FDA approved biologics for systemic treatment of moderate-to-severe plaque psoriasis.
\\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:"7454",leadTitle:null,fullTitle:"Industrial Engineering",title:"Industrial Engineering",subtitle:null,reviewType:"peer-reviewed",abstract:"Businesses across the world are aiming for increased productivity and greater efficiency. 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This book presents the current state of the art of industrial engineering and provides useful information to those who wish to optimize their business practices while increasing customer service and quality.",isbn:"978-1-83880-346-9",printIsbn:"978-1-83880-345-2",pdfIsbn:"978-1-83880-633-0",doi:"10.5772/intechopen.75414",price:119,priceEur:129,priceUsd:155,slug:"industrial-engineering",numberOfPages:102,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7008bbdc804192f8969a34deda417b05",bookSignature:"Ainul Akmar Mokhtar and Masdi Muhammad",publishedDate:"May 2nd 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7454.jpg",numberOfDownloads:5135,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 20th 2018",dateEndSecondStepPublish:"March 13th 2018",dateEndThirdStepPublish:"May 12th 2018",dateEndFourthStepPublish:"July 31st 2018",dateEndFifthStepPublish:"September 29th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"219461",title:"Associate Prof.",name:"Ainul Akmar",middleName:null,surname:"Mokhtar",slug:"ainul-akmar-mokhtar",fullName:"Ainul Akmar Mokhtar",profilePictureURL:"https://mts.intechopen.com/storage/users/219461/images/6967_n.jpg",biography:"Dr. Ainul Akmar binti Mokhtar is an associate professor in the Department of Mechanical Engineering at Universiti Teknologi Petronas (UTP), Malaysia. She is also a programme manager for the MSc programme in Asset Management and Maintenance at the university. Prior to joining UTP, she worked with Seagate Technology (M) Sdn Bhd as a process engineer. Dr. Mokhtar earned a BSc in Industrial Engineering from Purdue University, Indiana, USA, and an MSc in Manufacturing Systems from Nottingham University, England, UK. She earned a PhD in Mechanical Engineering at UTP for her research on “Failure Probability Model for Piping Systems subject to Corrosion under Insula-tion.” She is actively involved in research and industrial projects related to reliability and maintenance, asset management, and operations research, and she supervises graduate students in these areas. She is also a trainer for training related to reliabil-ity engineering, asset life cycle analysis, and risk-based inspection, to name a few. 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Dr. Muhammad earned a BSc in Mechanical Engi-neering and an MSc in Manufacturing System Engineering from Lehigh University, Pennsylvania, USA. He earned his PhD in Mechanical Engineering at UTP with research on “Reliability Model for Repairable Systems with Multi-State Degradation.” He is actively involved in research col-laboration and consultancy with industries, and he supervises graduate students studying reliability and maintenance. He has twelve years of experience working in various positions at one of the leading semiconductor companies, involving pro-cess and equipment engineering, product development and material quality. He is a chartered engineer and member of the Board of Engineers Malaysia (BEM), the Institute of Engineers, Malaysia (IEM), and the American Society of Mechanical Engineers (ASME). He is also a Certified Reliability Engineer by the American Soci-ety for Quality (ASQ ) and a Certified Maintenance and Reliability Professional by the Society for Maintenance and Reliability Professionals (SMRP)",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"799",title:"Industrial Engineering",slug:"industrial-engineering-and-management-industrial-engineering"}],chapters:[{id:"65764",title:"Supplier Evaluation and Selection in Automobile Industry",doi:"10.5772/intechopen.84383",slug:"supplier-evaluation-and-selection-in-automobile-industry",totalDownloads:1841,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In automobile industry, to operate effectively the supply chain management, the purchasing function is very important to perform effectively. 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Sunnapwar"}],corrections:null},{id:"64398",title:"Optimal Control Promotional Policy for a New Product Incorporating Repeat Purchase in Segmented Market: A Control Theoretic Approach",doi:"10.5772/intechopen.81385",slug:"optimal-control-promotional-policy-for-a-new-product-incorporating-repeat-purchase-in-segmented-mark",totalDownloads:860,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter considers an optimal control model to obtain dynamic promotional policies for a product considering a segmented market where first-time and additional repeat purchase sales are assumed to be generated through mass and differentiated promotions. Mass promotion is carried out in the whole market which reaches each segment with a fixed spectrum, and differentiated promotion is catered to each segment individually. The firm’s finite promotional resources are to be allocated for promoting a product at mass and segment levels of the market in a finite time period. The formulated control problem obtains optimal promotional effort policy for each segment using the maximum principle. The applicability of the proposed control model is illustrated through a numerical example by discretizing the model.",signatures:"Kuldeep Chaudhary and Prakash C. Jha",downloadPdfUrl:"/chapter/pdf-download/64398",previewPdfUrl:"/chapter/pdf-preview/64398",authors:[{id:"249727",title:"Dr.",name:"Kuldeep",surname:"Chaudhary",slug:"kuldeep-chaudhary",fullName:"Kuldeep Chaudhary"},{id:"257593",title:"Prof.",name:"P.C.",surname:"Jha",slug:"p.c.