Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\n
This 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.
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We 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\n
Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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The emerging food crisis calls for development of sustainable food production, and the quality and safety of the food produced should be guaranteed. The book contains thirteen chapters and is divided into two sections. The first section is related to social issues rising from food insufficiency in the third world countries, and is titled "Sustainable food production: Case studies". The case studies of semi-arid Africa, Caribbean and Jamaica, Burkina Faso, Nigeria, Pacific Islands, Mexico and Brazil are discussed. \nThe second section, titled "Scientific Methods for Improving Food Quality and Safety", covers the methods for control and avoidance of food contaminants. 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Coordinator of 15 international education and scientific projects for Bulgaria : Altener, Thermie, PECO, Bulgarian Research Fund, Socrates-Erasmus Institutional Co-ordinator (2000-2007), Quality Culture (2003-2004), Round II, Quality Culture Round III (2005 ), ISEKI-FOOD (Erasmus Network; 2005 –2012 ), FP7, Horizon2020. \n\nEuropean Expert for evaluation of ALTENER proposals in 2002 and European Expert for evaluation of ERASMUS proposals in 2006 – 2009. \n\nShe has published over 150 scientific papers.",institutionString:null,position:"Co-founder",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"324",title:"Food Chemistry",slug:"agricultural-and-biological-sciences-bromatology-food-chemistry"}],chapters:[{id:"26513",title:"To Meet Future Food Demands We Need to Change from Annual Grain Legumes to Multipurpose Semi-Perennial Legumes",doi:"10.5772/32618",slug:"to-meet-future-food-demands-we-need-to-change-from-annual-grain-legumes-to-multipurpose-semi-perenni",totalDownloads:1807,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Henning Høgh-Jensen",downloadPdfUrl:"/chapter/pdf-download/26513",previewPdfUrl:"/chapter/pdf-preview/26513",authors:[{id:"92132",title:"Dr.",name:"Henning",surname:"Hogh-Jensen",slug:"henning-hogh-jensen",fullName:"Henning Hogh-Jensen"}],corrections:null},{id:"26514",title:"Issues in Caribbean Food Security: Building Capacity in Local Food Production Systems",doi:"10.5772/32157",slug:"issues-in-caribbean-food-security-building-capacity-in-local-food-production-systems",totalDownloads:6769,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:null,signatures:"Clinton Beckford",downloadPdfUrl:"/chapter/pdf-download/26514",previewPdfUrl:"/chapter/pdf-preview/26514",authors:[{id:"90387",title:"Dr.",name:"Clinton",surname:"Beckford",slug:"clinton-beckford",fullName:"Clinton Beckford"}],corrections:null},{id:"26515",title:"Permanent Internal Migration as Response to Food Shortage: Implication to Ecosystem Services in Southern Burkina Faso",doi:"10.5772/33857",slug:"permanent-internal-migration-as-response-to-food-shortage-implication-to-ecosystem-services-in-south",totalDownloads:2014,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:null,signatures:"ssa Ouedraogo, Korodjouma Ouattara, Séraphine Kaboré/Sawadogo, Souleymane Paré and Jennie Barron",downloadPdfUrl:"/chapter/pdf-download/26515",previewPdfUrl:"/chapter/pdf-preview/26515",authors:[{id:"97411",title:"Dr.",name:"Issa",surname:"Ouedraogo",slug:"issa-ouedraogo",fullName:"Issa Ouedraogo"},{id:"100865",title:"Dr.",name:"Korodjouma",surname:"Ouattara",slug:"korodjouma-ouattara",fullName:"Korodjouma Ouattara"},{id:"100866",title:"Dr.",name:"Souleymane",surname:"Paré",slug:"souleymane-pare",fullName:"Souleymane Paré"},{id:"128319",title:"Dr.",name:"Séraphine",surname:"Kaboré/Sawadogo",slug:"seraphine-kaboresawadogo",fullName:"Séraphine Kaboré/Sawadogo"},{id:"136548",title:"Dr.",name:"Jennie",surname:"Barron",slug:"jennie-barron",fullName:"Jennie Barron"}],corrections:null},{id:"26516",title:"Food Security and Challenges of Urban Agriculture in the Third World Countries",doi:"10.5772/34569",slug:"food-security-and-challenges-of-urban-agriculture-in-the-third-world-countries",totalDownloads:3826,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"R.A. 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1. Introduction
The bile duct carcinoma or known as cholangiocarcinoma (CCA) by the definition is a malignancy that originate from cholangiocytes lining the biliary tree. It is included in liver malignancy and become the second most common primary liver malignancy after hepatocellular carcinoma. [1, 2] Incidence of this malignancy is 10–20% cases of all hepatic cancer. [2, 3] Although cholangiocarcinoma is a rare cancer, it has an aggressive feature with very poor prognosis. The data showed that the incidence of cholangiocarcinoma among gastrointestinal cancer approximately reaches 3% but has nearly 20% of death from all hepatobiliary cancer. [3, 4] In addition, cholangiocarcinoma is a clinically silent disease at early stage. Therefore, the diseases are usually diagnosed at advanced stage with poor prognosis.
CCA may occur anywhere in the biliary tract, however, based on where the tumor arises in the biliary tree, it is classified into intrahepatic (iCCA) and extrahepatic bile duct cholangiocarcinoma (eCCA). Extrahepatic bile duct cholangiocarcinoma is divided into two types, perihilar (pCCA) and distal (dCCA) cholangiocarcinoma. iCCAs arises above the second - order of the bile ducts. In contrary, the point anatomical which is distinction pCCA and dCCA is the insertion of the cystic duct. The majority of cholangiocarcinoma are in the perihilar (50–60% cases) and distal region (20–30% cases), and only 10% of CCA are located in intrahepatic. [5]
The tumor is considered rare in most countries with incidence rate from 2001 to 2015 was 1.26 cases per 100,000 persons and has a mortality rate 1–6 per 100,000. [1, 6] Nevertheless, this malignancy is still an endemic disease with high prevalence and incidence in some countries or regions such as Thailand and South Korea. The epidemiological profile of cholangiocarcinoma varies widely across the world, which is reflecting the exposure of different risk factor, such as chronic inflammatory disease of the biliary tract, specific infectious disease, and congenital malformation. In western countries, primary sclerosing cholangitis (PSC) causing biliary obliterative fibrosis, is the major etiology of CCA. [7] Specific in endemic area, Northeast Thailand, with incidence rate 118.5 per 100.000, which is 100 times higher than the global rate. [8] Number of mortality cases from liver and bile duct cancer is the leading cause of death in Thai males and places the third place in female with total number 28.000 deaths per year. [9] Northeast region of Thailand showed the highest number of liver mortality, comprising 70% of cases. [9] In this area, incidence of CCA is strongly related to liver fluke infestation that is endemic in Mekong River. Liver fluke infection is caused by water-borne parasites known as Opisthorchis viverrini, Clonorchis sinensis, and Opisthorchis feluneus. These parasites are transmitted to human by the consumption of raw, pickled, or undercooked infected fish associated with local tradition and poor income. [10, 11, 12]
The life cycle of this parasite is quite complex, involving two intermediate host (snail to fish) and including several changes of morphological feature. Fish contaminated with metacercaria is ingested by the human. [2] Infected human excretes the egg produced by the mature adult worms in their feces. [2, 13] Feces then contaminated the fresh water and then ingested by snail and the larva develop and hatch in the digestive tract of the snail. [2, 13] After that, thousands of cercariae were excreted into the water and penetrate the skin fish, encyst, and forming metacercaria. In the body of human, this parasite excyst in the duodenum and ascend to the bile duct via the ampulla of Vater then migrate further into the smaller and proximal bile duct, then become mature worm and able to sexually produce. [2, 13] Adult worm could survive up to 25 years in the biliary tree and causing mild symptoms such as malaise, abdominal discomfort, and diarrhea. Long term complication of this infection associated with hepatomegaly, chronic infection, cholecystitis, gallstone, and periportal fibrosis. [2, 13] Long term of chronic inflammation found to be a major etiological precursor of hepatobiliary malignancy, predominantly of CCA. Once a person is infected and suffered from chronic infection and inflammation, the risk for having CCA is increasing and could present within 30–40 years after infection. [11] Until now, the prognosis of CCA is remain poor and death tend to occur within 3–6 months after diagnosis. [11] There are several hypothesizes on the mechanism or pathway how the chronic infection could develop become malignancy: 1) mechanical damage caused by the fluke sucker, 2) fluke toxic secretary product, and 3) immunopathological host response. [11] These pathways then caused proliferative response and formation of precursor lesion such as epithelial and adenomatous hyperplasia, and goblet cell metaplasia. [11]
Beside parasite infection, primary sclerosing cholangitis (PSC) is another common etiology of cholangiocarcinoma, especially in the western population. PSC is a progressive cholestatic biliary characterized by the chronic inflammation that leads to destruction of the intra and extrahepatic bile duct. [14] The incidence rate of PSC ranges from 0 to 1.3 per 100.000 people. [15] At early stage, PSC is asymptomatic and is usually already diagnosed at advanced stage whereas jaundice and pruritus are the major complaint due to cholestasis. It has been also strongly associated with inflammatory bowel disease (IBD). On the other hand, PSC is often found with portal hypertension, cirrhosis, and in hepatobiliary and colorectal malignancies. [16, 17]
The other risk factor for developing CCA is biliary stones which is formed in the biliary tree, substantially in intrahepatic bile duct or known as hepatolithiasis. Biliary stones are typically concomitant with biliary stasis, cholangitis, strictures, and bacterial infection, leading to long term inflammation and biliary injury, and at the end, increasing the risk of malignant cholangiocytes growth. [18] Abnormal morphological also increase the risk for malignant transformation. Choledochal cysts is a rare congenital malformation characterized by dilatation of the biliary tree, can be single or multiple, and can be developed in the intra or extra hepatic bile ducts. [17, 19] Moreover, the coincidence of abnormal pancreatobiliary duct junctions increases the possibility of cholangiocarcinogenesis. This due to pancreatic enzyme reflux, cholestasis, and elevated bile acid concentrations. [19]
Exposure to chemical carcinogens such as Thorotrast, halogenated hydrocarbon solvent, and 1,2-dichloropropane were found to be associated with CCA incidence. [20, 21] Carcinogens-induced liver insult has been showed to promote hepatocyte remodeling, genomic instability, DNA methylation, and disrupt the liver architecture. Moreover, some studies reported few genetic mutations related to hepatobiliary malignancy. [22] Hepatic disease associated with CCA include alcoholic liver disease, cirrhosis, and cholangitis are included become risk factor. [17]
Diagnosis of CCA is quite challenging. CCA is generally asymptomatic in the early stage. Therefore, management of this malignancy is often delayed due to late diagnosed, where it already metastasis or compress the bile duct. The clinical features of CCA are heterogenous, with general malaise, cachexia, abdominal pain, night sweats, fatigue, weight loss, asthenia, and/or jaundice which is more frequent symptom in pCCA and dCCA due to biliary tract obstruction. [23, 24] Diagnosis of CCA is usually confirmed by combining nonspecific biomarkers in serum, biopsy specimens, and imaging technique. To date, there is no specific serum marker available for diagnosing CCA. Liver function parameters such as serum bilirubin, alkaline phosphatase, and aminotransferase enzyme usually elevate when biliary obstruction is presence. [24, 25] However, it is not specific signs for biliary malignancy. Serum tumor marker such as carbohydrate antigen (CA) 19–9, CA-125, and carcinoembryonic antigen (CEA) are the most widely used markers for suspected CCA. [25] But this diagnostic tool should not be used alone due to their poor diagnostic performance and inherent limitations.
