of AdV gene expression—an effect starting after initiation of early gene expression attaining a blocking of AdV DNA replication and of viral structural proteins. These findings open a novel approach of treating AdV infections and guide the development of novel antiviral therapies.
This compound inhibits selectively cellular binding sites (sialic acid-containing receptors) of several AdV serotypes. It was established that ADVs possess this cellular tropism. NMSO3 could be used for the topical treatment of ocular AdV infections [43, 44].
This substance markedly inhibits the AdV cystein protease, indispensable for the production of infectious AdV virions [45, 46].
As a result of the studies carried out by G. Wadell, N. Arnberg and others in University of Umea in Sweden (2014–2017), O. Sterner and U. Ellervik (University of Lund, Sweden) synthesized the substance APD-209, announced as ADENOVIR (Pharma). It was noted that this substance with unknown structure for the publicity is considered as a new solution for the treatment of viral eye infections [47].
Other Swedish authors [48] reported also that
In the search for discovery of efficient anti-AdV agents it was investigated the probable impact of silencing of a set of early, middle and late viral genes on the replication of AdV5 in vitro [49]. It was established that AdV replication was inhibited by siRNAs directed against AdV E1A, DNA polymerase, preterminal protein (pTR), IVa2, hexon, and protease genes. Besides, silencing of the early and middle genes was more effective in inhibiting AdV replication than the silencing of late genes, especially sharply manifested with effect on siRNA of the DNA polymerase gene. Besides, it was found that reducing the viral genome copy numbers (AdV DNA) is a more promising strategy than the reducing the number of proteins necessary for capsid formation.
Cyclic D,L-α-peptides, cycloferon, lactoferrin nitric oxide, doxovir, heterocyclic Schiff bases of aminohydroxyguanidine tosylate, PGD peptidomimetic molecules, some medical plant substances (ref. in [17]).
Prophylaxis with effective antivirals versus AdV EKC would be particularly useful for preventing AdV transmission to the second eye as well as to the contact persons.
Cidofovir eye drops 1% prevent severe corneal opacities in EKC patients, dose-dependent local toxicity at frequent administration been registered [50, 51]. This anomalous nucleoside at concentration of 1% applied topically in a combination with 1% cyclosporine demonstrated therapeutic effect on patients with EKC in a controlled clinical pilot study [51]. No placebo-controlled randomized trials have been carried out on immunocompromised patients.
Controversial results were obtained with cidofovir the treatment of AdV infections in children undergoing bone marrow or stem cell transplantation [52]. Evidence was accumulated that as earlier AdV infection is detected for starting cidofovir treatment the better curative results were registered. Although cidofovir exhibits antiviral activity versus all AdV species, it possesses low oral bioavailability and significant toxicity (tubular necrosis) and does not confer long-term protection [53].
However, the lipid conjugate of cidofovir, brincyclovir (BCV; hexadecyloxy propyl-cidofovir; CMX001) is currently in Phase II clinical trial [25, 54], unfortunately manifesting a significant toxicity to the kidney and gastrointestinal tract.
The topical ganciclovir application against EKC [55] merits special attention. In a published clinical study, treatment with 0.15% GCV ophthalmic gel improved outcome of AdV conjunctivitis [56]. Three other clinical trials evaluating 0.15% GCV ophthalmic gel were organized, two of them finished: (1) Efficacy and Safety of GV 550 in Acute Adenovirus Keratoconjunctivitis (Clinical Trials.gov. trial NCT01156025) and (2) Efficacy and Safety of GV 550 in Acute Adenovirus Keratoconjunctivitis (a Clinicaltrialsregister.eu trial). Both included placebo and treatment groups on 40 persons each (in fact Phase II of clinical trial). In the third trial, Clinical Trials.gov trial NCT1533480 (A Placebo Controlled Comparison of Topical ZIRGAN Versus Genteal for the treatment of Adenovirus Conjunctivitis) which is currently in course, GCV is administered topically as 0.15% gel (ZIRGAN®) compared with 0.3% Hypromellose gel (Genteal gel®), serving as placebo (Phase IV).
On the base of the promising results with povidone-iodine (PVP-I), a microbicidal agent possessing also virucidal properties [57], topical ganciclovir and PVP-I combination drops have shown the most recent potential, but both therapeutics need to be investigated in larger scale studies [58].
The experimental data in vivo are in favor of GCV to be considered as an option for the treatment of AdV infections in immunocompromised patients.
