Selected Respiratory diseases and related chromium-interacted gene.
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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
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This book is divided in two sections. First section includes the fundamental theories on excitons, trions, phase decoherence, and charge states, and the second section includes several applications of quantum dots.",isbn:null,printIsbn:"978-953-51-2155-8",pdfIsbn:"978-953-51-5766-3",doi:"10.5772/59735",price:119,priceEur:129,priceUsd:155,slug:"quantum-dots-theory-and-applications",numberOfPages:190,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"459966a20183c34738c03bd25831af22",bookSignature:"Vasilios N. 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Stavrou is currently an Adjunct Member at the Hellenic Naval Academy, Piraeus, Greece. He received an MSc and a Ph.D. in theoretical solid-state physics from the University of Essex in England, in 1995 and in 1999 respectively. He has held postdoctoral positions at the following research institutions: a) Deutsche Forschungsanstalt fuer Luft und Raumfahrt e.V (German Aerospace Research Center) in Germany, b) Helsinki University of Technology, c) State University of New York (SUNY) at Buffalo, USA and d) University of Iowa, USA. 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The effect of significantly increasing the exciton binding energy in quantum dots of zinc selenide, synthesized in a borosilicate glass matrix and relative to that in a zinc selenide single crystal is revealed. It is shown that the short-wavelength shift of the peak of the low-temperature luminescence spectrum of samples containing zinc selenide quantum dots, observed under experimental conditions, is caused by quantum confinement of the ground-state energy of the exciton with a spatially separated electron and hole.",signatures:"Sergey I. 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Their thechnology, opto-electronical and the structural properties are also discussed.",signatures:"Akos Nemcsics",downloadPdfUrl:"/chapter/pdf-download/48775",previewPdfUrl:"/chapter/pdf-preview/48775",authors:[{id:"107673",title:"Dr",name:"Akos",surname:"Nemcsics",slug:"akos-nemcsics",fullName:"Akos Nemcsics"}],corrections:null},{id:"48756",title:"Physical Reasons of Emission Varying in CdSe/ZnS and CdSeTe/ZnS Quantum Dots at Bioconjugation to Antibodies",doi:"10.5772/60821",slug:"physical-reasons-of-emission-varying-in-cdse-zns-and-cdsete-zns-quantum-dots-at-bioconjugation-to-an",totalDownloads:1997,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Photoluminescence, its excitation power dependence, and Raman scattering spectra have been studied in CdSe/ZnS and CdSeTe/ZnS QDs for the nonconjugated states and after the QD conjugation to the anti-Interleukin-10, Human papilloma virus and Pseudo rabies virus antibodies. The QD bioconjugation to charged antibodies stimulates the “blue” energy shift of PL bands related to exciton emission in the CdSe or CdSeTe cores. The “blue” energy shift of PL spectrum in bioconjugated CdSe/ZnS QDs has been attributed to the electronic quantum confined effects stimulated by decreasing the effective QD size at its bioconjugation to charged antibodies. It was shown that the attachment of a charge deals with the antibody to the exterior shell of CdSe/ZnS QDs, leads to blocking away a fraction of core’s volume. The energy band diagrams of CdSeTe/ZnS QDs in the nonconjugated and bioconjugated states have been designed, which permit to explain the types of optical transitions in QDs and their transformations at the QD bioconjugation. It is shown that the change of energy band profile and the “blue” shift of QD energy levels, owing to the change of potential barrier at the QD surface, are the dominant reasons of PL spectrum transformation in the double core CdSeTe/ZnS QDs conjugated to charged antibodies. Better understanding the QD bioconjugation to specific antibodies is expected to produce the major advances in biology and medicine and can be a powerful technique for early medical diagnostics.",signatures:"Tetyana V. 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He was a guest researcher at the National Institute of Environmental Health Sciences (NIEHS) between 2017 and 2018. Dr. Wu has authored 70 peer-reviewed papers in international journals.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"178661",title:"Dr.",name:"Wei",middleName:null,surname:"Wu",slug:"wei-wu",fullName:"Wei Wu",profilePictureURL:"https://mts.intechopen.com/storage/users/178661/images/system/178661.jpeg",biography:"Dr. Wei Wu is an associate professor and associate department\nchair in the Department of Toxicology, Nanjing Medical University, China, where he received his Ph.D. in Toxicology in 2012.\nHe was a guest researcher at the National Institute of Environmental Health Sciences (NIEHS) between 2017 and 2018. Dr.\nWu is a member of different national and international societies\nin the fields of human reproduction and toxicology and has\nreceived awards from many national societies for the originality and quality of his\nprojects. Dr. Wu has authored seventy-three peer-reviewed papers in international\njournals. He has edited four books and collaborated on ten others as well as seventeen patents and in the organization of three international conferences. He is a\nreviewer for ninety-eight journals.",institutionString:"Nanjing Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Nanjing Medical University",institutionURL:null,country:{name:"China"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1161",title:"Andrology",slug:"andrology"}],chapters:[{id:"79167",title:"The Concept of Male Reproductive Anatomy",slug:"the-concept-of-male-reproductive-anatomy",totalDownloads:238,totalCrossrefCites:0,authors:[{id:"348295",title:"Dr.",name:"Oyovwi",surname:"Mega Obukohwo",slug:"oyovwi-mega-obukohwo",fullName:"Oyovwi Mega Obukohwo"},{id:"421235",title:"Prof.",name:"Nwangwa",surname:"Eze Kingsley",slug:"nwangwa-eze-kingsley",fullName:"Nwangwa Eze Kingsley"},{id:"428844",title:"Dr.",name:"Rotu",surname:"Arientare Rume",slug:"rotu-arientare-rume",fullName:"Rotu Arientare Rume"}]},{id:"79287",title:"Endocrine Functions of the Testes",slug:"endocrine-functions-of-the-testes",totalDownloads:163,totalCrossrefCites:0,authors:[{id:"349696",title:"Dr.",name:"Victor",surname:"EMOJEVWE",slug:"victor-emojevwe",fullName:"Victor EMOJEVWE"},{id:"420885",title:"Ms.",name:"Osarugue",surname:"Igiehon",slug:"osarugue-igiehon",fullName:"Osarugue Igiehon"}]},{id:"79014",title:"Seminiferous Tubules and Spermatogenesis",slug:"seminiferous-tubules-and-spermatogenesis",totalDownloads:207,totalCrossrefCites:0,authors:[{id:"92657",title:"Prof.",name:"Mohamad Eid",surname:"Hammadeh",slug:"mohamad-eid-hammadeh",fullName:"Mohamad Eid Hammadeh"},{id:"337019",title:"Dr.",name:"Houda",surname:"Amor",slug:"houda-amor",fullName:"Houda Amor"},{id:"337221",title:"Dr.",name:"Nyaz",surname:"Shelko",slug:"nyaz-shelko",fullName:"Nyaz Shelko"},{id:"345468",title:"Dr.",name:"Peter Michael",surname:"Jankowski",slug:"peter-michael-jankowski",fullName:"Peter Michael Jankowski"},{id:"419473",title:"Dr.",name:"Bakry Mohamed Sobhy",surname:"Sobhy",slug:"bakry-mohamed-sobhy-sobhy",fullName:"Bakry Mohamed Sobhy Sobhy"},{id:"419475",title:"Dr.",name:"Almandouh Hussein",surname:"Bosilah",slug:"almandouh-hussein-bosilah",fullName:"Almandouh Hussein Bosilah"},{id:"419476",title:"Dr.",name:"Micu",surname:"Romeo",slug:"micu-romeo",fullName:"Micu Romeo"}]},{id:"77407",title:"Positional Relationships among Male Reproductive Organs in Insects",slug:"positional-relationships-among-male-reproductive-organs-in-insects",totalDownloads:194,totalCrossrefCites:0,authors:[{id:"348309",title:"Dr.",name:"Satoshi",surname:"Hiroyoshi",slug:"satoshi-hiroyoshi",fullName:"Satoshi Hiroyoshi"},{id:"348547",title:"Dr.",name:"Gadi",surname:"V.P. Reddy",slug:"gadi-v.p.