Imaging techniques which are required to help diagnosis CCA are trans-abdominal ultrasonography (US), contrast-enhanced ultrasonography (CEUS), CT scan, and MRI. Becoming diagnostic tools, imaging techniques play a key role in the management of CCA in term of diagnosis, staging, follow-up, and assessment of favorable treatment response. The accuracy of diagnosis is depending on the anatomical location and growth pattern of CCA. Magnetic resonance cholangiopancreatography (MRCP) has the higher diagnostic accuracy for sizing strictures and localizing. [24, 25]
But unfortunately, there are no specific CCA radiology pattern exists. Therefore, histopathology or cytological analysis is also necessary for confirming the diagnosis. Definitive diagnosis is usually made by undergoing endoscopic retrograde cholangiopancreatography (ERCP) procedure for fluid cytology, brush cytology, fluorescence in situ hybridization (FISH), and cholangioscope or chromoendoscopy-guided biopsy. [26, 27, 28] Those multiple diagnostic modalities are required to 1) establish strictures anatomical location; 2) distinguish between benign and malignant strictures; 3) differentiate CCA from gallbladder cancer; 4) stage and grade the tumor; and 5) plan treatment approach. Based on WHO classification of biliary tract cancer it is showing an adenocarcinoma or mucinous carcinoma, with tubular and/or papillary structures and a variable fibrous stroma. [24, 25]
Determine staging of CCA is important for choosing the treatment, its resectability, and the outcome of the treatment. TNM classification system of American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) has been used at present to determine the staging of CCA. TNM staging system is based on imaging tests which is evaluating the number of primary nodules, vascular invasion, direct extension in neighboring tissue, and bile duct involvement. [29] pCCA can be further divided according to the Bismuth-Corlette classification, depending on the size of the tumor, disease extension in the main bile duct, hepatic artery and/or portal involvement, lymph node involvement, distant metastasis, and remnant liver volume after resection. [30] iCCA could be classified based on 3 growth pattern which has different prognosis of each pattern: mass-forming (MF-iCCA), periductal infiltration (PI-iCCA), and intraductal growth (IG-iCCA). [31]
Treatment for managing cholangiocarcinoma is quite difficult too and should be managed in the tertiary hospital with a multidisciplinary team experienced in endoscopic, percutaneous, and surgical approaches. Management of this malignancy also depends on the staging of the tumor. Surgical treatment with complete resection could give benefit only for patient with early stage of the disease [32].
Resection could be performed in approximately 30% of patient with CCA. This is the only option that provides a real possibility for long-term survival in patient diagnosed with CCA. The indication and extension of surgery are determined based on clinical features of the patient, functional liver reserve, and the location and extension of the tumor, which include the association with vascular structure and negative metastatic disease. [33, 34]
Criteria for patients who are considered as absolute unresectability are the presence of nonresectable extrahepatic, hepatic metastases, bilateral extension of the tumor with involvement of the secondary biliary tract, complete occlusion of the main portal vein, thrombosis in portal vein contralateral to the tumor. [23] The most common postoperative complications are hemorrhage, infection, liver failure, cardiorespiratory failure, and adrenal failure. Mortality and morbidity for postoperative patient are still remaining high, 8,2% and 50%, respectively. [35] In several condition, drainage should be applied. But in the recent years, increasing number of patients with unresectable intrahepatic and extrahepatic CCA are being included to be candidate for liver transplant. Other treatment modalities as adjuvant therapy are also developed to improve the survival of the patient, such as chemotherapy, radiotherapy, molecular targeted therapy, targeting angiogenesis and EGFR, and immunotherapy.
2. Role of immunotherapy in cancer management
2.1 History and definition
Cancer immunotherapy is significantly progressing and rapidly advancing. In the recent years, immunotherapy is considered to be the fifth pillar of cancer therapy and management modality besides surgery, cytotoxic chemotherapy, radiation, and targeted therapy. The mechanism of immunotherapy in cancer management is to determine a manipulation of the immune system by using immune agents such as vaccine, cytokine, cell therapies and humoral, transfection agent. Cancer immunotherapy has to stimulate the host anti-tumor response by increasing the effector cell number and production of soluble mediators, decrease the host’s suppressor mechanism by inducing tumor killing environment, and could modulate immune checkpoint. [36, 37]
In 1891, William Coley, who is known today as the Father of Immunotherapy, injected heat inactivated bacteria or known as Coley toxins to the sarcoma patient who was inoperable. [38] This first experiment resulted in long term regression of the sarcoma after an erysipelas infection after injecting the toxin. [38] By late 1970s, immunotherapy for managing cancer was discovered. The first experiment was done in bladder cancer case which is managed by using BCG (Bacillus Calmette-Guerin). Then, it is continued with IFN therapy in malignant melanoma. [39] Brief background review of immune system is classically considered to be comprised of the innate and adaptive arms. Immune system which are included in innate immune system are dendritic cells, natural killer cells (NK), macrophages, neutrophils, eosinophils, basophils, and mast cells. As we known, this group of immune system does not need prior stimulation by antigen, and it plays role as first line of defense against foreign antigens. In the contrary, adaptive immune system consists of B lymphocytes, CD4 helper T lymphocytes, and CD 8 cytotoxic T lymphocytes (CTLs). This group of immune system requires formal presentation by antigen presenting cells (APCs) for its activation. [40, 41]
Several kinds of malignant cells are able to evade the tumor immunosurveillance system by manipulating their own characteristic as well as the cells in their microenvironment to become successful tumors. The concept that the immune system is capable for detecting and killing nascent non-self-malignant cells was developed. Elimination, equilibrium, and escape are three main phases of immunoediting process. [42] The elimination phase is the initial damage process and destruction of the tumor cell by innate immune system, then tumor antigens are presented to the dendritic cells, followed by presentation to the T cell and then create tumor-specific CD4 and CD8 T-cells. Second phase occurs when tumor cells survive after the initial destruction but are not able to progress and being maintained in an equilibrium state. The last phase is escape phase. [42] In this phase, tumor cells are growing rapidly, followed by metastasize of tumor cell due to loss control of the immune system and the tumor cells do not presented antigens on its surface or even losing their MHC class1 expression. Tumor cell could protect their self from T cell by expressing immune checkpoint (IC) molecules on their surface. [42]
The ability of this malignant cells to evade immune destruction by modulating its own cellular characteristic and creating its own “tumor microenvironment” by recruiting apparently normal immune cells to help shield it from attack of immune system. In addition, tumor cell can influence the systemic environment by altering hematopoiesis and tissue parenchyma of organs at distant sites. Cancer immunotherapies play role in manipulating these tumor microenvironments. But the loss of MHC class 1 expression manipulating is remaining challenge. [43, 44, 45]
First, older, and non-specific immunotherapies are the kind of immune stimulator cytokines such as interleukin-2 IL-2) and interferon (IFN). [46] Beside that, synthetic analogue of bacterial cell wall called L-MTP could activate monocytes and macrophages is one of the immunostimulatory cytokines. Vaccine trials using multiple neoantigens specific to and individual patient’s tumor have shown promising results in two small early trials with the aim to expose patients to those tumor antigens which can provoke an antitumor immune response via the generation of tumor specific antibodies and T cells. [46] BCG was the first vaccine used as cancer immunotherapy for treating bladder carcinoma. [47]
Oncolytic viruses are the combination of biologic therapy and immunotherapy. Viruses which are used for this method has genetically modified to lack virulence against normal cell but has a selective feature to invade and lyse cancer cells. Viral-induced tumor cell destruction undergoing further attack by an immune system. [48]
Adoptive cell therapy (ACT) is one type of immunotherapy which involves in the isolation and in-vitro expansion of tumor-specific T-cells, which is given through infusion in the cancer patient. ACT using NK cells could be used to treat solid tumor metastasis and hematological cancers. [49] Several forms of ACT using different techniques are culturing tumor infiltrating lymphocytes directly from the tumor, isolating and expanding one particular T-cell or the clone, using T cell which have been engineered in vitro so that it could recognize and attack the tumor cells or known as chimeric antigen receptor T-cell (CAR T-cell) therapy. ACT has produced remarkable result in clinical trials with melanoma and hematologic malignancies. But some studies reported death have occurred in the trial phase due to cytokine release syndrome or cytokine storm. [50]
Another immunotherapy, Immune checkpoint, work by targeting molecules that serve as checks in the regulation of immune responses and block inhibitory molecules or activate stimulatory molecules and enhance pre-existing anti-cancer immune response. [51]
2.2 The clinical importance of immunotherapy
Cancer immunotherapy works to stimulate the host’s anti-tumor response. The mechanism included are increasing the effector cell number and production of soluble mediators, decreasing the host’s suppressor mechanism by inducing tumor killing environment, and modulating immune checkpoints. The usefulness of cancer immunotherapy was introduced in the beginning to manage bladder cancer. The overall 5-year survival after transmitting immunotherapy is 77%. [39] Patients with moderate and high-grade bladder cancer who received intravesical immunotherapy with BCG have shown good result. Immune checkpoint inhibitors showed a promising clinical research in managing anti-cancer immune responses. Several studies using Nivolumab, Ipilimumab, and Pertuzumab are still on progress in metastatic bladder cancer. Some cytokines which are messenger molecules, play a role to control the growth and activity of immune system cells. [52] Treatment using cytokines as immunotherapy can enhance the activity of the immune system against tumors. The link of IL-2 to the antibody, ALT-801, and cytokines can target IL-2 to cancer cells. [53] Oncolytic virus therapy could also be used to treat bladder cancer using adenovirus which expresses the immune stimulating cytokine GM-CSF. [54]
