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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5318",leadTitle:null,fullTitle:"Sickle Cell Disease - Pain and Common Chronic Complications",title:"Sickle Cell Disease",subtitle:"Pain and Common Chronic Complications",reviewType:"peer-reviewed",abstract:"This book addresses a wide range of clinically relevant topics and issues in sickle cell disease. This is written by experts in their own field offering a robust, engaging discussion about the presentations and mechanisms of actions in the multiple complications associated with sickle cell disease. This first of the series addresses pain, which is considered the hallmark of sickle cell presentation. It looks at the basic mechanism of pain in sickle cell disease. A more detailed review of precision medicine gives a clear well laid out presentation that is incisive and yet gives in-depth detail relevant to both the clinician and the researcher in the basic laboratory. The same pattern is shown in the discussion on respiratory, cardiac and neurological complications. The 14 chapters also include an overview of sickle cell disease especially in the paediatric age. The content is organized into well-designed broad sections on overview regarding diagnosis including point of care and the role of digital apps in patient management. A key aspect of the book is the opportunity it affords expert physicians to express well-reasoned opinions regarding complex issues in sickle cell disease. The readership would find that it provides a well-described, concise and immediate applicable answers to complex questions. This is highly recommended for scientists and clinicians alike.",isbn:"978-953-51-2767-3",printIsbn:"978-953-51-2766-6",pdfIsbn:"978-953-51-4154-9",doi:"10.5772/62012",price:119,priceEur:129,priceUsd:155,slug:"sickle-cell-disease-pain-and-common-chronic-complications",numberOfPages:282,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"b0d3e289ff1a87bb491889c5115af188",bookSignature:"Baba Psalm Duniya Inusa",publishedDate:"November 10th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5318.jpg",numberOfDownloads:27373,numberOfWosCitations:12,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:26,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:49,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 1st 2015",dateEndSecondStepPublish:"January 12th 2016",dateEndThirdStepPublish:"March 27th 2016",dateEndFourthStepPublish:"June 25th 2016",dateEndFifthStepPublish:"July 25th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"36120",title:"Dr.",name:"Baba P.D.",middleName:null,surname:"Inusa",slug:"baba-p.d.-inusa",fullName:"Baba P.D. Inusa",profilePictureURL:"https://mts.intechopen.com/storage/users/36120/images/4974_n.jpg",biography:"Baba PD Inusa, qualified from Zaria, Nigeria, leads the paediatric haematology at Evelina London and Guy’s and St Thomas’ NHS Foundation Trust, London, and he is a visiting professor at the Kaduna State University. He is a fellow of the Royal College of Paediatrics and Child Health and American Society of Hematology and a member of the international management committee responsible for global haematology. He is a director at the Academy for Sickle Cell and Thalassaemia (ASCAT) which now is in its 10th anniversary. He founded the sickle cell cohort research (www.score-international.org). His research includes neurological disorders (stroke, neuropsychological studies) and renal impairment in sickle cell disease, and he leads a number of drug trials in the UK and extensive research collaboration in the USA, UK and Africa. He is also a reviewer of over ten high-impact journals and currently editing a book on sickle cell disease.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1027",title:"Hematopathology",slug:"hematopathology"}],chapters:[{id:"52844",title:"Introductory Chapter: Introduction to the History, Pathology and Clinical Management of Sickle Cell Disease",doi:"10.5772/65648",slug:"introductory-chapter-introduction-to-the-history-pathology-and-clinical-management-of-sickle-cell-di",totalDownloads:1825,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Baba Inusa, Maddalena Casale and Nicholas Ward",downloadPdfUrl:"/chapter/pdf-download/52844",previewPdfUrl:"/chapter/pdf-preview/52844",authors:[{id:"36120",title:"Dr.",name:"Baba P.D.",surname:"Inusa",slug:"baba-p.d.-inusa",fullName:"Baba P.D. Inusa"}],corrections:null},{id:"51910",title:"A Global Perspective on Milestones of Care for Children with Sickle Cell Disease",doi:"10.5772/64656",slug:"a-global-perspective-on-milestones-of-care-for-children-with-sickle-cell-disease",totalDownloads:1917,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Sickle cell disease (SCD) is one of the most common severe and monogenic disorders worldwide. Acute and chronic complications deeply impact the health of children with SCD. Milestones of treatment include newborn screening, comprehensive care and prevention of cerebrovascular complications.",signatures:"Laura Sainati, Maria Montanaro and Raffaella Colombatti",downloadPdfUrl:"/chapter/pdf-download/51910",previewPdfUrl:"/chapter/pdf-preview/51910",authors:[{id:"183388",title:"Dr.",name:"Raffaella",surname:"Colombatti",slug:"raffaella-colombatti",fullName:"Raffaella Colombatti"},{id:"184414",title:"Dr.",name:"Laura",surname:"Sainati",slug:"laura-sainati",fullName:"Laura Sainati"},{id:"189261",title:"Dr.",name:"Maria",surname:"Montanaro",slug:"maria-montanaro",fullName:"Maria Montanaro"}],corrections:null},{id:"51872",title:"New Perspectives in Prenatal Diagnosis of Sickle Cell Anemia",doi:"10.5772/64646",slug:"new-perspectives-in-prenatal-diagnosis-of-sickle-cell-anemia",totalDownloads:2314,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Hemoglobin disorders such as thalassemias and sickle cell anemias can be avoided by detecting carriers, ensuring genetic counseling and prenatal diagnosis. Nowadays Chorionic villus sampling (CVS amniocentesis, and cordocentesis are still the most widely used invasive sampling methods for prenatal diagnosis of the fetus. These traditional methods are associated with a risk of fetal loss. The revelation of cell-free fetal DNA (cffDNA) in maternal plasma and serum provides the opportunity of noninvasive prenatal diagnosis (NIPD). Different encouraging clinical applications have arose such as noninvasive identification of fetal sexing, fetal Rhesus D, and the determination of the paternal alleles in maternal plasma. The determination of the presence or absence of paternally inherited alleles in maternal plasma of sickle cell disease (SCD) and β-thalassemia would allow the diagnosis of autosomal dominant diseases or the exclusion of autosomal recessive diseases of the fetuses, respectively. prenatal diagnosis of genetic diseases. Analysis of cffDNA in maternal plasma for NIPD has the advantage of being safer versus the invasive methods. Different technologies were used since the discovery of cffDNA for NIPD—especially high-resolution melting (HRM) analysis is one of those methods. Genotyping can be done with HRM without using labeled probes and more complex regions can be analyzed with unlabeled hybridization probes. High-resolution melting is a rapid and useful method to detect paternal alleles for the NIPD of SCD and thalassemias when the fetus has a risk for double heterozygote.",signatures:"Ebru Dündar Yenilmez and Abdullah Tuli",downloadPdfUrl:"/chapter/pdf-download/51872",previewPdfUrl:"/chapter/pdf-preview/51872",authors:[{id:"183998",title:"Ph.D.",name:"Ebru",surname:"Dündar Yenilmez",slug:"ebru-dundar-yenilmez",fullName:"Ebru Dündar Yenilmez"}],corrections:null},{id:"52109",title:"Point‐of‐Care Testing in Sickle Cell Disease",doi:"10.5772/64862",slug:"point-of-care-testing-in-sickle-cell-disease",totalDownloads:2253,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Sickle cell disease is one of the most common inherited blood disorders. Universal screening and central laboratory diagnostics have improved early identification of affected individuals and helped to reduce childhood mortality in high‐resource countries. Additional methods of centralized diagnostics have also been developed in some low resource areas in partnership with private companies, local governments and academic US‐based institutions. However, these techniques require expansive infrastructure and government partnership for success. Thus, many individuals living in low‐resource settings are often not diagnosed until late childhood when they present with clinical symptoms. In addition, confirmation of disease in affected individuals in the urgent care setting remains limited in both high‐ and low‐resource areas due to the use of batched testing methods. All of the current diagnostic methods rely on advanced laboratory systems and are often prohibitively expensive and time‐consuming. To address this need and improve the capacity for timely diagnosis, novel methods for point‐of‐care testing for sickle cell disease are currently in process.",signatures:"Julie Kanter",downloadPdfUrl:"/chapter/pdf-download/52109",previewPdfUrl:"/chapter/pdf-preview/52109",authors:[{id:"184260",title:"Dr.",name:"Julie",surname:"Kanter",slug:"julie-kanter",fullName:"Julie Kanter"}],corrections:null},{id:"51854",title:"Mechanisms of Pain in Sickle Cell Disease",doi:"10.5772/64647",slug:"mechanisms-of-pain-in-sickle-cell-disease",totalDownloads:2253,totalCrossrefCites:0,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Pain is one of the most common features of sickle cell disease (SCD) lacking effective therapy. Pain in SCD is relatively more complicated than other conditions associated with pain requiring understanding of the pathobiology of pain specific to SCD. The characterization of pain to define the diverse modalities of nociception in SCD is currently under progress via human studies accompanied by transgenic mouse models of SCD. Sickle pathobiology characterized by oxidative stress, inflammation and vascular dysfunction contributes to both peripheral and central nociceptive sensitization via mast cell activation in the periphery, and reactive oxygen species and glial activation and endoplasmic reticulum stress in the spinal cord among other effectors. These effects are mediated via several cellular receptors, which can be targeted to produce positive therapeutic outcomes. In this chapter, we will discuss the present understanding of molecular mechanisms of SCD pain and outline the mechanism‐based translational potential of novel actionable targets to treat SCD pain.",signatures:"Anupam Aich, Alvin J Beitz and Kalpna Gupta",downloadPdfUrl:"/chapter/pdf-download/51854",previewPdfUrl:"/chapter/pdf-preview/51854",authors:[{id:"183384",title:"Prof.",name:"Kalpna",surname:"Gupta",slug:"kalpna-gupta",fullName:"Kalpna Gupta"},{id:"187313",title:"Prof.",name:"Alvin J",surname:"Beitz",slug:"alvin-j-beitz",fullName:"Alvin J Beitz"},{id:"187314",title:"Dr.",name:"Anupam",surname:"Aich",slug:"anupam-aich",fullName:"Anupam Aich"}],corrections:null},{id:"51643",title:"The Cardiomyopathy of Sickle Cell Disease",doi:"10.5772/64321",slug:"the-cardiomyopathy-of-sickle-cell-disease",totalDownloads:2131,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cardiac morbidity, early mortality, and sudden death are the major consequences of sickle cell disease (SCD) in patients surviving into adulthood. Pulmonary hypertension (PH), elevated tricuspid regurgitant jet velocity (TRV), and diastolic dysfunction have all been identified to correlate with early mortality in adults with SCD. However, the unifying pathophysiology behind these abnormalities and its connection with early mortality and sudden death have not been recognized previously. We have found that SCD patients have a unique cardiomyopathy characterized by restrictive physiology (diastolic dysfunction, left atrial dilation and normal systolic function) superimposed on features of hyperdynamic circulation (left ventricular [LV] enlargement and eccentric LV hypertrophy. The restrictive cardiomyopathy of SCD causes pulmonary congestion and post-capillary PH. This can be detected by a mild elevation in TRV, which is likely a marker of the SCD-related cardiomyopathy rather than pulmonary arterial disease. Similar to other restrictive cardiomyopathies, the SCD cardiomyopathy predisposes to arrhythmias and sudden death, even when pulmonary pressures are not severely elevated. We have also found that diffuse myocardial fibrosis is common in SCD and may underlie the diastolic dysfunction, but more studies are needed to understand the mechanisms of SCD-related cardiomyopathy and to identify new therapies to decrease cardiac morbidity and improve the life expectancy of SCD patients.",signatures:"Omar Niss and Charles T. Quinn",downloadPdfUrl:"/chapter/pdf-download/51643",previewPdfUrl:"/chapter/pdf-preview/51643",authors:[{id:"183945",title:"Dr.",name:"Charles",surname:"Quinn",slug:"charles-quinn",fullName:"Charles Quinn"},{id:"183952",title:"Dr.",name:"Omar",surname:"Niss",slug:"omar-niss",fullName:"Omar Niss"}],corrections:null},{id:"51391",title:"Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease",doi:"10.5772/64365",slug:"pulmonary-complications-and-lung-function-abnormalities-in-children-with-sickle-cell-disease",totalDownloads:1759,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The pulmonary complications of sickle cell disease (SCD) have a high morbidity and mortality. Fatal pulmonary complications occur in 20% of adults; those with sickle chronic lung disease (SCLD) and pulmonary hypertension have a significantly increased mortality. Treatment of SCLD is