-jha",fullName:"P.C. Jha"}],corrections:null},{id:"66441",title:"Integrated Batch Production and Maintenance Scheduling to Minimize Total Production and Maintenance Costs with a Common Due Date Constraint",doi:"10.5772/intechopen.85004",slug:"integrated-batch-production-and-maintenance-scheduling-to-minimize-total-production-and-maintenance-",totalDownloads:732,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter discusses an integrated model of batch production and machine maintenance scheduling on a single deteriorating machine and flow shop with a deteriorating machine that produces an item to be delivered at a common due date. The model describes the trade-off between production costs and maintenance costs as the increase of production run length. The objective function of the model is to minimize total cost consisting of in-process and complete inventory holding costs, setup cost, preventive and corrective maintenance costs, and rework cost. The problem is to determine the best production run length and maintenance actions that minimize the total cost.",signatures:"Zahedi Zahedi",downloadPdfUrl:"/chapter/pdf-download/66441",previewPdfUrl:"/chapter/pdf-preview/66441",authors:[{id:"247972",title:"Dr.",name:"Zahedi",surname:"Zahedi",slug:"zahedi-zahedi",fullName:"Zahedi Zahedi"}],corrections:null},{id:"64188",title:"Special Issues of Ensuring Electrical Safety in Networks with Isolated Neutral Voltage up to 1000 V at Mining Enterprises",doi:"10.5772/intechopen.81384",slug:"special-issues-of-ensuring-electrical-safety-in-networks-with-isolated-neutral-voltage-up-to-1000-v-",totalDownloads:833,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In the practice of operating mining machines and complexes, there are no effective ways to monitor the state of insulation and protect a person from electric shock in a network with voltages up to 1000 V. There is a risk of electric shock with a fatal outcome for personnel. Consequently, the issue of development of methods for monitoring the state of insulation and protection against electric shock in a network up to 1000 V for mining machines and complexes is relevant and urgent. The existing protection of a person from electric shock effectively works provided that the total insulation resistance is commensurate with the capacitive insulation resistance of the phases of the electrical network relative to the ground. But, at mining enterprises, a violation of ratio takes place between the total and capacitive insulation resistance of the network, which leads to failure of the protection against electric shock. 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Psoriasis is a chronic immune cell-mediated inflammatory skin disease characterized by the formation of scaly indurated erythema occurring most commonly on the elbows, knees, scalp, and lower back, but any skin surface can be involved [1]. The highly visible condition greatly affects people’s quality of life that can be stigmatizing. People with psoriasis are at an increased risk of developing other chronic and serious health conditions. Comorbidities include psoriatic arthritis, inflammatory bowel disease, hypertension, diabetes, obesity, and depression. The worldwide prevalence of psoriasis is estimated to be 2–4%, rising up to 9.7% in Scandinavian countries [2, 3].
Psoriasis can be classified into mild, moderate, or severe disease according to the Psoriasis Area and Severity Index (PASI). Treatment choices are often based on the severity of disease: mild disease often managed with topical therapy, and moderate-to-severe disease requiring systemic therapy for control, often with concomitant topical therapy [4, 5, 6]. Effects of systemic therapy in synergy with topical agents may help reduce the burden and achieve better quality of life that psoriasis patients deserve. In mild-to-moderate, as well as moderate-to-severe, psoriasis, 70–80% of patients start with topical agents and continue to use them with other active therapies.
Currently, high-potency topical glucocorticoid and vitamin D derivatives are the main treatments for psoriasis [7, 8, 9]. Topical glucocorticoids are effective but their use is limited to no more than 2–8 weeks due to their long-term side effects, such as atrophy [10]. This is particularly true in more sensitive areas, such as the face or intertriginous areas. There are numerous reports of low satisfaction for these topical agents [11]. Hence, there remains great unmet medical needs for developing a highly efficacious and safe topical treatment in psoriasis.
In psoriatic skin, immune response is overactive. Excess amounts of cytokines were produced, which caused prolonged inflammation and abnormal proliferation of keratinocytes. In recent decades, genetic and immunological studies have made progress in dissecting the mechanisms of psoriasis. Psoriasis was previously thought to be an interferon (IFN)-γ-producing T helper (TH) 1-driven autoimmune inflammatory disease [12, 13]. However, the discovery of TH17 cells shifted the view of psoriasis as an TH17-dependent pathology rather than TH1 cells [12, 13, 14].
IFN-γ is increased in serum from psoriasis patients and its mRNA is elevated in skin lesions [15, 16]. It was hypothesized that IFNγ blockade could decrease disease activity due to the appreciation of elevated IFN-γ expression in psoriasis. A neutralized humanized anti-IFN-γ antibody, HuZAF, was developed and tested in two small pilot studies between 2001 and 2003 [17]. In the study that was designed to determine the efficacy of miltidose HuZAF, of all 10 patients treated four times with 10 mg/kg of HuZAF, only 1 patient (10%) achieved a significant clinical response. The expression of CXCL9 was significantly suppressed by HuZAF through week 12. This finding suggests IFN-γ was successfully blocked by HuZAF in these patients since CXCL9 is heavily regulated by IFN-γ. The limited clinical efficacy of IFNγ blockade by HuZAF in patients with psoriasis suggest that infiltration of TH1 cells in psoriatic plaque likely contribute little to the pathogenesis of this disease.