-reddy",fullName:"Gadi V.P. Reddy"}]},{id:"79679",title:"Reproductive Toxicology: An Update",slug:"reproductive-toxicology-an-update",totalDownloads:143,totalCrossrefCites:0,authors:[{id:"27304",title:"Dr.",name:"Murigendra B.",surname:"Hiremath",slug:"murigendra-b.-hiremath",fullName:"Murigendra B. Hiremath"},{id:"227286",title:"Dr.",name:"Shridhar C.",surname:"Ghagane",slug:"shridhar-c.-ghagane",fullName:"Shridhar C. Ghagane"},{id:"227446",title:"Prof.",name:"Rajendra B.",surname:"Nerli",slug:"rajendra-b.-nerli",fullName:"Rajendra B. Nerli"},{id:"422289",title:"Dr.",name:"Makhadumsab",surname:"Toragall",slug:"makhadumsab-toragall",fullName:"Makhadumsab Toragall"}]},{id:"78966",title:"Testicular Histopathology and Spermatogenesis in Mice with Scrotal Heat Stress",slug:"testicular-histopathology-and-spermatogenesis-in-mice-with-scrotal-heat-stress",totalDownloads:198,totalCrossrefCites:0,authors:[{id:"340643",title:"Dr.",name:"Thuan",surname:"Dang-Cong",slug:"thuan-dang-cong",fullName:"Thuan Dang-Cong"},{id:"348281",title:"Dr.",name:"Tung",surname:"Nguyen-Thanh",slug:"tung-nguyen-thanh",fullName:"Tung Nguyen-Thanh"}]},{id:"78480",title:"Methods of Sperm Selection for In-Vitro Fertilization",slug:"methods-of-sperm-selection-for-in-vitro-fertilization-1",totalDownloads:268,totalCrossrefCites:0,authors:[{id:"349382",title:"M.Sc.",name:"Abimibola",surname:"Nanna",slug:"abimibola-nanna",fullName:"Abimibola Nanna"}]},{id:"77348",title:"Management of Post-Circumcision Glans/Penile Necrosis",slug:"management-of-post-circumcision-glans-penile-necrosis",totalDownloads:198,totalCrossrefCites:0,authors:[{id:"341061",title:"Dr.",name:"Yusuf",surname:"Arikan",slug:"yusuf-arikan",fullName:"Yusuf Arikan"},{id:"355828",title:"Dr.",name:"Ali",surname:"Ayten",slug:"ali-ayten",fullName:"Ali Ayten"}]},{id:"78100",title:"Epigenetics in Male Infertility",slug:"epigenetics-in-male-infertility",totalDownloads:225,totalCrossrefCites:0,authors:[{id:"349295",title:"Prof.",name:"Hayfa H.",surname:"Hassani",slug:"hayfa-h.-hassani",fullName:"Hayfa H. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"50754",title:"Medicinal Chemistry of Vitamin K Derivatives and Metabolites",doi:"10.5772/63511",slug:"medicinal-chemistry-of-vitamin-k-derivatives-and-metabolites",body:'\nVitamin K is a specific cofactor for γ‐glutamyl carboxylase (GGCX), which catalyzes formation of γ‐carboxyglutamyl (Gla) residues in vitamin K–dependent proteins (Figure 1) [1]. Various other biological activities of vitamin K and its derivatives have also been reported. For example, vitamin K3 (menadione), a vitamin K homologue that was considered as a synthetic vitamin K, has antitumor activity [2–5], as does vitamin K2 (menaquinone) [6, 7]. Among the homologues of vitamin K2, menaquinone‐4 (MK‐4), which contains four isoprene units, has been intensively investigated. It binds to nuclear receptor human pregnane X receptor (PXR), which is also called steroid and xenobiotic receptor (SXR), and regulates transcription of osteoblastic genes [8, 9]. It also exhibits anti‐inflammatory activity by suppressing the NF‐kB pathway [10], and has an inhibitory effect on arteriosclerosis [11]. It binds 17β‐hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism [12]. Further, it enhances testosterone production [13, 14], and shows growth‐inhibitory activity toward hepatocellular carcinoma (HCC) cells [6, 7]. These biological activities of vitamin K and its analogues are attractive targets of drug discovery, and the activities of vitamin K metabolites have also attracted much interest. A great many natural and synthetic biologically active 1,4‐naphthoquinone derivatives (i.e., vitamin K derivatives) have been reported. In this chapter, we will focus on three medicinal‐chemistry studies of vitamin K activities.
\nStructures of vitamin K homologues.
The antitumor activity of thioether derivatives is one of the most intensively investigated fields in the medicinal chemistry of menadione derivatives. Several series of naphthoquinone derivatives and benzoquinone derivatives bearing an alkyl, alkoxy, or alkylthio group as a side chain have been synthesized and biologically evaluated by assay of growth‐inhibitory activity toward human hepatoma cell line HepB3. Almost all of the tested compounds, as well as the parent menadione, exhibited significant inhibitory activity, and the alkylthio derivatives were more potent than the corresponding alkyl and alkoxy derivatives. Among these compounds, a 2‐hydroxyethylthio derivative Cpd 5 (compound 5; NSC 672121) exhibited the most potent activity (Figure 2) [15]. Subsequent studies revealed that Cpd 5 irreversibly inhibits growth‐regulatory phosphatase Cdc25 by arylating a cysteine residue in the catalytic site, causing cell‐cycle arrest [16–19].
\nCompounds tested in the initial work on development of Cpd5.
Based on the finding that Cpd5 inhibits Cdc25 and exerts antitumor activities, various menadione derivatives have been developed as candidate antitumor compounds. Bis(2‐hydroxyethylthio)naphthoquinone derivative NSC 95397 (Figure 3) showed potent Cdc25‐inhibitory activity and inhibited proliferation of several cancer cell lines with greater potency than that of Cpd 5 [20]. Hydroxylated NSC 95397 derivatives exhibited enhanced Cdc25‐inhibitory activity and inhibited growth of several cancer cell lines [21]. Fluorinated Cpd 5 was three times more potent than Cpd‐5 itself in Hep3B growth inhibition and induced phosphorylation of ERK1/2, JNK1/2 and p38 in HepB3 cells [22]. Calculations suggested that fluorinated Cpd 5 cannot generate reactive oxygen species because of its modified redox profile, and therefore, the compound appears to function as a pure arylating agent [23]. Modification of the core structure afforded a maleimide derivative PM‐20 with a submicromolar IC50 value for HepB3 growth inhibition. Structure‐activity relationship study indicated that the biphenyl structure of PM‐20 is essential for activity (Figure 3) [24].
\nStructures of Cpd 5 derivatives bearing a 2‐hydroxyethylthio moiety.
Modification of the hydroxyethyl side chain of Cpd‐5 and NSC 95397 was also investigated. Carboxylic acid derivatives such as compounds
Examples of side chain‐modified Cpd 5 derivatives.
A natural product, plumbagin (5‐hydroxymenadione, Figure 5), shows anticancer and antiproliferative activities [29]. It suppresses the NF‐kB activation pathway by modulating p65 and IkBα kinase activation to potentiate cytokine‐ and drug‐induced apoptosis [30]. Structurally related naphthoquinone derivatives juglone and 1,4‐naphthoquinone exerted similar TNFα‐induced NF‐kB inhibitory activities, whereas menadione did not [30]. Another natural product, lapachol, which has a hydroxyl group instead of the methyl group of MK‐1, has anticancer activity [31]. A synthetic analogue
Some vitamin K–related naphthoquinone derivatives with antitumor activity.
In the early twenty‐first century, it was found that MK‐4 binds a nuclear receptor, steroid, and xenobiotic receptor (SXR), which is a human homologue of pregnane X receptor (PXR), and regulates transcription of osteoblastic genes [8, 9]. Structure‐activity relationships of MK‐4 as an SXR ligand were intensively investigated by Suhara et al., using deuterated derivatives (Figure 6). Saturation of double bond(s) in the side chain significantly reduced the SXR agonistic activity. Triene derivative
Compounds used in SAR study of SXR.
The length of the side chain is important for the SXR activity of menaquinones. MK‐1 bearing one prenyl group showed little ligand potency, while MK‐2, MK‐3, and MK‐4 were more active. In the SXR‐GAL4 one hybrid assay system, MK‐3 was the most potent compound, and MK‐2 and MK‐4 showed somewhat lower activity. In the assay system using SXRE, MK‐2, and MK‐3 were the most potent compounds [35]. “Double side chain” vitamin K analogues bearing the same side chains at the 2‐position and 3‐position of the naphthoquinone ring were also designed and synthesized. MK‐1‐W and MK‐2‐W were as potent as MK‐3 and MK‐4, whereas MK‐3‐W, MK‐4‐W, and PK‐W showed little activity (Figure 7) [35].
\nStructures of double side chain vitamin K analogs.
