\r\n\tFurthermore, during the preparation of high-quality dairy products, several physical, chemical, enzymatic, and microbial transformations take place. We will consciously focus on this interaction of different constituents of milk under different processing conditions for the development of the products.
",isbn:"978-1-83768-093-1",printIsbn:"978-1-83768-092-4",pdfIsbn:"978-1-83768-094-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"420e687768b56ca7b3238d77f63f1302",bookSignature:"Dr. Neelam Upadhyay",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12173.jpg",keywords:"Protein, Fat, Lactose, Carbohydrates, Milk Processing, Milk Products, Milk Constituents, Acid Coagulated, Enzyme Treated, Heat Treated, Dairy Products, Protocols of Manufacturing",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 18th 2022",dateEndSecondStepPublish:"June 15th 2022",dateEndThirdStepPublish:"August 14th 2022",dateEndFourthStepPublish:"November 2nd 2022",dateEndFifthStepPublish:"January 1st 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"21 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Upadhyay has received many awards most notable being the Young Woman Scientist Award 2020 from the Agro-Environmental Development Society and the Best Poster Award 2021 from the National Conference on Moringa Food Conclave 2021. She is a dedicated researcher in food and dairy processing and has published many research articles and papers in both national and international journals and publications.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"269538",title:"Dr.",name:"Neelam",middleName:null,surname:"Upadhyay",slug:"neelam-upadhyay",fullName:"Neelam Upadhyay",profilePictureURL:"https://mts.intechopen.com/storage/users/269538/images/system/269538.jpg",biography:"BRIEF BIODATA\n1.\tName in full: Neelam Upadhyay \n2.\tDate & Place of Birth: 29th December, 1987 at Delhi\n3.\tField of specialization: Food Technology\n4.\tPresent Position/ Designation: Scientist- Senior Scale\n5.\tAddress:\t(a)\tOfficial:\tTel. No.:0184-2259258\n\t\t\t\tE-mail: \ticar.neelam@gmail.com; neelam.upadhyay@icar.gov.in \n\t\t\t\tAddress: \tLaboratory No. 146, Dairy Technology Division, ICAR- \n\t\t\t\t\t\tNational Dairy Research Institute, Karnal \n\t\t\t(b)\tResidential: Tel. No.: +91-9255772587\n\tAddress (Permanent): 41-D, MIG DDA Flats, Shivam Enclave, Delhi-110032\n6.\t(a) Academic career and (b) professional attainments\n(a) Examination\tClass/ Percentage\tYear of Passing\tSubjects Taken\tName of University / Board\nXth \t1st/83\n(415/500)\t2003\tMathematics, Social Science, Science, English, Hindi\tK.V., Mumbai (CBSE)\nXIIth\t1st/78.2 \n(391/500)\t2005\tPhysics, Mathematics, Chemistry, Biology, English\tK.V., Delhi (CBSE)\nB.A.Sc. (Hons.)\t1st/83.43 (2044/2450)\n(3rd position)\t2008\tFood Technology\tSRCASW, University of Delhi, Delhi\nM.Sc.\t1st/8.62\n(1st position)\t2010\tFood Science & Technology\tCCS Har. Agri. Uni., Hisar, Haryana\nTitle of Research:\tDevelopment of flavoured whey-soya milk beverage\nMajor Advisor:\tDr. R. S. Dabur (Professor and Head)\nPh.D.\t1st/8.0\n(1st position)\t2014\tDairy Chemistry\tNational Dairy Research Institute, Karnal, Haryana\nTitle of Research: \tDetection of vegetable oil and animal body fat adulteration in ghee using solvent fractionation technique\nMajor Advisor:\tDr. Darshan Lal (Principal Scientist and Ex-Head)\nDistinctions during Academics\nDegree\tDistinctions\nBachelor of Applied Science (Hons.)\ti.\tY.K. Kapoor Memorial Scholarship 2006 by All India Food Processor’s Association \nii.\t3rd position in university\niii.\tReceived highest attendance award\niv.\tReceived trophy for ‘Most Disciplined Student’ for the graduation period 2005-2008\nv.\tCertificate of Honor from Honb’le Mr. Justice K.G. Balakrishnan, Chief Justice of India\nMaster of Science\ti.\t1st position in discipline and 2nd position in college\nii.\tReceived recognition for academic excellence from Jawaharlal Nehru Memorial Fund; \niii.\tQualified GATE\niv.\t2nd in inter-college yoga competition\nv.\tParticipated in various events of All India Youth Festival organized at UAS, Bangalore.\nDoctor of Philosophy\ti.\tReceived Merit Certificate for Academic Excellence in PhD course work\nii.\tReceived Certificate of Appreciation for outstanding work in the field of Dairy Processing during PhD\niii.\tQualified ICAR’s National Eligibility Test in 2010; Qualified the ICAR’s All India Examination, ICAR-SRF (PGS_-2011-2012 for award of ICAR-SRF (PGS) with 2nd rank (both in first attempt) \niv.\tQualified Agricultural Research Service Examination-2013 conducted by Agricultural Scientist Recruitment Board against the single vacancy (for UR) in the discipline of Food Technology\nv.\tStage Management Secretary of student’s council 2010-11\nvi.\tLiterary secretary of Student’s Council 2011-12\nvii.\tCompleted certificate e-course on “Publishing a Journal Manuscript - the Groundwork” directed by Springer in 2013\nviii.\tHave successfully completed certificate e-course – “Peer Review Academy” directed by Springer in 2013\nix.\tReceived a certificate on accomplishment IRIS 4-2 Information Literacy Plagiarism Quiz (on-line) in 2013 developed by Distance Learning Council of Washington, USA \n (b) Position Held\tInstitution \tPeriod of Appointment\tNature of Appointment\nScientist (Food Technology)\tICAR- National Academy of Agricultural Research Management, Hyderabad\t3 months\n(1st January, 2015 till 31st March, 2015)\tPermanent\n(Received ‘A’ grade for FOCARS)\nScientist \n(Food Technology)\tICAR- National Dairy Research Institute, Karnal\t10th March, 2015 till 31st December, 2018\n(after availing 10 days of transfer period)\tPermanent\nScientist-Senior Scale\n(Food Technology)\tICAR- National Dairy Research Institute, Karnal\t1st January, 2019 till date\tPermanent\n\n7. Special attainments in Research\n(https://scholar.google.co.in/citations?hl=en&user=PRz0Tz4AAAAJ&view_op=list_works&sortby=pubdate)\nPublications\tNumbers\tRemarks \nResearch Articles\t35\n(24 Intl, 9 National, 2 others)\tTotal Impact: 72.302\n\nBook Chapters\t7\t5 APA/CRC Press; 1 InTech Open; \n1 National\nReview Articles\t2\tTotal Impact:8.327\nTechnical Articles\t7\tCompendium of trainings, seminars, etc\nInstitute publication\t1\t\nPopular Article\t12\t6 in English; 5 in hindi\nCitations \t1066\t(as per googlescholar)\nH-index/ i10-index\t15/ 17\t\n.