Demographic and clinical details of patients enrolled in Indian studies.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{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"}]},book:{item:{type:"book",id:"7233",leadTitle:null,fullTitle:"New Insights into Theriogenology",title:"New Insights into Theriogenology",subtitle:null,reviewType:"peer-reviewed",abstract:"This book covers a variety of topics on animal reproduction and reproductive medicine. With evolving technology and a continual increase in knowledge, regarding domestic pets or agricultural animals, new information is available on diverse topics in this broad field. The book contents reflect the individual experience of authors, who developed a number of themes identified as attracting interest in the field. As it is, new opportunities were opened for productive collaboration. We have tried to provide you with current, specialised information that may be useful to students, clinicians and researchers. We hope this book inspires you to embrace these themes, foster the debate on particular topics and may be used as a start-up source for exploring the theriogenology field.",isbn:"978-1-78984-773-4",printIsbn:"978-1-78984-772-7",pdfIsbn:"978-1-83881-782-4",doi:"10.5772/intechopen.74197",price:119,priceEur:129,priceUsd:155,slug:"new-insights-into-theriogenology",numberOfPages:160,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"74f4147e3fb214dd050e5edd3aaf53bc",bookSignature:"Rita Payan-Carreira",publishedDate:"December 5th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",numberOfDownloads:9949,numberOfWosCitations:13,numberOfCrossrefCitations:16,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:25,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:54,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2018",dateEndSecondStepPublish:"March 2nd 2018",dateEndThirdStepPublish:"May 1st 2018",dateEndFourthStepPublish:"July 20th 2018",dateEndFifthStepPublish:"September 18th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1382",title:"Theriogenology",slug:"genesiology-theriogenology"}],chapters:[{id:"63752",title:"Reproduction in the Female Mithun",doi:"10.5772/intechopen.81037",slug:"reproduction-in-the-female-mithun",totalDownloads:1191,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Mithun is a domesticated beef bovine species in Himalayan foothills of Southeast Asia. It inhabits at an altitude from 300 to 3000 m MSL, often under extensive grazing system. Mithun is a very fertile animal, able to produce one calf/year. Mithun can interbreed with other bovine species, but male offspring are sterile. This chapter intent is to gather and discuss available information on several aspects of reproduction in female Mithun. The morphology of the reproductive organs is different from cattle and has a longer reproductive tract and pregnancies compared to cattle. Although its estrus period is longer than in cow, Mithun usually displays silent heats, requiring a breeding bull for heat detection. Seasonal fluctuations on reproductive pattern have been reported, which are related to forage availability and quality. Calving in summer takes longer to resumption of cyclic ovarian activity than calving in winter. As Mithun is an important socio-cultural-religious-economic asset in India, to counter some short comings, new breeding strategies have been introduced like multiple ovulation and embryo transfer technology. A good understanding of different aspects of reproduction is crucial to support effective reproductive managements to enhance socio-economic status and cultural importance of tribals to preserve Mithun germplasm to be used in future.",signatures:"Perumal Ponraj",downloadPdfUrl:"/chapter/pdf-download/63752",previewPdfUrl:"/chapter/pdf-preview/63752",authors:[{id:"249114",title:"Dr.",name:"Ponraj",surname:"Perumal",slug:"ponraj-perumal",fullName:"Ponraj Perumal"}],corrections:null},{id:"63702",title:"Spermatogenesis and Its Significance in Reproductive Medicine",doi:"10.5772/intechopen.80764",slug:"spermatogenesis-and-its-significance-in-reproductive-medicine",totalDownloads:1155,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"As infertility rates across nations become a growing concern, the interest in the development of treatments, such as in vitro gametogenesis (IVG), increases. This is especially the case for male infertility. For instance, the average sperm count continues to decline across nations, while more adult and pediatric patients survive cancer only to be left with little to no options for fertility restorative therapies. Understanding the male reproductive system and the process of spermatogenesis, however, has proven to be a difficult task. Progress occurs slowly and inconsistencies remain in the literature while reports attempt to better understand spermatogonial stem cells (SSCs) in conjunction with spermatogenesis. Interestingly, stem cell behavior, the decision to self-renewal or commit to differentiation, has shown to be closely linked to the stem cell’s microenvironment (i.e. niche). Perhaps the missing pieces required to better understanding spermatogenesis are found in the re-defined perspective of SSC niche dynamics.",signatures:"Vittorio Sebastiano and Auriana Arabpour",downloadPdfUrl:"/chapter/pdf-download/63702",previewPdfUrl:"/chapter/pdf-preview/63702",authors:[{id:"180522",title:"Prof.",name:"Vittorio",surname:"Sebastiano",slug:"vittorio-sebastiano",fullName:"Vittorio Sebastiano"},{id:"252485",title:"Ms.",name:"Auriana",surname:"Arabpour",slug:"auriana-arabpour",fullName:"Auriana Arabpour"}],corrections:null},{id:"63607",title:"The Adipokines in Domestic Animal Reproduction: Expression and Role in the Regulation of Ovarian Function",doi:"10.5772/intechopen.81035",slug:"the-adipokines-in-domestic-animal-reproduction-expression-and-role-in-the-regulation-of-ovarian-func",totalDownloads:1157,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Currently, it is clear that female reproduction is regulated by the hypothalamic–pituitary-ovary axis, which produces many hormones that control reproductive stages. It is therefore important to have knowledge of new regulators/hormones controlling reproduction in domestic animals. In female animals, energy metabolism and fertility are tightly connected, and reciprocally regulated. The adipose tissue is well known to be implicated in the secretion of several hormones, such as the adiponectin, resistin, chemerin, visfatin, vaspin and apelin, the so-called adipokines or “adipose tissue-derived hormones”. Many reports indicate that adipokines regulate the ovarian follicles’ development, the onset of puberty and/or ovulation. This chapter summarizes that several adipokines are expressed in the ovary and that they can regulate ovarian physiology such as the steroid hormone production, cell proliferation, apoptosis and oocyte maturation in different domestic animals like pigs, cows, goats, ewes, chickens and turkeys.",signatures:"Patrycja Kurowska, Ewa Mlyczyńska, Alix Barbe, Namya Mellouk,\nJoelle Dupont and Agnieszka Rak",downloadPdfUrl:"/chapter/pdf-download/63607",previewPdfUrl:"/chapter/pdf-preview/63607",authors:[{id:"107080",title:"Dr.",name:"Agnieszka",surname:"Rak",slug:"agnieszka-rak",fullName:"Agnieszka Rak"},{id:"256956",title:"Mrs.",name:"Patrycja",surname:"Kurowska",slug:"patrycja-kurowska",fullName:"Patrycja Kurowska"},{id:"256957",title:"Mrs.",name:"Justyna",surname:"Chmielińska",slug:"justyna-chmielinska",fullName:"Justyna Chmielińska"},{id:"256959",title:"Mrs.",name:"Ewa",surname:"Mlyczyńska",slug:"ewa-mlyczynska",fullName:"Ewa