Summary of various studies on electrodeposition of Sn.
\\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:"10843",leadTitle:null,fullTitle:"Persistent Organic Pollutants (POPs) - Monitoring, Impact and Treatment",title:"Persistent Organic Pollutants (POPs)",subtitle:"Monitoring, Impact and Treatment",reviewType:"peer-reviewed",abstract:"Persistent organic pollutants (POPs) are toxic organic compounds that resist environmental degradation through biological, chemical, and photolytic processes. Many POPs are currently used as pesticides, pharmaceuticals, solvents, and industrial chemicals. Because of their persistence, POPs bioaccumulate and adversely affect human health and the environment. Persistent Organic Pollutants (POPs) - Monitoring, Impact and Treatment deals with several aspects of POP monitoring, occurrence, impact, and treatment technologies. The book is divided into two sections containing nine chapters that address such topics as the effect of POPs on wildlife, their role in hepatocarcinogenesis, treatment of POPs in wastewater, and much more.",isbn:"978-1-83968-207-0",printIsbn:"978-1-83968-206-3",pdfIsbn:"978-1-83968-208-7",doi:"10.5772/intechopen.95151",price:119,priceEur:129,priceUsd:155,slug:"persistent-organic-pollutants-pops-monitoring-impact-and-treatment",numberOfPages:172,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"f5b1589f0a990b6114fef2dadc735dd9",bookSignature:"Mohamed Nageeb Rashed",publishedDate:"April 13th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10843.jpg",numberOfDownloads:989,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 10th 2021",dateEndSecondStepPublish:"July 8th 2021",dateEndThirdStepPublish:"September 6th 2021",dateEndFourthStepPublish:"November 25th 2021",dateEndFifthStepPublish:"January 24th 2022",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",biography:"Prof. Mohamed Nageeb Rashed is Professor of Analytical and Environmental Chemistry and former vice-dean for environmental affairs, Faculty of Science, Aswan University, Egypt. He received his Ph.D. in Environmental Analytical Chemistry from Assiut University, Egypt, in 1989. His research interest is in analytical and environmental chemistry with special emphasis on: (1) monitoring and assessing biological trace elements and toxic metals in human blood, urine, water, crops, vegetables, and medicinal plants; (2) relationships between environmental heavy metals and human diseases; (3) uses of biological indicators for monitoring water pollution; (4) environmental chemistry of lakes, rivers, and well water; (5) water and wastewater treatment by adsorption and photocatalysis techniques; (6) soil and water pollution monitoring, control, and treatment; and (7) advanced oxidation treatment. Prof. Rashed has supervised several MSc and Ph.D. theses in the field of analytical and environmental chemistry. He served as an examiner for several Ph.D. theses in analytical chemistry in India, Kazakhstan, and Botswana. He has published about ninety scientific papers in peer-reviewed international journals and several papers in national and international conferences. He participated as an invited speaker at thirty international conferences. Prof. Rashed is the editor-in-chief and an editorial board member for several international journals in the fields of chemistry and environment. He is a member of several national and international societies. He received the Egyptian State Award for Environmental Research in 2001 and the Aswan University Merit Award for Basic Science in 2020. Prof. Rashed was recognized in Stanford University’s list of the World’s Top 2% Scientists in 2020 and 2021.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"133",title:"Environmental Pollution",slug:"environmental-pollution"}],chapters:[{id:"79742",title:"Endocrine Disruptor Impact on Zebrafish Larvae: Posterior Lateral Line System as a New Target",doi:"10.5772/intechopen.101609",slug:"endocrine-disruptor-impact-on-zebrafish-larvae-posterior-lateral-line-system-as-a-new-target",totalDownloads:21,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Endocrine-disrupting chemicals (EDCs), including polychlorinated biphenyls (PCBs), bisphenol A (BPA), pharmaceutical drugs, and pesticides, affect a variety of hormone-regulated physiological pathways in humans and wildlife. The occurrence of these EDCs in the aquatic environment is linked with vertebrates’ health alteration. EDCs exhibit lipophilic characteristics and bind to hydrophobic areas of steroid receptors, such as the estrogen receptor, which are involved in vertebrate developmental regulation. Mainly, EDCs modify the transcription of several genes involved in individual homeostasis. Zebrafish conserve many developmental pathways found in humans, which makes it an appreciated model system for EDCs research studies, especially on early organ development. In the current chapter, we emphasize on latest published papers of EDCs effects on lateral line regeneration in zebrafish larvae. Similarly, we describe other special impacts of EDCs exposure. In conclusion, we make the case that the zebrafish lateral line exposed to EDCs can provide important insights into human health.",signatures:"Ahmed Nasri, Patricia Aïssa, Ezzeddine Mahmoudi, Hamouda Beyrem and Véronique Perrier",downloadPdfUrl:"/chapter/pdf-download/79742",previewPdfUrl:"/chapter/pdf-preview/79742",authors:[{id:"354033",title:"Dr.",name:"Ahmed",surname:"Nasri",slug:"ahmed-nasri",fullName:"Ahmed Nasri"},{id:"420855",title:"Prof.",name:"Patricia",surname:"Aïssa",slug:"patricia-aissa",fullName:"Patricia Aïssa"},{id:"420856",title:"Prof.",name:"Hamouda",surname:"Beyrem",slug:"hamouda-beyrem",fullName:"Hamouda Beyrem"},{id:"420857",title:"Prof.",name:"Ezzeddine",surname:"Mahmoudi",slug:"ezzeddine-mahmoudi",fullName:"Ezzeddine Mahmoudi"},{id:"442300",title:"Prof.",name:"Véronique",surname:"Perrier",slug:"veronique-perrier",fullName:"Véronique Perrier"}],corrections:null},{id:"79938",title:"Role and Effect of Persistent Organic Pollutants to Our Environment and Wildlife",doi:"10.5772/intechopen.101617",slug:"role-and-effect-of-persistent-organic-pollutants-to-our-environment-and-wildlife",totalDownloads:148,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Persistent organic pollutants (POPs) are toxic substances composed of carbon-based chemical compounds and mixtures. In the recent times, persistent organic pollutants (POPs) came as a threat for the wildlife and environmental world. POPs are chemically stable, remain intact in the environment for long periods, are recalcitrant in nature, and are lipophilic in nature. Therefore, they accumulate in fatty tissue of living organisms and reside longer period of time finally affecting the human and wildlife. It is believed that approximately 90% of human beings are exposed to POPs from their diets that contain animal products. These foods lead to bioaccumulation in fat tissues that then cause health hazard. There are many studies such that its behavior in photocatalytic oxidation reactions are available; also many research studies are going to combat from these toxic substances. In this chapter, we will take you through how persistent organic pollutants are affecting our environment and wildlife and what are its roles.",signatures:"Nisha Gaur, Dhiraj Dutta, Aman Jaiswal, Rama Dubey and Dev Vrat Kamboj",downloadPdfUrl:"/chapter/pdf-download/79938",previewPdfUrl:"/chapter/pdf-preview/79938",authors:[{id:"425585",title:"Dr.",name:"NISHA",surname:"GAUR",slug:"nisha-gaur",fullName:"NISHA GAUR"},{id:"445178",title:"Mr.",name:"Dhiraj",surname:"Dutta",slug:"dhiraj-dutta",fullName:"Dhiraj Dutta"},{id:"445179",title:"Mr.",name:"Aman",surname:"Jaiswal",slug:"aman-jaiswal",fullName:"Aman Jaiswal"},{id:"445180",title:"Dr.",name:"Rama",surname:"Dubey",slug:"rama-dubey",fullName:"Rama Dubey"},{id:"446429",title:"Dr.",name:"Dev Vrat",surname:"Kamboj",slug:"dev-vrat-kamboj",fullName:"Dev Vrat Kamboj"}],corrections:null},{id:"79879",title:"Impact of PCBs, Furan and Dioxin on Hepatocarcinogenesis",doi:"10.5772/intechopen.101526",slug:"impact-of-pcbs-furan-and-dioxin-on-hepatocarcinogenesis",totalDownloads:112,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Stockholm