Overview of clinical trials that tested immunocheckpoint inhibitors for malignant pleural mesothelioma.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"1437",leadTitle:null,fullTitle:"Immunosuppression - Role in Health and Diseases",title:"Immunosuppression",subtitle:"Role in Health and Diseases",reviewType:"peer-reviewed",abstract:'A need for a book on immunology which primarily focuses on the needs of medical and clinical research students was recognized. This book, "Immunosuppression - Role in Health and Diseases" is relatively short and contains topics relevant to the understanding of human immune system and its role in health and diseases. Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Therapeutic immunosuppression has applications in clinical medicine, ranging from prevention and treatment of organ/bone marrow transplant rejection, management of autoimmune and inflammatory disorders. It brings important developments both in the field of molecular mechanisms involved and active therapeutic approaches employed for immunosuppression in various human disease conditions. There was a need to bring this information together in a single volume, as much of the recent developments are dispersed throughout biomedical literature, largely in specialized journals. This book will serve well the practicing physicians, surgeons and biomedical scientists as it provides an insight into various approaches to immunosuppression and reviews current developments in each area.',isbn:null,printIsbn:"978-953-51-0152-9",pdfIsbn:"978-953-51-6849-2",doi:"10.5772/1897",price:139,priceEur:155,priceUsd:179,slug:"immunosuppression-role-in-health-and-diseases",numberOfPages:486,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"fcf618a076bac784bcce3b4974da05e3",bookSignature:"Suman Kapur and Maristela Barbosa Portela",publishedDate:"February 24th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1437.jpg",numberOfDownloads:61229,numberOfWosCitations:25,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:23,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:57,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2011",dateEndSecondStepPublish:"March 9th 2011",dateEndThirdStepPublish:"July 14th 2011",dateEndFourthStepPublish:"August 13th 2011",dateEndFifthStepPublish:"December 11th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"67886",title:"Dr.",name:"Suman",middleName:null,surname:"Kapur",slug:"suman-kapur",fullName:"Suman Kapur",profilePictureURL:"https://mts.intechopen.com/storage/users/67886/images/2473_n.jpg",biography:"Dr. Suman Kapur, born and educated in New Delhi joined BITS, Pilani on 17th July 2004 as Professor in the Center for Biotechnology, Biological Sciences Group She has worked in the capacity of Unit Chief, Community Welfare and International Relations since 1st January 2007. From 16th April 2010 she has taken charge as Dean, Research & Consultancy at the Hyderabad Campus of BITS\n\nDr. Kapur is a popular teacher at BITS, Pilani and has been instrumental in introducing several new courses, namely and has developed the curriculum for a new degree program “Master of Public Healthâ€, incorporating learning through field visits and interdisciplinary teaching. Several students, trained by her have gone to make excellent careers for themselves as CEO’s of start up companies and faculty at some of the best institutions in USA.\n\nDr. Kapur with her team of a dozen research scholars has been instrumental in building a state of the art Human Genomics laboratory from funds (Rs 363.19 lacs) received as Principal and/or Co-Investigator of now more than eighteen grants awarded since her joining BITS in 2004. As a mentor she has been able to motivate younger faculty to submit and execute independent grants in the form Women scientist (DST), Research Associate and senior research fellows (ICMR & CSIR). She has published more than 80 research articles in International and journals.