only supportive. Recurrent acute chest syndrome (ACS) episodes are the major risk factor for SCLD, and ACS is the leading cause of death. Adults with SCD tend to have restrictive lung function abnormalities, whereas, in children, obstructive abnormalities are more frequent. Lung function abnormalities are common even in young children and may reflect their chronic anaemia and increased pulmonary capillary blood volume, which increases airway obstruction and may be responsible for their increased wheezing. Whether more aggressive treatment of anaemia would improve lung function and long-term outcomes merits testing. Children with SCD experience a decline in lung function, which is most rapid in younger children in whom ACS episodes are most common highlighting the importance of identifying effective strategies to prevent and optimally treat ACS.",signatures:"Anne Greenough",downloadPdfUrl:"/chapter/pdf-download/51391",previewPdfUrl:"/chapter/pdf-preview/51391",authors:[{id:"183766",title:"Prof.",name:"Anne",surname:"Greenough",slug:"anne-greenough",fullName:"Anne Greenough"}],corrections:null},{id:"51430",title:"Neurological Complications and MRI",doi:"10.5772/64143",slug:"neurological-complications-and-mri",totalDownloads:1664,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Cerebrovascular diseases (cerebral infarction, intracranial haemorrhage and vasculopathy) are common manifestations of sickle cell disease (SCD) associated with significant morbidity and mortality. These neurological complications and potential corresponding neuropsychological compromise may have devastating consequences for a child with SCD. This chapter aims to review the neurological complications in SCD using magnetic resonance imaging (MRI) as both a qualitative and a quantitative tool for detecting abnormality. Advanced MRI pulse sequences, such as high-resolution 3D T1-weighted imaging for brain volumetrics, diffusion tensor imaging for white matter integrity and non-invasive perfusion MRI for cerebral blood flow (CBF) measurement, can provide additional information about the structure and function of brain tissue beyond the scope of conventional clinical imaging. These studies have set to establish quantitative biomarkers that relate to disease severity and neuropsychological sequelae.",signatures:"Jamie M. Kawadler and Fenella J. Kirkham",downloadPdfUrl:"/chapter/pdf-download/51430",previewPdfUrl:"/chapter/pdf-preview/51430",authors:[{id:"184006",title:"Dr.",name:"Jamie",surname:"Kawadler",slug:"jamie-kawadler",fullName:"Jamie Kawadler"},{id:"193781",title:"Dr.",name:"Fenella J.",surname:"Kirkham",slug:"fenella-j.-kirkham",fullName:"Fenella J. Kirkham"}],corrections:null},{id:"51382",title:"Asthma, Airway Hyperresponsiveness, and Lower Airway Obstruction in Children with Sickle Cell Disease",doi:"10.5772/64328",slug:"asthma-airway-hyperresponsiveness-and-lower-airway-obstruction-in-children-with-sickle-cell-disease",totalDownloads:1496,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"As a comorbid condition of sickle cell disease (SCD), asthma leads to increased complications and mortality. However, poor understanding of asthma phenotypes in SCD and the complex interaction with SCD-related airway inflammation, manifested by bronchial hyperresponsiveness or obstructive airway, pose a unique clinical challenge. The objective of this chapter is to provide a comprehensive review and discussion of epidemiology, pathophysiology, interactions, and clinical implications of airway hyperresponsiveness (AHR), obstructive airway, and asthma in SCD. Discussion will cover new understanding and limitations of asthma diagnosis and management in SCD. AHR, lower obstructive airway, and asthma are highly prevalent in SCD. Despite overlapping features, these entities are nonetheless distinct as demonstrated by basic science and clinical data. Diagnosis of asthma should be based on a physician assessment. We provide new unpublished data of a prospective study on diagnosing asthma in a small preschool population. Administered validated asthma-screening questionnaire to SCD children reveals good sensitivity and specificity as an asthma detection tool. It is unclear at this time if detection of bronchial lability or asthma early in life would result in better outcome of patients, or if improved control of SCD attenuates lower airway pathology. Being able to distinguish asthma from bronchial lability in the preschool age children would allow for appropriate intervention early in life.",signatures:"Aravind Yadav, Ricardo A. Mosquera and Wilfredo De Jesus Rojas",downloadPdfUrl:"/chapter/pdf-download/51382",previewPdfUrl:"/chapter/pdf-preview/51382",authors:[{id:"184226",title:"Dr.",name:"Aravind",surname:"Yadav",slug:"aravind-yadav",fullName:"Aravind Yadav"},{id:"184227",title:"Dr.",name:"Wilfredo De Jesus",surname:"Rojas",slug:"wilfredo-de-jesus-rojas",fullName:"Wilfredo De Jesus Rojas"},{id:"184228",title:"Dr.",name:"Ricardo A.",surname:"Mosquera",slug:"ricardo-a.-mosquera",fullName:"Ricardo A. Mosquera"}],corrections:null},{id:"51543",title:"Leg Ulceration in Sickle Cell Disease: An Early and Visible Sign of End‐Organ Disease",doi:"10.5772/64234",slug:"leg-ulceration-in-sickle-cell-disease-an-early-and-visible-sign-of-end-organ-disease",totalDownloads:2049,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Introduction: Leg ulcers are a frequent and debilitating complication of sickle cell disease (SCD), particularly of the SS genotype. The prevalence of leg ulcers in patients with sickle cell disease (SCD) varies geographically ranging widely from 75% in Jamaica to as low as 1% in Saudi Arabia. The prevalence of leg ulcers in the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States was 5% in SS genotype with the incidence increasing with age. As patients with SCD have increasingly improved survival, the prevalence of leg ulcers is likely to be higher. These ulcers are slow to heal, have a high rate of recurrence, and are associated with severe unremitting pain and depression, thus leading to high healthcare costs. Despite being a well‐recognized complication of SCD, there are no specifically designed evidence‐based guidelines to help clinicians manage these patients.",signatures:"Aditi P. Singh and Caterina P. Minniti",downloadPdfUrl:"/chapter/pdf-download/51543",previewPdfUrl:"/chapter/pdf-preview/51543",authors:[{id:"184747",title:"M.D.",name:"Caterina",surname:"Minniti",slug:"caterina-minniti",fullName:"Caterina Minniti"},{id:"186829",title:"Dr.",name:"Aditi",surname:"Singh",slug:"aditi-singh",fullName:"Aditi Singh"}],corrections:null},{id:"52831",title:"Stem Cell Transplantation in Patients with Sickle Cell Disease",doi:"10.5772/64917",slug:"stem-cell-transplantation-in-patients-with-sickle-cell-disease",totalDownloads:1856,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Hematopoietic stem cell transplantation (HSCT) is currently the only established cure for sickle cell disease (SCD). Replacement of the stem cell that has the defective beta globin allele with the normal gene decreases hemoglobin S and the risk of complications of SCD. The first case reported was a girl with acute myeloid leukemia and SCD who received HSCT and achieved long-term SCD and leukemia-free survival. Given the favorable outcomes of HSCT with thalassemia major using myeloablative preparative regimens, this approach became widely used in the initial studies of HSCT in SCD. The current standard of care is to use a myeloablative stem cell transplantation in patients with severe disease who have human leukocyte antigen–identical sibling. HSCT improves organ function, quality of life, and overall and disease-free survival. However, this is associated with high risk of gonadal dysfunction and graft versus host disease in addition to the mortality associated with the myeloablative HSCT. Reduced-intensity HSCT has also been reported with high rates of engraftment and favorable outcomes. This has been introduced to lower the gonadal dysfunction, mortality, and graft versus host disease associated with myeloablative approaches. Other approaches include HSCT using matched unrelated donors, cord blood units, and human leukocyte antigen haploidentical donors. Unfortunately, graft rejection is a common complication with these approaches. In this chapter, we review the indications of HSCT for SCD and outcomes of different transplant strategies including alternative donor transplant, graft rejection, and infertility after transplantation.",signatures:"Murtadha Al-Khabori, Mohammed Al-Huneini and Abdulhakim Al-\nRawas",downloadPdfUrl:"/chapter/pdf-download/52831",previewPdfUrl:"/chapter/pdf-preview/52831",authors:[{id:"183778",title:"Dr.",name:"Murtadha",surname:"Al-Khabori",slug:"murtadha-al-khabori",fullName:"Murtadha Al-Khabori"},{id:"184249",title:"Dr.",name:"Mohammed",surname:"Al-Huneini",slug:"mohammed-al-huneini",fullName:"Mohammed Al-Huneini"},{id:"184250",title:"Dr.",name:"Abdulhakeem",surname:"Al-Rawas",slug:"abdulhakeem-al-rawas",fullName:"Abdulhakeem Al-Rawas"}],corrections:null},{id:"52068",title:"Precision Medicine for Sickle Cell Disease: Discovery of Genetic Targets for Drug Development",doi:"10.5772/64817",slug:"precision-medicine-for-sickle-cell-disease-discovery-of-genetic-targets-for-drug-development",totalDownloads:1887,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sickle cell disease (SCD) consists of inherited monogenic hemoglobin disorders affecting over three million people worldwide. Efforts to establish precision medicine based on the discovery of genetic polymorphisms associated with disease severity are ongoing to inform strategies for novel drug design. Numerous gene mutations have been associated with the clinical complications of SCD such as frequency of pain episodes, acute chest syndrome, and stroke among others. However, these discoveries have not produced additional treatment options. To date, Hydroxyurea remains the only Food and Drug Administration-approved agent for treating adults with SCD; recently it was demonstrated to be safe and effective in children. The main action of Hydroxyurea is the induction of fetal hemoglobin, a potent modifier of SCD clinical severity. Three inherited gene loci including XmnI-HBG2, HBS1L-MYB and BCL11A have been linked to HBG expression, however the greatest progress has been made to develop BCL11A as a therapeutic target. With the expanded availability of next generation sequencing, there exist opportunities to discover additional genetic modifiers of SCD. The progress made over the last two decades to define markers of disease severity and the implications for achieving precision medicine to treat the complications of SCD will be discussed.",signatures:"Betty S. Pace, Nicole H. Lopez, Xingguo Zhu and Biaoru Li",downloadPdfUrl:"/chapter/pdf-download/52068",previewPdfUrl:"/chapter/pdf-preview/52068",authors:[{id:"183784",title:"Dr.",name:"Betty",surname:"Pace",slug:"betty-pace",fullName:"Betty Pace"}],corrections:null},{id:"51531",title:"Phytotherapy and the Relevance of Some Endogenous Antioxidant Enzymes in Management of Sickle Cell Diseases",doi:"10.5772/64273",slug:"phytotherapy-and-the-relevance-of-some-endogenous-antioxidant-enzymes-in-management-of-sickle-cell-d",totalDownloads:2355,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Introduction: Sickle cell disease (SCD) is one of the most devastating diseases ravaging most populations.",signatures:"Israel Sunmola Afolabi, Iyanuoluwa O. Osikoya and Adaobi Mary-Joy Okafor",downloadPdfUrl:"/chapter/pdf-download/51531",previewPdfUrl:"/chapter/pdf-preview/51531",authors:[{id:"183395",title:"Associate Prof.",name:"Israel",surname:"Afolabi",slug:"israel-afolabi",fullName:"Israel Afolabi"}],corrections:null},{id:"51358",title:"Digital Health Interventions (DHIs) to Support the Management of Children and Adolescents with Sickle‐Cell Disease",doi:"10.5772/64315",slug:"digital-health-interventions-dhis-to-support-the-management-of-children-and-adolescents-with-sickle-",totalDownloads:1616,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Sickle‐cell disease (SCD) is a very complex disorder alluding to all areas of medicine. Nevertheless, basic preventive and therapeutic interventions in patients suffering from SCD are extremely simple. However, in everyday life it is sometimes virtually impossible to motivate children and young adolescents to effectively self‐manage their disorder at an early stage. Digital health interventions (DHIs) provide new opportunities to support self‐management behaviours. DHIs may facilitate daily and recurrent routines such as drug intake or appointments along with helping the patients to better cope with their disease. This may be realized through mobile‐training programmes, disease‐specific social networks using secure communication channels, diaries, blogs and even games. Indeed, there are fascinating opportunities for modern disease‐training programmes to take advantage of several media that can be combined and didactically optimized to meet the individual needs and intellectual abilities of different patients. The technological progress is rapid, extremely dynamic and highly creative. Our chapter gives an overview of the multifarious world of DHIs with a focus on smartphone applications known as mobile health apps (mHealth apps). 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\r\n\tThis book concerns autonomous mobile mapping robots capable of digitizing the surrounding environment in the form of a map easily interpretable by humans. This functionality is related to fundamental algorithmic challenges in the mobile robotic domain.
