Omics approaches target for different molecules.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"9615",leadTitle:null,fullTitle:"Chikungunya Virus - A Growing Global Public Health Threat",title:"Chikungunya Virus",subtitle:"A Growing Global Public Health Threat",reviewType:"peer-reviewed",abstract:"The chikungunya virus (CHIKV) is an RNA virus that is transmitted to humans by Aedes mosquitos commonly found in tropical and subtropical countries. In humans, CHIKV causes an infection with symptoms strikingly like those of the dengue virus and Zika disease, both of which are also transmitted to humans by the same genus of mosquitos. This book delves into the history of the disease and the molecular characterization of the virus. It sheds light on modern diagnosis tools that allow unambiguous identification of CHIKV infection. In addition, this book addresses the epidemiology of chikungunya fever, the distribution and spread of the disease, and the promising approaches under consideration for preventing and treating the disease.",isbn:"978-1-83969-090-7",printIsbn:"978-1-83969-089-1",pdfIsbn:"978-1-83969-091-4",doi:"10.5772/intechopen.87411",price:119,priceEur:129,priceUsd:155,slug:"chikungunya-virus-a-growing-global-public-health-threat",numberOfPages:102,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c960d94a63867dd12a8ab15176a3ff06",bookSignature:"Jean Engohang-Ndong",publishedDate:"February 9th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/9615.jpg",numberOfDownloads:614,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 13th 2020",dateEndSecondStepPublish:"December 21st 2020",dateEndThirdStepPublish:"February 25th 2021",dateEndFourthStepPublish:"May 16th 2021",dateEndFifthStepPublish:"July 15th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Kent State University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"79877",title:"Introductory Chapter: Introduction to Chikungunya",doi:"10.5772/intechopen.101892",slug:"introductory-chapter-introduction-to-chikungunya",totalDownloads:70,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Jean Engohang-Ndong",downloadPdfUrl:"/chapter/pdf-download/79877",previewPdfUrl:"/chapter/pdf-preview/79877",authors:[{id:"180733",title:"Dr.",name:"Jean",surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong"}],corrections:null},{id:"77968",title:"History and Geographic Distribution of Chikungunya Virus",doi:"10.5772/intechopen.98662",slug:"history-and-geographic-distribution-of-chikungunya-virus",totalDownloads:110,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chikungunya fever (CHIKF) is a mosquito-borne disease caused by an arbovirus endemic to Africa and Asia. It was initially seen in the early 1950s at the boundary of Tanzania and Mozambique. Due to the ease with which its vectors propagate, the virus has spread to India, Europe, and recently it arrived in the Caribbean, eventually extending into North, Central, and South America. According to the World Health Organization (WHO), the most common clinical manifestations are abrupt fever, polyarthralgia, headache, maculopapular rash, myalgia, and nausea/vomiting. Severe joint pain and stiffness have been known to incapacitate some patients from a few days to several months after infection. The re-emergence of the CHIKV and its spread to new places around the globe has encouraged the development of new preventive, diagnostic, and treatment strategies. This chapter will discuss the history of CHIKV and expanding geographic distribution.",signatures:"Maria Zavala-Colon and Juan A. Gonzalez-Sanchez",downloadPdfUrl:"/chapter/pdf-download/77968",previewPdfUrl:"/chapter/pdf-preview/77968",authors:[{id:"337443",title:"Dr.",name:"Juan",surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez"},{id:"337446",title:"Dr.",name:"Maria",surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon"}],corrections:null},{id:"77207",title:"Epidemiology of Chikungunya in Indonesia",doi:"10.5772/intechopen.98330",slug:"epidemiology-of-chikungunya-in-indonesia",totalDownloads:56,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chikungunya is a zoonotic disease which is caused by the Chikungunya virus (CHIKV) and transmitted by infected Aedes spp mosquito. In Indonesia, CHIKV is a re-emerging disease, which means that it is a disease that has gone for a long time, but then it spreads again and causes outbreaks frequently. CHIKV presence in Indonesia was first reported in 1979 in Bengkulu City causing substantial acute and chronic morbidity. After disappearing for 16 years, the CHIKV outbreak spreaded again in 24 regions throughout Indonesia from 2001 to 2003. In 2009 and 2010, CHIKV outbreaks hit western and central regions of Indonesia and increased from 3,000 cases per year to 83,000 and 52,000 cases per year. The burden of this disease is unclear due to insufficient monitoring and diagnosis. The spread and transmission of CHIKV in Indonesia is very high, due to travel, competent vectors, and the vulnerability of the population. In addition, the evolution of viruses, globalization and climate change has accelerated the spread of this virus. Effective antiviral treatment and vaccines do not yet exist, so early detection and appropriate management can help reducing the burden of this disease. Monitoring and risk assessment to reduce human-vector contact are also needed to reduce the impact of chikungunya.",signatures:"Tri Baskoro Tunggul Satoto and Nur Alvira Pascawati",downloadPdfUrl:"/chapter/pdf-download/77207",previewPdfUrl:"/chapter/pdf-preview/77207",authors:[{id:"338853",title:"Associate Prof.",name:"Tri Baskoro Tunggul",surname:"Satoto",slug:"tri-baskoro-tunggul-satoto",fullName:"Tri Baskoro Tunggul Satoto"},{id:"338856",title:"Mrs.",name:"Nur Alvira",surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati"}],corrections:null},{id:"78915",title:"Chikungunya Virus Transmission",doi:"10.5772/intechopen.100199",slug:"chikungunya-virus-transmission",totalDownloads:59,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chikungunya virus (CHIKV) is a mosquito-borneAlphavirus that causes Chikungunya fever (CHIKF) in humans. In 1952, the CHIKV was found in East Africa in a sylvatic and urban cycle between Aedes mosquitoes, and human and nonhuman primates in tropical regions. Since 2004, CHIKF has spread rapidly in Asia, Africa, Europe, and the Americas. Both Aedes aegypti and Aedes albopictus are known to be arboviral mosquito vectors of CHIKV. Ae. aegypti is mostly found within the tropics, whereby Ae. albopictus also occurs in temperate and cold temperate regions. Host-seeking female mosquitoes are infected after feeding on a viremic animal. The replication of CHIKV happens in the midgut and then enters the hemocoel before disseminating to the salivary glands of the mosquito. The disseminated virus can be transmitted by injecting infectious saliva into the host skin during blood feeding. In the naïve host body, CHIKV replicates in the dermal fibroblasts through blood circulation, and disseminates to other parts of the body such as brain cells, kidney, heart, lymphoid tissues, liver, and joints. Symptoms of CHIKV infection include high fever, rigors, headache, photophobia, and maculopapular rash. It is advised to avoid mosquito bites; also, larvae management systems should be applied in endemic environments.",signatures:"Lucille Lyaruu",downloadPdfUrl:"/chapter/pdf-download/78915",previewPdfUrl:"/chapter/pdf-preview/78915",authors:[{id:"251365",title:"Ms.",name:"Lucile",surname:"Lyaruu",slug:"lucile-lyaruu",fullName:"Lucile Lyaruu"}],corrections:null},{id:"77184",title:"Treatment and Prevention of Chikungunya Fever: Current Status and Prospective",doi:"10.5772/intechopen.98523",slug:"treatment-and-prevention-of-chikungunya-fever-current-status-and-prospective",totalDownloads:150,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chikungunya fever is a vector borne tropical disease that was first described in an outbreak in Tanzania. The disease is caused by Chikungunya virus (CHIKV), an alpha virus belonging to the family Togaviridae and which is transmitted from one person to another via the bite of mosquitoes. Active disease is characterized by high grade fever, pain and joint symptoms. Although debilitating at times, the disease seldom progresses to result in a serious outcome like death. There are no specific treatments for Chikungunya virus at the moment. Clinical case management is highly dependent on providing palliative care which in turn is expected to alleviate symptoms and accelerate recovery from the infection. An important element in the control of outbreaks of CHIKV infection is prevention. Preventive strategies involve initiatives like vector control, immunizations and extra care to patients with the infection. There have been several tens of researches focusing on the introduction of newer drugs and vaccines against Chikungunya. That being said, so far, no single agent has completed the entire drug or vaccine development process. Chikungunya fever is a neglected tropical disease. Although it has no specific treatment till date, the number of vaccine and drug candidates under study provides promising insights on the prospects on chikungunya treatment.",signatures:"Merhawi Debesai Oqbazgi",downloadPdfUrl:"/chapter/pdf-download/77184",previewPdfUrl:"/chapter/pdf-preview/77184",authors:[{id:"342462",title:"B.Sc.",name:"Merhawi Debesai",surname:"Oqbazgi",slug:"merhawi-debesai-oqbazgi",fullName:"Merhawi Debesai Oqbazgi"}],corrections:null},{id:"76721",title:"Treatment of Chikungunya Virus (CHIKV) Using Targeted Immunotherapy",doi:"10.5772/intechopen.97811",slug:"treatment-of-chikungunya-virus-chikv-using-targeted-immunotherapy",totalDownloads:169,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chikungunya virus (CHIKV) is the most common mosquito-borne Alphavirus infecting humans worldwide. Up to date, there are no antiviral treatments or vaccines approved to treat or prevent CHIKV for which treatments remain symptomatic based on clinical manifestations. Hence, designing effective therapies to either prevent or treat CHIKV infection is of paramount importance. Interestingly, monoclonal antibodies (mAbs) are known to be significantly important in mediating protective immunity in CHIV infection. During the last decades, numerous animal studies have reported the protective and prophylactic efficacy of human and mouse anti-CHIKV mAbs isolated from convalescent patients. However, the therapeutic benefits of these anti-CHIKV mAbs can be limited by multiple factors. Thus, it becomes pertinent to better understand the CHIKV infection dynamics, mitigate the undesired mAbs-associated effects and improve therapies. In this review, we critically discuss CHIKV antiviral infectious mechanisms and address how the improved understanding of the latter may pave the way to better targeted immunotherapies.",signatures:"Fleury Augustin Nsole Biteghe, Chalomie Nyangone Ekome Toung, Jean De La Croix Ndong, Neelakshi Mungra, Tahir B. Dar and Arnaud John Kombe Kombe",downloadPdfUrl:"/chapter/pdf-download/76721",previewPdfUrl:"/chapter/pdf-preview/76721",authors:[{id:"335859",title:"Dr.",name:"Fleury",surname:"Augustin Nsole Biteghe",slug:"fleury-augustin-nsole-biteghe",fullName:"Fleury Augustin Nsole Biteghe"},{id:"345816",title:"Dr.",name:"Chalomie",surname:"Nyangone Ekome Toung",slug:"chalomie-nyangone-ekome-toung",fullName:"Chalomie Nyangone Ekome Toung"},{id:"345817",title:"Mr.",name:"Arnaud John",surname:"Kombe Kombe",slug:"arnaud-john-kombe-kombe",fullName:"Arnaud John Kombe Kombe"},{id:"345818",title:"Dr.",name:"Tahir. B",surname:"Dar",slug:"tahir.-b-dar",fullName:"Tahir. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. 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Research interest on biomarkers has increased in recent years. In MedLine search in 1990, there were only 21 hits on cardiovascular risk markers, while by 2010, it is increased to 2032 hits, thus indicating huge increase in number of publications in biomarkers in the last decade [2]. There were 37% more biomarker studies in 2014 as compared to 2013 [3]. However, only few biomarkers are routinely used in clinical practice. For example, fasting blood sugar, glycated haemoglobin, cardiac troponin T (cTnT), cardiac troponin I (cTnI), and B-type natriuretic peptide (BNP) are used regularly for diabetes, myocardial infarction, and heart failure. Biomarkers should have specific characteristics, i.e. specific to the particular diseases and easily detectable. Biomarker can be predictive to identify disease progression after treatment. The detection method should be fast, simple, and low cost. It should be stable at any time of the day and samples should be available easily by invasive method (blood and urine). Identified biomarker should be proven of its importance preclinically and clinically. Biomarker can be used for different purposes such as the early detection of disease, evaluation of acute and chronic clinical condition, risk stratification of patients to suspect or confirm the diagnosis, selection of appropriate therapeutic treatment, and observation of patient response for the treatment (Figure 1) [4]. Identification of early biomarkers for noncommunicable chronic diseases such as diabetes is very important for finding appropriate therapeutic strategy.