\n\nDr. Kapur’s research interests lie in identifying biomarkers for unraveling the genetic basis of human diseases such as psychiatric disorders like depression, schizophrenia, addiction and alzheimer’s disease and metabolic disorders such as diabetes (T2DM), obesity, cataract and metabolic syndrome. The group is specifically studying several genes,viz., APOE, CAPN, PPARï§, ï€¬ï€ ALDH2, ADH1B, ADH1C, OPRM1, OB, TPH, CRYGA, CRYGB, D2, D5, ADCY4, ADCY3, CCKAR, CCKBR, CFTR, CF508, SPNK-1, PS-1, CYP2E1, CTSB, HSP70, TNFï¡, ï€ PRSS-1 and several micro-satellite markers on chromosome segments 2, 6 and 10. Chronic diseases have a long latency period and genetic markers can be effectively used for identifying individuals at an increased risk for developing these diseases and advocating appropriate lifestyle measures to delay the onset and progression of such diseases. On the other hand identification of specific disease associated protein markers play a pivotal role in early diagnosis and prognosis/follow up of any given disease. Ours is the first group to show that in the Indian population a mutation in the mu Opiate receptor is linked to risk for addiction to opiates and alcohol and a mutation in the Ob (leptin) gene is linked to hypertension in depressed subjects. Her group is also involved in developing clonal variants of Indian Medicinal plants and screening natural products for anti-diabetic, anti-inflammatory and anit-obesity activities. Strength of the group lies in under-taking work related to DNA, RNA and protein analysis using both in-vitro and in-vivo models. In-vitro, models constitute cell based assays using natural or derived cell lines, genetically modified cell lines and in-vivo studies hinge on animal models for specific diseases like diabetes, arthritis, etc.\n\nAs Chief of Community Welfare and International Relations Unit Dr. Kapur has ably conducted the day to day activities of this unit and was instrumental in orchestrating several student exchanges introduction of new fellowships and opportunities for both students and faculty at BITS campuses.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Birla Institute of Technology and Science, Pilani",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"73206",title:"Dr.",name:"Maristela",middleName:"Barbosa",surname:"Portela",slug:"maristela-portela",fullName:"Maristela Portela",profilePictureURL:"https://mts.intechopen.com/storage/users/73206/images/system/73206.jpg",biography:"Dr. Maristela Portela is an Adjunct IV Professor of Pediatric Dentistry at the Universidade Federal Fluminense/Niterói, School of Dentistry, Brazil. She researches in areas of oral microbiology, Candida spp. virulence of HIV-infected children and restorative biomaterials. Additionally, she received her DDS degree in 1999 from Universidade Federal do Rio de Janeiro, Brazil (UFRJ, Brazil), her Master Degree in Pediatric Dentistry in 2002 from UFRJ, Brazil and her PhD degree in Biology Sciences (Microbiology and Immunology) from UFRJ, Brazil in 2006. In 2007, she awarded the National Honorable Mention for her doctoral thesis research entitle “Study of functional proteins of Candida spp. Isolated from oral cavities of Human Virus Immunodeficiency Infected children”. Dr. Portela has published about 40 peer-reviewed papers and she is a member of the International Association for Dental Research (IADR).",institutionString:null,position:"Adjunct Professor",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1041",title:"Immunotoxicology",slug:"immunotoxicology"}],chapters:[{id:"29064",title:"Role of Opioidergic System in Humoral Immune Response",doi:"10.5772/26803",slug:"role-of-opioidergic-system-in-humoral-immune-response",totalDownloads:2673,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Suman Kapur, Anuradha Pal and Shashwat Sharad",downloadPdfUrl:"/chapter/pdf-download/29064",previewPdfUrl:"/chapter/pdf-preview/29064",authors:[{id:"67886",title:"Dr.",name:"Suman",surname:"Kapur",slug:"suman-kapur",fullName:"Suman Kapur"},{id:"80113",title:"Dr.",name:"Shashwat",surname:"Sharad",slug:"shashwat-sharad",fullName:"Shashwat Sharad"},{id:"80117",title:"Ms.",name:"Anuradha",surname:"Pal",slug:"anuradha-pal",fullName:"Anuradha Pal"}],corrections:null},{id:"29065",title:"Endotoxin Tolerance as a Key Mechanism for Immunosuppression",doi:"10.5772/27368",slug:"endotoxin-tolerance-as-a-key-mechanism-for-immunosuppression",totalDownloads:3668,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Subhra K. 