Convention defined polychlorinated biphenyls (PCBs) as a group of persistent organic pollutants (POPs) such as dioxin/furan, dichlorodiphenyltrichloroethane, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, aldrin, polychlorinated dibenzofurans and organometallic compounds (such as organotin and organomercury) which share the same characteristics of being persistent, bioaccumulative and toxic and can travel long distance through various media. They have diverse health impacts with different underlined molecular mechanisms. Recently, PCBs were referred as potent carcinogens with persistent existence in the environment. As the liver is the organ of detoxification, it is the major target organ for toxic effects induced by environmental contaminants, including PCBs. PCBs, furan and dioxin exert their hepatocarcinogenic effect through different mechanisms such as induction of oxidative stress, an increase of reactive oxygen species (ROS), mutagenic induction to oncogenes and epigenetic alteration to hepatic cells. In this chapter, we will provide an updated overview about PCBs, furan and dioxins, their impact on liver cancer initiation and progression on various in vivo and in vitro systems and its underlined molecular mechanisms. Also, a special emphasis will be directed to highlight zebrafish as in vivo model system to analyse the hepatocarcinogenic effect of these pollutants.",signatures:"Mohamed Helal, Sara Ghanem and Amany El-Sikaily",downloadPdfUrl:"/chapter/pdf-download/79879",previewPdfUrl:"/chapter/pdf-preview/79879",authors:[{id:"226635",title:"Prof.",name:"Amany",surname:"El-Sikaily",slug:"amany-el-sikaily",fullName:"Amany El-Sikaily"},{id:"424992",title:"Dr.",name:"Mohamed",surname:"Helal",slug:"mohamed-helal",fullName:"Mohamed Helal"},{id:"435668",title:"Dr.",name:"Sara",surname:"Ghanem",slug:"sara-ghanem",fullName:"Sara Ghanem"}],corrections:null},{id:"79056",title:"Persistent Organic Pollutants in the Bizerte Lagoon Ecosystem: Occurrence, Distribution, and Ecotoxicological Assessment Using Marine Organism",doi:"10.5772/intechopen.100549",slug:"persistent-organic-pollutants-in-the-bizerte-lagoon-ecosystem-occurrence-distribution-and-ecotoxicol",totalDownloads:42,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Marine ecosystem represents an ecologically and economically important water bodies for human and animal living. Their increasing pollution by persistent organic pollutants has represented a major environmental alarm during the last years. In the current study, we examined the occurrence, local distribution and ecotoxicological menace of organic pollutants, comprising brominated flame retardants (BFR), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and organochlorine pesticides (OCPs) in different matrices from the Northern Tunisian Coastal Ecosystem (Bizerte lagoon). The pollutant existence in this biome is related with a negative impact on the biocenosis health. Many approach including (i) chemical analyses; (ii) taxonomic structure and ecological indices analyses; (iii) and biochemical experimental studies, were investigated to determine the ecosystem quality and the contaminant effects. Our chapter introduces the baseline information on the organic contaminations extent and toxicological impact, as well as, it contribute to evaluate the ecological quality of this marine coastal ecosystem.",signatures:"Ahmed Nasri, Takoua Mhadhbi, Mohamed Allouche, Amel Hannachi, Hary Demey, Patricia Aïssa, Hamouda Beyrem and Ezzeddine Mahmoudi",downloadPdfUrl:"/chapter/pdf-download/79056",previewPdfUrl:"/chapter/pdf-preview/79056",authors:[{id:"354033",title:"Dr.",name:"Ahmed",surname:"Nasri",slug:"ahmed-nasri",fullName:"Ahmed Nasri"},{id:"420855",title:"Prof.",name:"Patricia",surname:"Aïssa",slug:"patricia-aissa",fullName:"Patricia Aïssa"},{id:"420856",title:"Prof.",name:"Hamouda",surname:"Beyrem",slug:"hamouda-beyrem",fullName:"Hamouda Beyrem"},{id:"420857",title:"Prof.",name:"Ezzeddine",surname:"Mahmoudi",slug:"ezzeddine-mahmoudi",fullName:"Ezzeddine Mahmoudi"},{id:"435699",title:"Dr.",name:"Takoua",surname:"Mhadhbi",slug:"takoua-mhadhbi",fullName:"Takoua Mhadhbi"},{id:"435701",title:"Dr.",name:"Mohamed",surname:"Allouche",slug:"mohamed-allouche",fullName:"Mohamed Allouche"},{id:"435702",title:"Dr.",name:"Amel",surname:"Hannachi",slug:"amel-hannachi",fullName:"Amel Hannachi"},{id:"435703",title:"Dr.",name:"Hary",surname:"Demey",slug:"hary-demey",fullName:"Hary Demey"}],corrections:null},{id:"79526",title:"Type, Sources, Methods and Treatment of Organic Pollutants in Wastewater",doi:"10.5772/intechopen.101347",slug:"type-sources-methods-and-treatment-of-organic-pollutants-in-wastewater",totalDownloads:293,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Persistent organic pollutants (POPs), which are synthetic organic chemical compounds, either intentionally or unintentionally produced, have widely aroused public concern in recent years. These chemicals are toxic and major environmental concern due to their persistence, long range transportability, bioaccumulation and potentially adverse effects on living organisms. Uncontrolled inputs combined with poor environmental management often result in elevated levels of persistent organic pollutants in affected estuaries. Since the Stockholm Convention on POPs was adopted, different techniques have been extensively developed. A major focus revealed the need for low cost methods that can be implemented easily in developing countries such as electrochemical techniques. Persistent organic pollutants are known to be resistant to conventional treatment methods such as flocculation, coagulation, filtration and oxidant chemical treatment. However, various advanced wastewater treatment technologies such as, activated carbon adsorption, biodegradation using membrane bioreactor and advanced oxidation processes (AOPs) have been applied in the treatment of POPs.",signatures:"Poslet Shumbula, Collet Maswanganyi and Ndivhuwo Shumbula",downloadPdfUrl:"/chapter/pdf-download/79526",previewPdfUrl:"/chapter/pdf-preview/79526",authors:[{id:"352155",title:"Dr.",name:"Poslet",surname:"Shumbula",slug:"poslet-shumbula",fullName:"Poslet Shumbula"},{id:"428329",title:"Mr.",name:"Collet",surname:"Maswanganyi",slug:"collet-maswanganyi",fullName:"Collet Maswanganyi"},{id:"428546",title:"MSc.",name:"Ndivhuwo",surname:"Shumbula",slug:"ndivhuwo-shumbula",fullName:"Ndivhuwo Shumbula"}],corrections:null},{id:"79384",title:"Nonthermal Mechanochemical Destruction of POPs",doi:"10.5772/intechopen.101088",slug:"nonthermal-mechanochemical-destruction-of-pops",totalDownloads:124,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The present chapter is dedicated to all relevant theoretical and application aspects of mechanochemical destruction technology for mineralization of POPs, both stockpiled ones and as contaminants in environmental and waste matrices. It will show that such solid-state technology, realized by high energy milling of POPs with a co-milling solid reagent, can achieve complete mineralization of haloorganics into graphitic/amorphous carbon, carbon oxides, and halides; it takes place at near environmental temperature, thus limiting unintentional formation of dioxins (if treatment conditions are selected carefully); and, in some cases, it can be used to produce useful materials instead of just detoxified waste. The chapter will also give a comprehensive picture of complex mechanochemical destruction mechanism, including mechanochemical activation of the co-milling reagent and the cascade of radical reactions that cause POP molecules mineralization. Finally, technological and economic considerations will be provided, which corroborate the validity and feasibility of the mechanochemical destruction as an effective and safe technology to treat POPs.",signatures:"Giovanni Cagnetta and Mohammadtaghi Vakili",downloadPdfUrl:"/chapter/pdf-download/79384",previewPdfUrl:"/chapter/pdf-preview/79384",authors:[{id:"423291",title:"Assistant Prof.",name:"Giovanni",surname:"Cagnetta",slug:"giovanni-cagnetta",fullName:"Giovanni