\nBiomarker characteristics (inner circle) and applications (outer circle).
Prevalence of diabetes is reaching epidemic proportions in developed and developing nations due to increase in life expectancy, sedentary lifestyle, and obesity. As per the International Diabetic Federation (IDF) Diabetes Atlas (Sixth Edition 2013), the number of people with diabetes is 382 million and it is going to rise to 592 million by 2035. Global burden of diabetes is huge and 548 billion dollars was spent in 2013. In India, approximately 65.1 million people are with diabetes. Cardiovascular diseases (CVDs) are the major complications of diabetes. The prevalence, incidence, and mortality of cardiovascular diseases are two- to fourfold higher in persons having diabetes than those without diabetes [5]. Prediction of cardiovascular disease (CVD) risk among people with diabetes is important not only to give better clinical therapy but also to distinguish higher risk patients for extra care. Biomarkers may help in early detection of diseases, distinguishing patients based on disease severity, and find the cardiovascular risk among diabetic patients.
\nDiabetes is characterised by high glucose level in blood due to either less insulin secretion from pancreas or developing insulin resistance in skeletal muscle. Type 2 diabetes (T2DM) is the commonest form and it is characterised by insulin resistance mostly in skeletal muscle and deficiency of insulin release at end stage. In general, T2DM causes elevation of blood glucose level and other components of metabolic syndrome. Parameters of metabolic syndrome are elevated blood pressure, increased triglycerides, reduced high density lipoprotein levels, and abdominal obesity [5]. In obese condition, increased adipocytes secrete adipocytokines. Released adipocytokines integrate the endocrine, autocrine, and paracrine signals to mediate the insulin sensitivity, oxidative stress, energy metabolism, blood coagulation, and inflammatory responses. Elevated levels of free fatty acids (FFAs) induce insulin resistance and increase fibrinogen and plasminogen activator inhibitor-1 (PAI-1). In the long run, high FFA and glucose together impair beta-cell function through lipotoxicity and glucotoxicity and develop macro- and microvascular complications [6,7].
\nDevelopment of biomarkers with the help of different omics approaches.
Diabetes and cardiovascular diseases are involved in different abnormalities in genes, proteins, metabolites, and lipids by different mechanisms such as oxidative stress, inflammation, and endothelial dysfunction. Identification of highly sensitive and specific potential biomarkers would be beneficial for the detection of cardiovascular diseases risk among diabetic patients with different advanced omics approaches such as genomics (genes), metabolomics (metabolites), proteomics (proteins), transcriptomics (mRNA), and lipidomics (lipids) (Figure 2). These new techniques are useful for simultaneous investigation of multiple molecules and to identify different kinds of biomarkers (Table 1).
\nDifferent omics approaches | \nStudy of different molecules | \nTechnology used | \n
---|---|---|
Genomics | \nDNA | \nDNA microarray Single nucleotide polymorphism Hot spot mutation Epigenomics | \n
Transcriptomics | \nmRNA tRNA rRNA Noncoding RNA | \nRNA microarray New-generation sequencing (NGS) Exome sequencing | \n
Proteomics | \nProteins and their abundance, variation, modific ations, and interactions | \n2D-PAGE Protein microarray Mass spectrometry MALDI-TOF-MS ESI-MS | \n
Metabo lomics | \nMetabolites | \nNMR Mass spectrometry–LC–MS | \n
Lipi domics | \nLipids | \nMass spectrometry–LC–MS/MS | \n
Omics approaches target for different molecules.
(
Diseases | \nStudy name | \nApproach | \nSample type | \nNo. of patients | \nBiomarkers identified | \nReference | \n
---|---|---|---|---|---|---|
Prediabetes | \nKORA | \nMetabo lomics | \nSerum | \n4297 | \nThree metabolites (glycine, lysoph osphatid\', and acetylcarnitine) that altered significant levels in impaired glucose tolerance (IGT) as compared with normal glucose tolerance | \n[98] | \n
Type 2 diabetes | \n– | \nProte omics (2D-LC– MS/MS) | \nSaliva | \n40 (10 control, 10 I FG, 10 IGT, 10 T2DM patients) | \n487 biomarkers identified | \n[99] | \n
T2DM | \nFrami ngham Off spring Study | \nMetabo lomics | \nPlasma | \nRando mly se lected 1561 ind ividuals | \nOut of 70 metabolites 2-AAA (2-amino adipic acid) had the strongest association with risk of future diabetes mellitus | \n[100] | \n
Cardio vascular diseases | \nBruneck study | \nLipi domics | \nPlasma | \n685 subj ects with 10-year observ ation period | \nCholesterol esters (CEs) , lysophosphatidylcholines, phosphatidylcholines, phosphatidylethanolamines (PEs), sphingomyelins, and triacylglycerols (TAGs) were associated with cardiovascular disease | \n[101] | \n
Obesity and insulin resistance | \nThe Western Australian Pregnancy Cohort (Raine) Study | \nLipi domics | \nPlasma | \n1126 patients with 20-year follow-up | \nSphingomyelins, particularly those with two double bonds, and lysophosphatidylcholines were identified between subjects with normal weight and obesity independent of LDL-C and HDL-C concentrations | \n[102] | \n
Cardiov ascular diseases | \nNational Finnish FINRISK study, SABRE study, and BWHH Study | \nMetabo lomics | \nSerum | \nFINRISK ( 800 events), SABRE ( 2622; 573 events), and British Women’s ( 368 events) | \nHigher phenylalanine and monounsaturated fatty acid levels were associated with increased cardiovascular risk, while higher omega-6 fatty acids and docos ahexaenoic acid levels were associated with lower risk | \n[103] | \n
Cardiova scular dis eases | \n– | \nMetabo lomics | \nPlasma | \n2023 consecutive patients undergoing cardiac catheter isation | \nFive metabolite factors were independently associated with mortality: factor 1 (medium-chain acylcarnitines, short-chain dic arboxylacylcarnitines, long-chain dicarboxylacyl carnitines), factor 6 (branched-cha in amino acids) | \n[104] | \n
Type 2 diabetes | \n– | \nLipidomics | \nPlasma | \n104 wo men with previ ous ges tational diabetes; 21 (20%) developed diabetes during the median follow-up period of 8.5 years | \nCholesteryl ester species CE 20:4 , alkenylphosphatidylethan olamine species PE (P-36:2), and the phosphatidyls erine species PS 38:4 were independently and positively associated with the development of type 2 diabetes | \n[105] | \n
Biomarkers identified by different omics approaches in diabetes and cardiovascular diseases.
Although there are a high number of research articles describing existing and promising biomarkers for diabetes and cardiovascular disease, here we are providing an overview of a few standard and exciting biomarkers that regularly used in clinic.
\nGlycated haemoglobin (HbA1c) and glucose levels are mostly used for the diagnosis of diabetes. These two tests give idea about sugar levels in the body in the presence and absence of medication. However, these tests can be used to predict the disease in the later stages not in the early stages. So, there is an urgent need to identify novel biomarkers to detect the early stage of diabetes, i.e. prediabetic stage.
\nTroponin T (cTnT), troponin I (cTnI), and creatinine kinase-MB (CK-MB) are the common markers for the diagnosis of myocardial injury and stratification of the risk in acute coronary syndrome. cTnI is as effective as cTnT in diagnosing myocardial necrosis in the setting of trauma and coronary bypass grafting [9]. Increased hs-cTnT concentrations are associated with extent and complexity of CAD as well as diabetic patients with stable CAD [10]. Recently, Brendan et al. reported that cardiac troponin T concentration was an independent predictor of death from cardiovascular causes, myocardial infarction, or stroke in patients who had both type 2 diabetes and stable ischemic heart disease [11]. European Society of Cardiology (ESC) and the American College of Cardiology (ACC) guidelines have recommended cardiac troponins are markers for the acute myocardial infarction. These sensitive markers (cTnT and cTnI) begin to rise in the first 4–8 h following injury and peak at 12–24 h. However, cTnT may remain raised for more than two weeks while cTnI for more than 5–7 days. These two detect myocardial injury below the detection limit of CK-MB. Some of the clinicians measured CK-MB to rule out myocardial infarction and to monitor for additional cardiac muscle injury over time [9].
\nNatriuretic peptides [brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP)] and their N-terminal pro-hormones [N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP)] were increased in patients with heart failure, i.e. left ventricular dysfunction. In general, these markers are produced initially within the heart and released into the circulation in response to increased wall tension. BNP and ANP are secreted not only from the atria but also from the ventricles, especially in patients with heart failure. BNP and NT-pro-BNP may be superior to ANP and NT-pro-ANP in the detection of left ventricular dysfunction [12].
\nC-reactive protein (CRP) is a liver-derived pattern recognition molecule and systemic inflammatory marker that is increased in inflammatory states. It releases rapidly after immediate tissue injury and work as host defence [13]. Interleukin-6 (IL-6) is the most potent inducer of CRP production, and hsCRP (high-sensitivity C-reactive protein) is released from activated leukocytes in response to infection or trauma and from vascular smooth muscle cells in response to atherosclerosis [14]. Inflammation plays a major role in type 2 diabetes and cardiovascular diseases. Inflammation is the one of the risk factors for the development of T2DM and CVD. Researchers have identified that increased hsCRP levels were associated with obesity, metabolic syndrome, type 1 diabetes, type 2 diabetes, atherosclerosis, and coronary artery diseases (CADs) [15]. Increased blood hsCRP levels indicate the coexistence of subclinical systemic inflammation and insulin resistance and correlated with elevated insulin, C-peptide, and HOMA-IR (Homeostatic Model Assessment-insulin resistance) [16]. Treatment with aspirin, statins, cyclooxygenase-2 inhibitors, and fibrates are able to reduce hsCRP levels [13]. Treatment with peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist pioglitazone also decreased hsCRP along with other cardiovascular risk markers [17].