Mlyczyńska"},{id:"256960",title:"Mrs.",name:"Alix",surname:"Barbe",slug:"alix-barbe",fullName:"Alix Barbe"},{id:"256961",title:"Mrs.",name:"Namya",surname:"Mellouk",slug:"namya-mellouk",fullName:"Namya Mellouk"},{id:"256962",title:"Prof.",name:"Joelle",surname:"Dupont",slug:"joelle-dupont",fullName:"Joelle Dupont"}],corrections:null},{id:"63455",title:"Application of Some Proteome Analysis Techniques in Animal Reproduction",doi:"10.5772/intechopen.80521",slug:"application-of-some-proteome-analysis-techniques-in-animal-reproduction",totalDownloads:1228,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter focuses on the application of proteome analysis techniques to animal reproduction and provides general information on one-dimensional (1D) and two-dimensional (2D) electrophoresis, chromatographic methods, and mass spectrometer (MS), widely used in proteomics studies. Proteome consists of an entire complement of proteins expressed by a cell, tissue, or organism. Proteomics reveals functions of proteins encoded in the genome. These functions include posttranslational modifications (PTMs) and alterations in the protein synthesis. Animal reproduction takes a key role in livestock, and increasing the reproduction rate in flocks plays an important role in livestock management. Studying the proteins related to reproduction could guide on how to increase fertility. Recent studies addressed the proteome constitution of both male and female reproductive system. Follicular fluid, endometrium, and ovary proteins were analyzed in females by proteomics study, while in males, sperm proteomics was more focused. Information obtained on this issue is also beneficial for the development of reproductive technologies such as in vitro fertilization and embryo transfer. Strategies to increase fertility in animals can be revealed by proteomic studies, and a more profound knowledge on proteomics may become helpful to develop and enhance the efficiency of reproductive technologies.",signatures:"Yasin Baykalir, Burcu Gul Baykalir and Ulku Gulcihan Simsek",downloadPdfUrl:"/chapter/pdf-download/63455",previewPdfUrl:"/chapter/pdf-preview/63455",authors:[{id:"245625",title:"Dr.",name:"Yasin",surname:"Baykalir",slug:"yasin-baykalir",fullName:"Yasin Baykalir"}],corrections:null},{id:"63404",title:"Subclinical Endometritis in Dairy Cattle",doi:"10.5772/intechopen.80229",slug:"subclinical-endometritis-in-dairy-cattle",totalDownloads:1859,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Subclinical endometritis is recognized as a cause of poor reproductive performance in dairy cows. Inflammation of the endometrium persisting after postpartum uterine involution has been related with prolonged calving-conception intervals and low fertility in dairy cows. The subclinical nature of this condition makes it necessary in the use of endometrial cytology or biopsy for diagnosing it. There are some controversies among authors in relation to the postpartum period from which a physiological endometrial inflammation should be considered a pathological subclinical endometritis. Therefore, depending on the sampling period after calving, different studies establish a different degree of polymorphonuclear leukocyte infiltration as cutoff point to diagnose subclinical endometritis. Controversies also exist regarding the pathogenesis of the disease and its consequences on the fertility of dairy cattle. The aim of this chapter was to review the current knowledge on this uterine pathology.",signatures:"Luis Angel Quintela Arias, Marcos Vigo Fernández, Juan José\nBecerra González, Mónica Barrio López, Pedro José García Herradón\nand Ana Isabel Peña Martínez",downloadPdfUrl:"/chapter/pdf-download/63404",previewPdfUrl:"/chapter/pdf-preview/63404",authors:[{id:"243272",title:"Prof.",name:"Luis Angel",surname:"Quintela Arias",slug:"luis-angel-quintela-arias",fullName:"Luis Angel Quintela Arias"},{id:"243886",title:"Prof.",name:"Ana Isabel",surname:"Peña Martínez",slug:"ana-isabel-pena-martinez",fullName:"Ana Isabel Peña Martínez"},{id:"243887",title:"Prof.",name:"Pedro",surname:"García Herradón",slug:"pedro-garcia-herradon",fullName:"Pedro García Herradón"},{id:"243888",title:"Prof.",name:"Juan José",surname:"Becerra González",slug:"juan-jose-becerra-gonzalez",fullName:"Juan José Becerra González"},{id:"256852",title:"Dr.",name:"Mónica",surname:"Barrio López",slug:"monica-barrio-lopez",fullName:"Mónica Barrio López"},{id:"256854",title:"Dr.",name:"Marcos",surname:"Vigo Fernández",slug:"marcos-vigo-fernandez",fullName:"Marcos Vigo Fernández"}],corrections:null},{id:"63835",title:"Apoptosis as the Major Cause of Embryonic Mortality in Cattle",doi:"10.5772/intechopen.81295",slug:"apoptosis-as-the-major-cause-of-embryonic-mortality-in-cattle",totalDownloads:1e3,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Besides several mechanisms such as autophagy, necroptosis, and pyroptosis, programmed cell death (PCD) also includes apoptosis which is characterized by membrane blebbing, chromatin condensation, and DNA fragmentation which involves a number of membrane receptors and a cascade of signal transduction steps resulting in the activation of an ample number of proteases known as caspases. Even though this mechanism plays a significant role in the progressions of gamete maturation and embryo development, contributing to the formation of different organs and structures, they also lead to the death of blastomeres and, consequently, the occurrence of structural abnormalities, increasing embryo and fetal mortality. Therefore, understanding the mechanisms involved in apoptosis dysregulation may contribute to the development of new therapeutic methods to prevent various developmental abnormalities. The purpose of this chapter is to review recent research into the mechanisms of programmed cell death, focusing on apoptosis during embryo development leading to embryo mortality. The final section includes a discussion of the implication of the findings for future research on reducing embryo mortality in the bovine.",signatures:"Helena Moreira da Silva, Loide Isabel Valadão and Fernando\nMoreira da Silva",downloadPdfUrl:"/chapter/pdf-download/63835",previewPdfUrl:"/chapter/pdf-preview/63835",authors:[{id:"191057",title:"Prof.",name:"Fernando",surname:"Moreira Da Silva",slug:"fernando-moreira-da-silva",fullName:"Fernando Moreira Da Silva"}],corrections:null},{id:"63632",title:"Embryo Manipulation Techniques in the Rabbit",doi:"10.5772/intechopen.81089",slug:"embryo-manipulation-techniques-in-the-rabbit",totalDownloads:1203,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Rabbits are both productive and classic laboratory animals. Some particularities of female reproductive physiology make the rabbit an extraordinary model for the study of embryology and assisted reproductive techniques. For instance, as the ovulation is induced, the embryo development can be known with accuracy. Embryos are surrounded by a mucin coat which is crucial to prevent embryo mortality. Besides, the anatomy of the uterus does not allow embryo transmigration between both uterine horns, and so it is possible to test different reproductive techniques. Knowledge on early embryo development, and on influencing factors, has allowed to develop new insights into embryo manipulation, such as recovery, transfer, cryopreservation, in vitro fertilisation, cloning, or transgenesis. Also the rabbit may be used as a model for human reproductive health, because rabbit embryo and feto-placental development are similar to the human. This chapter reviews the aspects of the reproductive physiology