\r\n\r\n\tSuch machines can execute the autonomous mission in unknown and harsh environments; thus, they can help humans in decreasing the time of digital map delivery. Many algorithmic challenges have to be addressed, such as Simultaneous Localisation and Mapping assuming low energy onboard computers. LiDAR and VISUAL odometry are t candidates for initial trajectory estimation. Furthermore, a robust Graph SLAM approach can efficiently reduce incremental odometry error. Moreover, recent advances in Deep Neural Networks DNN applied for image and LiDAR data processing and analysis (segmentation and classification) are also crucial. DNN can provide necessary information to improve autonomous task execution. This book will address the problem of path planning and autonomous task execution as large-scale mobile mapping applications. For this reason, some practical implementations are provided. This book will intend to provide the reader with a comprehensive overview of the current state-of-the-art in autonomous mobile mapping robots.
",isbn:"978-1-83768-009-2",printIsbn:"978-1-83768-008-5",pdfIsbn:"978-1-83768-010-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"405e1f7c0ef62700f4d590722cf428be",bookSignature:"Dr. Janusz Bȩdkowski",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11456.jpg",keywords:"LiDAR Odometry, VISUAL Odometry, Kalman Filter, SLAM, Pose Graph, Path Planning, Path Following, Classification, Segmentation, Automatic Reasoning, USAR Urban Search and Rescue, Underground Mapping",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 10th 2022",dateEndSecondStepPublish:"July 13th 2022",dateEndThirdStepPublish:"September 11th 2022",dateEndFourthStepPublish:"November 30th 2022",dateEndFifthStepPublish:"January 29th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Researcher in mobile mapping applications. Actively developing practical robotic applications testing in realistic conditions (ENRICH, ELROB). Dr. Bedkowski was granted a postdoctoral scholarship in the Royal Military Academy (RMA), Belgium, funded by the Center for Advanced Studies, Warsaw University of Technology. Since 2017 he has been involved in the development of the continent-scale Simultaneous Localization and Mapping Technologies for autonomous cars in TomTom.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"63695",title:"Dr.",name:"Janusz",middleName:null,surname:"Bȩdkowski",slug:"janusz-bdkowski",fullName:"Janusz Bȩdkowski",profilePictureURL:"https://mts.intechopen.com/storage/users/63695/images/system/63695.jpg",biography:"Janusz Bedkowski, Ph.D., D.Sc. in Automation and Robotics, is an adjunct professor at the Institute of Fundamental Technological Research Polish Academy of Sciences. From 2006 to 2018, he collaborated with Industrial Research Institute for Automation and Measurements, Warsaw, Poland, concerning multi robotic inspection-intervention systems development and integration. He was granted a postdoctoral scholarship in the Royal Military Academy (RMA), Brussels, Belgium, funded by Center for Advanced Studies, Warsaw University of Technology. His research interests are: inspection intervention robot systems, semantic mapping including 3D cloud of points and video processing, 6D SLAM, mobile robot operator training with AR techniques and GPGPU computing. From 2017 he is involved in development of the continent scale Simultaneous Localization and Mapping Technologies for autonomous cars in TomTom. He commercialized robotic 3D mapping technologies within the MANDALA company (www.mandalarobotics.com). 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Metals, paper, plastics and a host of other materials are now recycled, thereby conserving precious landfill space. One particularly important waste diversion is in the area of wood and garden waste [1]. These materials tend to be bulky and, more importantly, contribute to the production of methane as they degrade under anaerobic conditions in the landfill. Many communities now divert this material to be composted, separated and burned for energy production or, if the resource is sufficiently free of contaminants, even used to produce composite wood products. Composting has become especially attractive because this material can be combined with more putrescible wastes such as food compost to produce a very rich composted material.
One aspect of wood recycling operations that is often overlooked is the presence of contaminants in the chipped mixture. Metal fasteners can be removed using magnets, but many other materials wind up in this mixture. One of the more important potential contaminants is preservative treated wood [2,3]. Preservative treated wood is typically impregnated with combinations of heavy metals to provide resistance to biological attack. For decades, the most commonly used preservative for residential applications was chromated copper arsenate (CCA). CCA is no longer used for residual applications, but the replacement systems are primarily copper based including alkaline copper quaternary compound (ACQ) or alkaline copper azole (CA). The U.S. Environmental Protection Agency generally recommends that, wherever possible, treated wood be reused in a similar application. Once this is no longer possible, the wood should be disposed of in a licensed municipal solid waste facility with the appropriate liners and leachate management technology. The EPA specifically prohibits the burning of treated wood except in specially licensed facilities. The most common use of combustion for disposal of treated wood is with creosote, although it is technically possible to combust other treated wood products. These activities are generally associated with industrial products such as railroad ties or utility poles.
While industrial products are an important component of the potential treated wood disposal stream, the users of these products are generally aware of the requirements for disposal. However, a large amount of preservative treated wood is employed in residential applications for decking, fencing, and a host of other uses. These products have varying service lives and eventually find their way into the waste stream. As with other treated wood products, the EPA recommends reuse following by landfill disposal for these products at the end of their service lives; however, there are several factors that can make this difficult. First, treated wood in many parts of the country tends to fade and weather as it is exposed to ultraviolet light. In many cases, it is virtually impossible to visually distinguish between treated and non-treated wood once it has weathered. In addition, many homeowners do not know that treated wood needs to be disposed of in a landfill and therefore tend to place this material into their yard recycling container where they already place other woody debris. Finally, there is no specific collection pathway for treated wood products, making them difficult to assemble as a single material.
The potential for contamination of wood recycling streams was brought to light over a decade ago in Florida. Energy recovery facilities that used mixtures of bagasse and waste wood obtained from construction and demolition landfills as fuel sources discovered that their resulting ash contained very high levels of copper, chromium and arsenic. Further investigation revealed that high percentages of wood entering construction and demolition debris (C&D) facilities were treated with CCA. However, the wood had weathered to the extent that it was no longer possible to visually detect this material. The Florida situation is unique in a number of ways. The higher risk of decay in this state means that treated wood represents a much higher percentage of the total volume of wood used. In addition, these more severe exposure conditions lead to a shorter overall service life for a given product. The severe UV exposure conditions typically found in Florida tend to reduce the surface appearance of the material, leading to premature removal of wood that is structurally sound, but has a poor appearance. Florida also has a very limited landfill capacity and, at the time had a number of non-lined C&D facilities. This led to large amounts of materials entering combustion facilities. The occurrence of elevated metal levels stimulated a large research effort at the University of Miami and University of Florida to determine the levels of treated wood entering the recycling stream, and, once it became evident that a substantial volume of treated wood was present, how to rapidly detect it.
Copper based systems are currently the most commonly used wood preservatives, but older wood can also contain chromium and arsenic. The EPA labels associated with these chemicals specifically indicate that disposal of products treated with wood preservatives should be in a lined landfill; however, it can sometimes be difficult to determine if wood that has been subjected to extensive ultraviolet light contains preservative treatment. As a result, there is a risk that treated wood can enter the recycling stream. In the case of woody debris used for biofuels, the presence of metal based preservative can result in air-emissions as well as elevated metal levels in the resulting ash. Inadvertent inclusion of treated wood in composting operations could result in elevated metal levels in the subsequent compost. While this is unlikely to pose a risk to plants, it could lead to difficulties if the materials are marketed as being organic.
In either case, quantifying the amounts of treated wood entering a waste stream can help producers determine the level of risk so that they can develop appropriate mitigation measures. This risk is likely to differ regionally because of the differing degrees to which treated wood is employed and the length of time it remains in service. The Pacific Northwest is an excellent area in which to determine treated wood incidence in recycling streams because it has well developed recycling programs and the treated wood has distinctive features that make it easier to detect. In this chapter, we will discuss surveys of treated wood incidence in a wood recycling center over a 10 year period and then discuss possible methods for limiting the incidence of such materials [12].
Surveys were conducted at a recycling facility located near Corvallis, Oregon [4]. The facility is a regional composting and recycling facility that processes over 28,000 metric tons of material per year. The facility receives regular yard waste that includes branches, grass, brush, and seasonal influxes such as leaves and Christmas trees. The facility also accepts wood waste from various sources. These materials were formerly chipped separately with the yard debris being composted and the wood debris going to various facilities for combustion for either steam or electricity. This situation has recently changed as a result of the introduction of generation of food waste composting coupled with changes in wood demand in the surrounding area. The food composting operation has resulted in an increase demand for woody debris as a media for the composting, while lower natural gas prices have sharply curtailed the use of woody biomass for energy production. As a result, nearly all wood entering the facility now ends up in the compost mixture.