\nPro-inflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1-beta, and IL-8 and monocyte chemoattractant protein (MCP-1); cell adhesion molecules, i.e. intra-cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); and markers of cardiovascular risk, i.e. C-reactive protein (CRP), homocysteine, and plasminogen activator inhibitor-1 (PAI-1) and reactive oxygen species (ROS) are the common markers for inflammation and oxidative stress. Metabolic hormones such as resistin, leptin, adiponectin, ghrelin, and visfatin were also altered in diabetes and metabolic disorder and considered as important biomarkers for understanding the diabetic complication.
\nAll these above markers are used to predict diabetes and cardiovascular diseases independently but not in a combination to understand the disease complexity. Even these biomarkers are not able to predict the disease in the early stages. Thus, there is an urgent need to identify novel biomarkers to predict the early detection of the disease and disease progression.
\nGalectin-3 (Gal-3) a 30-kDa β-galactoside-binding lectin mainly present in the cytoplasm, and also in the nucleus, is expressed by different types of cells and regulates various T-cell functions and innate immune responses. Expression of galectin-3 increased in activated macrophages and involved in inflammation, tumour growth, and fibrosis [18,19]. Gal-3 protects β-cells from the cytotoxic effect of IL-1β [20] and advanced glycation end product (AGE)-induced tissue injury. Removal of Gal-3 accelerates AGE-induced kidney injury in diabetes [21], enhances atherogenesis [22], accelerates high-fat diet-induced obesity, and increases inflammation in adipose tissue and pancreatic islets. Gal-3 shows protective effect in obesity-induced inflammation and diabetes [18]. Ohkura et al. reported that low levels of Gal-3 were associated with insulin resistance in T2DM patients [23]. On the contrary, elevated levels of Gal-3 are associated with increased risk of heart failure and mortality [24]. Recently, Ozturk et al. identified that Gal-3 concentrations were significantly higher in the coronary artery disease (CAD) group than in the non-CAD group. Gal-3 levels were correlated positively with BMI (Body mass index), high-sensitivity C-reactive protein, the total number of diseased vessels, the number of plaques, and the calcified plaque type. In addition, galectin-3 levels were found to be independent predictor of coronary atherosclerosis in type 2 diabetic patients. Gal-3 is a novel and promising biomarker that may help to identify type 2 diabetic patients who may require early CAD intervention because of the potential risk of coronary atherosclerosis [25]. Jin et al. reported that elevated galectin levels were associated with increase in vascular complications, i.e. the heart failure, nephropathy, and peripheral artery diseases. Several research articles have shown association of Gal-3 with diabetes and cardiovascular diseases. However, many questions still need to be answered before considering Gal-3 as a biomarker in diabetes and cardiovascular diseases: Can Gal-3 specifically be used as a biomarker for diabetes-associated cardiovascular diseases (Gal-3 is usually expressed in the inflammatory and fibrinolytic conditions in the liver, kidney, and lungs; this shows lack of tissue specificity)? Can Gal-3 alone predict the disease prevention strategy? Can it be used with any other established marker to predict diabetes-associated cardiovascular complications?
\nIrisin is a newly discovered hormone which is mainly secreted by the heart, skeletal muscle, liver, and kidneys. Bostrom et al. reported that cardiac muscle produces more irisin than skeletal muscle. Irisin is mainly produced within heart and skeletal muscle [26]. Irisin is essential to convert white adipose tissue to brown adipose tissue. He et al. found that irisin levels were decreased and urotensin II (UII) levels were increased in type 2 diabetic subjects. Circulating urotensin II levels were increased in diabetes and could inhibit the glucose transport in skeletal muscle in diabetic mouse and aggravated the insulin resistant [27]. The study found the association between both irisin and urotensin II and concluded that urotensin II and high glucose may inhibit the release of irisin from skeletal muscle in diabetic patients [28]. Increased circulating irisin predicts the insulin resistance onset in association with weight regain and authors concluded that irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis [29]. Two-week treatment with simvastatin increased circulating irisin concentrations in healthy individuals and also in primary human skeletal muscle cells. Simvastatin induces both cellular stress markers as well as protective response markers. Simvastatin-induced irisin secretion can block mitochondrial oxidative stress and thus play an important role in the regulation of oxidative stress in human skeletal muscle [30]. Irisin is also secreted in response to the activation of PGC-1α. Previous studies have explained well regarding the regulation of PGC-1α in mitochondrial biogenesis, oxidative metabolism, mitochondrial function, and modulation of insulin resistance. Decreased PGC-1α levels in type 2 diabetic subjects as reported earlier [31–33] might be responsible for reduced irisin levels. There is a controversy regarding irisin levels in obesity, insulin resistance, and metabolic syndrome in type 2 diabetic patients. While some reported higher irisin levels in diabetic patients, others reported the opposite [34–36]. These discrepancies were due to the data analysed from different stages of diseases and the presence of other complications [26]. Researchers have reported that serum irisin levels were decreased in type 2 diabetes and myocardial infarction patients [37,38]. Aronis et al. reported that increased irisin levels predict the development of major cardiovascular events, especially unstable angina, in patients with CAD after percutaneous intervention (PCI) [39]. Hanatani et al. also reported that irisin is a novel biomarker providing prognostic information in patients with heart failure with reduced ejection fraction. However, further clinical studies are needed to find whether irisin is associated with cardiometabolic disease and evaluate whether circulatory irisin levels could serve as an independent prognostic marker in diabetic patients with cardiovascular complications and also elucidate beneficial effects by finding molecular mechanism and intervention studies in different animal models.
\nApelin is identified as a 36-amino acid peptide and is an endogenous ligand of G-protein-coupled receptors (GPCRs) of apelin receptor. Recently, apelin was recognised as adipokine and secreted from white adipose tissue. Apelin receptor is present in ventricular cardiomyocytes, vascular smooth muscle cells (VSMCs), and intra-myocardial endothelial cells (ECs) [40]. Apelin stimulates endothelium-dependent nitric oxide-mediated vasorelaxation and reduces arterial blood pressure. Apelin synthesis in adipocytes is stimulated by insulin, and apelin plasma levels are markedly increased in obesity associated with insulin resistance [41]. Apelin shows antioxidant effects and attenuates reactive oxygen species (ROS)-induced adipogenesis, lipogenesis, lipolysis, and release of free fatty acids [42]. Apelin knockout mice show diminished insulin sensitivity [43]. Tumour necrosis factor-α (TNF-α) induces the expression of apelin via phosphatidylinositol 3-kinase (PI3K), c-Jun N-terminal kinase (JNK) and MEK1/2 signalling pathways in adipocytes [44]. Chronic treatment with apelin ameliorates both glucose and lipid metabolism and also increases muscle mitochondrial performance through increased mitochondrial biogenesis and a tighter matching between fatty acid oxidation and the tricarboxylic acid cycle. Therefore, chronic apelin treatment can be a targeted therapy for type 2 diabetes and its complications [45]. Furthermore, in studies using lipopolysaccharide (LPS) and cytokines to elicit an immune response in rodents, the expression of apelin mRNA has been reported to be upregulated, involving the JAK/STAT pathway [40]. Ma et al. reported that plasma apelin is a novel biomarker for predicting type 2 diabetes in men [46]. It was reported that suppressed apelin levels were associated with increased cardiovascular risk in women with previous history of gestational diabetes [47]. Recently, Abd-Elbaky et al. reported that omentin levels were significantly lower and serum apelin and IL-1β concentrations were significantly higher in obese diabetic groups compared to nonobese controls. This study concluded that abnormal production of omentin and apelin can contribute to the pathogenesis of obesity-related complications including T2DM and cardiovascular disease [48]. However, further research is needed to confirm whether apelin can be used as biomarker in diabetes and cardiovascular diseases.
\nGrowth differentiation factor-15 (GDF-15) is a stress-responsive cytokine produced as a ≈40 kDa propeptide form and N-terminal cleaved to release as a ≈30 kDa disulphide-linked dimeric active protein form. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Researchers have reported that GDF-15 shows cardioprotective effect through activation of ALK (Activin receptor-like kinase) type 1 receptor (ALK 1–7) and GDF-15 phosphorylates Smad2/3 and Smad1/5/8 which translocate to the nucleus in the form of heteromeric complex with Smad4 and activates PI3K/AKT/eNOS/NO pathway. It also inhibits epidermal growth factor receptor (EGFR) transactivation and NF-kB/JNK/caspase-3 pathway. Many patents have been filed reporting GDF-15 as a marker for the diabetes and cardiovascular diseases. Patent no. EP2439535A1 claimed that GDF-15 can be distinguished between diabetes and diabetes with coronary artery diseases subjects. Recently, we have also shown that GDF-15 levels can be useful to distinguish diabetic patients from cardiovascular complications [5]. However, a large multinational study has to be conducted to validate GDF-15 as a biomarker to detect specific cardiovascular complication in diabetes.
\nGrowth differentiation factor-11 (GDF-11) is a cytokine that belongs to TGF-β super family and also known as bone morphogenetic protein-11 (BMP-11). GDF-11 works like myostatin to modulate metabolic function [49]. Previous scientific literature claimed that GDF-11 is an anti-ageing factor. Fadini et al. showed that circulating GDF-11 levels were decreased with age [50]. Peripheral supplementation of GDF-11 protein in mice attenuated the age-related dysfunction of skeletal muscle [51]. In recent years, researchers are focusing their interest on circulatory GDF-11 levels in heart diseases. GDF-11 levels reversed the age-related hypertrophied heart into a young heart [52]. GDF-11 is also an essential factor for the regeneration of pancreatic islets in diabetic patients [53]. The plasma GDF-11 levels with age and disease condition remain controversial. Egerman et al. in his study showed that an increased GDF-11 protein level was observed with age in rat skeletal muscle. However, serum GDF-11 levels in rat and human were not significantly increased [54]. In contrast, Poggioli et al. explained age-dependent decline in GDF-11 levels in multiple mammalian species such as mice, rats, horses, and sheep. They also showed that exogenous GDF-11 administration rapidly activates SMAD signalling to reduce cardiomyocyte size [55]. This property of reducing cardiomyocytes can be useful against cardiac hypertrophy. Two more recent studies supported the above statement. Heidecker et al. showed that low levels of GDF-11 and high levels of its inhibitor follistatin-like 3 are associated with adverse cardiovascular outcomes in humans [56]. Similarly Olson et al. reported that high levels of GDF-11 are associated with lower prevalence of left ventricular hypertrophy [57]. Recently, Adela et al. reported that plasma GDF-11 levels were decreased in diabetes and diabetes with cardiovascular complications as compared with control subjects [58]. To use GDF-11 as a biomarker for diabetes and diabetes associated with cardiovascular diseases, more research needs to be carried out with a different population. GDF-11 could be used as a biomarker or as an intervention therapy to reduce the disease progression.