Substitution at the terminal of the side chain of menaquinones significantly affects SXR ligand potency. Hydroxylated derivatives MK‐2‐ω‐OH, MK‐3‐ω‐OH, and MK‐4‐ω‐OH showed little activity in the SXR‐GAL4 one hybrid assay system, whereas compounds
Interestingly, Suhara et al. also found that menaquinone derivatives bearing a terminal hydrophobic substituent have the ability to induce selective neuronal differentiation of neuronal progenitor cells. The most potent compound
Structures of menaquinone derivatives with modified terminal.
The biological activities of metabolites of vitamin K are also important. MK‐4 is one of the most interesting vitamin K homologues because of its multifunctional properties, and ω‐carboxyl homologues of MK‐4 (MK‐4‐ω‐COOH), K acid I, K acid II and their glucuronides have been identified as metabolites [38–42]. It is considered that MK‐4 is initially metabolized to MK‐4‐ω‐COOH by ω‐oxidation, followed by β‐oxidation to afford intermediary carboxylic acids (Figure 9) [43]. These carboxylic acids can be categorized into two groups; MK‐n‐ω‐COOH derivatives bearing a α,β‐unsaturated carboxy group and MK‐n‐(ω‐2)‐COOH derivatives bearing a γ,δ‐unsaturated carboxy group. Chemical synthesis of these metabolites is essential for evaluation of their properties, and several synthetic routes have been reported.
\nPutative catabolic pathways of MK‐4.
The MK‐4 metabolites K acid I and K acid II are also metabolites of phylloquinone (vitamin K1). Several chemical syntheses of K acid I and K acid II have been reported. Watanabe et al. synthesized K acid I by direct addition of a carboxy side chain to the naphthoquinone framework using BF3 etherate [44]. A route involving a malonyl derivative and decarboxylation was also investigated (Figure 10) [45]. They also synthesized K acid II. Addition of a side chain moiety by Friedel‐Crafts acylation, followed by Clemmensen reduction, afforded naphthylcarboxylic acid, and oxidation of the naphthol moiety using Fremy\'s salt gave K acid II. Direct alkylation of naphthoquinone using peroxide also afforded K acid II (Figure 11) [44].
\nSynthetic route to K acid I (Watanabe et al.).
Synthetic route of K acid II (Watanabe et al.).
Synthetic routes of K acid I and K acid II (Teitelbaum et al.).
Teitelbaum et al. synthesized K acid I and K acid II by oxidation of MK‐2 and MK‐1, respectively. They prepared intermediary MK‐n using a menadione‐cyclopentadiene adduct as the same starting material (Figure 12) [46].
\nOkamoto et al. synthesized MK‐1‐ω‐COOH by using Wittig reaction as a key step. To prepare the intermediary aldehyde, they employed alkylation and oxidative cleavage (Figure 13) [47].
\nSynthesis of MK‐1‐ω‐COOH (Okamoto et al.).
Terao et al. synthesized MK‐3‐(ω‐2)‐COOH and MK‐4‐(ω‐2)‐COOH using Claisen rearrangement as a key reaction. Claisen reaction of triethyl orthoacetate and MK‐n derivative gave two‐carbon‐atom‐extended carboxylic acid esters, and then hydration afforded MK‐n‐(ω‐2)‐COOH derivatives (Figure 14) [48].
\nSynthesis of MK‐n‐(ω‐2)‐COOH derivatives (Terao et al.).
Masaki et al. employed sulfur‐contractive anionic [2,3]‐sigmatropic rearrangement for side chain elongation. Treatment of allyl sulfide with base afforded two‐carbon‐atom‐extended carboxylic acid esters in one pot (Figure 15). MK‐2‐(ω‐2)‐COOH and MK‐3‐(ω‐2)‐COOH were obtained in this way [49].
\nSynthesis of MK‐n‐(ω‐2)‐COOH derivatives (Masaki et al.).
Fujii et al. reported systematic synthesis of menaquinone metabolites. MK‐n‐ω‐COOH derivatives were synthesized by oxidation of the terminal carbon of MK‐n derivatives. Stereoselective oxidation with selenium oxide, followed by stepwise oxidation, gave MK‐n‐ω‐COOH derivatives. K acid II was synthesized by hydrogenation of MK‐1‐ω‐COOH (Figure 16) [50]. MK‐n‐(ω‐2)‐COOH derivatives were synthesized by oxidative cleavage of MK‐n derivatives. Epoxidation of terminal olefin followed by perchloric acid treatment afforded 1,2‐diols. Oxidative cleavage of the diol moiety followed by oxidative reactions gave MK‐n‐(ω‐2)‐COOH derivatives (Figure 17) [50]. These synthetic schemes correspond to the putative catabolic pathways of menaquinones, that is, ω‐oxidation and β‐oxidation.
\nSynthesis of MK‐n‐ω‐COOH derivatives (Fujii et al.).
Synthesis of MK‐n‐(ω‐2)‐COOH derivatives (Fujii et al.).
Suhara et al. designed and synthesized ω‐hydroxy derivatives (ω‐alcohols) and ω‐formyl derivatives (ω‐aldehydes) as menaquinone metabolite analogs. ω‐Oxidized side chain moieties were prepared from corresponding isoprene derivatives, and the side chain parts were introduced into the naphthalene core. Oxidation to quinone form afforded ω‐alcohols, and then PDC oxidation afforded ω‐aldehydes (Figure 18) [51, 52].
\nSynthesis of MK‐n‐ω‐alcohols and MK‐n‐ω‐aldehydes (Suhara et al.).
These menaquinone carboxylic acid derivatives and related quinone carboxylic acids, including ubiquinone derivatives and tocopheryl derivatives, show lysosomal membrane‐stabilizing activity [45, 47]. Appropriate hydrophobicity of the side chain appears to be essential for this activity. Some of these compounds also exert inhibitory effects on the generation of the slow‐reacting substance of anaphylaxis [48].
\nMK‐4 has various biological activities, such as anti‐inflammatory activity and antitumor activity, and these activities of the menaquinone metabolites were also investigated. All tested menaquinone metabolites inhibited LPS‐induced production of proinflammatory cytokines in RAW264.7 cells [50]. It is suggested that naphthoquinone structure is essential for the anti‐inflammatory activity of menaquinone derivatives. Regarding antitumor activity, several carboxylic acids, such as MK‐2‐ω‐COOH, significantly inhibited proliferation of JHH7 and HepG2 hepatocellular carcinoma cell lines. On the other hand, MK‐2‐ω‐COOH did not inhibit proliferation of normal hepatic cells. Anti‐proliferative activity may be associated with caspase/transglutaminase‐related pathways [53].
\nThe ω‐alcohols and ω‐aldehydes showed apoptosis‐inducing activity toward human leukemia cell line HL‐60 and human osteosarcoma cell line MG‐63. The ω‐aldehydes were more potent than the corresponding ω‐alcohols [51, 52]. The vitamin K potency of MK‐4‐ω‐OH, that is, its coenzyme activity for GGCX, was also evaluated. MK‐4‐ω‐OH showed a larger
Vitamin Ks are attractive lead compounds for drug discovery. One of the most promising applications is as candidate antitumor agents, though the mechanism of action of Cpd 5 could be different from that of intact vitamin Ks. In addition, bone homeostasis and neural effects are also possible targets of vitamin K derivatives. Vitamin K may also be used as a food supplement, and therefore, characterization of its metabolites is important. It is noteworthy that some menaquinone metabolites have characteristic activities distinct from those of intact vitamin K2. Though a clinical study of MK‐4 as an agent to prevent recurrence of hepatocellular carcinoma was terminated [54], the metabolites and their analogs still represent potential drug candidates.
\nFor the growth of economy of a country and improving living status of population, industrial functioning is mandatory which is in other hand associated activities including supply of power, raw materials, processing and discharge of waste. For a major section of industries, power supply is from coal or electricity generated from coal, and the raw materials are various form of ores received from mining. Mine tailing is the fine residual mine dump after completion of mining left with dug out soil, scattered residuals and disturbed ecosystem. The major source of chromium in the mine tailings is the residual ores present in traces not extracted with economic point of view and mineral processing chemicals that are left unattended. Chromium (Cr), a valuable element often finds its utility in metallurgical, chemical, and refractory industries due to its pigment property, hardness and persistence. From environment point of view, chromium exists in three oxidative states, elemental chromium (0) that does not exist naturally, whereas trivalent chromium (Cr III) is rather stable followed by hexavalent chromium (Cr VI) based on the different number of electrons and therefore varied properties [1]. Hexavalent chromium is extremely toxic even in low concentration and listed as carcinogenic, hematotoxic and altering genetic material whereas, Cr (III) is regarded as micronutrient in human diet. When Cr is left unattended in mine tailings, it can be transported by natural means to nearby waterbody, added with acid mine drainage, and surrounding ecosystem expanding the circumference of toxicity exposure [2]. This chapter emphasises on toxicity of hexavalent chromium in genetic level that influence expression of genes, the transcript factors controlling the differentially expressed genes and finally to find out the major indicating and influenced genetic factors with functional analysis of gene ontology for respiratory units of human.