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Kaindl",slug:"angela-m.-kaindl"},{id:"73080",title:"Dr.",name:"Stefanie",middleName:null,surname:"Endesfelder",fullName:"Stefanie Endesfelder",slug:"stefanie-endesfelder"},{id:"73081",title:"Dr.",name:"Clarissa",middleName:null,surname:"Von Haefen",fullName:"Clarissa Von Haefen",slug:"clarissa-von-haefen"},{id:"73083",title:"Dr.",name:"Ivo",middleName:null,surname:"Bendix",fullName:"Ivo Bendix",slug:"ivo-bendix"},{id:"73084",title:"Prof.",name:"Ursula",middleName:null,surname:"Felderhoff-Mueser",fullName:"Ursula Felderhoff-Mueser",slug:"ursula-felderhoff-mueser"}]},{id:"27132",title:"Preterm Birth and Long-Term Pulmonary Function",slug:"preterm-birth-and-long-term-pulmonary-function",signatures:"Indra Narang and Amal Al-Naimi",authors:[{id:"64755",title:"Dr.",name:"Indra",middleName:null,surname:"Narang",fullName:"Indra Narang",slug:"indra-narang"},{id:"150487",title:"Dr.",name:"Amal",middleName:null,surname:"Al-Naimi",fullName:"Amal Al-Naimi",slug:"amal-al-naimi"}]},{id:"27133",title:"Cardiovascular Consequences of Preterm Birth in the First Year of Life",slug:"cardiovascular-consequences-of-preterm-birth-in-the-first-year-of-life",signatures:"Karinna Fyfe, Stephanie R. Yiallourou and Rosemary S.C. Horne",authors:[{id:"65994",title:"Prof.",name:"Rosemary",middleName:null,surname:"Horne",fullName:"Rosemary Horne",slug:"rosemary-horne"},{id:"150467",title:"Dr.",name:"Karinna",middleName:null,surname:"Fyfe",fullName:"Karinna Fyfe",slug:"karinna-fyfe"},{id:"150468",title:"Dr.",name:"Stephanie",middleName:null,surname:"Yiallourou",fullName:"Stephanie Yiallourou",slug:"stephanie-yiallourou"}]},{id:"27134",title:"The Effect of Preterm Birth on Kidney Development and Kidney Function over Time",slug:"the-effect-of-preterm-birth-on-kidney-development-and-kidney-function-over-time",signatures:"M.G. Keijzer-Veen and A.J. van der Heijden",authors:[{id:"70693",title:"Dr.",name:"Mandy",middleName:"G",surname:"Keijzer-Veen",fullName:"Mandy Keijzer-Veen",slug:"mandy-keijzer-veen"},{id:"71252",title:"Prof.",name:"Aj",middleName:null,surname:"Van Der Heijden",fullName:"Aj Van Der Heijden",slug:"aj-van-der-heijden"}]}]}],publishedBooks:[{type:"book",id:"776",title:"Preterm Birth",subtitle:"Mother and Child",isOpenForSubmission:!1,hash:"4e5369103770cdbf61058ad75e2e63bb",slug:"preterm-birth-mother-and-child",bookSignature:"John C. Morrison",coverURL:"https://cdn.intechopen.com/books/images_new/776.jpg",editedByType:"Edited by",editors:[{id:"68209",title:"Dr.",name:"John",surname:"Morrison",slug:"john-morrison",fullName:"John Morrison"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"952",title:"Cesarean Delivery",subtitle:null,isOpenForSubmission:!1,hash:"cdde3ddf5707430e18678e9ed4c77f4e",slug:"cesarean-delivery",bookSignature:"Raed Salim",coverURL:"https://cdn.intechopen.com/books/images_new/952.jpg",editedByType:"Edited by",editors:[{id:"91354",title:"Dr.",name:"Raed",surname:"Salim",slug:"raed-salim",fullName:"Raed Salim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5937",title:"Obstetrics",subtitle:null,isOpenForSubmission:!1,hash:"092197b1191815505a23e7dd1c9edde6",slug:"obstetrics",bookSignature:"Hassan Salah Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/5937.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6295",title:"Pregnancy and Birth Outcomes",subtitle:null,isOpenForSubmission:!1,hash:"fc1274517f5c0c09b0a923b3027f3d8a",slug:"pregnancy-and-birth-outcomes",bookSignature:"Wei Wu",coverURL:"https://cdn.intechopen.com/books/images_new/6295.jpg",editedByType:"Edited by",editors:[{id:"178661",title:"Dr.",name:"Wei",surname:"Wu",slug:"wei-wu",fullName:"Wei Wu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7173",title:"Multiple Pregnancy",subtitle:"New Challenges",isOpenForSubmission:!1,hash:"f599a465410812da5aee0b247d427e9b",slug:"multiple-pregnancy-new-challenges",bookSignature:"Julio Elito Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7173.jpg",editedByType:"Edited by",editors:[{id:"35132",title:"Prof.",name:"Julio",surname:"Elito Jr.",slug:"julio-elito-jr.",fullName:"Julio Elito Jr."