\nCyclophilin A (CyPA) was discovered three decades ago as the intracellular receptor of the immunosuppressive drug cyclosporine. CyPA is secreted from vascular cell components of endothelial cells and vascular smooth muscle cells in response to the reactive oxygen species (ROS) and also expressed in T cells, neutrophils, monocytes, macrophages, and foam cells and shows cellular effects such as proliferation, migration, activation of NF-kB, induction of matrix metalloproteinases, adhesion of molecules, and induction of ROS [59]. Extracellular CyPA initiates expression of adhesion molecules in endothelial cells (EC), induces apoptosis, and works as a chemoattractant for inflammatory cells. Intracellular and extracellular CyPA promotes intimal thickening, abdominal aortic aneurysms, atherosclerosis, and cardiac hypertrophy in mice [60]. Recently Tsai et al. reported that hyperglycaemia causes release of CyPA in mesangial (MES-13) and tubular (HK-2) cells. Urinary CyPA correlated with the progression of renal function. Significant increase in urinary CyPA was noted in stage 2 diabetic nephropathy and persisted in later stages of the disease. This study concluded that CyPA is a new biomarker for diabetic nephropathy and can be used as an early maker [61]. Type 2 diabetes subjects have increased circulating levels of CyPA than the healthy subjects. CyPA is secreted by monocytes in response to high glucose treatment and responsible for the progression of atherosclerosis in type 2 diabetes [62]. Further authors found that plasma CyPA levels were increased in diabetes subjects with coronary artery disease. This study concluded that CyPA play important role to progress vascular disease in type 2 diabetes subjects. The scientific literature thus provides strong evidence that CyPA work as inflammatory mediator in the progression of atherogenesis [63]. Therefore, all data indicate that CyPA is a promising and potential biomarker for the detection of vascular diseases in type 2 diabetes [64].
\nProlactin is a polypeptide released as a pituitary hormone. Prolactin is named so for its ability to promote lactation in post pregnancy in female mammals. Other than lactogenic property, prolactin plays important role in the regulation of reproduction, growth and development, metabolism, immune regulation, brain function, and behaviour [65]. Prevalence of obesity was increased in hyperprolactinaemic patients [66]. Circulating levels of prolactin increase in diabetic patients. Increased prolactin levels were associated with lower prevalence of diabetes and impaired glucose regulation [65,67]. However, Balbach et al. reported that low circulatory prolactin concentration is associated with increased T2DM risk. However, this study did not show any evidence to prove prolactin as a cardiometabolic risk factor [68]. Prolactin levels were increased in essential hypertension, acute coronary syndromes, ischemic strokes, transient ischemic attacks, pre-eclampsia, and heart failure. Carrero et al. also reported that increased prolactin levels were associated with endothelial dysfunction, increased risk of cardiovascular events, and increased mortality in chronic kidney disease (CKD) patients [69]. In vitro studies show that prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelium and induces vascular smooth muscle cell proliferation. Reuwer et al. study did not predict the prolactin as predictor for the coronary artery diseases in spite of presence of prolactin receptors in human coronary artery plaques [70]. On the other hand, increased plasma prolactin can protect rat cardiomyocytes against hypoxia through the p-JAK2 and p-STAT5 pathways and the PI3Kα/AKT and MAPK survival pathways [71]. Landberg et al. reported that prolactin concentrations were not associated with cardiovascular mortality and thus not a marker of heart failure [72]. However, a cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy and authors claimed that inhibition of prolactin may be a new therapeutic strategy for the paripartum cardiomyopathy [73].
\nVitamin D is a secosteroid that exists in two forms, i.e. ergocalciferol (D2) and cholecalciferol (D3). Ergocalciferol (D2) is synthesised from the vegetable sources. Unlike D2, cholecalciferol (D3) is synthesised by the epidermis on exposure to the UV radiation (sunlight) and also from oily fish supplementation. Vitamin D (D2 and D3) is converted into active metabolite 1, 25(OH)2 D by the two hydroxylation steps. These active metabolites bind with the vitamin D receptor and exert its biological action [74]. Vitamin D receptors are present in many cells such as pancreatic β cells, cardiomyocytes, endothelial cells, and vascular smooth muscle cells. Vitamin D plays a pivotal role in the bone and mineral metabolism. Vitamin D deficiency is a common health problem worldwide and is the cause for osteoporosis and osteomalacia, rickets, and other bone-related disorders. In the recent decades, researchers have also identified that lower vitamin D levels were associated with metabolic diseases such as type 1 diabetes, obesity, insulin resistance, hypertension, cardiovascular diseases, and cancer [75,76]. Many epidemiological studies have reported that people from different countries are more prevalence to vitamin D deficiency [77–82]. Eight-week vitamin D replacement therapy in type 2 diabetic patients potentially has beneficial effects on cardiovascular disease risk factors such as HbA1c, total cholesterol, LDL-C, and diastolic blood pressure [83]. Tarcin et al. reported that 25(OH)D-deficient subjects has lower flow-mediated dilatation (FMD) which is useful to measure endothelial dysfunction and was improved after acute treatment with calcitriol [84]. Vitamin D is a negative regulator of renin–angiotensin system and blood pressure [85]. Recently Jisu et al. reported that deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice. This study suggested that vitamin D plays an important role in inflammation and thus responsible for the development of type 2 diabetes and atherosclerosis [86]. Vitamin D can be used as a biomarker to predict the disease severity of diabetes and cardiovascular complications. However, for better understanding the role of vitamin D in pathophysiology of diabetes and cardiovascular diseases, more intervention studies with long-term follow-up are required.
\nPAPP-A is a zinc-binding matrix metalloproteinase that regulates extracellular matrix remodelling. PAPP-A degrades IGFBP-4 and increases the levels of local IGF-1 in response to injury and involved in the pathogenesis of atherosclerosis. Two inflammatory cytokines, i.e. TNF-α and IL-1, are involved in insulin resistance development and most potent stimulators of PAPP-A [95]. Many researchers reported that elevated levels of PAPP-A were associated 36 with coronary artery diseases, e.g. acute coronary syndrome [[88]-[93]]. On this contrary, Pellitero et al. reported in their study that serum PAPP-A concentrations were significantly lower in diabetic subjects and correlated negatively with HbA1C. PAPP-A concentration was lower in patients with HbA1C > 8.2% (0.35 mUI/l [0.07–0.43]) compared with that in patients with HbA1C < 5.9% (0.72 mUI/l [0.2–0.92],
Cardiovascular complication is the major cause of the death of diabetes worldwide. At present, all standard available markers are useful to detect diabetes and cardiovascular disease separately but not suitable for identifying the cardiovascular complication at early and late stages of the diseases progression. There is an urgent need to identify novel biomarkers by using different omics approaches using large number of patients having desired phenotype. Identified markers can also able to assist in clinical decision making such as interventions and medications. Recently all new markers such as vitamin D, GDF-15, galectin-3, and cyclophilin-A identified have a strong association with type 2 diabetes and cardiovascular disease. However, these yet have not been implemented in the clinical practice. Before accepting any new markers as clinical biomarkers, the following questions need to be answered: whether new identified biomarkers can be used to take clinical decision for any particular diseases, whether it can be useful in therapeutic management and provide any diagnostic and prognostic information, and whether identified biomarkers can be used as a single marker or in a combination with other biomarkers. Identifying new biomarker may also help to understand the affected signalling pathways related to the disease and discover novel therapy against diabetes and cardiovascular complications.
\nFuture biomarker discovery is showing excitement and raising many challenges. One of the major challenges in biomarker discovery is to develop biomarkers for personalised medicine. Biomarkers can play a critical role in classifying patients into subpopulations. In the present days, predicting the therapeutic strategy through personalised medicine is more familiar. However, more research needs to be done to develop specific biomarker to make personalised medicine successful. Personalised medicine is developing tremendously in cancer treatment. However, researchers should focus more on diabetes and cardiovascular disease to initiate personalised medicine in metabolic diseases. Other challenges in biomarker discovery include active collaboration between basic scientists and clinicians. Formation of different societies and organisations need to be established like HUPO (Human Proteome Organization) organisation for the proteomics and to prepare biomarkers databases for free access. Scientific communities need to debate with the issue whether individual diagnostic and prognostic biomarker or combined panel of biomarkers are more useful to predict the cardiovascular outcome among diabetic patients.
\nHarmful algal “blooms”, or HABs, is a hazardous natural phenomenon that often occurs under the influence of anthropogenic factors, for example, during the anthropogenic eutrophication of water bodies. An increase in the frequency and duration of cyanobacterial “blooms” carries many serious threats, including local and global degradation of water resources and the impact of cyanotoxins [1, 2, 3]. This problem is especially relevant and acute for millions of small reservoirs widely used for various types of water consumption: fisheries and aquaculture, water supply for various industries, including agricultural, drinking, and domestic water supply, recreational purposes, including sporting events. HABs occur when algae or cyanobacteria (most often they are) develop beyond measure and produce harmful effects on other hydrobionts, fish, aquatic and terrestrial animals, and birds as well as people [4, 5]. HABs disrupt the esthetics of water bodies and render the water unsuitable for various kinds of water uses. Economic damage due to HABs can be millions of dollars [6, 7].
Widespread HABs is a phenomenon to which special attention should be drawn since such “blooms” pose a number of serious threats, including local and global degradation of water resources and exposure to cyanotoxins [8, 9, 10, 11, 12, 13, 14].
Cyanobacterial “blooms” of water bodies are officially recognized as a global problem of modern ecology. Seasonal intense cyanobacterial “blooms” of reservoirs bring additional undesirable properties to natural and drinking water, such as a specific smell, taste, and the presence of toxins (microcystins). In some regions, the importance of this problem has been increasing recently [15]. The Working Group on the Evaluation of Carcinogenic Risks to Humans listed cyanotoxins as a carcinogenic substance harmful to humans [16].
The introduction of biotechnological methods into the practice of water body management that have maximum efficiency is one of the tasks of modern science. These include, first of all, the so-called convergent nature-like technologies, i.e. technologies that are based on any natural mechanisms causing this or that effect. These are precisely technologies that may be intended to ensure the sustainable development of modern countries [17, 18, 19].
Such technologies, aimed at managing the development of plankton communities in general and phytoplankton communities, in particular, may be based on such a phenomenon as allelopathy. This natural phenomenon can be very useful for effectively preventing and stopping the development of cyanobacterial “blooms” in water bodies [20, 21, 22]. Many existing methods of combating cyanobacteria [23] do not effectively solve the problem of “blooms” of water bodies without damage to other components of the ecosystem [3]. Usually, they are associated with serious adventitious effects on aquatic organisms and ecological systems [24].
At the same time, the application of the method of metabolic allelopathic control of HABs in water bodies during eutrophication is an effective and innovative solution to this problem. This approach preserves and restores water quality in water bodies, makes them suitable for multifunctional use, and natural allelochemicals (metabolites of macrophytes and their synthetic analogs) can be an effective alternative to existing algicides [20, 22, 25].