Toxicity of chromium is directly influenced by the chromium species with valence with number of electrons and thus their properties. The Cr(VI), is a powerful oxidizing agent and plainly toxic to human and other organisms causing adverse effect to blood cells, renal cells, allergic conditions and organs of most part of body failure. Chromium can significantly find its route of exposures through dermal chromium contact in waste sites, inhalation of chromium emissions and ingestion of contaminated water or food grown in chromium contaminated soil. Also, erosion products and emissions from road and cement dust, leather, paints and or any Cr used materials contribute to inhalation of chromium. Dermal ulcers, irritation and sensitization of respiratory/lungs are consecutive result of chromium contact. In the plasma and cells, Cr(VI) readily get reduced to Cr(III), and thereafter excreted in the urine. Trivalent chromium is the form of chromium that is essential to human health and counted as an essential trace mineral in the human diet. Hexavalent chromium is recognised as genotoxic as it can damage genetic information in living cells, causes DNA mutations, and possibly the formation of cancerous tumours. Chromates (chromium salts) formed from hexavalent chromium also finds utilization in manufacture leather products, paints, cement, mortar, anti-corrosives, and other things. They are carcinogenic and allergenic.
Occupational exposures often include mixed exposure to both Cr(III) and Cr(VI) [3]. Chromium compounds, when inhaled, causes respiratory tract irritants, resulting in airway irritation, airway obstruction, and lung, nasal, or sinus cancer. Radiographic analysis from several reports revealed enlargement of the hilar region and lymph nodes [4, 5]. Consistent associations have been found between employment in the chromium industries and significant risk for respiratory cancer. Moller et al. [6] reported systemic reactions characterised with anaphylactoid reaction in a young welder having chromium (VI) vapor fume exposures. Following an experiment with sodium chromate inhalation at a concentration of 29 μg/m3, formation of static urticaria, angioedema and severe bronchospasm simultaneously with plasma histamine rising in threefold was documented and suggested direct positive leukocyte inhibitory factor of sodium chromate.
A number of nasal mucosa injury cases in Cr (VI) exposed workers at concertation of nearly 20 μg/m3 (against US permissible standard 5 μg/m3) for 5 months to 10 years characterised with inflamed mucosa and ulcerated/perforated septum was recorded in a study with 43 chrome-plating plants and tanneries in Sweden [7, 8]. Huge number of complaints for nasal irritations was documented in a detail epidemiological study with Tokyo (Japan) housewives residing near chromium slag contaminated construction site [7]. U.S has recommended chromate and chromic acid at workplace to be 5 μg/m3 as permissible standard. Gibb et al. [9] observed that with less than 30 days median time for nasal ulceration diagnosis from first exposure, median Cr (VI) concentration matched the Sweden report. Occupational exposure to Cr(III) has also been associated with respiratory effects. Persons developed coughing, wheezing, and decreased forced volume after an inhalation exposure to a sample of Cr(III) sulfate [10]. Combine effect of Cr(III) and Cr(VI) as total chromium (0.02–0.19 mg total chromium/m3) investigated among 60 ferrochromium workers squeezed out subjective symptoms of coughing, wheezing, and dyspnea whereas control remained neutral [11]. These symptoms might get puzzled with smoking issue to clarify the accurate problem of the diseases [11]. While considering respiratory issue, animals are also often exposed to chromium similar to the human. Henderson et al. [12] in histological examination with exposure of 0.9–25 mg Cr(III) trichloride for 30 min observed alterations in lung tissues associated with mild inflammation.
Comparative toxico-genomics database (CTD, http://ctdbase.org) is a recognised well informed/updated, openly accessible database. It purposes to provide detail knowledge and information about the impacts of exposure of environmental elements (pollutants) on human health.
The core block of the database basically manually curated contains updated information regarding interaction and relationships among chemicals, genes, proteins and their resulted specific disease in terms of functional and pathways to incorporate new hypotheses expressing underlying mechanisms of disease and environmental contamination [13].
In this work, all Chromium- gene /protein interactions for respiratory disease are downloaded from CTD, in which Chromium- gene /protein interactions associated to the following 04 respiratory disease are selected for further analysis according to MESH ID used in CTD— Lung Neoplasma, Pulmonary Fibrosis and Lung disease. Chromium- gene/protein interactions associated to this respiratory disease are collected for further analysis. According to the reference score on relationships between chemicals-genes, genes-diseases and chemicals-diseases [14], lung neoplasms is recognised as most likely having the maximum connectivity with chromium. (Table 1). From the identified 168 chromium gene with in respiratory disease, 131 genes are unique.
KEGG (http://www.genome.jp/) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher-order functional information [15]. For the analysis of Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, the Database for Annotation, Visualization and Integrated Discovery (DAVID, http://david.abcc.ncifcrf.gov/) is a great option. DAVID provides various functional annotation tools for researchers to understand biological meaning behind large list of genes. [16] Gene ontology (GO) analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis can be performed for analysing differentially expressed genes (DEGs) at the functional level based on DAVID Bioinformatics Resources 6.8. P < 0.05 as the cut-off criterion. Researchers can upload all DEGs to the online software DAVID to identify overrepresented GO categories and KEGG pathways. The curated genes in CTD for each respiratory disease can be uploaded to DAVID 6.8 Beta (https://david-d.ncif-crf.gov/tools.jsp) with
GO analysis results for Cr toxicity in respiratory organs shows that that chromium interacted genes in respiratory disease are involved in the biological processes (BP) such as positive regulation of gene expression, positive regulation of cell proliferation, response to drug positive regulation of protein phosphorylation. (Table 2) For molecular function (MF), genes are enriched in identical protein binding, enzyme binding, transcription factor binding and protein phosphatase binding (Table 2). In addition, GO cell component (CC) analysis also displayed that the gene are significantly enriched in the extracellular space, protein complex, extracellular region and extracellular exosome (Table 2).
Disease Name | Inference chromium-interacted genes (n) | Gene count | Inference Score |
---|---|---|---|
Lung Neoplasms (Cr VI) | ACE,AKT1,APOA1,APOC3,AR,AVPI1,BCL2L1,BRCA2,CASP8,CCND1,CDKN1A,CDKN1B,CDKN2A,CEACAM1,CHEK2,COL6A1,COX17,CRP,CTNNB1,CWH43,CYP1B1,DPYD,EEF2,EFNB2,EGFR,EGR1,ERBB2,ERBB3,ESR1,FAS,FEN1,FGF9,FOS,GCLC,GPX1,GPX3,GSTM1,GSTP1,HILPDA,HMOX1,HRAS,IDS,IER2,IFNG,IL1B,IL2,IL6,JUN,JUNB,LECT2,MAP2K7,MAPK1,MAPK14,MAPK3,MIR21,MIR494,MMP10,MYC,NOS2,OGG1,PCNA,PDCD4,PRDX1,PRDX6,PRKN,PTMA,SERPINA1,SERPING1,SFTPB,SIDT2,SMC2,SOX2,SOX9,TERT,TFRC,TGFBR2,TNF,TP53,TRP53,USP18,WNT5A | 81 | 74.7 |
Lung Neoplasms(Cr III) | ACE,AKT1,ANXA2,APOA1,AZGP1,CASP8,CAV1,CDKN1A,CDKN2A,CPE,CYP1B1,FOS,GCLC,GJA1,GPX1,GSTM1,HMOX1,IER2,IFNG,IL10,IL1B,IL6,JUN,MAPK1,MAPK3,MMP1,SFTPB,TGFB1,TLR4,TNF,TP53,TYMS | 32 | 58.22 |
Pulmonary Fibrosis | ACE2, ACTA2, CAT, CCL11, CCL2, CCL5, CXCL8, EDN1, FAM13A, FN1, FYN, HMGB1, HMOX1, IL1B, IL4, IL6, LAMB1, MMP2, MMP9, MTOR, NFE2L2, PARP1, PDGFB, PTX3, SERPINA1, SOD1,STAT3,TIMP1,TNF | 29 | 25.25 |
Lung Diseases | ACE, BST1, HARS, HIF1A, IGF1R, INSR, KIT, PDGFRA,PTGS2,SERPINA1,SFTPB,SOD2,TNF,VEGFA | 14 | 7.62 |
Asthma, Occupational | TGFB1, TNF | 02 | 5.86 |
Lung Injury | ACE, ACE2, CCL2, CYP1A1, HMOX1, IL6, PARP1, SIRT1, TNF | 09 | 3.12 |
Nose Neoplasms | MMP2 | 01 | 2.55 |
Selected Respiratory diseases and related chromium-interacted gene.