Immunotherapy is developed to manage some immunogenic cancer cases besides bladder cancer. The using of immunotherapy for managing breast cancer have been improved and approved in the recent years. Although the best treatment of breast cancer is surgery, but combination therapy followed by chemotherapy, radiation therapy, or immunotherapy could increase clinical outcome for patient. A promising immunotherapy using immune checkpoint inhibitors that work by targeting molecules that serve as checks in the regulation of immune response and block inhibitory molecules or activate stimulatory molecules. [39] The other form of immunotherapy which can be used for breast cancer is monoclonal antibodies and adoptive T cell transfer. By definition, adoptive T cell transfer is a process of removing T cell from the patient, then it would be modified genetically or treated with chemical to enhance its activity and re-introduced into the patient. Specifically, in breast cancer, T cell genetically is modified to target the carcinoembryonic antigen (CEA). [55]
Another immunogenic cancer is cervical cancer caused by infection of human papillomavirus (HPV). Cervical cancer is the third most frequent cancer among women in the world. [56] The prevalence of this cancer is decreasing due to development widespread of screening tools Pap test and vaccine to prevent HPV infection. In the recent years, monoclonal antibodies, checkpoint inhibitor, and adoptive T cell transfer have become additional therapy for managing progressivity of cancer cell. [39]
Immunotherapies are also developed as a new modality treatment to treat brain cancer, colorectal cancer, esophageal cancer, and biliary tract cancer. Probably, in time, immunotherapy could lead to personalized medicine that will increase overall survival and progression free survival for many treatments. [39]
2.3 The role of immunotherapy in managing bile duct malignancy
Biliary tract malignancy is an invasive carcinoma which can be originated from gallbladder or bile duct. It has been known that the immune system in human body has a significant role in the surveillance and eradication of cancer cells. Tumor that lack the mismatch repair system harbor more mutation than tumor without this deficiency. Thus, the neoantigen generated and be recognize as immunogenic antigen. The characteristic of mismatch repair deficient tumors is microsatellite instability (MSI). There are approximately 3% of CCA are mismatch repair-deficient/MSI-high. [56] This feature makes the tumor cells are susceptible to programmed cell death protein 1 (PD-1) inhibitors. Zhu et al. studied about efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and the correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome in a phase 2 study showed that combination of chemotherapy and immunotherapy have anti-tumor effect with tolerable safety and promising efficacy for managing advanced biliary tract malignancy. This combination treatment was generally well tolerated with less adverse event and manageable toxicity. [57]
Another clinical data about immune-directed therapy in CCA is still scanty. Vaccine for preventing CCA has been developed and tested but no data has showed successful result. [58] CAR T cell immunotherapy in recent years has been developed. Guo et al. in their study about expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor-engineered autologous T (CART) cell immunotherapy. The aim of this study is to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancer. Total sample of this study is 19 patients and showed that CART-EGFR cell infusion was tolerated, 1 achieved complete response and 10 achieved stable disease. We can conclude that CART-EGFR cell immunotherapy was a safe and active strategy for EGFR-positive advanced biliary tract cancer. [59] Wei et al. showed that in some patients, immune checkpoint blockade using monoclonal antibodies has shown remarkable and durable response rate in a many kind of malignancy cell. [60] Le et al. in their study concluded that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab and achieving objective responses in up to 40% of patients. [61] Study by Ott et al. in KEYNOTE-028 basket trial of pembrolizumab included patients with advanced biliary tract cancer resulted the objective response rate was 17% with median progression-free survival of 1.8 months. [62] However, further studies are required either combination immunotherapeutic approaches targeting both the innate and adaptive immune system or combined strategies involving chemotherapy or radiation.
3. Conclusions
Bile duct cancer is still one of the challenging malignancies in the gastroenterology field due to the difficulty in early detection and most of patients come in the late stage of the disease. Chemotherapy is still the main option of management despite surgery and biliary drainage. Immunotherapy is a promising treatment option in the future; however, further studies would be needed to give strong evidence before it can be used in common clinical practice.
\n',keywords:"bile duct carcinoma, bile duct carcinoma management, immunotherapy, gastroenterology",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74090.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74090.xml",downloadPdfUrl:"/chapter/pdf-download/74090",previewPdfUrl:"/chapter/pdf-preview/74090",totalDownloads:476,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:2,introChapter:null,impactScore:0,impactScorePercentile:35,impactScoreQuartile:2,hasAltmetrics:1,dateSubmitted:"July 15th 2020",dateReviewed:"October 26th 2020",datePrePublished:"November 17th 2020",datePublished:"December 9th 2020",dateFinished:"November 17th 2020",readingETA:"0",abstract:"Bile duct carcinoma or well known as cholangiocarcinoma (CCA) is the second most common of primary liver malignancy after hepatocellular carcinoma (HCC). Although cholangiocarcinoma is a rare cancer, it has an aggressive feature with very poor prognosis. The epidemiological profile of cholangiocarcinoma varies widely across the world, which is reflecting the exposure of different risk factors, such as chronic inflammatory disease of the biliary tract, specific infectious disease, and congenital malformation. Diagnosis of CCA is quite challenging. CCA is generally asymptomatic in the early stages. Therefore, the management of this malignancy is often delayed due to late diagnosed, where the metastasis has already present or even when it is causing bile duct obstruction. Treatment for CCA is often difficult and should be managed in the tertiary referral hospital with a multidisciplinary team approach. Surgical treatment with complete resection could be benefit only for patient with early stage of the disease. Other treatment modalities as adjuvant therapy are also have been developed to improve survival of the patient, such as chemotherapy, radiotherapy, molecular targeted therapy, targeting angiogenesis and EGFR, and immunotherapy. Recently, immunotherapy has also been developed as a new cancer treatment option and showed a promising result. Whether immunotherapy can be useful for treatment biliary malignancy is still controversial. Hence, a lot of studies is still required to confirm the preliminary findings.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74090",risUrl:"/chapter/ris/74090",book:{id:"9607",slug:"immunosuppression"},signatures:"Cosmas Rinaldi Adithya Lesmana and Baiq Kirana D. Mandasari",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Role of immunotherapy in cancer management",level:"1"},{id:"sec_2_2",title:"2.1 History and definition",level:"2"},{id:"sec_3_2",title:"2.2 The clinical importance of immunotherapy",level:"2"},{id:"sec_4_2",title:"2.3 The role of immunotherapy in managing bile duct malignancy",level:"2"},{id:"sec_6",title:"3. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Patel N, Benipal B. 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Clin Cancer Res. 2018;24(6):1277-1286. doi:10.1158/1078-0432.CCR-17-0432'},{id:"B60",body:'Wei SC, Duffy CR, Allison JP. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov. 2018;8(9):1069-1086. doi:10.1158/2159-8290.CD-18-0367'},{id:"B61",body:'Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372(26):2509-2520. doi:10.1056/NEJMoa1500596'},{id:"B62",body:'Ott PA, Bang YJ, Piha-Paul SA, et al. T-Cell-Inflamed Gene-Expression Profile, Programmed Death Ligand 1 Expression, and Tumor Mutational Burden Predict Efficacy in Patients Treated With Pembrolizumab Across 20 Cancers: KEYNOTE-028. J Clin Oncol. 2019;37(4):318-327. doi:10.1200/JCO.2018.78.2276'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Cosmas Rinaldi Adithya Lesmana",address:"medicaldr2001id@yahoo.com",affiliation:'
Division of Hepatobiliary, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Indonesia
Digestive Disease and GI Oncology Centre, Medistra Hospital, Indonesia
'},{corresp:null,contributorFullName:"Baiq Kirana D. Mandasari",address:null,affiliation:'
Division of Hepatobiliary, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Indonesia
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1. An overview of microwave heating
Microwaves (MWs) are electromagnetic (EM) waves, which are synchronized perpendicularly oscillations of electric and magnetic fields that propagate at the speed of light in a free space. MWs are characterized by the frequency (between 300 MHz and 300 GHz) and the wavelength (ranging from 1 m to 1 mm). According to the countries and regions, five frequencies (433, 896, 915, 2375, and 2450 MHz) are authorized for MW heating operations. The 2450 MHZ is the exclusive frequency for home appliances.
1.1 Mechanisms of microwave heating
The interaction of a wave with the material depends on its own characteristics (frequencies, wavelength) and the nature of the material, particularly its absolute permittivity ε*, a complex number that determines how the material stores the electrical energy of the EF and its dissipation into heat. The readers can consult more specialized references for detailed information [1]. We can define rapidly here the real permittivity, or dielectric constant, of a material which denotes the capacity of the material to store electrical energy and the effective loss factor which expresses the ability of the material to absorb energy of the wave and dissipate it into the heat by dielectric relaxation and ionic conduction. If a material contains free charges (ions) and polar molecules (e.g., water molecule) when this material is subjected to an EF, the ions will move at an accelerated rate according to their charge, which will cause collisions between them and, by the result, a conversion of the kinetic energy into heat (ohmic heating). In the same way, the polar molecules of this material, which was initially randomly oriented, will be oriented according to the polarity of the field. If the EF is an alternative, these molecules will rotate to remain aligned on it. This dipolar rotation will generate frictions between the molecules which will lead to an internal generation of heat (dielectric heating).