In reservoirs where macrophytes are developed (as a rule, at least 30% of the projective cover of the water area), water “bloom” is almost never observed. These circumstances are the causal basis for the development of nature-like technologies for the prevention and suppression of HABs with the help of new generation algicides based on allelochemical substances characteristic of aquatic macrophytes.
It has become apparent that metabolites-allelochemicals may be functioning in the processes of chemical suppressing of planktonic cyanobacteria in the aquatic ecosystems. However, data from field experiments are few concerning the effect of aquatic macrophyte allelochemicals on cyanobacteria, which is necessary for the development of nature-like technologies for preventing and suppressing cyanobacterial “blooms”, and therefore they are the objects of “hottest” areas of research. Utilization of allelochemicals from aquatic macrophytes or using their synthetic analogs to inhibit cyanobacterial overgrowth is an environment-friendly technology for suppressing HABs.
Some reviews are focusing on the practice of the application of allelochemicals in agriculture [26, 27], but the field of using nature-like allelopathic technology to manage aquatic ecosystems is still poorly developed.
In the present study, we aimed to provide the information on the suppressing of cyanobacteria by macrophytes allelochemicals and the possibility to develop an algaecide of the new generation as a convergent nature-like technology for preventing and stopping the development of HABs in water bodies based on such a phenomenon as allelopathy.
Allelopathy as a natural phenomenon had been repeatedly recorded for a very long time in the 3rd century BC in ancient Chinese literature [28]. The term “allelopathy” was coined comparatively recently, in 1937 by Austrian plant physiologist Hans Molisch [29], who can be named as the father of allelopathy [30]. In general, we can consider allelopathy as an area of science, which investigates inhibitory or stimulatory biochemical interactions between the two plant/plant or plant/microorganism species.
The recent history of the study of low molecular weight organic compounds, which are small molecules (less than 900 amu) and constitute the low molecular weight metabolic profiles of organisms, should apparently begin with the discovery of the inhibitory effect of volatile plant excreta on microorganisms by Tokin Boris Petrovitch during the experimental work of 1928–1930 [31]. The research resulted in a number of publications, in one of which (“Bactericides of plant origin (phytoncides)”) [32], the term “phytoncides” appeared. In the future, the doctrine of phytoncides was developed, which was reflected in the publication of several monographs. The history of research on phytoncides of aquatic and coastal plants began in the 40s of the XX century with the works of Gurevich Faiva Abramovich (1918–1992) [33], a student of B.P. Tokin. These studies ended in 1973 with the defense of a doctoral dissertation “Phytoncides of aquatic and coastal plants, their role in biocenoses” [34]. In particular, it was F.A. Gurevich who showed that the phytoncidal activity of aquatic plants is closely related to the macrophyte species and peculiarities of its development. He also showed that phytoncides are a very significant factor in the distribution of hydrobionts in a water body, including invertebrates.
At present, we can say that the macrophyte and algal allelopathy is paid much less attention than allelopathy in terrestrial ecosystems. Macrophytes and cyanobacteria are known to have an antagonistic relationship in different natural and experimental aquatic ecosystems [25, 35, 36].
It is a recognized fact that phytoplankton is poorly developed in macrophytic lakes. Even if we take into account the opinion that this is due to such factors as winning competition for nutrients and shading, then in the overwhelming number of cases, the main factor providing suppression of phytoplankton development is undoubtedly allelopathic suppression [37]. Apparently, the competition for nutrients cannot be recognized as a decisive factor in the outcome of the struggle between macrophytes and cyanobacteria, including considering that most aquatic macrophytes are rooted, and they usually obtain the main part of the necessary nutrients from the bottom sediments, which is characterized by high nutrient concentrations [38].
It is well known the phenomenon when shallow-water lakes can change their trophic status and the type of lake ecosystem, being either a pure water body with well-developed aquatic vegetation or a water body with low transparency, high turbidity, and intensive phytoplankton (mainly cyanobacteria) development. In other words, they can shift from one state to another [36, 39, 40, 41, 42, 43]. As this takes place, the mutual inhibitory allelopathic activities of macrophytes and phytoplankton may lead to the dominance of either macrophytes or phytoplankton [44].
We observed a similar effect in a floodplain lake with a changing trophic state in the Volga-Akhtuba interfluve, when cyanobacteria and macrophytes dominated in the same water body in different years [36]. Some evidence exists [45, 46, 47, 48] that allelopathy is a factor affecting the development of phytoplankton (including cyanobacteria) in shallow lakes at the projective cover of macrophytes from 20 to 100%.
The importance of allelopathy as a powerful regulatory mechanism initiates a lot of studies devoted to the study of the inhibitory (sometimes stimulating) allelopathic effect of macrophytes on cyanobacteria and algae in aquatic ecosystems [49, 50, 51, 52, 53, 54, 55, 56, 57, 58]. More than 60 species (67) of macrophytes are known to exhibit allelopathic activity against cyanobacteria. They are presented in Table 1.
Species of macrophytes | Ecological form | Study scale | Cyanobacteria inhibited Study Scale | Source |
---|---|---|---|---|
EM | L | Сyanobacteriaas a whole | [59, 60] | |
EM | L | [51, 57, 61, 62, 63] | ||
FM | L | [64] | ||
SM | L | [65, 66] | ||
EM | L | [67] | ||
SM | L, F | [58, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78]; Our data | ||
SM | L | [37, 79, 80, 81] | ||
SM | L | [82] | ||
SM | L | [81, 83] | ||
SM | L | [79] | ||
SM | L* | [71] | ||
SM | L | [68, 72, 79, 84] | ||
SM | L, F | Сyanobacteria as a whole | [83, 85] | |
SM | L | [79] | ||
SM | L, F | [79, 83, 86, 87] | ||
EM | L | [67] | ||
FM | L | [88, 89, 90, 91] | ||
SM | L | Сyanobacteria as a whole | [66] | |
SM | L | [92, 93] | ||
SM | L, F | [35, 68, 78, 94, 95] | ||
SM | L | [56, 58, 96] | ||
SM | L | [66] | ||
SM | [66] | |||
SM | L | [97] | ||
SM | L | [98] | ||
SM | L | [99] | ||
SM | L, F | [54, 65, 71, 78, 83, 100, 101, 102, 103, 104] | ||
SM | L | Сyanobacteria as a whole | [105, 106] | |
SM | L | [74, 94] | ||
EM | L | [107] | ||
FM | L, F | [108, 109] | ||
SM | L, F | [68, 79, 83] | ||
FM | L, F | Сyanobacteria as a whole | [110]; Our data | |
FM | F | Сyanobacteria as a whole | Our data | |
EM | Сyanobacteria as a whole | [111] | ||
EM | L | [108, 112] | ||
FM | L | [113, 114, 115] | ||
SM | L, F | [82, 116, 117] | ||
SM | L | [58] | ||
SM | L | [66] | ||
SM | L, F | [58, 71], Our data | ||
SM | L | [58, 118, 119] | ||
SM | L, F | [118, 119, 120] | ||
SM | L, F | [78], Our data | ||
SM | L | [76, 118, 121] | ||
SM/FM | L | [107] | ||
SM | L | [122, 123] | ||
FM | L, F | [49, 68, 71] | ||
EM | L | [57, 124, 125, 126] | ||
SM | L | [58, 66, 75, 127] |
The number and relative content (% of total essential oil) of the fatty acids in some species of freshwater macrophytes and macroalgae from different water bodies.
According to the principle of allelopathic action, it is possible to prevent or mitigate the massive development of Сyanobacteria (blue-green algae), which leads to the HABs in water bodies. The implementation of this research direction promises huge benefits since it will solve the problem of the “blooms” of water bodies without negative consequences for other components of the ecosystem [20, 22, 25].
As follows from Table 1, data from laboratory studies, in general, prevail in the observation and proof of the effect of macrophyte allelopathy on cyanobacteria. These studies are based on laboratory-scale experiments using the co-cultures systems, adding plant extracts, or leachate collection. This state of affairs is associated with a more complex organization and interpretation of field studies. In this regard, data from field experiments and observations, for example with mesocosms, are of particular value. Numerous studies (including those included in Table 1) strongly suggest that allelopathy might thus be relevant in natural waters and suppress cyanobacteria and algae.
There are observations on the differentiation of the inhibitory effect of macrophytes on various species of cyanobacteria and algae. For example, it was concluded that the extracts, exudates, and live material of macroalgae
The available data allow us to speak about the selective inhibition of various species of cyanobacteria by allelochemicals of various species of macrophytes. As a result, the allelopathic effect of macrophyte association on cyanobacteria (and all phytoplankton) seems to be stronger than the effect of one macrophyte species. This is evidenced by the fact that, as has been shown, the allelopathic effect of excretions of the association of macroalgae (
Lombardo et al. [129] suggested that lake trophic state and extent of submerged vegetation coverage maybe the most important factors during formation in situ macrophyte–phytoplankton patterns at a large scale of natural water bodies. In this case, with a larger projective cover, a greater allelopathic effect will be achieved [45, 46, 47, 48].
Not all macrophytes have the same allelopathic effect on cyanobacteria. Macrophytes that have the greatest suppressive effect on cyanobacteria (taking into account, among other things, information from Table 1) are such species and groups as
In the study [131], it was concluded that of all the 15 tested aquatic macrophytes,
Similar results were obtained with the macrophytes
For the sake of completeness, it should be noted that some terrestrial plant materials (for example, barley straw) exhibit a strong allelopathic effect on cyanobacteria under certain conditions [134, 135, 136], which is no coincidence, since terrestrial plants also contain numerous allelochemicals [28]. It was shown in [137] that salcolin (two enantiomers that differ in their anti-cyanobacterial abilities) is the key allelochemical in barley straw’s which exhibits an inhibitory effect on cyanobacteria and could be used as an agent in the control of cyanobacterial HABs. A review of typical terrestrial allelopathic plants with algistatic or algicidal effects is presented in [24].
Low-molecular-weight anti-cyanobacterial allelochemicals produced by aquatic macrophytes are very diverse. They belong to different classes of chemical compounds and are functionally diverse. Allelochemicals from the following groups of chemical compounds are the most important [22, 30, 55]: aldehydes, ketones, ethers, terpenes and terpenoids, phytoecdysteroids, fatty acids, sulfur-containing compounds, nitrogen-containing compounds, alcohols, lactones, polyacetylenes, quinines, phenolics, cinnamic acid and its derivatives, coumarins, flavonoids, tannins. These groups include hundreds of allelochemicals inhibiting cyanobacteria and algae [24], which should be discussed in detail in a special review.
These allelochemicals can be extracted from the plant biomass, but also their synthetic counterparts can be produced and used. This will reduce the consumption of natural plant resources. The effectiveness of synthetic allelochemicals can be similar to their natural counterparts. Thus, synthetic allelochemicals are a hopeful alternative to the use of natural metabolites-allelochemicals against HAB-forming cyanobacteria [20, 21].
Realizing that it is impossible to consider all groups of allelochemicals, here we will focus on considering only fatty acids and phenolic compounds as the most promising (in our opinion) for biotechnological use in the fight against HABs.