in the female rabbit and discusses some embryo manipulation techniques available in the species.",signatures:"María-Luz García",downloadPdfUrl:"/chapter/pdf-download/63632",previewPdfUrl:"/chapter/pdf-preview/63632",authors:[{id:"245306",title:"Dr.",name:"María Luz",surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo"}],corrections:null},{id:"62171",title:"Intraoviductal Instillation of a Solution as an Effective Route for Manipulating Preimplantation Mammalian Embryos in vivo",doi:"10.5772/intechopen.79106",slug:"intraoviductal-instillation-of-a-solution-as-an-effective-route-for-manipulating-preimplantation-mam",totalDownloads:1158,totalCrossrefCites:8,totalDimensionsCites:9,hasAltmetrics:0,abstract:"Preimplantation embryos of mammals are enclosed by a translucent layer called zona pellucida (ZP), which is composed of glycoproteins. ZP is important for protecting against infection by virus and bacteria, and to prevent attachment of embryos to the oviductal epithelia. Due to the presence of ZP, it has been difficult to transfect preimplantation embryos existing within the oviductal lumen, with exogenous nucleic acids, such as DNA and mRNA. However, intraoviductal instillation of nucleic acids, and subsequent in vivo electroporation in pregnant females, enables transfection of these embryos, leading to the production of gene-modified animals. This new method for production of genetically modified animals does not require any ex vivo handling of embryos, which has been essential for traditional transgenesis. In this article, we describe recent advances in the in vivo transfection of preimplantation mammalian embryos, and also the possibility of simple transfection of these embryos through intraoviductal instillation of a solution, alone.",signatures:"Masahiro Sato, Masato Ohtsuka and Shingo Nakamura",downloadPdfUrl:"/chapter/pdf-download/62171",previewPdfUrl:"/chapter/pdf-preview/62171",authors:[{id:"177440",title:"Dr.",name:"Masato",surname:"Ohtsuka",slug:"masato-ohtsuka",fullName:"Masato Ohtsuka"},{id:"177444",title:"Dr.",name:"Shingo",surname:"Nakamura",slug:"shingo-nakamura",fullName:"Shingo Nakamura"},{id:"245795",title:"Prof.",name:"Masahiro",surname:"Sato",slug:"masahiro-sato",fullName:"Masahiro Sato"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"28",series:{id:"13",title:"Veterinary Medicine and Science",issn:"2632-0517",editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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WHO 2016 classification for lymphomas [1] defines primary central nervous system lymphoma as a rare and aggressive form of extranodal diffuse large B-cell lymphoma (DLBCL) involving the brain, leptomeninges, or eyes without any systemic involvement. However, this entity responded poorly to conventional DLBCL regimens [2, 3] despite using radiotherapy or dexamethasone to enhance CNS efficacy. Further evidence supporting PCNSL as a distinct entity comes from studies showing unique GEP signatures [4] and transcriptomics (with heavy reliance on NF-KB) [5] compared to its nodal counterparts.
PCNSL is predominantly a disease of the elderly [6] and presents with focal deficits followed by features of raised intracranial pressure [7]. Initially suspected on MRI, it is typically diagnosed by a stereotactic biopsy or by cerebrospinal fluid evaluation in exceptional circumstances [8]. Modern management is based on HD-MTX based polychemotherapy followed by consolidative therapy in the form of WBRT, standard-dose chemotherapy or high-dose chemotherapy followed by stem cell transplantation. Rituximab addition may improve outcomes [9]. Novel ibrutinib-based combinations are used in relapsed settings and are being evaluated in the frontline settings as well [10].
In the LMIC, the lack of availability of HD-MTX and neurosurgical suites make management of PCNSL difficult. Novel MRI-based sequences, ibrutinib-based regimes, and utilization of consolidative WBRT may ease the burden. This review details the epidemiological, clinical, and radiological features of PCNSL with a focus on the Indian subcontinent. Furthermore, the current standard of therapy and potential modifications for easier delivery in the LMIC is also detailed.
Overall, the age-adjusted incidence rate (SEER database) of PCNSL is .47 cases per 10,000,000 people per year [11].
The incidence is increasing in elderly males for unclear reasons. Variations in CD4 subpopulations could be a likely cause [12].
From India, only two studies have reported temporal incidence trends. One study reported a 3.5× increase in the number of cases without any change in the proportion of all CNS neoplasms from 1980 to 2003 [13]. Another study done at a single center in northern India found no temporal variation in incidence [14].
PCNSL accounts for 4% of all primary CNS tumors as per western data [15]. Two Indian studies, however, report a more conservative estimate of 0.92–0.95% [13] and 1.2% [14].
PCNSL is an uncommon NHL accounting for 4–6% of all extranodal lymphomas [11] and less than 1% of all NHLs as per western literature. A study from Southern India reports that PCNSL accounts for 9.6% of all primary extranodal lymphomas and roughly 3% of all NHLs [16].
Table 1 contains the demographic details of PCNSL patients recruited in Indian studies.
Study (n) | Demographics | Clinical presentation | Investigations | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Median age (years) | Males (%) | HIV positive (%) | Median duration of symptoms (Months) | Most common presenting feature | Eye involvement (%) | Leptomeningeal involvement (%) | ECOG PS | Raised LDH (%) | Histopathology | Stereotactic biopsy (%) | Inadvertent resection (%) | Multiple lesions (%) | |
Patekar et al. (n = 99) | 50 | 65.60 | 1.10 | 3.5 | Neurological deficit | 19.40 | 15.8 | 58.5% PS ≥ 3 | 19.40 | DLBCL (97.7%) | 49 | 40 | 81.80 |
Adhikari et al. (n = 22) | 51.5 | 59 | 0 | 4 | Neurological deficit | 22.70 | 13.64 | 59.9% PS ≥ 3 | 45.45 | DLBCL (100%) | 50 | 50 | 75 |
Patel et al. (n = 73) | 46 | 66 | 0 | 2.5 | Raised ICP | — | — | — | — | DLBCL (95.9%) | 54.80 | 45.20 | 64.40 |
Powari et al. (n = 40) | 50 | 66 | 0 | — | Raised ICP | — | — | — | — | DLBCL (100%) | — | 100 | 87.50 |
Paul et al. (n = 56) | 42 | 60 | 0.90 | — | Raised ICP | — | — | — | — | DLBCL (93.2%) | — | — | 21.40 |
Mahadevan et al. (n = 24) | 53 | 58.33 | 0 | — | Raised ICP | — | — | — | — | DLBCL (100%) | — | — | — |
Dash et al. (n = 41) | 52 | 53.40 | 0 | — | Raised ICP | — | — | — | — | DLBCL (100%) | — | — | — |
Sarkar et al. (n = 116) | 44.4 | 69.30 | 0.80 | — | — | — | — | — | — | DLBCL (100%) | — | — | — |
Parischa et al. (n = 66) | 46 | 50 | 0 | — | Raised ICP | — | — | — | — | DLBCL (100%) | — | — | 15 |
Sharma et al. (n = 65) | 49 | 58.30 | 0 | — | — | — | 3 | — | — | DLBCL (100%) | — | — | 41.53 |
Yadav et al. (n = 32) | 50 | 71 | 0 | — | Raised ICP | 0 | 0 | — | — | DLBCL (100%) | — | — | 68.80 |
Rudresha et al. (n = 26) | 42.5 | 65.30 | — | Raised ICP | 0 | 4 | — | 30.70 | DLBCL (96%) | 46 | 54 | 38.50 | |
Rudresha et al. (n = 53) | 44 | 64 | 3.70 | — | Raised ICP | 0 | 6 | — | 32 | DLBCL (100%) | 49 | 51 | 30 |
Kumari et al. (n = 30) | 47.8 | 60 | 0 | — | Raised ICP | — | — | 70% with PS ≥ 3 | 70 | DLBCL (100%) | — | — | 66 |
Puligundla et al. (n = 42) | 46 | 68.70 | 4.70 | — | Raised ICP | 0 | 15.80 | 80.9% PS ≥ 2 | — | DLBCL (97.6%) | 42.80 | 57.10 | 23.80 |
Agarwal et al. (n = 26) | 59 | 61.50 | 7.60 | 3 | Neurological deficit | — | 19.20 | — | 34.60 | DLBCL (96.1%) | — | — | 77 |
Demographic and clinical details of patients enrolled in Indian studies.