Ribavirin efficacy for the treatment of AdV infections was very controversial [36, 59].
N-chlorotaurine (a week oxidant) manifested effectivity in phase II clinical trials with viral conjunctivitis [60].
During a severe outbreak of EKC caused by AdV 8 in 1972–1973 in Bulgaria abitylguanide was tested in two double-blind, randomized trials, carried out on total 349 patients (trial 1–151 patients; trial 2–198 patients) with virologically confirmed diagnosis.
Abitylguanide was applied as 1% eye drops (in saline). In each of the two trials, patients were divided in three groups: group I placebo (patients with symptomatic treatment), group II -abitylguanide 1% + symptomatic treatment, group III—patients treated with abitylguanide 1% only. Curative effect of abitylguanide was almost identical in group II and III in both trials. Moreover, the drug had a preventive effect on infection of the second eye. The abitylguanide treatment exerted a marked curative effect on the severity and duration of the disease: (1) more than twofold decrease in both trials in the number of patients with EKC form associated with keratitis; (2) five- and sixfold decrease in trial 1 an trial 2, respectively, in the incidence of severe keratitis; (3) two- and fivefold decrease in trial 1 and trial 2, respectively, in the number of patients with impaired vision; (4) twofold decrease of the healing time [61, 62, 63]. Effectivity toward AdV-induced EKC of the drug applied topically was confirmed in series of placebo controlled trials (not following the double-blind scheme) in three other ophthalmic clinics in the country, carried out in the second half of the 1980s. Pencheva et al. [64] in the Varna Medical Faculty registered marked decrease of the patients number with keratitis, twofold shortening of the healing time in abitylguanide treated patients, affection of the second eye—80% in the placebo group, and 22.6% in abitylguanide treated group.
In preliminary carried out study abitylguanide manifested a very high local tolerance (1, 2 and 3% eye drops in saline) tested in 21 volunteers (in rabbits—till 20% eye drop).
The pronounced effect of abitylguanide [65] in abovementioned trials on EKC patients served for the development and implementation in pharmaceutical industry of preparative ADENOSTATIN COLLYRIUM® (Pharmachim Ltd., Sofia) which clinical use marked favorable estimation by ophthalmologists in this country (tested in Japan, as well).
The clinical use of cardiotonic steroids as anti-AdV agents needs special consideration. As digitoxin has been associated with toxicity, the use of cardiac glycosides as antivirals would be short term, in contrast to the chronic use in patients with heart diseases. Having in mind that anti-AdV agents have to be used for the treatment of severe respiratory and disseminated diseases, these drugs seem more attractive as potential agents for the topical treatment of EKC and even for the prophylaxis of persons contact to EKC patients [3].
There is no doubt that chemotherapy of AdV infections occupies leading position as a tool for anti-etiological treatment. Therefore, the development of effective anti-AdV agents is especially a big task of the scientists and clinicians. The above-presented panorama of antivirals versus AdVs and AdV-caused infections shows that a lot of work is done for the realization of this problem. The author would like to mention the main directions that determined the development of antivirals and their implementation in the clinical practice: (1) discovery of the targets in virus growth cycle for chemotherapeutic attacks—a lot of “wide” places could be pointed in the AdVs; (2) attainment in the organic chemistry—modeling of new effective molecules with anti-AdV effects among anomalous nucleosides, end especially of non-nucleoside compounds ligands of AdV proteins; (3) development of adequate methodology for antiviral testing starting from the initial in vitro screening, and application of purified AdV structural and eventually nonstructural proteins as cell-free systems (approach contributed substantially for the successful development of anti-hepatitis C drugs; as concerns the in vivo testing, in the last years, several very convenient and adequate models were described and successfully used (more precisely ocular AdV infections in laboratory animals); (4) application of methods for express diagnostic of ADV infections, in order earliest start of the respective treatment with anti-AdV chemotherapeutic agents. More detailed consideration of this topic was presented by Kaufman [66] and Luchs [67].
