Tools for ADME evaluation.
\\n\\n
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
\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"6380",leadTitle:null,fullTitle:"Cytotoxicity",title:"Cytotoxicity",subtitle:null,reviewType:"peer-reviewed",abstract:"The book Cytotoxicity is aimed to be an essential reading to all medical students, biologists, biochemists and professionals involved in the field of toxicology. This book is a useful and ideal guide for novice researchers interested in learning research methods to study cytotoxic bioactive compounds. The parts of this book describe the replacement and different applications of the cytotoxic agents. All chapters are written by paramount experts in cytotoxicity research. This will hopefully stimulate more research initiatives, funding, and critical insight into the already increasing demand for cytotoxicity researches that have been evidenced worldwide.",isbn:"978-1-78923-431-2",printIsbn:"978-1-78923-430-5",pdfIsbn:"978-1-83881-443-4",doi:"10.5772/intechopen.69919",price:119,priceEur:129,priceUsd:155,slug:"cytotoxicity",numberOfPages:278,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"60d61573c9a66207b8bc54613cac5716",bookSignature:"Tülay Aşkin Çelik",publishedDate:"July 25th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6380.jpg",numberOfDownloads:22493,numberOfWosCitations:40,numberOfCrossrefCitations:29,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:58,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:127,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 14th 2017",dateEndSecondStepPublish:"July 5th 2017",dateEndThirdStepPublish:"October 1st 2017",dateEndFourthStepPublish:"December 30th 2017",dateEndFifthStepPublish:"February 28th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"74041",title:"Dr.",name:"Tulay",middleName:null,surname:"Askin Celik",slug:"tulay-askin-celik",fullName:"Tulay Askin Celik",profilePictureURL:"https://mts.intechopen.com/storage/users/74041/images/system/74041.png",biography:"Dr. Tülay AŞKIN ÇELİK gained her PhD from Fırat University, Art and Science Faculty, Department of Biology, Elazığ/TURKEY. Presently she is an Associate Professor at Aydın Adnan Menderes University, Art and Science Faculty, Department of Biology, Aydın/TURKEY in the field of genetics. She has been a referee for more than 25 international scientific journals and she worked as a researcher and project manager in 13 projects. She is a referent for issues related to the fields of genetic toxicology and anticancer and antioxidant plants. In 2008, she became a member of the European Association for Cancer Research (EACR) and Molecular Cancer Research Association (MOKAD) and in 2018, she became a member of the Medical Biology and Genetics Association (TBGDER). Currently, her scientific interests include bioactive phytochemicals and plant extracts on their cytogenetic and gentotoxic effects on chromosomes and cancer cells and in vivo /in vitro biological activities. Furthermore, she is also investigating the genotoxic and cytotoxic effects of environmental pollutants such as pesticides. She has authored one book and two book chapters in reputed books published by IntechOpen Access Publisher.",institutionString:"Aydın Adnan Menderes University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Adnan Menderes University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1208",title:"Medical Toxicology",slug:"medical-toxicology"}],chapters:[{id:"61438",title:"Introductory Chapter: Cytotoxicity",doi:"10.5772/intechopen.77244",slug:"introductory-chapter-cytotoxicity",totalDownloads:1346,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Tülay Aşkin Çelik",downloadPdfUrl:"/chapter/pdf-download/61438",previewPdfUrl:"/chapter/pdf-preview/61438",authors:[{id:"74041",title:"Dr.",name:"Tulay",surname:"Askin Celik",slug:"tulay-askin-celik",fullName:"Tulay Askin Celik"}],corrections:null},{id:"57702",title:"Cytotoxicity Caused by Asbestos Fibers and Acquisition of Resistance by Continuous Exposure in Human T Cells",doi:"10.5772/intechopen.72064",slug:"cytotoxicity-caused-by-asbestos-fibers-and-acquisition-of-resistance-by-continuous-exposure-in-human",totalDownloads:983,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The cytotoxic effects of asbestos fibers on human T cells and the acquisition of resistance against asbestos-induced apoptosis have been studied. These analyses are based on the establishment of a continuous and relatively low-dose exposure model of human immune cells exposed to asbestos that resembles actual exposure in the human body. The MT-2 T cell line was selected as the candidate for the investigations. A transient and high-dose exposure to chrysotile resulted in apoptosis with production of reactive oxygen species (ROS) and activation of the mitochondrial apoptotic pathway. However, sublines continuously exposed to low dose of asbestos exhibited resistance to asbestos-induced apoptosis. The mechanism of resistance acquisition involved excess production of IL-10, activation of STAT3, and enhanced expression of Bcl-2 located downstream of STAT3. These changes were also found in a subline continuously exposed to crocidolite. Furthermore, sublines showed a marked decrease in the expression of forkhead box O1 (FoxO1) transcription factor. FoxO1 is known to regulate apoptosis and various other cellular processes. Regarding apoptosis, sublines continuously exposed to asbestos showed reduction of FoxP1-driven proapoptotic genes. This pathway is also considered one of the mechanisms that result in resistance to asbestos-induced apoptosis in sublines. These sublines also exhibited several characteristics suggesting reduction of antitumor immunity.",signatures:"Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Yu Min,\nNagisa Sada, Kei Yoshitome, Yasumitsu Nishimura, Megumi Maeda\nand Takemi Otsuki",downloadPdfUrl:"/chapter/pdf-download/57702",previewPdfUrl:"/chapter/pdf-preview/57702",authors:[{id:"34101",title:"Prof.",name:"Takemi",surname:"Otsuki",slug:"takemi-otsuki",fullName:"Takemi Otsuki"},{id:"48627",title:"Dr.",name:"Naoko",surname:"Kumagai-Takei",slug:"naoko-kumagai-takei",fullName:"Naoko Kumagai-Takei"},{id:"48631",title:"Dr.",name:"Yasumitsu",surname:"Nishimura",slug:"yasumitsu-nishimura",fullName:"Yasumitsu Nishimura"},{id:"104893",title:"Dr.",name:"Suni",surname:"Lee",slug:"suni-lee",fullName:"Suni Lee"},{id:"104894",title:"Dr.",name:"Hidenori",surname:"Matsuzaki",slug:"hidenori-matsuzaki",fullName:"Hidenori Matsuzaki"},{id:"219725",title:"Dr.",name:"Kei",surname:"Yoshitome",slug:"kei-yoshitome",fullName:"Kei Yoshitome"},{id:"222581",title:"MSc.",name:"Yu",surname:"Min",slug:"yu-min",fullName:"Yu Min"},{id:"222582",title:"Dr.",name:"Nagisa",surname:"Sada",slug:"nagisa-sada",fullName:"Nagisa Sada"},{id:"222583",title:"Prof.",name:"Megumi",surname:"Maeda",slug:"megumi-maeda",fullName:"Megumi Maeda"}],corrections:null},{id:"58055",title:"The Cytotoxic, Antimicrobial and Anticancer Properties of the Antimicrobial Peptide Nisin Z Alone and in Combination with Conventional Treatments",doi:"10.5772/intechopen.71927",slug:"the-cytotoxic-antimicrobial-and-anticancer-properties-of-the-antimicrobial-peptide-nisin-z-alone-and",totalDownloads:7259,totalCrossrefCites:7,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Nisin is an antimicrobial peptide commonly used as a food preservative since 1969. This peptide has potent antimicrobial activity against several Gram-positive bacterial strains, including clinically important and resistant pathogens. The combination of nisin with conventional antibiotics has been shown to improve the antimicrobial activity of these antibiotic agents. Apart from the antimicrobial properties of nisin, this AMP also displays promising anticancer potential towards several types of malignancies. The nisin Z variant is able to induce selective cytotoxicity in melanoma cells compared to non-malignant cells. It was shown that nisin Z disrupts the cell membrane integrity of melanoma cells and that cytotoxicity is likely due to the activation of an apoptotic pathway. In addition, when used in combination with the conventional chemotherapeutic agents, nisin Z has the potential to enhance the cytotoxicity of these chemotherapeutic agents against cultured melanoma cells. Nisin Z has great potential for clinical application considering its low cytotoxicity to non-malignant cells and its effectiveness against Gram-positive bacterial strains and certain cancers.",signatures:"Angélique Lewies, Lissinda H. Du Plessis and Johannes F. Wentzel",downloadPdfUrl:"/chapter/pdf-download/58055",previewPdfUrl:"/chapter/pdf-preview/58055",authors:[{id:"214707",title:"Dr.",name:"Johannes",surname:"Wentzel",slug:"johannes-wentzel",fullName:"Johannes Wentzel"},{id:"216091",title:"Dr.",name:"Angélique",surname:"Lewies",slug:"angelique-lewies",fullName:"Angélique Lewies"},{id:"216092",title:"Prof.",name:"Lissinda",surname:"Du Plessis",slug:"lissinda-du-plessis",fullName:"Lissinda Du Plessis"}],corrections:null},{id:"58788",title:"Cytotoxic Colchicine Alkaloids: From Plants to Drugs",doi:"10.5772/intechopen.72622",slug:"cytotoxic-colchicine-alkaloids-from-plants-to-drugs",totalDownloads:1412,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Plants produce and store many organic compounds like amino acids, proteins, carbohydrates, fats, and alkaloids, which are usually treated as secondary metabolites. Many alkaloids are biologically active for humans. For thousand years, extracts from plants containing alkaloids had medicinal use as drugs and they owe their powerful effects thanks to presence of alkaloids. Alkaloids have anti-inflammatory, antibacterial, analgesic, local anesthetic, hypnotic, psychotropic, antimitotic, and antitumor activity. Nowadays, alkaloids from plants are still of great interest to organic chemists, pharmacologists, biologists, biochemists, and pharmacists. Plants of Liliaceae family contain colchicine as the main alkaloid, which has cytotoxic activity. Colchicine has limited pharmacological application because of its toxicity, but many derivatives have been synthesized and their cytotoxic activity and tubulin-binding properties have been tested. Many of the synthetic derivatives showed good cytotoxic activity.",signatures:"Joanna Kurek",downloadPdfUrl:"/chapter/pdf-download/58788",previewPdfUrl:"/chapter/pdf-preview/58788",authors:[{id:"214632",title:"Dr.",name:"Joanna",surname:"Kurek",slug:"joanna-kurek",fullName:"Joanna Kurek"}],corrections:null},{id:"58539",title:"Natural Products as Cytotoxic Agents in Chemotherapy against Cancer",doi:"10.5772/intechopen.72744",slug:"natural-products-as-cytotoxic-agents-in-chemotherapy-against-cancer",totalDownloads:1485,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Nature continues to produce a great wealth of natural molecules endowed with cytotoxic activity toward a large panel of tumor cells. Some of these molecules are used in chemotherapy, and others have shown great anti-tumor and anti-metastatic potential in preclinical trials. This review discusses some examples of these molecules that have been studied in our laboratory and others. We report a differential cytotoxic activity of some monoterpenes (carvacrol, tymol, carveol, carvone, and isopulegol) against a panel of tumor cell lines. The carvacrol was the most cytotoxic molecule both in vitro and in vivo as demonstrated by preclinical studies using the DBA2/P815 mice model. On the other hand, polyphenols were also studied with respect to their cytotoxic effects. Interestingly, these compounds showed a prominent cytotoxic activity toward a panel of cancer cells with differential molecular mechanisms. In addition, we report a very strong antitumor efficacy of artemisinin, a sesquiterpen lactone from Artemisia annua, together with an antimetastatic potential as demonstrated by preclinical experiments. Furthermore, some of the molecular mechanisms involved in these effects are described.",signatures:"Abdelmajid Zyad, Inass Leouifoudi, Mounir Tilaoui, Hassan Ait\nMouse, Mouna Khouchani and Abdeslam Jaafari",downloadPdfUrl:"/chapter/pdf-download/58539",previewPdfUrl:"/chapter/pdf-preview/58539",authors:[{id:"187827",title:"Dr.",name:"Inass",surname:"Leouifoudi",slug:"inass-leouifoudi",fullName:"Inass Leouifoudi"},{id:"204146",title:"Prof.",name:"Abdelmajid",surname:"Zyad",slug:"abdelmajid-zyad",fullName:"Abdelmajid Zyad"},{id:"216446",title:"Prof.",name:"Hassan",surname:"Ait Mouse",slug:"hassan-ait-mouse",fullName:"Hassan Ait Mouse"},{id:"216447",title:"Prof.",name:"Mouna",surname:"Khouchani",slug:"mouna-khouchani",fullName:"Mouna Khouchani"}],corrections:null},{id:"58323",title:"Cytotoxicity and Apoptosis Induction by Coumarins in CLL",doi:"10.5772/intechopen.72446",slug:"cytotoxicity-and-apoptosis-induction-by-coumarins-in-cll",totalDownloads:1158,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chronic lymphocytic leukemia (CLL) is one of the leukemia types. Leukemia is cancer of the body's blood-forming cells. Cancer is a disease that is often characterized by too little apoptosis and uncontrolled duplicate of body cells. Apoptosis, or programmed cell death, is a normal component of the development and health of multicellular organisms. Cells die in response to a variety of stimuli during apoptosis. During cancer, pathophysiology apoptosis of the cancerous cells is disrupted, so one of the strategies for cancer chemotherapy is inducing apoptosis in cancerous cells. Myeloid cell leukemia type 1 (Mcl-1) is one of the antiapoptotic Bcl-2 family proteins. It has been shown that the expression of Mcl-1 in CLL is significantly associated with a failure to achieve complete remission following cytotoxic therapy, so regulation of Mcl-1 expression by coumarins could be one of the mechanisms of CLL chemotherapy. Coumarins consist of a large class of phenolic substances found in plants. Different pharmacologic effects of coumarins were reported. One of these effects is cytotoxicity and apoptosis induction in cancerous cells by coumarins. In this chapter, the cytotoxic activity of coumarins and their role in Mcl-1 regulation are discussed.",signatures:"Omid Gholami",downloadPdfUrl:"/chapter/pdf-download/58323",previewPdfUrl:"/chapter/pdf-preview/58323",authors:[{id:"214865",title:"Dr.",name:"Omid",surname:"Gholami",slug:"omid-gholami",fullName:"Omid Gholami"}],corrections:null},{id:"58914",title:"Cyto(Geno)Toxic Endpoints Assessed via Cell Cycle Bioassays in Plant Models",doi:"10.5772/intechopen.72997",slug:"cyto-geno-toxic-endpoints-assessed-via-cell-cycle-bioassays-in-plant-models",totalDownloads:1022,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Environmental pollution is a matter of great concern. Therefore, researches that aim to access the risk of toxicity of these potential pollutants are welcome in the scientific community. The most common strategy to detect toxic agents is through chemical analysis. However, in the last years, the biological assays are often important for risk assessments. Among the bioassays using living organisms to detect toxicity of a compound, plant models have been highlighted as it is easy to be conducted, has low cost, high sensitivity and presents good correlation with other test systems, including mammals. Besides, it is in accordance with the Toxicology Guidelines for the twenty-first century, which claims for bioassays that could substitute the ones that use animals as models. At cellular level, the cytotoxicity, genotoxicity, and mutagenicity are the parameters determined by the endpoints as mitotic index, DNA fragmentation, induction of cell death, and malfunction of cellular structures leading to chromosome and cell cycle alterations. Each of these endpoints will be presented in details in this chapter.",signatures:"Larissa Fonseca Andrade Vieira and Graciele Lurdes Silveira",downloadPdfUrl:"/chapter/pdf-download/58914",previewPdfUrl:"/chapter/pdf-preview/58914",authors:[{id:"215258",title:"Prof.",name:"Larissa",surname:"Fonseca Andrade Vieira",slug:"larissa-fonseca-andrade-vieira",fullName:"Larissa Fonseca Andrade Vieira"},{id:"215260",title:"M.Sc.",name:"Graciele",surname:"Silveira",slug:"graciele-silveira",fullName:"Graciele Silveira"}],corrections:null},{id:"58235",title:"Role of Cytotoxicity Experiments in Pharmaceutical Development",doi:"10.5772/intechopen.72539",slug:"role-of-cytotoxicity-experiments-in-pharmaceutical-development",totalDownloads:1806,totalCrossrefCites:4,totalDimensionsCites:14,hasAltmetrics:0,abstract:"Through the twentieth century, the road from synthetizing a new drug molecule to become an actual product got longer than ever before. Cytotoxicity assays are a quick way to assess a certain chemical compound’s effects on a given human cell line. The most well-known techniques are the MTT- and the LDH-assays. These tests are cheap, easy to execute, but not very precise and dependent on various environmental factors and also, they show no detail about the time-dependency of the toxic effect. Cytotoxicity experiments are a crucial part of a modern pharmaceutical development process. They are a cheap and safe way to get vital information about a new molecule’s biological attributes focusing on its basic tolerability. These studies not only save human lives and test animals, but they save the time and resources to be spared on a test molecule which is a complete failure having no in vitro safety.",signatures:"Ildikó Bácskay, Dániel Nemes, Ferenc Fenyvesi, Judit Váradi, Gábor\nVasvári, Pálma Fehér, Miklós Vecsernyés and Zoltán Ujhelyi",downloadPdfUrl:"/chapter/pdf-download/58235",previewPdfUrl:"/chapter/pdf-preview/58235",authors:[{id:"215449",title:"Dr.",name:"Ildikó",surname:"Bácskay",slug:"ildiko-bacskay",fullName:"Ildikó Bácskay"},{id:"215453",title:"Dr.",name:"Dániel",surname:"Nemes",slug:"daniel-nemes",fullName:"Dániel Nemes"},{id:"215454",title:"Dr.",name:"Zoltán",surname:"Ujhelyi",slug:"zoltan-ujhelyi",fullName:"Zoltán Ujhelyi"},{id:"215456",title:"Dr.",name:"Ferenc",surname:"Fenyvesi",slug:"ferenc-fenyvesi",fullName:"Ferenc Fenyvesi"},{id:"215457",title:"Dr.",name:"Judit",surname:"Váradi",slug:"judit-varadi",fullName:"Judit Váradi"},{id:"215458",title:"Dr.",name:"Gábor",surname:"Vasvári",slug:"gabor-vasvari",fullName:"Gábor Vasvári"},{id:"215459",title:"Dr.",name:"Pálma",surname:"Fehér",slug:"palma-feher",fullName:"Pálma Fehér"},{id:"215460",title:"Dr.",name:"Miklós",surname:"Vecsernyés",slug:"miklos-vecsernyes",fullName:"Miklós Vecsernyés"}],corrections:null},{id:"61672",title:"Biocompatibility of Doped Semiconductors Nanocrystals and Nanocomposites",doi:"10.5772/intechopen.77197",slug:"biocompatibility-of-doped-semiconductors-nanocrystals-and-nanocomposites",totalDownloads:1077,totalCrossrefCites:6,totalDimensionsCites:9,hasAltmetrics:0,abstract:"Exposure