\n.\nJournal\tNumber of publications\tImpact factor\nResearch Articles\t35\t72.302\nInternational\t24 (15 as either corresponding or first author)\t72.302\nNational\t9 (3 as first or corresponding author)\tNAAS score\nOthers\t2\t\nReview article (International)\t2\t8.327\nInternational\t2\t8.327\n.\n \n\n\n\nRESEARCH ARTICLES\nInternational Journals \n1.\tTiwari, S., Upadhyay, N.*, Singh, A. K. (2022). Stability assessment of emulsion of carotenoids extracted from carrot bio-waste in flaxseed oil and its application in food model system. Food Bioscience, 47, 101631. https://doi.org/10.1016/j.fbio.2022.101631.\n2.\tPatil, A. T., Meena, G. S., Upadhyay, N., Khetra, Y., Singh, A. K., & Borad, S. G. (2021). Buffalo milk protein concentrate 60: Effect of skim milk heat treatment on its reconstitutability and functionality. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 148, 111638. \n3.\tUttamrao, H. J., Meena, G. S., Khetra, Y., Upadhyay, N., Singh, A. K., Arora, S., & Borad, S. G. (2022). Homogenization and sodium hydrogen phosphate induced effect on physical and rheological properties of ultrafilterd concentrated milk. Journal of Food Science and Technology, 59(3), 956-967. \n4.\tTiwari, S., Upadhyay, N.*, Malhotra, R. (2021). Three way ANOVA for emulsion of carotenoids extracted in flaxseed oil from carrot bio-waste. Waste Management, 121, 67-76. \n5.\tRanvir, S., Sharma, R., Gandhi, K., Upadhyay, N., Mann, B. (2020). Assessment of proteolysis in ultra-high temperature milk using attenuated total reflectance–Fourier transform infrared spectroscopy. International Journal of Dairy Technology. 73(2): 366-375. doi: 10.1111/1471-0307.12683. \n6.\tPonbhagavathi, T.R., Singh, A.K., Raju, P.N., Upadhyay, N. (2020). High performance liquid chromatographic (HPLC) determination of available lysine in milk protein-maize composite extrudates and its stability during storage. Journal of the Indian Chemical Society, 97(11a), 2344-2350\n7.\tTiwari, S., Upadhyay, N.*, Singh, A. K., Meena, G. S., & Arora, S. (2019). Organic solvent-free extraction of carotenoids from carrot bio-waste and its physico-chemical properties. Journal of Food Science and Technology, 1-10. 10.1007/s13197-019-03920-5\n8.\tBaria, B., Upadhyay, N.*, Singh, A. K., & Malhotra, R. K. (2019). Optimization of ‘green’extraction of carotenoids from mango pulp using split plot design and its characterization. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 104, 186-194. \n9.\tPatil, A. T., Meena, G. S., Upadhyay, N., Khetra, Y., Borad, S. G., & Singh, A. K. (2019). Effect of change in pH, heat treatment and diafiltration on properties of medium protein buffalo milk protein concentrate. Journal of Food Science and Technology, 56(3), 1462-1472. \n10.\tUttamrao, H. J., Meena, G. S., Borad, S. G., Punjaram, S. A., Khetra, Y., Upadhyay, N., & Singh, A. K. (2019). Effect of disodium phosphate and homogenization on physico-chemical and rheological properties of buffalo skim milk based ultrafiltered retentate. Journal of food science and technology, 56(5), 2426-2435. \n11.\tMeena, G.S., Dewan, A., Upadhyay, N., Barapatre, R., Kumar, N., Singh, A.K., & Rana, J.S. (2019). Fuzzy Analysis of Sensory Attributes of Gluten Free Pasta Prepared From Brown Rice, Amaranth, Flaxseed Flours and Whey Protein Concentrates. Journal of Food Science and Nutrition Research, 2(1), 022-037. DOI: 10.26502/jfsnr.2642-1100006\n12.\tPatil, A. T., Meena, G. S., Upadhyay, N.*, Khetra, Y., Borad, S., & Singh, A. K. (2018). Production and characterization of milk protein concentrates 60 (MPC60) from buffalo milk. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 91, 368-374. https://doi.org/10.1016/j.lwt.2018.01.028 \n13.\tUpadhyay, N.*, Jaiswal, P., & Jha, S. N. (2018). Application of attenuated total reflectance Fourier Transform Infrared spectroscopy (ATR–FTIR) in MIR range coupled with chemometrics for detection of pig body fat in pure ghee (heat clarified milk fat). Journal of Molecular Structure, 1153, 275-281. \n14.\tUpadhyay, N.*, Kumar A., Goyal A. and Lal, D. (2017). Complete liquification time test coupled with solvent fractionation technique to detect adulteration of foreign fats in ghee (heat-clarified milk fat). International Journal of Dairy Technology. 70(1): 110-118. doi: 10.1111/1471-0307.12323. \n15.\tUpadhyay, N.*, Goyal A., Kumar A. and Lal, D. (2017). Detection of adulteration of caprine body fat and mixture of caprine body fat and groundnut oil in bovine and buffalo ghee using Differential Scanning Calorimetry. International Journal of Dairy Technology. 70(2): 297-303. May 2017.doi:10.1111/1471-0307.12336. \n16.\tKumar, A., Upadhyay, N.*, Ghai, D.L., Kumar, A. Gandhi, K. and Sharma, V. (2016). Effect of preparation and storage of khoa on physico-chemical properties of milk fat. International Journal of Dairy Technology. 69(2): 294-300. doi: 10.1111/1471-0307.12266. \n17.\tUpadhyay, N.*, Jaiswal, P. & Jha, S.N. (2016). Detection of goat body fat adulteration in pure ghee using ATR-FTIR spectroscopy coupled with chemometric strategy. Journal of Food Science and Technology. 53 (10): 3752-3760. doi:10.1007/s13197-016-2353-2 ISSN 0022-1155\n18.\tRathi, M., Upadhyay, N.*, Dabur, R.S. and Goyal A. (2015). Formulation and physic-chemical analysis of whey –soymilk dahi. Journal of Food Science and Technology. 52(2): 968-975. doi 10.1007/s13197-013-1074-z. ISSN: 0022-1155. \n19.