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A free radical may be defined as any molecule that has one or more unpaired electrons. The superoxide anion, the hydroxyl radical, and the hypochlorite radical are some of the highest reactive radicals of oxygen. Owing to their high reactivity and to their capability of initiating an uncontrolled cascade of chain reactions, ROS produce extensive protein damage and cytoskeletal modifications and inhibit cellular mechanisms. Aerobic organisms are equipped with a powerful battery of mechanisms that protect them from the adverse effects of lipid peroxidation (LPO) and other manifestations of oxygen toxicity. Defective sperm function frequently causes male infertility, due to abnormal flagella movement, failure to recognize the zona, and inhibition of sperm-oocyte fusion. ROS are fundamental mediators of physiological sperm function, such as signal transduction mechanisms that have an effect on fertility. ROS can have positive effects on sperm and the concentration functions depending on the nature and the concentration of the ROS involved. They are necessary in regulating the hyperactivation and the ability of the spermatozoa to undergo acrosome reaction. An increased amount of superoxide anion (O2-) is one of the first steps required by the spermatozoa for induction and development of hyperactivation and capacitation. Numerous studies have shown that oxidative stress plays an important role in the pathophysiology of infertility and assisted fertility. The paternal genome is of primary importance in the normal embryo and fetal development. ROS-induced sperm damage during sperm translation, such as signal transduction through the seminiferous tubules and epididymis, is one of the most important mechanisms leading to sperm DNA damage. Male germ cells are extremely vulnerable to oxidative stress as the sperm membrane is rich in unsaturated fatty acids and lacks the capacity for DNA repair. Spermatozoa are particularly susceptible to ROS-induced damage because their plasma membranes contain large quantities of polyunsaturated fatty acids (PUFA) and their cytoplasm contains low concentrations of the scavenging enzymes. Many clinical and research institutes are investigating the usefulness of antioxidant supplementation and their role in prevention of the infertility problems. Incubation under oxygen in vitro was detrimental to human spermatozoa, decreasing motility and viability. Since then, many reports have associated ROS with impaired sperm function, including decreased motility, abnormal morphology, and decreased sperm-egg penetration. Increasing knowledge of the mechanisms whereby ROS and endogenous antioxidant systems influence reproductive processes can assist to optimize the application of exogenous antioxidants to fertility treatment.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Simona Tafuri, Francesca Ciani, Eugenio Luigi Iorio, Luigi Esposito\nand Natascia Cocchia",authors:[{id:"32033",title:"Dr.",name:"Natascia",middleName:null,surname:"Cocchia",slug:"natascia-cocchia",fullName:"Natascia Cocchia"},{id:"117666",title:"Prof.",name:"Francesca",middleName:null,surname:"Ciani",slug:"francesca-ciani",fullName:"Francesca Ciani"},{id:"173334",title:"Prof.",name:"Simona",middleName:null,surname:"Tafuri",slug:"simona-tafuri",fullName:"Simona Tafuri"},{id:"173338",title:"Prof.",name:"Luigi",middleName:null,surname:"Esposito",slug:"luigi-esposito",fullName:"Luigi Esposito"},{id:"173431",title:"Prof.",name:"Eugenio Luigi",middleName:null,surname:"Iorio",slug:"eugenio-luigi-iorio",fullName:"Eugenio Luigi Iorio"}]},{id:"48988",doi:"10.5772/61003",title:"Influence of ROS on Ovarian Functions",slug:"influence-of-ros-on-ovarian-functions",totalDownloads:1943,totalCrossrefCites:6,totalDimensionsCites:14,abstract:"High level of ROS (Reactive Oxygen Species), due to an increased production of oxidant species and/or a decreased efficacy of antioxidant system, can lead to oxidative stress (OS) an emerging health risk factor involved in the aging and in many diseases, either in humans or in animals. ROS are a double-edged sword – they serve as key signal molecules in physiological processes, but also have a role in pathological processes involving the female reproductive tract.