}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"952",title:"Cesarean Delivery",subtitle:null,isOpenForSubmission:!1,hash:"cdde3ddf5707430e18678e9ed4c77f4e",slug:"cesarean-delivery",bookSignature:"Raed Salim",coverURL:"https://cdn.intechopen.com/books/images_new/952.jpg",editedByType:"Edited by",editors:[{id:"91354",title:"Dr.",name:"Raed",surname:"Salim",slug:"raed-salim",fullName:"Raed Salim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"75020",title:"Immunotherapy in Malignant Pleural Mesothelioma",doi:"10.5772/intechopen.95823",slug:"immunotherapy-in-malignant-pleural-mesothelioma",body:'Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy, which is mainly caused by asbestos exposure [1]. The benefit of surgical resection is controversial, because only a minority of patients with MPM meets the criteria for surgery, and it is unrealistic to assume that surgery will achieve a complete tumor resection without a micro residual tumor. Systemic chemotherapy with platinum plus pemetrexed is the recommended first-line systemic therapy for advanced MPM. However, the median overall survival (OS) is only approximately 12 months [2]. For patients that fail first-line chemotherapy, a standard second-line chemotherapy has not been defined [3]. Hence, it is critically essential to develop a new treatment option.
Recently, immunocheckpoint inhibitors (ICIs) have achieved great success in treating several cancer types [4, 5, 6, 7]. Basic research about the immune-suppressive tumor microenvironment in MPM has suggested that MPM might be a good candidate for immune therapy [8, 9]. CD8+ tumor-infiltrating lymphocytes were reported to predict a favorable prognosis after a resection of MPM [10]. In fact, recently, ICIs have shown promising results for patients with MPM.
In this chapter, we summarize recent studies on immunotherapy for MPM.
Anti-cytotoxic T-lymphoctye antigen 4 (CTLA-4) antibody was the first reported ICI for treating MPM. To date, three clinical trials have tested anti CTLA 4 antibody monotherapy for MPM.
In the first phase II trial (MESOT-TREM-2008), the anti-CTLA-4 monoclonal antibody, tremelimumab (15 mg/kg) was administered intravenously once every 90 days to patients with MPM [11]. Twenty-nine patients with MPM that had failed a first-line platinum-based regimen were enrolled. Of these, no patients achieved a complete response, 2 patients achieved a partial response, and 7 others achieved durable disease control. The median progression-free survival (PFS) was 6.2 months, and the median OS was 10.7 months. The second phase II trial (MESOT-TREM-2012), enrolled 29 patients with MPM that were treated with 10 mg/kg tremelimumab, initially every 4 weeks for 6 doses, then every 12 weeks [12]. The disease control rate was slightly improved after this regimen modification; one patient achieved a partial response, and 11 patients achieved disease control.
Based on these two trials, a large scale, randomized trial (DETERMINE) was conducted [13] with 571 patients with MPM. Of these, 382 patients were assigned to tremelimumab and 189 patients were assigned to placebo. However, there was no significant difference in PFS or OS between these two groups. After the DETERMINE trial, anti-CTLA-4 antibodies were investigated only in combination with an anti-programmed cell death protein 1 (anti-PD-1) antibody or anti-programmed death ligand 1 (PD-L1) antibody.
Mansfield et al. reported that PD-L1 was expressed in approximately 42 of 106 MPM specimens, and that PD-L1 expression was significantly correlated with poor survival (OS: 5 months in a PD-L1-positive group vs. 14.5 months in a PD-L1-negative group) [14]. Cedrés et al. also reported that PD-L1 expression was a negative prognostic factor in patients with MPM [15]. These results supported the notion that PD-L1 might serve as a potential target for immunotherapy in MPM.