Most materials arrive at the facility by commercial haulers, but nearby residents can also drop off materials for a fee. Loads can be inspected at the gate house, but it is not feasible to inspect every load. As a result, it is possible for contaminants to enter the recycling stream. Wood entering the facility is segregated into a separate pile for chipping. Chipping occurs as equipment becomes available and the resulting wood chips are stored until needed for constructing a compost pile. Once the wood is chipped, it is virtually impossible to detect the presence of treated wood.
Detecting treated wood prior to chipping is relatively simple. The wood is normally piled in such a way that the vast majority of the pile is accessible. Treated wood in the Pacific Northwest is much easier to detect because it is generally stained with a brown pigment to makes it appear like western redcedar. In addition, a large percentage of the material is incised. This process drives metal teeth into the wood to improve the depth of preservative treatment. Incision marks are easily seen, even in older wood, making detection of treated wood in a pile relatively simple (Figure 1).
Example of wood with incisions that make it relatively easy to detect preservative treated wood in recycling facilities in the Western U.S.
The amount of treated wood has been visually assessed 168 times over the 12 year period [10]. At each time point, the size of the entire pile was estimated. The presence of treated wood of a given dimension in the pile was then visually determined (for example 4 by 4 inches, 2 by 4 inches, etc.) and the length was estimated to the nearest 300 mm. As mentioned, treated wood is readily detected in this part of the United States because of the distinctive brown stain and/or the presence of incisions. Depending on pile size, visual detection of treated wood is possible 1 to 3 m inward from the outside of the pile. In addition, we estimated the relative proportions of yard debris, pallets, panels, and demolition debris. This latter categorization only began after we had performed for the first 40 observations.
Ideally, wood mass would be used to estimated treated wood proportions, however, this was not possible because of safety issues related to the placement of the materials in a pile. Instead, the lineal footage of each piece of dimension material detected was used to determine overall volume of wood using actual dimensions. Lumber for residential applications was primarily treated with chromated copper arsenate (CCA) until 2003 when this material was withdrawn from the market. Alkaline copper quaternary (ACQ) compound or copper azole (CA) largely replaced CCA for this application [5]. It is not possible to visually distinguish wood treated with these three chemicals because of the brown pigments. The use of a copper indicator also would not help since all three systems contain copper as the primary biocide. For the purpose of determining chemical loading, we assumed that all of the wood had been treated to the American Wood Protection Association Standards ground contact retention for treatment of lumber with any of the water borne materials (6.4 kg/m3 for ACQ or CCA) and that the entire cross section had been treated to that level. Average wood densities were then used to calculate the total amount of metal present in the material [6,7]. This is an extremely conservative approach because wood in this region is difficult to penetrate with preservatives. As a result, somewhere between 40 and 60 % of the cross section is actually preservative treated and not all wood is treated to the higher retention level. However, since we could not visually assess treatment depth or retention, we used the conservative approach. As a result, the estimates of total chemical in the wood were intentionally high.
Pallets, yard debris, and demolition debriswere the most abundant materials detected in piles at the site (Figure 2). The average volume of material present at any given inspection was 338.8 m3. Pallets were the most abundant manufactured material at the site (39 of 128 times), while yard debris, which include branches and leaves was the most common 68 times [10]. A variety of other materials were also present including panel trim scraps and shingles, but these represented minor volumes compared to the two most common materials. For example, Christmas trees were seasonally abundant, but represented an overall low percentage of the total mass delivered to the site.
Frequency of a given woody material being the dominant substrate present at the recycling center (from 10)
Percentages of treated wood detected in a recycling facility located in Western Oregon as determined by period visual surveys over a 12 year period.
Frequency of different levels of treated wood in a wood recycling center in Western Oregon assessed over a 10 year period. Values are based upon 112 surveys (from 10).
Treated wood was present in 155 out of 168 inspections or 92.3 % of the samples (Figure 3). The percentages of treated wood were generally low in the samples, ranging from <0.01 % to 2.0 % of the estimated volume (Figure 4). Levels at or above 1 % were only detected 3 times over the 12 year period. The average volume of treated wood present was 0.15 % over the 12 years. Treated wood levels were > 0.2 % of the volume in 20.5 % of the inspections,while they were between 0.1 and 0.2 % of the volumes in another 16.1 % of the inspections. Treated wood represented less than 0.1 % of the volume in a majority of inspections (63.4%), indicating that this material was a relatively small proportion of the recycling stream.
These data provide an example of the potential for inadvertent presence of treated wood in the recycling stream and a relatively simple method for assessing the extent. However, it is important to recognize that every site is different. In some cases, the overall volumes of wood in a facility are too great for this approach or the materials are processed directly and not available for inspection. In addition, the proportions of treated wood at this site were relatively low and the treated products were relatively easily detected. Never the less, it is important to develop reliable estimates of the levels of treated wood entering recycling streams. In the cases of materials that are combusted for energy production, excess amounts of treated wood in the feedstock can lead to releases of arsene gases and produce residual ash with excessively high metal contents that can pose a disposal hazard. This becomes quite important in some facilities. For example, previous studies of wood recycling facilities have shown that 5.9 % of volume at a C&D facility in Florida was treated wood [8], while 2.5 % of the wood entering the waste stream in Virginia was treated [9]. The risk can be examined by considering the potential inputs of metals into ash resulting from combustion of the materials. If we used the Oregon facility data indicating that if an average of 0.15 % of the incoming wood was CCA treated, then As, Cr and Cu levels would be 2380,2640 and 1580 ppm in the resulting ash [10]. Cu levels would be much higher if the wood was treated with either alkaline copper azole or alkaline copper quat but no arsenic or chromium would be present. It is important to realize that material from this particular facility was used to supplement other fuel supplies at local wood processing facilities. As a result there is likely to be considerable dilution with non-treated wood so that the resulting ash would not pose a disposal issue. However, the results do illustrate the potential for creating metal contaminated ashes in areas where large amounts of treated wood are employed. For example, if the treated wood levels present in the C & D facility in Florida were used, then As, Cr and Cu levels in the resulting ash would be 92820, 102,960, and 61620 ppm, respectively, and ash disposal would pose a major challenge. It is important to remember that metals do not disappear from compost. Thus, these same metal input levels would be present in any compost. The Oregon facility received 1318.2 metric tons of wood waste in 2013 along with other materials. If we use the 0.15 % treated wood composition figure, this material would result in an input of 28.2 kg of CCA. CCA Type C is composed of 47.5 % chromic acid, 18.5 % copper oxide and 34 % arsenic pentoxide [5]. These elements are expressed on an oxide basis. If we convert the total CCA input to elemental metals, the treated wood would input 6.97 kg of Cr, 4.50 kg of copper and 4.61 kg of arsenic into the system. The facility produced over 58,707,273 kg of compost (wet weight) from all of the inputs. If we use a 50 % moisture content for the compost, then the metal inputs would represent potential increases of 0.119 ppm, 0.077 ppm, and 0.079 ppm for Cr, Cu and As, respectively. Obviously, the potential impacts of such small inputs would be lost within the inherent variability of other material inputs such as the components of the food compost (for example, some seafoods contain elevated levels of arsenic). The results illustrate the minimal impact of treated wood on either combustion or composting of the incoming material at the Oregon site. A comparative operation in Florida where the treated wood input was estimated to be 39 times higher would increase metal levels in the resulting compost by 4.6, 3.0 and 3.1 ppm respectively. There are limited publically available data on metal levels in compost from facilities such as these, but a survey of Florida composting operations suggests that these inputs would not markedly alter the metal levels in the compost [11]. Some Florida soils have extremely low metal levels and these concentrations would certainly have the potential to increase overall soil metal levels if compost were repeatedly used on the same site; however, these inputs would likely be balanced by plant uptakes. It is important to note that these levels would still be well below those found in soils from most other locations in North America.
The volumes of treated wood entering the facility we surveyed were 1.9 to 4 % of those found at other sites. Furthermore, the levels have actually declined slightly over the past decade.The reasons for the decline are unclear since the facility made no specific effort to exclude materials. While attempts should be made to divert as much of this material as possible from the recycling stream and into a lined landfill, it is obvious that there is a far greater need to accomplish this at the other sites.
Diverting this material; however, is problematic because most of those disposing treated wood materials are homeowners or small contractors who have little basic knowledge about wood treatments. While end-tags on most treated lumber do warn against burning the product, few read these tags and most of the tags are no longer on the wood at the end of its service life. Thus, recycling facilities need to consider alternative methods. Detection at the recycling center would be ideal because it would eliminate the need for consumers to be aware of proper disposal. However, this approach requires that the material be processed so that every piece of wood can be examined. In the case of the Oregon facility, the chipper is mobile and has a relatively short conveyor system that would make it difficult to assess every piece of wood. Even when assessment is possible, problems arise because of the difficulty in sorting individual samples. A number of approaches have been examined for detecting wood treated with waterborne preservatives which would most likely be present in a recycling stream. As mentioned earlier, metal treated wood in many locations tends to weather to a greyish colour that makes it virtually indistinguishable from weathered non-treated wood. Thus, visual detection is likely to be very inaccurate except where other factors, such as the use of dyes or incising in the western U.S. make the wood more recognizable. Nearly all of these systems are copper-based and there are several very sensitive indicators that might be useful. These indicators would have to be sprayed on all of the wood pieces in order to be used. That would require sizable quantities of indicator and some time for the reaction to become evident. This would make it difficult to apply in an industrial environment. There are similar indicators capable of detecting arsenic but these systems would suffer from the same problems. These indicators would also not be suitable for newer materials entering the waste stream, since arsenic based systems were phased out of the residential market in 2003 and will therefore represent an ever-decreasing percentage of the treated material of potential concern.
Heavy metals can also be detected using x-ray technologies, notably x-ray fluorescent spectroscopy (XRF). XRF is widely used in quality control programs for assessing the amounts of copper, zinc, arsenic and chromium in preservative treated wood. It is fairly sensitive to low levels of metal and preliminary studies indicate that the method even detected residual metals in wood through surface coatings [12, 13]; however, it does use ionizing radiation and most current systems use x-ray tubes that may be somewhat fragile for operations within an industrial environment with a great deal of contamination. These are, however, technical issues that could be overcome if there were sufficient levels of treated wood in a waste stream. At present, routine x-ray screening for the presence of treated wood is probably not feasible or economical given the low value of the resulting compost or biomass chips.
An emerging technology for sorting treated wood is laser induced breakdown spectroscopy (LIBS), which uses a laser beam to degrade a segment of the wood surface to produce plasma. The wavelength of the emission from this plasma flash can be characterized spectroscopically to detect the presence of specific elements of interest. This system can also detect coatings, including those with lead based paints, and, if additional pulses are used, can remove the surface coating to detect a preservative underneath [12]. However, each additional laser pulse adds to the time required to assess each sample, thereby slowing production. The system is also sensitive to moisture, which requires additional laser pulses. This technology, while promising, would require additional research to more fully develop it for this application and is probably not feasible given the relatively low value of the resulting products.