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Francesca Ciani, Natascia Cocchia, Danila d’Angelo and Simona\nTafuri",authors:[{id:"32033",title:"Dr.",name:"Natascia",middleName:null,surname:"Cocchia",slug:"natascia-cocchia",fullName:"Natascia Cocchia"},{id:"117666",title:"Prof.",name:"Francesca",middleName:null,surname:"Ciani",slug:"francesca-ciani",fullName:"Francesca Ciani"},{id:"173334",title:"Prof.",name:"Simona",middleName:null,surname:"Tafuri",slug:"simona-tafuri",fullName:"Simona Tafuri"},{id:"173336",title:"Prof.",name:"Danila",middleName:null,surname:"D'Angelo",slug:"danila-d'angelo",fullName:"Danila D'Angelo"}]},{id:"49200",doi:"10.5772/61453",title:"Human Embryology",slug:"human-embryology",totalDownloads:3573,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"The study of human embryology has a very long history. Modern embryology owes its initial development to the key embryo collections that began in the 19th century. The first large collection was that of Carnegie, and this was followed later by the major 7 collections. The second role of the Carnegie collection was for researchers to establish a defined set of Carnegie stages based on embryo morphological features. Today, embryos are imaged three-dimensionally (3D) by a range of imaging modalities including, magnetic resonance microscopy (MRM), episcopic fluorescence image capture (EFIC), phase-contrast X-ray computed tomography (pCT), and optical projection tomography (OPT). Historically, embryo serial images were reconstructed using wax-plate and model techniques. The above new 3D imaging techniques now allow 3D computer reconstructions, analysis, and even 3D printing. This chapter will describe how the classical embryology collections and techniques have developed into today’s imaging and analysis techniques, giving new insights to human embryonic development.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Shigehito Yamada, Mark Hill and Tetsuya Takakuwa",authors:[{id:"49486",title:"Prof.",name:"Shigehito",middleName:null,surname:"Yamada",slug:"shigehito-yamada",fullName:"Shigehito Yamada"},{id:"90205",title:"Prof.",name:"Tetsuya",middleName:null,surname:"Takakuwa",slug:"tetsuya-takakuwa",fullName:"Tetsuya Takakuwa"},{id:"175453",title:"Dr.",name:"Mark",middleName:null,surname:"Hill",slug:"mark-hill",fullName:"Mark Hill"}]},{id:"48710",doi:"10.5772/61004",title:"Assisted Reproductive Technologies in Safeguard of Feline Endangered Species",slug:"assisted-reproductive-technologies-in-safeguard-of-feline-endangered-species",totalDownloads:2321,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"The growth of the human population and the escalating consumption of natural resources have reduced wild habitats, modifying the existing balance of biological cycles. Therefore, ex situ conservation efforts have received renewed attention as a potential safeguard for species with an uncertain future in the wild. Most wild felid species are classified as rare, vulnerable, or endangered due to poaching and habitat loss. Any directed action taken by humans to enhance animal reproduction results in assisted reproductive technologies (ART) development. These technologies have been included in programs for the conservation of endangered species. Therefore, ART provide a new approach in the safeguard programs of felid biodiversity. Currently, ART mainly include Artificial Insemination (AI); In Vitro Embryo Production (IVEP) consisting of In Vitro Maturation (IVM), In Vitro Fertilization (IVF), In Vitro Culture (IVC), Embryo Transfer (ET), and Intra Cytoplasmic Sperm Injection (ICSI); gamete/embryo cryopreservation; gamete/embryo sexing; gamete/embryo micromanipulation; Somatic Cell Nuclear Transfer (SCNT); and genome resource banking.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Natascia Cocchia, Simona Tafuri, Lucia Abbondante, Leonardo\nMeomartino, Luigi Esposito and Francesca Ciani",authors:[{id:"32033",title:"Dr.",name:"Natascia",middleName:null,surname:"Cocchia",slug:"natascia-cocchia",fullName:"Natascia Cocchia"},{id:"117666",title:"Prof.",name:"Francesca",middleName:null,surname:"Ciani",slug:"francesca-ciani",fullName:"Francesca Ciani"},{id:"173334",title:"Prof.",name:"Simona",middleName:null,surname:"Tafuri",slug:"simona-tafuri",fullName:"Simona Tafuri"},{id:"173338",title:"Prof.",name:"Luigi",middleName:null,surname:"Esposito",slug:"luigi-esposito",fullName:"Luigi Esposito"},{id:"175465",title:"Dr.",name:"Lucia",middleName:null,surname:"Abbondante",slug:"lucia-abbondante",fullName:"Lucia Abbondante"},{id:"175843",title:"Prof.",name:"Leonardo",middleName:null,surname:"Meomartino",slug:"leonardo-meomartino",fullName:"Leonardo Meomartino"}]},{id:"48736",doi:"10.5772/60825",title:"Sperm DNA Fragmentation and Its Relation With Fertility",slug:"sperm-dna-fragmentation-and-its-relation-with-fertility",totalDownloads:2519,totalCrossrefCites:5,totalDimensionsCites:5,abstract:"Sperm DNA integrity is vital for successful fertilization, embryo development, pregnancy, and transmission of genetic material to the offspring. DNA fragmentation is the most frequent DNA anomaly present in the male gamete that has been associated to poor semen quality, low fertilization rates, impaired embryo quality, and preimplantation development and reduced clinical outcomes in assisted reproduction procedures. This work summarizes the causes of fragmentation in the spermatic DNA, and its relation with seminal parameters, male aging, and results in assisted reproduction procedures.