Cagnetta"},{id:"435064",title:"Dr.",name:"Mohammadtaghi",surname:"Vakili",slug:"mohammadtaghi-vakili",fullName:"Mohammadtaghi Vakili"}],corrections:null},{id:"79945",title:"Physiochemical Properties and Removal Methods of Phenolic Compounds from Waste Waters",doi:"10.5772/intechopen.101545",slug:"physiochemical-properties-and-removal-methods-of-phenolic-compounds-from-waste-waters",totalDownloads:111,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, phenol and chlorophenols are investigated in terms of their production histories, physiochemical properties, pollution resources, and removal methods. It is seen that both phenol and chlorophenols are highly toxic compounds, produced from natural and anthropogenic sources, which are hazardous to both humans and the environment even at very low concentrations. The typical industries which produce phenol and chlorophenol pollution are petrochemical, textile, plastics, resin, dye, pharmaceutical, iron and steel, pulp and paper industries as well as the petroleum refineries, and coal gasification operations. Phenol is a highly corrosive and nerve poisoning agent. It causes harmful health effects, such as sour mouth, diarrhea, and impaired vision. It is also toxic for the ecosystem with toxicity levels ranging between 10-24 mg/L for humans, 9-25 mg/l for fish, and lethal blood concentration around 150-mg/100 ml. Chlorophenols found in natural waters or drinking water also cause serious health problems such as histopathological alterations, genotoxicity, mutagenicity, and carcinogenicity among others. Due to the aforementioned reasons, the phenolic compounds in wastewaters or drinking water must be removed using a suitable wastewater treatment method such as adsorption, extraction, electrochemical oxidation, biodegradation, catalytic wet air oxidation, or enzyme treatment among others.",signatures:"Yesim Gucbilmez",downloadPdfUrl:"/chapter/pdf-download/79945",previewPdfUrl:"/chapter/pdf-preview/79945",authors:[{id:"426808",title:"Associate Prof.",name:"Yesim",surname:"Gucbilmez",slug:"yesim-gucbilmez",fullName:"Yesim Gucbilmez"}],corrections:null},{id:"78924",title:"Occurrence and Removal of Persistent Organic Pollutants (POPs)",doi:"10.5772/intechopen.100387",slug:"occurrence-and-removal-of-persistent-organic-pollutants-pops-",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Since the revelation in the detection of the persistent organic pollutants (POPs) in industrial wastewater in the early 1990s, a notable progress has been achieved on the research and different removal applications or methods of this challenge at hand. This book chapter entails a decent understanding on the occurrence, effects, and amputation of POPs in the water sector in advancement of municipal performances of treating industrial wastewaters and environment at large. This current chapter also presents an overview of research associated to the amputation of persistent organic pollutants (POPs) from various water bodies, i.e., river sediments, sewage plants, industrial sludges, and wastewater. Also, discussing the relationships with actual pre-treatment and removal rates. Vital characteristics such as the wastewater matrix, location, sources of POPs, materials and modules, operational parameters and problems are presented with a clear focus on removal of these organic pollutant’s different sources (like, textile wastewater). The particular methods to the removal of POPs can be associated with the application of ultrafiltration, nanofiltration and reverse osmosis as advanced treatment stages are considered in correlation with the textile wastewater characteristics and removal efficiencies requirements. This gives significance to the amalgamation of physico-chemical and biological treatment with membrane processes which is likely to represent an efficient solution for the removal of POPs from textile wastewater. However, since membrane fouling and hydrophilicity are apparent in the execution of this process, this chapter also covers the effective strategies like fabrication of membrane with a suitable additive to counterattack these challenges, which are often used in membrane technological research. This chapter also proposes an updated understanding of fouling and improvement of membrane properties.",signatures:"Siyabonga Aubrey Mhlongo, Linda Lunga Sibali, Kholofelo Clifford Malematja and Peter P. Ndibewu",downloadPdfUrl:"/chapter/pdf-download/78924",previewPdfUrl:"/chapter/pdf-preview/78924",authors:[{id:"424106",title:"Ph.D. Student",name:"Siyabonga",surname:"Aubrey Mhlongo",slug:"siyabonga-aubrey-mhlongo",fullName:"Siyabonga Aubrey Mhlongo"},{id:"425026",title:"Mr.",name:"Kholofelo",surname:"Clifford Malematja",slug:"kholofelo-clifford-malematja",fullName:"Kholofelo Clifford Malematja"},{id:"437268",title:"Dr.",name:"Linda Lunga",surname:"Sibali",slug:"linda-lunga-sibali",fullName:"Linda Lunga Sibali"},{id:"437269",title:"Dr.",name:"Peter P.",surname:"Ndibewu",slug:"peter-p.-ndibewu",fullName:"Peter P. Ndibewu"}],corrections:null},{id:"79427",title:"Recent Developments in the Application of Advanced Oxidative Processes for Remediation of Persistent Organic Pollutants from Water",doi:"10.5772/intechopen.101304",slug:"recent-developments-in-the-application-of-advanced-oxidative-processes-for-remediation-of-persistent",totalDownloads:90,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Environmental pollution as a result of industrialization is a continuous menace. In our precious environment, Persistent organic pollutants (POPs) are constantly present and these pollutants are of great concern because of their high level of toxicity, persistency and bioaccumulation. Therefore, this chapter discusses different types and sources of POPs in the environment. The chapter also introduces Advanced oxidative processes (AOPs) and the classes of AOPs. Removal of selected POPs from aqueous solutions by AOPs, such as sulfate radical, ionizing radiation, heterogeneous photocatalysis, electrohydraulic discharge system, ozonation, and Fenton processes, were discussed. The major aim of the chapter is to make available to environmental scientists the recent developments in the removal of POPs by AOPs.",signatures:"Ifeoluwa Oluwafunmilayo Daramola and Matthew Ayorinde Adebayo",downloadPdfUrl:"/chapter/pdf-download/79427",previewPdfUrl:"/chapter/pdf-preview/79427",authors:[{id:"424233",title:"Ph.D. Student",name:"Ifeoluwa Oluwafunmilayo",surname:"Daramola",slug:"ifeoluwa-oluwafunmilayo-daramola",fullName:"Ifeoluwa Oluwafunmilayo Daramola"},{id:"424419",title:"Dr.",name:"Matthew",surname:"Ayorinde Adebayo",slug:"matthew-ayorinde-adebayo",fullName:"Matthew Ayorinde Adebayo"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"38",series:{id:"25",title:"Environmental Sciences",issn:"2754-6713",editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}}}},tags:null},relatedBooks:[{type:"book",id:"3426",title:"Organic Pollutants",subtitle:"Monitoring, Risk and Treatment",isOpenForSubmission:!1,hash:"4dafb52ed4f5e21f079ab4b2f6825e78",slug:"organic-pollutants-monitoring-risk-and-treatment",bookSignature:"M. 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\r\n\tMore than half a century has elapsed since the first solid-state transistor was invented by Brattain, Shockley, and Bardeen in December 1947. In comparison to its predecessor (i.e., the vacuum tubes), the solid-state transistor is diminutive in size, consumes much lower power, operates at relatively lower temperature, and exhibits significantly faster response time. As a result of its advantages and viability, the solid-state transistor swiftly replaced the vacuum tubes. The widespread application of the solid-state transistors in electronic circuits has triggered a dramatic revolution in the electronic industries, kicking off the era of semiconductor microchips. Today, microchips are now interwoven with human's life and the fundamental building blocks of the microchips are made from field-effect transistors of FETs. Considering the impact that it has imposed on mankind, this book intends to compile a list of interesting topics which are related to the latest technological advancement and scientific breakthroughs of field-effect transistors.