Term | Count | P value | FDR | Genes |
---|---|---|---|---|
Positive regulation of gene expression | 26 | 1.17E-21 | 2.49E-18 | CRP, PDGFB, HIF1A, TNF, GJA1, FGF9, ERBB3, MYC, ERBB2, HRAS, TGFB1, CAV1, STAT3, FN1, MAPK14, MTOR, VEGFA, ACTA2, AR, IL6, IFNG, IL1B, KIT, TP53, TLR4, NFE2L2 |
Positive regulation of nitric oxide biosynthetic process | 14 | 1.39E-18 | 1.49E-15 | EDN1, INSR, PTGS2, SOD2, ESR1, TNF, EGFR, MTOR, IL6, IFNG, IL1B, AKT1, PTX3, TLR4 |
Positive regulation of cell proliferation | 26 | 1.23E-15 | 8.80E-13 | CDKN1B, HILPDA, PDGFB, EGFR, IGF1R, EFNB2, FGF9, MYC, MAPK1, SOX9, TIMP1, HRAS, PDGFRA, EDN1, TGFB1, INSR, STAT3, FN1, IL2, TGFBR2, VEGFA, AR, IL6, IFNG, KIT, BCL2L1 |
Aging | 18 | 1.68E-15 | 8.89E-13 | JUN, TGFB1, OGG1, STAT3, FOS, TYMS, EEF2, TGFBR2, SOD1, GCLC, IL6, CAT, CYP1A1, SERPING1, CCL2, AKT1, TIMP1, NFE2L2 |
Response to drug | 22 | 2.08E-15 | 8.89E-13 | CDKN1A, JUN, TGFB1, CDKN1B, OGG1, STAT3, APOA1, FOS, TYMS, PTGS2, SOD2, TGFBR2, SOD1, IL4, IL6, IFNG, CCND1, MYC, CAT, CYP1A1, CTNNB1, FYN |
Positive regulation of smooth muscle cell proliferation | 13 | 7.81E-15 | 2.78E-12 | JUN, EDN1, PDGFB, PTGS2, TNF, EGFR, MTOR, TGFBR2, IL6, MYC, CCL5, AKT1, HMOX1 |
Positive regulation of protein phosphorylation | 16 | 1.07E-14 | 3.27E-12 | TGFB1, ANXA2, INSR, TNF, MMP9, EGFR, MTOR, VEGFA, CCND1, CHEK2, IL1B, ERBB2, AKT1, SOX9, HRAS, MAPK3 |
Term | Count | P value | FDR | Genes |
Extracellular space | 49 | 1.61E-24 | 3.37E-22 | SERPINA1, CXCL8, TFRC, HILPDA, LECT2, HMGB1, TNF, FGF9, TIMP1, SFTPB, EDN1, ANXA2, GPX3, MMP2, WNT5A, APOA1, MMP9, MMP10, ACTA2, ACE2, AZGP1, IFNG, IL1B, CAT, KIT, SERPING1, CRP, CCL11, GSTP1, PDGFB, EGFR, ERBB3, PRDX1, CCL5, CCL2, HMOX1, TGFB1, ACE, FN1, APOC3, LAMB1, PRDX6, IL2, SOD1, VEGFA, IL4, IL6, CPE, PTX3 |
Protein complex | 21 | 1.48E-12 | 1.55E-10 | PDGFRA, CDKN1A, FEN1, CDKN1B, PARP1, CDKN2A, OGG1, CAV1, BRCA2, PTGS2, SOD1, ACTA2, AR, MYC, COL6A1, AKT1, MAPK1, CTNNB1, SOX9, TP53, MAPK3 |
Extracellular region | 37 | 9.09E-12 | 6.36E-10 | CRP, SERPINA1, CCL11, CXCL8, TFRC, PDGFB, HMGB1, TNF, FGF9, CCL5, CCL2, TIMP1, SFTPB, EDN1, TGFB1, ACE, GPX3, MMP2, WNT5A, FN1, APOA1, APOC3, LAMB1, MMP9, MMP10, IL2, SOD1, VEGFA, IL4, ACE2, IL6, AZGP1, IFNG, IL1B, COL6A1, SERPING1, PTX3 |
Cytosol | 49 | 4.84E-09 | 2.54E-07 | CDKN1A, CDKN1B, FAM13A, SMC2, SOX2, GJA1, CASP8, CCND1, MYC, AKT1, HRAS, GPX1, ANXA2, APOA1, FOS, TGFBR2, ACTA2, AR, IL1B, DPYD, CAT, TP53, GSTP1, TYMS, USP18, HIF1A, PRDX1, HMOX1, MAPK1, FYN, HARS, MAP2K7, MAPK3, JUN, GSTM1, NOS2, CDKN2A, STAT3, EEF2, MAPK14, PRDX6, MTOR, SOD1, GCLC, PDCD4, CTNNB1, FAS, NFE2L2, BCL2L1 |
Mitochondrion | 26 | 7.77E-07 | 2.62E-05 | FEN1, GSTP1, OGG1, COX17, TYMS, GJA1, CASP8, MYC, PRDX1, CYP1B1, AKT1, MAPK1, FYN, HARS, MAPK3, GPX1, PARP1, CDKN2A, MMP2, MAPK14, SOD2, SOD1, CAT, CYP1A1, TP53, BCL2L1 |
Membrane raft | 11 | 7.89E-07 | 2.62E-05 | ACE2, GJA1, CASP8, ANXA2, CAV1, FAS, FYN, EEF2, TNF, EGFR, TGFBR2 |
Extracellular exosome | 40 | 8.72E-07 | 2.62E-05 | CRP, SERPINA1, PCNA, TFRC, GSTP1, SMC2, GJA1, FGF9, PRDX1, MAPK1, TIMP1, MAPK3, ACE, GPX1, ANXA2, GPX3, INSR, WNT5A, FN1, APOA1, APOC3, LAMB1, EEF2, MAPK14, SOD2, MMP9, PRDX6, SOD1, ACTA2, ACE2, BST1, AZGP1, CEACAM1, IL1B, COL6A1, CAT, SERPING1, CPE, CTNNB1, FAS |
Identical protein binding | 31 | 2.03E-15 | 8.34E-13 | SERPINA1, PCNA, TFRC, LECT2, PDGFB, TNF, EGFR, IGF1R, CASP8, ERBB3, CHEK2, PRDX1, ERBB2, AKT1, MAPK1, FYN, JUN, PARP1, CAV1, STAT3, FN1, APOA1, SOD2, MMP9, ESR1, SOD1, VEGFA, FAS, PTX3, TP53, BCL2L1 |
Enzyme binding | 22 | 9.84E-15 | 2.02E-12 | JUN, TGFB1, GSTM1, PCNA, PARP1, CAV1, APOA1, PTGS2, MAPK14, HIF1A, ESR1, EGFR, AR, CCND1, CAT, CYP1A1, AKT1, HMOX1, CTNNB1, FYN, MAP2K7, TP53 |
Transcription factor binding | 15 | 9.22E-09 | 1.13E-06 | JUN, PARP1, CDKN2A, GPX3, STAT3, HMGB1, FOS, HIF1A, ESR1, AR, CCND1, MYC, MAPK1, CTNNB1, TP53 |
Protein phosphatase binding | 9 | 1.10E-08 | 1.13E-06 | CEACAM1, CDKN1B, ERBB2, STAT3, CTNNB1, MAPK14, MAP2K7, TP53, EGFR |
Protein binding | 90 | 3.45E-08 | 2.41E-06 | CDKN1A, FEN1, CDKN1B, SERPINA1, CXCL8, TFRC, OGG1, HILPDA, HMGB1, BRCA2, TNF, IGF1R, SMC2, SOX2, GJA1, CASP8, CCND1, MYC, CHEK2, AKT1, SOX9, TIMP1, HRAS, PDGFRA, EDN1, PARP1, ANXA2, GPX3, MMP2, WNT5A, APOA1, FOS, MMP9, TGFBR2, ACE2, AR, AZGP1, CEACAM1, DPYD, KIT, SERPING1, TLR4, TP53, AVPI1, CRP, CCL11, PCNA, GSTP1, COX17, PDGFB, PTGS2, USP18, HIF1A, EGFR, EFNB2, ERBB3, TERT, PRDX1, CCL5, ERBB2, HMOX1, MAPK1, FYN, MAP2K7, MAPK3, EGR1, JUN, TGFB1, NOS2, CDKN2A, INSR, CAV1, STAT3, FN1, EEF2, MAPK14, ESR1, PRDX6, MTOR, SOD1, VEGFA, IL4, IL6, CYP1A1, PDCD4, CTNNB1, FAS, PTX3, NFE2L2, BCL2L1 |
Cytokine activity | 12 | 3.53E-08 | 2.41E-06 | IL4, IL6, EDN1, TGFB1, IFNG, IL1B, WNT5A, TIMP1, HMGB1, TNF, IL2, VEGFA |
Protein homodimerization activity | 21 | 1.14E-07 | 6.65E-06 | PDGFRA, JUN, TGFB1, GSTM1, NOS2, TFRC, PDGFB, TYMS, PTGS2, SOD1, VEGFA, CEACAM1, TERT, ERBB3, CHEK2, CCL5, KIT, DPYD, CAT, HMOX1, BCL2L1 |
Gene ontology analysis of Cr interacted genes.