Avelumab is a human IgG1 monoclonal antibody that binds to PD-L1 [16]. Hassan et al. described a phase I trial (JAVELIN Solid Tumor) that enrolled 53 patients with unresectable MPM. Those patients had failed first-line chemotherapy with platinum and pemetrexed. When they were treated with avelumab, the objective response rate was 9% (one complete response and four partial responses) [17]. Responses were durable (median, 15.2 months), and they were observed both in patients with PD-L1-positive tumors (objective response rate [ORR]: 19%) and in those with PD-L1-negative tumors (ORR: 7%). The median PFS was 4.1 months, and median OS was 10.7 months.
Another anti-PD-L1 antibody, durvalumab, was recently evaluated for efficacy in 54 patients with MPM that were not treated previously. Durvalumab was combined with cisplatin and pemetrexed as a first-line chemotherapy (DREAM trial) [18]. The ORR was 48%, and, 31/54 (57%) patients were progression-free at 6 months. Based on the phase II trial results, a phase III trial is currently planned.
Pembrolizumab is an antibody against PD-1. Pembrolizumab was tested for efficacy in 25 patients with PD-L1-positive MPM in a non-randomized, phase Ib trial [19]. Five patients (20%) achieved a partial response, and 72% of patients achieved disease control. The median OS was 18 months.
A phase II trial of pembrolizumab monotherapy was conducted in 65 patients with MPM that had been treated previously [20]. Among those patients, 19% achieved a partial response to pembrolizumab. The median PFS and OS were 4.5 and 11.5 months, respectively.
Based on these two trials, pembrolizumab was administered, off-label, to 93 patients with MPM in Switzerland and Australia [21]. The ORR was 18%, and the median PFS and OS were 3.1 months and 7.2 months, respectively. Patients with high PD-L1 expression showed improved ORR (44%) and PFS (6.2 months). Recently, a retrospective study from Australia analyzed data from patients with MPM that received pembrolizumab as the first-, second-, or subsequent-line treatment. They found an ORR of 18%, and a disease control rate of 56%. The median PFS was 4.8 months, and the median OS was 9.5 months [22].
Nivolumab is a fully humanized monoclonal anti-PD-1 antibody. It was first tested in 34 patients with recurrent MPM in the Netherlands [23]. In that single-center trial, patients with MPM received 3 mg/kg intravenous nivolumab every 2 weeks. Among 34 patients, 8 patients (24%) achieved a partial response, and another 8 patients (24%) displayed stable disease at 12 weeks.
A Japanese group also evaluated the efficacy and safety of nivolumab in 34 patients with advanced MPM. That study tested nivolumab as a salvage therapy in a single-arm phase II study (MERIT study) [24]. Patients received 240 mg nivolumab intravenously every 2 weeks. Ten (29%) patients showed an objective response. The median duration of the response was 11.1 months, and the disease control rate was 68%. The median PFS and OS were 6.1 and 17.3 months, respectively. Among patients with PD-L1-positive tumors (≥1% expression), the ORR was 40%. Based on those results, nivolumab was approved in Japan for unresectable recurrent MPM.
Based on the favorable results obtained with ICI monotherapy, recent investigations tested combination treatments, with an anti-PD-1 or anti-PD-L1 antibody combined with an anti-CTLA-4 antibody. This combination was expected to maximize T-cell activation.
NIBIT-MESO-1 was open-label, non-randomized, phase II trial, in which 40 patients with MPM received at least one dose each of tremelimumab and durvalumab [25]. Eleven patients (28%) displayed an objective response. The median PFS was 5.7 months and the median OS was 16.6 months.