\r\n\t
Lead-bearing solders are in use till date due to their indispensable properties [1–3]. Firstly, it is very cheap, available in abundance and provides good physical and chemical bonding to the substrate without interfering with the substrate [4–5]. Secondly, lead (Pb) reduces the surface tension of pure tin, which is 550 mN/m at 232°C, and the lower surface tension of 63Sn-37Pb solder (470 mN/m at 280°C) facilitates wetting [4, 6, 7]. The presence of Pb also helps to prevent the white tin (
There are many technology-based problems that can serve as reasons for the elimination of Sn-Pb solders. First, it has been already proved in the past that many lead-free candidate solders exhibit significantly better strength and fatigue life properties [4, 6]. Secondly, Pb and Pb compounds have been cited by the Environmental Protection Agency (EPA) as one of the top 17 chemicals posing the greatest threat to human life and the environment [7, 8]. In view of these reasons, elimination of Pb from electronics is necessary in electronics packaging [1, 6].
Legislations to restrict the use of Pb were first implemented in the USA in 1991 with the Lead Exposure Reduction Act of 1991 and the Lead Exposure Act of 1992, which bans Pb in some applications and limits Pb content in others to less than 0.1% [7, 8]. In the United States, the National Electronics Manufacturing Initiative (NEMI) program was developed to research on lead-free alternatives [9]. In Japan, this movement is connected to the Lead-free Soldering Research Council (1994 to 2000) within the Japan Institute of Electronic Packaging. Japan Electronics and Information Technology Industries Association (JEITA) has set guidelines for lead-free products, which was published in 1999 [10, 11]. These companies aimed to use lead-free solders in mass-produced consumer products and to implement lead-free soldering technologies in their products by 2003 [2]. In Europe, the EU directives (WEEE) and (RoHS) have issued a ban on the use of lead in consumer goods [12, 13].
Pure Sn has two allotropes, white tin (
A relatively large number of Pb-free solder alloys have thus been proposed so far, Sn being the primary or major constituent. The two other elements that are major constituents are indium (In) and bismuth (Bi). Other alloying elements are zinc (Zn), silver (Ag), antimony (Sb), copper (Cu), and magnesium (Mg), and in one case, a minor amount of Pb [1–3]. The most popular Pb-free alloy system candidates are listed in a thorough review paper by Abtew and Selvaduray [1]. The most important characteristics that must be considered in selecting suitable Pb-free solder candidates are: nontoxic; availability; sufficient electrical as well as thermal conductivity; adequate mechanical properties compatible with metallic substrates such as Cu, nickel (Ni), Ag, or gold (Au); economically viable; acceptable melting and processing temperatures; and less temperature effects on substrates, printed circuit boards(PCBs), etc. [1–4, 6].
Due to the Pb-free solder implementation, pure Sn and Sn-Cu, Sn-Ag are commonly used to replace eutectic Sn-Pb as the surface finish on the lead-frames and metal terminations of passive devices [17, 18, 19]. However, in Sn-rich lead-free finish, Sn whiskers have been found to form, which poses a serious threat for the reliability of passive devices. The Sn whisker formation was first reported in 1946 [20]. It is generally accepted that the driving forces of Sn whiskers mainly attribute to the internal stresses, the dissolution of the metal under-layer, and the interfacial compound formation. There are two intermetallic compounds of Cu and Sn below 300ºC, they are Cu6Sn5 and Cu3Sn. The Cu6Sn5 forms at room temperature while Cu3Sn forms after annealing at elevated temperatures [21, 22]. Some intermetallic compounds (IMCs), such as AuSn4 for Sn/Au couples, Cu6Sn5 for Sn/Cu couples, and Ni3Sn4 for Sn/Ni couples, even form at room temperature [23, 24].
Based on these three main root-causes of Sn whisker formation, three methods are devised by researchers to retard the Sn whiskers formation: (1) choosing optimal thickness of the finish layer, (2) alloying with other metal elements, and (3) adding a reaction barrier layer beneath the finish layer [25–27].
There are many synthesis routes for the fabrication of solders varying from solid state mechanical alloying, powder metallurgy, sol gel, melting and casting route, chemical routes, gaseous phase sputtering or evaporation methods, electrodeposition method, etc. [28-35]. Among all these methods, we will discuss techniques related to thin film pulse electrodeposition of solders. The other methods are not discussed here because they are out of the scope of this chapter.
Both evaporation and sputter deposition techniques require high vacuum and/or high temperature processing, which increases operation costs and cause inter-diffusion problems. Compared to these fabrication processes, electrodeposition is an economically viable process [36]. It can be used to plate either single layer or multilayer deposits with easy and precise control of the thickness and composition of each layer. Electrodeposition can be performed on substrates with varying sizes and complex shapes and the deposit can be very thin or very thick [37–38]. There are, however, safety and environmental concerns related with chemical treatment and safe disposal of wastes. Numerous metals and metal alloys have been successfully electrodeposited from aqueous solutions. The most useful electrodeposited metals include Sn, Cr, Cu, Ni, Ag, Au, Zn, and alloys such as chromium-nickel (Cr-Ni), iron-cobalt (Fe-Co), and various Sn alloys [36–38].
In electrodeposition, metal ions present in a solution, the electrolyte, are reduced at the surface of an electrode to form a metal layer, as shown in Fig. 1.
A schematic for the electrodeposition process.
This process essentially consists of: (1) an anode (the positive electrode), (2) a cathode (the item to be electroplated, which is the negative electrode), (3) the electrolyte acts as a transport medium for the tin ions to be deposited at the cathode as a coating on the item to be electroplated, (4) an electric current or voltage source for controlling the deposition, and (5) various peripherals for contacting the electrodes, stirring and heating the solution, etc. [36–37].
In electrodeposition, the metal is deposited over a conductive substrate by the application of electric current through the electrolytic bath. The current provides sufficient energy to proceed the oxidation-reduction reactions at anode and cathode, respectively. The metal ions in the electrolyte accept the electrons and get deposited on the substrate. The weight of the deposited material can be calculated from the relation given by Faraday’s laws [37–39]:
where thickness of the deposit is in mg, time in seconds, J = current density, ECE = electrochemical equivalent, CCE = current efficiency (ratio of actual/theoretical weight deposited), and density of deposit is in g/cm3.