While these technologies have the potential to remove treated wood from the recycling stream, they are less efficient because they operate at the end of the disposal path and must, therefore process large quantities of material that do not contain any treatment. Most of these techniques require additional employees or a substantial investment in sophisticated equipment. This renders such approaches inherently inefficient and costly. It is not clear that such approaches would be necessary in cases where the levels of treated wood present are low.
A far better approach to minimizing the presence of treated wood in the recycling stream would be prevention. It is not practical for haulers to remove treated wood during collection. Most haulers have nearly fully automated collection, making it extremely difficult and unsafe to attempt to remove specific contaminants during collection. However, it is possible to begin an education process for homeowners and contractors to make them more aware of the proper disposal of treated wood. For example, many haulers send notices to customers, either in conjunction with their monthly bills or as separate newsletters. These could provide venues for a gradual education of the customer base concerning disposal of treated wood. Publically operated haulers can use their local government newsletters for the same purpose. Most consumers are willing to take positive steps for the environment, provided they are not too onerous. Placing waste in different containers should fit within this arena. Informing customers about the reasons for these efforts may require a bit of education about what treated wood is and why it does not belong in the recycling bin. This would need to be coupled with regular reminders and education as the customer base changes. It may also be useful to educate contractors about proper disposal of decking removed during renovations and to prepare any information in multiple languages in recognition that many employees do not speak English as their first language.
At the same time, where facilities allow customers to drop off materials, creating signage about sorting treated wood could help better inform facility users. In addition, creating a space where customers can drop off material inadvertently mixed into their waste will reduce the need to”sneak” materials. While these efforts are unlikely to eliminate treated wood from the recycling stream, they can reduce the incidence to the point where it does not pose a risk to the final product.
One longer term concern about the incidence of treated wood in the recycling stream will be the gradual introduction of non-metal based systems, particularly for above ground application such as decking. These so-called “organic” preservatives are just emerging in the market and require much more sophisticated instrumentation to detect in treated wood. Most cannot be detected visually or through the use of chemical indicators. In some cases, traces of metals or boron to overcome the problem of using indicators to detect these components; however, it is unclear whether these materials will remain for long periods in the treated products. On the positive side, many of these preservative systems are more rapidly degraded in soil and should not pose a risk of long term accumulation. Some of these systems can also be burned provided the proper temperatures are maintained to ensure complete thermal destruction.
Treated wood appears to be a consistent presence in the recycled wood stream. Ideally, systems would be developed to sort and exclude this material; however, the low value of the resulting wood makes it difficult to justify the costs for sophisticated instrumentation required to accurately distinguish between treated and non-treated wood. The relatively small amounts present at some facilities also make it difficult to justify major capital expenses to remove a minor contaminant. Continuing customer education appears to have the greatest potential for reducing the amounts of treated wood entering the waste stream and can be accomplished with minimal cost.
The incidence of liver cancer is growing worldwide [1, 2] and research estimates that millions of people will be affected by the disease annually by 2025 [3]. Hepatocellular carcinoma (HCC) describes the most common type of liver cancer, responsible for nearly 90% of all cases. The most significant risk factor for HCC development is infection with the hepatitis B virus (HBV), accounting for 50% of all cases [4]. With antiviral drugs, patients have achieved sustained virological response (SVR), reducing the risk of hepatitis C virus (HCV) infection substantially [5]. Nevertheless, the risk of HCC for individuals with cirrhosis remains even after HCV clearance. Nonalcoholic steatohepatitis (NASH) is becoming the main cause of HCC in the West, since it is associated with metabolic syndrome and diabetes mellitus [6]. Furthermore, there have also been reports that aristolochic acid and tobacco are potentially pathogenic cofactors for HCC [7].
The incidence of HCC differs depending on the etiology and type of genotoxins, although there is a greater understanding of the pathophysiology and drivers of HCC over the past few years; clinical applications of these insights have yet to emerge. There are actionable mutations of HCC tumors in approximately 25% of cases; however, most mutations are less than 10%, making proof-of-concept studies difficult [7, 8]. The majority of mutations in HCC remain unsolvable, including those in TERT, TP53, and CTNNB1 [9]. Researchers are also still working on how to establish biomarkers that guide therapy based on molecular and immune classes.
Since the early 2010s, HCC management has vastly improved [8, 10, 11, 12]. The mainstay curative treatments in HCC cases have been hepatic resection and liver transplantation. For tumors down-staged beyond Milan criteria, refinements in patient selection have led to improved surgical resection results and outstanding 10-year post-liver transplantation survival rates [10, 13]. In nonsurgical early-stage HCCs, image-guided ablation using radiofrequency remains the gold standard despite advancements in alternative approaches [12]. Following these potentially curative methods, adjuvant therapies to prevent relapse are an unmet medical need, as randomized controlled trials (RCTs) have so far given poor results. The most frequently used and standard treatment for intermediate-stage HCC for the past two decades has been transarterial chemoembolization (TACE) [14]. Transarterial radioembolization (TARE) has been demonstrated to be effective in phase II studies [15], but guidelines have not yet established it as a primary standard of therapy. The arsenal of intermediate therapy is unlikely to improve in the immediate term with more locoregional devices or radiation oncology methods.
There has been a threat to the use of traditional HCC treatments from systemic medicines, such as tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and monoclonal antibodies. Patients with HCC are predicted to be exposed to systemic therapy 50–60% of the time over their lives, especially in advanced stages of the disease [8]. The development of systemic medicines has progressed dramatically in the last 5 years, with studies showing significant improvements in overall survival and quality of life for patients [8]. As a result of the combination of anti-PDL1 antibody atezolizumab and anti-VEGF antibody bevacizumab, patients with advanced-stage HCC have a quadrupled life expectancy and improved patient-reported outcomes [16]. The most successful single-drug therapies are still sorafenib [17] and lenvatinib [18]. Regorafenib [19], cabozantinib [20], and ramucirumab [21] have similarly shown enhanced survival advantages when switched to single-agent regimens. In 15–20% of responders, single-agent ICIs produce significant therapeutic advantages, although biomarkers have thus far failed to identify this group [22, 23]. Phase III trials are also underway that examine combinations of ICIs with TKIs or PD1/PDL1 axis inhibitors with CTLA4 inhibitors to examine the efficacy of these therapies. The findings of these studies are expected to alter the landscape of managing HCC at all stages of the disease.
In 2018, there were 841,080 new cases of liver cancer, making it the sixth most common cancer worldwide and the fourth leading cause of cancer-related death [3]. Despite an increase in HCC incidence and mortality in different parts of Europe and the United States [24], the highest rates are seen in East Asia and Africa. SEER reports that HCC has been the fastest-growing cancer-related cause of death in the United States since the early 2000s. HCC is expected to be the third leading cause of cancer-related death by 2030 if current trends continue [25].
Chronic liver disease is responsible for more than 90% of all cases of HCC. All forms of cirrhosis are major risk factors for HCC [10, 11]. Annually, 1–6% of patients with cirrhosis die of HCC. HBV and HCV infection, chronic alcohol consumption, and diabetes- or obesity-related NASH all increase the risk for HCC [26]. Hemochromatosis, antitrypsin deficiency, and cirrhosis from primary biliary cholangitis all represent less common risk factors for HCC. Up to 45% of people with hemochromatosis who develop cirrhosis over their lifetime will develop HCC [27].
The cause of HCC in Asia and Africa is 60% HBV infection, while it is 20% in the West [4]. HBV is a DNA virus that can cause insertional mutagenesis and activate oncogenes by integrating into the host genome [28]. HBV increases the risk of liver cancer even if there is no cirrhosis in most patients with HBV-induced HCC. Due to the high prevalence of endemic HBV in East Asia, males (40 years of age) and females (50 years of age) have a high risk of developing HCC, which necessitates surveillance programs. The incidence of HCC in patients in their early 30s or 40s in Africa is likely due to their exposure to aflatoxin B1, a carcinogen, which increases the risk of developing HCC in combination with HBV [29]. Many Asian countries still do not have universal immunization programs, despite the fact that HBV vaccination programs have reduced HCC incidence in some regions [30].
The most common underlying liver disease in North America, Europe, and Japan is chronic HCV infection [4]. In contrast to HBV, HCV is an RNA virus that does not integrate into the host genome, so those who develop cirrhosis or chronic liver disease with bridging fibrosis are at risk of developing HCC. Direct-acting antiviral (DAA) medications have enabled more and more people to achieve a sustained viral response (SVR), thereby reducing their risk of developing HCC by 50–80% [5]. A number of patients, especially those from minority racial or ethnic groups and those from low-income socioeconomic areas, have not been tested for HCV and thus have no idea of their infection [31]. Additionally, people with HCV-induced cirrhosis remain at risk of developing HCC even after they have achieved sustained virologic response (>2% per year) and, thus, they have to be monitored closely [32, 33].
HBV surface antigens are necessary for HDV to replicate and infect. HDV is an RNA virus. Twenty to forty million people are estimated to be infected with HDV worldwide, and these individuals experience more severe liver disease, notably fibrosis and cirrhosis, than people who have only HBV. Furthermore, several cohort studies have found that co-infection with HDV and HBV may lead to an increased risk of HCC than HBV infection alone. A study reported that patients with acute or chronic HDV infection were at a significantly higher risk of HCC than those with a sole HBV infection [34].
A fatty liver, cirrhosis, and HCC are all caused by excessive alcohol consumption. Cirrhosis caused by persistent alcohol consumption, also known as NASH, is becoming increasingly common. HCC is associated with alcohol-induced cirrhosis in 15–30% of cases depending on geographic region, with an annual incidence varying between 1% observed in population-based studies and 2–3% recorded in tertiary care referral centers [35]. There is also evidence that chronic alcohol consumption increases the risk of HCC from other causes; for example, several studies suggest that those who drink alcohol and are HBV carriers are more likely to develop HCC [36]. Although alcohol consumption has some similarities with other forms of cirrhosis, particularly NASH, in some pathophysiological processes, there is an indication that alcohol consumption may have different pro-tumorigenic mechanisms in individuals.
Patients with diabetes mellitus or obesity may also develop HCC from NASH, another major factor contributing to cirrhosis. Due to the rising incidence of obesity, NASH has become a leading cause of cirrhosis around the world. Since 2010, the proportion of HCC caused by NASH has risen quickly, now accounting for 15–20% of cases in the Western world [6]. The proportion of metabolic syndrome and NASH attributable to the population is expected to exceed 20% due to the co-occurrence of these two disorders [37]. The incidence of HCC in NASH-associated cirrhosis (1–2% per year) is lower than in virus-related cirrhosis (3–5% per year), but it remains >1.1% per year, demonstrating that surveillance is cost-effective [38]. Several studies have shown that 25–30% of NASH-related HCC occurrences develop without cirrhosis, limiting the relevance of current surveillance programs that primarily target individuals with cirrhosis. However, the National Veterans Affairs Health System has discovered that the incidence of HCC annually is below the cost-effective threshold in people with non-cirrhotic NASH and surveillance should not be performed [38, 39].