In Western settings, non-HIV infected PCNSL is typically diagnosed at 45–65 years of age (median age of diagnosis in the fifth decade) with no gender predilection [6, 17, 18, 19]. However, the Indian demographic differs in having a younger affected population (median age at diagnosis ranging from 42 to 59 years) with slight male preponderance [13, 14, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31]. These changes are more likely from different population demographics rather than inherent disease biology, given that individuals aged more than 60 or 65 consistently amount to less than 9% and 7% of the total Indian population respectively [32].
HIV-infected individuals are also a younger cohort (Median age: 37 years) with a male preponderance [12].
Among transplant recipients: CNS involvement is present in 15% of all NHL cases [33] and is associated with a poorer prognosis [34]. However, amounting to only 0.9% of all PCNSL cases, this subset is not well studied [12].
The prevalence of HIV in PCNSL patients is estimated to be 6.1% globally, with significant variation among nations [35]. Prevalence in India is significantly lesser [35], with some studies not reporting even a single case [14, 25, 26, 27, 30]. Similarly, PCNSL accounts for 2.5% of all CNS lesions in HIV-positive patients compared to 10–17% in the western population [36]. Autopsy series show similar findings with the only published Indian series reporting no cases of PCNSL over 8 years [37] while western studies report the share to be between 1.4 and 3% [38, 39]. Shorter survival among AIDS patients in the Indian subcontinent could be the likely cause [40].
The most common presenting features reported are focal neurological deficits, neuropsychiatric symptoms, headache from raised intracranial pressure (ICP), seizures, and ocular symptoms [7]. Diagnosis may not be evident at presentation, with one study reporting a median time lag of 70 days from symptom onset to neuroimaging [41]. Personality changes and visual hallucinations are usually detected late, and a lower threshold to pursue neuroimaging is needed [41].
Any suspected case of PCNSL should undergo neuroimaging in the form of a contrast-enhanced MRI of the brain and spine, CSF analysis unless contraindicated (ideally before stereotactic biopsy), slit-lamp examination, and testicular examination (in males) [42].
In some cases, pathological evaluation of ocular material or CSF may diagnose. In most cases, however, a stereotactic biopsy is needed [43]. The stark difference in the initial management of PCNSL, compared to high-grade gliomas, underlines the importance of early clinical suspicion and radiological expertise.
Table 1 contains the clinical features of patients enrolled in studies in Indian settings.
In the Indian subcontinent, delayed health-seeking behavior combined with high initial misdiagnosis rates leads to a high disease burden at presentation. Median time from symptom onset to diagnosis is reported around 3.5–5 months in Indian studies [20, 24, 29, 44], compared to 2.5–3 months in western studies [7, 41].
Delayed health-seeking behavior is evident if we compare clinicoradiological features at index presentation. While two studies report focal neurological deficits as the most common presenting feature [20, 29], most studies report headache from raised ICP as the index presentation [14, 21, 22, 23, 27, 28, 30, 31], which is typically a late feature in the western literature. Furthermore, while most western patients are ambulatory and capable of self-care at presentation [7], roughly 2/3rd of Indian patients are ECOG performance status (ECOG-PS) three or worse in retrospective [22, 25, 29] and prospective [44] studies. Similarly, multifocal lesions, reported in 25% of patients at presentation as per western literature [7], are seen in 30–82% of all patients presenting in the Indian settings [20, 22, 24, 25, 26, 27, 28, 29, 31, 44]. However, some studies do give estimates nearing their western counterparts [14, 23, 30], perhaps highlighting differential health-seeking behavior.
Erroneous evaluation and emergent management are also common. Indian studies report misdiagnosis rates as high as 54% [20] to 100% [29], and inadvertent open surgical resection in 36-57% [20, 44] of PCNSL patients compared to 25% in western literature. In addition, inadvertent steroids are given before diagnosis in up to 2/3rd patients referred from primary care [20] although prospective studies document only 9% requiring corticosteroid therapy for life-threatening indications [44].
These delays and errors result in a patient population with advanced disease and a poorer prognosis. While the proportion of patients with LDH elevation (1/3rd) and CSF Protein elevation (2/3rd) are similar in Indian [22, 25, 28, 29, 31] and western studies [45], fewer patients are IESLG low risk in the Indian settings with concomitant better outcomes [22, 25, 29]. However, the MSKCC risk classification seems to underestimate the risk in the Indian population because of its weightage to older age [28, 31].
Table 2 shows treatment details and outcomes of important studies from the Indian subcontinent.