of humans and environment to nanocrystals are inevitable, and nanotoxicological analyses are a requirement. The wide variety of nanocrystals with different applications is increasing, and characterization of their effects after exposure includes their potential toxicity and uses. This review summarizes the characterization of doped nanocrystals and nanocomposites, Ca-doped ZnO, Ag- and Eu-doped ZnO and Ni-doped ZnO NCs, their biocompatibility and applications. This review uncovers how these nanocrystals present desirable biocompatible properties, which can be useful as antitumoral and antimicrobial inducing agents, which differ markedly from toxic properties observed in other general nanocrystals.",signatures:"Anielle Christine Almeida Silva, Mariana Alves Pereira Zóia, Lucas Ian Veloso Correia,\nFernanda Van Petten Vasconcelos Azevedo, Aline Teodoro de\nPaula, Larissa Prado Maia, Layara Santana de Carvalho, Loyna\nNobile Carvalho, Maria Paula Camargo Costa, Layssa Carrilho\nGiaretta, Renata Santos Rodrigues, Veridiana de Melo Ávila, Luiz\nRicardo Goulart and Noelio Oliveira Dantas",downloadPdfUrl:"/chapter/pdf-download/61672",previewPdfUrl:"/chapter/pdf-preview/61672",authors:[{id:"13001",title:"Dr.",name:"Noelio",surname:"Oliveira Dantas",slug:"noelio-oliveira-dantas",fullName:"Noelio Oliveira Dantas"},{id:"217672",title:"Prof.",name:"Anielle",surname:"Silva",slug:"anielle-silva",fullName:"Anielle Silva"},{id:"227086",title:"MSc.",name:"Fernanda",surname:"Van Petten Vasconcelos Azevedo",slug:"fernanda-van-petten-vasconcelos-azevedo",fullName:"Fernanda Van Petten Vasconcelos Azevedo"},{id:"227087",title:"MSc.",name:"Mariana",surname:"Alves Pereira Zóia",slug:"mariana-alves-pereira-zoia",fullName:"Mariana Alves Pereira Zóia"},{id:"227089",title:"BSc.",name:"Lucas Ian",surname:"Veloso Correia",slug:"lucas-ian-veloso-correia",fullName:"Lucas Ian Veloso Correia"},{id:"227090",title:"Dr.",name:"Aline",surname:"Teodoro De Paula",slug:"aline-teodoro-de-paula",fullName:"Aline Teodoro De Paula"},{id:"227099",title:"Prof.",name:"Renata",surname:"Santos Rodrigues",slug:"renata-santos-rodrigues",fullName:"Renata Santos Rodrigues"},{id:"227100",title:"Prof.",name:"Veridiana",surname:"De Melo Ávila",slug:"veridiana-de-melo-avila",fullName:"Veridiana De Melo Ávila"},{id:"227101",title:"Prof.",name:"Luiz Ricardo",surname:"Goulart",slug:"luiz-ricardo-goulart",fullName:"Luiz Ricardo Goulart"},{id:"227368",title:"Ms.",name:"Maria Paula",surname:"Camargo Costa",slug:"maria-paula-camargo-costa",fullName:"Maria Paula Camargo Costa"},{id:"227369",title:"Ms.",name:"Layssa",surname:"Carrilho Giaretta",slug:"layssa-carrilho-giaretta",fullName:"Layssa Carrilho Giaretta"}],corrections:null},{id:"57853",title:"Toxicity of Titanate Nanosheets on Human Immune Cells",doi:"10.5772/intechopen.72234",slug:"toxicity-of-titanate-nanosheets-on-human-immune-cells",totalDownloads:936,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Titanium oxide is regarded as a bio-inert material, but studies concerning the toxic effects of titanium dioxide (TiO2), particularly nano-scaled TiO2 particles, have been accumulating that indicate nano-scaled TiO2 particles show more harm and cause greater alteration of immune functions compared with large particles. Inorganic nanosheets have been the focus of increasing interest because of their ultrathin structure, as well as diversity of compounds and structures leading to various functions. Oxide nanosheets are included in the group comprising inorganic nanosheets, and titanate nanosheets (TiNSs) represent a form of oxide nanosheets. We therefore examined the toxicity of nano-scaled 2D materials of TiNSs on human immune cells. Our study revealed that TiNSs have the potential to cause harm through caspase-dependent apoptosis of human peripheral blood mononuclear cells (PBMCs) to the same degree as asbestos. Furthermore, isolated monocytes developed marked vacuoles prior to cell death upon exposure to TiNSs, which were found in the vacuoles and indicated engulfment of TiNSs. A consideration of these findings with the co-localization of vacuoles with endocytosed fluorescence-labeled dextran indicates that TiNSs entered the endosomal pathway, leading to the formation of vacuoles in monocytes and subsequent cell death. TiNSs might therefore affect immune functions through interference of endo-lysosomal functions.",signatures:"Yasumitsu Nishimura, Daisuke Yoshioka, Naoko Kumagai-Takei,\nSuni Lee, Hidenori Matsuzaki, Kei Yoshitome and Takemi Otsuki",downloadPdfUrl:"/chapter/pdf-download/57853",previewPdfUrl:"/chapter/pdf-preview/57853",authors:[{id:"48631",title:"Dr.",name:"Yasumitsu",surname:"Nishimura",slug:"yasumitsu-nishimura",fullName:"Yasumitsu Nishimura"}],corrections:null},{id:"58365",title:"General Cytotoxicity and Its Application in Nanomaterial Analysis",doi:"10.5772/intechopen.72578",slug:"general-cytotoxicity-and-its-application-in-nanomaterial-analysis",totalDownloads:1560,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"The recent increasing interest in the use of different nanoparticles in biological and medical applications encouraged scientists to analyse their potential impact on biological systems. The biocompatibility analyses of novel materials for medical applications are conducted using quantitative and qualitative techniques collected by the International Standards Organization (ISO). The well-known assays, such as tetrazolium-based assays used for mitochondrial function monitoring, LDH for membrane permeability determination and neutral red uptake (NRU) describing lysosome function, need to be optimised due to specific properties of wide range of nanomaterials. Physicochemical properties of nanoparticles (NPs) such as size, composition, concentration, shape and surface (e.g., charge, coating, aspect ratio), as well as the cell type play a crucial role in determining the nanomaterial toxicity (also uptake pathway(s) of NPs). Different nanomaterials exhibit different cytotoxicity from relatively non-toxic hexagonal boron nitride to rutile TiO2 NPs that induce oxidative DNA damage in the absence of UV light. Finally, the results of the nanomedical analysis can be enriched by holographic microscopy that gives valuable information about the doubling time (DT), cell segmentation, track cell movement and changes in cell morphology. The results can be also completed by phenotype microarrays (PMs) and atomic force microscopy (AFM) techniques that fulfil experimental data.",signatures:"Magdalena Jedrzejczak-Silicka and Ewa Mijowska",downloadPdfUrl:"/chapter/pdf-download/58365",previewPdfUrl:"/chapter/pdf-preview/58365",authors:[{id:"186478",title:"Dr.",name:"Magdalena",surname:"Jedrzejczak-Silicka",slug:"magdalena-jedrzejczak-silicka",fullName:"Magdalena Jedrzejczak-Silicka"},{id:"231014",title:"Prof.",name:"Ewa",surname:"Mijowska",slug:"ewa-mijowska",fullName:"Ewa Mijowska"}],corrections:null},{id:"61587",title:"Review of In vitro Toxicity of Nanoparticles and Nanorods: Part 1",doi:"10.5772/intechopen.76365",slug:"review-of-in-vitro-toxicity-of-nanoparticles-and-nanorods-part-1",totalDownloads:1101,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The specific use of engineered nanostructures in biomedical applications has become very attractive, due to their ability to interface and target specific cells and tissues to execute their functions. Additionally, there is continuous progress in research on new nanostructures with unique optical, magnetic, catalytic, and electrochemical properties that can be exploited for therapeutic or diagnostic methods. On the other hand, as nanostructures become widely used in many different applications, the unspecific exposure of humans to them is also unavoidable. Therefore, studying and understanding the toxicity of such materials is of increasing importance. Previously published reviews regarding the toxicological effects of nanostructures focuses mostly on the cytotoxicity of nanoparticles and their internalization, activated signaling pathways, and cellular response. Here, the most recent studies on the in vitro cytotoxicity of NPs, nanowires, and nanorods for biomedical applications are reviewed and divided into two parts. The first part considers nonmagnetic metallic and magnetic nanostructures. While part 2 covers carbon structures and semiconductors. The factors influencing the toxicity of these nanostructures are elaborated, to help elucidating the effects of these nanomaterials on cells, which is a prerequisite for their save clinical use.",signatures:"Jose Efrain Perez, Nouf Alsharif, Aldo Isaac Martínez Banderas,\nBasmah Othman, Jasmeen Merzaban, Timothy Ravasi and Jürgen\nKosel",downloadPdfUrl:"/chapter/pdf-download/61587",previewPdfUrl:"/chapter/pdf-preview/61587",authors:[{id:"141848",title:"Prof.",name:"Jurgen",surname:"Kosel",slug:"jurgen-kosel",fullName:"Jurgen Kosel"},{id:"225868",title:"Mr.",name:"Jose",surname:"Perez",slug:"jose-perez",fullName:"Jose Perez"},{id:"225869",title:"Mrs.",name:"Nouf",surname:"Alsharif",slug:"nouf-alsharif",fullName:"Nouf Alsharif"},{id:"225870",title:"Mr.",name:"Aldo Martinez",surname:"Banderas",slug:"aldo-martinez-banderas",fullName:"Aldo Martinez Banderas"},{id:"225871",title:"Prof.",name:"Jasmeen",surname:"Merzaban",slug:"jasmeen-merzaban",fullName:"Jasmeen Merzaban"},{id:"225872",title:"Prof.",name:"Timothy",surname:"Ravasi",slug:"timothy-ravasi",fullName:"Timothy Ravasi"}],corrections:null},{id:"62231",title:"Review of In Vitro Toxicity of Nanoparticles and Nanorods—Part 2",doi:"10.5772/intechopen.78616",slug:"review-of-in-vitro-toxicity-of-nanoparticles-and-nanorods-part-2",totalDownloads:1351,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The specific use of engineered nanostructures in biomedical applications has become very attractive, due to their ability to interface and target specific cells and tissues to execute their functions. Additionally, there is continuous progress in research on new nanostructures with unique optical, magnetic, catalytic and electrochemical properties that can be exploited for therapeutic or diagnostic methods. On the other hand, as nanostructures become widely used in many different applications, the unspecific exposure of humans to them is also unavoidable. Therefore, studying and understanding the toxicity of such materials are of increasing importance. Previously published reviews regarding the toxicological effects of nanostructures focus mostly on the cytotoxicity of nanoparticles and their internalization, activated signaling pathways and cellular response. Here, the most recent studies on the in-vitro cytotoxicity of NPs, nanowires and nanorods for biomedical applications are reviewed and divided into two parts. The first part considers nonmagnetic metallic and magnetic nanostructures, while, the second part covers carbon structures and semiconductors. The factors influencing the toxicity of these nanostructures are elaborated to help elucidate the effects of these nanomaterials on cells, which is a prerequisite for their safe clinical use.",signatures:"Jose E. Perez, Nouf Alsharif, Aldo I. Martínez-Banderas, Basmah\nOthman, Jasmeen Merzaban, Timothy Ravasi and Jürgen Kosel",downloadPdfUrl:"/chapter/pdf-download/62231",previewPdfUrl:"/chapter/pdf-preview/62231",authors:[{id:"141848",title:"Prof.",name:"Jurgen",surname:"Kosel",slug:"jurgen-kosel",fullName:"Jurgen Kosel"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8073",title:"Chromosomal Abnormalities",subtitle:null,isOpenForSubmission:!1,hash:"6a9d3c58434edf5e65f9849a6858edfe",slug:"chromosomal-abnormalities",bookSignature:"Tülay Aşkın Çelik and Subrata Dey",coverURL:"https://cdn.intechopen.com/books/images_new/8073.jpg",editedByType:"Edited by",editors:[{id:"74041",title:"Dr.",name:"Tulay",surname:"Askin Celik",slug:"tulay-askin-celik",fullName:"Tulay Askin Celik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3408",title:"New Insights into Toxicity and Drug Testing",subtitle:null,isOpenForSubmission:!1,hash:"71cbc4a6caf1e19add9556925b6d2974",slug:"new-insights-into-toxicity-and-drug-testing",bookSignature:"Sivakumar Gowder",coverURL:"https://cdn.intechopen.com/books/images_new/3408.jpg",editedByType:"Edited by",editors:[{id:"118572",title:"Dr.",name:"Sivakumar Joghi",surname:"Thatha Gowder",slug:"sivakumar-joghi-thatha-gowder",fullName:"Sivakumar Joghi Thatha Gowder"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7111",title:"Poisoning in the Modern World",subtitle:"New Tricks for an Old Dog?",isOpenForSubmission:!1,hash:"08164f9300bc6bf4900c9166d960278b",slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",bookSignature:"Ozgur Karcioglu and Banu Arslan",coverURL:"https://cdn.intechopen.com/books/images_new/7111.jpg",editedByType:"Edited by",editors:[{id:"221195",title:"Prof.",name:"Ozgur",surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8068",title:"Cytotoxicity",subtitle:"Definition, Identification, and Cytotoxic Compounds",isOpenForSubmission:!1,hash:"20a09223d92829b5478b5f241f6a03ce",slug:"cytotoxicity-definition-identification-and-cytotoxic-compounds",bookSignature:"Erman Salih Istifli and Hasan Basri Ila",coverURL:"https://cdn.intechopen.com/books/images_new/8068.jpg",editedByType:"Edited by",editors:[{id:"179007",title:"Dr.",name:"Erman Salih",surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editedByType:"Edited by",editors:[{id:"109978",title:"Prof.",name:"Pınar",surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"81444",slug:"corrigendum-to-the-role-of-ultra-radical-surgery-in-the-management-of-advanced-ovarian-cancer-state-",title:"Corrigendum to: The Role of Ultra-Radical Surgery in the Management of Advanced Ovarian Cancer: State of the Art",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/81444.pdf",downloadPdfUrl:"/chapter/pdf-download/81444",previewPdfUrl:"/chapter/pdf-preview/81444",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/81444",risUrl:"/chapter/ris/81444",chapter:{id:"78061",slug:"the-role-of-ultra-radical-surgery-in-the-management-of-advanced-ovarian-cancer-state-of-the-art",signatures:"Felicia Elena Buruiana, Lamiese Ismail, Federico Ferrari and Hooman Soleymani Majd",dateSubmitted:"March 15th 2021",dateReviewed:"April 8th 2021",datePrePublished:"August 12th 2021",datePublished:"October 6th 2021",book:{id:"10342",title:"Ovarian Cancer",subtitle:"Updates in Tumour Biology and Therapeutics",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",publishedDate:"October 6th 2021",bookSignature:"Gwo-Yaw Ho and Kate Webber",coverURL:"https://cdn.intechopen.com/books/images_new/10342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"297757",title:null,name:"Gwo-Yaw",middleName:null,surname:"Ho",slug:"gwo-yaw-ho",fullName:"Gwo-Yaw Ho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"325727",title:"Dr.",name:"Felicia Elena",middleName:null,surname:"Buruiana",fullName:"Felicia Elena Buruiana",slug:"felicia-elena-buruiana",email:"f.buruiana@nhs.net",position:null,institution:null},{id:"325746",title:"Dr.",name:"Lamiese",middleName:null,surname:"Ismail",fullName:"Lamiese Ismail",slug:"lamiese-ismail",email:"lamiese.ismail@ouh.nhs.uk",position:null,institution:{name:"Oxford University Hospitals NHS Trust",institutionURL:null,country:{name:"United Kingdom"}}},{id:"325747",title:"Dr.",name:"Hooman",middleName:null,surname:"Soleymani Majd",fullName:"Hooman Soleymani Majd",slug:"hooman-soleymani-majd",email:"hooman.soleymani@ouh.nhs.uk",position:null,institution:{name:"Oxford University Hospitals NHS Trust",institutionURL:null,country:{name:"United Kingdom"}}},{id:"353890",title:"Dr.",name:"Federico",middleName:null,surname:"Ferrari",fullName:"Federico Ferrari",slug:"federico-ferrari",email:"f.ferrari.obgyn@gmail.com",position:null,institution:{name:"Oxford University Hospitals NHS Trust",institutionURL:null,country:{name:"United Kingdom"}}}]}},chapter:{id:"78061",slug:"the-role-of-ultra-radical-surgery-in-the-management-of-advanced-ovarian-cancer-state-of-the-art",signatures:"Felicia Elena Buruiana, Lamiese Ismail, Federico Ferrari and Hooman Soleymani Majd",dateSubmitted:"March 15th 2021",dateReviewed:"April 8th 2021",datePrePublished:"August 12th 2021",datePublished:"October 6th 2021",book:{id:"10342",title:"Ovarian Cancer",subtitle:"Updates in Tumour Biology and Therapeutics",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",publishedDate:"October 6th 2021",bookSignature:"Gwo-Yaw Ho and Kate Webber",coverURL:"https://cdn.intechopen.com/books/images_new/10342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"297757",title:null,name:"Gwo-Yaw",middleName:null,surname:"Ho",slug:"gwo-yaw-ho",fullName:"Gwo-Yaw Ho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"325727",title:"Dr.",name:"Felicia Elena",middleName:null,surname:"Buruiana",fullName:"Felicia Elena Buruiana",slug:"felicia-elena-buruiana",email:"f.buruiana@nhs.net",position:null,institution:null},{id:"325746",title:"Dr.",name:"Lamiese",middleName:null,surname:"Ismail",fullName:"Lamiese Ismail",slug:"lamiese-ismail",email:"lamiese.ismail@ouh.nhs.uk",position:null,institution:{name:"Oxford University Hospitals NHS Trust",institutionURL:null,country:{name:"United Kingdom"}}},{id:"325747",title:"Dr.",name:"Hooman",middleName:null,surname:"Soleymani Majd",fullName:"Hooman Soleymani Majd",slug:"hooman-soleymani-majd",email:"hooman.soleymani@ouh.nhs.uk",position:null,institution:{name:"Oxford University Hospitals NHS Trust",institutionURL:null,country:{name:"United Kingdom"}}},{id:"353890",title:"Dr.",name:"Federico",middleName:null,surname:"Ferrari",fullName:"Federico Ferrari",slug:"federico-ferrari",email:"f.ferrari.obgyn@gmail.com",position:null,institution:{name:"Oxford University Hospitals NHS Trust",institutionURL:null,country:{name:"United Kingdom"}}}]},book:{id:"10342",title:"Ovarian Cancer",subtitle:"Updates in Tumour Biology and Therapeutics",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",publishedDate:"October 6th 2021",bookSignature:"Gwo-Yaw Ho and Kate Webber",coverURL:"https://cdn.intechopen.com/books/images_new/10342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"297757",title:null,name:"Gwo-Yaw",middleName:null,surname:"Ho",slug:"gwo-yaw-ho",fullName:"Gwo-Yaw Ho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"9489",leadTitle:null,title:"Neurological and Mental Disorders",subtitle:null,reviewType:"peer-reviewed",abstract:"Mental disorders can result from disruption of neuronal circuitry, damage to the neuronal and non-neuronal cells, altered circuitry in the different regions of the brain and any changes in the permeability of the blood brain barrier. Early identification of these impairments through investigative means could help to improve the outcome for many brain and behaviour disease