Electrochemical deposition of metals and alloys involves the reduction of metal ions from aqueous, organic, and fused-salt electrolytes. In this thesis, electrodeposition from aqueous solutions is being considered. The reduction of metal ions Mn+ in aqueous solution is represented by [37–39]:
Reaction (2) is often accompanied by hydrogen evolution. In acid solutions, we have:
In neutral and basic solutions, hydrogen evolution follows the equation:
At the anode, the anodic reactions are as follows. In an acidic solution, we have:
In an alkaline solution, the anode reaction is:
For a soluble anode, oxidation reactions, which will dissolve the anode into solution:
The equilibrium electrode potential between a metal and a solution of its ions is given by the Nernst equation:
where
The conductivity of an electrolyte depends on the degree of dissociation, the mobility of individual ions, temperature (and thus viscosity), and the electrolyte composition. In aqueous solutions, the ionic conduction depends on the degree of dissociation of dissolved species in the solution [38, 39]. In order to increase the conductivity of electrolytes, certain salts and acids or alkali are added; these are known as supporting electrolytes. For acid electrolytes, chlorides and acids are useful; for neutral electrolytes, chlorides are useful; and for alkaline electrolytes, sodium hydroxide or cyanides are useful [39]. Generally, a marked decrease in conductivity at higher concentration is due to the greater coulombic forces acting between the ever closer ions in solution. This leads to the loose association of opposite charged ions that are effectively neutral and thus no longer contribute to the overall conductivity [39].
The equilibrium potential of an electrode differs in an electrochemical cell after the application of current. Suppose the equilibrium potential of an electrode when there is no external current flowing is E. After the application of an external current (I), the potential of the electrode change by E(I), the overpotential (
It can be also expressed as in terms of current and voltage by the Tafel equation:
where
The overpotential
Thus, four different kinds of overpotential are distinguished and the total overpotential
Processes in an electrode reaction represented as resistances (From A.J. Bard, and L.R. Faulkner, Chapter 1: Introduction and Overview of Electrode Processes, Page 24, Electrochemical Methods - Fundamentals and Applications, 2nd Edition. Reprinted by permission of John Wiley & Sons, Inc. Copyright 2001 © John Wiley & Sons, Inc.
In olden times, direct current (DC) electrodeposition had only one parameter, namely, current density that is variable. In modern times, pulsed current (PC) plating where the potential or current density alternates rapidly between two different values is used [36–39]. This is accomplished with a series of pulses of equal amplitude, duration, and polarity, separated by a period of zero current, and time (t) axis as shown in Fig. 3. Each pulse consists of an on-time (
Schematic diagram of pulsed current waveform.
The duty cycle is given by the equation:
The average current density is defined as:
Sn can be electrodeposited from both acidic and alkaline aqueous solutions [42, 43]. In acidic baths, Sn usually exists as Sn2+ ions, while in alkaline baths, Sn4+ is the more stable species. The various Sn plating baths available in literature are discussed below.
The alkaline stannate electrolytes usually contain sodium or potassium stannate and the corresponding alkali metal hydroxide. These electrolytes are environment friendly, as they are non-corrosive in nature and do not require other organic additives [42, 43]. The alkaline tin baths have a very high throwing power and can be operated over a wide current density range. The tin coatings electroplated from alkaline electrolytes possess improved solderability, since they do not require any organic additive agents [44, 45]. This leads to a great improvement in wettability. One major disadvantage of alkaline plating baths is that highly alkaline baths may dissolve the photoresist used to define areas on semiconductor wafers. Alkaline plating baths also usually require higher plating temperatures (60–70°C) as compared to acidic ones [46].
Sulfate baths are primarily used for bright acid Sn plating. Organic agents are necessary if bright and dense films are to be obtained. Electroplating of tin from acidic stannous (divalent Sn) solutions consumes less electricity than alkali stannate solutions (tetravalent Sn) [42–45]. The major drawback of this system is Sn oxidation. At high current density, soluble Sn anodes are passivated due to the formation of SnO2. Irregular, dendritic, needle-like electrodeposits of tin are in general obtained from acidic electrolytes without organic additives [47–49]. To improve the surface finish, morphology, and adhesion during acidic tin plating, various organic chemicals as additives have been investigated in the past [50–52]. In the literature, we observe that sulfate baths have been used widely to plate pure Sn and various Sn alloys in electronics industries [53].
For tin electroplating, sulfate baths use a number of additives to produce a homogeneous deposit [47–53]. However, in-spite of these advantages, the use of additives is undesirable for health concerns. Moreover, adverse effects on plating efficiency and the working environment have been observed [54, 55]. In case of alkaline baths, the same is true as it requires heating the solution that causes bubble formation [44–46]. Also tin is tetravent in alkaline baths causing more power. In view of these disadvantages, recently, He
The problem of oxidation of Sn2+ to Sn4+ can be minimized by using a reducing acid Methanesulfonic acid (MSA) bath as compared to sulfate bath. MSA is much less corrosive to electronic materials than sulfuric acid [55]. It forms a clear solution, have high dissolving power and less sensitive to Sn oxidation at higher current densities [57]. Different combinations of methanesulfonate baths have been developed to electrodeposit both pure Sn and various Sn alloys by adding different additives [58].
There are a number of pyrophosphate baths available in the literature [42]. These types of baths containing P2O22- is considered as one of the most stable systems and is widely used for Sn plating [59, 60]. However, its use is limited in literature due to one disadvantage, that it requires more control and maintenance than the other plating baths. The operational temperature should not exceed 43–60°C because the pyrophosphate complex hydrolyzes to orthophosphate at temperatures higher than 60°C, which degrades the solution [42, 61].
According to the electrochemical series of metals, we know that the reduction potential of two elements would be different [35]. For a solution containing two or more different metal ions at low overpotential, the metal with the most noble reduction potential will deposit at a faster rate [35, 36]. If the electrode potential difference is far apart, then metal alloy electrodeposition may be impossible. The difference can be eliminated in view of the Nernst equation by modifying the activity values and feasibility of the co-deposition can thus be determined [37, 39]. This can be achieved by inducing a considerable change in ionic concentrations via complex ion using certain complexing agents. In the past, thiourea has been utilized as a complexing agent for the electrodeposition of Sn-Ag and Sn-Ag-Cu alloys [62, 63]. The formation of complexes by bonding the metal ions with complexing agents will decrease the concentration of the free metal ions in the solution significantly and modify the reduction potential of the metal ions [64, 65]. With an increase in overpotential, the electrodeposition reaction will progress from the charge transfer region to the mix and then to the mass-transfer regime. Under mass transfer control at sufficiently higher overpotentials, the relative deposition rates of two or more metals will be governed by the concentrations and the diffusion coefficients of the metal ions [38, 39]. For alloy deposition, the basic mechanism remains the same as the Sn deposition discussed in the previous section. The summary of the previous studies on different types of plating baths are given in Table 1.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tSodium stannate bath + halides | \n\t\t\tLead-free | \n\t\t\tAbdel Rahim | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tSodium stannate bath + sorbitol | \n\t\t\tSoldering | \n\t\t\tBroggi | \n\t\t
\n\t\t\t\t | \n\t\t\tPulse electroplating | \n\t\t\tSodium stannate bath | \n\t\t\tLead-free | \n\t\t\tSharma | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate Gluconate bath | \n\t\t\tLead-free | \n\t\t\tRehim | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate bath + aldehydes | \n\t\t\tSolder joints | \n\t\t\tTzeng | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate bath + Benzal acetone and N,N-bis(tetraoxyethylene)octadecylamine | \n\t\t\tLead-free | \n\t\t\tNakamura | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate bath + polyoxyethylene laurylether | \n\t\t\tLead-free | \n\t\t\tFukuda | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate bath + DS-10 synthanol, coumarin, formalin (37% solution) | \n\t\t\tFlip Chip technology | \n\t\t\tMedvedev | \n\t\t
\n\t\t\t\t | \n\t\t\tPulse electroplating | \n\t\t\tStannous sulfate bath + triton X 100 | \n\t\t\tSolder joints | \n\t\t\tSharma | \n\t\t
\n\t\t\t\t | \n\t\t\tPulse electroplating | \n\t\t\tStannous chloride bath | \n\t\t\tWafer bumps | \n\t\t\tHe et al., 2008 [53] | \n\t\t
\n\t\t\t\t | \n\t\t\tPulse electroplating | \n\t\t\tStannous chloride bath | \n\t\t\tLead-free | \n\t\t\tSharma | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tMSA bath + PEG, PPG+ Phenolphthalein | \n\t\t\tSolder bumps | \n\t\t\tMartyak | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tMSA bath + per-fluorinated cationic surfactant | \n\t\t\tSolders | \n\t\t\tLow | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tPyrophosphate bath + dextrin+ gelatin | \n\t\t\tSolders | \n\t\t\tVaid | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tPyrophosphate bath + gelatin | \n\t\t\tLi-ion battery | \n\t\t\tKim | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate bath+thiourea | \n\t\t\tSolders | \n\t\t\tOzga | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous sulfate bath +thiourea+ polyoxyethylene laurylether | \n\t\t\tLead-free | \n\t\t\tFukuda | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tStannous chloride bath + PEG | \n\t\t\tLead-free | \n\t\t\tLin | \n\t\t
\n\t\t\t\t | \n\t\t\tElectroplating | \n\t\t\tPyrophosphate-glycine bath | \n\t\t\tLead-free | \n\t\t\tLacnjevac | \n\t\t
Summary of various studies on electrodeposition of Sn.