The naive T cells are differentiated into TH1, TH2, TH17, or Treg cells depending on specific cytokines released by antigen-presenting cells and T-cell receptor stimulation and costimulation. The differentiation of TH17 cells are induced by interleukin (IL)-6, transforming growth factor (TGF)-β, and IL-21 [18, 19, 20]. Maintenance of TH17 population requires IL-23, a heterodimeric cytokine expressed by macrophages and dendritic cells [21, 22]. The intracellular transcription factors RORγt and STAT3 are also critical in the development of TH17 cells. Binding of IL-23 to IL-23 receptor (IL23R) attracts a heterodimer of kinase JAK2 and TYK2 and induces phosphorylation of STAT3, which enhances RORγ-mediated transcription of IL-17A and IL-17F [23, 24]. TGF-β1 is abundantly expressed in plasma and scales from psoriatic lesions and transgenic mice that overproduce human TGF-β1 in basal keratinocytes exhibit classic signs of psoriasis [25]. Similar observations were made with STAT3, which is overproduced in psoriasis, and its transgenic mice also exhibit psoriasis-like phenotypes [26]. Under the regulation of IL-23, activated TH17 cells in the skin produce high levels of IL-17, which is often referred to as the IL-23/IL-17 axis.
On developing TH17 cells, the expression of IL-23R is induced by intracellular signaling through RORγt and STAT3 and extracellular TGF-β1. The expression of IL-23R then promotes responsiveness to IL-23, which is the key cytokine in the survival and proliferation of TH17 cells [27, 28]. In psoriasis lesions, IL-23 is overproduced by dendritic cells and keratinocytes [29, 30, 31].
The importance of IL-23 in psoriasis has been confirmed by genetic studies. Polymorphisms in both subunits of IL-23, IL23A (p19) and IL12B (p40), and IL23R have been reported to be associated with an increased risk of psoriasis in North Americans, Europeans and Asians [32, 33]. A common risk haplotype of IL-23R, proline at amino acid 310 and arginine at amino acid 381, was identified. A single amino acid change from arginine to glutamine at amino acid 381 in IL-23R was found to be protective against psoriasis. Interestingly, this amino acid is located at the JAK2 kinase-binding domain of IL-23R. It is likely the change to glutamine breaks the IL-23R signaling and blocks inflammatory response induced by TH17 cell. In mouse studies, intradermal injection of recombinant IL-23 in normal-appearing skin induces skin inflammation and produces erythematous, thick and scaly skin with histologic features reminiscent of psoriasis [34], and IL-23 deficient mice were resistant to imiquimod-induced psoriasis-like inflammation [35]. Similarly, mice lacking IL-23 are resistant to experimental autoimmune encephalomyelitis (EAE) [21].
IL-23 belongs to the IL-12 family of cytokines and consists of two subunits: p19 and p40. P19 is unique for IL-23 and p40 is shared with IL-12. There are several lines of evidence to demonstrate the central role of IL-23, but not IL-12, in the pathogenesis of psoriasis [14]. The high expression of p19 and p40, but not IL-12 specific p35 expression, was observed in psoriatic lesions as compared to nonlesional skin [36]. Mice lacking the p35 subunit of IL-12 (
IL-23 is required for autoimmune inflammation mediated by TH17 cells and produces large amounts of IL-17
Among six isoforms of IL-17, IL-17A and IL-17F are the most pathogenic in psoriasis [31]. IL-17A is often referred to as IL-17, for which the TH17 cell lineage is named. Besides TH17 cells, a large number of other skin cells also produce IL-17, including γδ T cells, αβ T cells, neutrophils, mast cells, ILC3s and Tc17 cells. Some production is independent of IL-23 [12]. In psoriatic skin, IL-17 expression is higher, and the number of TH17 cells, γδ T cells, Tc17 cells were all greatly increased compared to normal skin [30, 41]. Genes that are up-regulated in keratinocytes treated by IL-17A
Even in nonlesional skin from psoriasis patients, expression of IL-17-downstream genes is higher compared to normal skin, and disease severity is significantly correlated with levels of IL-17 and TNF-α in blood. There is also a strong correlation between PASI scores and pathways related to IL-17 [44]. All the evidence suggests that IL-17 is the central effector cytokine in psoriasis.
Table 1 summarizes biologics approved by the US Food and Drug Administration (FDA) for the systemic treatment of plaque psoriasis [45, 46, 47, 48]. These biologics specifically target cytokines and the receptors involved in psoriasis pathogenesis. Treatment with biologics results in a greater efficacy and better safety profile compared to conventional systemic agents that do not target specific components of the immune system, and demonstrates the essential role of the IL-23/IL-17 axis in psoriasis [49, 50].