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Javier García-Ferreyra",authors:[{id:"173256",title:"Ph.D.",name:"Javier",middleName:null,surname:"García-Ferreyra",slug:"javier-garcia-ferreyra",fullName:"Javier García-Ferreyra"}]}],mostDownloadedChaptersLast30Days:[{id:"49200",title:"Human Embryology",slug:"human-embryology",totalDownloads:3573,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"The study of human embryology has a very long history. Modern embryology owes its initial development to the key embryo collections that began in the 19th century. The first large collection was that of Carnegie, and this was followed later by the major 7 collections. The second role of the Carnegie collection was for researchers to establish a defined set of Carnegie stages based on embryo morphological features. Today, embryos are imaged three-dimensionally (3D) by a range of imaging modalities including, magnetic resonance microscopy (MRM), episcopic fluorescence image capture (EFIC), phase-contrast X-ray computed tomography (pCT), and optical projection tomography (OPT). Historically, embryo serial images were reconstructed using wax-plate and model techniques. The above new 3D imaging techniques now allow 3D computer reconstructions, analysis, and even 3D printing. This chapter will describe how the classical embryology collections and techniques have developed into today’s imaging and analysis techniques, giving new insights to human embryonic development.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Shigehito Yamada, Mark Hill and Tetsuya Takakuwa",authors:[{id:"49486",title:"Prof.",name:"Shigehito",middleName:null,surname:"Yamada",slug:"shigehito-yamada",fullName:"Shigehito Yamada"},{id:"90205",title:"Prof.",name:"Tetsuya",middleName:null,surname:"Takakuwa",slug:"tetsuya-takakuwa",fullName:"Tetsuya Takakuwa"},{id:"175453",title:"Dr.",name:"Mark",middleName:null,surname:"Hill",slug:"mark-hill",fullName:"Mark Hill"}]},{id:"49198",title:"A Novel Discipline in Embryology — Animal Embryo Breeding",slug:"a-novel-discipline-in-embryology-animal-embryo-breeding",totalDownloads:2473,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The modern animal biotechnologies, such as animal cloning, transgenesis, sex determination, stem cells, designing new livestock, must be performed on animal gametes including sperm and oocytes, and embryos based on embryology theory. Currently, some key biotechnologies in embryology have become the most powerful tool for animal scientists and breeders to improve genetic construction of animal herds. Here, authors put forward a new concept of Animal Embryo Breeding Science to describe this discipline formation, development, and application in animal genetic improvement and breeding. The relationship of embryo breeding with other disciplines has been profiled. Thus, animal scientists and breeders can easily understand and apply embryo breeding theory and related key techniques to accelerate animal improvement speed, to modify genetic construction of animal population, and to design and create new animal individual or breed.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Bin Wu, Linsen Zan, Fusheng Quan and Hai Wang",authors:[{id:"108807",title:"Ph.D.",name:"Bin",middleName:null,surname:"Wu",slug:"bin-wu",fullName:"Bin Wu"}]},{id:"56335",title:"Improving ART Pregnancy Rate with Two Kinds of Media and Two Types of Incubators",slug:"improving-art-pregnancy-rate-with-two-kinds-of-media-and-two-types-of-incubators",totalDownloads:1908,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Culture media and incubators have played a key role in embryo quality. Here, we observed individual patient’s embryos to have different response for media and incubators. Patient’s 1850 zygotes were divided into two groups randomly and were cultured in Global and in P1 medium. The cleavage rate and embryo quality were recorded. The result showed that the cleavage, top quality embryos on Day 2 and Day 3 were not statistically different between media. However, 45% patient’s embryos grew very well in both Global and P1. 