states.The chapters in this book describe how these abnormalities can lead to neurological and mental diseases such as ADHD (Attention Deficit Hyperactivity Disorder), anxiety disorders, Alzheimer’s disease and personality and eating disorders. Psycho-social traumas, especially during childhood, increase the incidence of amnesia and transient global amnesia, leading to the temporary inability to create new memories.Early detection of these disorders could benefit many complex diseases such as schizophrenia and depression.",isbn:"978-1-83962-974-7",printIsbn:"978-1-83962-973-0",pdfIsbn:"978-1-83962-975-4",doi:"10.5772/intechopen.87273",price:119,priceEur:129,priceUsd:155,slug:"neurological-and-mental-disorders",numberOfPages:222,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"3c29557d356441eccf59b262c0980d81",bookSignature:"Kaneez Fatima Shad and Kamil Hakan Dogan",publishedDate:"September 23rd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9489.jpg",keywords:null,numberOfDownloads:9527,numberOfWosCitations:1,numberOfCrossrefCitations:5,numberOfDimensionsCitations:11,numberOfTotalCitations:17,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 30th 2019",dateEndSecondStepPublish:"March 24th 2020",dateEndThirdStepPublish:"May 23rd 2020",dateEndFourthStepPublish:"August 11th 2020",dateEndFifthStepPublish:"October 10th 2020",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"31988",title:"Prof.",name:"Kaneez",middleName:null,surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRhwqQAC/Profile_Picture_1643703122186",biography:"Professor of Neuroscience and translational clinical researcher from Sydney Australia. Researcher and academic of major Australian and other International Universities such as:\r\n• University of Technology Sydney, Australia\r\n• Australian Catholic University, Australia\r\n• University of NSW\r\n• University of Brunei Darussalam, Brunei Darussalam\r\n• PCMD, University of Karachi, Pakistan\r\n• United Arab Emirate University, UAE\r\n• University of Newcastle, Australia\r\n• Arabian Gulf University, Bahrain\r\nDr Kaneez Fatima Shad has more than thirty-five years of experience in teaching in Neuroscience and Biological Sciences in various universities in Australia, USA, UAE, Bahrain, Brunei, and Pakistan. She has generated over three million USD in grants from different private and government agencies of six countries. Dr Shad published more than seventy articles in refereed journals, edited seven books, wrote eight book chapters. She has supervised thirty-four postgraduate students and she was Invited as keynote or plenary speaker at over 80 international conferences.",institutionString:"University of Technology Sydney",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"University of Technology Sydney",institutionURL:null,country:{name:"Australia"}}}],coeditorOne:{id:"30612",title:"Prof.",name:"Kamil Hakan",middleName:null,surname:"Dogan",slug:"kamil-hakan-dogan",fullName:"Kamil Hakan Dogan",profilePictureURL:"https://mts.intechopen.com/storage/users/30612/images/system/30612.jpg",biography:"Kamil Hakan Dogan MD, PhD is a Full Professor and Chair in the Department of Forensic Medicine at Selcuk University, Faculty of Medicine in Turkey. Dr. Dogan received his MD from Gazi University, Faculty of Medicine in 2000. After his extensive research in the forensic medicine field, he received his PhD in Biochemistry in 2012. He gives lectures on Forensic Medicine and Medical Ethics to medical students as well as students of the dentistry and law faculties. He is the editor of five books and Bulletin of Legal Medicine, a reviewer for several international journals and he has published over 200 articles in refereed journals, chapters in textbooks and abstracts in scientific meetings. His publications have been cited more than 900 times.",institutionString:"Selçuk University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Selçuk University",institutionURL:null,country:{name:"Turkey"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"187",title:"Mental and Behavioural Disorders and Diseases of the Nervous System",slug:"mental-and-behavioural-disorders-and-diseases-of-the-nervous-system"}],chapters:[{id:"72324",title:"BDNF Protein and Anxiety Disorders",slug:"bdnf-protein-and-anxiety-disorders",totalDownloads:653,totalCrossrefCites:1,authors:[null]},{id:"72617",title:"Personality Disorders in Adolescents and Different Therapeutic Approaches",slug:"personality-disorders-in-adolescents-and-different-therapeutic-approaches",totalDownloads:538,totalCrossrefCites:0,authors:[{id:"53417",title:"Prof.",name:"Hojka",surname:"Gregoric Kumperscak",slug:"hojka-gregoric-kumperscak",fullName:"Hojka Gregoric Kumperscak"}]},{id:"70786",title:"Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve",slug:"neurofeedback-training-on-aging-prospects-on-maintaining-cognitive-reserve",totalDownloads:693,totalCrossrefCites:0,authors:[null]},{id:"71936",title:"Feeding and Eating Disorders",slug:"feeding-and-eating-disorders",totalDownloads:2115,totalCrossrefCites:0,authors:[null]},{id:"72143",title:"Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning-Impaired Rat Model of Alzheimer’s Disease",slug:"neuroprotective-effects-of-curcumin-and-vitamin-d3-on-scopolamine-induced-learning-impaired-rat-mode",totalDownloads:628,totalCrossrefCites:1,authors:[null]},{id:"72123",title:"Attention Deficit Hyperactivity Disorder",slug:"attention-deficit-hyperactivity-disorder",totalDownloads:604,totalCrossrefCites:0,authors:[null]},{id:"69322",title:"Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases",slug:"suicide-attempts-from-height-and-injury-patterns-an-analysis-of-64-cases",totalDownloads:873,totalCrossrefCites:1,authors:[null]},{id:"71828",title:"Advances in Emotion Recognition: Link to Depressive Disorder",slug:"advances-in-emotion-recognition-link-to-depressive-disorder",totalDownloads:901,totalCrossrefCites:2,authors:[{id:"172423",title:"Dr.",name:"Xiaoxia",surname:"Wang",slug:"xiaoxia-wang",fullName:"Xiaoxia Wang"}]},{id:"73001",title:"Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation for People with Borderline Personality Disorder",slug:"reimagining-attachment-traumas-perspectives-on-using-image-making-in-psychoeducation-for-people-with",totalDownloads:486,totalCrossrefCites:0,authors:[null]},{id:"69607",title:"Amnesia among Indigenous Australians",slug:"amnesia-among-indigenous-australians",totalDownloads:583,totalCrossrefCites:0,authors:[null]},{id:"69300",title:"Psychosocial Autopsy of Mass Suicides: Changing Patterns in Contemporary Times",slug:"psychosocial-autopsy-of-mass-suicides-changing-patterns-in-contemporary-times",totalDownloads:792,totalCrossrefCites:0,authors:[null]},{id:"69615",title:"Neurocognitive Perspective of Transient Global Amnesia",slug:"neurocognitive-perspective-of-transient-global-amnesia",totalDownloads:664,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"247041",firstName:"Dolores",lastName:"Kuzelj",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/247041/images/7108_n.jpg",email:"dolores@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1624",title:"Patch Clamp Technique",subtitle:null,isOpenForSubmission:!1,hash:"24164a2299d5f9b1a2ef1c2169689465",slug:"patch-clamp-technique",bookSignature:"Fatima Shad Kaneez",coverURL:"https://cdn.intechopen.com/books/images_new/1624.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1359",title:"Underlying Mechanisms of Epilepsy",subtitle:null,isOpenForSubmission:!1,hash:"85f9b8dac56ce4be16a9177c366e6fa1",slug:"underlying-mechanisms-of-epilepsy",bookSignature:"Fatima Shad Kaneez",coverURL:"https://cdn.intechopen.com/books/images_new/1359.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5780",title:"Serotonin",subtitle:"A Chemical Messenger Between All Types of Living Cells",isOpenForSubmission:!1,hash:"5fe2c461c95b4ee2d886e30b89d71723",slug:"serotonin-a-chemical-messenger-between-all-types-of-living-cells",bookSignature:"Kaneez Fatima Shad",coverURL:"https://cdn.intechopen.com/books/images_new/5780.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6683",title:"Ion Channels in Health and Sickness",subtitle:null,isOpenForSubmission:!1,hash:"8b02f45497488912833ba5b8e7cdaae8",slug:"ion-channels-in-health-and-sickness",bookSignature:"Kaneez Fatima Shad",coverURL:"https://cdn.intechopen.com/books/images_new/6683.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7842",title:"Basic and Clinical Understanding of Microcirculation",subtitle:null,isOpenForSubmission:!1,hash:"a57d5a701b51d9c8e17b1c80bc0d52e5",slug:"basic-and-clinical-understanding-of-microcirculation",bookSignature:"Kaneez Fatima Shad, Seyed Soheil Saeedi Saravi and Nazar Luqman Bilgrami",coverURL:"https://cdn.intechopen.com/books/images_new/7842.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10494",title:"Erythrocyte",subtitle:"A Peripheral Biomarker For Infection and Inflammation",isOpenForSubmission:!1,hash:"fa5f4b6ef59e28b6e7c1a739c57c5d2f",slug:"erythrocyte-a-peripheral-biomarker-for-infection-and-inflammation",bookSignature:"Kaneez Fatima Shad",coverURL:"https://cdn.intechopen.com/books/images_new/10494.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"22062",title:"Generation of Insulin Producing Cells for the Treatment of Diabetes",doi:"10.5772/18633",slug:"generation-of-insulin-producing-cells-for-the-treatment-of-diabetes",body:null,keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/22062.pdf",chapterXML:null,downloadPdfUrl:"/chapter/pdf-download/22062",previewPdfUrl:"/chapter/pdf-preview/22062",totalDownloads:1714,totalViews:79,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:18,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"October 28th 2010",dateReviewed:"May 24th 2011",datePrePublished:null,datePublished:"October 26th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/22062",risUrl:"/chapter/ris/22062",book:{id:"504",slug:"update-on-mechanisms-of-hormone-action-focus-on-metabolism-growth-and-reproduction"},signatures:"Guo Cai Huang and Min Zhao",authors:[{id:"32071",title:"Dr.",name:"Guo",middleName:null,surname:"Huang",fullName:"Guo Huang",slug:"guo-huang",email:"guo.huang@kcl.ac.uk",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"136868",title:"Dr.",name:"Min",middleName:null,surname:"Zhao",fullName:"Min Zhao",slug:"min-zhao",email:"min_zhao@intechweb.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"King's College London",institutionURL:null,country:{name:"United Kingdom"}}}],sections:null,chapterReferences:null,footnotes:null,contributors:null,corrections:null},book:{id:"504",type:"book",title:"Update on Mechanisms of Hormone Action",subtitle:"Focus on Metabolism, Growth and Reproduction",fullTitle:"Update on Mechanisms of Hormone Action - Focus on Metabolism, Growth and Reproduction",slug:"update-on-mechanisms-of-hormone-action-focus-on-metabolism-growth-and-reproduction",publishedDate:"October 26th 2011",bookSignature:"Gianluca Aimaretti with Paolo Marzullo and Flavia Prodam",coverURL:"https://cdn.intechopen.com/books/images_new/504.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:null,printIsbn:"978-953-307-341-5",pdfIsbn:"978-953-51-6531-6",reviewType:"peer-reviewed",numberOfWosCitations:12,isAvailableForWebshopOrdering:!0,editors:[{id:"42439",title:"Prof.",name:"Gianluca",middleName:null,surname:"Aimaretti",slug:"gianluca-aimaretti",fullName:"Gianluca Aimaretti"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"44241",title:"Dr.",name:"Flavia",middleName:null,surname:"Prodam",slug:"flavia-prodam",fullName:"Flavia Prodam"},coeditorTwo:{id:"56182",title:"Dr.",name:"Paolo",middleName:null,surname:"Marzullo",slug:"paolo-marzullo",fullName:"Paolo Marzullo"},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1014"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"22054",type:"chapter",title:"The Gut Peptide Hormone Family, Motilin and Ghrelin",slug:"the-gut-peptide-hormone-family-motilin-and-ghrelin",totalDownloads:3123,totalCrossrefCites:0,signatures:"Ichiro Sakata and Takafumi Sakai",reviewType:"peer-reviewed",authors:[{id:"26199",title:"Dr.",name:"Ichiro",middleName:null,surname:"Sakata",fullName:"Ichiro Sakata",slug:"ichiro-sakata"},{id:"26646",title:"Prof.",name:"Takafumi",middleName:null,surname:"Sakai",fullName:"Takafumi Sakai",slug:"takafumi-sakai"}]},{id:"22055",type:"chapter",title:"Functions of Adipose Tissue and Adipokines in Health and Disease",slug:"functions-of-adipose-tissue-and-adipokines-in-health-and-disease",totalDownloads:3274,totalCrossrefCites:0,signatures:"Francisca Lago, Rodolfo Gómez, Javier Conde, Morena Scotece, Carlos Dieguez and Oreste Gualillo",reviewType:"peer-reviewed",authors:[{id:"25655",title:"Dr.",name:"Oreste",middleName:null,surname:"Gualillo",fullName:"Oreste Gualillo",slug:"oreste-gualillo"},{id:"29339",title:"Dr.",name:"Carlos",middleName:null,surname:"Dieguez",fullName:"Carlos Dieguez",slug:"carlos-dieguez"},{id:"34695",title:"Dr.",name:"Francisca",middleName:null,surname:"Lago",fullName:"Francisca Lago",slug:"francisca-lago"},{id:"34697",title:"Dr.",name:"Rodolfo",middleName:null,surname:"Gomez",fullName:"Rodolfo Gomez",slug:"rodolfo-gomez"},{id:"72030",title:"Ms.",name:"Morena",middleName:null,surname:"Scotece",fullName:"Morena Scotece",slug:"morena-scotece"},{id:"72050",title:"BSc.",name:"Javier",middleName:null,surname:"Conde",fullName:"Javier Conde",slug:"javier-conde"}]},{id:"22056",type:"chapter",title:"Glucokinase as a Glucose Sensor in Hypothalamus - Regulation by Orexigenic and Anorexigenic Peptides",slug:"glucokinase-as-a-glucose-sensor-in-hypothalamus-regulation-by-orexigenic-and-anorexigenic-peptides",totalDownloads:2703,totalCrossrefCites:0,signatures:"Carmen Sanz, Isabel Roncero, Elvira Alvarez, Verónica Hurtado and Enrique Blázquez",reviewType:"peer-reviewed",authors:[{id:"40639",title:"Dr.",name:"Carmen",middleName:null,surname:"Sanz",fullName:"Carmen Sanz",slug:"carmen-sanz"},{id:"40671",title:"Dr.",name:"Isabel",middleName:null,surname:"Roncero",fullName:"Isabel Roncero",slug:"isabel-roncero"},{id:"40672",title:"Dr.",name:"Elvira",middleName:null,surname:"Álvarez",fullName:"Elvira Álvarez",slug:"elvira-alvarez"},{id:"40673",title:"Dr.",name:"Verónica",middleName:null,surname:"Hurtado-Carneiro",fullName:"Verónica Hurtado-Carneiro",slug:"veronica-hurtado-carneiro"},{id:"40674",title:"Mr.",name:"Enrique",middleName:null,surname:"Blazquez",fullName:"Enrique Blazquez",slug:"enrique-blazquez"}]},{id:"22057",type:"chapter",title:"‘Exercise-Eating Linkage’ Mediated by Neuro-Endocrine Axis and the Relevance in Regulation of Appetite and Energy Balance for Prevention of Obesity",slug:"-exercise-eating-linkage-mediated-by-neuro-endocrine-axis-and-the-relevance-in-regulation-of-appetit",totalDownloads:1352,totalCrossrefCites:0,signatures:"Takahiro Yoshikawa",reviewType:"peer-reviewed",authors:[{id:"25741",title:"Dr.",name:"Takahiro",middleName:null,surname:"Yoshikawa",fullName:"Takahiro Yoshikawa",slug:"takahiro-yoshikawa"}]},{id:"22058",type:"chapter",title:"Estrogen Receptors in Glucose Homeostasis",slug:"estrogen-receptors-in-glucose-homeostasis",totalDownloads:4417,totalCrossrefCites:0,signatures:"Malin Hedengran Faulds and Karin Dahlman-Wright",reviewType:"peer-reviewed",authors:[{id:"32162",title:"Dr.",name:"Malin",middleName:null,surname:"Hedengran Faulds",fullName:"Malin Hedengran Faulds",slug:"malin-hedengran-faulds"}]},{id:"22059",type:"chapter",title:"Expression of Neuropeptide Y of GIFT Tilapia (Oreochromis sp.) in Yeast Pichia Pastoris and Its Stimulatory Effects on Food Intake and Growth",slug:"expression-of-neuropeptide-y-of-gift-tilapia-oreochromis-sp-in-yeast-pichia-pastoris-and-its-stimula",totalDownloads:1593,totalCrossrefCites:2,signatures:"Guangzhong Wang, Caiyun Sun, Haoran Lin and Wensheng Li",reviewType:"peer-reviewed",authors:[{id:"28501",title:"Dr.",name:"Wensheng",middleName:null,surname:"Li",fullName:"Wensheng Li",slug:"wensheng-li"},{id:"39300",title:"MSc.",name:"Guangzhong",middleName:null,surname:"Wang",fullName:"Guangzhong Wang",slug:"guangzhong-wang"},{id:"39301",title:"Dr.",name:"Caiyun",middleName:null,surname:"Sun",fullName:"Caiyun Sun",slug:"caiyun-sun"},{id:"39302",title:"Mr.",name:"Haoran",middleName:null,surname:"Lin",fullName:"Haoran Lin",slug:"haoran-lin"}]},{id:"22060",type:"chapter",title:"Hormones and Metabolism in Poultry",slug:"hormones-and-metabolism-in-poultry",totalDownloads:10310,totalCrossrefCites:0,signatures:"Colin G. Scanes",reviewType:"peer-reviewed",authors:[{id:"34037",title:"Prof.",name:"Colin",middleName:null,surname:"Scanes",fullName:"Colin Scanes",slug:"colin-scanes"}]},{id:"22061",type:"chapter",title:"Metabolic Control Targets for Patients with Type 1 Diabetes in Clinical Practice",slug:"metabolic-control-targets-for-patients-with-type-1-diabetes-in-clinical-practice",totalDownloads:1606,totalCrossrefCites:0,signatures:"María Gloria Baena-Nieto, Cristina López-Tinoco, Jose Ortego-Rojo and Manuel Aguilar-Diosdado",reviewType:"peer-reviewed",authors:[{id:"29477",title:"Dr.",name:"Manuel",middleName:null,surname:"Aguilar-Diosdado",fullName:"Manuel Aguilar-Diosdado",slug:"manuel-aguilar-diosdado"},{id:"44261",title:"Dr.",name:"María Gloria",middleName:null,surname:"Baena-Nieto",fullName:"María Gloria Baena-Nieto",slug:"maria-gloria-baena-nieto"},{id:"44262",title:"Dr.",name:"Cristina",middleName:null,surname:"López-Tinoco",fullName:"Cristina López-Tinoco",slug:"cristina-lopez-tinoco"},{id:"44263",title:"Dr.",name:"Jose",middleName:null,surname:"Ortego-Rojo",fullName:"Jose Ortego-Rojo",slug:"jose-ortego-rojo"}]},{id:"22062",type:"chapter",title:"Generation of Insulin Producing Cells for the Treatment of Diabetes",slug:"generation-of-insulin-producing-cells-for-the-treatment-of-diabetes",totalDownloads:1714,totalCrossrefCites:0,signatures:"Guo Cai Huang and Min Zhao",reviewType:"peer-reviewed",authors:[{id:"32071",title:"Dr.",name:"Guo",middleName:null,surname:"Huang",fullName:"Guo Huang",slug:"guo-huang"},{id:"136868",title:"Dr.",name:"Min",middleName:null,surname:"Zhao",fullName:"Min Zhao",slug:"min-zhao"}]},{id:"22063",type:"chapter",title:"GH-IGF-IGFBP Axis and Metabolic Profile in Short Children Born Small for Gestational Age",slug:"gh-igf-igfbp-axis-and-metabolic-profile-in-short-children-born-small-for-gestational-age",totalDownloads:1896,totalCrossrefCites:0,signatures:"Daniëlle C.M. van der Kaay and Anita C.S. Hokken-Koelega",reviewType:"peer-reviewed",authors:[{id:"32606",title:"Dr.",name:"Danielle",middleName:null,surname:"van der Kaay",fullName:"Danielle van der Kaay",slug:"danielle-van-der-kaay"},{id:"89041",title:"Prof.",name:"Anita",middleName:null,surname:"Hokken-Koelega",fullName:"Anita Hokken-Koelega",slug:"anita-hokken-koelega"}]},{id:"22064",type:"chapter",title:"Failure to Thrive: Overview of Diagnosis and