Many sociodemographic factors have been linked to HCC, particularly in individuals with cirrhosis. The risk of HCC increases with age, with those over 70 years of age showing the highest incidence [40]. HCC is also disproportionately male (male-to-female ratio of 2–3:1), which may reflect a clustering of risk factors among men, as well as differences in sex hormones [41]. HCC is more common in racial or ethnic minorities, particularly Hispanics, than in White people, according to studies. This disparity in prevalence could be related in part to the increased prevalence of single-nucleotide polymorphisms in PNPLA3, which are connected to NASH-associated HCC [42]. Smoking has also been linked to an increased risk of HCC in epidemiological studies [43]. Except for studies demonstrating a protective benefit of coffee and aspirin [44], the impact of diet in reducing the incidence of HCC is unknown.
HCC pathophysiology is a multistep process. The early stages of hepatocyte malignant transformation and HCC development are caused by the interaction of several variables. The cellular environment, immune cells, and the severity of chronic liver disease must all be considered, including genetic predisposition, and reciprocal interactions among viral and nonviral risk factors. From the early stages of transformation to invasion and then metastasis, the microenvironment plays an important role in cancer progression.
HCC’s cell of origin is a point of contention. It is possible for liver cancer to originate from liver stem cells, transit-amplifying populations, or mature hepatocytes, just like in any other type of cancer. There is general controversy over whether liver stem cells exist and function. Additionally, mature hepatocytes have a high proliferation capacity after injury, which allows them to survive for long periods of time. Several studies on mouse models reported that HCC is believed to develop from transformed mature hepatocytes; however, other studies suggest HCC may originate from putative stem cells in the liver [45]. Intrahepatic cholangiocarcinomas and tumors with mixed HCC or cholangiocarcinoma form, on the other hand, often appear to emerge from adult hepatocytes, highlighting the principles of metaplasia and cell plasticity (i.e. trans-differentiation). These data back the idea that a tumor’s form and epigenetic landscape may not always represent its cell of origin [46, 47].
High-throughput next-generation sequencing has identified cancer-driver genes recurrently changed in HCC with oncogenic or tumor-suppressive properties. In 80% of cases of HCC, driver gene alterations are found in the TERT promoter, chromosome translocations, telomerase activation, and gene amplification [7, 48]. Studies have shown that mutations in AXIN1 (inhibitors of the Wnt pathway), CTNNB1 (encoding-catenin), or APC (inhibitors of the Wnt pathway) inactivation activate the Wnt-β catenin signaling pathway in 30–50% of cases [7, 48]. CCNE1, TP53, ARID1A, RB1, CCNA2, PTEN, RPS6KA3, ARID2, and NFE2L2 are all known to have mutations or genetic changes that affect cell cycle control. AKT-mTOR and MAPK pathways, as well as genes involved in epigenetic regulation and oxidative stress, have been linked to HCC. AKT-mTOR and MAPK pathways, as well as genes involved in epigenetic regulation and oxidative stress, have been linked to HCC. The recurrent overexpression and activation of oncogenic signaling pathways, including receptor tyrosine kinases, are also linked to focal chromosomal amplification of MYC, CCND1, VEGFA, FGF19, and MET [49]. In spite of the fact that cancer-driver gene mutations can occur at random, certain genes seem to be associated with specific molecular HCC subclasses based on transcriptome profiles and histological phenotypes [8, 9, 50]. At least 20–25% of HCC patients have a potentially actionable mutation, according to current standards [7, 8, 51]. In the pathogenesis of HCC, it has been well documented that risk factors cooperate with cancer-driver mutations. In patients with a GSTT1 null mutation, for instance, the harmful effects of aflatoxin B1 are amplified by HBV infection [52, 53]. In addition, patients who use a lot of alcohol are more likely to have polymorphisms in PNPLA3, TM6SF2, and HSD17B13 [54, 55].
The TERT promoter is the most common locus of HBV-mediated insertional mutagenesis, resulting in overexpression of telomerase, the enzyme responsible for telomere length maintenance [56]. Telomerase activation inhibits the chromosomal erosion that occurs naturally with each cell division as people age. Telomerase activity on the ectopic enhances cell transformation and protects cells against senescence [57]. Other HBV-associated recurrent insertions have been shown to activate potent oncogenes involved in cell cycle control, such as CCNA2 or CCNE1. Replicative stress and complex rearrangements are caused by these oncogenic changes throughout the genome [58]. Adeno-associated virus 2 (AAV2) showed identical insertional oncogenic mutagenesis in a small group of HCC patients, with a shared hot point of the viral insertion inside the TERT promoter, CCNA2, and CCNE1 [59]. These findings show that viral infection activates particular oncogenes, which act as early facilitators of hepatocyte transformation. HCV infection, on the other hand, has no direct carcinogenic effect, and the induction of mutations is driven by the oxidative stress caused by persistent inflammation.
Hepatocytes are subjected to multiple genetic mutations and epigenetic alterations throughout the progression of chronic liver disease and cirrhosis, which are the most common causes of HCC. Several risk factors that cause DNA changes are linked to particular mutational signatures during this process [7, 60]. In exome sequencing analyses of HCC, patients from Asia and Africa who had been exposed to aristolochic acid (A > T mutations in CTG trinucleotide) and aflatoxin B1 (C > A mutations) had mutational signatures 22 and 24, respectively [7, 61]. Mutations of the C > A at dinucleotide sequences in signature 4 were linked with tobacco smoking, while the T > C mutations at TpA dinucleotide in signature 16 were related to alcohol consumption [62]. It remains to be seen whether this discovery can be turned into preventative measures. It is well known that the liver is capable of detoxifying a variety of chemicals that may cause mutations in the hepatocyte genome, leading to the development of cancer.
Several studies have created a molecular and immune categorization for HCC based on genomic, epigenomic, histopathological, and immunological analysis [1, 9, 63]. Molecular classes of HCC have been identified based on the principal molecular drivers and pathways involved [9, 63, 64, 65, 66, 67] or the tumor’s immunology status [8, 68]. The molecular classifications are associated with specific genomic abnormalities, histological signatures, and clinical outcomes. Approximately half of all HCCs are of the proliferation type [49]. The proliferation type is characterized by mutations in TP53 and FGF19 or CCND1 amplification, and it is more common in HBV-associated cancers with poor prognosis. Within the proliferation class, there are two subclasses: proliferation progenitor cells and proliferation-Wnt-TGF cells. Twenty-five to thirty percent of HCC are proliferation-progenitor cells, which are characterized by activation of classical cell proliferation pathways, i.e. the expression of progenitor cell markers (such as EPCAM and FTP) is also related to the activation of signaling pathways (PI3K-AKT-mTOR, RAS-MAPK, and MET and IGF signaling cascades [49, 64]. In alcohol- and HCV-related HCC, non-proliferative tumors represent more than half of all cases; these tumors have better outcomes and correspond to TCGA cluster 2 [65]. Within the nonproliferative class, at least two distinct subgroups have been described: one with dominant canonical Wnt signaling and mutations in CTNNB1 [69] and the other with IFN signaling activation [49].
Reports on the classification of HCC based on immune cell status have added to the knowledge of HCC’s molecular characteristics [68]. This categorization classifies HCC tumors into four subclasses: immunological-active, immune-exhausted, immune-intermediate, and immune-excluded, and gives additional information based on immune features. Immune cell infiltrations are categorized into two subclasses: immune-active and immune-exhausted. In HCC tumors that are immune-active, helper T (CD4+) and cytotoxic T (CD8+) cells are enriched and ICIs are effective. The depletion of CD8+ cells driven by TGF is prevalent in immune-exhausted tumors. In contrast, immune-excluded tumors lack T cell infiltrates and are characterized by a disproportionate increase in regulatory T cells (Tregs), as well as canonical Wnt signaling and other immune-suppressive pathways. Immune-excluded tumors often develop ICI resistance [70].
Obesity has been related to a higher risk of cancer in a variety of organs [71]. Obesity can cause systemic alterations, such as impaired immune function and endocrine abnormalities, which are common in cancers of many types. According to current research, fatty liver disease is quickly becoming the primary cause of HCC in the Western world [6]. The effects of metabolic and oxidative stress, immune dysfunction, abnormal inflammatory responses, impaired endocrine, and adipokine signaling have all been identified as pathways by which NAFLD or NASH cause HCC (Figure 1) [72, 73].
The molecular mechanism of HBV-induced HCC.
Several classical cell proliferation pathways are activated in HBV-associated HCC tumors, including PI3K-AKT-mTOR, RAS-MAPK, MET, and Wnt-TGF. A high chromosomal instability level and frequent TP53 and AXIN1 mutations are additional features of HBV-induced HCC (Figure 2).
The molecular pathogenesis of HCC induced by NASH, HCV, HDV, and alcohol.
Nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis, and hepatitis C virus (HCV) infection promote the development of HCC tumors. Here, the risk factors cause chromosomal instability with frequent mutations in the TERT promoter sequence which, in turn, leads to the CTNNB1 mutations and activation of either WNT-β-catenin signaling pathway or IL6-JAK-STAT signaling pathway. The activation of either or both of these signaling pathway promote the proliferation of progenitor cells leading to an inflammatory tumor microenvironment and ultimately to HCC.
Fatty acid overload causes oxidative stress and endoplasmic reticulum (ER) stress in hepatocytes, resulting in pathological inflammation and cell death [72, 74]. HCC was induced in one study in mice following ER stress-induced inflammation via NF-κB and TNF-α signaling pathways [75]. These toxicological processes of HCC, however, are yet to be demonstrated in human. Hepatocytes with abnormal fatty acid metabolism are susceptible to DNA damage caused by reactive oxygen species (ROS) resulting from mitochondrial dysfunction [76]. Hepatocytes are also affected by changes in the expression of particular metabolic enzymes, which reduces their ability to repair DNA damage [77]. Changes in inflammatory signaling are also a result of the metabolic failure; for example, elevated levels of IL-17 (a tumor-promoting cytokine) have been seen in human NASH [78]. A number of pathogenic lipids are produced as oncometabolites in NASH in addition to increased lipid production [79, 80]. When mTORC2 is continuously activated in mouse hepatocytes, a high level of glucosylceramide is produced, increasing ROS production, which can lead to HCC [79]. Alterations in cholesterol metabolism may also have a role in HCC pathogenesis [80], possibly by causing the generation of pro-tumorigenic nuclear receptor ligands. Although autophagy has antitumor properties, one study found that lipophagy (autophagic destruction of lipid droplets) plays a crucial role in HCC progression. Hepatocytes from NASH patients and a mouse model of HCC overexpress sequestosome 1 (also called p62), a lipophagy regulator [81]. Patients with NASH had a higher risk of HCC than those with NAFLD according to studies [6]. In one experiment, fatty acid-induced oxidative stress in hepatocytes increased the expression of STAT1 and STAT3, two pro-inflammatory transcription factors that generally operate in tandem [82]. Surprisingly, a high level of STAT1 promoted NASH progression in this mouse model, while a high level of STAT3 promoted HCC, both independently [82]. Accordingly, similar inflammatory signals may promote progression from NAFLD to NASH or HCC in different ways. This is because NAFLD is more common in the general population than NASH [6]; the data indicate the need to understand how NAFLD, regardless of NASH, can lead to HCC. When hepatocytes are overloaded with fatty acids, the increased ER stress, pathological lipophagy, ROS generation, and a lowered reducing power (low NADH or NADPH levels) may combine to generate oncogenic genetic changes and accelerate the development of malignant cells.