Studies of potential biological activities of major low molecular weight organic compounds of aquatic macrophytes using the QSAR method [138, 139] have shown that fatty acids and gallic acid are characterized by various types of bioactivity with the highest probability of manifestation (Pa > 0.9) that can induce cyanobacteria growth suppression. Further studies based on the results obtained suggest clarifying experimental studies of the reaction of various species of cyanobacteria to the effects of selected allelochemicals.
As it was received in laboratory experiments conducted with fatty acids for their effect on the cyanobacteria
The highest SI values for Synechocystis aquatilis were obtained when the culture of cyanobacteria was exposed to gallic acid (SI = 30) and a mixture of heptanoic, octanoic, tetradecanoic, and gallic acids (SI = 35.3).
In works [141, 142] problems have been raised concerning effective algal inhibitors and control HABs. To address these issues, the authors suggested using unsaturated fatty acid (linoleic acid) in conjunction with alginate – chitosan microcapsule technology. They demonstrated that the linoleic acid microsphere had good encapsulation efficiency and release property. Besides, linoleic acid sustained-released microspheres could inhibit
Studies on the use of microgranules saturated with an allelochemical or a combination of allelochemicals (for example, a combination of fatty acids and phenolic compounds) to suppress cyanobacteria look very promising. The inhibitory agent, gradually releasing from the microgranules, prolongs its allelopathic effect on cyanobacteria. A sustained-release time of allelochemicals can range from 40 to 120 days [142, 143, 144]. A review of the studies carried out in this direction is presented in [128]. Results obtained in different investigations open up new promising areas for scientific research and practical use of allelochemicals of aquatic macrophytes.
According to results received in [112], nonanoic acid can inhibit the growth of cyanobacteria
In earlier works [113, 125], it was also found, that three fatty acids (α − linolenic, linoleic, and an unidentified C8∶2) inhibited cyanobacteria (particularly T 625
The essential oil of some allelopathic plants (
Recently, Wang et al. [95] reported the inhibitory effects of some fatty acids on
We showed [140] that such plants as
Our studies of the metabolome of
Dependence of the concentration of cyanobacteria (BGA, cells/ml) on the concentration of fatty acids (Cca, μg/g.dr.w.) in
The study by Gao et al. [145] demonstrates that nonanoic acid may be involved in synergistic interactions with other allelochemicals, demonstrating a stronger allelopathic effect against Microcystis aeruginosa.
Similar results were obtained for octadecanoic acid [146], which may participate in synergistic, antagonistic, and additive allelopathic interactions. These findings led to the conclusion that joint effects of different allelochemicals depend on various factors such as the chemicals used, their respective proportions, the total concentration of the mixture, and the receptor species [146].
In addition to fatty acids, among allelochemicals, special attention should be paid to phenolic compounds.
As early as in 1981 [100], the results were published, which demonstrated that phenolic compounds extracted from
Additionally, a study [78] has revealed that the major allelochemicals identified in tested macrophyte ethyl acetate extract of
In a study [54] during the investigation of contributions of five allelochemicals, (+) catechin, eugeniin, and ellagic, gallic, and pyrogallic acid, in the allelopathic effects of
It is beyond question that there is a huge amount of scientific material regarding the allelopathic properties of fatty acids and gallic acid ([52, 54, 56, 67, 88, 103, 112, 113, 118, 119, 124, 125, 126, 146, 148, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166], etc.). This circumstance gives every reason to use them to create a new generation of algicides based on allelochemical substances of aquatic macrophytes. The use of this information, as well as the results of our researches [36, 138, 140], formed a prerequisite for the development of a new generation algicide based on allelochemicals of aquatic macrophytes against cyanobacteria. It is precisely fatty acids (heptanoic, octanoic, tetradecanoic acids) and gallic acid that were included in its composition [167].
Evidence of suppression of the development of phytoplankton, including planktonic cyanobacteria, in real natural conditions by traditional observations, even in the most obvious cases [36], is nevertheless indirect and often contradictory [48, 168]. Taking this into account, the way of assessing the effect of allelochemicals on cyanobacteria in experiments with mesocosms in natural conditions is more promising and makes it possible to obtain results corresponding to natural aquatic ecosystems.
A good example is a field study by Hilt et al. [169] in which the authors found an allelopathic effect of the macrophyte
In another mesocosm study [171], similar results were obtained, demonstrating that another species of the genus Myriophyllum (
After the development of an algicide containing fatty acids (heptanoic, octanoic, tetradecanoic acids) and gallic acid, the rationale for the use of which is presented in detail in [140], we conducted the first experiments with this algicide with natural phytoplankton communities under conditions mesocosms.
In the field experiments, mesocosms with a volume of 700 liters were used. The experiments were carried out on two ponds on the territory of St. Petersburg (Russia): at Pulkovo Pond (pond 1; coordinates 59.835899, 30.328642) and Aviator’s Pond (Pond 2; coordinates 59.868343, 30.300443). The depth of the ponds at the location of the experiments was about 3 m. The mesocosms were filled with water from the pond, then algicide was added to them in an amount so that its concentration in the water of the mesocosms was 1 mg/l.
In Pulkovo Pond, the experiment was carried out from June 25 to July 5, 2019. In the Aviatorov Pond, the experiment was carried out from July 2 to July 16, 2019. The temperature and light conditions in the mesocosms corresponded to those in the water of the pond outside the mesocosms. The change in water temperature in the surface layer of the studied ponds is shown in Figure 2.
Change in water temperature (o C) in the surface layer of the investigated ponds.
The results of the algicide impact on the phytoplankton of pond 1 are shown in Figures 3–6.
Changes in the abundance and biomass of total phytoplankton in pond 1 and the mesocosm under the influence of algicide with a concentration of 1 mg/l.
Change in the optical density of the water mass in pond 1 and the mesocosm when exposed to algicide with a concentration of 1 mg/l.
The contrast in the state of water mass in pond 1 and mesocosm 4 (a) and 11 (B) days after exposure to algicide.
Changes in the abundance and biomass of cyanobacteria in pond 1 and the mesocosm upon exposure to algicide at a concentration of 1 mg/l.
As can be seen from Figure 3, in the water of pond 1, both the abundance and the biomass of all phytoplankton increased during the experiment. At the same time, this was not observed in the mesocosm. In the first three days, a decrease in phytoplankton biomass without a change in its abundance occurred. Subsequently, the abundance and biomass of phytoplankton in the mesocosm remained approximately at the same level as they grew in the pond. By the end of the experiment (on the 11th day), the phytoplankton biomass in the pond exceeded that in the mesocosm by about 5 times, and the abundance - by almost 12 times. The greatest differences were observed on the 8th day of the experiment; the difference in biomass and abundance was 7 and 20 times, respectively. Thus, the action of an algicide based on fatty acids and gallic acid inhibited the growth of phytoplankton.
The data of phytoplankton analysis are confirmed by the data on the measurement of optical density in the pond and the mesocosm (Figure 4). By the end of the experiment, an increase in optical density in the pond and a significant decrease in optical density in the mesocosm were observed (Figure 4). By the end of the experiment, the difference was about 2.3 times. This was also noticeable visually: the water in the mesocosm was more transparent than the water in the pond surrounding the mesocosm (Figure 5).
It is interesting to trace how the quantitative indicators of cyanobacteria in the pond and the mesocosm changed.
Thus, the action of an algicide based on fatty acids and gallic acid prevented the growth of the number of cyanobacteria and changed their species structure.
In pond 2, the beginning of the experiment coincided with an intense cyanobacterial “bloom” (Figure 7), while their biomass was more than 55 mg/l. At the same time, in the surface layer of the pond, the maximum water temperature (20.5°C) for the entire duration of the experiment was noted (Figure 2). The cyanobacteria
Cyanobacterial HAB in pond 2 and water-filled mesocosm on July 2, 2019.
By the fourth day of the experiment, the water temperature in the pond dropped to about 18°C. This led to a decrease in the number and biomass of cyanobacteria, apparently, mainly due to their sinking into the lower layers of the reservoir. However, an even greater decrease in the development of cyanobacteria was observed in the mesocosm, in which cyanobacteria could not sink so deeply (Figure 8). This is also confirmed by data on the optical density of water in the pond and in the mesocosm, where a more significant decrease was noted (Figure 9). Subsequently, the optical density slightly decreased to approximately the same level in the pond and mesocosm and almost did not change in the pond and mesocosm. At the same time, the control of the development of cyanobacteria from pond 2 in the laboratory, where there was no decrease in temperature, showed their significant growth in the control. With that, under the influence of allelochemicals, significant suppression of plankton growth was observed, recorded by optical density (Figure 10).
Changes in the abundance and biomass of total phytoplankton in pond 2 and the mesocosm under the influence of algicide with a concentration of 1 mg/l.
Change in the optical density of the water mass in pond 2 and the mesocosm when exposed to algicide with a concentration of 1 mg/l.
Change in the optical density of the water mass in pond 2 and the mesocosm when exposed to algicide with a concentration of 1 mg/l during exposure in the laboratory.
By the 8th day of the experiment, a further decrease in the optical density of plankton under the influence of algicide was noted in the laboratory. At the same time, a decrease in optical density and the control was observed, obviously, due to the inability of natural plankton to laboratory conditions (the experiment was carried out in 0.5-liter jars).
By July 8, the species of cyanobacteria
In the last phase of the experiment (from July 12), representatives of Cryptophyta -
Changes in the abundance and biomass of cyanobacteria (a) and Cryptophyta (B) in pond 2 and the mesocosm under the influence of algicide at a concentration of 1 mg/l.
It is noteworthy that by the end of the experiment in the mesocosm, the total phytoplankton biomass returned to almost the same high values as at the beginning of the experiment. However, if at the beginning of the experiment cyanobacteria prevailed (about 99% of the total biomass of phytoplankton), then by the end of the experiment cryptophyte algae accounted for more than 98% of the biomass of phytoplankton.
Thus, the main results of the experiments carried out on the effect of an algicide of four allelochemical components (heptanoic, octanoic, tetradecanoic, and gallic acids) on the phytoplankton of natural water bodies can be considered the following results, indicating that allelochemical substances of aquatic macrophytes: 1) are able to effectively reduce phytoplankton development and suppress even intense HABs; 2) may lead to the replacement of dangerous cyanobacteria in phytoplankton with safe algae, whose production can be used in the food chains of aquatic organisms.
In this way, available data show that the use of allelochemicals from aquatic macrophytes to inhibit cyanobacterial overgrowth is an environment-friendly and perspective technology for suppressing HABs. Allelochemicals can be considered as natural algaecides and become the basis of a nature-like convergent technology to mitigate the development of plankton cyanobacteria and prevent HABs in water bodies.
One can quite agree with the conclusion of work [24] that allelopathy is a promising strategy to control HABs as the effectiveness of allelochemicals on inhibiting microalgae cells has been discovered, investigated, and confirmed in many works and for many years [175]. However, there are several problems that must be investigated in order to understand what determines the strength of the manifestation of the allelopathic effect. One of these problems is undoubtedly the action of various environmental factors.