The electrodeposition method is dependent on several processing parameters involved in the electrodeposition process. Therefore, to obtain the desired properties, it is essential to optimize the operating parameters. The effect of these parameters on tin electrodeposition is discussed in the following sections.
The current density is the primary controlling parameter in pulse electrodeposition. The average current density
The dendritic or irregular shaped morphology in response to the current density is due to the fact that if there is a significant increase in the current density, it increases the nucleation rate and is also associated with a higher rate of hydrogen evolution. Due to high overpotential at this state, the rate of diffusion of Sn2+ ions towards cathode becomes significant over its replenishment from the electrolyte [68, 69]. This phenomenon creates a concentration gradient in the vicinity of electrolyte/cathode interface. As a consequence, the deposition occurs preferentially on certain protrusions (heterogeneous active sites on the cathode in a random manner. This type of non-uniform growth kinetics has also been observed in copper plating [70]. The cathodic current efficiency at this stage is poor indicating a rapid hydrogen evolution which decreases the concentration of Sn2+ ions in the electrolyte.
The effect of pH in tin plating has not been discussed in detail in the literature. The majority of the tin plating baths available in literature are acidic in nature. As a general statement the rate of deposition increases with pH [71]. Bath pH not only affects the deposition rate but modifies the crystal orientation. Some people have noted a pH induced texture in Sn grains from acidic electrolyte [72]. Ebrahimi
The majority of acid type formulations operate at room temperature, while alkaline tin baths need to be heated at higher optimum temperatures. As the temperature increases, the rate of deposition also increases [41, 54, 74]. The velocity (diffusion and migration) of the metal ions and inhibitor molecules are functions of the temperature. The viscosity of the electrolyte decreases at high temperature, therefore, the diffusion rate and the velocity of metal ions and inhibitor molecules are increased. Sahaym
where
Although literature review about composite films and nanocrystalline films contains information about additives, additives for conventional metal deposition are still important as those additives would provide another aspect of information about deposition mechanism and novel additives. Popular organic additives that have been used in electrodeposition are gelatin, thiourea, EDTA (Ethylenediaminetetracetic acid), citric acid, benzotriazole (BTA), and inorganic additives such as chloride, are covered in this chapter. Nakamura
For alkaline stannate bath additives, few reports are available in literature. They usually do not require any additives since deposition occurs at a very negative potential and hydrogen evolution runs parallel with tin deposition acting as a leveler. However, the disadvantage is the diffusion of hydrogen inside the tin deposits [74–79]. In literature, the effect of additives has not been discussed in detail for chlorides electrolytes. Sekar
At higher concentration of additives, the progressive evolution of hydrogen gas leads to the development of non-uniform powdery deposits. The powdery deposits generally arise due to the adsorption and absorption of the hydrogen gases in the deposits according to the following reactions [54, 83]:
The additive blocks the association of generated hydrogen atoms according to Equation (14). Consequently, the concentrations of Hads rises following Equation (15). The combined effect of these two phenomena (Equations 15 and 16) results in absorption of hydrogen atoms in the deposits according to Equation (16).
The pulse deposition rate is given by the pulse current density and other parameters such as ‘on’ time (
The frequency of the pulse is the reciprocal of the total pulse duration consisting of
The deposition rate in the pulse technique is governed by the pulse current density (
As discussed already, the average current density (
where
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
4 | \n\t\t\t0.00042 | \n\t\t\t0.01 | \n\t\t
10 | \n\t\t\t0.0011 | \n\t\t\t0.01 | \n\t\t
20 | \n\t\t\t0.0025 | \n\t\t\t0.01 | \n\t\t
40 | \n\t\t\t0.0067 | \n\t\t\t0.01 | \n\t\t
60 | \n\t\t\t0.0150 | \n\t\t\t0.01 | \n\t\t
Pulse parameters at various duty cycles.
(Reprinted “With kind permission from Springer Science+Business Media: Journal of Metallurgical and Materials Transactions A, Volume 45, 2014, Issue 10, Page 4610-4622, A. Sharma, S. Bhattacharya, S. Das, K. Das, Table II. © The Minerals, Metals & Materials Society and ASM International 2014”).
However, at a duty cycle of 100%, the grain size observed is usually much coarser. Thus, it is inferred that the grain size of the deposits decreases with an increase in
The pulse current (PC) with lower duty cycle (<20%) produces uniform and compact deposits. At higher duty cycles (>20%) and at direct current (DC) deposition, severe increase porosity is observed. This may be due to higher average current flow time
A reduced porosity in case of PC deposition with lower duty cycles can be correlated to the two factors. (i) partial diffusion of the hydrogen and oxygen gas away from the substrate during off time (
The morphology of electrodeposits is also influenced by the pulse frequency in the electrodeposition. The pulse frequency parameters varied according to Sharma
Frequency (
\n\t\t\t\t | \n\t\t\t10 Hz | \n\t\t\t50 Hz | \n\t\t\t100 Hz | \n\t\t\t500 Hz | \n\t\t||||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t0.01 | \n\t\t\t0.09 | \n\t\t\t0.002 | \n\t\t\t0.018 | \n\t\t\t0.001 | \n\t\t\t0.009 | \n\t\t\t.0002 | \n\t\t\t.0018 | \n\t\t
Pulse frequency parameters
(Reprinted “With kind permission from Springer Science+Business Media: Journal of Metallurgical and Materials Transactions A, Volume 45, 2014, Issue 10, Page 4610-4622, A. Sharma, S. Bhattacharya, S. Das, K. Das, Table III. © The Minerals, Metals & Materials Society and ASM International 2014”).