Drug Class | Target molecule | Therapeutic Agent (Trade name) | Year of FDA approval | Dose and Administration | Other Indications |
---|---|---|---|---|---|
TNF blocker (biologics) | TNF | Etanercept (Enbrel®) | 2004 | 50 mg twice weekly for 3 months, followed by 50 mg once weekly; S.C. injection | RA; JIA; PsA; AS |
Infliximab (Remicade®) | 2006 | 5 mg/kg at weeks 0, 2, 6 followed by 5 mg/kg every 8 weeks; I.V. infusion | RA; PsA; AS; CD; UC | ||
Adalimumab (Humira®) | 2008 | 80 mg on day 1 followed by 40 mg every other week; S.C. injection | RA; JIA; PsA; AS; CD; UC; HS; Uveitis | ||
Certolizumab pegol (Cimzia®) | 2018 | 400 mg every other week; S.C. injection | RA; PsA; AS; CD; non-radio -graphic AS | ||
IL-12/23 antagonist (biologics) | IL-12/23 p40 | Ustekinumab (Stelara®) | 2009 | 45 mg or 90 mg at weeks 0, 4, followed by 45 mg or 90 mg every 12 weeks; S.C. injection | PsA; CD; UC |
IL-17 antagonist (biologics) | IL-17A | Secukinumab (Cosentyx®) | 2015 | 300 mg at weeks 0, 1, 2, 3, 4, followed by 300 mg every 4 weeks; S.C. injection | PsA; AS; non-radio -graphic AS |
Ixekizumab (Taltz®) | 2016 | 160 mg at week 0; 80 mg every 2 weeks for 3 months, followed by 80 mg every 4 weeks; S.C. injection | PsA; AS; non-radiographic AS | ||
IL-17RA | Brodalumab (Siliq®-US; Kyntheum®-Europe) | 2017 | 210 mg at weeks 0, 1, 2, followed by 210 mg every 2 weeks; S.C. injection | none | |
IL-23 antagonist (biologics) | IL-23 p19 | Guselkumab (Tremfya®) | 2017 | 100 mg at weeks 0, 4, followed by 100 mg every 8 weeks; S.C. injection | PsA |
Tildrakizumab (Ilumya™) | 2018 | 100 mg at weeks 0, 4, followed by 100 mg every 12 weeks; S.C. injection | none | ||
Risankizumab (Skyrizi™) | 2019 | 150 mg at weeks 0, 4, followed by 150 mg every 12 weeks; S.C. injection | none |
FDA approved biologics for systemic treatment of moderate-to-severe plaque psoriasis.
TNF = tumor necrosis factor; IL = interleukin; S.C. = subcutaneous; I.V. = intravenous; RA = rheumatoid arthritis; JIA = juvenile idiopathic arthritis; PsA = psoriatic arthritis; AS = ankylosing spondylitis; CD = crohn’s disease; UC = ulcerative colitis; HS = hidradenitis suppurativa.
The first-generation anti-psoriatic biologics targeting cytokines focussed on TNF, an inflammatory cytokine implicated in psoriasis pathogenesis for a long time. High levels of TNF and its receptors (TNFR1 and TNFR2) are expressed in psoriatic lesional skin [51]. Four TNF blockers were approved by the FDA for psoriasis treatment (Table 1). TNF inhibition showed good therapeutic efficacy. At week 24, about 50 to 80 percent of patients reached 75% improvement in the psoriasis area and severity index (PASI75), and 10 to 20 percent got PASI100, which means 100% improvement [14]. Infliximab is the most efficacious TNF blocker followed by adalimumab and etanercept [50]. The primary mechanism of action of TNF blockers in improvement of psoriasis treatment is most likely due to its indirect effect on IL-23/IL-17 signaling pathway. The therapeutic effects of TNF blockade are observed to be associated with a strong reduction of IL-17-dependent genes [52]. In addition, TNF induces IL-23 expression in keratinocytes [53]. The exact roles of TNF in the pathogenesis of psoriasis are not yet completely understood.
Nevertheless, TNF is a versatile cytokine that not only involves inflammatory immune responses, but also contributes to cell death, cell cycling and tissue remodeling [54]. TNF blockers are well-known associated risk factors of serious infections, such as lower respiratory tract and skin and soft tissue infections like pneumonia and cellulitis [55]. After initial treatment of around 2 weeks, 2% ~ 5% of the patients developed paradoxical psoriasis: new lesions developed or the existing lesions got worse [54]. This side effect also happened when TNF blockers were used to treat other autoimmune diseases, including Crohn’s disease and rheumatoid arthritis [53, 56]. It has been reported that IL-17A expression was strong in skin lesions from patients who had paradoxical psoriasis and needed other therapy [57]. This suggests that under some conditions, IL-17 is not down-regulated while blocking TNFα so that skin lesions continue to develop.
After TNF blockers, biologics that directly target the IL-23/IL-17 axis have been developed. The second-generation monoclonal antibody, ustekinumab, is targeting the subunit p40 common to IL-12 and IL-23, blocking signaling of their cognate receptors that induce a nonspecific inhibition of TH1 and TH17 [58, 59]. Ustekinumab has efficacy similar to TNFα inhibitors. It is better than etanercept, but not as good as infliximab. Ustekinumab received FDA approval for the treatment of moderate-to-severe psoriasis in 2009 (Table 1).
IL-17 is a central proinflammatory effector cytokine downstream of IL-23 and implicated in the pathogenesis of psoriasis. The third-generation monoclonal antibodies that neutralize IL-17 became available for the treatment of psoriasis (Table 1). Secukinumab and ixekizumab are human monoclonal antibodies against IL-17A. Brodalumab is blocking IL-17RA, which is the receptor for IL-17A, IL-17C, IL-17E, IL-17F and IL-17 A/F heterodimers. As IL-17A, IL-17C and IL-17F are all up-regulated in psoriatic skin [31], it is likely that brodalumab would have a better effect. In a study that brodalumab was given to patients who experienced unsuccessful treatment with either secukinumab or ixekizumab, PASI75, PASI90 and PASI100 scores were achieved in 69%, 44% and 28% of patients [60]. In phase III trials, 30–60% of patients treated with IL-17 antagonists reached PASI100 [61, 62, 63, 64, 65]. The superior efficacy of IL-17 blockade over neutralizing IL-12/IL23 and blocking TNF has been demonstrated in head-to-head clinical trials of brodalumab versus ustekinumab [62] and ixekizumab versus etanercept [61, 62].