1.2 Penetration and absorption of a wave in a material
When an EM wave is directed toward a material, a part of the wave is reflected on the surface, while the other part penetrates it to be absorbed. The absorption of the wave during its crossing results in a decrease of the amplitude of the internal EF and so of its power. For small or thin materials, the accurate calculation of the internal electric field is recommended by using the Maxwell equations. Lambert’s law (exponential EF decayed) may be used for larger objects.
The penetration depth is defined as the penetration distance in the material for which the 63% of incident power of the incident wave has been absorbed. This depth depends on the dielectric properties of the material as well as the wavelength. The penetration depth at 915 MHz is larger than the penetration depth at 2450 MHz at the same conditions. More power will be absorbed when the loss factor is high [1].
1.3 About the heterogeneity of microwave heating
MW heating is inherently heterogeneous for several reasons:
For most cases, product size is very large compared to the penetration depth; thus, the energy of the EM wave will be completely absorbed before being able to reach the core or the bottom of the product. All the parts of the product not crossed by the EM wave will not undergo heating. Smaller products will heat faster than large ones, because MWs are able to penetrate the entire product. However, small products are also more sensitive to variations in EM fields that exist in the oven, particularly in a multimode cavity.
Dimensional resonance phenomena: sometimes, the wave is reflected against the lower edge of the product leading to interference phenomena. This results in producing cold spots (transmitted and reflected waves cancel each other) and/or hot spots (transmitted and reflected waves add up).
If the product is made of several components, the component with the highest dielectric constant tends to concentrate the energy, and its temperature will increase strongly compared to the other components which leads to selective overheating. The dependence of dielectric properties with the temperature often leads to increase the local temperature of the already hot points. As foods are generally low thermal conductivities, this phenomenon leads to local overheating (thermal runaway).
The shape of the product plays a major role in the heterogeneity of MW heating. The shape of the sample influences the penetration depth of the MWs and the location of the hot spots. In general, the presence of sharp edges and right angles leads to significant local overheating at these locations. Sundberg et al. [2, 3] found that the power density at the edge decreased with the increase of the opening angle; thus, oval or circular forms may in some cases reduce this problem. However, in these forms the MW power is concentrated in the center [4].
2. Microwave drying
2.1 Introduction
Drying is one of the most used methods for preserving food and preventing microbiological degradation. Food drying is also used for economic interests by lightening the product to minimize the transport costs (e.g., milk powder) or even for consumption aspects by creating new textures and/or products (e.g., prunes). This process aims to reduce the water activity (Aw) of the food product by removing some of its water. The amount of water to be removed to achieve the microbiological stability can be determined thanks to the sorption isotherm curve which shows the relationship between the water content and the water activity of a product. Generally, the water activity threshold from which there is no further development of pathogenic bacteria is 0.85–0.86 and 0.7 and 0.6 for yeasts and molds, respectively.
It is interesting to note that Aw does not only control the development of microorganisms, it also influences the rate of the chemical and biochemical reactions that take place within the food. The nonenzymatic browning (Maillard reaction) has a maximal activity for an Aw of 0.6–0.7, while the oxidation of lipids develops rather at very low and very high values of Aw. Thus, it is proper to adjust the final moisture of the product according to these considerations. The area generally targeted for good stability of the dried product is the range of Aw between 0.3 and 0.4. An important aspect must be emphasized here, namely, that drying has almost no lethal effect on the microorganisms present on the product due to insufficient product temperatures reached during drying. Proper packaging is therefore essential to avoid moisture recovery and keep the quality of the dehydrated product.
Industrial drying techniques are very varied depending on the nature of the product to dry (liquid, pasty, solid, or particulate) and of the desired final qualities. Most often, hot air (HA) convective drying is the main dehydration technique used in food industries. However, this method undergoes several problems such as poor end-product quality and low operation performance. Generally, in conventional drying method, two steps take place: a heat transfer from hot and dry surrounding medium to the product and then a mass (water and/or volatile compounds) transfer from the product to the surrounding atmosphere. In general, external heat and mass transfer can be easily controlled by a good monitoring of the drying air characteristics (velocity, temperature, relative humidity); thus, the internal transfer is the limiting step and the effective driving force for the drying operation. The drying rate decreases with time, and the removal of water becomes difficult. Therefore, conventional HA drying requires the application of severe conditions, particularly at the end of operation, which result in overheating and overdrying of the product surface. These reasons have greatly encouraged engineers to develop and propose new drying techniques such as MW drying. For example, MW drying was successfully applied to dry potatoes chips, pasta, and snacks [5]. Several studies of MW drying were resumed in the literature [6].
2.2 Microwave drying versus hot air drying
During MW drying of strong moisture content product, EM energy is supplied directly to the volume of the product, which causes a rapid increase of the product temperature and an instantaneous vaporization of water inside the product [7]. This phenomenon causes an increase in the internal pressure and drives the water to liquid state toward the product surface [8]. This forced outflow of water increases the drying rate and so reduces the operation time (up to five times less than HA air drying for many products). Likewise, the increase in internal pressure prevents food shrinkage and case hardening during drying, which have a positive impact on the texture of the MW dried product. Indeed, it promotes a greater porosity and increases the rehydration ability [9].
The action of conservation provided by the drying to foodstuffs is mainly due to the decrease of Aw which thus makes it possible to limit the development of microorganisms. However, an additional action is observed in the case of MW drying. In fact, the rapid rise in temperature for water-rich products seems to produce a thermal shock effect on thermosensitive microorganisms. Laguerre et al. [10] have shown, in a comparative study of drying of onions either by HA or by MWs, a reduction of the total microbial count ten times greater for MW drying (about one to two log reductions). This is a significant advantage of MW drying compared to hot air drying.
Although the selectivity of EF may cause heating heterogeneity, this selectivity is rather an advantage in the case of MW drying. The level of energy absorption is controlled by the wet parts, resulting in positive selective heating of the inner layers of the product still having a relatively high moisture content without affecting the relatively dry outer layers, thereby facilitating the outflow of water to the surface.
However, even if the MW drying is faster than that of HA method, the MW drying efficiency is limited because of the rapid saturation of the surrounded air due to its low temperature. For this reason, MWs are usually associated with HA flow to improve water transfer at the surface of the product. Another difference between MW and HA drying is the surface temperature. During HA drying, the surface temperature does not exceed the controlled surrounding air temperature, which may be low (30–40°C) during thermosensitive product drying (e.g., aromatic plants), whereas excessive surface temperature may occur during MW drying, especially along the corner or edges, resulting in product carbonization and production of off-flavors especially during the final stages of operation [6].
2.3 Controlled power microwave drying: innovative method to prevent runaway heating
In many works, a constant MW applied power is usually used throughout the drying period. This practice promotes the phenomena of thermal runaway (local overheating) at the end of drying. During MW drying performed at constant power, the applied specific power (power/product mass) increases exponentially as can be seen in Figure 1 for the drying of tomato as an example [11]. Thus, the product receives more and more energy over time while it needs less and less. Moreover, the thermal properties of the product (specific heat and thermal diffusivity) decrease at the same time as the moisture of the product; therefore, it becomes easier to heat the product while the heat accumulated in a zone can less easily diffuse to the whole product. All this, combined with the phenomenon of dimensional resonance, can lead to thermal runaway. This phenomenon can be observed in the case of drying onions [10, 12]. Figure 2 shows the evolution of hot spots up to charring on onion slices during MW drying. The fact that the black spots are very localized initially confirms the presence of dimensional resonance phenomena in this case.
Figure 1.
Evolution of the specific power (W/g) as a function of time (min) for different initial specific power values during drying of tomatoes [11].
Figure 2.
Evolution of hot spot during MW drying of onion slices [10].
To improve the quality of MW dried foods, the control of the applied power throughout the drying was studied in the literature. Li et al. [13] proposed the control of applied power according to the set product temperature, whereas Soysal et al. [14] adapted the applied power as a function of processing time. A very good quality product was obtained by Laguerre et al. [10, 15]. The authors controlled the power as a function of the product mass. This method was successfully tested for drying onions and tomatoes as presented in Table 1. A final product of fresh-like color, without any black spots, was obtained.
Table 1.
Effect of the adaptation of the power applied on the color of the dried product.
2.4 Combined microwave drying technologies
Despite its several advantages over the conventional methods, MW drying has some crucial problems as explained above. However, MW drying combined with other conventional heating methods enhances the drying efficiency as well as the dried product quality compared to MW drying alone. Applications of combined MW drying, principally, include MW-assisted hot air (HA) drying, MW vacuum drying, and MW freeze drying.
2.4.1 MW-assisted hot air drying
The application of MW energy (internal heating) associated with hot air flow (superficial heating) is a good method to overcome certain problems related to the use of these two methods separately. MW heating may be applied at the beginning of the drying process to heat the internal layers of the product rapidly. MW heating can be also applied at the second step of drying process, when the temperature profile is established, to force vapor out of the product which leads to create a porous structure. MW heating can also be applied at the end of drying process, where the mass transfer is reduced to improve the drying rate by removing the bound water [9]. For example, MW drying combined with HA drying at the last stage reduced the drying time by 64% as compared to convective air drying [16]. Saving drying time and improved quality were also reported, using this method, for other fruits such as blueberries [17], macadamia nuts [18], and green peas [19].
2.4.2 MW vacuum drying
In order to reduce the boiling point of water and to prevent the oxidation reactions, MW heating can be associated with a vacuum to maintain the quality (color and flavor) of the dried products. This method was successfully used to dry apple slices [20], pumpkin [21], and cranberries [22]. This method is better than MW air drying in terms of energy consumption, drying time, and quality of the dried products [6].