Study (n) | Pre-treatment details | Induction chemotherapy details | Post-induction chemotherapy | Long-term outcomes | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
IESLG low risk (%) | Treatment received (%) | Type of chemotherapy | Median induction cycles | Rituximab | Overall response rate, complete response rate (ORR/CR %) | Median follow-up duration (months) | Median event-free survival (months) | Median overall survival (months) | Severe late neurotoxicity (%) | ||
Patekar et al. (n = 99) | 7.10 | 77.70 | MVP with Rituximab (94.8%) CHOP + HTMTX (2.6%) CHOP + IT MTX (1.3%) HD - MTX only (1.3%) | 5 | In affording patients | 81.8% (46.8%) | WBRT in 54% (Ara - C in 86% of WBRT recipients) 11% HiDAC only | 34 | 20.4 | 31.7 | 10 |
Adhikari et al. (n = 22) | — | 100 | MVP | 5 | In affording patients | 93.7% (52.63%) | 50% WBRT 50% reduced dose WBRT 68.18% post-WBRT HiDAC | 11.25 | Not reached | 19 | — |
Parischa et al. (n = 66) | — | 100 | MPV followed by WBRT + HiDAC (DeAngelis protocol) | — | No | — | — | — | — | — | — |
Yadav et al. (n = 32) | — | 100 | WBRT (36-50 Gy) followed by 6 cycles CHOP | 6 | No | 87.5% (75%) | None | 18 | — | 14 months | — |
Rudresha et al. (n = 26) | — | 100 | DeAngelis protocol (92%), MTR followed by EA (8%) | 5 | No | ORR for DeAngelis: 92%, ORR for MTR regime: 100% | WBRT followed by HiDAC given in DeAngelis protocol, EA given to MTR recipients | — | — | 20.5 | — |
Rudresha et al. (n = 53) | — | 100 | DeAngelis protocol (n = 31) CHOP + WBRT (n = 14) WBRT only (n − 6) | — | No | — | WBRT followed by HiDAC in DeAngelis protocol | — | — | 23 months for DeAngelis protocol, 13 months for standard CHOP + WBRT treated, 6 months for WBRT only subset | 26% in DeAngelis treated, 14% in CHOP + WBRT subset |
Kumari et al. (n = 30) | 10 | 100 | 40–52 Gy WBRT followed by 6 cycles of CHOP/PCV | — | No | — | — | — | — | — | — |
Puligundla et al. (n = 42) | 19 | 80.90 | Modified DeAngelis (50%) Modified DeAngelis protocol + rituximab (29.4%) Steroids + radiotherapy (17.7%) BFM- NHL protocol (3%) | — | Given to 29.4% of patients | — | — | 18 | 11 | 15.9 | — |
Agarwal et al. (n = 26) | 36.3 | 84.60 | MVP + Cytarabine | — | No | CR: 72.7% | WBRT in patients aged <60 years (45%) | 14.5 | — | 10 | 31.25% |
Treatment administered and long term prognosis of PCNSL patients enrolled in Indian studies.
Left untreated, PCNSL has a uniformly dismal prognosis (median OS = 2 months) [46]. Only marginally better are conventional DLBCL regimes with response rates ranging from 19 to 59% and less than half patients surviving at two years from diagnosis [2, 3]. A significant improvement in prognosis comes from modern multi-drug regimens incorporating high-dose methotrexate (HD-MTX) with appropriate consolidation (2 years OS of 80% and a five-year OS of 77%) [47]. More recent regimes utilizing autologous stem cell transplantation as consolidation report two-year OS as high as 81% [48].
Indian studies report modest outcomes. Up to 20% of PCNSL patients never receive therapy [20, 22, 29]. A single-institution reported a median EFS of 20.4 months and a median OS of 31.7 months at a median follow–up of 34 months with HD-MTX-based multiagent regimes and Rituximab and consolidative WBRT. [20] A prospective phase 2 trial evaluating response adapted radiotherapy showed a median OS of 19 months, underlining the necessity of consolidative WBRT to optimize outcomes [44]. A study evaluating the importance of HD-MTX therapy in the Indian setting [28] reported a median OS of 8 months, 13 months, and 23 months in WBRT, R-CHOP with WBRT, and HD-MTX with WBRT, respectively. Thus, there is a scope for improvement in the outcomes of PCNSL seen in the Indian sub-continent.
Studies using HD-MTX-based induction and WBRT consolidation report 15% long-term neurotoxicity rates [49]. However, no such delayed sequelae are documented in prospective studies using abbreviated WBRT [50, 51]. On the other hand, regimes using ASCT as consolidation report continuous cognitive improvement until 12–18 months after completion of therapy [48].
In the Indian setting, reliable estimates of long-term neurological toxicity are lacking given that most of the reported literature does not have adequate follow-up or assessment [22, 25, 26, 27, 30, 31]. However, limited studies report severe long-term neurotoxicity rates of 10–33%, with elderly patients and WBRT recipients at a higher risk [20, 28, 29].
PCNSL requires multi-disciplinary care in resource-intense settings to optimize outcomes. However, in lower-middle-income countries (LMIC), the main barriers to applying modern evidence-based management of PCNSL are the lack of neurosurgical facilities and oncology units capable of handling HD-MTX.
Radiological differential diagnosis of PCNSL includes high-grade gliomas, tumefactive demyelinating lesions, metastasis, and granulomatous diseases/infections. Although, the radiological appearance of PCNSL is very distinctive with homogenous contrast enhancement, optic pathway, and cranial nerve infiltration, a predilection for deeper structures, lesser necrosis, and nearly no bleeding, many studies still report diagnostic difficulties while using conventional MRI only [52]. This differentiation is crucial because while PCNSL requires stereotactic biopsy followed by systemic chemotherapy, high-grade gliomas are usually treated with upfront gross total resection. With 40% of patients responding, prior steroid usage compounds this problem with high false-negative biopsy rates [53]. Thus, early radiological suspicion may allow many patients to undergo appropriate management in the form of no inadvertent steroid therapy, stereotactic biopsy, and early institution of HD-MTX-based therapy.
Diffusion-weighted imaging is an essential diagnostic tool. PCNSL shows more restricted ADC than high-grade gliomas, given its higher cellular density and N: C ratio. However, solid portions of high-grade gliomas may mimic [52]. Therefore, a different measure,“ Relative minimum ADC,” is often used given its reasonable diagnostic certainty [54]. Furthermore, dynamic contrast-enhanced MRI adds to ADC’s diagnostic performance as well [55].
Another crucial diagnostic aid is the 1H-magnetic resonance spectroscopy (1H-MRS). Choline to creatine ratio, a marker of membrane turnover, is identical for PCNSL and high-grade gliomas. However, N-acetyl aspartate peaks (NAA), a marker of neuronal damage, may have variable results. The lipid peak arises from necrosis in GBM and release of fatty moieties via lymphocytes in PCNSL, making lipid resonance without necrosis the most specific finding [56].
1H-MRS may allow assessment of other peaks as well. Conventional 1.5 T MRI cannot differentially assess glutamate (Glu) and glutamine (Gln) peaks, and there is no difference in Glutamate + Glutamine/ Creatinine peaks among PCNSL and high-grade gliomas. However, because of impaired Glutamate internalization in high-grade gliomas, glutamate to glutamine conversion is upscaled. Thus, 3 Tesla MRI machines which can differentially quantify glutamate and glutamine, allow assessment of Glu/Glu + Gln ratios which are reproducibly different in PCNSL and high-grade gliomas [57].
Amide proton transfer weighted studies (based on 3 T MRI machines) also detect endogenous mobile proteins and peptides predominantly seen in the cytoplasm. PCNSL, with its high N:C ratio and thus, a low concentration of mobile proteins, shows much shows limited hyperintensities as compared to heterogenous hyperintensities much larger than the gadolinium-enhancing areas in high grade gliomas [55].