Management",slug:"failure-to-thrive-overview-of-diagnosis-and-management",totalDownloads:8117,totalCrossrefCites:0,signatures:"Ayse Pinar Cemeroglu, Lora Kleis and Beth Robinson-Wolfe",reviewType:"peer-reviewed",authors:[{id:"28161",title:"Prof.",name:"Ayse",middleName:"Pinar",surname:"Cemeroglu",fullName:"Ayse Cemeroglu",slug:"ayse-cemeroglu"},{id:"38859",title:"Ms.",name:"Lora",middleName:null,surname:"Kleis",fullName:"Lora Kleis",slug:"lora-kleis"}]},{id:"22065",type:"chapter",title:"Hormonal Regulation of Circadian Pacemaker in Ovary and Uterus",slug:"hormonal-regulation-of-circadian-pacemaker-in-ovary-and-uterus",totalDownloads:2079,totalCrossrefCites:1,signatures:"Masa-aki Hattori",reviewType:"peer-reviewed",authors:[{id:"30090",title:"Prof.",name:"Masa-aki",middleName:null,surname:"Hattori",fullName:"Masa-aki Hattori",slug:"masa-aki-hattori"}]},{id:"22066",type:"chapter",title:"Role of Leptin in the Reproduction and Metabolism: Focus on Regulation by Seasonality in Animals",slug:"role-of-leptin-in-the-reproduction-and-metabolism-focus-on-regulation-by-seasonality-in-animals",totalDownloads:3004,totalCrossrefCites:1,signatures:"Malgorzata Szczesna and Dorota A. Zieba",reviewType:"peer-reviewed",authors:[{id:"25647",title:"Prof.",name:"Dorota",middleName:null,surname:"Zieba",fullName:"Dorota Zieba",slug:"dorota-zieba"},{id:"42592",title:"Dr.",name:"Malgorzata",middleName:null,surname:"Szczesna",fullName:"Malgorzata Szczesna",slug:"malgorzata-szczesna"}]},{id:"22067",type:"chapter",title:"Attenuin: What It Is, How It Works and What It Does",slug:"attenuin-what-it-is-how-it-works-and-what-it-does",totalDownloads:1263,totalCrossrefCites:0,signatures:"Ana Gordon, José C. Garrido-Gracia, Rafaela Aguilar, Carmina Bellido, Juana Martín de las Mulas and José E. Sánchez-Criado",reviewType:"peer-reviewed",authors:[{id:"26125",title:"Prof.",name:"José",middleName:"Eugenio",surname:"Sánchez-Criado",fullName:"José Sánchez-Criado",slug:"jose-sanchez-criado"},{id:"39371",title:"Dr",name:"Ana",middleName:null,surname:"Gordon",fullName:"Ana Gordon",slug:"ana-gordon"},{id:"39372",title:"Prof.",name:"José",middleName:"Carlos",surname:"Garrido-Gracia",fullName:"José Garrido-Gracia",slug:"jose-garrido-gracia"},{id:"39373",title:"Prof.",name:"Juana",middleName:null,surname:"Martín de las Mulas",fullName:"Juana Martín de las Mulas",slug:"juana-martin-de-las-mulas"},{id:"39374",title:"Dr.",name:"Rafaela",middleName:null,surname:"Aguilar",fullName:"Rafaela Aguilar",slug:"rafaela-aguilar"},{id:"77717",title:"Dr.",name:"Carmina",middleName:null,surname:"Bellido",fullName:"Carmina Bellido",slug:"carmina-bellido"}]},{id:"22068",type:"chapter",title:"Calcitonin Functions Both as a Hypocalcemic Hormone and Stimulator of Steroid Production and Oocyte Maturation in Ovarian Follicles of Common Carp, Cyprinus carpio",slug:"calcitonin-functions-both-as-a-hypocalcemic-hormone-and-stimulator-of-steroid-production-and-oocyte-",totalDownloads:3263,totalCrossrefCites:0,signatures:"Dilip Mukherjee, Sourav Kundu, Kousik Pramanick, Sudipta Paul and Buddhadev Mallick",reviewType:"peer-reviewed",authors:[{id:"27881",title:"Prof.",name:"Dilip",middleName:null,surname:"Mukherjee",fullName:"Dilip Mukherjee",slug:"dilip-mukherjee"},{id:"50545",title:"Mr.",name:"Sourav",middleName:null,surname:"Kundu",fullName:"Sourav Kundu",slug:"sourav-kundu"},{id:"50546",title:"Dr.",name:"Kousik",middleName:null,surname:"Pramanick",fullName:"Kousik Pramanick",slug:"kousik-pramanick"},{id:"50547",title:"Dr.",name:"Sudipta",middleName:null,surname:"Paul",fullName:"Sudipta Paul",slug:"sudipta-paul"},{id:"116202",title:"Mr.",name:"Buddhadev",middleName:null,surname:"Mallick",fullName:"Buddhadev Mallick",slug:"buddhadev-mallick"}]},{id:"22069",type:"chapter",title:"Ascidians: New Model Organisms for Reproductive Endocrinology",slug:"ascidians-new-model-organisms-for-reproductive-endocrinology",totalDownloads:2069,totalCrossrefCites:1,signatures:"Honoo Satake, Tsuyoshi Kawada, Masato Aoyama, Toshio Sekiguchi and Tsubasa Sakai",reviewType:"peer-reviewed",authors:[{id:"25799",title:"Dr.",name:"Honoo",middleName:null,surname:"Satake",fullName:"Honoo Satake",slug:"honoo-satake"},{id:"35691",title:"Dr.",name:"Tsuyoshi",middleName:null,surname:"Kawada",fullName:"Tsuyoshi Kawada",slug:"tsuyoshi-kawada"},{id:"35692",title:"Dr.",name:"Toshio",middleName:null,surname:"Sekiguchi",fullName:"Toshio Sekiguchi",slug:"toshio-sekiguchi"},{id:"35693",title:"Dr.",name:"Tsubasa",middleName:null,surname:"Sakai",fullName:"Tsubasa Sakai",slug:"tsubasa-sakai"},{id:"75124",title:"Mrs.",name:"Masato",middleName:null,surname:"Aoyama",fullName:"Masato Aoyama",slug:"masato-aoyama"}]},{id:"22070",type:"chapter",title:"Estrogen Receptors in Leukocytes - Possible Impact on Inflammatory Processes in the Female Reproductive System",slug:"estrogen-receptors-in-leukocytes-possible-impact-on-inflammatory-processes-in-the-female-reproductiv",totalDownloads:2586,totalCrossrefCites:0,signatures:"Chellakkan Selvanesan Blesson",reviewType:"peer-reviewed",authors:[{id:"28141",title:"Dr.",name:"Chellakkan",middleName:"Selvanesan",surname:"Blesson",fullName:"Chellakkan Blesson",slug:"chellakkan-blesson"}]},{id:"22071",type:"chapter",title:"Physiological Relevance of Pregnanolone Isomers and Their Polar Conjugates with Respect to the Gender, Menstrual Cycle and Pregnancy",slug:"physiological-relevance-of-pregnanolone-isomers-and-their-polar-conjugates-with-respect-to-the-gende",totalDownloads:1539,totalCrossrefCites:0,signatures:"Martin Hill, Antonín Pařízek, Radmila Kancheva, David Cibula, Nikolaj Madzarov and Luboslav Stárka",reviewType:"peer-reviewed",authors:[{id:"25926",title:"Dr.",name:"Martin",middleName:null,surname:"Hill",fullName:"Martin Hill",slug:"martin-hill"},{id:"84293",title:"Dr.",name:"Radmila",middleName:null,surname:"Kancheva",fullName:"Radmila Kancheva",slug:"radmila-kancheva"},{id:"137429",title:"Dr.",name:"Antonín",middleName:null,surname:"Pařízek",fullName:"Antonín Pařízek",slug:"antonin-parizek"},{id:"137430",title:"Dr.",name:"David",middleName:null,surname:"Cibula",fullName:"David Cibula",slug:"david-cibula"},{id:"137431",title:"Dr.",name:"Nikolaj",middleName:null,surname:"Madzarov",fullName:"Nikolaj Madzarov",slug:"nikolaj-madzarov"},{id:"137781",title:"Prof.",name:"Luboslav",middleName:null,surname:"Stárka",fullName:"Luboslav Stárka",slug:"luboslav-starka"}]},{id:"22072",type:"chapter",title:"Menstrual Cycle Disturbances at Reproductive Age",slug:"menstrual-cycle-disturbances-at-reproductive-age",totalDownloads:2931,totalCrossrefCites:0,signatures:"Skałba Piotr",reviewType:"peer-reviewed",authors:[{id:"26913",title:"Prof.",name:"Piotr",middleName:"Henryk",surname:"Skalba",fullName:"Piotr Skalba",slug:"piotr-skalba"}]},{id:"22073",type:"chapter",title:"Primary and Secondary Amenorrhea",slug:"primary-and-secondary-amenorrhea",totalDownloads:9285,totalCrossrefCites:1,signatures:"Valentina Chiavaroli, Ebe D’Adamo, Laura Diesse, Tommaso de Giorgis, Francesco Chiarelli and Angelika Mohn",reviewType:"peer-reviewed",authors:[{id:"29091",title:"Dr.",name:"Angelika",middleName:null,surname:"Mohn",fullName:"Angelika Mohn",slug:"angelika-mohn"},{id:"40331",title:"Dr.",name:"Valentina",middleName:null,surname:"Chiavaroli",fullName:"Valentina Chiavaroli",slug:"valentina-chiavaroli"},{id:"40332",title:"Prof.",name:"Francesco",middleName:null,surname:"Chiarelli",fullName:"Francesco Chiarelli",slug:"francesco-chiarelli"},{id:"82399",title:"Dr.",name:"Tommaso",middleName:null,surname:"De Giorgis",fullName:"Tommaso De Giorgis",slug:"tommaso-de-giorgis"},{id:"82402",title:"Dr.",name:"Ebe",middleName:null,surname:"D'Adamo",fullName:"Ebe D'Adamo",slug:"ebe-d'adamo"},{id:"82405",title:"Dr.",name:"Laura",middleName:null,surname:"Diesse",fullName:"Laura Diesse",slug:"laura-diesse"}]},{id:"22074",type:"chapter",title:"The Management of Dysfunctional Uterine Bleeding",slug:"the-management-of-dysfunctional-uterine-bleeding",totalDownloads:6733,totalCrossrefCites:0,signatures:"Aytul Corbacioglu",reviewType:"peer-reviewed",authors:[{id:"49110",title:"Dr.",name:"Aytul",middleName:null,surname:"Corbacioglu",fullName:"Aytul Corbacioglu",slug:"aytul-corbacioglu"}]}]},relatedBooks:[{type:"book",id:"805",title:"Sex Steroids",subtitle:null,isOpenForSubmission:!1,hash:"69b8296a72c662d5d96bf61a1b394eda",slug:"sex-steroids",bookSignature:"Scott M. Kahn",coverURL:"https://cdn.intechopen.com/books/images_new/805.jpg",editedByType:"Edited by",editors:[{id:"66905",title:"Dr.",name:"Scott",surname:"M. Kahn",slug:"scott-m.-kahn",fullName:"Scott M. Kahn"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"27063",title:"Evolutionary Perspectives on Sex Steroids in the Vertebrates",slug:"evolutionary-perspectives-on-sex-steroids-in-the-vertebrates",signatures:"Nigel C. Noriega",authors:[{id:"72556",title:"Dr.",name:"Nigel",middleName:null,surname:"Noriega",fullName:"Nigel Noriega",slug:"nigel-noriega"}]},{id:"27064",title:"Sex Hormone-Binding Globulin as a Modulator of the Prostate “Androgenome”",slug:"sex-hormone-binding-globulin-as-a-modulator-of-the-prostate-androgenome-",signatures:"Scott M. Kahn, Nicholas A. Romas and William Rosner",authors:[{id:"66905",title:"Dr.",name:"Scott",middleName:null,surname:"M. Kahn",fullName:"Scott M. Kahn",slug:"scott-m.-kahn"},{id:"135155",title:"Dr.",name:"Nicholas",middleName:null,surname:"Romas",fullName:"Nicholas Romas",slug:"nicholas-romas"},{id:"135156",title:"Dr.",name:"William",middleName:null,surname:"Rosner",fullName:"William Rosner",slug:"william-rosner"}]},{id:"27065",title:"Estrogens in the Control of Growth Hormone Actions in Liver",slug:"estrogens-in-the-control-of-growth-hormone-actions-in-liver",signatures:"Leandro Fernández-Pérez and Amilcar Flores-Morales",authors:[{id:"64207",title:"Prof.",name:"Leandro",middleName:null,surname:"Fernandez-Perez",fullName:"Leandro Fernandez-Perez",slug:"leandro-fernandez-perez"},{id:"70660",title:"Dr.",name:"Amilcar",middleName:null,surname:"Flores-Morales",fullName:"Amilcar Flores-Morales",slug:"amilcar-flores-morales"}]},{id:"27066",title:"Somatostatin in the Periventricular Nucleus of the Female Rat: Age Specific Effects of Estrogen and Onset of Reproductive Aging",slug:"somatostatin-in-the-periventricular-nucleus-of-the-female-rat-age-specific-effects-of-estrogen-and-o",signatures:"Eline M. Van der Beek, Harmke H. Van Vugt, Annelieke N. Schepens-Franke and Bert J.M. Van de Heijning",authors:[{id:"71915",title:"Dr.",name:"Eline M.",middleName:null,surname:"Van Der Beek",fullName:"Eline M. Van Der Beek",slug:"eline-m.-van-der-beek"},{id:"130351",title:"Dr.",name:"Harmke H.",middleName:null,surname:"Van Vugt",fullName:"Harmke H. Van Vugt",slug:"harmke-h.-van-vugt"},{id:"130353",title:"Dr.",name:"Annelieke N.",middleName:null,surname:"Schepens-Franke",fullName:"Annelieke N. Schepens-Franke",slug:"annelieke-n.-schepens-franke"},{id:"130355",title:"Dr.",name:"Bert J.M.",middleName:null,surname:"Van De Heijning",fullName:"Bert J.M. Van De Heijning",slug:"bert-j.m.-van-de-heijning"}]},{id:"27067",title:"Telocytes in Human Fallopian Tube and Uterus Express Estrogen and Progesterone Receptors",slug:"telocytes-in-human-fallopian-tube-and-uterus-express-estrogen-and-progesterone-receptors",signatures:"Sanda M. Cretoiu, Dragos Cretoiu Anca Simionescu and Laurentiu M. Popescu",authors:[{id:"65176",title:"Dr.",name:"Dragos",middleName:null,surname:"Cretoiu",fullName:"Dragos Cretoiu",slug:"dragos-cretoiu"},{id:"71558",title:"Dr.",name:"Sanda",middleName:"Maria",surname:"Cretoiu",fullName:"Sanda Cretoiu",slug:"sanda-cretoiu"},{id:"71561",title:"Dr.",name:"Anca",middleName:null,surname:"Simionescu",fullName:"Anca Simionescu",slug:"anca-simionescu"},{id:"71562",title:"Prof.",name:"Laurentiu M.",middleName:null,surname:"Popescu",fullName:"Laurentiu M. Popescu",slug:"laurentiu-m.-popescu"}]},{id:"27068",title:"Sex Differences and the Role of Sex Steroids in Sympatho-Adrenal Medullary System and Hypothalamo-Pituitary Adrenal Axis Responses to Stress",slug:"sex-differences-and-the-role-of-sex-steroids-in-sympatho-adrenal-medullary-system-and-hypothalamo-pi",signatures:"Anne I. Turner, Charlotte L. Keating and Alan J. Tilbrook",authors:[{id:"63906",title:"Dr.",name:"Anne",middleName:null,surname:"Turner",fullName:"Anne Turner",slug:"anne-turner"},{id:"68259",title:"Prof.",name:"Alan",middleName:null,surname:"Tilbrook",fullName:"Alan Tilbrook",slug:"alan-tilbrook"},{id:"135282",title:"Dr.",name:"Charlotte",middleName:null,surname:"Keating",fullName:"Charlotte Keating",slug:"charlotte-keating"}]},{id:"27069",title:"Estrogen and Brain Protection",slug:"estrogen-and-brain-protection",signatures:"Xiaohua Ju, Daniel Metzger and Marianna Jung",authors:[{id:"71285",title:"Prof.",name:"Marianna",middleName:null,surname:"Jung",fullName:"Marianna Jung",slug:"marianna-jung"},{id:"71286",title:"Dr.",name:"Xiaohua",middleName:null,surname:"Ju",fullName:"Xiaohua Ju",slug:"xiaohua-ju"},{id:"71287",title:"Mr.",name:"Daniel",middleName:null,surname:"Metzger",fullName:"Daniel Metzger",slug:"daniel-metzger"}]},{id:"27070",title:"Estrogen Influences on Cognition",slug:"estrogen-influences-on-cognition",signatures:"Antonella Gasbarri and Carlos Tomaz",authors:[{id:"66712",title:"Prof.",name:"Antonella",middleName:null,surname:"Gasbarri",fullName:"Antonella Gasbarri",slug:"antonella-gasbarri"},{id:"67420",title:"Prof.",name:"Carlos",middleName:null,surname:"Tomaz",fullName:"Carlos Tomaz",slug:"carlos-tomaz"}]},{id:"27071",title:"An Integrative Review of Estradiol Effects on Dendritic Spines and Memory over the Lifespan",slug:"an-integrative-review-of-estrogen-effects-on-memory-and-dendritic-spines-over-the-lifespan",signatures:"Victoria Luine and Maya Frankfurt",authors:[{id:"64746",title:"Prof.",name:"Victoria",middleName:null,surname:"Luine",fullName:"Victoria Luine",slug:"victoria-luine"},{id:"80026",title:"Prof.",name:"Maya",middleName:null,surname:"Frankfurt",fullName:"Maya Frankfurt",slug:"maya-frankfurt"}]},{id:"27072",title:"Sex Steroids Modulate Fish Immune Response",slug:"sex-steroids-modulate-fish-imnune-response",signatures:"Elena Chaves-Pozo, Isabel Cabas and Alfonsa García-Ayala",authors:[{id:"68013",title:"Prof.",name:"Alfonsa",middleName:null,surname:"Garcia-Ayala",fullName:"Alfonsa Garcia-Ayala",slug:"alfonsa-garcia-ayala"},{id:"68015",title:"Dr.",name:"Elena",middleName:null,surname:"Chaves-Pozo",fullName:"Elena Chaves-Pozo",slug:"elena-chaves-pozo"},{id:"68016",title:"Ms.",name:"Isabel",middleName:null,surname:"Cabas",fullName:"Isabel Cabas",slug:"isabel-cabas"}]},{id:"27073",title:"Interactions Between Reproductive and Immune Systems During Ontogeny: Roles of GnRH, Sex Steroids, and Immunomediators",slug:"interactions-between-the-reproductive-and-immune-systems-during-ontogenesis-the-role-of-gnrh-sex-ste",signatures:"Liudmila A. Zakharova and Marina S. Izvolskaia",authors:[{id:"64834",title:"Dr.",name:"Liudmila",middleName:"Alekseevna",surname:"Zakharova",fullName:"Liudmila Zakharova",slug:"liudmila-zakharova"},{id:"119140",title:"Dr.",name:"Marina",middleName:null,surname:"Izvolskaya",fullName:"Marina Izvolskaya",slug:"marina-izvolskaya"}]},{id:"27074",title:"Modulation of Immune Senescence by Menopause and Hormone Therapy",slug:"modulation-of-immune-function-by-menopause-and-hormone-therapy",signatures:"Flora Engelmann, Mark Asquith and Ilhem Messaoudi",authors:[{id:"63789",title:"Prof.",name:"Ilhem",middleName:null,surname:"Messaoudi",fullName:"Ilhem Messaoudi",slug:"ilhem-messaoudi"},{id:"63790",title:"BSc",name:"Flora",middleName:null,surname:"Engelmann",fullName:"Flora Engelmann",slug:"flora-engelmann"},{id:"129981",title:"Dr.",name:"Mark",middleName:null,surname:"Assquith",fullName:"Mark Assquith",slug:"mark-assquith"}]},{id:"27075",title:"The Role of Sex Steroids in the Host-Parasite Interaction",slug:"the-role-of-sex-steroids-in-the-host-parasite-interaction",signatures:"Karen Nava-Castro, Romel Hernández-Bello, Saé Muñiz-Hernández and Jorge Morales-Montor",authors:[{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",fullName:"Jorge Morales-Montor",slug:"jorge-morales-montor"},{id:"69556",title:"Dr.",name:"Romel",middleName:null,surname:"Hernandez-Bello",fullName:"Romel Hernandez-Bello",slug:"romel-hernandez-bello"},{id:"69557",title:"Dr.",name:"Karen",middleName:null,surname:"Nava",fullName:"Karen Nava",slug:"karen-nava"},{id:"69558",title:"Dr.",name:"Saé",middleName:null,surname:"Muñiz-Hernández",fullName:"Saé Muñiz-Hernández",slug:"sae-muniz-hernandez"}]},{id:"27076",title:"Adipose Tissue Metabolism and Effect of Postmenopausal Hormone Therapy on Change of Body Composition",slug:"effect-of-postmenopausal-hormone-therapy-on-adipose-tissue",signatures:"Kyong Wook Yi and Seung Yup Ku",authors:[{id:"66174",title:"Prof.",name:"Seung-Yup",middleName:null,surname:"Ku",fullName:"Seung-Yup Ku",slug:"seung-yup-ku"}]},{id:"27077",title:"Standard Gonadotropin-Suppressive Therapy in Japanese Girls with Idiopathic Central Precocious or Early Puberty Does Not Adversely Affect Body Composition",slug:"standard-gonadotropin-suppressive-therapy-in-japanese-girls-with-idiopathic-central-precocious-or-ea",signatures:"Toshihide Kubo",authors:[{id:"63897",title:"Dr.",name:"Toshihide",middleName:null,surname:"Kubo",fullName:"Toshihide Kubo",slug:"toshihide-kubo"}]},{id:"27078",title:"Hormone Therapy for the Treatment of Patients with Malignant Salivary Gland Tumor (MSGT)",slug:"hormone-therapy-for-the-treatment-of-patients-with-malignant-salivary-gland-tumors",signatures:"Tomoki Sumida and Akiko Ishikawa",authors:[{id:"65488",title:"Dr.",name:"Tomoki",middleName:null,surname:"Sumida",fullName:"Tomoki Sumida",slug:"tomoki-sumida"},{id:"141893",title:"Dr.",name:"Akiko",middleName:null,surname:"Ishikawa",fullName:"Akiko Ishikawa",slug:"akiko-ishikawa"}]}]}],publishedBooks:[{type:"book",id:"504",title:"Update on Mechanisms of Hormone Action",subtitle:"Focus on Metabolism, Growth and Reproduction",isOpenForSubmission:!1,hash:"f24c739037cec7a5dd8e9f89da59c6d9",slug:"update-on-mechanisms-of-hormone-action-focus-on-metabolism-growth-and-reproduction",bookSignature:"Gianluca Aimaretti with Paolo Marzullo and Flavia Prodam",coverURL:"https://cdn.intechopen.com/books/images_new/504.jpg",editedByType:"Edited by",editors:[{id:"42439",title:"Prof.",name:"Gianluca",surname:"Aimaretti",slug:"gianluca-aimaretti",fullName:"Gianluca Aimaretti"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"804",title:"Sex Hormones",subtitle:null,isOpenForSubmission:!1,hash:"0b136b00e0db35efcd27b4655045f5e1",slug:"sex-hormones",bookSignature:"Raghvendra K. Dubey",coverURL:"https://cdn.intechopen.com/books/images_new/804.jpg",editedByType:"Edited by",editors:[{id:"67895",title:"Prof.",name:"Raghvendra",surname:"Dubey",slug:"raghvendra-dubey",fullName:"Raghvendra Dubey"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2013",title:"Steroids",subtitle:"Clinical Aspect",isOpenForSubmission:!1,hash:"31dfd32a77f71bc348d7922af48b8e62",slug:"steroids-clinical-aspect",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/2013.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6762",title:"Advances in Testosterone Action",subtitle:null,isOpenForSubmission:!1,hash:"c7bfdea5f2e1d85ba08b6f07b8d3af5a",slug:"advances-in-testosterone-action",bookSignature:"Manuel Estrada",coverURL:"https://cdn.intechopen.com/books/images_new/6762.jpg",editedByType:"Edited by",editors:[{id:"29615",title:"Dr.",name:"Manuel",surname:"Estrada",slug:"manuel-estrada",fullName:"Manuel Estrada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6891",title:"Estrogen",subtitle:null,isOpenForSubmission:!1,hash:"89b39414c7a2b95f9d25786d39e00af2",slug:"estrogen",bookSignature:"Wahid Ali Khan",coverURL:"https://cdn.intechopen.com/books/images_new/6891.jpg",editedByType:"Edited by",editors:[{id:"64042",title:"Dr.",name:"Wahid Ali",surname:"Khan",slug:"wahid-ali-khan",fullName:"Wahid Ali Khan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"504",title:"Update on Mechanisms of Hormone Action",subtitle:"Focus on Metabolism, Growth and Reproduction",isOpenForSubmission:!1,hash:"f24c739037cec7a5dd8e9f89da59c6d9",slug:"update-on-mechanisms-of-hormone-action-focus-on-metabolism-growth-and-reproduction",bookSignature:"Gianluca Aimaretti with Paolo Marzullo and Flavia Prodam",coverURL:"https://cdn.intechopen.com/books/images_new/504.jpg",editedByType:"Edited by",editors:[{id:"42439",title:"Prof.",name:"Gianluca",surname:"Aimaretti",slug:"gianluca-aimaretti",fullName:"Gianluca Aimaretti"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"66969",title:"ADME Profiling in Drug Discovery and a New Path Paved on Silica",doi:"10.5772/intechopen.86174",slug:"adme-profiling-in-drug-discovery-and-a-new-path-paved-on-silica",body:'Drug discovery and development grew into a wide interdisciplinary field during the last decades and many factors played and play an important role in the successful evolution from a bioactive compound, or so-called new molecular entity (NME), into a potential drug [1]. Herein, we discuss the drug discovery and development (DDD) process where the pharmacokinetic profiling in terms of ADME assessment is concerned. Therefore, we provide a short overview of the