Based on transcriptomic-based phenotypic classes, hepatocellular carcinoma (HCC) can be divided into two primary molecular groupings [49, 64, 65, 66, 67]. More aggressive tumors with weak histological differentiation, high vascular invasion, and higher levels of alpha-fetoprotein (AFP) belong to the proliferation class [50]. In S1 or iCluster 3 [64, 65], Wnt-TGF activation leads to an immune-exhausted phenotype [68], while in S2 or iCluster 1 [64, 65], stem cells markers (CK19, EPCAM) as well as IGF2 and EPCAM signaling pathways are expressed [50]. In hepatitis B virus (HBV)-associated tumors, cell proliferation pathways such as PI3K-AKT-mTOR, RAS-MAPK, MET, and IGF are usually activated. Furthermore, numerous TP53 mutations, high chromosomal instability, and widespread DNA hypomethylation are also characteristics of this group. The nonproliferation class consists of tumors that are less aggressive, well-differentiated histologically, have low AFP levels, and have fewer vascular invasions [50]. These tumors can be caused by nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), or infection with hepatitis C virus (HCV) [49, 64, 65, 66, 67]. This class is divided into two distinct subgroups: the WNT––catenin CTNNB1 subclass has frequent CTNNB1 mutations and activated WNT––catenin signaling, leading to an immune-excluded phenotype with low immune infiltration [49, 67, 68]; and the interferon subclass has a highly activated IL6-JAK-STAT signaling pathway, leading to a more inflamed microtumor with many TERT promoter mutations, and this class has chromosomal stability [63, 64, 65, 66, 67, 68].
The histological characteristic of NASH is immune cell infiltration of the obese liver [72]. The establishment of animal models that accurately reproduce human HCC is critical for basic pathogenesis research as well as translational research [83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97]. Immune cells and cytokines have been found to have an essential role in the pathogenesis of HCC in several experimental types. In mouse models, for example, persistent NASH causes CD8+ T cell activation, which leads to hepatocyte destruction and HCC [98]. As a consequence of NAFLD, intrahepatic CD4+ T cells are selectively depleted, which are necessary to initiate an effective adaptive immune response against tumors [99]. Additionally, B cells, Treg cells, natural killer cells, and other myeloid cells have been associated with NASH-induced HCC [72, 73]. The activation and recruitment of platelets in the liver also contribute to HCC formation in mice, specifically via platelet glycoprotein Ib (GPIb) signaling, which is in line with clinical data [100], implying that this pathway has the therapeutic potential [101]. The causal function of NASH in HCC was also linked to a changed cytokine milieu [74]. NASH, for example, has been demonstrated to overexpress hepatic IL-6 and TNF-α, which are both causes of HCC in various etiologies [102].
On the background of fatty liver disease, all of the mechanisms described earlier could promote HCC at the same time. Their relative involvement to human HCC, however, is uncertain at this time. The comparison of mutational signatures in NASH-associated HCC versus HCC from other causes should aid in determining the relative contributions of different variables.
HCC is an archetypal inflammation-related malignancy, with chronic inflammation caused by viral hepatitis, excessive alcohol consumption, NAFLD, or NASH accounting for 90% of the HCC burden. In the development of HCC [103], the immunological microenvironment plays a critical role. Immune infiltrates are associated with a better prognosis in HCC, possibly due to more effective antitumor immunity [68, 104]. Immune signals such as IL-6, lymphotoxin-, and TNF-α have been shown to accelerate hepatocarcinogenesis and impact tumor aggressiveness in mouse models of HCC [47, 105], yet immune responses can also slow the course of liver cancer [103]. In addition, the liver has the greatest number of immune cells in the body and has a unique immunological state that allows it to survive the constant influx of inflammatory signals coming from the gut [103]. Understanding this specific hepatic immune system is likely important given the intricate interplay between malignant hepatocytes and the liver immune system [103, 106]. A surprising finding in mice and humans is that VEGF released by malignant hepatocytes creates an immune-tolerant, pro-tumorigenic microenvironment [49, 107], suggesting that inhibiting the VEGF cascade might have a positive effect on liver immunity by modifying VEGF production. Interestingly, the combination of ICIs and certain targeted medicines such as VEGF inhibitors had greater survival advantages than the use of single agents [16, 108].
It has been shown that hepatocytes in chronically inflamed livers interact with numerous cell types including macrophages, endothelial cells, stellate cells, and various types of lymphocytes [103, 106]. Due to its importance in immuno-oncology therapy, researchers are paying more attention to the adaptive immune system’s involvement. Mouse models have revealed that practically every immune cell type can play both pro-tumor and antitumor roles [103]. In addition to producing pro-tumorigenic cytokines and growth factors that support tumor cell proliferation or inhibit apoptosis, immune cells also diminish nearby lymphocytes’ antitumorigenic function. The NF-B and JAK-STAT pathways have been identified as major inflammatory signaling pathways implicated in the promotion of HCC in studies [109], and this assertion was confirmed in a transcriptomic analysis of human HCC [110]. Immune monitoring and the destruction of premalignant or completely changed malignant hepatocytes are the adaptive immune system’s main antitumor functions [104].
The main effectors of antitumor immunity are cytotoxic T (CD8+) cells. As a result, one study found that depleting these T cells in mice increased HCC burden [111], while another found that these T cells promote premalignant hepatocyte surveillance [112]. Several studies in mice have shown that the depletion of CD8+ T cells can also reduce tumor burden [98]. Analyses of human HCC samples suggest that some individuals have functional CD8+ T lymphocytes that produce antitumor effector molecules such as granzyme A, granzyme B, and perforin [113]. However, single-cell sequencing of human HCC T cells has revealed that the CD8+ T cells are often dysfunctional in HCC [114]. There is no clear understanding of the causes of CD8+ T cell dysfunction, which leads to diminished proliferation and the inability to generate cytotoxic effector molecules. Increasing numbers of Treg cells within the tumor are linked with poorer clinical outcomes in HCC, and Treg cells are thought to be a primary cause of T cell dysfunction [115]. Treg cells’ immunosuppressive capabilities may be mediated by CD10 and TGF116 production, suggesting that blocking these cytokines could make HCC more susceptible to ICIs. HCC-infiltrating Treg cells are known to suppress immune responses through the hyaluronic acid receptor, layilin, which is interesting [116]. As a result of a layilin induction, CD8+ T cells exhibited dysfunction in human HCC, and layilin overexpression was associated with distinct mRNA expression signatures in lymphocytes [114].
Although B cells were once assumed to be innocent bystanders in cancer, new data suggest that they have an active role in the adaptive immune system’s interaction with cancer [117]. B lymphocytes both stimulated and inhibited tumor growth in mice models of HCC [118]. Furthermore, one study found that IgA-expressing cells actively suppressed CD8+ T cell activity, which aided HCC growth [111]. Furthermore, studies in humans and mice have shown that tertiary lymphoid structures, which are crucial for adaptive immune responses to cancer [119], have both pro-tumor and antitumor capacity in HCC [120, 121].
The risk of HCC is high enough to warrant surveillance once the patient has reached cirrhosis, even though some etiologies (for instance, HCV versus autoimmune hepatitis) are more likely to cause HCC than others [10, 11]. In response to chronic injury, hepatic stellate cells play an important role [122]. Upon activation, it undergoes phenotypic changes and synthesizes components of the extracellular matrix, mainly collagen, as well as growth factors, which promote neoangiogenesis, endothelial cell migration, and fibrosis [123]. Cirrhosis and portal hypertension have a histological substrate in which the hepatic architecture is distorted and the vasculature is disordered. Premalignant senescent hepatocytes respond to this condition by secreting chemokines that impair senescent surveillance and immune-mediated tumor suppression in vivo [112]. Experimental models have also demonstrated that CD4+ cells are relevant in promoting NAFLD-related HCC [99], and the interaction between the innate immune system and the intestinal microbiota plays a role in promoting the development of HCC [124, 125]. In HCC, the immune system, in addition to fibrosis, plays a significant role in the cancer field effect. The cancer field effect refers to the favorable microenvironment in cirrhosis that favors tumor formation. The primary molecular elements unregulated in this microenvironment have been identified through various genomic investigations. Several gene profiles obtained from cirrhotic tissue are associated with the probability of developing HCC and can be utilized to risk stratify patients [110, 126, 127]. The presence of these gene signatures is associated with cancer risk, the incidence of hepatic decompensation in patients, and overall survival [126, 127]. More research has been done on the genetic characteristics of the cirrhosis inflammatory milieu that contribute to HCC development [128]. In 50% of neighboring cirrhotic tissue from HCC patients, an immune-mediated cancer field molecular subclass was observed. In addition to lymphocyte infiltration, this subclass can be further divided based on pro-inflammatory or immunosuppressive signal activation. In the immunosuppressive subclass, which accounted for 10% of patients and had a threefold higher risk of developing HCC, TGF signaling, T-cell exhaustion, and overexpression of immunological checkpoints (such as CTLA4, TIGIT, and LAG3) were shown to be more prevalent [128]. Modulating the tumor microenvironment’s role in HCC’s natural history would be a compelling reason for altering the dynamic crosstalk between hepatocytes and the hepatic immune system [103].