Dynamic susceptibility contrast-enhanced MRI can differentiate based on different tumor microenvironments. PCNSL lacks florid neovascularization compared to high-grade gliomas, as assessed by FVIII staining on resected specimens [58]. Contrast enhancement stems from breakage of the blood-brain barrier rather than increased vascularity resulting in a relatively lower rCBV than high-grade gliomas [59]. Neovascularization of surrounding infiltrated tissue can result in a specific shoulder-like pattern of signal intensity and enhance diagnostic performance [60]. Prospectively validated studies report an rCBV threshold of 2.56 having >90% sensitivity and specificity [54].
Fundamental differences of neovascularization and necrosis between PCNSL and high-grade gliomas may lead to subtle differences in imaging, which, although may not be evident to the human eye, are picked by metadata-based machine learning (ML) models. A recent meta-analysis assessing the utility of ML models for PCNSL diagnosis reports 0.878 as the lowest AUC across eight studies [61]. Another prospectively validated model reported an AUC of 0.978 using only T1 weighted images [62]. ML-based algorithms have advantages of being open access, easily accessible, and minimal reliance on novel machines or software. However, overfitting of models compromising external validity and prompting institute-specific algorithms is a challenge.
Given its high cellular density, PCNSL shows intense homogenous FDG uptake (as opposed to heterogeneous uptake in high-grade gliomas) with SUVmax values around 12–14 (2.5 times of normal gray matter). However, surrounding physiological gray matter uptake hinders accurate assessment [63]. A study assessing the diagnostic utility of PET/CT for PCNSL reported an optimal SUVmax cut-off of 15 with only a single false positive [64]. Another study reported that a SUVmax cut-off of 12 had 86% accuracy as a standalone modality and 95% when combined with CE-MRI with DWI [65].
The tumor/normal (T/N) ratio overcomes the reliance of SUVmax on plasma glucose concentrations. A study reported good diagnostic performance with a cut-off 2.0. Prior Steroids may hinder both SUVmax, as well as T/N ratio [66]. PET/CT has additional utility in ruling out secondary CNS lymphoma and a 7% additional yield over CT and bone marrow examination [67].
CSF analysis may allow diagnosis without neurosurgical procedures and its associated complications in up to 40% of patients. Therefore, patients without evidence of raised ICP should undergo CSF analysis with cytomorphology, flow-cytometry, and PCR for IGHV rearrangements either before or at least 1 week after the stereotactic biopsy [42].
A recent systematic review of 27 studies evaluating CSF cytomorphology and flow cytometry across different lymphoid neoplasms with meningeal involvement reported around 0.3-42.9% positive results with dual testing. Furthermore, 48% and 89% of studies reported samples positive on cytomorphology or flow cytometry alone, respectively, highlighting the importance of co-testing [68]. Another study assessing only PCNSL patients reported 13.3% and 23.3% positivity rates with CSF cytomorphology and flow cytometry, respectively [69].
CSF cell fragility impairs the diagnostic performance of cytomorphology and flow cytometry. However, PCR-based analysis of IGHV rearrangements to assess clonality does not require intact cells and may circumvent this problem. A study assessing IGHV rearrangement status in CSF among patients with PCNSL reported a sensitivity of 54% and specificity of 97% among the 84% patients having CSF with extractable DNA. The positive predictive value was 93%, with a further rise if only therapy naïve patients were considered [70]. However, a study prospectively evaluating CSF of 282 patients with PCNSL reported 10% samples with positive IGHV rearrangement PCR but negative cytomorphology and 12% samples with positive cytomorphology but negative IGHV rearrangement analysis [71]. Thus, IGHV rearrangement analysis may be better suited as an add-on than a replacement.
Novel approaches such as digital droplet PCR (ddPCR) analysis of MYD88 mutations [72], IL-10 levels [73], Osteopontin levels [74], neopterin levels [75], and miR-21 levels [76] may allow further diagnostic aid and potential negation of neurosurgical procedures in the future. Specifically, a meta-analysis reported that CSF IL-10 levels have a sensitivity of 81%, specificity of 97%, and an area under ROC of 0.95 at a cut-off of 6.88 pg/ml [77].
Like CSF analysis, Ocular involvement may also allow early diagnosis without reliance on neurosurgical procedures. Ocular involvement is seen in 15–25% of PCNSL patients, and slit-lamp examination is the diagnostic procedure of choice [78]. If involvement is suspected, a biopsy of vitreous fluid, choroid, or retina may allow histopathological diagnosis. Routine use of slit-lamp microscopy and a high index of suspicion is warranted given that more than 1/3rd of patients with ocular involvement are asymptomatic [79]. In cases with equivocal appearances, ocular ultrasound, fundus fluorescein angiography, and optical coherence tomography are adjunctive studies used for diagnosis [80].
Combined cytopathology, flow cytometry, and analysis of IGHV gene arrangement studies on multiple vitrectomy specimens have a combined sensitivity and specificity of 64% and 100%, respectively [81]. A chorioretinal biopsy is an option in suspicious cases with a normal vitreous biopsy [82].
Novel techniques may enhance diagnostic yields. For example, ARMS PCR-based MYD88 L265P mutation analysis is diagnostic in 86.7% FFPE samples of primary vitreoretinal lymphoma [83]. Techniques independent of DNA input such as ddPCR allow similar rates of MYD88 mutation detection from less invasive specimens like aqueous humor [72]. Lastly, elevated IL-10 levels or an IL-10/IL-6 ratio > 1 is suggestive but not diagnostic, and its utility as a standalone modality requires validation [78].
High-dose methotrexate-based multiagent chemotherapy followed by consolidation with WBRT or autologous stem cell transplantation is the modern standard of care for PCNSL [42]. However, centers with facilities and experience for HD-MTX are lacking, necessitating the evaluation of alternative regime backbones.
Methotrexate doses of more than 3 g/m2 are needed to cross the BBB and doses as high as 8 g/m2 have been used without any guiding prospective randomized data. A recent observational study has reported higher CR rates and PFS with higher dose HD-MTX (8 g/m2) [84]. An infusion time of 3 hours and 6 hours for doses of 3 g/m2 and 8 g/m2 respectively allows better CNS penetration per unit dose, allowing enhanced efficacy and an attenuated toxicity profile [85]. 5–7 cycles of HD-MTX-based polychemotherapy spaced at 2 weeks intervals rather than 3-week intervals are associated with optimal oncological outcomes [86]. Leucovorin rescue is typically started 24 h after infusion and at least 12 doses are given at 6-hour intervals [51]. The utility of therapeutic drug monitoring remains to be proven in these settings with a recommendation for assessment at 24 h, 48 h, and 72 h after initial infusion [87].