Table 3 contains the most significantly enriched pathways of the chromium interacting genes by KEGG analysis. The interacting genes are enriched in Pathways in cancer, Proteoglycans in cancer, HIF-1 signalling pathway and TNF signalling pathways.
Term | Count | P value | FDR | Genes |
---|---|---|---|---|
Pathways in cancer | 41 | 5.78E-24 | 5.60E-22 | CDKN1A, CDKN1B, CXCL8, GSTP1, PDGFB, BRCA2, PTGS2, HIF1A, EGFR, IGF1R, CASP8, FGF9, CCND1, MYC, ERBB2, AKT1, MAPK1, HRAS, MAPK3, PDGFRA, JUN, TGFB1, NOS2, CDKN2A, MMP2, WNT5A, STAT3, FN1, LAMB1, FOS, MMP9, MTOR, TGFBR2, VEGFA, AR, IL6, KIT, CTNNB1, FAS, TP53, BCL2L1 |
Proteoglycans in cancer | 30 | 1.79E-21 | 8.69E-20 | CDKN1A, HIF1A, TNF, EGFR, IGF1R, ERBB3, CCND1, MYC, ERBB2, AKT1, MAPK1, HRAS, MAPK3, TGFB1, CAV1, MMP2, WNT5A, STAT3, FN1, MIR21, MAPK14, MMP9, ESR1, MTOR, VEGFA, PDCD4, CTNNB1, FAS, TP53, TLR4 |
HIF-1 signaling pathway | 21 | 3.91E-18 | 1.26E-16 | CDKN1A, EDN1, CDKN1B, NOS2, TFRC, INSR, STAT3, HIF1A, EGFR, MTOR, IGF1R, VEGFA, IL6, IFNG, ERBB2, AKT1, HMOX1, MAPK1, TIMP1, TLR4, MAPK3 |
Chagas disease (American trypanosomiasis) | 21 | 2.09E-17 | 5.07E-16 | JUN, TGFB1, ACE, CXCL8, NOS2, FOS, MAPK14, TNF, IL2, TGFBR2, IL6, CASP8, IFNG, IL1B, CCL5, FAS, CCL2, AKT1, MAPK1, TLR4, MAPK3 |
Bladder cancer | 14 | 1.10E-14 | 2.13E-13 | CDKN1A, CXCL8, CDKN2A, MMP2, MMP9, EGFR, VEGFA, CCND1, MYC, ERBB2, MAPK1, HRAS, TP53, MAPK3 |
Hepatitis B | 21 | 1.87E-14 | 3.02E-13 | CDKN1A, JUN, TGFB1, CDKN1B, PCNA, CXCL8, STAT3, FOS, TNF, MMP9, IL6, CASP8, CCND1, MYC, FAS, AKT1, MAPK1, HRAS, TP53, TLR4, MAPK3 |
Prostate cancer | 16 | 1.94E-12 | 2.69E-11 | PDGFRA, CDKN1A, CDKN1B, PDGFB, EGFR, MTOR, IGF1R, AR, CCND1, ERBB2, AKT1, MAPK1, CTNNB1, HRAS, TP53, MAPK3 |
TNF signaling pathway | 17 | 2.75E-12 | 3.34E-11 | JUN, EDN1, FOS, PTGS2, MAPK14, TNF, MMP9, IL6, CASP8, IL1B, CCL5, FAS, CCL2, AKT1, MAPK1, MAP2K7, MAPK3 |
Pancreatic cancer | 14 | 7.57E-12 | 8.16E-11 | TGFB1, CDKN2A, STAT3, BRCA2, EGFR, TGFBR2, VEGFA, CCND1, ERBB2, AKT1, MAPK1, TP53, BCL2L1, MAPK3 |
HTLV-I infection | 23 | 1.29E-11 | 1.25E-10 | PDGFRA, EGR1, CDKN1A, JUN, TGFB1, PCNA, CDKN2A, WNT5A, PDGFB, FOS, TNF, IL2, TGFBR2, IL6, TERT, CCND1, CHEK2, MYC, AKT1, CTNNB1, HRAS, TP53, BCL2L1 |
Pathway analysis for the chromium interacting genes related to Respiratory Disease.
The transcription factors (TFs) as well as microRNAs (miRNAs), are recognised for their huge share in transacting and gene regulations with various common logics and regulatory factors for gene regulation in multicellular genomes [18, 19]. The library of ENCODE and ChEA Consensus TFs from ChIP-X in EnrichR (http://amp.pharm.mssm.edu/Enrichr/ [20, 21]) can be used for the possible TFs and related networks. The TargetScan library in EnrichR can be used for the possible miRNA interaction. TFs are identified to be significantly associated with the genes involved in the respiratory disease. TRIM28, NFE2L2, EGR1 GATA2, PPARG, ZMIZ1 and ESR1 are significant for respiratory disease influencing DEGs. The regulated genes for each of these TFs for chromium toxicity are shown in Table 4 followed by the miRNAs identified for chromium interacting genes involved in the Respiratory diseases in Figure 1.
Term | Overlap | P-value | Adjusted P-value | Combined Score | Gene |
---|---|---|---|---|---|
TRIM28 | 9/210 | 1.02E-05 | 9.92E-04 | 82.94725092 | EFNB2;EGR1;JUN;PARP1;ERBB3;WNT5A;SOX9;HIF1A;SOD1 |
NFE2L2 | 19/1022 | 3.76E-05 | 0.001413873 | 32.51065582 | CDKN1A;GSTM1;WNT5A;FN1;PTGS2;ESR1;PRDX6;VEGFA;EFNB2;GJA1;GCLC;PRDX1;DPYD;CAT;CYP1B1;HMOX1;FYN;PTX3;AVPI1 |
EGR1 | 10/315 | 4.37E-05 | 0.001413873 | 53.21069483 | EGR1;JUN;SERPINA1;STAT3;AKT1;MAPK1;ESR1;MMP9;EGFR;SOD1 |
GATA2 | 15/772 | 1.64E-04 | 0.003970477 | 28.45933865 | JUN;CDKN1A;EDN1;GPX1;MMP2;LAMB1;FOS;MAPK14;IGF1R;IL4;CHEK2;PDCD4;IDS;IER2;BCL2L1 |
PPARG | 12/535 | 2.10E-04 | 0.004075587 | 31.58677746 | EFNB2;PDGFRA;JUN;CDKN1A;CASP8;INSR;HILPDA;CYP1B1;FOS;BCL2L1;SOD1;VEGFA |
ZMIZ1 | 16/914 | 3.19E-04 | 0.005162124 | 23.65905038 | EGR1;TGFB1;CDKN1B;GSTP1;MIR21;SOD1;VEGFA;GCLC;MYC;PRDX1;CAT;IDS;MAPK1;CTNNB1;IER2;AVPI1 |
ESR1 | 6/154 | 5.36E-04 | 0.006683025 | 48.17527072 | EDN1;SERPINA1;STAT3;CYP1B1;FOS;ESR1 |
CTCF | 24/1790 | 5.51E-04 | 0.006683025 | 17.25236108 | PDGFRA; EGR1; JUN; EDN1; TGFB1; PCNA; CAV1; APOA1; EEF2; MAPK14; IGF1R; VEGFA; EFNB2; GCLC; IL6; CEACAM1;CASP8;ERBB3;MYC;CYP1B1;MAP2K7;TP53;BCL2L1;NFE2L2 |
MYC | 11/573 | 0.001387281 | 0.014951805 | 20.72253353 | GJA1; GCLC; PCNA; TFRC; CCND1; TERT;PARP1;EEF2;TP53;IER2;SOD1 |
RAD21 | 17/1265 | 0.003726145 | 0.036105828 | 12.44311845 | PDGFRA; JUN; EDN1; PCNA; APOA1; EEF2; MAPK14; SOD2; VEGFA; EFNB2; IL6; CEACAM1; CASP8; MYC; TP53; BCL2L1;NFE2L2 |
Transcription factors for the chromium interacting genes involved in the Respiratory diseases.