The most common adverse effects of IL-17 antagonists are nasopharyngitis, upper respiratory tract infections, mucocutaneous candidiasis, transient neutropenia and injection site reactions. Mucocutaneous candidiasis observed by IL-17 inhibition or inborn genetic errors of IL-17 gene [66] suggests the innate, protective role of IL-17 against microbial pathogens on the skin. There is a black box warning for brodalumab due to the results from AMAGINE 1 and 2, where four patients committed suicide during the treatment period [64, 65].
IL-23 is known as the master regulator of TH17 cells. A fourth-generation of monoclonal antibodies against p19 subunits of IL-23, guselkumab, tildrakizumab and risankizumab, have been approved for treatment of moderate-to-severe psoriasis (Table 1). In contrast to ustekinumab, these biologics target IL-23 by neutralizing the p19 subunit without disrupting the IL-12 signaling pathway. Selectively targeting IL-23p19 provides better efficacy than ustekinumab [50]. IL-23 antagonists can reach a PASI90 in more than 50% of patients, confirming the provital role of IL-23 in the pathogenesis of psoriasis [67, 68, 69].
The head-to-head trial of guselkumab versus ustekinumab demonstrates superiority of selectively targeting p19 subunit of IL-23 among patients who had an inadequate response to ustekinumab with similar types of safety profiles [70]. As demonstrated by clinical trial outcomes, double blockade of IL-12 and IL-23 with ustekinumab resulted in lesser disease improvement versus single blockade of IL-23, confirming IL-23, but not IL-12, is a major player in psoriasis.
In addition, IL-23p19 antagonists exhibit significantly higher efficacy compared to all tested TNF blockers while maintaining a favorable safety profile [69, 71]. For example, guselkumab was superior (p < 0.001) to adalimumab for PASI90 response at week 48 (76.3% versus 47.9%), respectively. Compared with IL-17 antagonists, guselkumab exhibits a longer duration of therapeutic effect in patients with psoriasis [69]. This is probably because IL-23 is a key driver of TH17 cell differentiation and survival, and an upstream regulator of IL-17A. IL-17 producing cells are dependent on IL-23 for survival. IL-23 stimulates production of not only IL-17, but also other TH17 cytokines (for example, IL-22) by other immune cell types, including γδ T cells.
The most common adverse events with the use of guselkumab and tildrakizumab are nasopharyngitis, upper respiratory tract infections, and headaches [67, 68, 69]. In contrast to IL-17 antagonists, the rate of mucocutaneous candidiasis was infrequent and comparable to healthy control subjects.
In conclusion, clinical outcomes of these biologics targeting IL-23p19 and IL17 are a strong argument for the IL-23/IL-17 axis in driving disease pathology. These molecular targeted therapies not only remarkably alleviate symptoms but also provide a deep understanding of the molecular mechanism of psoriatic disease.
Targeting a spectrum of inflammatory mediators involved in the pathogenesis of psoriasis will ensure a favorable safety profile and limited side effects. As discussed above, biological treatment, along with evolving systemic therapy, has revolutionized severe psoriasis management. Development of new and effective biologics has made much progress in our understanding of psoriasis immunopathology. Topical therapy implies good compliance for the psoriatic patients, few adverse systemic reactions as compared to systemic medications. However, biologics targeting proinflammatory cytokines are not suitable for topical route delivery due to the large size and poor permeability into skin. Small molecules targeting intracellular signaling pathway have some advantages over biologic agents, particularly the possibility of topical administration, lack of immunogenicity, the simplified synthesis processes, low-cost production, placing these drugs in a very attractive position for future drug discovery and development in topical treatment of psoriasis. New topical targeted therapeutics undergoing efficacy and safety studies are summarized in Table 2 based on the information available from the website of ClinicalTrials.gov [72].
Drug Class | Target molecule | Agent/company | Administration | Highest clinical trial stage | Status |
---|---|---|---|---|---|
RORγ antagonist (small molecule) | RORγ | GSK2981278 /Glaxosmithkline | Topical | Phase 1/2 | Completed (May 2017) |
ESR-114 /Escalier Biosciences B.V. | Topical | Phase 1/2 | Completed (June 2019) | ||
JAK inhibitor (small molecule) | pan-JAKs | Tofacitinib (CP-690550)/Pfizer | Topical | Phase 2 | Completed (Jul 2009) (Nov 2011) (Sept 2014) |
JAK1/2 | Ruxolitinib (Opzelura™)/Incyte | Topical | Phase 2 | Completed (Apr 2009) (Apr 2009) (May 2009) | |
CT327/Creabilis SA | Topical | Phase 2 | Completed (Jan 2011) (Sept 2012) | ||
TYK2/JAK1 | PF-06700841/Pfizer | Topical | Phase 2 | Completed (Apr 20, 2021) | |
DNMT Inhibitor (small molecule) | DNMTs | DUR-928/Durect | Topical | Phase 2 | Completed (May 20, 2020) |
PDE4 inhibitor (small molecule) | PDE4 | AN-2728 (crisaborole)/Pfizer | Topical | Phase 2 | Completed (Mar 2008) (Dec 2008) (June 2010) (June 2011) |
ARQ-151 (roflumilast)/Arcutis Biotherapeutics, Inc. | Topical | Phase 3 | Completed (Nov 2020) (Est. Dec 2022) | ||
AhR agonist (small molecule) | AhR | GSK2894512 (Tapinarof, WBI-1001)/Glaxosmithkline | Topical | Phase 3 | Withdrawn (Sept 2018) (The decision is a business decision based on the need to prioritize and focus resources within GSK) |
Tapinarof (WBI-1001, GSK2894512, DMVT-505)/Dermavant Sciences | Topical | Phase 3 | Completed (May 2020); FDA acceptance of NDA for Tapinarof in plaque psoriasis |
New targeted therapeutics under clinical trials for topical treatment of plaque psoriasis.