Thiotepa, a lipid-soluble organophosphorus-derived alkylator, is a potential answer. Evidence suggests that Methotrexate is optimally given in doses more than 3.5 g/m2 over shorter infusion times (3 h) at a gap of 2–3 weeks for 5–8 cycles [42]. High dose cytarabine (Ara-C) addition to HD-MTX therapy led to more than doubling of responses, likely from prolonged exposure to S-phase cytostatics [88]. Subsequently, the IESLG32 study evaluated Rituximab addition and autologous SCT’s utility in PCNSL and added Thiotepa to a third induction arm (MATRIx regime), which outperformed both combination chemotherapy and chemoimmunotherapy arms [9]. Thus, with a 100% plasma-to-cerebrospinal fluid ratio, 30-min infusion time, and synergy with anti-metabolites, Thiotepa might be a convenient alternative to HD-MTX, and the comparative efficacy of Thiotepa-high-dose Ara-C vs. HD-MTX is worth exploring. Notably, a study using high dose Ara-C with Thiotepa after initial HD-MTX showed an increase in responses [89].
Single-agent temozolomide [90], topotecan [91], and temsirolimus [92] have also shown modest activity in relapsed PCNSL settings, and different combinations may be worth evaluating.
Frequent mutations in the BCR subunit CD79B and Toll-like receptor adaptor protein MYD88 suggest addiction of PCNSL to BCR signaling [93], making Ibrutinib an attractive option. However, since Ibrutinib-driven responses in ABC DLBCL last for less than a year [94], cotherapy with blood-brain barrier crossing synergistic drugs is prudent. Recent studies have built on this, and Ibrutinib-based combination regimes are a promising HD-MTX-free approach. While Ibrutinib is antagonistic with most anti-folate drugs, it is synergistic with etoposide, doxorubicin, Ara-C, and mitomycin C [95]. Additionally, doxorubicin, a broad spectrum lymphocytic but BBB impermeable agent, may be given as a liposomal formulation that maintains CSF concentrations throughout therapy duration, likely from a reservoir-like effect [96]. On these lines, the dose-adjusted TEDDi-R regime given after a 14-day run-in of ibrutinib monotherapy showed 86% complete responses in a phase 1b study with 18 patients [97]. Notably, the activity of this regime did not become dependent on the presence of the specific MYD88 L265P mutation. However, severe adverse effects in the form of grade 4 neutropenia, grade 4 thrombocytopenia, and invasive fungal infections (most commonly aspergillosis) were noted in 53%, 30%, and 50%, respectively. These rates of invasive fungal infections are not found in other studies evaluating Ibrutinib (with or without steroids), and monocyte BTK inhibition may be causative [98]. Recognizing the need for prophylaxis, a recent phase 1b trial reported 75% CR rates and no invasive fungal infections with DA-TEDDi R with Isavuconazole prophylaxis [95]. In the Indian settings, concomitant dose reduction of both ibrutinib and liposomal doxorubicin [99] makes Voriconazole prophylaxis an attractive option offering maintained efficacy and reduced financial toxicity.
Lenalidomide may offer a potentially less intensive ibrutinib-based option. Given its capability to expand NK-cell pools, Lenalidomide is known to be synergistic with Rituximab (R2-regimen) [100]. A proof-of-concept phase 2 study documented ORR and CR rates of 32% and 29%, respectively, in relapsed/refractory PCNSL with a tolerable safety profile [101]. Building on data from systemic DLBCL, ibrutinib and R2 (IR2) leads to complete responses in 1/3rd relapsed/ refractory PCNSL cases, and studies testing this regime in frontline settings are eagerly awaited [10].
Intrathecal delivery may enhance synergy between rituximab and lenalidomide. At conventional doses (375 mg/m2), CSF compartment achieves only 0.1% of systemic rituximab concentrations [102]. Evidence suggesting that incorporation of systemic rituximab in lymphoma protocols does not impact the incidence of CNS relapse also points to potential inadequacy of intravenous rituximab in clearing the leptomeningeal compartment [103]. Given the acceptable safety profile of intrathecal rituximab in non-human primates [104], intrathecal rituximab-based combinations deserve consideration for further research. On these lines, a phase 1 study reported 25 mg as the optimal intraventricular dose (via ommaya reservoir) leading to an ORR of 60% and a CR rate of 40% with one parenchymal remission as well [105]. A subsequent study reported a CR rate of 43% in relapsed PCNSL when treated with a combination of intraventricular rituximab and methotrexate [106]. Thus, while intraventricular rituximab is an option with promising efficacy and cost benefits, larger studies are needed. Additionally, the utility of intrathecal rather than intraventricular therapy also requires consideration.
More than 50% of PCNSL patients relapse within 5 years of therapy if treated with induction alone, necessitating some form of consolidation therapy [107]. The two largest comparative trials indicate comparable efficacy but lesser long-term neurotoxicity with HDT-ASCT than WBRT [108, 109]. While a longer follow-up may tell a different story [50], upfront HDT-ASCT for all PCNSL patients is not feasible for resource-limited settings.
In Indian settings, WBRT followed by HiDAC [107] remains the most common consolidation therapy. However, while western studies report comparable efficacy and lesser neurotoxicity by reduced dose WBRT [51, 110], studies in the Indian settings in our experience are less favourable [44].
Non-myeloablative chemotherapy may offer a balance of efficacy and cognition. For example, Etoposide-Cytarabine (EA regimen) showed efficacy comparable to historic WBRT treated cohorts in a single-arm phase 2 study. However, lack of randomized comparisons and high rates of grade ¾ hematological toxicity with the possible requirement of autologous stem-cell rescue are barriers to frequent utilization [111].
Maintenance with oral procarbazine, assessed in a phase 2 trial of elderly PCNSL patients, is a safe alternative, although randomized evidence is lacking [112]. Another study showed lesser relapse rates (non-randomized) with oral Temozolomide maintenance than WBRT, although atypical induction protocols used in this study negatively impact the external validity of findings [113]. Lenalidomide maintenance is also a safe option in elderly patients, although the efficacy in this setting is yet to be proven [114].
PCNSL, although morphologically like any other DLBCL, has distinct pathobiology and prognosis. The requirement of early radiological diagnosis and referral to a center equipped with neurosurgical facilities and safe administration of HD-MTX for every patient makes management of PCNSL challenging in resource-limited settings. Non-invasive methods of diagnosis and non-HD-MTX-based therapies need more research to allow PCNSL cases to be managed optimally in such settings.
For improving efficiency, an increasing number of devices are operated at high-voltage levels to reduce losses in power transmission and power conversion. In the case of energy and power systems for electrical vehicles (EVs), a high-efficiency electrical device can be achieved using a high-voltage design. State-of-charge (SoC) and state-of-health (SoH) define the capability and reliability of a high-voltage battery, respectively. To determine these two parameters instantaneously, it is required to develop a simple, training-free, and easily implemented scheme. Based on an equivalent-circuit model (ECM), the electrical performance of a battery can be formulated into a state-space representation. Besides, underdetermined model parameters can be arranged linearly so that an adaptive control approach can be applied [1]. However, electric shock may be harmful to passengers if insulation failure occurs. As insulation resistance in EVs varies with the operation environment and the reliability of the dielectric material [2], an online insulation-fault detection method is required to ensure that the insulation resistance stays within safe limits before startup or during the operation of high-voltage systems.