The current state of pharmaceutical DDD estimates that only up to ten compounds out of thousand screened hits would result in optimized leads and enter preclinical testing, with a chance of 9.6% to pass the clinical testing phase [1, 2]. Additionally, the drug approval process is estimated to last in average 15 years, with major expenses in phases II and III of clinical trials, which highlights the drawback a failure in (pre-) clinical testing causes [3, 4, 5, 6], where the overall DDD cost for each drug can reach as high as ~$2.56 billion preapproval rising to $2.87 billion including postapproval investments [6, 7, 8]. From the initial small molecule screened as hit to the optimized lead, a variety of
The drug development phase starts with preclinical testing followed by the clinical stage comprising phase I–III human trials. Each of the phases aims to answer a specific question. Initially, preclinical trials are conducted in animals and can provide information about whether a drug is toxic or not. Compounds that show no toxicity in animals then advance to phase I trials, which will study whether the drug is also safe in healthy humans and provide an initial idea for appropriate dosage. In phase II, the efficacy of the drug is examined in parallel to potential side effects to answer the question if it principally meets the expected performance. Phase II presents the biggest hurdle with a transition success rate as low as 30%. Ultimately, drug candidates enter clinical phase III in which the preliminary results found so far need to be proofed and any adverse reactions monitored to make sure that the drug really helps treating the disease [2, 11].
Starting from the generation of a lead compound assessment, and optimization of pharmacokinetic properties and correlation to pharmacodynamic effects increases in importance as one of the three major attrition causes among toxicity and efficacy [8, 12]. In this sense, it is not surprising that the period between lead and the clinical candidate is sometimes referred to as “valley of death” due to the often occurring failures and dead ends during this time of the DDD process, which results in high costs and missing deadlines [13].
In a long ongoing effort, more and more
Latter approach can save time and resources by eliminating in early stages molecules that have predicted low efficacy against the target or to suggest the next round of chemical modifications [14, 15]. Still, lead generation and/or optimization will eventually also include
When using
Furthermore, the choice of the number and type of molecular descriptors has a high impact, since it influences the accuracy and interpretability of the model. One would expect that using the maximum number of descriptors would be beneficial, but in reality, the risk of overfitting the data or losing the interpretability is a trade-off. This leads to the point that it is fundamental for a “good” model to find the perfect compromise between quality and quantity. Nevertheless, it is crucial to test and train a model and to evaluate its predictability by different means, such as statistical measures and internal and external validation as recommended by organizations as OECD [18], and also includes outlier analysis to reduce the noise in the model. An extensive review of different adequate validation methods is discussed in [19].
As a result of newly achieved advances in computational capability, more complex models and algorithms can now be applied. Despite this, it is still a challenge to create a model for the pharmacokinetic and pharmacodynamic phenomena and interactions within an organism as complex as a mammal, let alone humans [10]. Finally, notwithstanding the apparent linearity, the development of a new chemical entity into a drug is an iterative process, even more, where modeling is concerned, with data from failed attempts being integrated into the new predictions [13].
Pharmacology is a major part of the DDD process and describes the interaction of an organism and the drug. It can be divided into two main branches: while pharmacodynamics (PD) describes what the drug does to the body, pharmacokinetics (PK) is interested in what the body does to the drug [20]. The main processes of PK are absorption, distribution, metabolism, and excretion (ADME), finally complemented by toxicity (ADMET). While ADME tries to maximize the pharmacological performance of a small molecule, toxicology aims to ensure that it causes no harm in any kind of side effect [21].
The big hurdle to overcome is to combine appropriate physicochemical properties of the drug, which would drive its interaction with the organism and show biological activity [22]. Or according to Hodgson: “A chemical cannot be a drug, no matter how active nor how specific its action, unless it is also taken appropriately into the body (absorption), distributed to the right parts of the body, metabolized in a way that does not instantly remove its activity, and eliminated in a suitable manner—a drug must get in, move about, hang around, and then get out” [21].
As already reviewed [23] and suggested by the FDA, PK/PD assessment is one of the main focuses for optimization in the drug development process. This is apparently an idea that was shared among many: whereas ADME evaluation was previously addressed in the late stages of preclinical development, currently it became a major concern throughout the whole DDD process, starting from the very beginnings in drug discovery approaches until the very last steps in lead optimization [21, 24].
For each step in the drug’s path through the body, several parameters determine the destination of the drug. In respect to this, each of those parameters would be addressed directly and individually. Unfortunately, to address experimentally each potential parameter is timely unviable, due to the complexity of the human body where all those parameters influence each other. This is not only restricted to mechanisms within the body between different compartments but also extends to interpersonal variations introduced through gender, age, genetic state, disease, etc. To find an approximation, most of the important variables are indirectly evaluated by either models or surrogates (Table 1). In an approach to characterize the properties of compounds, facilitate calculations, and allow standardization between experiments, descriptors are introduced as numerical representations encoding aspects of the chemical information of a molecule. Examples of descriptors and properties include molecular weight and H-bond donors/acceptors and they can be directly obtained from experimental or generated by computational techniques [25].
Absorption | Physicochemical properties Dissolution and solubility Cell monolayers Artificial membranes | MDCK Caco-2 Transfected cells | Mouse model Knock-out/down mice Humanized mice | QSPR/QSAR pKa log Binding and expression of transporters Inhibition of efflux pumps |
Distribution | PAMPA IAM HAS-coupled (RP-) HPLC | Plasma/tissue binding | Vd Plasma protein binding | Vd Plasma protein binding Activity and expression of transporters |
Metabolism | S9 fraction Liver microsomes Recombinant enzymes | Hepatocytes (HepG2) Isolated tissue Isolated organ | Humanized animals | Half-life Activity and expression of transporters |
Excretion | Isolated tissue Isolated organ Transfected cells | Urine analysis | Half-life prediction |
Tools for ADME evaluation.
For instance, although the perfect approach of PK profiling would also reflect the kinetics of drug administration and concentration at the site of action, most
Each compound possesses individual physicochemical properties, such as solubility or lipophilicity, which are influenced by biochemical properties of the body as the different pH of tissues. Although they can be similar, each compound will behave differently, and it is futile to address
Furthermore, every PK assessment varies depending on the route of administration and requires different models and assays. While some routes depend on absorption mechanisms like oral and transdermal administration, others (i.e., intravenous) directly target the bloodstream and the bioavailability is essentially equal to 100%. Hereafter, we will discuss oral administration parameters of small molecules as the most common form due to many advantages like reliability, safety, price, their experimental approaches, and most common prediction modes [27, 28].
Passive transport across membranes is defined as permeability, which is dependent on lipophilicity, since biological membranes are virtually lipid bilayers, and is by far the most important transport for small molecules, especially in oral absorption [8, 24, 29]. Nonlipophilic compounds normally do not traverse membranes passively, while highly lipophilic molecules run the risk to get stuck within the membranes [30].
Properties utilized for measuring lipophilicity are the logarithm of the partition coefficient (log
Ionizability and lipophilicity provide a strong indication if a compound is likely to be orally absorbed or not [21].
Ultimately, also the molecular size of the compound is involved in successful absorption due to the aforementioned effects on permeability and solubility [31]. Usually, increasing molecular weight by adding new chemical moieties leads to decreased solubility in aqueous solutions [32] and while big lipophilic compounds partition passively along membranes (transcellular), small charged molecules can also cross membranes via tight junctions (paracellular) [26]. For oral absorption in terms of permeability, Lipinski and collaborators already proposed in 1997 [33, 34] that orally active compounds should fit at least three of observed four parameters: molecular weight < 500 g mol−1, log
Despite the criticism and overinterpretation of Lipinski and derived rules, the influence of physicochemical parameters on oral bioavailability and related parameters (as log
As already mentioned, ionizability is one of the most important properties in PK, thus making pKa the physicochemical property with the highest impact.
Early attempts to increase the efficiency of pKa evaluation were reported by Morgan and colleagues by scaling down the classical titration and spectrophotometric methods introducing microscale versions [43].
These alterations, however, could not overcome the principle demands of each technique, which are moderate precision and frequent calibration (potentiometric), and the need for a chromophore within the analyte (spectrophotometric) [44]. Starting in 1998, capillary electrophoresis (CE) was effectively used to determine pKa of many compounds and was further upgraded from Pfizer by implementing pressure-assisted capillary electrophoresis (PACE) as a standard method, which is nowadays readily applied in industry settings showing superior features compared to the aforementioned methods [44, 45]. Other variants such as vacuum-assisted multiplexed capillary electrophoresis also exist (VAMCE) [46]. A different approach better suited for HTS is called pH gradient titration offered from Sirius Analytical Instruments but is still limited due to the UV spectroscopy technology [30].
It is well established that solubility in aqueous media is one of the most important physicochemical properties to be evaluated in oral administration. It is not only necessary for absorption in the GI tract but also a requirement for almost all
On the other hand, generally speaking, lipophilicity is the ability of a compound to dissolve in lipids and/or organic solvents thus being able to pass biological membranes. Descriptors for lipophilicity are the logarithm of the partition coefficient (log
In recent years, a great effort has been made to improve the ability of
General solubility equation as proposed by Yalkowsky and Jain’s [52]:
Modifications in terms of the GSE have been proposed, for instance with the SCRATCH model, which replaces the melting point by molar aqueous activity coefficient, with comparable accuracy (R2 = 0.956, RMSE = 0.859 in a dataset of 883 compounds) [54]. Ali and collaborators suggested replacing the melting point descriptor of the GSE with TPSA, aiming to overcome the issues with compounds with high melting points and also to explicitly take into account the effect of polar and polarizable atoms on the aqueous solubility [55].
The argument that real drugs are actually more soluble than drug-like molecules, filtered by Lipinski’s rule of five [56], pointed out the studies in the direction of more complex models. Indeed, nowadays, the quantitative structure-property relationship (QSPR) models correlating the aqueous solubility with various molecular descriptors are often employed. As an example, Chevillard et al. reported the use of a random forest protocol to select the most accurate model among several available, both in commercial or free software packages, for each compound [57]. They report that the multimodel approach can enlarge the applicability domain given that more accurate results for solubility prediction were obtained in comparison to using individual models. This approach agrees with other reports that consensus of local QSAR models can generate predictive workflows, especially for datasets with large structural diversity [58, 59]. It is worth noting that Lipinski himself recently revisited his own rules [60], in vision of new potential classes of drugs, such as natural products, peptide-like, and fragments, which, despite the validated effect, would defy the original Ro5 limits.
Early pKa measurement proves beneficial in lipophilicity assessment since log
The prediction of ionization state of compounds, which is indicated by the pKa value, is relevant to derive several other physicochemical and ADME properties of drugs, including solubility, lipophilicity, and pharmacokinetic profile. The use of pKa prediction can be placed in two different stages along the DDD, in the beginning with fast models for larger libraries, intending to generate all possible state populations of particular compounds, and/or later on with more refined semiempirical and, computationally expensive, the density functional theory (DFT), in which more accurate ionization states can be accessed. Examples of fast prediction methods for ionization states, which are available as computer programs, are SPARC [61], MoKa [62], and Epik, which use the Hammett and Taft approaches for the pKa prediction [63]. On the other hand, once smaller subsets of molecules are being addressed, the use of semiempirical or density functional theory (DFT) with more computationally expensive models was reported to accurately incorporate the structural features and diversity into the pKa prediction [64, 65].
As already seen, lipophilicity (log
Cell culture methods have been applied to study intestinal absorption for several decades already [66]. Finding the correct model or cell line is crucial to assess the desired parameters such as passive or active transport. In general, it cannot be distinguished between the different transport mechanisms when using cell culture approaches, but several models exist to shift the focus on one of the parameters.
Two main cell lines are in use as models for intestinal absorption: Caco-2 and MDCK cells. Caco-2 cells are derived from a human colorectal carcinoma and possess many of the typical properties of the small intestine, therefore representing a well-established and validated assay system for absorption, permeability, and secretion studies [21, 67]. This assay is mainly used for rank ordering of compounds in terms of oral absorption and permeability in early phases of drug design. Unfortunately, results obtained in different batches and laboratories vary heavily due to several reasons, which make control compound usage necessary and represent a drawback of the technique [26]. Additional disadvantages include long preparation times (about 3 weeks) and no specific permeation mechanism evaluation. Caco-2 assays are usually used as a primary assay followed and complemented by other
As already stated above, transcellular permeation either occurs passively via diffusion of lipophilic molecules or is driven by membrane transporters. Important transporter includes ATP-dependent efflux transporter such as MRP2, BCRP, and P-gp and the organic solute transporter and the multidrug resistance protein 3 (MRP3) on the luminal and basolateral membranes, respectively [26].