\tKanthale, P., Kumar, A. Upadhyay, N.*, Lal, D., Rathod G. and Sharma, V. (2015). Qualitative test for the detection of extraneous Thiocyanate in Milk. Journal of Food Science and Technology. 52(3): 1698-1704. DOI: 10.1007/s13197-013-1174-9. ISSN: 0022-1155.\n20.\tGoyal, A., Sharma, V., Upadhyay, N., Singh, A.K., Arora, S. and Ghai, D.L. (2015). Development of stable flaxseed oil emulsions as a potential delivery system of ω-3 fatty acids. Journal of Food Science and Technology. 52(7):4256-4265. \n21.\tUpadhyay, N.*, Kumar, A., Rathod, G., Goyal, A. and Lal, D. (2015). Development of a method employing reversed-phase thin-layer chromatography for establishing milk fat purity with respect to adulteration with vegetable oils. International Journal of Dairy Technology. 68(2): 207-217. doi. 10.1111/1471-0307.12178. \n22.\tGoyal, A., Siddiqui, S. Upadhyay, N., Soni, J. (2014). Effects of ultraviolet irradiation, pulsed electric field, hot water and ethanol vapours treatment on functional properties of mung bean sprouts. Journal of Food Science and Technology. 51(4): 708-714. doi 10.1007/s13197-011-0538-2. Publisher Springer. ISSN (electronic version): 0975-8402. \n23.\tKundu, H., Grewal, R.B., Goyal, A., Upadhyay, N.*, and Prakash S. (2014). Effect of incorporation of pumpkin (Cucurbita moshchata) powder and guar gum on the rheological properties of wheat flour. Journal of Food Science and Technology. 51(10):2600-2607. DOI: 10.1007/s13197-012-0777-x. ISSN: 0022-1155. \n24.\tUpadhyay, N.*, Kumar, A., Goyal, A. and Lal, D. (2014). A planar chromatographic method to detect adulteration of vegetable oils in ghee. JPC-Journal of Planar Chromatography-Modern TLC. 27 (6): 431-437. DOI: 10.1556/JPC.27.2014.6.5 \nNational Journals\n1.\tPonbhagavathi, T. R., Singh, A. K., Raju, P. N., Upadhyay, N. (2021). Textural and Sensory Characteristics of Milk Protein-Maize Flour-based Extrudates. Journal of Agricultural Engineering, 58(2), 124-136. 10.52151/jae2021581.1740\n2.\tPonbhagavathi, T.R., Singh, A.K., Raju, P.N., Upadhyay, N. (2020). Effect of Rennet Casein and Whey Protein Concentrate on Extrusion Behavior of Maize Flour. Current Journal of Applied Science and Technology. 39(33), 16-27, Article no.CJAST.57830.\n3.\tUpadhyay, N.*, Kumar, A., Lal, D., Kant, R., & Goyal, A. (2018). Detection of groundnut oil and goat body fat adulteration in ghee using principal component analysis on fatty acid profile. Indian Journal of Dairy Science. 71(5):464-472. \n4.\tUpadhyay, N.*, Kumar, A., Gandhi, K., Goyal, A. and Lal, D. (2014). Standardization of solvent fractionation technique for detection of adulteration in ghee by enriching animal body fat and vegetable oil in different fractions. Indian Journal of Dairy Science. 67 (4):323-327.\n5.\tGandhi. K., Upadhyay, N., Aghav, A.D., Sharma, V., and Lal, D. (2014). Detection of adulteration of ghee (clarified milk fat) with palmolein and sheep body fat using Reichert-Meissl (RM) value coupled with solvent fractionation technique. Indian Journal of Dairy Science. 67(5): 387-393. Received Second Best Paper Award during 44th Dairy Industry Conference organized by ICAR-NDRI, Karnal and Indian Dairy Association from 18-20, February 2016.\n6.\tAghav, A.D., Gandhi, K., Upadhyay, N., Kumar, A. and Lal, D. (2014). A study on the physico-chemical changes occurring in the milk fat during preparation of Paneer. Indian Journal of Dairy Science. 67 (5): 398-404.\n7.\tKumar, A., Upadhyay, N., Gandhi, K., Lal, D. and Sharma, V. (2013). Detection of soybean oil and buffalo depot fat in ghee using Normal-Phase Thin Layer Chromatography. Indian Journal of Dairy Science. 66(4): 294-99. ISSN: 0019-5146.\n8.\tKumar, A., Upadhyay, N., Gandhi, K., Kumar, A., Lal, D. and Sharma, V. (2013). Reverse-Phase Thin Layer Chromatography of Unsaponifiable Matter of ghee for detecting adulteration with soybean oil and buffalo depot fat. Indian Journal of Dairy Science. 66(6): 496-501. ISSN: 0019-5146.\n9.\tUpadhyay, N.*, Dabur R.S. and Rathi, M. (2011). Development and Shelf life Study of Flavoured Whey-soya milk beverage. Indian Journal of Dairy Science. 64(2): 92-101. ISSN: 0019-5146.\nOther Journals\n1.\tDewan, A., Meena, G.S., Upadhyay, N., Barapatre, R. Singh, A.K., Rana, J.S. (2017). Formulation of non-Gluten Pasta from the Optimized levels of Dairy and Non-Dairy ingredients. Madridge Journal of Food Technology. 2(2): 92–98. \n2.\tGalmessa, U., Prasad, S., Kumaresan, A., Oberoi, P. S., Baithalu, R. K., Upadhyay, N., and Dang, A. K. (2015). Modulation of Milk Fatty acid profile milk yield and composition through supplementation of omega-3 fatty acid in transition cow’s diet. Journal of Science and Sustainable Development. 3(1): 25-38. ISSN: 2070-1748\nREVIEW ARTICLES\n1.\tUpadhyay, N.*, Goyal, A. Kumar, A., Lal, D. and Singh, D. (2014). Preservation of milk and milk products for analytical purposes: A review. Food Reviews International. 30(3):203-224. DOI 10.1080/87559129.2014.913292. ISSN: 1525-6103\n2.\tGoyal, A., Sharma, V., Upadhyay, N., Gill, S. and Sihag, M. (2014). Flax and flaxseed oil: an ancient medicine & modern functional food. Journal of Food Science and Technology. 51(9): 1633-1653. DOI 10.1007/s13197-013-1247-9. ISSN: 0975-8402. \nBOOK CHAPTERS\n1.\tKumari, L., Sharma, M., & Upadhyay, N. (2021). Three-Dimensional Printing of Food Products: Printing Techniques, Novel Applications, and Printable Food Materials. Handbook of Research on Food Processing and Preservation Technologies: Volume 3: Computer-Aided Food Processing and Quality Evaluation Techniques, 55. Boca Raton, CRC Press\n2.\tUpadhyay, N.*, Harshitha, C. G., Pathak, N. K., & Sharma, R. (2021). Fourier Transform Infrared (FTIR) Spectroscopy with Chemometrics: Evaluation of Food Quality and Safety. Handbook of Research on Food Processing and Preservation Technologies: Volume 5: Emerging Techniques for Food Processing, Quality, and Safety Assurance, 271.