Another problem is the resistance of allelochemicals in the aquatic environment and their chemical or biochemical (under the influence of bacteria) changes [26, 74, 168, 176]. In this regard, very promising are works in which systems are being developed that allow dosing and prolonging the release of allelochemicals into the aquatic environment [141, 142, 143].
The development and research of allelopathy and its application for suppressing the HABs are striving toward a future for sustainable, rational, and effective using the water resources worldwide. The algicides of the new generation developed based on the phenomenon of allelopathy can definitely reduce the amount of synthetic algicides and herbicides used.
While allelochemicals have shown growth inhibition of planktonic cyanobacteria, there is still insufficient knowledge of the impact on various species of cyanobacteria (especially their action in real aquatic ecosystems), the influence of various factors on the action of allelochemicals, and the molecular mechanisms of their action. These gaps may limit their use as conventional biotechnology for the mitigation and prevention of HABs in aquatic ecosystems.
All the laboratory studies can propose only the potential for allelopathy of macrophytes metabolites toward cyanobacteria, its real use as biotechnology for the management of planktonic communities and HABs will be possible only after convincing field studies using mesocosms and entire ecosystems.
In addition, if we are to understand more about the mechanisms of allelochemicals actions that cyanobacterial cells respond to, more cognizance needs to be taken of the molecular peculiarities of interactions between allelochemicals and cyanobacterial cells.
The work was performed within the framework of the state task of the Russian Academy of Sciences on topic 0154-2019-0002. The authors thank Dr. Alexandr Rusanov and Mr. Denis Bardinskij as well as Ms. Elena Fisak for their kind help in the field experiments.
The authors declare that there is no conflict of interest.
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Tzallas, Markos G. Tsipouras, Dimitrios G. Tsalikakis, Evaggelos C. Karvounis, Loukas Astrakas, Spiros Konitsiotis and Margaret Tzaphlidou",authors:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",slug:"alexandros-tzallas",fullName:"Alexandros Tzallas"},{id:"94709",title:"Dr.",name:"Markos",middleName:null,surname:"Tsipouras",slug:"markos-tsipouras",fullName:"Markos Tsipouras"},{id:"94710",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Tsalikakis",slug:"dimitrios-tsalikakis",fullName:"Dimitrios Tsalikakis"},{id:"94712",title:"Dr.",name:"Loukas",middleName:null,surname:"Astrakas",slug:"loukas-astrakas",fullName:"Loukas Astrakas"},{id:"94714",title:"Dr.",name:"Spiros",middleName:null,surname:"Konitsiotis",slug:"spiros-konitsiotis",fullName:"Spiros Konitsiotis"},{id:"94873",title:"Prof.",name:"Margarita",middleName:null,surname:"Tzaphlidou",slug:"margarita-tzaphlidou",fullName:"Margarita Tzaphlidou"},{id:"128137",title:"Dr.",name:"Evaggelos",middleName:null,surname:"Karvounis",slug:"evaggelos-karvounis",fullName:"Evaggelos Karvounis"}]},{id:"26608",doi:"10.5772/28363",title:"Sex Differences in PTSD",slug:"sex-differences-in-ptsd",totalDownloads:5154,totalCrossrefCites:14,totalDimensionsCites:41,abstract:null,book:{id:"773",slug:"post-traumatic-stress-disorders-in-a-global-context",title:"Post Traumatic Stress Disorders in a Global Context",fullTitle:"Post Traumatic Stress Disorders in a Global Context"},signatures:"Dorte Christiansen and Ask Elklit",authors:[{id:"73642",title:"Prof.",name:"Ask",middleName:null,surname:"Elklit",slug:"ask-elklit",fullName:"Ask Elklit"},{id:"113525",title:"MSc.",name:"Dorte",middleName:null,surname:"M. Christiansen",slug:"dorte-m.-christiansen",fullName:"Dorte M. Christiansen"}]},{id:"51342",doi:"10.5772/63824",title:"Autoimmune Processes in Multiple Sclerosis: Production of Harmful Catalytic Antibodies Associated with Significant Changes in the Hematopoietic Stem Cell Differentiation and Proliferation",slug:"autoimmune-processes-in-multiple-sclerosis-production-of-harmful-catalytic-antibodies-associated-wit",totalDownloads:1344,totalCrossrefCites:6,totalDimensionsCites:32,abstract:"Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. MS pathogenesis is not clear. Destruction of myelin by inflammation caused by autoimmune reactions has been proposed. Interestingly, healthy humans usually do not develop abzymes (Abzs). It was shown that DNase and MBP-hydrolyzing Abzs are easily detectable at the beginning of autoimmune diseases (ADs) including MS, when concentrations of antibodies to autoantigens are not yet significantly increased and correspond to levels in healthy donors. In addition, the relative enzymatic activity of antibodies from cerebrospinal fluid (CSF) is ~50-fold higher than that from the sera of the same MS patients. Experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a model mimicking relevant aspects of human MS was used. During development of spontaneous and MOG35-55-induced EAE in C57BL/6 mice, a specific reorganization of the immune system of mice was observed. It leads to a condition which was associated with the generation of catalytically active IgGs-hydrolyzing DNA, myelin basic protein (MBP), and MOG. Production of Abzs was associated with increased proteinuria, leading changes in differentiation of mice bone marrow hematopoietic stem cells (HSCs) and an increase in proliferation of lymphocytes in bone marrow, spleen, and thymus as well as a significant suppression of cell apoptosis in these organs. Treatment of control non-autoimmune CBA mice with MOG led to the different differentiation and proliferation of HSCs comparing with EAE C57BL/6 mice. The treatment of EAE mice with cuprizone inducing demyelination lead to a significant decrease in the size of the brain corpus callosum, but do not significantly change the differentiation profile of HSCs differentiation when compared with untreated mice. It indicates that cuprizone treatment is associated with demyelination, but not autoimmune reactivity. The possible differences in immune system reorganizations during preclinical phases of the disease, acute and late EAE, leading to production of different autoantibodies and Abzs as well other changes are discussed.",book:{id:"5156",slug:"trending-topics-in-multiple-sclerosis",title:"Trending Topics in Multiple Sclerosis",fullTitle:"Trending Topics in Multiple Sclerosis"},signatures:"Georgy A. Nevinsky",authors:[{id:"47119",title:"Dr.",name:"Georgy",middleName:null,surname:"Nevinsky",slug:"georgy-nevinsky",fullName:"Georgy Nevinsky"}]},{id:"20033",doi:"10.5772/18507",title:"Parenting Stress in Mothers and Fathers of Children with Autism Spectrum Disorders",slug:"parenting-stress-in-mothers-and-fathers-of-children-with-autism-spectrum-disorders",totalDownloads:18739,totalCrossrefCites:16,totalDimensionsCites:30,abstract:null,book:{id:"463",slug:"a-comprehensive-book-on-autism-spectrum-disorders",title:"A Comprehensive Book on Autism Spectrum Disorders",fullTitle:"A Comprehensive Book on Autism Spectrum Disorders"},signatures:"Ewa Pisula",authors:[{id:"31714",title:"Prof.",name:"Ewa",middleName:null,surname:"Pisula",slug:"ewa-pisula",fullName:"Ewa Pisula"}]}],mostDownloadedChaptersLast30Days:[{id:"62216",title:"Subtypes of Psychotic-Like Experiences and Their Significance for Mental Health",slug:"subtypes-of-psychotic-like-experiences-and-their-significance-for-mental-health",totalDownloads:3158,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"More recently, the interest in studying subclinical psychosis has increased, as it might provide critical information regarding mechanisms that are implicated in the exacerbation of subclinical symptoms and the maintenance of mental health. However, psychosis research has tended to focus on clinical outcomes and not to differentiate between subtypes of psychotic-like experiences (PLE) that might differ regarding their psychopathological significance. Importantly, this might have obscured a more accurate picture of the complex structure of psychosis and the significance of particular risk and protective factors. Notably, while studies point toward a continuity of psychotic experiences and accompanying factors across the general population, there is evidence indicating that some PLE in healthy individuals might also be associated with a weaker expression of other subclinical symptoms, increased well-being and even resilience to some degree. Importantly, such findings might have implications on strategies in psychosis prevention and therapy, early detection, as well as the construction of continuum models of psychosis. The present chapter aims at drawing together findings that necessitate a more differentiated view and assessment of PLE. It intends to provoke new questions that might offer starting points for future investigations, such as longitudinal studies investigating the interplay of subclinical symptoms.",book:{id:"7117",slug:"psychosis-biopsychosocial-and-relational-perspectives",title:"Psychosis",fullTitle:"Psychosis - Biopsychosocial and Relational Perspectives"},signatures:"Lui Unterrassner",authors:[{id:"245870",title:"Ph.D. Student",name:"Lui",middleName:null,surname:"Unterrassner",slug:"lui-unterrassner",fullName:"Lui Unterrassner"}]},{id:"18334",title:"Challenges and Opportunities in Diagnosis and Management of Generalized Anxiety Disorder in Primary Care",slug:"challenges-and-opportunities-in-diagnosis-and-management-of-generalized-anxiety-disorder-in-primary-",totalDownloads:3836,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"236",slug:"anxiety-and-related-disorders",title:"Anxiety and Related Disorders",fullTitle:"Anxiety and Related Disorders"},signatures:"Mehtap Kartal",authors:[{id:"33369",title:"Dr.",name:"Mehtap",middleName:null,surname:"Kartal",slug:"mehtap-kartal",fullName:"Mehtap Kartal"}]},{id:"67627",title:"Borderline Personality Disorder and Childhood Trauma: The Posited Mechanisms of Symptoms Expression",slug:"borderline-personality-disorder-and-childhood-trauma-the-posited-mechanisms-of-symptoms-expression",totalDownloads:1213,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Traumatic events are reported in a large percentage of the population, however, only in some individuals it will lead to a diagnosable trauma-related disorder. Borderline personality disorder (BPD) is deemed to be a form of acute reaction to childhood trauma. Therein experiences of childhood abuse and neglect take on an important etiological role, generating severely disorganized attachment relationships, which in turn affect the development of emotional regulation systems, and significantly inhibit the development of mentalization and metacognitive skills. Furthermore, the last decade has seen important contribution of neuroscientific research in shedding light on the neurobiological correlates of traumatic experiences. A wealth of scientific literature links the onset of BPD to the combination between genetic and environmental factors (G×E), in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood. Although no research can predict with certainty which trauma will translate into symptoms, there are indications as to who is more at risk of developing a trauma-related disorder. Herein we describe the psychological and epigenetic mechanisms affected by childhood trauma and altered in BPD patients.",book:{id:"7834",slug:"psychological-trauma",title:"Psychological Trauma",fullTitle:"Psychological Trauma"},signatures:"Maria Uscinska, Nicolo’ Gagliano, Andrea Polla Mattiot and Silvio Bellino",authors:[{id:"285336",title:"Dr.",name:"Maria",middleName:null,surname:"Uscinska",slug:"maria-uscinska",fullName:"Maria Uscinska"},{id:"288179",title:"Dr.",name:"Andrea",middleName:null,surname:"Polla Mattiot",slug:"andrea-polla-mattiot",fullName:"Andrea Polla Mattiot"},{id:"302735",title:"Dr.",name:"Nicolo'",middleName:null,surname:"Gagliano",slug:"nicolo'-gagliano",fullName:"Nicolo' Gagliano"}]},{id:"69569",title:"Introductory Chapter: Psychological Trauma",slug:"introductory-chapter-psychological-trauma",totalDownloads:906,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"7834",slug:"psychological-trauma",title:"Psychological Trauma",fullTitle:"Psychological