Lower pulse frequency (
The Sn atoms can migrate freely to the most stable position facilitating the grain growth. An increase in the pulse frequency shortens the pulse duration, i.e., both
Agitation in the plating solution can be produced either by agitating the electrolyte or by moving the cathode. At low agitation rates, the effect of agitation on deposit composition is not visible, while the agitation rates may decrease the tin content in the coatings. Moreover, agitation may also increase the deposit roughness up to some extent [42, 54]. Agitation has beneficial effects of increasing the plating rate and permits the use of higher current densities by lowering polarization [36, 37, 38, 39]. Wen and Szpunar studied the nucleation and growth of tin and pointed out that agitation should not exceed beyond a certain limit where turbulent flow occurs that cause the difficulty of tin ions supply to the cathode even at high current densities [87]. Thus the cathode coverage is poor and the deposition rate decreases.
It is interesting to note that the stirring rate of the bath has a significant effect on the deposit morphology. The deposition parameters, except the stirring speed that controls the bath agitation, are kept constant. During still deposition, the cathode coverage is poor, and irregular and non-uniform deposits are obtained. This can be explained as when no agitation is provided, the depositing ions from the electrolyte get deposited preferentially on the cathode. Thus, a concentration gradient is established in the vicinity of electrolyte/cathode interface. The deposition is uneven at this stage and morphology is very poor. When the bath stirring is increased, the concentration gradient is decreased and deposition rate increases [87, 88]. Further stirring of the bath will cause fast transportation of metal ions towards cathode. At a sufficiently high stirring rates of the plating bath, the flow of the electrolyte will be turbulent and the metal ions may move away from the cathode vigorously and a lowering in the deposition rate is observed [88].
\n\t\t\tThe electrodeposition parameters considered in this investigation include current density, concentration of the additive, duty cycle, frequency, pH, temperature, and agitation. The obtained results in this work indicate that the pulsed current electrodeposition can be an efficient method for the electrosynthesis of tin deposits. The surface morphology evolution depends on the electrodeposition parameter that tries to modify the overpotential, in a direct or indirect way. The current density is the most sensitive of all the plating parameters which affects the deposit morphology severely. The nucleation rate and grain growth can be significantly controlled by changing the duty cycle to lower values up 5 to 20%. At higher duty cycles, the porous deposits are produced.
Smaller pulse frequency gives large grained deposits. Thus, a combination of duty cycle and pulse frequency can be optimized for an ultrafine grained or an optimum grain morphology depending upon the application. The presence of additives in the plating bath improves the surface finish and morphology if it is added up to its optimum concentration. The current density is found to decrease with bath pH increase. The grain size decreases as pH value increases due to the increase in the cathodic polarization. It is also noteworthy point that powdery deposits are too developed at very high pH due to the precipitation of stannic hydroxides. An increase in bath temperature is noticed to raise the grain size of the deposits. However, a decrease in the electrolyte conductivity and current efficiency is noted at elevated temperatures due to the precipitation of metal ions in the plating bath. Bath stirring improves the availability of metal ions towards cathode and thus the deposition rate is enhanced before the flow of electrolyte turns turbulent where the metal ions move away from the cathode. The grain size is also increased due to the decrease in overpotential with bath stirring rate
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
Our journals are currently in their launching issue. They will be applied to all relevant indexes as soon as they are eligible. These include (but are not limited to): Web of Science, Scopus, PubMed, MEDLINE, Database of Open Access Journals (DOAJ), Google Scholar and Inspec.
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The chapter describes the design, implementation and integration of a ground penetrating radar (GPR) using a software defined radio (SDR) platform into the aerial drone. The chapter?s goal is first to tackle in detail the development of a custom-designed lightweight GPR by approaching interplay between hardware and software radio on an SDR platform. The SDR-based GPR system results on a much lighter sensing device compared against the conventional GPR systems found in the literature and with the capability of re-configuration in real-time for different landmines and terrains, with the capability of detecting landmines under terrains with different dielectric characteristics. Secondly, the chapter introduce the integration of the SDR-based GPR into an autonomous drone by describing the mechanical integration, communication system, the graphical user interface (GUI) together with the landmine detection and geo-mapping. This chapter approach completely the hardware and software implementation topics of the on-board GPR system given first a comprehensive background of the software-defined radar technology and second presenting the main features of the Tx and Rx modules. Additional details are presented related with the mechanical and functional integration of the GPR into the UAV system.",book:{id:"5905",slug:"robots-operating-in-hazardous-environments",title:"Robots Operating in Hazardous Environments",fullTitle:"Robots Operating in Hazardous Environments"},signatures:"Manuel Ricardo Pérez Cerquera, Julian David Colorado Montaño\nand Iván Mondragón",authors:[{id:"177422",title:"Dr.",name:"Julian",middleName:null,surname:"Colorado",slug:"julian-colorado",fullName:"Julian Colorado"},{id:"197884",title:"Prof.",name:"Ivan",middleName:null,surname:"Mondragon",slug:"ivan-mondragon",fullName:"Ivan Mondragon"},{id:"199958",title:"Prof.",name:"Manuel",middleName:null,surname:"Perez",slug:"manuel-perez",fullName:"Manuel Perez"}]},{id:"15855",title:"Kinematics of AdeptThree Robot Arm",slug:"kinematics-of-adeptthree-robot-arm",totalDownloads:14668,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"152",slug:"robot-arms",title:"Robot Arms",fullTitle:"Robot Arms"},signatures:"Adelhard Beni Rehiara",authors:[{id:"29287",title:"Dr.",name:"Adelhard",middleName:"Beni",surname:"Rehiara",slug:"adelhard-rehiara",fullName:"Adelhard Rehiara"}]},{id:"62978",title:"Intelligent Robotic Perception Systems",slug:"intelligent-robotic-perception-systems",totalDownloads:2443,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Robotic perception is related to many applications in robotics where sensory data and artificial intelligence/machine learning (AI/ML) techniques are involved. Examples of such applications are object detection, environment representation, scene understanding, human/pedestrian detection, activity recognition, semantic place classification, object modeling, among others. Robotic perception, in the scope of this chapter, encompasses the ML algorithms and techniques that empower robots to learn from sensory data and, based on learned models, to react and take decisions accordingly. The recent developments in machine learning, namely deep-learning approaches, are evident and, consequently, robotic perception systems are evolving in a way that new applications and tasks are becoming a reality. Recent advances in human-robot interaction, complex robotic tasks, intelligent reasoning, and decision-making are, at some extent, the results of the notorious evolution and success of ML algorithms. This chapter will cover recent and emerging topics and use-cases related to intelligent perception systems in robotics.",book:{id:"7227",slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Cristiano Premebida, Rares Ambrus and Zoltan-Csaba Marton",authors:[{id:"203409",title:"Ph.D.",name:"Cristiano",middleName:null,surname:"Premebida",slug:"cristiano-premebida",fullName:"Cristiano Premebida"},{id:"254880",title:"Dr.",name:"Rares",middleName:null,surname:"Ambrus",slug:"rares-ambrus",fullName:"Rares Ambrus"},{id:"254881",title:"Dr.",name:"Zoltan-Csaba",middleName:null,surname:"Marton",slug:"zoltan-csaba-marton",fullName:"Zoltan-Csaba Marton"}]},{id:"67705",title:"Advanced UAVs Nonlinear Control Systems and Applications",slug:"advanced-uavs-nonlinear-control-systems-and-applications",totalDownloads:1971,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Recent development of different control systems for UAVs has caught the attention of academic and industry, due to the wide range of their applications such as in surveillance, delivery, work assistant, and photography. In addition, arms, grippers, or tethers could be installed to UAVs so that they can assist in constructing, transporting, and carrying payloads. In this book chapter, the control laws of the attitude and position of a quadcopter