\n3.\tNagarajappa, V., Upadhyay, N., Chawla, R., Mishra, S.K., & Nath, S. (2019). Functional Properties of Milk Proteins. In: Engineering Practices for milk products- Dairyceuticals, Novel Technologies, and Quality (pp 3-26). Apple Academic Press.\n4.\tUpadhyay, N., Kumar, M. C. T., Sharma, H., Borad, S., & Singh, A. K. (2019). Pulse Electric Field Processing of Milk and Milk Products. In: Non-thermal Processing of Foods (pp.129-144). Boca Raton, CRC Press\n5.\tUpadhyay, N., Nagaraj, V., & Singh, A. K. (2019). Advances in Fractionation of Milk Lipids: Analysis and Applications of fractions In: Recent Technologies in Dairy Science (pp. 325-344). Today and Tomorrow’s Printers and Publishers.\n6.\tNagaraj, V., Upadhyay, N.*, Nath, B. S., & Singh, A. K. (2018). Advances in Fractionation and Analysis of Milk Carbohydrates. In Technological Approaches for Novel Applications in Dairy Processing (pp. 127-147). IntechOpen. http://dx.doi.org/10.5772/intechopen.76312\n7.\tUpadhyay, N.*, Veena, N., Borad, S., & Singh, A. K. (2017). Application of Natural Antioxidants in Dairy Foods. In Natural Antioxidants (pp. 281-318). London: Apple Academic Press.\nINSTITUTE PUBLICATION\n1.\tDr. T. K. Datta, Dr. Meena Malik and Dr. Neelam Upadhyay (2017). Foundation Programme for Freshers at ICAR-NDRI 2017.\nPOPULAR AND LEAD ARTICLES\n1.\tPatil, A. T., Meena, G. S., Upadhyay, N., & Singh, A.K. (2017). Milk protein concentrates- Their Applications. Indian Dairyman, 69(9), 44-48.\n2.\tUpadhyay, N.* and R.K. Malik (2015). Nutritive Value of Milk. In: In Touch, Heinz Nutrition Foundation of India. Volume 17, Number 2&3, 2-11. (Lead Article). \n3.\tGoyal, A., Sharma, V., Upadhyay, N., Sihag, M. and Kaushik, R. (2013). High Pressure Processing and its impact on milk proteins: A Review. Research and Reviews: Journal of Dairy Science and Technology. 2 (1): 1-9. ISSN: 2319-3409.\n4.\tKumar, A., Upadhyay, N., and Naagar, S. (2012). Allergenicity of Milk Proteins, and its Management. Indian Food Industry. 31 (5&6): 45-50. ISSN: 0972-2610.\n5.\tGoyal, A. and Upadhyay, N. (2012). Nuclear Magnetic Resonance Spectroscopy in Dairy Science. Indian Food Industry. 31(1): 39-45. ISSN: 0972-2610.\n6.\tUpadhyay, N.*, Goyal, A. and Rathod, G. (2011). Microwave Spectroscopy and its applications in online processing. Indian Food Industry. 30(5&6): 63-73. ISSN: 0972-2610.\n7.\tउपाध्याय, नी*. (२०१८) भारत में कुपोषण: स्थिति और इससे निपटने के लिए रणनीतियाँ. दुग्ध—गंगा (आठवाँ अंक). अप्रैल-सितम्बर. २४-२९. \n8.\tउपाध्याय, नी.*, सिंह, आ.कु., गांगुली, स., सबिखी, ल. (२०१८) खाध्य और डेयरी क्षेत्र मे महिला उद्यमिता: कारण, समस्याए एवम उपलब्ध मंच. दुग्ध—गंगा (आठवाँ अंक). अप्रैल-सितम्बर. ६४-६९.\n9.\tउपाध्याय, नी*. (२०१९) ek¡ dk nw/k % f'k'kqvksa ds ekufld] 'kkjhfjd ,oa lkekftd mRFkku gsrq ve`r. दुग्ध—गंगा (नवाँ अंक). अकटूबर –मार्च १०२-१०४.\n10.\tउपाध्याय, नी*, fç;k ;koys (२०१९) [kk| inkFkksaZ esa —f=e ds cnys çk—frd jax o.kZd ds mi;ksx dh vko';drk दुग्ध—गंगा (दसवाँ अंक). अकटूबर –मार्च १०२-१०५.\n11.\tuhye mikè;k;, fuys'k dqekj ikBd (२०१९) d`f\"k] [kk| ,oa Ms;jh m|ksx ds Hkfo\"; eas lkSj ÅtkZ dk egRo दुग्ध—गंगा (दसवाँ अंक). अकटूबर –मार्च १२६-१३०. \n12.\tवैज्ञानिक और तकनीकी विषय के मूल हिंदी लेख जोकि गेहूँ एवम् जौ स्वर्णिमा में प्रकाशित हुए: उपाध्याय, नी*, राकेश कुमार (2020) महिला उद्यमिता के माध्यम से महिला सशक्तिकरण. गेहूँ एवम् जौ स्वर्णिमा (बारहवााँ अंक), पृष्ठ सं. 55-58; भाकृअनुप- भारतीय गेहूँ एवम् जौ अनुसंधान संस्थान, करनाल- १३२००१ द्वारा प्रकाशित\n\n8. Concepts/Processes/Products/Technologies/Patents/Others\n(i)\tConcepts \nCurrently, I am working on the integrated approach of application of green technology for the development of functional foods by utilizing under-utilized/ indigenous fruits and vegetables and/ or bio-waste. In the research projects, I am also keenly working on food chemistry and instrumental food analysis and applications of technologies/ products in dairy and non-dairy products. \nBesides this, I am working on development of functional food for addressing menopausal symptoms in osteopenic mice model. \n(ii)\tProducts/ Technologies ready for commercialization- 5\n1. Production of Milk Protein Concentrate 60 (MPC60), a high protein low lactose powder from buffalo milk (Co-Inventor)\n2. Technology for omega-3 rich mixed fat table spread (Inventor)\n3. Lipid and water soluble yellow natural colouring ingredient from bio-waste (Inventor)\n4. Technology for preparation of encapsulated flaxseed oil for its applications in foods (Inventor)\n5. Production of buffalo milk based Milk Protein Concentrate 60 (MPC60) powder with improved solubility (Co-Inventor)\n(iii) Expertise on\n1.Gas Liquid Chromatography\t5.Thin Layer Chromatography\n2.Fourier Transform Infra-red Spectroscopy\t6. Spectrophotometry\n3.Differential Scanning Calorimetry\t7.Chemical analysis including titration, distillation, etc.\n4.High Pressure Liquid Chromatography\t\n\n\n9. List of completed, on-going and submitted projects\nTitle of Project\tDuration\tRole\tFunding\tStatus\tRemarks\nEffect of storage on Baudouin test, sesamin test and RP-TLC test to detect adulteration of vanaspati and vegetable oils in ghee\t2015-2017\tCo-PI\tICAR-NDRI\n\tCompleted\tTwo research articles on RP-TLC\nPreparation and Characterization of Micro/nano delivery systems for “green” carotenoids\t2016-2019\tPI\t-Do-\t\t3 research articles+ 3 products/ technologies\nTechnology Development for the Production of Milk Protein Concentrate (MPC60) From Buffalo Milk\t2016-2019\tCo-PI\t-Do-\t\t4 research articles+ 2 products/ technologies\nTechnology of Goat Milk based Functional Beverage\t2017-2020\tCo-PI\t-Do-\t\tOne oral presentation\nTechnology for Moringa oleifera enriched cheese spread\t2020-2023\tPI\t-Do-\tOn-going\tCharacterization and incorporation of M. oleifera- pods in cheese spread is complete; shelf life study and animal trial is in progress\nDevelopment of flaxseed-rich