2.4.3 MW freeze drying
Lyophilization, also known as freeze drying, is a low-temperature dehydration process, which involves freezing the product at the first step and then removing the ice by sublimation under low-pressure conditions. It is used for dehydration of very heat-sensitive materials particularly in food and pharmaceutical industries. This method preserves the structure and minimizes the loss of valuable compounds. However, this technology is limited by its high cost. In MW freeze drying, MW heating can be applied concurrently during the sublimation to supply the heat under vacuum conditions. MW heating can also be applied separately after a traditional lyophilization step. MW freeze drying offers many advantages due to its low processing temperature and lack of oxygen in the processing environment [23, 24]. However, as the MW energy does not interact with frozen water, thermal runaway might take place which may result in poor product quality [6].
3. Microwave pasteurization and sterilization of foods
Pasteurization and sterilization are widely used to extend the shelf life of most foods. The main goals of pasteurization are to destroy vegetative pathogenic microorganisms and to deactivate some enzymes in foods. Pasteurization temperatures and treatment time vary, primarily, depending on the nature, the pH of the product, and the target microorganism. In most pasteurization processes, the food is heated up to 60–85°C for a time varying from a few seconds to an hour. Pasteurization requires refrigerated storage conditions (3–4°C) for a storage life of 2–6 weeks. Sterilization, which can be seen as further pasteurization, destroys bacterial spores [25]. In solid or semisolid products, the heat transfer takes place mainly by conduction from the surface to the center often considered as the “cold” point. This leads to apply more severe conditions to reach the target temperature at the cold point, which results in an overcooking of the surface and a degradation of the quality of products. Optimizing thermal treatments (i.e., maximizing inactivation of bacteria while minimizing nutrient degradation) is therefore an important issue. However, this is not an easy task and it is always a technical and scientific challenge. Thanks to the direct and volumetric interaction between MWs and food, MW heating has the advantage of overcoming the limitation imposed by slow thermal diffusion of conventional heating.
3.1 Microbial decontamination by microwave heating
Many studies demonstrated the effectiveness of using MW heating for pasteurization and sterilization of food [26, 27, 28]. Furthermore, different strains of microorganisms have been inactivated by MW heating, for example, Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Salmonella [29, 30].
3.2 Thermal and athermal effects of microwave heating on microorganisms
The study of microbial destruction mechanisms during an MW heating has attracted a lot of interest [31, 32]. In particular, the possible existence of nonthermal (athermal) effects of microwaves is a subject of debate. Several theories have been proposed to explain how electromagnetic fields can inactivate microorganisms at sublethal temperature conditions. This effect would be due to the interaction between microwaves and certain cellular constituents. In contrast, many studies have refuted the lethal nonthermal effect of MWs. To distinguish between thermal and nonthermal effects, most studies are based on the experimental evaluation of conventional and MW inactivation under identical heating conditions.
Fujikawa et al. [33] showed no difference between inactivation treatments for E. coli (suspended in PB phosphate buffer) in a conventional water bath and in a MW oven. Welt et al. [34] have developed a device to evaluate the possible nonthermal effects of microwaves. They compared the inactivation of Clostridium sporogenes spores in a model medium (a phosphate buffer) under a same time-temperature condition for conventional and MW treatment. The results demonstrate the absence of a nonthermal effect.
On the other hand, several studies demonstrated that the microwaves have a more important bactericidal effect [35, 36]. Sato et al. [37] found that the inactivation of E. coli K12 exposed to MW radiation was higher than that obtained in a water bath at the same temperature (45, 47, and 50°C).
Some authors support the thesis of improved bactericidal effect of microwaves. Kozempel et al. [38] developed an experimental device for detecting a possible nonthermal effect of microwaves on microorganisms at low temperature. The process combines instantaneous energy input to the food system by microwaves with rapid removal of thermal energy. The system used is a double-tube heat exchanger installed inside a continuous MW tunnel. The outer tube is microwaveable, while the inner tube is stainless steel and was used to cool the system instantly to keep the temperature at 45°C. The nonthermal effect of MW radiation has not been observed for yeast, Pediococcus sp., Escherichia coli, Listeria innocua, or Enterobacter aerogenes, in various liquids. However, the author has reported that MWs can improve or amplify the thermal effect in lethal conditions [38]. In the same context, Ramaswamy et al. [39] found that the inactivation of S. cerevisiae inoculated in apple juice treated with steam, hot water, or MW was not significantly different at sublethal temperature (<40°C). However, they found that MW radiations enhanced inactivation for same lethal temperature conditions (55–65°C).
Numerous studies on the interactions between MWs and certain cellular constituents, such as DNA, the cell membrane, enzymes, and proteins, have been carried out. Kakita et al. [40] studied the survival of bacteriophage PL-1, which is specific for Lactobacillus casei, under MW irradiation. More viral DNA fragmentation was found for MW heating over conventional heating. Shamis et al. [41] studied the effects of MW radiation on the membrane of the E. coli cell under sublethal temperature conditions (<40°C). Compared to conventional treatment, a different cellular morphology was observed (the cells are contracted and dehydrated). Nevertheless, this effect seems to be temporary; 10 min after the end of the exposure, the morphology of the cell seemed to return to the initial state of untreated controls. In this experiment, cell viability test revealed that the MW treatment was not bactericidal, since 88% of the cells were recovered. Similarly, Woo et al. [42] reported that MW radiation of Escherichia coli and Bacillus subtilis resulted in an increase in the amounts of nucleotides and protein released from cells. This leak was strongly correlated to MW power. The authors observed, by scanning electron microscopy, a significant damage on the surface of MW-treated E. coli cells; however, there was no significant change observed for B. subtilis cells. Likewise, Shin and Pyun [43] showed that MW treatment (at 50°C) causes irreversible damage to the membrane of Lactobacillus plantarum, associated with increase of the permeability. Also, observations by electron microscopy showed a change in cellular morphology on Candida albicans treated with MW [44].
To prove the existence of nonthermal effect of microwaves on microorganisms, exactly the same thermal history must be reproduced for MW and conventional treatments. Most of studies previously cited applied temperature measurement techniques inappropriate to MW heating, where the temperature was monitored at a single point of the sample. In addition, it is also important to eliminate the heating heterogeneity inherent in MW processing. Consequently, microorganisms are subjected to uneven heating as a result of the presence of cold and hot spots within the same sample. In summary, so far, the existence of nonthermal effect of MWs on microorganisms has not been proven; even if this effect exists, it has no significant consequence on the MW heating of foods.
3.3 Advantages and limitations of microwave microbial decontamination
In fact, it is difficult to compare the efficiency of MW over conventional heating process because of the inherent differences of heating principle between the two technologies [45].
In the case of conventional heating, a slow heat exchange occurs between the heating medium and the product. The heat diffusion inside the product depends on its physical properties (specific heat, thermal conductivity, porosity, etc.). However, it is well known that foods are bad thermal conductors, heat diffusion toward the cold spot is usually slow, and MW heating is generally faster than conventional heating. The heat is generated directly within the food. This direct volumetric heating significantly reduces the processing time resulting in greater retention of nutrients, sensitive vitamins, and aromatic constituents. Microwave-processed foods may also have better texture, taste, and appearance than products processed by conventional methods. For example, a two times faster MW pasteurization treatment of pickled asparagus at 915 MHz was published [46]. This advantage reduced significantly the thermal degradation of asparagus compared to a conventional treatment in a water bath. Similarly, an acceptable MW pasteurization of foie gras was reported with a time saving of 50% and better organoleptic qualities compared to a traditional method [47]. Moreover, MW pasteurization of packaged products is possible for different packaging materials (plastic, paper, and glass) [48, 49]. Furthermore, this technology can be combined with other technologies such as infrared heating for surface cooking, for example [50].
Despite the numerous advantages of MW decontamination technology, heating heterogeneity is a serious problem that leads to incomplete inactivation of microorganisms. Several studies have reported the survival of pathogens such as Salmonella spp. [51] and L. monocytogenes [52], in foods heated in MW ovens.
Goksoy et al. [53, 54] studied the effect of short-time MW exposures on Escherichia coli K12 and Campylobacter jejuni inoculated on chicken meat. A temperature variation of 20°C was measured between different parts of the sample. The auteurs reported that the samples subjected to MWs showed signs of partial cooking areas. There was no evidence that short-time exposure (up to 30 s) to MWs had any bactericidal effect on microorganisms. Apostolou et al. [55] confirmed these results. MW heating of chicken portions did not eliminate E. coli O157: H7. A significant variation of temperature (from 66.7 to 92°C) was also observed.
On the other hand, the heterogeneous heating causes a severe deterioration of food quality. Local overheating often results in irremediable changes of color where the temperature is highest [56]. These phenomena are mainly observed at the corners and the edges of the product due to wave reflection.
Another difficulty concerning MW decontamination is the problem of cold spot localization. During a typical thermal process, the cold point is well defined and located often at the center of the product. During MW pasteurization, one point temperature monitoring within the product is not sufficient to ensure food safety [57]. For example, Schnepf and Barbeau [58] studied the inactivation of inoculated Salmonella in poultry. Their results showed that measuring the internal temperature during MW treatment does not reflect the surface inactivation, where the temperature was lower. To locate the cold spot, the chemical marker method developed by Kim and Taub [59] was successfully used [60, 61, 62]. Combined with experimental investigations, numerical simulations are highly recommended to find the cold spot and to achieve an accurate study to develop a reliable MW decontamination process [57, 63, 64].
3.4 Minimizing the heterogeneity of microwave heating
Before accepting MW technology as a reliable method for pasteurization and/or sterilization of food, it is important to ensure uniform heating during treatment. Several studies have been conducted to improve the quality and safety of MW-treated products, and various solutions have been proposed.