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Catarina Guedes and F. Xavier Malcata",authors:[{id:"83136",title:"Prof.",name:"F. Xavier",middleName:null,surname:"Malcata",slug:"f.-xavier-malcata",fullName:"F. Xavier Malcata"}]},{id:"30642",doi:"10.5772/34423",title:"Meiofauna as a Tool for Marine Ecosystem Biomonitoring",slug:"meiofauna-as-a-tool-for-marine-ecosystem-monitoring",totalDownloads:3912,totalCrossrefCites:22,totalDimensionsCites:84,abstract:null,book:{id:"1689",slug:"marine-ecosystems",title:"Marine Ecosystems",fullTitle:"Marine Ecosystems"},signatures:"Maria Balsamo, Federica Semprucci, Fabrizio Frontalini and Rodolfo Coccioni",authors:[{id:"100075",title:"Prof.",name:"Maria",middleName:null,surname:"Balsamo",slug:"maria-balsamo",fullName:"Maria Balsamo"},{id:"104309",title:"Dr.",name:"Federica",middleName:null,surname:"Semprucci",slug:"federica-semprucci",fullName:"Federica Semprucci"},{id:"104311",title:"Dr.",name:"Fabrizio",middleName:null,surname:"Frontalini",slug:"fabrizio-frontalini",fullName:"Fabrizio Frontalini"},{id:"104313",title:"Prof.",name:"Rodolfo",middleName:null,surname:"Coccioni",slug:"rodolfo-coccioni",fullName:"Rodolfo Coccioni"}]},{id:"35136",doi:"10.5772/29571",title:"Transmission Biology of the Myxozoa",slug:"transmission-biology-of-the-myxozoa",totalDownloads:2726,totalCrossrefCites:35,totalDimensionsCites:64,abstract:null,book:{id:"2052",slug:"health-and-environment-in-aquaculture",title:"Health and Environment in Aquaculture",fullTitle:"Health and Environment in Aquaculture"},signatures:"Hiroshi Yokoyama, Daniel Grabner and Sho Shirakashi",authors:[{id:"78409",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Yokoyama",slug:"hiroshi-yokoyama",fullName:"Hiroshi Yokoyama"},{id:"83562",title:"Dr.",name:"Daniel",middleName:"Stefan",surname:"Grabner",slug:"daniel-grabner",fullName:"Daniel Grabner"},{id:"122643",title:"Dr.",name:"Sho",middleName:null,surname:"Shirakashi",slug:"sho-shirakashi",fullName:"Sho Shirakashi"}]},{id:"24078",doi:"10.5772/26795",title:"Photobacterium damselae subsp. damselae, an Emerging Pathogen Affecting New Cultured Marine Fish Species in Southern Spain",slug:"photobacterium-damselae-subsp-damselae-an-emerging-pathogen-affecting-new-cultured-marine-fish-speci",totalDownloads:3795,totalCrossrefCites:19,totalDimensionsCites:45,abstract:null,book:{id:"612",slug:"recent-advances-in-fish-farms",title:"Recent Advances in Fish Farms",fullTitle:"Recent Advances in Fish Farms"},signatures:"A. Labella, C. Berbel, M. Manchado, D. Castro and J.J. Borrego",authors:[{id:"67855",title:"Prof.",name:"Juan J.",middleName:null,surname:"Borrego",slug:"juan-j.-borrego",fullName:"Juan J. Borrego"},{id:"71146",title:"Dr.",name:"Alejandro",middleName:null,surname:"Labella",slug:"alejandro-labella",fullName:"Alejandro Labella"},{id:"71148",title:"Dr.",name:"Concepcion",middleName:null,surname:"Berbel",slug:"concepcion-berbel",fullName:"Concepcion Berbel"},{id:"71149",title:"Dr.",name:"Manuel",middleName:null,surname:"Manchado",slug:"manuel-manchado",fullName:"Manuel Manchado"},{id:"71151",title:"Dr.",name:"Dolores",middleName:null,surname:"Castro",slug:"dolores-castro",fullName:"Dolores Castro"}]}],mostDownloadedChaptersLast30Days:[{id:"35141",title:"Antibiotics in Aquaculture – Use, Abuse and Alternatives",slug:"antibiotics-in-aquaculture-use-abuse-and-alternatives",totalDownloads:19357,totalCrossrefCites:138,totalDimensionsCites:293,abstract:null,book:{id:"2052",slug:"health-and-environment-in-aquaculture",title:"Health and Environment in Aquaculture",fullTitle:"Health and Environment in Aquaculture"},signatures:"Jaime Romero, Carmen Gloria Feijoo and Paola Navarrete",authors:[{id:"72898",title:"Dr.",name:"Jaime",middleName:null,surname:"Romero",slug:"jaime-romero",fullName:"Jaime Romero"},{id:"79684",title:"Dr.",name:"Paola",middleName:null,surname:"Navarrete",slug:"paola-navarrete",fullName:"Paola Navarrete"},{id:"83411",title:"Dr.",name:"Carmen",middleName:null,surname:"Feijoo",slug:"carmen-feijoo",fullName:"Carmen Feijoo"}]},{id:"69948",title:"Floating Cage: A New Innovation of Seaweed Culture",slug:"floating-cage-a-new-innovation-of-seaweed-culture",totalDownloads:974,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Eucheumatoid cultivation continues to expand with a variety of methods that can increase production. This chapter will discuss an innovation in seaweed cultivation of the genus Eucheuma, which is the prime marine commodity in the tropical regions of the world. Research conducted during 2015-2017 and 2019 in Southeast Sulawesi Province, Indonesia, provided an overview of the use of floating cage that showed very significant growth results. The research result showed that the growth rates of Eucheuma denticulatum and Kappaphycus alvarezii in floating cage seemed faster and resulted in better thallus morphology. Daily production of E. denticulatum and K. alvarezii that were cultivated in floating cage was higher than daily production of E. denticulatum and K. alvarezii cultivated on longline. Specific growth rate (SGR) of E. denticulatum and K. alvarezii cultivated by using floating cage method was also higher than E. denticulatum and K. alvarezii cultivated by using longline method. Moreover, the cultivation by using floating cages produces good growth rates with no effect of herbivore attacks.",book:{id:"8928",slug:"emerging-technologies-environment-and-research-for-sustainable-aquaculture",title:"Emerging Technologies, Environment and Research for Sustainable Aquaculture",fullTitle:"Emerging Technologies, Environment and Research for Sustainable Aquaculture"},signatures:"Ma’ruf Kasim, Abdul Muis Balubi, Ahmad Mustafa, Rahman Nurdin, Rahmad Sofyan Patadjai and Wardha Jalil",authors:[{id:"309893",title:"Prof.",name:"Maruf",middleName:null,surname:"Kasim",slug:"maruf-kasim",fullName:"Maruf Kasim"},{id:"313040",title:"MSc.",name:"Abdul Muis",middleName:null,surname:"Balubi",slug:"abdul-muis-balubi",fullName:"Abdul Muis Balubi"},{id:"313041",title:"MSc.",name:"Wardha",middleName:null,surname:"Jalil",slug:"wardha-jalil",fullName:"Wardha Jalil"},{id:"313042",title:"MSc.",name:"Ahmad",middleName:null,surname:"Mustafa",slug:"ahmad-mustafa",fullName:"Ahmad Mustafa"},{id:"313043",title:"MSc.",name:"Rahman",middleName:null,surname:"Nurdin",slug:"rahman-nurdin",fullName:"Rahman Nurdin"},{id:"313044",title:"MSc.",name:"Rahmat Sofyan",middleName:null,surname:"Patadjai",slug:"rahmat-sofyan-patadjai",fullName:"Rahmat Sofyan Patadjai"}]},{id:"62842",title:"Integrated Rice and Aquaculture Farming",slug:"integrated-rice-and-aquaculture-farming",totalDownloads:1919,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The burning problems like scarcity of food for ever-growing human population in the present world are addressed by adapting various methods for production of protein, carbohydrate, oils and other food materials. One of the methods to produce high amount of food is integrated farming including rice-aquaculture farming, which produces protein and carbohydrate as major components besides others. Rice-aquaculture farming produces grain (carbohydrate) and animal protein without affecting the quality and quantity of rice yield on the same piece of land and renders additional financial gain besides main crop (rice) like conventional monoculture. The aquatic species grown in the integrated culture are mainly distinct types of fishes, selected crustaceans and other selected species. Profitable rice-aquaculture integrated farming is popular in Asian countries than in Western countries. However, the integrated rice-aquaculture farming has its own limitations. The type of methods, culture species, influencing factors, and pros and cons of rice-aquaculture integrated farming are discussed in the present chapter.",book:{id:"7229",slug:"aquaculture-plants-and-invertebrates",title:"Aquaculture",fullTitle:"Aquaculture - Plants and Invertebrates"},signatures:"Pamuru Ramachandra Reddy and Battina Kishori",authors:[{id:"242524",title:"Dr.",name:"Ramachandra Reddy",middleName:null,surname:"Pamuru",slug:"ramachandra-reddy-pamuru",fullName:"Ramachandra Reddy Pamuru"},{id:"255022",title:"Dr.",name:"Kishori",middleName:null,surname:"Battina",slug:"kishori-battina",fullName:"Kishori Battina"}]},{id:"24074",title:"Embryonic and Larval Development of Freshwater Fish",slug:"embryonic-and-larval-development-of-freshwater-fish",totalDownloads:7466,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"612",slug:"recent-advances-in-fish-farms",title:"Recent Advances in Fish Farms",fullTitle:"Recent Advances in Fish Farms"},signatures:"Faruk Aral, Erdinç Şahınöz and Zafer Doğu",authors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"},{id:"29132",title:"Dr.",name:"Zafer",middleName:null,surname:"Dogu",slug:"zafer-dogu",fullName:"Zafer Dogu"},{id:"39952",title:"Dr.",name:"Erdinc",middleName:null,surname:"Sahinoz",slug:"erdinc-sahinoz",fullName:"Erdinc Sahinoz"}]},{id:"68966",title:"Novel Biofloc Technology (BFT) for Ammonia Assimilation and Reuse in Aquaculture In Situ",slug:"novel-biofloc-technology-bft-for-ammonia-assimilation-and-reuse-in-aquaculture-in-situ",totalDownloads:1951,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Ammonia is one of the most harmful risks for success of fish and shrimp culture. There is no effective solution for harmlessness of ammonia in traditional aquaculture operations except exchanging water, which would bring negative effects on environment, or fixing expensive equipment. Biofloc technology (BFT) that appeared in recent years supplies a novel solution for this issue without exchanging huge water and fixing equipment. This technology could assimilate ammonia almost in real time with many other supplemental benefits. Because of the very high nutritional value for fish and shrimp, bioflocs, the by-product of BFT, could also be reused as a complemented food in situ or a gradient for feedstuff to replace expensive fishmeal or be processed to pellet diet to feed fish and shrimp directly. However, some aspects with regard to the effective use of biofloc as a food source for fish and shrimp, such as high lipid content, productivity, and palatability, need to be further researched in detail.",book:{id:"8928",slug:"emerging-technologies-environment-and-research-for-sustainable-aquaculture",title:"Emerging Technologies, Environment and Research for Sustainable Aquaculture",fullTitle:"Emerging Technologies, Environment and Research for Sustainable Aquaculture"},signatures:"Hai-Hong Huang",authors:[{id:"305215",title:"Dr.",name:"Hai-Hong",middleName:null,surname:"Huang",slug:"hai-hong-huang",fullName:"Hai-Hong Huang"}]}],onlineFirstChaptersFilter:{topicId:"32",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. Since 2014 she has been responsible for the Clinical Analysis Laboratory of the CEU-Cardenal Herrera University Veterinary Clinical Hospital.",institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"439435",title:"Dr.",name:"Feda S.",middleName:null,surname:"Aljaser",slug:"feda-s.-aljaser",fullName:"Feda S. Aljaser",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"428600",title:"MSc.",name:"Adriana",middleName:null,surname:"García-Alarcón",slug:"adriana-garcia-alarcon",fullName:"Adriana García-Alarcón",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428599",title:"MSc.",name:"Gabino",middleName:null,surname:"De La Rosa-Cruz",slug:"gabino-de-la-rosa-cruz",fullName:"Gabino De La Rosa-Cruz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428601",title:"MSc.",name:"Juan Carlos",middleName:null,surname:"Campuzano-Caballero",slug:"juan-carlos-campuzano-caballero",fullName:"Juan Carlos Campuzano-Caballero",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular Economy, Contingency Planning and Response to Disasters, Ecosystem Services, Integrated Urban Water Management, Nature-based Solutions, Sustainable Urban Development, Urban Green Spaces",scope:"