probiotic dairy foods to address menopause symptoms\t2020-2023\tCo-PI\tDST\t\tDeveloped method -estimation of phytoestrogen; validation -in progress\nNutritional and therapeutic validation of chhachh and ghee prepared from indigenous cows by traditional method\tThree years (proposed)\tPI\tSEED Division, DST\tSubmitted \n \t\nCharacterization of Moringa oleifera leaves for functional bioactives and its application in table spread as model food system\tThree years (proposed)\tPI\tSYST, DST\t\t\nOther research work: \nDetection of adulteration of goat body fat and pig body fat in ghee using ATR-FTIR coupled with chemometrics; carried out during Professional Attachment Training at ICAR-CIPHET, Ludhiana\n\n\n\n10. Awards & honours \nName of Award\tYear\tAwarding Agency\nBest Paper Award\t2022\tGSAT (Gender Advancement for Transforming Institutions Self-Assessment Team), NDRI\nBest Poster Award\t2021\tNational Conference on Moringa Food Conclave-2021\nYoung Woman Scientist Award\t2020\tAgro Environmental Development Society during International Web-conference \nSecond Best Poster Award\t2020\tIndian Dairy Association\nCommendation certificate for Institute’s Magazine in which I am co-Editor\t2020\tTown Official Language Implementation Committee, Karnal\nLetter of Appreciation to editorial board of Institute’s magazine for receiving ICAR’s Second Prize and Trophy under Ganesh Shankar Vidyarthi Hindi Patrika Puraskar (2018-19)\t2020\tICAR- National Dairy Research Institute, Karnal\nAssociate Fellowship\t2019\tNational Academy of Dairy Science India\nFirst Prize in E-poster \t2018\tIndian Dairy Association\nOne Best oral Presentation\t2018\tHome Science Association of India\nBest Oral Presentation to my Master’s student\t2018\tICMR- National Institute of Nutrition\nBest Poster Award\t2016\tIndian Dairy Association\nSecond Best Paper Award\t2016\tIndian Dairy Association\nICAR-SRF (PGS) with 2nd rank\t2011-12\tICAR\nGATE (Engg Sciences: Food Tech; Thermodynamics)\t2010\tMHRD, GoI\nInstitution level awards\nThird prize in poster presentation \t2021\tICAR- National Dairy Research Institute, Karnal\nInstitute’s Rajbhasha Gaurav Certificate\t2020\t\nFirst prize in Scientific and Technical writing\t2019\t\nConsolation prize in Scientific and Technical writing \t2020, 2019 \t\nFirst prize in Poster Presentation- 2020, 2018, 2017\t\t\nThird prize in poster presentation\t2019\t\nFirst Prize in hindi extempore\t2017\t\nThird, first and second prize in hindi essay writing in consecutive years – 2020, 2019, 2018\t\t\n\n\n11. Teaching Assignments \n(a) Teaching: Actively involved either as course in-charge or associate \nClass\tB.Tech (DT)\tMSc/ MTech\n(FT) (till 2021)\tM.Tech (DT)\tPhD (DT/ DC/ FSQA)\nNo. of courses\t1-2\t2-3\t0-1\t2-3\nDT- Dairy Technology, DC- Dairy Chemistry, FT- Food Technology, FSQA- Food Safety Quality Assurance\n(b) Student’s guided\nDegree\tMajor Advisor \tCo-Advisory\tStatus/ Remarks\nM. Tech (DT)\t8\t2\tCompleted\n\t1\t0\tOn going\nM. Tech/ M Sc (FT/ FSN)\t2\t1\tCompleted\nM. Tech (DC)\t0\t3\tCompleted\nM. Tech (DM)\t0\t1\tCompleted\nPhD (DT)\t2 \t0\tOngoing \n\t0\t2\tCompleted\nPhD (DC)\t0\t1 \tCompleted\n\t\t1\tOn going\ni.\tThree students under my guidance as major advisor and one student as co-advisory member nominated for Best thesis award; \nii.\tOne represented NDRI at zonal-level student research convention ANVESHAN-2018\n\n12. Lectures/ member/convener of committees: \ni.\tLectures: \na.\tEntrepreneurship Development Programme (EDP) (conducted by SINED-TBI/BPD unit, ICAR-NDRI) and Online Training of Master Trainers on Fat and Oilseed processing conducted by SINED-TBI/BPD unit (ICAR-CIPHET); \nb.\tStudent’s Counselling session at SRCASW, University of Delhi, \nc.\tWorkshop conducted at DAV college, Karnal, etc\nd.\tDelivered talks at various villages on the importance of mother’s milk, nutrition in first 1000 days of an infant’s life, nutri-thali, etc\nii.\tTraining Organized: \na.\tTwenty one days Training at Centre for Advanced Faculty Training (DT Division) on ‘R & D strategies and interventions for effective agribusiness and entrepreneurship development in dairy and food sector’; \nb.\tone/two months or shorter duration trainings for students and others under BPD unit and KVK, NDRI, Karnal\nc.\tFive days training on the aspects of dairy processing to the farmers of Karnal district. \niii.\tGeneral Secretary, Staff Club, NDRI, Karnal\niv.\tMember: Student Empowerment Unit, Conferences organized from 2015 till 2018, convocation, credit seminar evaluation committees; Mera Gaon Mera Gaurav program, Farmer’s First Door programme, Swatchh Bharat Abhiyan, coordinator and mentor of different groups for organizing Foundation Program-2017, 2018, Nodal officer of Poshan Maah-2020 etc\nv.\tConvener/ Rapporteur of sessions: Conference, Dr. K. K. Iya Memorial oration; International conference of Proteomics Society of India\nvi.\tOther responsibilities: Management Representative of QMS-IS/ISO 9001:2008 and HACCP- IS 15000:2013 of Experimental Dairy (essential part of institute) until Jan 2019; one of the editors of Institute hindi magazine Dudgh Ganga which also received coveted award from ICAR (until 2019).\nvii.\tResource Generation on account of consultancy provided in field of dairy processing and by conducting sponsored trainings \nMore than ₹ 2 50 000/- (Two lakhs fifty thousand only)\nviii.\tBesides research, teaching and extension activities, I am also involved in promotion of Hindi language and have won several prizes during competitions (like extempore, essay, e-mail writing) organized by Official Language Units.\nix.\tLifetime Member of three scientific bodies: Indian Dairy Association- RE/NZ/LM/10852/HR; Association of Food Scientists & Technologists (INDIA)- AFST/LM/9-2018/KRN/2444; Lifetime member of Home Science Association of India; Membership number: HSAI-2017-HR-127-LF\nx.\tReviewed research papers of Journal of Ayurveda and Integrative Medicine (Elsevier), LWT, International Journal of Food Properties, Indian Journal of Dairy Science, Indian Journal of Natural Products and Resources, United Scientific Group, etc. \n\n\n\n\n\n\n\n\nDated: 12-04-2022\t \nNeelam Upadhyay",institutionString:"National Dairy Research Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Dairy Research Institute",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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1. Introduction