Fung and Cunningham [65] reported that MW heating in combination with conventional heating results in more uniform heating of food and better inactivation of bacteria. Datta et al. [66] found that MW heating in combination with infrared heating or air jets decreases the nonuniformity of temperature distribution. In the same field, Maktabi et al. [67] investigated the synergistic killing effect of laser, MW, and UV radiation on E. coli and on some other spoilage and pathogenic bacteria. It was found that the overall reduction in viable counts was significantly higher than the sum of the reduction values for the individual treatments. The order of the treatment processes had also a significant influence on microbial destruction. A successive process by laser, MW, and then UV was the most effective. Similarly, Lau and Tang [46] studied the heating uniformity and textural quality of pickled asparagus pasteurized by MW in comparison with the conventional hot-water pasteurization method. Two successive heating steps, first in water bath and then in 915 MHz MW oven, were successfully applied. Moreover, covering the top one-third of the product glass bottle with aluminum foil eliminated the overheating at the edges. MW pasteurization also reduced the cook value for pickled asparagus and reduced textural degradation.
On the other hand, the presence of an absorbent medium around the product can reduce the overheating of edges and corners. For example, some authors reported that immersion of the sample in hot water [48] or the use of a steam flow into the oven cavity [68] may be used to ensure a safer and better quality end product. Microwave-circulated water combination (MCWC) heating system demonstrated a relatively uniform heat distribution within packaged food products. Guan et al. [48] reported that microbial destruction by a pilot-scale MCWC heating system matched with designed degrees of sterilization (F0 value) for a conventional treatment.
Koskiniemi et al. [69] improved the heating uniformity of packaged acidified vegetables using a continuous 915 MHz MW system with a two-stage rotation device to rotate the products 180° during treatment. This method increased also the average temperature at the cold point to meet the industrial standard for in-pack pasteurization of acidified vegetables.
Pulsed MW heating technique was also successfully tested. In this method, pulsed application of energy—i.e., turning the magnetron power “on” and “off” intermittently—leads to thermal energy equalization via conduction from hot to cold region during the power-off periods. This results in more uniform temperature distribution within the sample than during continuous application of energy [70, 71]. Sato et al. [37] reported also an enhanced killing rate of Escherichia coli K12 by using pulsed waves compared to continuous treatment.
3.5 Modeling and optimization of microwave heating
Computational fluid dynamics (CFD) is widely used as an established approach for understanding and then optimizing food processing based on the solution to partial differential equations of mass, momentum, and energy transport. MW heating is a multiphysics phenomenon that requires electromagnetic propagation equations (i.e., Maxwell’s equation) to be combined simultaneously with the heat transfer equation to predict the MW power absorption as well as the temperature distribution inside the product [72]. Modeling of MW heating is widely studied in the literature. Interested readers can consult specialized references for more details [73].
In order to design and optimize a reliable MW pasteurization and/or sterilization process, heating model needs to be coupled with kinetic models correlating microbial decontamination. The resulting global model has to mimic the spatial temperature distribution as well as the microbial inactivation at every point within the sample. Few coupled numerical studies of bacterial inactivation by MW heating are reported in the literature. Recently, Masood et al. [64] published an excellent review about emerging technologies modeling to ensure microbial safety of foods.
The classical concept of decimal reduction time and thermal resistance constant (D and z values) was also used to characterize the microbial inactivation by MW heating. Cañumir et al. [74] determined D-values at constant power levels and proposed a z-value in watt to represent the resistance of a target germ during MW heating. Laguerre et al. [75] proposed new specific power destruction parameters, Dp- and zp-values, to qualify MW heating. The decimal reduction time (Dp value) is the treatment time required to reduce microbial population by 90% at a constant applied specific power expressed in W/mL or in W/g. The zp value is the change of specific power necessary to cause a tenfold change in the Dp values of microorganism under specified conditions. This concept has been successfully tested for sterilization of infant food in a lab-scale MW pilot. The optimal condition for MW sterilization of infant food was also determined.
Because of the heterogeneity of MW heating, microbial inactivation kinetics need to be coupled with nonlinear heat transfer model to calculate the temporospatial survival of bacteria [63]. Mallikarjunan et al. [76] developed a mathematical model that includes mass heat transfer to microbial inactivation kinetics. The variation of the dielectric properties with respect to the temperature is taken into account in the simulation process. A good agreement with experimental data was obtained. Hamoud-Agha et al. [57, 63] used COMSOL Multiphysics to investigate the inactivation of E. coli K12 suspended in a gel medium, comparing MW processing with conventional thermal treatment in a water bath. The authors coupled the thermal nonlinear microbiological inactivation model of Geeraerd et al. [77] with heat transfer and Maxwell’s equations integrated into a finite element model under dynamic heating conditions. The results revealed uneven temperature distribution during MW heating which led to a lower inactivation efficiency than water bath treatment. Simulation results were in good agreement with experimental data. The modeling approach to estimate efficiency of microbial inactivation was reliable despite the thermal heterogeneity inherent in the MW treatment. Application of holding time at lethal temperatures (55 and 57°C) did not help to homogenize the temperature distribution within the sample [57, 63].
However, because of digital resources required and time consumption, the use of physical models as presented before could be delicate for real industrial applications in the food industry. On the other hand, another approach based on experimental designs (EDs) and response surface methodology (RSM) can be relatively easy, fast to implement, and quite useful [78]. Nevertheless, RSM has some limitations [8]: (1) it uses a priori models (quadratic model whatever the studied response); (2) the number of tests to be reset can increase very quickly with the number of factors in the plan; (3) the factors must be completely independent; and (4) uncontrolled factors cannot be taken into account.
Another method proposed by Lesty et al. [79], based on iconographic correlations (CORICO), makes it possible to circumvent these difficulties [8]. After analysis of the experimental plan data, CORICO proposes regression models whose regressors are logical interactions (AND, Exclusive OR, IF, etc.) between factors. In addition, CORICO tolerates linked factors and allows the consideration of uncontrolled factors. Furthermore, it needs few numbers of essays comparatively to classical EDs, (17 essays for a 9-factor CORICO designs against 533 for a 9-factor Doehlert design), which allows to minimize costs. This method has recently been used in the agri-food sector for the optimization of the drying process of different food products (tomato, microalgae, apple) [11, 80, 81] as well as for MW cooking processes (beef burgundy, fish) [82, 83].
4. Conclusions
Conventional heat treatments for food preservation are generally characterized by poor end-product quality. Furthermore, these methods are not optimized for solid foods because of slow heat transfer from the surface to the cold point, often at the center of the product. Enhanced organoleptic and nutritional food properties combined with food safety is the aim of modern food processing technologies. Microwave (MW) heating has the advantages to overcome the limitation of slow thermal diffusion imposed by conventional heating. This technology knows a growing industrial demand thanks to its flexible and rapid heating performance. MW heating is successfully used for food drying and decontamination. However, this process is still relatively poorly controlled because of complex interactions between foods and MWs. Furthermore, the heating heterogeneity is the major drawback of this technology. Several methods were, nevertheless, proposed in the literature to improve the heating homogeneity. In general, coupling MW heating with other heating methods largely improved the microbiological safety, the drying efficiency, and the quality of various food products. Physical modeling and simulation are important tools to understand and to optimize MW heating processes. The application of these models is limited in industrial scale; however, experimental design-based approaches could be promising methods. Even so, developing a reliable industrial MW heating process is still a challenge.