To ensure electrical safety in high insulation resistance, insulation inspection technologies have been widely applied in distribution networks [3, 4, 5] and EVs [6, 7, 8, 9, 10, 11, 12, 13]. To analyze the dynamic insulation signals, the monitoring circuit is conventionally modeled by using two individual resistors connected with a DC high-voltage line to the earth ground. The basic concept used in estimating these two resistance values is to connect an additional circuit bridge composed of resistors and switches to obtain the differential current loops and corresponding voltages [8, 9, 10, 11], but the resistance can only be measured if no current is conducted. As a result, these methods are barely suitable even for offline detection. A more practical approach for online detection is to continuously inject an excitation pulse signal into the negative terminal through a capacitor. The insulation resistance value can be acquired by analyzing the time-constant or the amplitude of the voltage waveform [12, 13]. However, parasitic or stray capacitance generally occurs in insulation loops, and causes considerable estimation error if they are ignored in the circuit model. In this chapter, we employ one typical capacitance in the monitoring circuit and propose a new adaptive algorithm for estimating both the resistance and capacitance values.
To follow the process illustrated by Sottile and Tripathi [14], the high-voltage system we consider in this chapter could be an EV driving system that is powered by a high-voltage battery or a UPS that stores electricity to provide emergency power. As illustrated in Figure 1, a high-voltage system consists of a high-voltage battery pack, an inverter, a converter, an AC load, and an AC source. The DC sides of the inverter and converter are connected in parallel with the high-voltage battery pack. The AC side of the inverter is connected to a two-phase or three-phase load. In other cases, the AC side of the converter could be connected to a two-phase or three-phase source. Here, to consider an EV power system, we assume the AC load to be a traction motor driven by an inverter, with the converter acting as a charger that converts AC power from the grid or generator to DC power for charging the battery pack. In a UPS or a renewable energy system, however, both the AC load and source have the same grid network. Moreover, the inverter must be properly controlled to deliver power in phase with the grid power waveform.
Proposed insulation monitoring circuit.
The DC power line of the circuit connected to the high-voltage system is electrically isolated from the enclosure, i.e., the ground or chassis. Thus, we can determine the insulation status by measuring or estimating the resistance between the node on the positive-voltage line (+) or negative-voltage line (−) and the node with the equivalent electric potential to the ground. The electrical insulation in such a high-voltage system can be simply modeled by a resistor and a stray capacitor in a parallel connection, as shown in Figure 1, where
PWM signal generated using the PRBS method. (a) Photo-coupler circuit for electrical isolation and multiple-voltage generation. (b) General topology of the isolated DC/DC converter.
Several topologies for implementing the proposed isolation circuit.
This high-voltage system connected to the insulation monitoring circuit can be modeled as an equivalent circuit, as illustrated in Figure 4, where
Equivalent circuit model for the insulation monitoring system.
Therefore, we estimate the insulation resistances
Substituting Eq. (1) into Eq. (2), together with
yields:
which can be rewritten as follows:
Let us define the parametric vector as follows:
and the variable vector as:
such that the dynamics of the insulation monitoring system are formulated as follows:
where the parametric vector includes all the resistance and capacitance values that must be known and the variable vector is composed of the variables that can be evaluated from all the measurements in the system, i.e.,
If we suppose all the actual parameter values and the voltage
where
Invoking the Lyapunov stability criteria shows that the positive-definite function:
will approach zero for the negative semi-definite of its derivative; that is:
provided that the adaptation law is as follows:
where
Figure 5 shows a calculation flowchart for estimating the insulation resistance. A detailed description of the process is as follows:
Start the online estimation at time
The voltage values are acquired from the measured
The estimated voltage error is computed by Eq. (7) together with the updated parameters, where the initial value of the estimated
Based on the measured voltage data and estimated
The insulation resistances are calculated by Eq. (12) based on the updated parameters. The minimum value is used to check whether it is under the predetermined threshold. If so, it is shown in the indicator.
The waiting time required for the parameters’ convergence is calculated and
Either the insulation resistance or an alert message is displayed, depending on whether it is below the mandatory threshold.
For continuous online monitoring, once started, this flow is an infinite loop.
Flowchart for online parameter estimation.
To verify the proposed algorithm, for simplicity, we assumed a scenario in which an electric vehicle is driven on the road such that the battery and AC line voltages are
We constructed the circuit model and the estimation algorithm using Simulink software. The simulation estimation results for
Estimation of
Estimation of
To simply validate the proposed algorithm in the laboratory, we connected a variable resistor to the proposed circuit to form a left-hand side loop of the circuit shown in Figure 4, in which the resistance, as represented by
On the other hand, we modify the estimated model to yield:
The experimental results are shown in Figure 8. In Figure 8(a), the two estimated parameters converge after 25 s. In Figure 8(b), we depict the online estimated resistances based on the straight evaluation of Eq. (8) and the proposed method in Eq. (9). It is realized that the estimated value by using the straight evaluation varies roughly 10% between its maximum and minimum values. This may be due to either measurement noise or the dynamic uncertainty of the parasitic capacitance. However, the proposed method shows a steadier and more exact estimation after the convergence of the model parameters.
Experimental results. (a) Estimated parameters
In this chapter, to improve existing techniques for enhancing the safety and reliability of high-voltage systems, we proposed a new insulation resistance online monitoring method for EV high-voltage DC lines, which takes into account the parasitic capacitance effect. The estimation scheme based on an adaptive control algorithm guarantees the asymptotical convergence of the parameters in the circuit model. Hence, as demonstrated in our simulation and experimental results, this method can steadily and accurately track the insulation resistance even when the parasitic capacitance is unknown. Due to the simplicity of the proposed algorithm and circuit, they can be easily implemented via electronic circuit design in real cases. According to the results, the estimated
AC | alternating current |
BMS | battery management system |
DC | direct current |
DC/DC | conversion of a DC source from one voltage level to another |
ECM | equivalent-circuit model |
EV | electric vehicle |
MCU | micro-control unit |
PRBS | pseudo random binary sequence |
PWM | pulse-width modulation |
SoC | state of charge |
SoH | state of health |
UPS | uninterrupted power supply |
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\\n\\nCo-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
\\n\\nBut, one thing we have in common is -- we are all scientists at heart!
\\n\\nSara Uhac, COO
\\n\\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\\n\\nAdrian Assad De Marco
\\n\\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\\n\\nDr Alex Lazinica
\\n\\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Our business values are based on those any scientist applies to their research. We have created a culture of respect and collaboration within a relaxed, friendly and progressive atmosphere, while maintaining academic rigour.
\n\nCo-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
\n\nBut, one thing we have in common is -- we are all scientists at heart!
\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\n\nAdrian Assad De Marco
\n\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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