DNMT = DNA methyltransferase; PDE4 = phosphodiesterase-4; AhR = aryl hydrocarbon receptor.
RORγt is a master transcription factor of TH17 cells, which activates the transcription of IL-23 receptor gene as well as pro-inflammatory cytokines such as IL-17A, IL-17F, IL-21, and IL-22, and enhances the inflammatory process. Clinical success of biologics in the IL23/IL17 axis suggests that inhibiting RORγ could be an effective alternative therapy for psoriasis.
Vitae Pharmaceuticals (acquired by Allergan, later by Abbvie) developed an orally active RORγt antagonist VTP-43742 for the treatment of autoimmune diseases, including psoriasis through suppression of IL-17A production and down-regulation of the IL-23 receptor [73]. VTP-43742 with high systemic exposure demonstrated a clear signal of efficacy over a short four-week period from a Phase 2a clinical trial in psoriatic patients [74]. It provides a proof of concept of RORγ antagonists for the treatment of psoriasis, consistent with the clinical success of biologics in the IL23/IL17 axis.
Nevertheless, two drug candidates terminated their clinical trials due to potential safety liability. Four patients in the 700 mg VTP-43742 dose group showed reversible transaminase elevations, which led the company to terminate the development of VTP-43742. In addition, Takeda Pharmaceutical Company terminated a phase 1 trial of oral RORγ antagonist TAK828 for evaluation of the safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating multiple doses in healthy volunteers in the United states (NCT02817516). The decision was based on critical non-monitorable toxicology findings in both monkeys and rats, combined with the potential for teratogenicity in humans [75].
RORγ has two isoforms, RORγ1 and RORγ2 (most commonly referred to as RORγt) [76]. RORγt is a differentially spliced isoform of RORγ1, 19 amino acids shorter at N-terminus. The biochemical assay for evaluation of the compounds using LBD of the receptor will result in pan-RORγ antagonists. RORγt is exclusively expressed in a few distinct cell types of the immune system, including Th17, Tc17, γδ T cells and regulatory T cells [43, 77, 78, 79, 80] whereas, RORγ1 exhibits oscillatory expression in liver, brown adipose tissue, and kidney [76, 81]. Systemic exposure of the Pan-RORγ antagonists may have off-target effects against the not-intended target, RORγ1, during the treatment of the diseases. In addition, a mouse genetics study indicated that 50% of embryonic RORγ deficient mice developed T-cell lymphoma [82]. Lymphoma was also observed in adult RORγ knockout mice with immune systems intact [83]. The phenotypes of RORγ knockout mice cause concerns of the consequences of systemic treatment of RORγ antagonists in the patients with psoriasis.
Developing RORγ antagonists with the skin-restricted exposure may alleviate the safety risk of systemic exposure while still maintaining similar efficacy as biologics in the IL-23/IL17 pathway, and may provide a new option as topical targeted therapeutics for psoriasis patients. Phase 1 trial of topical RORγ antagonist GSK2981278 for the treatment of psoriasis was not advanced further (Table 2) [84]. 0.03%, 0.1%, 0.8% and 4% GSK2981278 ointments were used in the tria, respectively. Across all doses, infiltrate thickness was not altered. Biomarker results did not support that the target was engaged. Although GSK2981278 was shown
More effort was then focused on developing RORγ antagonists in restricted exposure and prolonged action at the skin while being rapidly eliminated from the systemic circulation for topical therapy in psoriasis. ESR114 topical gel is a selective, potent inhibitor of RORγ designed to have its pharmacological activity targeted to the skin with minimal systemic absorption [86]. In 2019, Escalier Biosciences completed a phase I/II trial evaluating ESR-114 topical gel in patients with mild-to-moderate psoriasis in USA and Canada (NCT03630939, Table 2). Nevertheless, no trial results were disclosed yet. In addition, it was reported that a novel series of benzimidazole with RORγ antagonistic activity, SHR168442, was developed with desirable skin-restricted PK properties for a topical drug [87]. SHR168442 suppressed the IL-17 gene transcription, and reduced IL-17 cytokine secretion, and, more importantly, achieved skin-restricted exposure suitable for topical delivery. In the IMQ-induced and IL-23-induced psoriasis-like skin inflammation mouse models, SHR168442 ointment exhibited excellent efficacy, which correlated with the reduction of Th17 pathway cytokines, IL-17A, IL-6 and TNFα. This novel RORγ antagonist may represent a new option as topical targeted therapeutics for mild to moderate psoriasis patients. Results from further clinical evaluation of this specific mechanism for the treatment of mild to moderate psoriasis are highly anticipated.
The Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway plays a crucial role in intracellular signaling of cytokine of many cellular processes, important in both normal and pathological states of immune-mediated inflammatory diseases [88]. There are four different types of JAK proteins: JAK1, JAK2, JAK3 and TYK2. The IL-23 receptor relies on a heterodimer of JAK2 and TYK2 for signal transduction, thus highlighting the role of JAKs in the pathogenesis of psoriasis and the therapeutic potential of JAK inhibitors in psoriasis. TYK2-deficient mice, as compared to wild-type mice, exhibit significantly reduced ear swelling and less epidermal hyperplasia when injected with IL-23 [89, 90]. In the absence of TYK2, the production of IL-17 and IL-22 and skin infiltration of various immune cells were also impaired. Taken together with the clinical success of biologics blocking either IL-23 or IL-17 signaling (Table 1), these results suggest the great potential for JAK inhibitors and, especially, for TYK2 inhibitors in the treatment of psoriasis.
JAK inhibitors are already on the market for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis [24]. JAK inhibitors have been tested as potential treatments for psoriasis. The first generation of JAK inhibitors target multiple members of the JAK family and thus display a broader effect but also present more side effects. Many JAK inhibitors tested for oral treatment of psoriasis have only been examined in phase II trials except tofacitinib (reached phase III). It is doubtful that they will be tested further. In recent years, selective TYK2 inhibitors have been developed, and several phase III trials are in progress. The highly selective TYK2 inhibitor BMS-986165 has shown high efficacy toward psoriasis, confirming the important role of the IL-23/IL-17 axis in pathogenesis of psoriasis [91]. Several JAK inhibitors with different selectivity spectrums are under clinical development for the topical treatment of psoriasis (Table 2).
Tofacitinib (pan-JAK inhibitor) has been approved for the treatment of psoriatic arthritis, but not of psoriasis. Oral tofacitinib has been tested in phase III for psoriasis. Although tofacitinib shows a favorable clinical effect on plaque psoriasis symptoms, herpes zoster occurs during tofacitinib treatment, especially in Asian populations including the Japanese [48]. In phase 2b trial, the ointment formulation of tofacitinib was found to have no considerable effect at week 12 in comparison to that of the vehicle [92].
Ruxolitinib is a selective JAK1 and JAK2 inhibitor that inhibits various cytokines involved in the signaling of TH1 and TH17 pathways, including IL-12, IL-23 and IFNγ, which are associated with psoriasis. Its cream formulation has been approved by FDA for the treatment of atopic dermatitis, but not of psoriasis [93]. In phase II studies, ruxolitinib was studied as a topical ointment for mild-to-moderate psoriasis (Table 2). In an open phase 2 study conducted with 28 patients, a greater reduction in lesion severity score was observed for topical ruxolitinib as compared with vehicle and with calcipotriene [94]. The systemic absorption of the product was minimal. In a subsequent phase IIb, double-blind, randomed, vehicle-controlled study, 200 patients with mild-to-moderate chronic plaque psoriasis were treated with topical ruxolitinib for 3 months and the results indicated the mean PASI improvement was 40% compared with placebo [95]. Both studies reported the main adverse event was local irritation, which was more frequent in patients treated with placebo. To date, no phase III study of ruxolitinib in psoriasis has begun yet.
PF-06700841 is a potent dual inhibitor of TYK2 and JAK1, which was shown to be safe and well tolerated in the oral treatment at doses up to 200 mg once daily in a phase I clinical trial [96]. No other clinical trials with oral PF-06700841 in psoriasis are now ongoing. A phase IIb study of topical application of PF-06700841 cream involving patients with mild-to-moderate psoriasis (NCT03850483) was recently completed (April 20, 2021). The trial results are not yet available.
DUR-928 is an endogenous sulfated oxysterol that acts as an epigenetic regulator [97]. It binds to and inhibits the activity of DNMTs, DNMT-1, 3a and 3b, inhibiting DNA methylation, and thereby modulating the expression of the genes associated with stress response, lipid biosynthesis and cell death. Improvement of cell survival and reduction of lipotoxicity and inflammation by DUR-928 were observed in animal models and from DURECT’s clinical trials in alcohol-associated hepatitis (AH) and nonalcoholic steatohepatitis (NASH). The rationale of topical application of DUR-928 in psoriasis is not clear. A phase IIb study of topical application of DUR-928 topical solution in patients with mild-to-moderate psoriasis (NCT03837743) was completed on August 20, 2020 (Table 2). The trial results are not yet disclosed.
The oral phosphodiesterase-4 (PDE4) inhibitor apremilast was approved for the treatment of moderate to severe plaque psoriasis [98]. However, apremilast has only modest efficacy with PASI75 rates clearly lower than biologics. Inhibition of PDE4 indirectly down regulates immune modulators, including TNFα, IFNγ, IL-17 and IL-23 [99]. Due to the potential adverse events associated with oral administration, the topical PDE4 inhibitors, crisaborole and roflumilast, are being investigated as an alternative treatment of psoriasis aiming to avoid systemic adverse effects (Table 2).