Gene-TFs-miRNA Interaction Network.
Information about biological effects of a chemical at genetic level can be extensively extracted from CTD to create new hypotheses with a lot of interaction pathways and networks among genes-contaminants and diseases [22].
This highly contributes in identifying similar contaminants responsible for specific diseases. Comparable chemicals extracted from CTD for the possible sharing with many of the networks common to chromium in respiratory disease are given in Table 5. Mercury, SB 203580, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, 2,3-dimethoxy-1,4-naphthoquinone, were found interacting with 102, 81,77and 61 chromium-iInteracting genes in Respiratory disease.
Chemical | CAS RN | Similarity Index | Common Interacting Genes for Respiratory disease |
---|---|---|---|
2,3-dimethoxy-1,4-naphthoquinone | 6956-96-3 | 0.174285714 | 61 |
Niacin | 0.150997151 | 53 | |
Antimony | 7440-36-0 | 0.143333333 | 43 |
Antimony Potassium Tartrate | 28300-74-5 | 0.132183908 | 46 |
naringin | 10236-47-2 | 0.131016043 | 49 |
SB 203580 | 0.13022508 | 81 | |
Mercury | 7439-97-6 | 0.129606099 | 102 |
Rutin | 153-18-4 | 0.129518072 | 43 |
alpha-Tocopherol | 59-02-9 | 0.126262626 | 50 |
cobaltiprotoporphyrin | 14325-03-2 | 0.124338624 | 47 |
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole | 0.122615804 | 45 | |
Luteolin | 491-70-3 | 0.122395833 | 47 |
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one | 154447-36-6 | 0.122222222 | 77 |
Thioctic Acid | 62-46-4 | 0.121890547 | 49 |
Cholesterol, Dietary | 0.120943953 | 41 | |
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one | 0.120385233 | 75 | |
pyrazolanthrone | 0.117117117 | 65 | |
Docosahexaenoic Acids | 25167-62-8 | 0.117073171 | 48 |
Chemicals having comparable sets of interacting genes to chromium.
Chromium (VI) is a vital toxic environmental pollutant having various sources including mine tailings. This chapter enlighten respiratory disease accelerated as well as caused due to chromium exposure at genetic level following bioinformatics method that leverages curated data from the public database CTD to generate novel sets of information. This strategy does not require a priori knowledge of the toxicant, biological system, or adverse outcome, and it can be used to identify potential molecular and biological intermediary steps that help fill in knowledge gaps connecting chemical exposures with outcomes for environmentally influenced diseases. With the existed data libraries (mainly CTD, GO, pathway, TFs and miRNA relate databases), bioinformatics web-based tools (David and EnrichR), BPs, CCs, MFs, KEEG signal pathways and gene regulation in the chromium-gene-disease networks were presented. In this study, 127 genes are identified as affected by exposure CR(VI), which are majorly regulated by 10 TFs and 10 very high target miRNAs. The Gene-TFs-miRNAs network recognises maximum interacted genes (EFNB2, IGF1R, CYP1B1, INSR, and VEGFA) and TFs (ZMIZ1, NFE2L2, CTCF and RAD21) and miRNAs (hsa-miR-4506, hsa-miR-379, hsa-miR-3529, hsa-miR-4535, hsa-miR-3684, and hsa-miR-409-5p). The significant biological process (positive regulation of gene expression and positive regulation of nitric oxide biosynthetic process), Cellular Component (extracellular space and protein complex) and Molecular Function (identical protein binding and enzyme binding) are influenced by chromium exposures. From pathway analysis of Cr (VI) influence on respiratory disease, maximum of DEGs are identified to be involved in various pathways in cancer (41 nos.) followed by proteoglycans in cancer (30 nos.), and HTLV-I infection (23 nos.) and so on. Comparable contaminants analysis has recognised Mercury, SB 203580, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one to have maximum common DEGs with Cr (VI) exposure.
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It is a leading cause of disability in children. Congenitally infected neonates often appear asymptomatic at birth or have nonspecific symptoms. An early diagnosis and subsequent early antiviral therapy associated to nonpharmacological therapy (e.g., hearing rehabilitation, speech-language therapy, and cochlear implants) can reduce long-term disability. Much research has been done in this field, but further studies are still necessary. Looking back at the most recent papers, we will draw a review on this topic trying to answer to the question: could universal CMV screening be a useful and cost-effective diagnostic tool?",book:{id:"8728",slug:"update-on-critical-issues-on-infant-and-neonatal-care",title:"Update on Critical Issues on Infant and Neonatal Care",fullTitle:"Update on Critical Issues on Infant and Neonatal Care"},signatures:"Sara Lunardi, Francesca Lorenzoni and Paolo Ghirri",authors:null},{id:"44446",doi:"10.5772/54310",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14797,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"68113",doi:"10.5772/intechopen.86715",title:"Platelets in the Newborn",slug:"platelets-in-the-newborn",totalDownloads:957,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Platelets were first described in the mid-nineteenth century. Since then, their roles were identified in hemostasis and thrombosis, inflammation, leukocyte interactions, angiogenesis, and cancer growth. But there is little information about such platelet functions in the newborn. Several studies highlighted some platelet differences between newborns and adults. Yet, in spite of these differences, healthy newborns appear to be adequately protected. A number of factors, however, were reported to negatively affect neonatal platelets. These include maternal hypertensive disorders or infections, neonatal asphyxia or respiratory distress, therapies such as ampicillin or indomethacin, and treatment modalities such as ventilators, nitric oxide, or extracorporeal membrane oxygenation (ECMO). Their effects on newborn platelets are usually transitory, lasting from several hours to a few days or weeks. If these effects are well characterized, they could serve as reporters for diagnosis and monitoring during therapy. Careful studies of neonatal platelets are needed to improve the understanding of basic physiology and pathophysiology in this cohort and to identify possible targets for intervention and therapy.",book:{id:"7527",slug:"neonatal-medicine",title:"Neonatal Medicine",fullTitle:"Neonatal Medicine"},signatures:"Ijeoma Esiaba, Iman Mousselli, Giulia M. Faison, Danilyn M. Angeles and Danilo S. Boskovic",authors:[{id:"255308",title:"Ph.D.",name:"Danilo",middleName:null,surname:"Boskovic",slug:"danilo-boskovic",fullName:"Danilo Boskovic"},{id:"274914",title:"Prof.",name:"Ijeoma",middleName:null,surname:"Esiaba",slug:"ijeoma-esiaba",fullName:"Ijeoma Esiaba"},{id:"274915",title:"Prof.",name:"Danilyn",middleName:null,surname:"Angeles",slug:"danilyn-angeles",fullName:"Danilyn Angeles"}]}],mostDownloadedChaptersLast30Days:[{id:"44446",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14796,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"53683",title:"Pre and Postoperative Management of Pediatric Patients with Congenital Heart Diseases",slug:"pre-and-postoperative-management-of-pediatric-patients-with-congenital-heart-diseases",totalDownloads:4931,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Stabilization during preoperative cardiac surgery especially in neonates has an important role to predict outcome for pediatric congenital heart surgery. We tried to elaborate general guidelines on how to diagnose and some anticipations for emergency treatments tailored by the type of congenital heart disease in neonates. Stabilization consists of medical treatment including emergent prostaglandin institution in some types of duct dependent lesion. The role of interventional catheterization such as patent ductus arteriosus (PDA) stent, balloon pulmonary valvotomy, etc. as modalities for stabilization before surgery was also elaborated. Some general and specific guidelines based on the type of surgeries for postoperative management were also discussed.",book:{id:"5473",slug:"pediatric-and-neonatal-surgery",title:"Pediatric and Neonatal Surgery",fullTitle:"Pediatric and Neonatal Surgery"},signatures:"Eva Miranda Marwali, Beatrice Heineking and Nikolaus A. Haas",authors:[{id:"191397",title:"Dr.",name:"Eva",middleName:"Miranda",surname:"Marwali",slug:"eva-marwali",fullName:"Eva Marwali"},{id:"191414",title:"Prof.",name:"Nikolaus",middleName:null,surname:"Haas",slug:"nikolaus-haas",fullName:"Nikolaus Haas"},{id:"202373",title:"Dr.",name:"Beatrice",middleName:null,surname:"Heineking",slug:"beatrice-heineking",fullName:"Beatrice Heineking"}]},{id:"68042",title:"Neonatal Bacterial Meningitis",slug:"neonatal-bacterial-meningitis",totalDownloads:1195,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Despite improvements in neonatal intensive care, neonatal bacterial meningitis continues to be a serious disease with mortality rates varying between 10 and 15%. Additionally, long-term complications are observed among 20–50% of survivors, depending on time of diagnosis and therapy and virulence of the infecting pathogen. It is more common during the neonatal period than at any other age with the estimated incidence of 0.25 per 1000 live births. The absence of specific clinical presentation makes diagnosis of meningitis more difficult in neonates than in older children. Culture of cerebrospinal fluid is the traditional gold standard for diagnosis of bacterial meningitis, so all newborn infants with proven or