Pandemics and epidemics of infectious origin are large-scale outbreaks that can greatly increase morbidity and mortality globally or over a wide geographic area, respectively [1]. Pandemics have occurred throughout history and appear to be increasing in frequency in the last centuries. Noteworthy examples include the Black Death at the end of the Middle Ages, Spanish flu in 1918, the 2014 West Africa Ebola epidemic or the current COVID-19 pandemic. The direct impact of pandemics on health can be dramatic. These large outbreaks can disproportionally affect younger or active workers, but vulnerable populations such as the elderly are at a particular high-risk. Pandemics can cause acute, short-term as well as longer-term damage to economic growth due to public health efforts, health system expenditures, and aid to affected sectors. Evidence suggests that epidemics and pandemics can have significant social and political consequences too, by debilitating institutions, amplifying political tensions, stigmatizing minority populations, or encouraging sharp differences between social classes [2].
Outbreaks by respiratory ribonucleic acid (RNA) viruses such as influenza or coronaviruses entail the principal threat due to their ease of spreading among humans, their potential severity and recurrence. However, other RNA viruses such as flaviviruses (Zika) or filoviruses (Ebola) must be taken into consideration due to a great overall burden of morbidity and mortality [3]. Antiviral drugs can help mitigate a viral outbreak by reducing the disease in infected patients or their infectiousness. While these drugs can be very successful against some viruses (e.g. hepatitis C virus [HCV]) [4], they are not universally effective as exemplified in the current SARS-CoV-2 pandemic [5]. Nowadays, having effective vaccines may be the only tool to reduce susceptibility to infection and thus, prevent the rate of virus spread [2].
Vaccination has dramatically decreased the burden of infectious diseases. Vaccines have saved hundreds of millions of lives over the years [6]. It has been estimated that approximately 103 million cases of childhood diseases were prevented in the United States through vaccination between 1924 and 2010 [7]. The eradication of smallpox in 1980 through vaccination is considered one of the crown accomplishments of medicine. Despite these achievements, effective vaccines have been developed against just over 30 pathogens among bacteria and viruses. There are many pathogens, including viruses such as human immunodeficiency virus (HIV) or respiratory syncytial virus (RSV), for which all efforts for vaccine development have failed so far. In addition, current available vaccines for worldwide important viral diseases like influenza are suboptimal, especially in the elderly, resulting in vulnerability among billions of at-risk populations [6]. On the other hand, having a new effective and safe vaccine in time to control highly contagious emerging viruses that cause epidemic or pandemic threats is an almost impossible task considering the timeframes for vaccine development. This includes preclinical and clinical research, its approval by the regulatory authorities, as well as its production and distribution [3].
Altogether, it has been postulated that one possibility of filling the gap between the appearance of a viral outbreak by an emerging pathogen and the availability of a specific vaccine is to take advantage of the heterologous protection of some existing vaccines, in order to increase the non-specific resistance of the host through trained immunity [8, 9].
2. Specific anti-infectious vaccines
Conventional (specific) anti-infectious vaccines are biological preparations containing live-attenuated or dead microorganisms, their antigens or nucleic acids encoding for them, designed for specific pathogens. The purpose of vaccination is to induce a long lasting adaptive immune response against key antigens able to confer host resistance for future encounters with the corresponding pathogen. Either the production of antibodies, generation of T helper/effector cells, or both, may play a critical role in such a resistance, which greatly depends on the type of pathogen, the route of entrance and the host-pathogen relationship (e.g., extracellular and/or intracellular) [10]. Successful vaccines are highly effective not only in inducing long-lasting immunity against disease-causing pathogens, but also in providing herd immunity to the community that substantially restricts the spread of infection [6].
Most of the vaccines available today have been developed empirically and used successfully long before their mechanism of action on the immune system was understood. Early protection is associated to induction of antigen-specific antibodies, being their quality (avidity, specificity, or neutralizing capacity) key factors for their efficacy. Long-term protection relies on the persistence of vaccine antibodies and availability of immune memory cells capable of rapid and effective reactivation with subsequent microbial exposure. On the other hand, T cells have a critical role in the induction of high affinity antibodies and immune memory. Furthermore, T cells have a direct role in protection conferred by some vaccines, including the tuberculosis Bacille Calmette-Guérin (BCG) vaccine [11].