22% patient’s embryos grew well only in Global but poor quality in P1, while 21% grew well in the Global but poorly in the P1. Only 12% patient embryos did not grow well in both. The pregnant rate was only 40% in P1 or 42.5% in Global (P>0.05). However, when two media were used simultaneously, the pregnant rate increased to 70.1%. Also, two incubators showed significant higher pregnant rate than in single incubator (73.2% vs. 60%, P<0.05). In conclusion, the favorable response of individual patient’s embryos to media and incubators suggests that using two media and two incubators for embryo culture could significantly improve embryo quality and pregnant rates.",book:{id:"5817",slug:"embryo-cleavage",title:"Embryo Cleavage",fullTitle:"Embryo Cleavage"},signatures:"Bin Wu, Jinzhou Qin, Suzhen Lu, Linda Wu and Timothy J. Gelety",authors:[{id:"108807",title:"Ph.D.",name:"Bin",middleName:null,surname:"Wu",slug:"bin-wu",fullName:"Bin Wu"}]},{id:"48710",title:"Assisted Reproductive Technologies in Safeguard of Feline Endangered Species",slug:"assisted-reproductive-technologies-in-safeguard-of-feline-endangered-species",totalDownloads:2321,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"The growth of the human population and the escalating consumption of natural resources have reduced wild habitats, modifying the existing balance of biological cycles. Therefore, ex situ conservation efforts have received renewed attention as a potential safeguard for species with an uncertain future in the wild. Most wild felid species are classified as rare, vulnerable, or endangered due to poaching and habitat loss. Any directed action taken by humans to enhance animal reproduction results in assisted reproductive technologies (ART) development. These technologies have been included in programs for the conservation of endangered species. Therefore, ART provide a new approach in the safeguard programs of felid biodiversity. Currently, ART mainly include Artificial Insemination (AI); In Vitro Embryo Production (IVEP) consisting of In Vitro Maturation (IVM), In Vitro Fertilization (IVF), In Vitro Culture (IVC), Embryo Transfer (ET), and Intra Cytoplasmic Sperm Injection (ICSI); gamete/embryo cryopreservation; gamete/embryo sexing; gamete/embryo micromanipulation; Somatic Cell Nuclear Transfer (SCNT); and genome resource banking.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Natascia Cocchia, Simona Tafuri, Lucia Abbondante, Leonardo\nMeomartino, Luigi Esposito and Francesca Ciani",authors:[{id:"32033",title:"Dr.",name:"Natascia",middleName:null,surname:"Cocchia",slug:"natascia-cocchia",fullName:"Natascia Cocchia"},{id:"117666",title:"Prof.",name:"Francesca",middleName:null,surname:"Ciani",slug:"francesca-ciani",fullName:"Francesca Ciani"},{id:"173334",title:"Prof.",name:"Simona",middleName:null,surname:"Tafuri",slug:"simona-tafuri",fullName:"Simona Tafuri"},{id:"173338",title:"Prof.",name:"Luigi",middleName:null,surname:"Esposito",slug:"luigi-esposito",fullName:"Luigi Esposito"},{id:"175465",title:"Dr.",name:"Lucia",middleName:null,surname:"Abbondante",slug:"lucia-abbondante",fullName:"Lucia Abbondante"},{id:"175843",title:"Prof.",name:"Leonardo",middleName:null,surname:"Meomartino",slug:"leonardo-meomartino",fullName:"Leonardo Meomartino"}]},{id:"48736",title:"Sperm DNA Fragmentation and Its Relation With Fertility",slug:"sperm-dna-fragmentation-and-its-relation-with-fertility",totalDownloads:2519,totalCrossrefCites:5,totalDimensionsCites:5,abstract:"Sperm DNA integrity is vital for successful fertilization, embryo development, pregnancy, and transmission of genetic material to the offspring. DNA fragmentation is the most frequent DNA anomaly present in the male gamete that has been associated to poor semen quality, low fertilization rates, impaired embryo quality, and preimplantation development and reduced clinical outcomes in assisted reproduction procedures. This work summarizes the causes of fragmentation in the spermatic DNA, and its relation with seminal parameters, male aging, and results in assisted reproduction procedures.",book:{id:"4588",slug:"new-discoveries-in-embryology",title:"New Discoveries in Embryology",fullTitle:"New Discoveries in Embryology"},signatures:"Javier García-Ferreyra",authors:[{id:"173256",title:"Ph.D.",name:"Javier",middleName:null,surname:"García-Ferreyra",slug:"javier-garcia-ferreyra",fullName:"Javier García-Ferreyra"}]}],onlineFirstChaptersFilter:{topicId:"398",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},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:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,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:129,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:105,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:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,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:14,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. 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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). 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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. 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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. 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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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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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