UAV have been derived basically utilizing three methods including backstepping, sliding mode control, and feedback linearization incorporated with LQI optimal controller. The main contribution of this book chapter would be concluded in the strategy of deriving the control laws of the translational positions of a quadcopter UAV. The control laws for trajectory tracking using the proposed strategies have been validated by simulation using MATLAB®/Simulink and experimental results obtained from a quadcopter test bench. Simulation results show a comparison between the performances of each of the proposed techniques depending on the nonlinear model of the quadcopter system under investigation; the trajectory tracking has been achieved properly for different types of trajectories, i.e., spiral trajectory, in the presence of unknown disturbances. Moreover, the practical results coincided with the results of the simulation results.",book:{id:"7792",slug:"unmanned-robotic-systems-and-applications",title:"Unmanned Robotic Systems and Applications",fullTitle:"Unmanned Robotic Systems and Applications"},signatures:"Abdulkader Joukhadar, Mohammad Alchehabi and Adnan Jejeh",authors:null}],onlineFirstChaptersFilter:{topicId:"22",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82223",title:"Biomechanical Design Principles Underpinning Anthropomorphic Manipulators",slug:"biomechanical-design-principles-underpinning-anthropomorphic-manipulators",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.105434",abstract:"The biomechanical design of an artificial anthropomorphic manipulator is the focus of many researchers in diverse fields. Current electromechanical artificial hands are either in the research stage, expensive, have patents, lack severely in function, and/or are driven by robotic/mechanical principles, which tend to ignore the biological requirements of such designs. In response to the challenges addressed above this chapter discusses the potential of current technology and methods used in design to bridge the chasm that exists between robot manipulators and the human hand. This chapter elucidates artificial anthropomorphic manipulator design by outlining biomechanical concepts that contribute to the function, esthetics and performance of artificial manipulators. This chapter addresses joint stabilization, tendon structures and tendon excursion in artificial anthropomorphic manipulators.",book:{id:"11455",title:"Recent Advances in Robot Manipulators",coverURL:"https://cdn.intechopen.com/books/images_new/11455.jpg"},signatures:"Mahonri William Owen and Chikit Au"},{id:"82056",title:"Learning Robotic Ultrasound Skills from Human Demonstrations",slug:"learning-robotic-ultrasound-skills-from-human-demonstrations",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.105069",abstract:"Robotic ultrasound system plays a vital role in assisting or even replacing sonographers in some cases. However, modeling and learning ultrasound skills from professional sonographers are still challenging tasks that hinder the development of ultrasound systems’ autonomy. To solve these problems, we propose a learning-based framework to acquire ultrasound scanning skills from human demonstrations1. First, ultrasound scanning skills are encapsulated into a high-dimensional multi-modal model, which takes ultrasound images, probe pose, and contact force into account. The model’s parameters can be learned from clinical ultrasound data demonstrated by professional sonographers. Second, the target function of autonomous ultrasound examinations is proposed, which can be solved roughly by the sampling-based strategy. The sonographers’ ultrasound skills can be represented by approximating the limit of the target function. Finally, the robustness of the proposed framework is validated with the experiments on ground-true data from sonographers.",book:{id:"10823",title:"Cognitive Robotics",coverURL:"https://cdn.intechopen.com/books/images_new/10823.jpg"},signatures:"Miao Li and Xutian Deng"},{id:"82057",title:"An Episodic-Procedural Semantic Memory Model for Continuous Topological Sensorimotor Map Building",slug:"an-episodic-procedural-semantic-memory-model-for-continuous-topological-sensorimotor-map-building",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.104818",abstract:"For humans to understand the world around them, learning and memory are two cognitive processes of the human brain that are deeply connected. Memory allows information to retain and forms an experiences reservoir. Computational models replicating those memory attributes can lead to the practical use of robots in everyday human living environments. However, constantly acquiring environmental information in real-world, dynamic environments has remained a challenge for many years. This article proposes an episodic-procedure semantic memory model to continuously generate topological sensorimotor maps for robot navigation. The proposed model consists of two memory networks: i) episodic-procedural memory network (EPMN) and ii) semantic memory network (SMN). The EPMN comprises an Incremental Recurrent Kernel Machines (I-RKM) that clusters incoming input vectors as nodes and learns the activation patterns of the nodes for spatiotemporal encoding. The SMN then takes neuronal activity trajectories from the EPMN and task-relevant signals to update the SMN and produce more compact representations of episodic experience. Thus, both memory networks prevent catastrophic forgetting by constantly generating nodes when the network meets new inputs or updating node weights when the incoming input is similar to previously learned knowledge. In addition, idle or outlier nodes will be removed to preserve memory space.",book:{id:"10823",title:"Cognitive Robotics",coverURL:"https://cdn.intechopen.com/books/images_new/10823.jpg"},signatures:"Wei Hong Chin, Naoyuki Kubota and Chu Kiong Loo"},{id:"81922",title:"Skill Acquisition for Resource-Constrained Mobile Robots through Continuous Exploration",slug:"skill-acquisition-for-resource-constrained-mobile-robots-through-continuous-exploration",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.104996",abstract:"We present a cognitive mobile robot that acquires knowledge, and autonomously learns higher-level abstract capabilities based on play instincts, inspired by human behavior. To this end, we (i) model skills, (ii) model the robot’s sensor and actuator space based on elementary physical properties, and (iii) propose algorithms inspired by humans’ play instincts that allow the robot to autonomously learn the skills based on its sensor and actuator capabilities. We model general knowledge in the form of competencies (skills) of the mobile robot based on kinematic properties using physical quantities. Thus, by design, our approach has the potential to cover very generic application domains. To connect desired skills to the primitive capabilities of the robot’s sensors and actuators, it playfully explores the effects of its actions on its sensory input, thus autonomously learning relations and dependencies and eventually the desired skill. KnowRob is used for knowledge representation and reasoning, and the robot’s operation is based on ROS. In the experiments, we use a millirobot, sized 2 cm2, equipped with two wheels, motion, and distance sensors. We show that our cognitive mobile robot can successfully and autonomously learn elementary motion skills based on a playful exploration of its wheels and sensors.",book:{id:"10823",title:"Cognitive Robotics",coverURL:"https://cdn.intechopen.com/books/images_new/10823.jpg"},signatures:"Markus D. Kobelrausch and Axel Jantsch"},{id:"81693",title:"The Neo-Mechanistic Model of Human Cognitive Computation and Its Major Challenges",slug:"the-neo-mechanistic-model-of-human-cognitive-computation-and-its-major-challenges",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104995",abstract:"The neo-mechanistic theory of human cognition is currently one of the most accepted major theories in fields, such as cognitive science and cognitive neuroscience. This proposal offers an account of human cognitive computation, and it has been considered by its proponents as revolutionary and capable of integrating research concerning human cognition with new evidence provided by fields of biology and neuroscience. However, some complex cognitive capacities still present a challenge for explanations constructed by using this theoretical structure. In this chapter, I make a presentation of some of the central tenets of this framework and show in what dimensions it helps our understanding of human cognition concerning aspects of capacities, such as visual perception and memory consolidation. My central goal, however, is to show that to understand and explain some particular human cognitive capacities, such as self-consciousness and some conscious informal reasoning and decision making, the framework shows substantial limitations. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. 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He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. 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She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. 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