Vaccines using whole pathogens have been classically classified as either live attenuated or inactivated (killed). Subunit vaccines contain just selected antigens (e.g., proteins, polysaccharides). Recently, due to a growing availability of bioinformatics and sequencing tools, there has been an increase interest on so-called “rational” vaccine design approaches for subunit vaccines, such as the reverse vaccinology [12]. In this regard, modern vaccines include recombinant proteins or nucleic acids [13]. Rather than administering the antigen itself, DNA and mRNA vaccines targeting dendritic cells (DCs) encode the antigen of interest that will be produced by the vaccinated host, representing a new era in vaccinology [14]. In fact, the first RNA vaccine licensed for humans in Western countries has been recently developed for SARS-CoV-2.
As commented before, a vaccine response is linked to the induction of T and B cell specific responses to the antigens contained in the vaccine. This requires lymphocyte activation, proliferation and differentiation on specialized lymphoid tissues (e.g lymph nodes), where antigen presenting cells, like DCs for T cells or follicular dendritic cells (FDCs) for B cells, are present. Mature DCs are recruited into the T cell areas of lymph nodes from the periphery, e.g., at the site of injection of the vaccine. DCs express pattern recognition receptors (PRR) that recognize evolutionary conserved pathogen-associated molecular patterns (PAMPs) that are not contained in self-antigens and are identified as “danger signals” [15]. When immature DCs are exposed to the vaccine-derived antigens at the site of vaccination, they uptake them and become activated [16]. This activation will lead to their maturation with the expression of homing receptors at their surface, triggering DC migration to the draining lymph node through afferent lymphatic vessels, where the activation of T and B lymphocytes will occur. Mature DCs process the up-taken antigens and present them to naïve T cells associated to molecules of the major histocompatibility complex (MHC) within the T cell areas of lymph nodes. On the other hand, unprocessed native antigens, either free or complexed with antibodies or complement, access the B cell areas of lymph nodes (lymphoid follicles) where they are captured by FDCs and displayed from their cell surface to the B cells. Antigen-specific B cells will rapidly proliferate forming a germinal center and differentiate into plasma cells producing low-affinity immunoglobulin (Ig) M antibodies. The B cells will then receive additional signals from activated T cells, undergoing isotype antibody switch from IgM to IgG or IgA and affinity maturation of the antibodies produced.
For a vaccine to be immunogenic enough, DC activation, that can be achieved by adjuvants, is essential. Live attenuated and inactivated whole-cell vaccines are considered “self-adjuvanted” as they naturally present sufficient PAMPs to activate innate immune cells, including DCs; thus, promoting a robust antigen-specific immune response. In contrast, subunit vaccines generally require different types of adjuvants to enhance and/or drive the immune response in the desired direction [15, 17].
2.1 Difficulties for novel specific vaccines in a viral outbreak situation
Viral outbreaks appear when there is a sufficient number of susceptible individuals within a nearby population. Although susceptibility is a balance between host factors (high/low resistance) and pathogens (high/low virulence), in many cases it reflects a lack of prior contact with a given pathogen. In general, this is related to the emergence of new viruses or the lack of effective vaccines against known viruses. As pointed above, the development of effective vaccines is not an easy task against certain viruses. We are still lacking vaccines for some of the most lethal viral infections, including HIV and MERS-CoV, among others. These pathogens are difficult to tackle, as we do not fully understand their mechanisms to evade the immune system or how to elicit protective immunity against them [13]. However, encouraging progress is being made against these pathogens and there are currently several “pipeline vaccines” in development, such as RSV, universal influenza vaccine, and SARS-CoV-2 [18, 19, 20]. Apart of SARS-CoV-2 for obvious reasons in the current pandemic, there is an urgency to have a universal influenza vaccine that provides a broad and durable protection from influenza virus infection. Yet, the high level of antigenic diversity and variability, and antigenic drift in the surface antigens, enable these viruses to escape antibody-mediating neutralization [21]. On the other hand, there is a number of vaccines currently licensed, including the influenza A virus vaccine, that provide incomplete protection, especially in high-risk groups [22]. Mumps outbreaks observed in Ireland, United Kingdom and United States in vaccinated subjects with Measles Mumps Rubella (MMR) vaccine is another example [23]. Different factors have been postulated to contribute to mumps outbreak, including waning immunity and primary and secondary vaccine failure. Yet, their actual contribution is not fully understood [23].
Vaccine efficacy must consider different target populations as well. Adaptive immune response to vaccines may be limited in newborn and the elderly. Early in life, immune responses are dampened compared to adults [24, 25]. Neonates have underdeveloped germinal centers in lymph nodes and the spleen, and low expression of B cell receptors which in turn results in low levels of primary IgG responses to infections and vaccines [26]. As we age, our immune system undergoes age-related changes that lead to progressive deterioration of the innate and the adaptive immune responses, this is termed immunosenescence. The most common features of immunosenescence are short-lived memory responses, impaired response to new antigens, increased predisposition to autoimmune diseases and low-grade systemic inflammation (inflammaging) [27, 28]. Immunosenesence results in increased susceptibility to infections and deficient response to vaccination causing high hospitalization and mortality rates. For example, influenza vaccine efficiency has been reported to be 17–53% in the elderly, compared with the 70–90% efficacy in young adults [29]; and vaccination with Varicella zoster virus (VZV), also an important pathogen in elderly people, only partially prevents reactivation of herpes zoster [27].
If the difficulties listed above are outlined for existing or developing vaccines, quickly obtaining an effective vaccine to urgently control a new virus outbreak is almost an impossible task in the short-term as pointed above. This is well exemplified by the SARS-CoV-2 vaccine race pushed by the devastating COVID-19, with more than 100 vaccine candidates in the running. It is considered that no less than 1 year will last the time until the first licensed vaccine can provide protection in the best scenario [30]. This, in spite of greatly shortening the usual clinical development time and regulatory obstacles for a new vaccine and, therefore, without knowing its true performance and/or safety in the medium term compared to other authorized vaccines [31].
3. Trained immunity and infections
It has become evident from epidemiological, clinical and experimental data that some conventional whole-cell vaccines, like BCG and others, also provide resistance to infectious diseases not related with the specific pathogen targeted by the vaccine [32, 33, 34]. Much of these non-specific “heterologous” effects appear to depend on the activation of innate immune cells by the PAMPs contained naturally in these vaccines [10], although other mechanisms such as cross-reactive epitopes between different pathogens could also account for this protection in some cases [35].