\n',keywords:"microwave heating, microwave modeling, drying, pasteurization, sterilization, microbial decontamination, food safety, food quality",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65345.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65345.xml",downloadPdfUrl:"/chapter/pdf-download/65345",previewPdfUrl:"/chapter/pdf-preview/65345",totalDownloads:1396,totalViews:0,totalCrossrefCites:4,dateSubmitted:"July 18th 2018",dateReviewed:"November 14th 2018",datePrePublished:"January 25th 2019",datePublished:"February 26th 2020",dateFinished:"January 24th 2019",readingETA:"0",abstract:"Since food is generally of low thermal conductivity, heating by conventional methods remains relatively slow. Thanks to its volumetric and rapid heating, microwave (MW) technology is successfully used in many applications of food processing. In this chapter, fundamental principles of MW heating are briefly presented. MW drying and MW microbial decontamination are extensively reviewed as innovative methods for food preservation. However, the complex interactions between microwaves and materials to be heated are not yet sufficiently controlled. Moreover, MW heating heterogeneity and thermal runaway are the main drawbacks of this technology. Several methods have been proposed and investigated in the literature to overcome these problems in order to assure the microbiological safety and quality of food products.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65345",risUrl:"/chapter/ris/65345",signatures:"Jean-Claude Laguerre and Mohamad Mazen Hamoud-Agha",book:{id:"8544",type:"book",title:"Food Preservation and Waste Exploitation",subtitle:null,fullTitle:"Food Preservation and Waste Exploitation",slug:"food-preservation-and-waste-exploitation",publishedDate:"February 26th 2020",bookSignature:"Sonia A. Socaci, Anca C. F?rca?, Thierry Aussenac and Jean-Claude Laguerre",coverURL:"https://cdn.intechopen.com/books/images_new/8544.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-426-8",printIsbn:"978-1-78985-425-1",pdfIsbn:"978-1-78984-084-1",isAvailableForWebshopOrdering:!0,editors:[{id:"191241",title:"Ph.D.",name:"Sonia A.",middleName:null,surname:"Socaci",slug:"sonia-a.-socaci",fullName:"Sonia A. Socaci"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. An overview of microwave heating",level:"1"},{id:"sec_1_2",title:"1.1 Mechanisms of microwave heating",level:"2"},{id:"sec_2_2",title:"1.2 Penetration and absorption of a wave in a material",level:"2"},{id:"sec_3_2",title:"1.3 About the heterogeneity of microwave heating",level:"2"},{id:"sec_5",title:"2. Microwave drying",level:"1"},{id:"sec_5_2",title:"2.1 Introduction",level:"2"},{id:"sec_6_2",title:"2.2 Microwave drying versus hot air drying",level:"2"},{id:"sec_7_2",title:"2.3 Controlled power microwave drying: innovative method to prevent runaway heating",level:"2"},{id:"sec_8_2",title:"2.4 Combined microwave drying technologies",level:"2"},{id:"sec_8_3",title:"2.4.1 MW-assisted hot air drying",level:"3"},{id:"sec_9_3",title:"2.4.2 MW vacuum drying",level:"3"},{id:"sec_10_3",title:"2.4.3 MW freeze drying",level:"3"},{id:"sec_13",title:"3. Microwave pasteurization and sterilization of foods",level:"1"},{id:"sec_13_2",title:"3.1 Microbial decontamination by microwave heating",level:"2"},{id:"sec_14_2",title:"3.2 Thermal and athermal effects of microwave heating on microorganisms",level:"2"},{id:"sec_15_2",title:"3.3 Advantages and limitations of microwave microbial decontamination",level:"2"},{id:"sec_16_2",title:"3.4 Minimizing the heterogeneity of microwave heating",level:"2"},{id:"sec_17_2",title:"3.5 Modeling and optimization of microwave heating",level:"2"},{id:"sec_19",title:"4. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Datta AK, Anantheswaran RC. The Handbook of Microwave Technology for Food Applications. 1st ed. New York: Marcel Dekker; 2001. Epub ahead of print 2001. DOI: 10.1017/CBO9781107415324.004'},{id:"B2",body:'Sundberg M, Kildal P, Ohlsson T. Moment method analysis of a microwave tunnel oven. 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Applied and Environmental Microbiology. 2000;66:2243-2247'},{id:"B43",body:'Shin JK, Pyun YR. Inactivation of Lactobacillus plantarum by pulsed-microwave irradiation. Journal of Food Science. 1997;62:163-166'},{id:"B44",body:'Rosaspina S, Salvatorelli G, Anzanel D, et al. Effect of microwave radiation on Candida albicans. Microbios. 1994;78:55-59'},{id:"B45",body:'Shamis Y, Croft R, Taube A, et al. Review of the specific effects of microwave radiation on bacterial cells. Applied Microbiology and Biotechnology. 2012;96:319-325'},{id:"B46",body:'Lau MH, Tang J. Pasteurization of pickled asparagus using 915 MHz microwaves. Journal of Food Engineering. 2002;51:283-290'},{id:"B47",body:'Massoubre E. Foie gras et plats cuisinés: Micro onde pour une bonne qualité sensorielle. Viandes et Produits Carnés. 2003;23:49-52'},{id:"B48",body:'Guan D, Gray P, Kang DH, et al. Microbiological validation of microwave-circulated water combination heating technology by inoculated pack studies. Journal of Food Science. 2003;68:1428-1432'},{id:"B49",body:'Tang Z, Mikhaylenko G, Liu F, et al. Microwave sterilization of sliced beef in gravy in 7-oz trays. Journal of Food Engineering. 2008;89:375-383'},{id:"B50",body:'Datta AK, Rakesh V. Principles of microwave combination heating. Comprehensive Reviews in Food Science and Food Safety. 2013;12:24-39'},{id:"B51",body:'Heddleson RA, Doores S, Anantheswaran RC, et al. Viability loss of salmonella species, Staphylococcus aureus, and Listeria monocytogenes in complex foods heated by microwave energy. Journal of Food Protection. 1996;59:813-818'},{id:"B52",body:'Farber JM, D’Aoust JY, Diotte M, et al. Survival of listeria spp. on raw whole chickens cooked in microwave ovens. Journal of Food Protection. 1998;61:1465-1469'},{id:"B53",body:'Goksoy EO, James C, James SJ. Non-uniformity of surface temperatures after microwave heating of poultry meat. Journal of Microwave Power and Electromagnetic Energy. 1999;34:149-160'},{id:"B54",body:'Göksoy EO, James C, Corry JEL. Effect of short-time microwave exposures on inoculated pathogens on chicken and the shelf-life of uninoculated chicken meat. Journal of Food Engineering. 2000;45:153-160'},{id:"B55",body:'Apostolou I, Papadopoulou C, Levidiotou S, et al. The effect of short-time microwave exposures on Escherichia coli O157:H7 inoculated onto chicken meat portions and whole chickens. International Journal of Food Microbiology. 2005;101:105-110'},{id:"B56",body:'Tang J. JFS Special Issue: 75 Years of Advancing Food Science, and Preparing for the Next 75 Unlocking Potentials of Microwaves for Food Safety and Quality. 80. Epub ahead of print. 2015. DOI: 10.1111/1750-3841.12959'},{id:"B57",body:'Hamoud-Agha MM, Curet S, Simonin H, et al. Holding time effect on microwave inactivation of Escherichia coli K12: Experimental and numerical investigations. Journal of Food Engineering. 2014;143:102-113'},{id:"B58",body:'Schnepf M, Barbeau WE. Survival of Salmonella Typhimurium in roasting chickens cooked in a microwave, convection microwave, and a conventional electric oven. Journal of Food Safety. 1989;9:245-252'},{id:"B59",body:'Kim HJ, Taub IA. Intrinsic chemical markers for aseptic processing of particulate foods. Food Technology. 1993;47:91-97'},{id:"B60",body:'Auksornsri T, Bornhorst ER, Tang J, et al. Developing model food systems with rice based products for microwave assisted thermal sterilization. LWT—Food Science and Technology. 2018;96:551-559'},{id:"B61",body:'Pandit RB, Tang J, Liu F, et al. Development of a novel approach to determine heating pattern using computer vision and chemical marker (M-2) yield. Journal of Food Engineering. 2007;78:522-528'},{id:"B62",body:'Bornhorst ER, Tang J, Sablani SS, et al. Development of model food systems for thermal pasteurization applications based on Maillard reaction products novas. LWT—Food Science and Technology. 2017;75:417-424'},{id:"B63",body:'Hamoud-Agha MM, Curet S, Simonin H, et al. Microwave inactivation of Escherichia coli K12 CIP 54.117 in a gel medium: Experimental and numerical study. Journal of Food Engineering. 2013;116:315-323'},{id:"B64",body:'Masood H, Trujillo FJ, Knoerzer K, et al. Designing, Modeling, and Optimizing Processes to Ensure Microbial Safety and Stability Through Emerging Technologies. Elsevier Inc. Epub ahead of print 2018. DOI: 10.1016/B978-0-12-811031-7.00006-6'},{id:"B65",body:'Fung DYC, Cunningham FE. Effect of microwaves on microorganisms in foods. Journal of Food Protection. 1980;43:641-650'},{id:"B66",body:'Datta AK, Geedipalli SSR, Almeida MF. Microwave combination heating. Food Technology. 2005;59:36-40'},{id:"B67",body:'Maktabi S, Watson I, Parton R. Synergistic effect of UV, laser and microwave radiation or conventional heating on E. coli and on some spoilage and pathogenic bacteria. Innovative Food Science and Emerging Technologies. 2011;12:129-134'},{id:"B68",body:'Lacroix K, Orsat V, Nattress DF, et al. Dielectric heating of fresh meat for antimicrobial treatment. In: The 93rd Annual International Meeting of American Society of Agricultural Engineers (ASAE); Milwaukee. 2000'},{id:"B69",body:'Koskiniemi CB, Den TV, Simunovic J, et al. Improvement of heating uniformity in packaged acidified vegetables pasteurized with a 915 MHz continuous microwave system. Journal of Food Engineering. 2011;105:149-160'},{id:"B70",body:'Yang HW, Gunasekaran S. Comparison of temperature distribution in model food cylinders based on Maxwell’s equations and Lambert’s law during pulsed microwave heating. Journal of Food Engineering. 2004;64:445-453'},{id:"B71",body:'Gunasekaran S, Yang HW. Effect of experimental parameters on temperature distribution during continuous and pulsed microwave heating. Journal of Food Engineering. 2007;78:1452-1456'},{id:"B72",body:'Curet S, Rouaud O, Boillereaux L. Microwave tempering and heating in a single-mode cavity: Numerical and experimental investigations. Chemical Engineering and Processing: Process Intensification. 2008;47:1656-1665'},{id:"B73",body:'Zhao X, Huang K, Yan L. Review of Numerical Simulation of Microwave Heating Process. Intech Open Access Publisher 2011;27-28'},{id:"B74",body:'Cañumir JA, Celis JE, de Bruijn J, et al. Pasteurisation of apple juice by using microwaves. LWT—Food Science and Technology. 2002;35:389-392'},{id:"B75",body:'Laguerre JC, Pascale GW, David M, et al. The impact of microwave heating of infant formula model on neo-formed contaminant formation, nutrient degradation and spore destruction. Journal of Food Engineering. 2011;107:208-213'},{id:"B76",body:'Mallikarjunan P, Hung Y-C, Gundavarapu S. Modeling microwave cooking of cocktail shrimp. Journal of Food Process Engineering. 1996;19:97-111'},{id:"B77",body:'Geeraerd AH, Herremans CH, Van Impe JF. Structural model requirements to describe microbial inactivation during a mild heat treatment. International Journal of Food Microbiology. 2000;59:185-209'},{id:"B78",body:'Bas D, Boyacı İH. Modeling and optimization I: Usability of response surface methodology. Journal of Food Engineering. 2007;78:836-845'},{id:"B79",body:'Lesty M. Une nouvelle approche dans le choix des régresseurs de la régression multiple en présence d’interactions et de colinéarités. La Revue Modulad. 1999;22:41-77'},{id:"B80",body:'Laguerre J-C, Ratoandromalala LP, Humeau A, et al. Iconographic correlation method and Fourier transform infrared spectroscopy (FTIR) for the optimization of a combined microwave hot air drying of the microalgae Isochrysis sp. In: Procedings of the 17th World Congress of Food Science and Technology—IUFOST. Montreal; 2014'},{id:"B81",body:'Laguerre J-C, Ratovoarisoa LG, Vivant A-C, et al. An iconographic correlation method for optimizing a combined microwave/hot air drying of apple Malus domestica sp. Journal of Food Processing & Technology. 2017;8:7110'},{id:"B82",body:'Jouquand C, Tessier FJ, Bernard J, et al. Optimization of microwave cooking of beef burgundy in terms of nutritional and organoleptic properties. LWT—Food Science and Technology. 2015;60:271-276'},{id:"B83",body:'Laguerre J-C, Douiri-Bedoui I, Chireux C, et al. The iconographic correlation (CORICO) method, a new approach for the optimization of microwave cooking processes: Application for cooking fish. In: EFFOST Annual Meeting. 2013'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Jean-Claude Laguerre",address:"jean-claude.laguerre@unilasalle.fr",affiliation:'
The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
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1,400 GBP Chapter - Edited Volume
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850 GBP Chapter - Book Series Topic (Annual Volume)
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10,000 GBP Monograph - Long Form
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During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
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Personal contact and support throughout the publishing process from your dedicated Author Service Manager
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Discoverability - electronic citation and linking via DOI
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Permanent and unrestricted online access to your work
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What isn't covered by the Open Access Publishing Fee?