Madin-Darby canine kidney (MDCK) cells are an alternative to Caco-2 cell-based assays and the next most common cell line for passive permeability assessment as well as drug-receptor interaction [70]. MDCK cells also are ideal for transfection and overexpression experiments with human transporters and receptors due to the lack of P-glycoprotein [68, 71]. For instance, the MDCK-MDR1 cell line overexpresses the multidrug resistance protein 1 (MDR1, P-glycoprotein) and can be used in concert with other cell-based assays to specifically address the influence of MDR1 in drug efflux [72].
Immobilized artificial membranes (IAMs) were already used very early on for lipophilicity determination and are gaining interest again in recent years for direct permeability measures [25]. IAMs are also intensively used in the measurement of the volume of distribution to mimic
The parallel artificial membrane permeability assay (PAMPA) [73] is a cheap and fast
Although high-throughput applications of newly developed and standardized techniques allow gathering of an exorbitant amount of data, it is crucial to also (cor)relate the physicochemical and biomimetic properties to structural features of the compound. This will facilitate the development of QSPRs and allows the construction of
When dealing with oral administration, it is important to note that the drug is not only confronted with the hurdles of solubility and permeability in the absorption process but is also facing metabolizing mechanisms (
Permeability has a direct influence on the drug absorption rate and, as discussed, despite the several
However, we are far from a model that can predict overall permeability and, the current status, rather focuses on individual compartments and tissues, such as the gastrointestinal (GI) tract, skin, buccal membrane, and the blood-brain barrier (BBB). Since the first BBB permeability correlations with log
Log
Finally, beyond the usual ADME parameters of interest in DDD, there are several other unusual ones that also can be predicted; as examples, we here point the permeability of the models for skin permeability, which evolved from simple diffusion models based on molecular weight and
Oral bioavailability is defined as the amount of drug that reaches the site of action after oral administration and is influenced by factors like drug solubility and dissolution, chemical and enzymatic stability in the gastric and intestinal lumen, interacting luminal contents (food), gastrointestinal transit time, enterocyte permeability, and intestinal and hepatic metabolism [24]. Recently, bioavailability has been also described as the rate and speed of the drug to reach systemic bloodstream, considering the initial formulation as the starting point.
Oral administration includes a pharmaceutical phase—prior to PK and PD phases—that comprises disintegration and dissolution of the dosage form. When using oral dosage forms, the shape and chemical composition (
Following the pharmaceutical phase, absorption is the first step in the pharmacokinetic phase and is defined as the movement of the drug from the site of administration to the bloodstream. The main properties determining the rate of oral absorption for small molecules are permeability and solubility [87].
As such, the rate of dissolution and ionization, which are described by the Noyes-Whitney and Henderson-Hasselbalch equation, respectively, is the key factors in lead optimization for oral administration and is complemented by lipophilicity as an additional factor influencing membrane permeation and solubility of the compound [31].
Dissolution can be expressed by a function of the aqueous solubility of a compound, the surface area of the administered tablet (or the particles in other solid formulation), and a specific dissolution rate constant. Altering any of these parameters directly affects the dissolution profile [26]. While solubility is an endpoint value indicating the amount of a compound that is soluble in a solvent, dissolution describes the kinetic process of a compound being solved in a solvent [88].
On the other hand, ionization reflects if a compound is present in the charged or uncharged state and is at least influenced by two major parameters. The physicochemical property responsible for ionization is the pKa and describes the ionization state of that entity at a given pH. It is also referred to as aqueous ionization constant [30]. Thereby, it is directly influenced by the pH of the environment, the second parameter, which drastically changes on the way through the GI tract, from about pH 1 to 8 in the stomach and ileum, respectively.
The determination of the ionization state of a compound in the gastrointestinal system (stomach, jejunum, ileum, and colon) is crucial for absorption since it not only influences the solubility of a compound but also the lipophilicity and permeability [26, 30, 89]. About 60–70% of all drugs (effective 1999) are ionizable, which underlines the role that ionization plays in ADME assessment [30, 90]. While charged molecules easily dissolve in aqueous systems (GI tract), they do not permeate membranes via passive diffusion and are reliant on active transport. The contrary is true for uncharged molecules, which pass biological membranes passively but show low solubility in aqueous solutions. Mechanisms of drug absorption include passive diffusion, active transport, and receptor-mediated endocytosis, which are influenced by different factors and can themselves influence the bioavailability.
Similar to model and prediction, the absorption of a drug is a complex process, which is influenced not only by the physicochemical properties of drugs themselves but also by the physiological state of the tissue in question. As such, there are a large number of prediction models available, which were generated based on the physicochemical properties involved in the absorption process, such as membrane permeability and drug solubility. These models can help formulation scientists to optimize drugs with poor absorption due to low aqueous solubility.
Initial absorption models can be separated into dispersion and compartmental models [91]. While dispersion models treat the GI as a continuous system, with variable pH and surface area, compartmental models take into account physiological factors such as transporters. The compartmental absorption transit (CAT) was one of the first models to regard distinct physiological properties, such as the minimal absorption in the stomach and colon, while assuming some mathematical simplifications, such as the instant dissolution of the drug and linear kinetics [92]. CAT was further modified as advanced CAT (ACAT), by including nonlinear absorption kinetics and the effects of the first-pass metabolism. ACAT also considers the gastrointestinal tract as nine subsections, each with unique physicochemical properties, such as pH, allowed solubility, particle size, and permeability [93]. Novel developments have included other absorption routes other than the GI, which have been recently included in commercially available software, such as oral absorption for the development of sublingual zolpidem tablets [94]. The absorption constant (Ka, expressed in terms of h−1 min−1), or also called first-order absorption rate constant (to not be confounded with pKa), is employed in most of the aforementioned models and is determined as a result from the changes in mass of absorbable drug over time at the site of administration. Ka can be derived from the decrease in the drug amount of absorbable present at the site of administration over time; however, it is often indirectly determined by the drug amounts measured in the blood and/or urine.
Along physicochemical models, which have a global application, machine-learning techniques were extensively employed to model absorption (as comprehensively reviewed by Kumar et al. [95]) and are inclined to be local models, since they are mostly based on a small, homogeneous dataset that influences their applicability domain.
After being absorbed and entering the circulatory system, the drug moves reversibly between different compartments within the body, which is described as distribution and influenced by several physicochemical properties of the drug and biological factors of the body. One of the most important properties is lipophilicity, and as such log
Volume distribution (Vd) is defined by the ratio between the amount of drug in the body (A) and the drug concentration in plasma (C, comprising both free drug and protein-bound drug):
The parameter describing protein binding is the plasma protein affinity constant Ki. Many efforts to determine distribution led to chromatography-based methods, such as (RP-)HPLC to mimic
A method to address plasma protein binding is the use of HSA and other plasma proteins (
To calculate the Vd “a priori”/nonexperimentally, plasma protein binding, experimental log
Expanding these studies, the work of Lombardo and Jing generated a set of models to predict the Vd in the steady state (Vss), using a dataset of 1096 diverse compounds [104]. They compared models generated by linear (PLS) with nonlinear (Random Forest) models, recommending the latter, with 33 descriptors, as the optimal method for Vss prediction.
The Vd of drugs is greatly influenced by binding to plasma proteins with several machine-learning–based models generated to predict this interaction. Protein-protein interaction (PPI) information derived from molecular docking was employed to derive a PPI-QSAR model for a small dataset of antibiotics (65 unique compounds), which resulted in an accurate model (R2 = 0.86 for the test set) [105]. Additionally, global quantitative models using an array of classification and regression models using physicochemical and molecular descriptors derived from a dataset of 794 compounds were shown to correctly classify the binding status of the test set compounds and could be used as a prescreening [106]. Another recent QSAR study using an extensively curated training set of 967 diverse pharmaceuticals aimed to predict plasma protein-bound fractions (fb) using models generated by six machine-learning algorithms with 26 molecular descriptors [107]. This study is particularly interesting where the applicability domain is concerned allowing to differentiate whether the classification derives from (un-)favorable regions.
del Amo et al. recently reported one of the first QSPR models to predict intravitreal volume of distribution and clearance of small molecules [108]; the model relies on the Log
Recently, as a novel approach bridging the animal experiments with human results, it was shown that in PXB mice, a chimeric mice linage with a humanized liver, plasma concentration-time profiles could be used to infer human’s compound half-life [110].
Volume of distribution is also closely related to half-life and clearance parameters. As the Vd is a relative measurement of the free concentration of drug in the blood, this same amount could be excreted by kidneys in the glomerular filtration (clearance). Consecutively, the rate of clearance (discussed below in Excretion section) directly influences the amount of available drug. Naturally, the concentration of free drug that can bind its molecular target is related to the therapeutic dosage and the half-life of the administered drug (as seen in Eq. (4)).
Half-life definition. Half-life is calculated by a ratio between the Napierian logarithm multiplied by the volume of distribution (Vd) and renal clearance (CL):
Drug metabolism normally involves enzymatic modification or degradation of the compound to facilitate excretion via one of the major clearance organs: liver, kidney, spleen, or bile. While phase I enzymatic reactions include modifications such as oxidation, hydrolysis, and reduction to either introduce a functional group to the molecule or make it accessible, phase II reactions are conjugation mechanisms (
When available, the 3D structure of those proteins could be employed in molecular docking and molecular dynamics simulations aiming to predict the binding affinity of drugs or drug candidates aiming the estimation of a PK profile [112]. The metabolism prediction combines mathematical models to predict whether the target compound could be a substrate of a specific enzyme in combination with metabolism site predictions. Usually, those initial predictions are followed by molecular docking simulations and quantum mechanics simulations due to the dependency of electronics structure from both substrate and enzyme in catalyzed reaction [113, 114].
Nowadays, several attempts have been made to develop
IDSite approach aims to overcome the ligand-based bias of SOM prediction by using it as a part of a large framework, more precisely by combining it with molecular docking, where an atom can be considered a significant SOM by a P450 enzyme when accessible to the reactive heme iron center, and/or quantum calculations, where the candidate atom must have some degree of reactivity in the absence of the enzyme [119]. Similarly, the work of Kingsley et al. combined different approaches into a framework to predict CYP2C9 substrates. They validated the predictions from SMARTCyp in an ensemble docking, followed by a QSAR model to account for influences of both the inherent reactivity of each atom and the physical structure of the CYP2C9 binding site [120]. This combined approach resulted in 88% of true SOMs accurately predicted among the top ranked sites.
Excretion is guided by one of the major clearance organs, and the assessment of clearance behavior sometimes involves isolated organs or tissues [24]. Humans rely on the kidney clearance as a major route for xenobiotic excretion, despite other available routes such as feces, bile, sweat, and breath. The excretion pathways directly impact the concentration of available drugs and are often measured in terms of half-life and the initial administered dose.
The renal clearance of a drug is another important parameter, which is usually employed to predict drug excretion. Experimentally, clearance is defined by the drug concentration drug along a defined time of renal excretion by a linear equation (Eq. (5)).
Equation for renal clearance.
Gombar et al. developed SVM- and MLR-based QSAR models to predict both systemic clearance and apparent volume of distribution from intravenous data [121] using as input structural fingerprints and electro-topological states (so-called E-states), respectively. The model performed with high accuracy, despite the highly diverse initial dataset employed for its generation, which points the importance of those models in early steps of the drug-discovery pipeline.
Also, the work of Kusama et al. established a chemoinformatic-based classification model to predict the major clearance pathways of 141 approved drugs based on four physicochemical parameters: charge, molecular weight, lipophilicity, and protein unbound fraction in plasma, resulting in a final model with an accuracy of 88% [122]. This model approach was further refined by using support vector machine and increasing the number of relevant descriptors [123]. In order to better model the biotransformation processes, often the major triggers of excretion, the work of Berellini et al. used ELASTICO (Enhanced Leave Analog-Structural, Therapeutic, Ionization Class Out) to provide an appropriate sampling during the validation process. Their partial least-square models resulted in a highly accurate model derived from 754 compounds [124].
On another topic, ABCB1, also known as P-glycoprotein (P-gp or MDR1), is a membrane protein member of the ATP-binding cassette (ABC) transporters superfamily. Together with the hERG channel and CYP3A4, P-gp is one of the most widely studied antitarget, where its inhibition could bring consequences for several processes, such as the absorption, distribution, and excretion of drugs. Classical studies used chemometric methods to describe bioavailability in terms of P-gp and CYP enzyme activities, generating QSAR models based on 805 unique drug molecules with high accuracy (R2 = 0.80 for the test set) [125]. Alternatively, an approach to predict P-glycoprotein inhibition using molecular interaction fields, derived from a literature collection of more than 1200 structures, generated a pharmacophore model for competitive P-gp inhibition [126].
The most recent reported studies involving prediction of drug clearance, both from human and rat hepatic
As the pinnacle of ADME
One of PBPK models’ important features is the perspective for the mechanistic and prospective prediction of a drug’s pharmacokinetic profiles. The use of drug-dependent parameters includes, but is not limited to, physicochemical properties, solubility and permeability values, and also the role of individual enzymes and transporters in the metabolism. Those parameters can be determined
Name | Description | Link/reference |
---|---|---|
ADME prediction | ||
vNN-ADMET | Public web server for ADMET property prediction based on 15 nearest neighbor models. | https://vnnadmet.bhsai.org/ [132] |
Swiss-ADME | Public web server for ADME property prediction. It has a very unique Log | http://www.swissadme.ch [133] |
pkCSM | ADME web server based on chemical fragment similarity (the so-called graph-based signatures). | http://biosig.unimelb.edu.au/pkcsm/ [134] |
ADMETlab | Web server using similarity-based ADME calculator models and drug-likeness analyses. | http://admet.scbdd.com/home/index/ [135] |
Schrodinger—QikProp | Calculates pKa; Log | https://www.schrodinger.com/ QikProp, Schrödinger, LLC, NY, 2019 |
DDI-Predictor | DDI-Predictor is able to make quantitative predictions of drug exposure even in cases where the interaction has not been studied yet. | https://www.ddi-predictor.org |
PBPK models and platforms | ||
GastroPlus | Comprises 10 different modules including PBPK modeling and | www.simulations-plus.com |
PKSIM | PBK modeling tool with integrated database of anatomical and physiological parameters for humans, mouse, rat, dog, and monkey. Can model different scenarios depending on the chosen building blocks. | www.systemsbiology.com/products/pk-sim.html |
Simcyp | Incorporates databases of genetic, physiological, and epidemiological information to enable simulation of different populations and species, ultimately is able to predict ADME parameters. | www.simcyp.com |
ADMEWORKS DDI Simulator | As a differential is able to predict drug-drug interactions using nonlinear models. | http://www.fqs.pl/chemistry_ materials_life_science/products/ddi_simulator |
Tools for ADME prediction and PBPK modeling.
Early PBPK models, such as the work of Varma et al., described another layer of complexity by including drug-drug interactions (DDI). The dosing time-dependent model considering the interaction between repaglinide with rifampicin was able to predict repaglinide plasma concentrations along a day. The model also predicted the drug interaction with other CYP3A4 and OATP1B1 inhibitors, which could result in further DDIs. Reports of DDI leading to complications in patients with particular genotype stimulated studies such as the one performed by Fermier et al. [131], where the effects of polymorphic cytochromes provided the basis for a more accurate DDI prediction.
During recent years, larger molecules (LM) have gained in significance and popularity, due to achievements and approvals, as new molecular entities. These “
The main differences between small and large molecules, despite the molecular weight, the number of heavy atoms, and torsions, can be found in the physicochemical properties, such as permeability, oral bioavailability, stability, specificity, and immunogenicity [138, 139]. New parameters, unique for large molecules, are also of interest, such as the physical particle size and the hydrodynamic radius, which has a dramatic effect on the absorption. Both parameters are related to the overall shape and correlate well with MW for globular proteins, but not necessarily for unstructured or highly modified entities. As a result, biologics are normally administered parenterally, only targeting extracellular structures; they are also more likely to trigger an immune response; and their production costs are considerably higher [139]. Interestingly, with the exception of the costs, these disadvantages can potentially be circumvented by appropriate delivery systems, for example, nanoparticle-based delivery to facilitate membrane permeation.
Other parameters, such as charges, which were previously modeled by pKa in case of small molecules, are heavily heterogeneous in LMs. The charge can be represented by the use of isoelectric points (pI), which are calculated from the available amino-acid sequence, and surface charge, which can use individual pKa’s and structural information to be inferred. Overall protein charge often influences the biologic excretion [140], since negatively charged molecules undergo less renal filtration disregarding size effect [141].
While representing difficulties in the development of new molecular entities, the aforementioned properties also offer special advantages that small molecules cannot cover. As such, LMs normally have longer t1/2, slower clearance, and higher selectivity; are multifunctional; and rarely expose drug interactions [139]. Apart from those, it was suggested that only 2–5% of the human genes can be targeted by small molecules, offering a niche for LMs’ application against several diseases [138].
The increasing effort and development of new technologies, driven by the belief in higher success rates, enabled the latest advances in the field [138]. For instance, currently, peptide drugs only account for ~2% of the drug market but are in use in a wide range of diseases such as acromegaly and multiple sclerosis, together with different cancer types such as prostate and breast cancer.
Several other biologics are currently in use, namely monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), as example agents that activate or enhance the immunologic response. Of special interest in cancer therapy is a subclass of bsAbs, so-called bispecific T-cell engager (BiTEs), which can recruit CD3 cells at the tumor site by binding to both cell types thereby directing the immunological response [142].
Other interesting examples for biologics comprise hormones (e.g., insulin), cytokines (such as erythropoietin, EPO; IL-1; IL-2; IL-6) [143], nucleic acids such as siRNA (ONPATTRO) [144], and aptamers (Pegaptanib) [145]. While such a broad spectrum of molecule classes offers also a wide range of treatments, at the same time, it exacerbates the need for new developments since every molecule type exhibits different properties. In the field of predicting the biologics activity against specific targets, classical modeling tools, such as Monte Carlo sampling, genetic algorithms, docking, and molecular dynamics simulation, were adapted or even developed anew to accommodate the specifics (as extensively reviewed by [146, 147]).
On the other hand, the absence of standard techniques to assess ADME properties hampers the PK profiling and thus further development [136]. In fact, the current knowledge of LM pharmacokinetics is even impaired compared to the basic knowledge of ADME principles for small molecules in the 1980s [136]. Although the basic PK principles are similar between SMs and LMs, the specific mechanisms influencing each step of ADME are different. To begin with, the route of administration between them can differ, which leads to different mechanisms of absorption and first-pass metabolism. Furthermore, LMs are not metabolized by CYPs but can still trigger the release of pro-inflammatory cytokines leading to heavy side effects known as cytokine storm [136, 139]. Also, other modifications play a role in biologics ADME, namely glycosylation, PEGylation, and neonatal Fc receptor (FcRn) interactions [139, 148]. Unfortunately, up until now, most of the evaluation of those factors is only addressed on
In this regard, the development of
The main difficulties in PK profiling lie in the high costs and comparable low throughput of
What distinguishes the DDD “then” and “now” is principally two main changes. First, in the past, pharmaceutical companies as well as academic laboratories were not that concerned with ADMET assessment in the early stages of drug discovery (hit and lead generation) and only addressed PK from preclinical stages on forward. Instead, HTS/HCS, genomics, and computational chemistry were high-profile areas. Today, almost all pharmaceutical big-players have shifted pharmacokinetic profiling to discovery phases. However, only the future will tell whether those changes will yield fruit.