Trauma"},signatures:"Ana Starcevic",authors:[{id:"182584",title:"Dr.",name:"Ana",middleName:null,surname:"Starcevic",slug:"ana-starcevic",fullName:"Ana Starcevic"}]},{id:"71936",title:"Feeding and Eating Disorders",slug:"feeding-and-eating-disorders",totalDownloads:2127,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Eating disorders, which are well known as a substantial mental health problem in society, have been reclassified as feeding and eating disorders in DSM-5 and also in the 11th revision of ICD. The new classification includes binge eating disorder and avoidant-restrictive food intake disorder (ARFID), in addition to anorexia and bulimia nervosa. They are considered serious disorders, with high morbidity and mortality risks, that affect the young community in particular. Current research shows increases in all genders and age groups. Various genetic and biologic factors, an insecure personality type, impulsive traits, dysfunctional emotion regulation, and society’s ideal of slimness have been found to play a role in the development of these disorders. A dual approach with focus on the symptom and the underlying problems is needed for all types of eating disorders throughout the psychotherapeutic interventions. Assessing comorbid psychiatric and medical symptoms is extremely important. Further research and new directions of treatment are needed with regard to the expanded classifications.",book:{id:"9489",slug:"neurological-and-mental-disorders",title:"Neurological and Mental Disorders",fullTitle:"Neurological and Mental Disorders"},signatures:"Bianca Suciu and Cătălina-Angela Crișan",authors:null}],onlineFirstChaptersFilter:{topicId:"187",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81566",title:"New and Emerging Technologies for Integrative Ambulatory Autonomic Assessment and Intervention as a Catalyst in the Synergy of Remote Geocoded Biosensing, Algorithmic Networked Cloud Computing, Deep Learning, and Regenerative/Biomic Medicine: Further Real",slug:"new-and-emerging-technologies-for-integrative-ambulatory-autonomic-assessment-and-intervention-as-a-",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.104092",abstract:"While the important role of the autonomic nervous system (ANS) has been historically underappreciated, recently there has been a rapid proliferation of empirical, methodological and theoretical progress in our more detailed understanding of the ANS. Previous more simplistic models of the role of the ANS using the construct of homeostasis have been enhanced by the use of the construct of allostasis and a wide variety of technological innovations including wearable and implantable biosensors have led to improved understanding of both basic and applied knowledge. This chapter will explore in particular heart rate variability (HRV) as a rich variable which has developed an extensive literature, beginning with predicting all-cause mortality, but now encompassing a wide variety of disease and illness states; cognitive, affective and behavioral processes and performance optimization. A critical analysis of HRV from the perspective of complex adaptive systems and non-linear processes will be included and innovative future uses of HRV will be described.",book:{id:"10835",title:"Autonomic Nervous System - Special Interest Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10835.jpg"},signatures:"Robert L. Drury"},{id:"80949",title:"The Cerebral Venous System: New Pathophysiological Theories and Diseases Related to Veins Occlusion",slug:"the-cerebral-venous-system-new-pathophysiological-theories-and-diseases-related-to-veins-occlusion",totalDownloads:44,totalDimensionsCites:0,doi:"10.5772/intechopen.102351",abstract:"Cerebral physiology and pathology are still frequently missing a comprehensive explanation and a complete description, but new data and hypothesis are emerging on a daily basis. Particularly, comprehension of the cerebral venous system’s functions and functioning has undergone through the last decades a deep and extended change. Depiction of the perivascular spaces and the mechanisms of glymphatic system has given light about venous system pivotal role in the genesis of different pathologies such as multiple sclerosis, hydrocephalus, cerebral hemorrhages, and strokes. After a key point discussion about embryology, physiology, and anatomy of the cerebral venous system, an overview is provided on the main pathologies, both well-known and newly described ones, in which cerebral veins act a major pathogenic role.",book:{id:"11371",title:"Cerebral Circulation - Updates on Models, Diagnostics and Treatments of Related Diseases",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg"},signatures:"Giorgio Mantovani and Alba Scerrati"},{id:"80939",title:"Diagnosis and Treatment of Ophthalmology Related Cerebral Arterial Circulation Diseases: A 3D Animated Encyclopedia",slug:"diagnosis-and-treatment-of-ophthalmology-related-cerebral-arterial-circulation-diseases-a-3d-animate",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.102846",abstract:"Cerebral circulation is the flow of blood through a group of arteries and veins which supply the brain. There are various diseases related to ophthalmology, due to pathologies in the cerebral arterial system. Arteries inside the skull can be blocked by plaque or disease, which in turn triggers a series of events leading to various cranial nerve palsies, visual fields defects, retinal diseases, etc. The highlights of this chapter are the novel three-dimensional (3D) animative videos created by us, to simplify various cerebral arterial circulation diseases and their diagnostic concepts for neophytes. 3D animative videos can aid learning and help in the cognitive concept building of these complex pathologies.",book:{id:"11371",title:"Cerebral Circulation - Updates on Models, Diagnostics and Treatments of Related Diseases",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg"},signatures:"Prasanna Venkatesh Ramesh, Shruthy Vaishali Ramesh, Prajnya Ray, Aji Kunnath Devadas, Tensingh Joshua, Anugraha Balamurugan, Meena Kumari Ramesh and Ramesh Rajasekaran"},{id:"80895",title:"Heart Rate Variability as a Marker of Homeostatic Level",slug:"heart-rate-variability-as-a-marker-of-homeostatic-level",totalDownloads:26,totalDimensionsCites:0,doi:"10.5772/intechopen.102500",abstract:"Many variables have been used as homeostatic level markers. Heart Rate Variability (HRV) has been frequently cited as an indicator of homeostatic status. Low levels of HRV are associated with aging, disease, or increased risk of death. We present a study based on more than 10.5 million data collected from the literature, associating the degree of global clinical impairment of individuals, with their respective HRV data, seeking to establish a classification of Homeostatic Levels. Three specific variables were evaluated: heart rate (HR), the root-mean-square of successive differences between adjacent normal RR intervals in a time interval (RMSSD) and the HF band (HF ms2). It was possible to detect significant differences between the 83,927 data from healthy individuals and the 382,039 data from individuals with significant homeostatic impairment. It was demonstrated that the RMSSD is very sensitive to the worst homeostatic state, presenting a behavior independent of age and that the values found in the general population do not match the values of apparently healthy individuals. An alphanumeric classification of the homeostatic level in a three-level architecture was proposed, with three stages for each level, which may be extremely useful in prognostic assessment and decision-making about individual people.",book:{id:"10835",title:"Autonomic Nervous System - Special Interest Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10835.jpg"},signatures:"Moacir Fernandes de Godoy and Michele Lima Gregório"},{id:"80456",title:"Cerebrospinal Venous Obstruction: Anatomy, Clinical Presentation, Diagnosis, and Treatment of Chronic Infective Cerebrospinal Venulitis",slug:"cerebrospinal-venous-obstruction-anatomy-clinical-presentation-diagnosis-and-treatment-of-chronic-in",totalDownloads:90,totalDimensionsCites:0,doi:"10.5772/intechopen.102685",abstract:"This review chapter describes the normal anatomy and function of the cerebrospinal venous system, ultrasound diagnosis of obstructions in the system, and the clinical implications and treatment of chronic cerebrospinal venous obstruction (CCSVO) associated with chronic persistent Chlamydophila pneumoniae (Cpn) infection. The normal patterns of flow in the cerebrospinal venous system are described and guidelines for the interpretation of the extracranial duplex ultrasound (ECDU) examination of the neck veins are presented. An infective cause of CCSVO is proposed and relevant pathology tests necessary for a diagnosis of chronic persistent Cpn venulitis are discussed. A treatment protocol for Cpn chronic venulitis is described and recommended. The progress of the patient with CCSVO can then be followed and monitored by using the ECDU and relevant pathology tests after 3 and 6 months. CCSVO is a relatively common condition encountered in chronic diseases of unknown etiology and is often neglected by medical practitioners when managing patients with symptoms of brain fog, chronic headaches, and fatigue. Objective diagnostic and treatment protocols are required to make further progress with these conditions.",book:{id:"11371",title:"Cerebral Circulation - Updates on Models, Diagnostics and Treatments of Related Diseases",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg"},signatures:"Paul K. Thibault"},{id:"80543",title:"Measurement of Cerebral Circulation in Human",slug:"measurement-of-cerebral-circulation-in-human",totalDownloads:55,totalDimensionsCites:0,doi:"10.5772/intechopen.102383",abstract:"In this chapter, we review state-of-the-art non-invasive techniques to monitor and study cerebral circulation in humans. The measurement methods can be divided into two categories: direct and indirect methods. Direct methods are mostly based on using contrast agents delivered to blood circulation. Clinically used direct methods include single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI) with contrast agents, xenon computed tomography (CT), and arterial spin labeling (ASL) MRI. Indirect techniques are based on measuring physiological parameters reflecting cerebral perfusion. The most commonly used indirect methods are near-infrared spectroscopy (NIRS), transcranial Doppler ultrasound (TCD), and phase-contrast MRI. In recent years, few more techniques have been intensively developed, such as diffuse correlation spectroscopy (DCS) and microwave-based techniques, which are still emerging as methods for cerebral circulation monitoring. In addition, methods combining different modalities are discussed and, as a summary, the presented techniques and their benefits for cerebral circulation will be compared.",book:{id:"11371",title:"Cerebral Circulation - Updates on Models, Diagnostics and Treatments of Related Diseases",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg"},signatures:"Sadegh Moradi, Hany Ferdinando, Aleksandra Zienkiewicz, Mariella Särestöniemi and Teemu Myllylä"}],onlineFirstChaptersTotal:14},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. 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He has published research in Research Policy, Applied Economics, Review of Economic Philosophy, Strategic Change, International Journal of Logistics, Sustainability, Journal of Environmental Management, Journal of Global Information Management, Journal of Cleaner Production, M@N@GEMENT, and more. He is a member of CEDIMES Institut (France), Academy of International Business (AIB), Strategic Management Society (SMS), Academy of Management (AOM), Administrative Science Association of Canada (ASAC), and Canadian council of small business and entrepreneurship (CCSBE). He is currently the director of the Research Group on Contemporary Asia (GERAC) at Laval University. 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MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. 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Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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