AN-2728 (crisaborole) ointment has been approved for the treatment of atopic dermatitis [100]. AN-2728 is a newer generation of PDE4 inhibitors [101]. Its binding mode to the catalytic site of PDE4 is distinct from traditional PDE4 inhibitors and can reduce pro-inflammatory cytokines TNFα, IL-2, IFNγ, and IL-5. In phase 2 studies to treat mild-to-moderate plaque-type psoriasis, AN-2728 ointment showed modest efficacy (40% of patients achieved a ≥ 2 grade improvement as assessed by the overall target Plaque Severity Score) [102]. Most adverse effects were mild to moderate.
The oral PDE4 inhibitor roflumilast has been approved by FDA for the treatment of chronic obstructive pulmonary disease (COPD) exacerbation since 2011 [103]. The topical roflumilast, in a high-water-content moisturizing cream base vehicle containing the cosmetic solvent ethoxydiglycol, is being investigated for the treatment of plaque psoriasis [104]. Its inhibitor affinity (IC50 values) is 25 to 300 folds more potent than either apremilast or crisaborole depending on PDE4 isoform analyzed [105]. In the phase 2b trial, approximately 85% of the enrolled patients had moderate-to-severe psoriasis and a generally similar percentage of patients in the roflumilast 0.3% group (31%) met the criterion for the PASI75 response at week 8 although differences in trial design do not allow to make direct comparisons [104, 105]. Oral apremilast has been associated with gastrointestinal adverse events of diarrhea and nausea, whereas topical roflumilast cream was associated with less than 1% of each of these events in this phase 2b trial. This may be a result of topical administration bypassing the gastrointestinal tract. Longer and larger trials are in progress to determine the durability and safety of roflumilast in psoriasis (Table 2).
Tapinarof (also known as WBI-1001, GSK2894512, DMVT-505) is a naturally derived small molecule produced by bacterial symbionts of entomopathogenic nematodes [106]. Broad cellular profiling of tapinatof identified aryl hydrocarbon receptor (AhR) as a primary target [107]. Tapinarof activates the AhR pathway through direct binding. It was reported that AhR activation can modify transcriptional regulation of the immune system and, specifically, affect the differentiation of Th17 and Treg cells [108]. Tapinarof has been shown to inhibit IL-17A message expression by approximately 50% and robustly increase IL-22 levels [107]. Furthermore, 1% tapinarof cream can reduce imiquimod (IMQ)-induced skin inflammation and suppress IMQ-induced IL-17A and IL-17F gene expression in AhR-sufficient, but not AhR-deficient mice.
Topical 1.0% tapinarof met its primary endpoint in patients with mild-to-moderate psoriasis from a randomized double-blind placebo-controlled phase II trial [109]. The improvement in PGA at week 12 was 62.8% for patients randomized to tapinarof when compared with 13.0% for patients randomized to placebo (p < 0.0001). The adverse events observed in patients treated with tapinarof were all mild to moderate in intensity.
In 2018, GlaxoSmithKline (GSK) withdrew its phase III trial of tapinarof (GSK2894512) and sold mostly global rights of its Phase III-bound psoriasis candidate tapinarof to Dermavant Sciences [110]. On 9/30/2021, Dermavant Sciences disclosed final results from Phase III PSOARING 3 long-term extension study of tapinarof, a 1.0% once a daily, in patients with plaque psoriasis [111]. 58.2% (302/519) of patients with a PGA score ≥ 2 achieved a PGA score of 0 or 1. Moreover, 40.9% (312/763) of all patients achieved complete disease clearance (PGA score of 0). Those results demonstrate tapinarof’s continued improvement in efficacy beyond the 12-week pivotal studies. Treatment-emergent adverse events (TEAEs) were mostly mild to moderate, at application sites, and associated with a low discontinuation rate (5.4%). Incidence and severity of folliculitis and contact dermatitis remained stable with long-term use (up to 52 weeks) and were associated with low discontinuation rates (1.2% and 1.4%, respectively). The FDA accepted the New Drug Application submitted in May 2021, and assigned a Prescription Drug User Fee Act target action date in the second quarter of 2022.
A rapidly growing body of literature suggests that the IL-23/IL-17 axis is the major pathway that drives the chronic inflammation underlying psoriasis pathophysiology. The recent years have witnessed that superior clinical efficacy of IL-23/IL-17 pathway biologics in the systemic treatment of psoriasis brings to a major paradigm shift for the management of moderate-to-severe psoriasis. Nevertheless, lack of molecular targeted therapies remains for topical treatment of psoriasis.
With the rapid development of small molecule drugs for the topical treatment of psoriasis, molecular targeted therapies in the IL-23/IL17 axis have the potential to ascertain their role as effective and safe therapy. Although tapinarof and roflumilast are promising therapies in topical treatment of psoriasis, there are still considerable challenges in topical treatment. Many other topical therapeutic agents hold promise and warrant further investigation. Limitations of this chapter include a paucity of randomized controlled clinical trials for topical agents in the treatment of psoriasis, especially for most agents with none or only preliminary data available. Some studies report on a limited duration and a limited number of participants challenging generalizability to the clinic population. Much work is still required for the next breakthrough in the discovery of novel effective and safe topical therapy for psoriasis.
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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. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. 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The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}}]}},subseries:{item:{id:"3",type:"subseries",title:"Bacterial Infectious Diseases",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools",scope:"