suspected sepsis should undergo lumbar puncture. However, deciding when to perform lumbar puncture and interpretation of the results are challenging. Although the pathophysiology of neonatal meningitis is complex and not fully understood, researches on diagnostic and prognostic tools are ongoing. Prevention of neonatal sepsis, early recognition of infants at risk, development of novel, rapid diagnostics and adjunctive therapies, and appropriate and aggressive antimicrobial treatment to sterilize cerebrospinal fluid as soon as possible may prevent the lifelong squeal of bacterial meningitis in newborn infants.",book:{id:"7527",slug:"neonatal-medicine",title:"Neonatal Medicine",fullTitle:"Neonatal Medicine"},signatures:"Mehmet Şah İpek",authors:[{id:"267903",title:"Associate Prof.",name:"Mehmet Şah",middleName:null,surname:"İpek",slug:"mehmet-sah-ipek",fullName:"Mehmet Şah İpek"}]},{id:"71427",title:"Factors Influencing Maternal Decision-Making on Infant Feeding Practices",slug:"factors-influencing-maternal-decision-making-on-infant-feeding-practices",totalDownloads:1014,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The decision to formula feed or breastfeed a child typically begins with an established prenatal intention. This chapter will examine the multiple dimensions influencing maternal decision-making in regards to the feeding practices of infants including 1) individual maternal characteristics, 2) organizational factors, 3) hospital/provider recommendations, and 4) systematic/policy factors. The chapter will also examine the impact of infant feeding practices on early infant and childhood health outcomes. Research has demonstrated the benefits of breastfeeding on infants and early childhood which includes but is not limited to protection against common illnesses and infections, improved IQ , and even increased school attendance. Moreover, the World Health Assembly global nutrition objectives focus on encouraging breastfeeding support across all sectors in addition to implementing tailored community-based approaches, limiting the excessive marketing of infant formula, and enforcing supportive breastfeeding legislation. The aim of this chapter is to provide an overview of the dynamic interplay between individual, interpersonal, community, and societal factors, such as policies that impact breastfeeding rates and more specifically the health of infants.",book:{id:"9805",slug:"infant-feeding-breast-versus-formula",title:"Infant Feeding",fullTitle:"Infant Feeding - Breast versus Formula"},signatures:"Whitney N. 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Reaching all rightly and robustly is required. All this will contribute greatly towards the growth & development of infants and grandly towards the Sustainable Development Goals. We propose the “ABC mothers” plan. Progress for required practices for results possible with making mothers—“Able for practices advantageous, bold with pertinent awareness, and confident with propitious attitude”. Strong efforts on sound footing are necessary for health of all our infants and happiness all around with sustainable development. Scientific infant feeding will contribute to advance the attainment of this. Medical education teaching best beneficial practices is for excellence. One promoting breastfeeding is the best. The US Surgeon General’s Implementation Strategies elaborate “Education content”, “Enabling competency”, & “Education continuing”. Competency-based curriculum for Indian Medical Graduates includes “to promote and support optimal breast feeding”. Need for inclusion in teaching curriculum across US, UK, & internationally has been documented. Given all the evidence for breastfeeding benefits, it should be a consistent essential component of training in all medical schools worldwide.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Sunil Jain, Arvind Singh Kushwaha and Vishal Marwaha"},{id:"81544",title:"Infant and Young Child Feeding in the Developed and Developing Countries",slug:"infant-and-young-child-feeding-in-the-developed-and-developing-countries",totalDownloads:33,totalDimensionsCites:0,doi:"10.5772/intechopen.103012",abstract:"Infant feeding challenges continue to manifest in developed and developing countries. Worldwide, more than 80% of babies are breastfed in the first few weeks of birth. However, about 37%, 25%, and less than 1% are exclusively breastfed at 6 months of age in Africa, the United States of America, and the United Kingdom, respectively. These statistics are far below the World Health Organization targets of 50% and 70% by 2025 and 2030, respectively. Complementary feeding practices are varied as well due to nonadherence to Infant and Young Child Feeding (IYCF) guidelines among parents. This accounts for the current trends in malnutrition in children under−5 years of age, adolescents, and the youth, and leads to intergeneration malnutrition. In this chapter we have included sections on appropriate infant feeding; including how to initiate breastfeeding in the first hour of birth, how to exclusively breastfeed infants until 6 months of age, how to complement breastfeeding after 6 months of infant’s age as well as continuing to breastfeed until 24 months of age and even beyond. Furthermore, we have included a description of how mothers who are unable to breastfeed can feed their infants on expressed breastmilk or replace breastmilk with appropriate homemade or commercial formula. This chapter as well covers infant feeding in prematurity.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Enos Mirembe Masereka, Clement Munguiko, Alex Tumusiime and Linda Grace Alanyo"},{id:"81207",title:"Breastfeeding during COVID Pandemic",slug:"breastfeeding-during-covid-pandemic",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.104604",abstract:"As new mothers are understandably concerned about COVID-19 and its high rate of infection, they are often unsure if they should breastfeed their infants. In general, hospitals do not allow direct breastfeeding by mothers with an active infection of SARS-CoV-2. Some neonatal units in Hong Kong maintain safe practices by isolating infants and mothers for at least 7 to 14 days, even if the infant remains SARS-CoV-2 negative. During isolation, mothers encourage the expression of milk to maintain milk duct patency and to prepare for lactation when they and their infants are discharged. Infants are fed formula milk by cup feeding with added supplements based on the recommended daily feeding volume for neonates and their appetite during hospitalization. At present, data that indicates COVID-19 could be transmitted from mother to infant postnatally through breastfeeding are insufficient. Major organizations recommend that mothers should breastfeed exclusively for the first 6 months, and thereafter continue to provide their infants with breast milk up until the age of two or beyond. With new findings arising from research, updated information is important to reassure mothers that breastfeeding at home during the COVID-19 pandemic is safe and recommended for both the mother and the infant.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Ka-Huen Yip, Mei-Kuen Chow, Yuk-Chiu Yip and Wai-King Tsui"},{id:"81129",title:"Research of Fat Component Safety and Pre-Clinical Evaluation of Infant Adapted Dry Milk Mixtures Physiological Effect",slug:"research-of-fat-component-safety-and-pre-clinical-evaluation-of-infant-adapted-dry-milk-mixtures-phy",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.103069",abstract:"The aim of the study deals with determination of fat component safety and quality key indicators of adapted infant dry milk formulas provided by various manufacturers. The most popular in Russia adapted infant dry milk formulas were selected as study objects. It was found that the qualitative composition of the fat component of dry milk mixtures corresponds to the information placed on the package. However none of the samples under study in terms of the average composition of the prevailing fatty acids fully corresponds to human breast milk. The regulation documents of the Customs Union (TR CU 021/2011, TR CU 024/2011, TR CU 033/2013) establish only the organoleptic evaluation of the adapted breast milk formulas quality indicators. Among the fat component safety indicators only the determination of the peroxide value characterizing the accumulation of primary fat oxidation products. It was also found that the peroxide values of the studied mixtures do not exceed the regulated values. Meanwhile the samples of infant milk food made from dry milk mixtures almost all have unsatisfactory organoleptic characteristics. Defects of taste and smell are associated with the accumulation in the original adapted milk mixtures of a significant amount of secondary products of fat oxidation, which in a biological experiment on animals lead to a decrease in the content of leukocytes and a change of its blood count.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Ekaterina Yurievna Volf, Inna Vladimirovna Simakova, Andrey Anatolyevich Terentyev, Aleksandr Sergeevich Fedonnikov, Nina Viktorovna Bolotova, Gloria Vladimirovna Guzeeva and Viktor Veniaminovich Zakrevsky"}],onlineFirstChaptersTotal:4},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",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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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. 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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