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If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
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To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Choosing to publish with IntechOpen ensures the following benefits:
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+5,700 OA books published
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Most competitive prices in the market
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Fully compliant with OA funding requirements
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Currently strongest OA platform with over 175 million downloads
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
\n\n
The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
\n\n
OAPF Publishing Options
\n\n
\n\t
1,400 GBP Chapter - Edited Volume
\n\t
850 GBP Chapter - Book Series Topic (Annual Volume)
\n\t
10,000 GBP Monograph - Long Form
\n\t
4,000 GBP Compacts Monograph - Short Form
\n\t
850 GBP Journal Article (Across Portfolio)
\n
\n\n
During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
\n\n
\n\t
An online manuscript tracking system to facilitate your work
\n\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\n\t
Assurance that your manuscript meets the highest publishing standards
\n\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\n\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
\n
\n\n
What isn't covered by the Open Access Publishing Fee?
\n\n
If your manuscript:
\n\n
\n\t
Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+5,700 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes that assure your research is made available to the scientific community without delay
\n\t
Personal support during every step of the publication process
\n\t
+184,650 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 175 million downloads
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Next, an image is compressed by using different principal components, and concepts such as image dimension reduction and image reconstruction quality are explained. Also, using the almost periodicity of the first principal component, a quality comparative analysis of a compressed image using two and eight principal components is carried out. Finally, a novel construction of principal components by periodicity of principal components has been included, in order to reduce the computational cost for their calculation, although decreasing the accuracy.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Wilmar Hernandez and Alfredo Mendez",authors:null}],mostDownloadedChaptersLast30Days:[{id:"59209",title:"Utilization of Response Surface Methodology in Optimization of Extraction of Plant Materials",slug:"utilization-of-response-surface-methodology-in-optimization-of-extraction-of-plant-materials",totalDownloads:5458,totalCrossrefCites:63,totalDimensionsCites:96,abstract:"Experimental design plays an important role in several areas of science and industry. Experimentation is an application of treatments applied to experimental units and is then part of a scientific method based on the measurement of one or more responses. It is necessary to observe the process and the operation of the system well. For this reason, in order to obtain a final result, an experimenter must plan and design experiments and analyzes the results. One of the most commonly used experimental designs for optimization is the response surface methodology (RSM). Because it allows evaluating the effects of multiple factors and their interactions on one or more response variables it is a useful method. In this section, recent studies have been compiled which aim to extraction of plant material in high yield and quality and determine optimum conditions for this extraction process.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Alev Yüksel Aydar",authors:[{id:"218870",title:"Dr.",name:"Alev Yüksel",middleName:null,surname:"Aydar",slug:"alev-yuksel-aydar",fullName:"Alev Yüksel Aydar"}]},{id:"60864",title:"Statistical Methodology for Evaluating Business Cycles with the Conditions of Their Synchronization and Harmonization",slug:"statistical-methodology-for-evaluating-business-cycles-with-the-conditions-of-their-synchronization-",totalDownloads:1357,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The importance of the topic of business cycle research and their interaction is due to the fact that the cyclical nature of development is a universal feature of the market economy (regardless of the level of development of the country’s economy and the principles of its organization). In all cases, cyclical ups and downs depend not only on internal system cyclical processes and their factors in countries but also on the consequences of intercountry interaction. The ability to measure and predict business cycles, taking into account their mutual influence, is a prerequisite for the development of an adequate business policy of countries and their associations.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Elena Zarova",authors:null},{id:"60246",title:"Statistical Research of Investment Appeal of Russian Regions",slug:"statistical-research-of-investment-appeal-of-russian-regions",totalDownloads:1012,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In this chapter, the methodological results directed on realization statistical research of investment appeal of Russian regions are offered. Methodological basis of research is the method of the dynamic standard, index and the coefficient analysis and the method of paired comparisons. The results of the study: (1) the method of the dynamic standard for creation of statistical model of region investment appeal is offered; (2) the normative model of region investment appeal to measure the productivity of the realization of regions investment policy in Russia is created; (3) new factors of region investment appeal are investigated and (4) statistically valid conclusions are drawn and practical recommendations are made. The results of the study are addressed to the Ministry of Economic Development of the Russian Federation in order to justify the amount of federal targeted investment programs financing in Russian regions.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Burtseva Tatiana Alexsandrovna",authors:null},{id:"56460",title:"Application of Taguchi-Based Design of Experiments for Industrial Chemical Processes",slug:"application-of-taguchi-based-design-of-experiments-for-industrial-chemical-processes",totalDownloads:3218,totalCrossrefCites:26,totalDimensionsCites:54,abstract:"Design of experiment is the method, which is used at a very large scale to study the experimentations of industrial processes. It is a statically approach where we develop the mathematical models through experimental trial runs to predict the possible output on the basis of the given input data or parameters. The aim of this chapter is to stimulate the engineering community to apply Taguchi technique to experimentation, the design of experiments, and to tackle quality problems in industrial chemical processes that they deal with. Based on years of research and applications, Dr. G. Taguchi has standardized the methods for each of these DOE application steps. Thus, DOE using Taguchi approach has become a much more attractive tool to practicing engineers and scientists. And since the last four decades, there were limitations when conventional experimental design techniques were applied to industrial experimentation. And Taguchi, also known as orthogonal array design, adds a new dimension to conventional experimental design. Taguchi method is a broadly accepted method of DOE, which has proven in producing high-quality products at subsequently low cost.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Rahul Davis and Pretesh John",authors:[{id:"199438",title:"Mr.",name:"Rahul",middleName:null,surname:"Davis",slug:"rahul-davis",fullName:"Rahul Davis"}]},{id:"59936",title:"Application of Principal Component Analysis to Image Compression",slug:"application-of-principal-component-analysis-to-image-compression",totalDownloads:1819,totalCrossrefCites:12,totalDimensionsCites:15,abstract:"In this chapter, an introduction to the basics of principal component analysis (PCA) is given, aimed at presenting PCA applications to image compression. Here, concepts of linear algebra used in PCA are introduced, and PCA theoretical foundations are explained in connection with those concepts. Next, an image is compressed by using different principal components, and concepts such as image dimension reduction and image reconstruction quality are explained. Also, using the almost periodicity of the first principal component, a quality comparative analysis of a compressed image using two and eight principal components is carried out. Finally, a novel construction of principal components by periodicity of principal components has been included, in order to reduce the computational cost for their calculation, although decreasing the accuracy.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Wilmar Hernandez and Alfredo Mendez",authors:null}],onlineFirstChaptersFilter:{topicId:"166",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:107,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:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,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. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:10,paginationItems:[{id:"82858",title:"Corporate Social Responsibility a Case of the Provision of Recreational Facilities",doi:"10.5772/intechopen.105608",signatures:"Peter Musa Wash, Shida Irwana Omar, Badaruddin Mohamed and Mohd Ismail Isa",slug:"corporate-social-responsibility-a-case-of-the-provision-of-recreational-facilities",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg",subseries:{id:"86",title:"Business and Management"}}},{id:"82786",title:"Discussion of Purchasing Virtual Digital Nature and Tourism",doi:"10.5772/intechopen.105869",signatures:"Hiroko Oe and Yasuyuki Yamaoka",slug:"discussion-of-purchasing-virtual-digital-nature-and-tourism",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"A New Era of Consumer Behavior - Beyond the Pandemic",coverURL:"https://cdn.intechopen.com/books/images_new/11581.jpg",subseries:{id:"88",title:"Marketing"}}},{id:"82289",title:"Consumer Culture and Abundance of Choices: Having More, Feeling Blue",doi:"10.5772/intechopen.105607",signatures:"Ondřej Roubal",slug:"consumer-culture-and-abundance-of-choices-having-more-feeling-blue",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"A New Era of Consumer Behavior - Beyond the Pandemic",coverURL:"https://cdn.intechopen.com/books/images_new/11581.jpg",subseries:{id:"88",title:"Marketing"}}},{id:"82405",title:"Does Board Structure Matter in CSR Spending of Commercial Banks? Empirical Evidence from an Emerging Economy",doi:"10.5772/intechopen.105589",signatures:"Bishnu Kumar Adhikary and Ranjan Kumar Mitra",slug:"does-board-structure-matter-in-csr-spending-of-commercial-banks-empirical-evidence-from-an-emerging-",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg",subseries:{id:"86",title:"Business and Management"}}}]},overviewPagePublishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"11392",title:"Leadership in a Changing World",subtitle:"A Multidimensional Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11392.jpg",slug:"leadership-in-a-changing-world-a-multidimensional-perspective",publishedDate:"May 11th 2022",editedByType:"Edited by",bookSignature:"Muhammad Mohiuddin, Bilal Khalid, Md. 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He has published research in Research Policy, Applied Economics, Review of Economic Philosophy, Strategic Change, International Journal of Logistics, Sustainability, Journal of Environmental Management, Journal of Global Information Management, Journal of Cleaner Production, M@N@GEMENT, and more. He is a member of CEDIMES Institut (France), Academy of International Business (AIB), Strategic Management Society (SMS), Academy of Management (AOM), Administrative Science Association of Canada (ASAC), and Canadian council of small business and entrepreneurship (CCSBE). He is currently the director of the Research Group on Contemporary Asia (GERAC) at Laval University. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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