IFCT-1501 MAPS2 was a multicenter, open-label, randomized, phase II trial, in which 108 patients with MPM were randomly assigned to receive intravenous nivolumab or intravenous nivolumab plus ipilimumab. In the intention-to-treat population, 12-week disease control (primary endpoint) was achieved by 25/63 (40%) patients in the nivolumab group and 32/62 (52%) patients in the combination group [26]. The INITIATE study also evaluated the efficacy of nivolumab combined with ipilimumab in patients with MPM. In that study, among 34 patients included in the efficacy assessment, ten (29%) patients achieved a partial response, and 23 patients (68%) achieved 12 weeks of disease control [27]. Based on these favorable results, a phase III randomized study was conducted to compare nivolumab plus ipilimumab to platinum doublet chemotherapy as a first-line therapy in unresectable MPM. In that study, 303 patients were randomized to nivolumab plus ipilimumab and 302 patients were randomized to platinum doublet chemotherapy. With a minimum follow-up of 22 months, the primary endpoint, OS, was significantly improved with nivolumab plus ipilimumab compared to chemotherapy (median, 18.1 vs. 14.1 months; hazard ratio, 0.74; 95% confidence interval, 0.61–0.89; P = 0.002) [28].
Overview of clinical trials of that tested ICIs for MPM was summarized in Table 1.
Agent | Year | N | ORR (%) | mPFS (mo) | mOS (mo) | Study type | Reference |
---|---|---|---|---|---|---|---|
Tremelimumab | 2013 | 29 | 7 | 6.2 | 10.7 | 2 | Calabro et al. [11] |
Tremelimumab | 2015 | 20 | 3 | 6.2 | 11.3 | 2 | Calabro et al. [12] |
Tremelimumab | 2017 | 571 | 5 | 2.8 | 7.7 | 2b | Maio et al. [13] |
Avelumab | 2019 | 53 | 9 | 4.1 | 10.7 | 1b | Hassen et al. [17] |
Pembrolizumab | 2017 | 25 | 20 | 5.4 | 18 | 1b | Alley et al. [19] |
Pembrolizumab | 2018 | 65 | 19 | 4.5 | 11.5 | 2 | Desai et al. [20] |
Nivolumab | 2018 | 34 | 24 | 2.6 | 11.8 | 2 | Quispel-Janssen et al. [23] |
Nivolumab | 2018 | 34 | 29 | 6.1 | 17.3 | 2 | Okada et al. [24] |
Tremelimumab/Durvalumab | 2018 | 40 | 28 | 5.7 | 16.6 | 2 | Calabro et al. [25] |
Nivolumab/Ipilimumab | 2019 | 62 | 28 | 5.6 | 15.9 | 2 | Scherpereel et al. [26] |
Nivolumab | 63 | 19 | 4 | 11.9 | |||
Nivolumab/Ipilimumab | 2019 | 34 | 29 | 6.2 | NR | 2 | Disselhorst et al. [27] |
Nivolumab/Ipilimumab | 2020 | 303 | 40 | 6.8 | 18.1 | 3 | Baas et al. [28] |
Overview of clinical trials that tested immunocheckpoint inhibitors for malignant pleural mesothelioma.
ORR: objective response rate; mPFS: median progression free survival; mo: months; mOS: median overall survival; CTLA: cytotoxic T-lymphocyte antigen; PD-L1: programmed death ligand 1; PD-1: programmed cell death protein 1.
Cancer vaccines have been tested for various cancer types. These vaccines have included tumor lysate, attenuated bacteria, and single or multiple peptides. Wilms tumor 1 (WT-1) is one of the most well investigated cancer antigens. WT-1 was expressed in tumors in 97% of patients with MPM [29]. Galinpepimut-S, a multivalent vaccine against the WT 1 peptide, can activate both CD4+ and CD8+ T-cells [30]. The efficacy and safety of galinpepimut-S was investigated in a phase II trial. The pilot study demonstrated that the median PFS was 7.4 months in the placebo group and 10.1 months in the vaccine group. The median OS was 18.3 months in the placebo group and 22.8 months in the vaccine group. Based on th0se findings, a clinical trial is currently ongoing to investigate a combination treatment of galinpepimut-S plus nivolumab in patients with MPM (with WT-1-positive tumors). Combining cancer vaccines with ICIs might improve the clinical outcome and open a new avenue of therapeutic strategies for MPM.