Second, CADD became more and more part of the DDD pipeline in different stages facilitating fast screening of compounds
The authors would like to acknowledge the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grants 2018/08820-0, 2017/03966-4, and 2015/26722-8). The authors would like to thank Prof Dr. José Eduardo Gonçalves for his valuable comments on the manuscript.
The authors declare no conflict of interest.
ORCID numbers of all authors:
Thales Kronenberger: 0000-0001-6933-7590
Carsten Wrenger: 0000-0001-5987-1749
Vinicius Goncalves Maltarollo: 0000-0001-9675-5907
Arne Krüger: 0000-0002-5531-9508
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links.
",metaTitle:"List of Institutions by Country",metaDescription:"If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. However, if your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).",metaKeywords:null,canonicalURL:"open-access-funding-institutions-list",contentRaw:'[{"type":"htmlEditorComponent","content":"Book Chapters and Monographs
\\n\\nBook Chapters
\\n\\nMonographs Only
\\n\\n\\n\\nBook Chapters and Monographs
\\n\\nMonographs Only
\\n\\nBook Chapters and Monographs
\\n\\n\\n\\nBook Chapters and Monographs
\\n\\n\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\nCSIC affiliated authors can also take advantage of a central Open Access fund (amounting to 10,000 EUR) to cover up to 50% of the rest of the OAPF until it expires. Effective for chapters accepted from January 1, 2020.
\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\n\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\nBook Chapters and Monographs
\\n\\nBook Chapters and Monographs
\\n\\nBook Chapters and Monographs
\\n\\nBook Chapters and Monographs
\\n\\nThe Claremont Colleges are pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\\n\\nCorresponding authors will receive a 15% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\\n\\nThe University of Massachusetts, Amherst is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\\n\\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\\n\\nThe University of Surrey is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\\n\\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\\n\\nMonographs Only
\\n\\n\\n\\nImportant: You must be a member or grantee of the above listed institutions in order to apply for their Open Access publication funds.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Book Chapters and Monographs
\n\n\n\nBook Chapters
\n\nMonographs Only
\n\n\n\nBook Chapters and Monographs
\n\nMonographs Only
\n\nBook Chapters and Monographs
\n\n\n\nBook Chapters and Monographs
\n\n\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\nCSIC affiliated authors can also take advantage of a central Open Access fund (amounting to 10,000 EUR) to cover up to 50% of the rest of the OAPF until it expires. Effective for chapters accepted from January 1, 2020.
\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\n\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\nBook Chapters and Monographs
\n\nBook Chapters and Monographs
\n\nBook Chapters and Monographs
\n\n\n\nBook Chapters and Monographs
\n\nThe Claremont Colleges are pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 15% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nThe University of Massachusetts, Amherst is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nThe University of Surrey is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nMonographs Only
\n\n\n\nImportant: You must be a member or grantee of the above listed institutions in order to apply for their Open Access publication funds.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"58592",title:"Dr.",name:"Arun",middleName:null,surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58592/images/1664_n.jpg",biography:"Arun K. Shanker is serving as a Principal Scientist (Plant Physiology) with the Indian Council of Agricultural Research (ICAR) at the Central Research Institute for Dryland Agriculture in Hyderabad, India. He is working with the ICAR as a full time researcher since 1993 and has since earned his Advanced degree in Crop Physiology while in service. He has been awarded the prestigious Member of the Royal Society of Chemistry (MRSC), by the Royal Society of Chemistry, London in 2015. Presently he is working on systems biology approach to study the mechanism of abiotic stress tolerance in crops. His main focus now is to unravel the mechanism of drought and heat stress response in plants to tackle climate change related threats in agriculture.",institutionString:null,institution:{name:"Indian Council of Agricultural Research",country:{name:"India"}}},{id:"4782",title:"Prof.",name:"Bishnu",middleName:"P",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4782/images/system/4782.jpg",biography:"Bishnu P. Pal is Professor of Physics at Mahindra École\nCentrale Hyderabad India since July 1st 2014 after retirement\nas Professor of Physics from IIT Delhi; Ph.D.’1975 from IIT\nDelhi; Fellow of OSA and SPIE; Senior Member IEEE;\nHonorary Foreign Member Royal Norwegian Society for\nScience and Arts; Member OSA Board of Directors (2009-\n11); Distinguished Lecturer IEEE Photonics Society (2005-\n07).",institutionString:null,institution:{name:"Indian Institute of Technology Delhi",country:{name:"India"}}},{id:"69653",title:"Dr.",name:"Chusak",middleName:null,surname:"Limsakul",slug:"chusak-limsakul",fullName:"Chusak Limsakul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Prince of Songkla University",country:{name:"Thailand"}}},{id:"23804",title:"Dr.",name:"Hamzah",middleName:null,surname:"Arof",slug:"hamzah-arof",fullName:"Hamzah Arof",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/23804/images/5492_n.jpg",biography:"Hamzah Arof received his BSc from Michigan State University, and PhD from the University of Wales. Both degrees were in electrical engineering. His current research interests include signal processing and photonics. Currently he is affiliated with the Department of Electrical Engineering, University of Malaya, Malaysia.",institutionString:null,institution:{name:"University of Malaya",country:{name:"Malaysia"}}},{id:"41989",title:"Prof.",name:"He",middleName:null,surname:"Tian",slug:"he-tian",fullName:"He Tian",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"East China University of Science and Technology",country:{name:"China"}}},{id:"33351",title:null,name:"Hendra",middleName:null,surname:"Hermawan",slug:"hendra-hermawan",fullName:"Hendra Hermawan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/33351/images/168_n.jpg",biography:null,institutionString:null,institution:{name:"Institut Teknologi Bandung",country:{name:"Indonesia"}}},{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRglaQAC/Profile_Picture_1626411846553",biography:"Hiroshi Ishiguro is an award-winning roboticist and innovator. As the Director of the Intelligent Robotics Laboratory, which is part of the Department of Systems Innovation in the Graduate School of Engineering Science at Osaka University, Japan, Ishiguro concentrates on making robots that are similar as possible to humans to understand the human species. A notable project of his laboratory is the Actroid, a humanoid robot with a lifelike appearance and observable behavior such as facial movements. (Sources: http://www.geminoid.jp/en/index.html, https://en.wikipedia.org/wiki/Hiroshi_Ishiguro)",institutionString:null,institution:{name:"Osaka University",country:{name:"Japan"}}},{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Chiayi University",country:{name:"Taiwan"}}},{id:"61581",title:"Dr.",name:"Joy Rizki Pangestu",middleName:null,surname:"Djuansjah",slug:"joy-rizki-pangestu-djuansjah",fullName:"Joy Rizki Pangestu Djuansjah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61581/images/237_n.jpg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"94249",title:"Prof.",name:"Junji",middleName:null,surname:"Kido",slug:"junji-kido",fullName:"Junji Kido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Yamagata University",country:{name:"Japan"}}},{id:"12009",title:"Dr.",name:"Ki Young",middleName:null,surname:"Kim",slug:"ki-young-kim",fullName:"Ki Young Kim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12009/images/system/12009.jpg",biography:"Http://m80.knu.ac.kr/~doors",institutionString:null,institution:{name:"National Cheng Kung University",country:{name:"Taiwan"}}},{id:"132595",title:"Prof.",name:"Long",middleName:null,surname:"Wang",slug:"long-wang",fullName:"Long Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Peking University",country:{name:"China"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:6581},{group:"region",caption:"Middle and South America",value:2,count:5888},{group:"region",caption:"Africa",value:3,count:2381},{group:"region",caption:"Asia",value:4,count:12507},{group:"region",caption:"Australia and Oceania",value:5,count:1006},{group:"region",caption:"Europe",value:6,count:17529}],offset:12,limit:12,total:12507},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"7,21,23"},books:[{type:"book",id:"11481",title:"Active Learning - Research and Practice",subtitle:null,isOpenForSubmission:!0,hash:"3aba1eb3600a8c9ff880c628f70b3298",slug:null,bookSignature:"Ph.D. Delfín Ortega-Sánchez",coverURL:"https://cdn.intechopen.com/books/images_new/11481.jpg",editedByType:null,editors:[{id:"302925",title:"Ph.D.",name:"Delfín",surname:"Ortega-Sánchez",slug:"delfin-ortega-sanchez",fullName:"Delfín Ortega-Sánchez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11603",title:"People Management - Highlighting Futures",subtitle:null,isOpenForSubmission:!0,hash:"982c56a5fb4684d966f8f5e76b2638f5",slug:null,bookSignature:"Dr. Diana Dias and Dr. Carla Magalhães",coverURL:"https://cdn.intechopen.com/books/images_new/11603.jpg",editedByType:null,editors:[{id:"450553",title:"Dr.",name:"Diana",surname:"Dias",slug:"diana-dias",fullName:"Diana Dias"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11440",title:"Aggression and Violent Behaviour",subtitle:null,isOpenForSubmission:!0,hash:"7f1d671b6a9e4df140f63d940ee2a1e1",slug:null,bookSignature:"Dr. Catherine Athanasiadou-Lewis",coverURL:"https://cdn.intechopen.com/books/images_new/11440.jpg",editedByType:null,editors:[{id:"287692",title:"Dr.",name:"Catherine",surname:"Lewis",slug:"catherine-lewis",fullName:"Catherine Lewis"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",subtitle:null,isOpenForSubmission:!0,hash:"8d41fa5f3a5da07469bbc121594bfd3e",slug:null,bookSignature:"Prof. Margherita Mori",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",editedByType:null,editors:[{id:"335401",title:"Prof.",name:"Margherita",surname:"Mori",slug:"margherita-mori",fullName:"Margherita Mori"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11439",title:"Crisis Management - Principles, Roles and Application",subtitle:null,isOpenForSubmission:!0,hash:"89fd49a084aea68bc39838042bdfce66",slug:null,bookSignature:"Ph.D. Carine J. Yi",coverURL:"https://cdn.intechopen.com/books/images_new/11439.jpg",editedByType:null,editors:[{id:"200332",title:"Ph.D.",name:"Carine",surname:"Yi",slug:"carine-yi",fullName:"Carine Yi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11479",title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",subtitle:null,isOpenForSubmission:!0,hash:"dbf515446deb32a56696801cd224984d",slug:null,bookSignature:"Ph.D. Andrzej Klimczuk",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",editedByType:null,editors:[{id:"320017",title:"Ph.D.",name:"Andrzej",surname:"Klimczuk",slug:"andrzej-klimczuk",fullName:"Andrzej Klimczuk"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11441",title:"Psychometrics - New Insights",subtitle:null,isOpenForSubmission:!0,hash:"c0fb1dfb98e0ae76496610595407145e",slug:null,bookSignature:" Sandro Misciagna",coverURL:"https://cdn.intechopen.com/books/images_new/11441.jpg",editedByType:null,editors:[{id:"103586",title:null,name:"Sandro",surname:"Misciagna",slug:"sandro-misciagna",fullName:"Sandro Misciagna"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11480",title:"Second Language Acquisition - Learning Theories and Recent Approaches",subtitle:null,isOpenForSubmission:!0,hash:"353e6f5278b4862f1f610fe7f1842125",slug:null,bookSignature:"Assistant Prof. Tabassum Maqbool",coverURL:"https://cdn.intechopen.com/books/images_new/11480.jpg",editedByType:null,editors:[{id:"450261",title:"Assistant Prof.",name:"Tabassum",surname:"Maqbool",slug:"tabassum-maqbool",fullName:"Tabassum Maqbool"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11772",title:"Corruption - New Insights",subtitle:null,isOpenForSubmission:!0,hash:"9cda6d2feaa52a6d523da74f2e2d7ffb",slug:null,bookSignature:"Dr. Josiane Fahed-Sreih",coverURL:"https://cdn.intechopen.com/books/images_new/11772.jpg",editedByType:null,editors:[{id:"103784",title:"Dr.",name:"Josiane",surname:"Fahed-Sreih",slug:"josiane-fahed-sreih",fullName:"Josiane Fahed-Sreih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11434",title:"Indigenous Populations - Perspectives From Scholars and Practitioners in Contemporary Times",subtitle:null,isOpenForSubmission:!0,hash:"c0d1c1c93a36fd9d726445966316a373",slug:null,bookSignature:"Dr. Sylvanus Gbendazhi Barnabas",coverURL:"https://cdn.intechopen.com/books/images_new/11434.jpg",editedByType:null,editors:[{id:"293764",title:"Dr.",name:"Sylvanus",surname:"Barnabas",slug:"sylvanus-barnabas",fullName:"Sylvanus Barnabas"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11782",title:"Personality Traits - The Role in Psychopathology",subtitle:null,isOpenForSubmission:!0,hash:"d3a491e5194cad4c59b900dd57a11842",slug:null,bookSignature:" Vladimir V. Kalinin",coverURL:"https://cdn.intechopen.com/books/images_new/11782.jpg",editedByType:null,editors:[{id:"31572",title:null,name:"Vladimir V.",surname:"Kalinin",slug:"vladimir-v.-kalinin",fullName:"Vladimir V. Kalinin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11601",title:"Econometrics - Recent Advances and Applications",subtitle:null,isOpenForSubmission:!0,hash:"bc8ab49e2cf436c217a49ca8c12a22eb",slug:null,bookSignature:"Dr. Brian Sloboda",coverURL:"https://cdn.intechopen.com/books/images_new/11601.jpg",editedByType:null,editors:[{id:"452331",title:"Dr.",name:"Brian",surname:"Sloboda",slug:"brian-sloboda",fullName:"Brian Sloboda"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:41},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:11},{group:"topic",caption:"Business, Management and Economics",value:7,count:6},{group:"topic",caption:"Chemistry",value:8,count:20},{group:"topic",caption:"Computer and Information Science",value:9,count:20},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:15},{group:"topic",caption:"Engineering",value:11,count:60},{group:"topic",caption:"Environmental Sciences",value:12,count:8},{group:"topic",caption:"Immunology and Microbiology",value:13,count:9},{group:"topic",caption:"Materials Science",value:14,count:27},{group:"topic",caption:"Mathematics",value:15,count:9},{group:"topic",caption:"Medicine",value:16,count:122},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:9},{group:"topic",caption:"Neuroscience",value:18,count:3},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:11},{group:"topic",caption:"Psychology",value:21,count:10},{group:"topic",caption:"Robotics",value:22,count:4},{group:"topic",caption:"Social Sciences",value:23,count:9},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:4}],offset:12,limit:12,total:25},popularBooks:{featuredBooks:[{type:"book",id:"10584",title:"Engineered Wood Products for Construction",subtitle:null,isOpenForSubmission:!1,hash:"421757c56a3735986055250821275a51",slug:"engineered-wood-products-for-construction",bookSignature:"Meng Gong",coverURL:"https://cdn.intechopen.com/books/images_new/10584.jpg",editors:[{id:"274242",title:"Dr.",name:"Meng",middleName:null,surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10222",title:"Demyelination Disorders",subtitle:null,isOpenForSubmission:!1,hash:"b6c26ceccacdde70c41c587361bd5558",slug:"demyelination-disorders",bookSignature:"Stavros J. Baloyannis, Fabian H. Rossi and Welwin Liu",coverURL:"https://cdn.intechopen.com/books/images_new/10222.jpg",editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",middleName:"J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9544",title:"Global Trade in the Emerging Business Environment",subtitle:null,isOpenForSubmission:!1,hash:"fb8cb09b9599246add78d508a98273d5",slug:"global-trade-in-the-emerging-business-environment",bookSignature:"Muhammad Mohiuddin, Jingbin Wang , Md. Samim Al Azad and Selim Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/9544.jpg",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10979",title:"Parenting",subtitle:"Challenges of Child Rearing in a Changing Society",isOpenForSubmission:!1,hash:"6f345ebcf4fd61e73643c69063a12c7b",slug:"parenting-challenges-of-child-rearing-in-a-changing-society",bookSignature:"Sayyed Ali Samadi",coverURL:"https://cdn.intechopen.com/books/images_new/10979.jpg",editors:[{id:"52145",title:"Dr.",name:"Sayyed Ali",middleName:null,surname:"Samadi",slug:"sayyed-ali-samadi",fullName:"Sayyed Ali Samadi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9808",title:"Contemporary Topics in Patient Safety",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"fb6371607c2c6c02c6a2af8892765aba",slug:"contemporary-topics-in-patient-safety-volume-1",bookSignature:"Stanislaw P. Stawicki and Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/9808.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10681",title:"Biodegradation Technology of Organic and Inorganic Pollutants",subtitle:null,isOpenForSubmission:!1,hash:"9a6e10e02788092872fd249436898e97",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants",bookSignature:"Kassio Ferreira Mendes, Rodrigo Nogueira de Sousa and Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",editors:[{id:"197720",title:"Ph.D.",name:"Kassio",middleName:null,surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10764",title:"Antenna Systems",subtitle:null,isOpenForSubmission:!1,hash:"2fbf1c7a5d92723f08198fc9b526a8ad",slug:"antenna-systems",bookSignature:"Hussain Al-Rizzo and Said Abushamleh",coverURL:"https://cdn.intechopen.com/books/images_new/10764.jpg",editors:[{id:"153384",title:"Prof.",name:"Hussain",middleName:null,surname:"Al-Rizzo",slug:"hussain-al-rizzo",fullName:"Hussain Al-Rizzo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10668",title:"Sustainability of Concrete With Synthetic and Recycled Aggregates",subtitle:null,isOpenForSubmission:!1,hash:"55856c6a8bc3a5b21dae5a1af09a56b6",slug:"sustainability-of-concrete-with-synthetic-and-recycled-aggregates",bookSignature:"Hosam M. Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/10668.jpg",editors:[{id:"144691",title:"Prof.",name:"Hosam",middleName:null,surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10803",title:"Reactive Oxygen Species",subtitle:null,isOpenForSubmission:!1,hash:"176adcf090fdd1f93cb8ce3146e79ca1",slug:"reactive-oxygen-species",bookSignature:"Rizwan Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",editors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9032",title:"Corporate Social Responsibility",subtitle:null,isOpenForSubmission:!1,hash:"f609bf3251d7cc7bae0099a4374adfc3",slug:"corporate-social-responsibility",bookSignature:"Beatrice Orlando",coverURL:"https://cdn.intechopen.com/books/images_new/9032.jpg",editors:[{id:"232969",title:"Prof.",name:"Beatrice",middleName:null,surname:"Orlando",slug:"beatrice-orlando",fullName:"Beatrice Orlando"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10351",title:"Enhanced Liposuction",subtitle:"New Perspectives and Techniques",isOpenForSubmission:!1,hash:"f08ed6de16da357614586c5b58ed4dfa",slug:"enhanced-liposuction-new-perspectives-and-techniques",bookSignature:"Diane Irvine Duncan",coverURL:"https://cdn.intechopen.com/books/images_new/10351.jpg",editors:[{id:"279869",title:"Dr.",name:"Diane Irvine",middleName:null,surname:"Duncan",slug:"diane-irvine-duncan",fullName:"Diane Irvine Duncan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10779",title:"21st Century Nanostructured Materials",subtitle:"Physics, Chemistry, Classification, and Emerging Applications in Industry, Biomedicine, and Agriculture",isOpenForSubmission:!1,hash:"72c67f97f9bef68200df115b5fd79884",slug:"21st-century-nanostructured-materials-physics-chemistry-classification-and-emerging-applications-in-industry-biomedicine-and-agriculture",bookSignature:"Phuong V. Pham",coverURL:"https://cdn.intechopen.com/books/images_new/10779.jpg",editors:[{id:"236073",title:"Dr.",name:"Phuong",middleName:"Viet",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4386},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"10584",title:"Engineered Wood Products for Construction",subtitle:null,isOpenForSubmission:!1,hash:"421757c56a3735986055250821275a51",slug:"engineered-wood-products-for-construction",bookSignature:"Meng Gong",coverURL:"https://cdn.intechopen.com/books/images_new/10584.jpg",publishedDate:"April 28th 2022",numberOfDownloads:3665,editors:[{id:"274242",title:"Dr.",name:"Meng",middleName:null,surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10222",title:"Demyelination Disorders",subtitle:null,isOpenForSubmission:!1,hash:"b6c26ceccacdde70c41c587361bd5558",slug:"demyelination-disorders",bookSignature:"Stavros J. Baloyannis, Fabian H. Rossi and Welwin Liu",coverURL:"https://cdn.intechopen.com/books/images_new/10222.jpg",publishedDate:"May 4th 2022",numberOfDownloads:1713,editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",middleName:"J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9544",title:"Global Trade in the Emerging Business Environment",subtitle:null,isOpenForSubmission:!1,hash:"fb8cb09b9599246add78d508a98273d5",slug:"global-trade-in-the-emerging-business-environment",bookSignature:"Muhammad Mohiuddin, Jingbin Wang , Md. Samim Al Azad and Selim Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/9544.jpg",publishedDate:"April 28th 2022",numberOfDownloads:2481,editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10979",title:"Parenting",subtitle:"Challenges of Child Rearing in a Changing Society",isOpenForSubmission:!1,hash:"6f345ebcf4fd61e73643c69063a12c7b",slug:"parenting-challenges-of-child-rearing-in-a-changing-society",bookSignature:"Sayyed Ali Samadi",coverURL:"https://cdn.intechopen.com/books/images_new/10979.jpg",publishedDate:"May 4th 2022",numberOfDownloads:1107,editors:[{id:"52145",title:"Dr.",name:"Sayyed Ali",middleName:null,surname:"Samadi",slug:"sayyed-ali-samadi",fullName:"Sayyed Ali Samadi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9808",title:"Contemporary Topics in Patient Safety",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"fb6371607c2c6c02c6a2af8892765aba",slug:"contemporary-topics-in-patient-safety-volume-1",bookSignature:"Stanislaw P. Stawicki and Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/9808.jpg",publishedDate:"April 20th 2022",numberOfDownloads:3307,editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10681",title:"Biodegradation Technology of Organic and Inorganic Pollutants",subtitle:null,isOpenForSubmission:!1,hash:"9a6e10e02788092872fd249436898e97",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants",bookSignature:"Kassio Ferreira Mendes, Rodrigo Nogueira de Sousa and Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",publishedDate:"April 20th 2022",numberOfDownloads:3266,editors:[{id:"197720",title:"Ph.D.",name:"Kassio",middleName:null,surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10764",title:"Antenna Systems",subtitle:null,isOpenForSubmission:!1,hash:"2fbf1c7a5d92723f08198fc9b526a8ad",slug:"antenna-systems",bookSignature:"Hussain Al-Rizzo and Said Abushamleh",coverURL:"https://cdn.intechopen.com/books/images_new/10764.jpg",publishedDate:"April 28th 2022",numberOfDownloads:1868,editors:[{id:"153384",title:"Prof.",name:"Hussain",middleName:null,surname:"Al-Rizzo",slug:"hussain-al-rizzo",fullName:"Hussain Al-Rizzo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10668",title:"Sustainability of Concrete With Synthetic and Recycled Aggregates",subtitle:null,isOpenForSubmission:!1,hash:"55856c6a8bc3a5b21dae5a1af09a56b6",slug:"sustainability-of-concrete-with-synthetic-and-recycled-aggregates",bookSignature:"Hosam M. Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/10668.jpg",publishedDate:"May 4th 2022",numberOfDownloads:856,editors:[{id:"144691",title:"Prof.",name:"Hosam",middleName:null,surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10803",title:"Reactive Oxygen Species",subtitle:null,isOpenForSubmission:!1,hash:"176adcf090fdd1f93cb8ce3146e79ca1",slug:"reactive-oxygen-species",bookSignature:"Rizwan Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",publishedDate:"April 28th 2022",numberOfDownloads:1704,editors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9032",title:"Corporate Social Responsibility",subtitle:null,isOpenForSubmission:!1,hash:"f609bf3251d7cc7bae0099a4374adfc3",slug:"corporate-social-responsibility",bookSignature:"Beatrice Orlando",coverURL:"https://cdn.intechopen.com/books/images_new/9032.jpg",publishedDate:"March 16th 2022",numberOfDownloads:7489,editors:[{id:"232969",title:"Prof.",name:"Beatrice",middleName:null,surname:"Orlando",slug:"beatrice-orlando",fullName:"Beatrice Orlando"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8737",title:"Rabies Virus at the Beginning of 21st Century",subtitle:null,isOpenForSubmission:!1,hash:"49cce3f548da548c718c865feb343509",slug:"rabies-virus-at-the-beginning-of-21st-century",bookSignature:"Sergey Tkachev",coverURL:"https://cdn.intechopen.com/books/images_new/8737.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10861",title:"Furan Derivatives",subtitle:"Recent Advances and Applications",isOpenForSubmission:!1,hash:"fdfc39cecd82f91b0effac994f75c877",slug:"furan-derivatives-recent-advances-and-applications",bookSignature:"Anish Khan, Mohammed Muzibur Rahman, M. Ramesh, Salman Ahmad Khan and Abdullah Mohammed Ahmed Asiri",coverURL:"https://cdn.intechopen.com/books/images_new/10861.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"293058",title:"Dr.",name:"Anish",middleName:null,surname:"Khan",slug:"anish-khan",fullName:"Anish Khan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10356",title:"Natural Medicinal Plants",subtitle:null,isOpenForSubmission:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",slug:"natural-medicinal-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10870",title:"Ultrasound Imaging",subtitle:"Current Topics",isOpenForSubmission:!1,hash:"2f0bc3733ab226d67fa73759ef0e12ad",slug:"ultrasound-imaging-current-topics",bookSignature:"Felix Okechukwu Erondu",coverURL:"https://cdn.intechopen.com/books/images_new/10870.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"68312",title:"Prof.",name:"Felix",middleName:null,surname:"Okechukwu Erondu",slug:"felix-okechukwu-erondu",fullName:"Felix Okechukwu Erondu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11392",title:"Leadership in a Changing World",subtitle:"A Multidimensional Perspective",isOpenForSubmission:!1,hash:"86a6d33cf601587e591064ce92effc02",slug:"leadership-in-a-changing-world-a-multidimensional-perspective",bookSignature:"Muhammad Mohiuddin, Bilal Khalid, Md. Samim Al Azad and Slimane Ed-dafali",coverURL:"https://cdn.intechopen.com/books/images_new/11392.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10400",title:"The Application of Ant Colony Optimization",subtitle:null,isOpenForSubmission:!1,hash:"f4fdfd07ee1ab99fb7c740d6d0c144c6",slug:"the-application-of-ant-colony-optimization",bookSignature:"Ali Soofastaei",coverURL:"https://cdn.intechopen.com/books/images_new/10400.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"257455",title:"Dr.",name:"Ali",middleName:null,surname:"Soofastaei",slug:"ali-soofastaei",fullName:"Ali Soofastaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10915",title:"Leadership",subtitle:"New Insights",isOpenForSubmission:!1,hash:"0d72e79892f2a020cee66a52d09de5a4",slug:"leadership-new-insights",bookSignature:"Mário Franco",coverURL:"https://cdn.intechopen.com/books/images_new/10915.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"105529",title:"Dr.",name:"Mário",middleName:null,surname:"Franco",slug:"mario-franco",fullName:"Mário Franco"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10683",title:"Technological Innovations and Advances in Hydropower Engineering",subtitle:null,isOpenForSubmission:!1,hash:"7ce7ad8768bd2cad155470fe1fd883f4",slug:"technological-innovations-and-advances-in-hydropower-engineering",bookSignature:"Yizi Shang, Ling Shang and Xiaofei Li",coverURL:"https://cdn.intechopen.com/books/images_new/10683.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7102",title:"Pneumonia",subtitle:null,isOpenForSubmission:!1,hash:"9fd70142814192dcec58a176749f1b60",slug:"pneumonia",bookSignature:"Nima Rezaei",coverURL:"https://cdn.intechopen.com/books/images_new/7102.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9670",title:"Current Trends in Wheat Research",subtitle:null,isOpenForSubmission:!1,hash:"89d795987f1747a76eee532700d2093d",slug:"current-trends-in-wheat-research",bookSignature:"Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9670.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1147",title:"Microsurgery",slug:"microsurgery",parent:{id:"202",title:"Surgery",slug:"surgery"},numberOfBooks:3,numberOfSeries:0,numberOfAuthorsAndEditors:70,numberOfWosCitations:54,numberOfCrossrefCitations:29,numberOfDimensionsCitations:86,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1147",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"3434",title:"Breast Reconstruction",subtitle:"Current Perspectives and State of the Art Techniques",isOpenForSubmission:!1,hash:"6628e9605fb2786daff7995a63f6b141",slug:"breast-reconstruction-current-perspectives-and-state-of-the-art-techniques",bookSignature:"Aldona J. Spiegel",coverURL:"https://cdn.intechopen.com/books/images_new/3434.jpg",editedByType:"Edited by",editors:[{id:"84552",title:"Dr.",name:"Aldona",middleName:null,surname:"Spiegel",slug:"aldona-spiegel",fullName:"Aldona Spiegel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"565",title:"Breast Reconstruction",subtitle:"Current Techniques",isOpenForSubmission:!1,hash:"2f615cbc43fe8e385eec27115a59defe",slug:"breast-reconstruction-current-techniques",bookSignature:"Marzia Salgarello",coverURL:"https://cdn.intechopen.com/books/images_new/565.jpg",editedByType:"Edited by",editors:[{id:"71121",title:"Dr.",name:"Marzia",middleName:null,surname:"Salgarello",slug:"marzia-salgarello",fullName:"Marzia Salgarello"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"784",title:"Selected Topics in Plastic Reconstructive Surgery",subtitle:null,isOpenForSubmission:!1,hash:"8c900031e8c6bc725799ec77cc210718",slug:"selected-topics-in-plastic-reconstructive-surgery",bookSignature:"Stefan Danilla",coverURL:"https://cdn.intechopen.com/books/images_new/784.jpg",editedByType:"Edited by",editors:[{id:"59459",title:"Dr.",name:"Stefan",middleName:null,surname:"Danilla",slug:"stefan-danilla",fullName:"Stefan Danilla"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"26559",doi:"10.5772/28833",title:"Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections",slug:"local-antibiotic-therapy-in-the-treatment-of-bone-and-soft-tissue-infections",totalDownloads:6534,totalCrossrefCites:5,totalDimensionsCites:21,abstract:null,book:{id:"784",slug:"selected-topics-in-plastic-reconstructive-surgery",title:"Selected Topics in Plastic Reconstructive Surgery",fullTitle:"Selected Topics in Plastic Reconstructive Surgery"},signatures:"Stefanos Tsourvakas",authors:[{id:"75532",title:"Dr.",name:"Stefanos",middleName:null,surname:"Tsourvakas",slug:"stefanos-tsourvakas",fullName:"Stefanos Tsourvakas"}]},{id:"27943",doi:"10.5772/39212",title:"One-Stage Immediate Breast Reconstruction with Implants in Conservative Mastectomies",slug:"one-stage-immediate-breast-reconstruction-with-implants-in-conservative-mastectomies",totalDownloads:5845,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"565",slug:"breast-reconstruction-current-techniques",title:"Breast Reconstruction",fullTitle:"Breast Reconstruction - Current Techniques"},signatures:"Marzia Salgarello, Giuseppe Visconti and Liliana Barone-Adesi",authors:[{id:"71121",title:"Dr.",name:"Marzia",middleName:null,surname:"Salgarello",slug:"marzia-salgarello",fullName:"Marzia Salgarello"}]},{id:"26564",doi:"10.5772/31520",title:"Reconstruction of Perineum and Abdominal Wall",slug:"reconstruction-of-perineum-and-abdominal-wall",totalDownloads:6591,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"784",slug:"selected-topics-in-plastic-reconstructive-surgery",title:"Selected Topics in Plastic Reconstructive Surgery",fullTitle:"Selected Topics in Plastic Reconstructive Surgery"},signatures:"J.J. Vranckx and A. D’Hoore",authors:[{id:"83351",title:"Prof.",name:"Jan Jeroen",middleName:null,surname:"Vranckx",slug:"jan-jeroen-vranckx",fullName:"Jan Jeroen Vranckx"}]},{id:"27944",doi:"10.5772/29373",title:"The Effect of Breast Reconstruction on Maintaining a Proper Body Posture in Patients After Mastectomy",slug:"the-influence-of-immediate-breast-reconstruction-on-proper-body-posture-in-women-after-mastectomy-fo",totalDownloads:9958,totalCrossrefCites:3,totalDimensionsCites:6,abstract:null,book:{id:"565",slug:"breast-reconstruction-current-techniques",title:"Breast Reconstruction",fullTitle:"Breast Reconstruction - Current Techniques"},signatures:"Sławomir Cieśla and Małgorzata Bąk",authors:[{id:"77539",title:"M.D.",name:"Slawomir",middleName:"Szczepan",surname:"Ciesla",slug:"slawomir-ciesla",fullName:"Slawomir Ciesla"},{id:"81605",title:"Dr.",name:"Malgorzata",middleName:null,surname:"Bak",slug:"malgorzata-bak",fullName:"Malgorzata Bak"}]},{id:"45501",doi:"10.5772/56465",title:"Treatment of Breast Cancer-Related Lymphedema Using Combined Autologous Breast Reconstruction and Autologous Lymph Node Transplantation",slug:"treatment-of-breast-cancer-related-lymphedema-using-combined-autologous-breast-reconstruction-and-au",totalDownloads:2390,totalCrossrefCites:1,totalDimensionsCites:6,abstract:null,book:{id:"3434",slug:"breast-reconstruction-current-perspectives-and-state-of-the-art-techniques",title:"Breast Reconstruction",fullTitle:"Breast Reconstruction - Current Perspectives and State of the Art Techniques"},signatures:"Corinne Becker",authors:[{id:"162398",title:"Dr.",name:"Corinne",middleName:null,surname:"Becker",slug:"corinne-becker",fullName:"Corinne Becker"}]}],mostDownloadedChaptersLast30Days:[{id:"44328",title:"Septocutaneous Gluteal Artery Perforator (Sc-GAP) Flap for Breast Reconstruction: How We Do It",slug:"septocutaneous-gluteal-artery-perforator-sc-gap-flap-for-breast-reconstruction-how-we-do-it",totalDownloads:2787,totalCrossrefCites:0,totalDimensionsCites:1,abstract:null,book:{id:"3434",slug:"breast-reconstruction-current-perspectives-and-state-of-the-art-techniques",title:"Breast Reconstruction",fullTitle:"Breast Reconstruction - Current Perspectives and State of the Art Techniques"},signatures:"Stefania Tuinder, Rene Van Der Hulst, Marc Lobbes, Bas Versluis\nand Arno Lataster",authors:[{id:"89389",title:"Dr.",name:"Marc",middleName:null,surname:"Lobbes",slug:"marc-lobbes",fullName:"Marc Lobbes"},{id:"161517",title:"Dr.",name:"Stefania",middleName:null,surname:"Tuinder",slug:"stefania-tuinder",fullName:"Stefania Tuinder"},{id:"167270",title:"Dr.",name:"Rene",middleName:null,surname:"Van Der Hulst",slug:"rene-van-der-hulst",fullName:"Rene Van Der Hulst"},{id:"167272",title:"Dr.",name:"B",middleName:null,surname:"Versluis",slug:"b-versluis",fullName:"B Versluis"},{id:"167273",title:"Dr.",name:"Arno",middleName:null,surname:"Lataster",slug:"arno-lataster",fullName:"Arno Lataster"}]},{id:"26561",title:"Head and Neck Reconstructive Surgery",slug:"head-and-neck-reconstructive-surgery",totalDownloads:4510,totalCrossrefCites:1,totalDimensionsCites:1,abstract:null,book:{id:"784",slug:"selected-topics-in-plastic-reconstructive-surgery",title:"Selected Topics in Plastic Reconstructive Surgery",fullTitle:"Selected Topics in Plastic Reconstructive Surgery"},signatures:"J.J. Vranckx and P. Delaere",authors:[{id:"83351",title:"Prof.",name:"Jan Jeroen",middleName:null,surname:"Vranckx",slug:"jan-jeroen-vranckx",fullName:"Jan Jeroen Vranckx"}]},{id:"44470",title:"Implant-Based Dual-Plane Reconstruction of the Breast Following Sparing Mastectomy",slug:"implant-based-dual-plane-reconstruction-of-the-breast-following-sparing-mastectomy",totalDownloads:3308,totalCrossrefCites:0,totalDimensionsCites:3,abstract:null,book:{id:"3434",slug:"breast-reconstruction-current-perspectives-and-state-of-the-art-techniques",title:"Breast Reconstruction",fullTitle:"Breast Reconstruction - Current Perspectives and State of the Art Techniques"},signatures:"Egidio Riggio and Maurizio B. Nava",authors:[{id:"74479",title:"Dr.",name:"Egidio",middleName:null,surname:"Riggio",slug:"egidio-riggio",fullName:"Egidio Riggio"},{id:"162971",title:"Dr.",name:"Maurizio",middleName:null,surname:"Nava",slug:"maurizio-nava",fullName:"Maurizio Nava"}]},{id:"45197",title:"Robotic Harvest of the Latissimus Dorsi Muscle for Breast Reconstruction",slug:"robotic-harvest-of-the-latissimus-dorsi-muscle-for-breast-reconstruction",totalDownloads:1898,totalCrossrefCites:0,totalDimensionsCites:3,abstract:null,book:{id:"3434",slug:"breast-reconstruction-current-perspectives-and-state-of-the-art-techniques",title:"Breast Reconstruction",fullTitle:"Breast Reconstruction - Current Perspectives and State of the Art Techniques"},signatures:"Jesse Selber",authors:[{id:"161370",title:"Dr",name:"Jesse",middleName:null,surname:"Selber",slug:"jesse-selber",fullName:"Jesse Selber"}]},{id:"26564",title:"Reconstruction of Perineum and Abdominal Wall",slug:"reconstruction-of-perineum-and-abdominal-wall",totalDownloads:6598,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"784",slug:"selected-topics-in-plastic-reconstructive-surgery",title:"Selected Topics in Plastic Reconstructive Surgery",fullTitle:"Selected Topics in Plastic Reconstructive Surgery"},signatures:"J.J. Vranckx and A. D’Hoore",authors:[{id:"83351",title:"Prof.",name:"Jan Jeroen",middleName:null,surname:"Vranckx",slug:"jan-jeroen-vranckx",fullName:"Jan Jeroen Vranckx"}]}],onlineFirstChaptersFilter:{topicId:"1147",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:285,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"