Vaccination strategies have been developed that involve dendritic cells (DCs), which are antigen-presenting cells for T-cell activation. The DCs are pulsed with tumor lysate to overcome the shortcomings of autologous DCs. These strategies have shown remarkable anti-tumor activity, with low toxicity, in several cancer types. In the area of MPM, 9 patients received three vaccinations of autologous mature DCs loaded with autologous tumor cell lysate [31]. Among these patients, 3 showed a partial response in the first 8 weeks after the DC vaccination. However, two of those three patients had received chemotherapy before the DC vaccination, which might have influenced the anti-tumor effect. In the next step of treatment, they added cyclophosphamide to increase the anti-tumor activity by inhibiting regulatory T cells [32]. Ten patients with MPM received cyclophosphamide and a vaccination of autologous mature DCs loaded with autologous tumor cell lysate. Of those ten patients, seven lived longer than 24 months, and the mean OS was 37 months.
Obtaining autologous tumor cell lysate is time consuming, because patients have to undergo multiple tumor biopsies. In one study, allogeneic tumor lysate obtained from a tumor cell line was applied to autologous DCs [33]. Nine patients with MPM were treated with DC vaccinations (autologous DCs pulsed with tumor lysate from five mesothelioma cell lines). Of these, two patients experienced a partial response and all nine patients established disease control. The median OS was longer than 22.8 months. Based on those promising results, an ongoing phase II/III study is currently testing DCs loaded with allogeneic tumor cell lysate as a maintenance therapy after chemotherapy (DENIM trial) [34].
Chimeric antigen receptor (CAR) T-cells can be used to target specific tumor antigens directly. CAR T-cell therapy has shown clinical efficacy for hematological malignancies, and it was approved by the United States Food and Drug Administration for B cell acute leukemia and diffuse large B-cell lymphoma. Several clinical trials are ongoing to test CAR T-cell therapy on both hematological malignancies and solid tumors [35]. CAR T-cells that targeted WT-1, fibroblast activation protein (FAP), or mesothelin (MSLN) were tested in a clinical trial on MPM. Hass et al. reported the results of a clinical trial for testing CAR T-cells that targeted MSLN on 15 patients with MPM. The CAR T-cells were applied as a monotherapy or in combination with low-dose cyclophosphamide, for solid tumors [36]. The best overall response was stable disease (11 of 15 patients). Currently, several phase I trials are ongoing to examine the efficacy of CAR T-cell therapy in solid tumors, including MPM.
The prognosis of MPM remains poor. A PD-1/PD-L1 blockade is an effective treatment option for MPM. The combination of nivolumab (anti-PD-1 antibody) and ipilimumab (anti-CTLA-4 antibody) could be a standard first-line treatment. Additionally, the combination of an ICI with conventional chemotherapy might be a promising treatment option. Cellular therapies and cancer vaccines must overcome many challenges, such as T-cell migration to the tumor and infiltration into the tumor. Improvements in cancer therapies are urgently needed to overcome these difficulties. Further research with large-scale clinical trials are needed to clarify the utility and safety of these immunotherapies in MPM. In addition, in this new era of precision medicine, we need to develop biomarkers to identify which patients would benefit from ICI-ICI combinations, ICI plus chemotherapy, or cellular therapy.
This study was supported by grants-in-aid from the Ministry of Health, Labor, and Welfare, Japan.
Dr. Fujimoto received consultancy fees from Boehringer Ingelheim, Ono, Bristol-Myers Squibb, Kyorin, and Kissei. Dr. Fujimoto also received honoraria or research funding from Hisamitsu, Chugai, Ono, Taiho, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, GlaxoSmithKline, and MSD.
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Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. Gómez-Virgilio, G. Ramírez-Rodríguez, E. Vera-\nArroyo, R. Fiorentino-Pérez, U. García, J. 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MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. 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Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. 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Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. 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Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"}],onlineFirstChaptersTotal:17},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"May 19th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:"Universidad Michoacana de San Nicolás de Hidalgo",institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",slug:"maria-dos-anjos-pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",slug:"marina-spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",slug:"sara-savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. 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Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"14",type:"subseries",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:17,paginationItems:[{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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