Immunological memory, understood as the ability to “remember” past encounters with pathogens, has been classically attributed to the adaptive branch of the immune system exclusively, by virtue of the antigen-driven clonal expansion of T and B lymphocytes and exemplified by the mechanism of conventional specific vaccines pointed above. However, the notion that innate immunity was unable to induce immunological memory has been challenged in recent years, particularly from studies in organisms that lack adaptive immunity, such as plants or invertebrates, as well as early studies in mice lacking the adaptive immune system [8, 36]. Altogether, the term ‘trained immunity’ was coined to define an innate immune memory that lead the innate immune system to an enhanced response to secondary challenges [37]. Importantly, trained immunity seems to be underlying the heterologous effects of an increasing number of vaccines [38, 39, 40].
3.1 The concept
What is trained immunity? - Trained immunity is defined as the memory of the innate immune system, where an encounter with a first stimulus (e.g. a microbial insult) results in a subsequent long-term adaptation and enhanced non-specific response by innate immune cells against a secondary challenge (the same or unrelated), thus providing non-specific, broad-spectrum, long-term protection in case of infection [8, 9, 37, 41].
Which cells can be trained? - Trained immunity properties have been defined for distinct cell subsets of the innate immune system [9, 42], including natural killer (NK) cells and innate lymphoid cells [43]. Of note, training of myeloid cells [42], particularly monocytes and macrophages [44, 45], and more recently DCs [46, 47] and hematopoietic stem cells [48], have been extensively studied. Finally, the acquisition of this immunological memory has also been demonstrated to a lesser extent for non-immune cells [49].
How to get trained? - A wide variety of stimuli can train innate immune cells, particularly when considering monocytes and macrophages [9, 50]. Among infectious agents, live microorganisms such as the tuberculosis vaccine BCG [51], Candida spp [52] or viruses [53, 54]; bacterial components, such as flagellin, lipopolysaccharide, muramyl dipeptide [55], fungal components as β-glucan [52] or even helminth products [56]. In general, microbial ligands engaging some PRR, like C-type lectin receptors (CLRs), nucleotide-binding oligomerization domain-like receptors (NLRs) are well established training inducers, whereas those engaging toll-like receptors (TLRs) may have opposite effects depending on the TLR type and concentration [55, 57]. Intriguingly, not only infectious agents but also endogenous inducers and metabolites such as oxidized low-density lipoprotein or mevalonate can induce trained immunity [50].
What hallmarks define trained immunity? - In contrast to adaptive immune responses, epigenetic reprogramming of transcriptional pathways — rather than gene recombination — mediates trained immunity. This training phenomenon comprises three key hallmarks that occur at the intracellular level: increased cytokine production upon rechallenge, changes in the metabolism and epigenetic reprogramming [9, 58, 59], which eventually support increased protection upon infection.
Among those cytokines whose production is augmented after re-exposure in trained cells, proinflammatory molecules such as tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β and interferon γ (IFN-γ) are fairly constant [45, 52, 55, 60, 61]. Modulation of IL-10 varies between studies [45, 52, 56, 62, 63]. A noted shift from oxidative phosphorylation to aerobic glycolysis (Warburg effect) is the main change in cellular metabolism during the induction trained immunity [64]. Moreover, glutaminolysis, cholesterol synthesis and the tricarboxylic acid cycle are non-redundant pathways required for trained immunity to take place [64, 65]. Epigenetic reprogramming, mainly mediated by histone modifications, is one of the bases for the long-lasting effect of trained immunity [8, 66, 67, 68]. Immune pathway activation and changes in metabolism serve as basis for epigenetic rewiring [65]. As a result, epigenetic modifications have been found at the level of important promoters for the training process, which makes chromatin more accessible and conditions gene expression patterns of trained cells upon stimulation with a secondary challenge [69].
As a result of the whole process, enhanced, broad-spectrum, non-specific protection mediated by innate immune cells is found upon infection. This cross-protection has been observed for a wide range of human pathogens including fungi [51, 52], parasites [70, 71] and different bacterial infections [72, 73, 74, 75]. Importantly, induction of trained immunity has been proved to be effective against viral infections including yellow fever [76], influenza A virus [77] and others [78, 79]. In this line, the induction of this phenomenon has been also proposed as a tool for reducing susceptibility to emergent SARS-CoV-2 infection, as will be described at the end of the chapter [78, 80].
How long does trained immunity last? – Trained immunity phenotypes have been observed for months and up to one year after the training insult. This was initially controversial, as trained immunity properties had been attributed to short-lived myeloid cells such as monocytes or DCs [38]. In this regard, several studies have shown that modulation of bone marrow progenitors is also an integral component of trained immunity, supporting the long-lasting effect of this phenomenon [9, 81]. In this way, trained immunity inducers [82, 83, 84, 85] would be able to reprogram and induce expansion of hematopoietic progenitors with a particular bias to the myeloid lineage. Thus, bone marrow-derived mature cells would be also trained [86], showing improved clearance of infection [83].
Complementary to progenitor reprogramming, peripheral trained immunity induction would take place in tissue-resident cells [9]. This is especially relevant at the mucosal level, where cells encounter most of the infectious training inducers. Alveolar macrophage (AM) memory was demonstrated following viral infection [87, 88]. Training of these long-living cells led to increase antimicrobial properties, independently of systemic immunity [87, 89]. This local training of AM was further reproduced following respiratory mucosal administration of tuberculosis vaccine, being crucial for Mycobacterium tuberculosis clearance [90]. On the other hand, training of NK cells lead to long-lived, self-renewing, stable expanded cells with memory-like properties, both in an antigen-dependent or independent manner [91, 92, 93]. Finally, it was also reported that self-renewing long-living skin epithelial stem cells exhibited local trained immunity, providing faster wound healing in primed mice than in naïve mice [94, 95].
3.2 Trained immunity on ongoing immune responses
3.2.1 Effect on adaptive immunity
Non-specific effects of vaccines have been extensively studied and reported over the last decades. Although trained innate cells could partially account for these effects, involvement of adaptive immunity has also been suggested [96]. An adaptive immune mechanism of non-specific effects could be heterologous immunity; vaccine antigens can give rise to T cell cross-reactivity against other antigens that may confer some protection against unrelated pathogens [96, 97].
However, innate immune cells constitute the bridge between the intrusion of microbial threats and the activation of adaptive immunity. As said before, following sensing of pathogens by PRRs, activated innate immune cells secrete different factors and act as antigen-presenting cells (APCs) to initiate activation of adaptive immunity [98]. Thus, it would not be unexpected that trained innate immune cells, within their acquired enhanced properties, would be able to induce stronger adaptive immune responses [39]. In this regard, BCG vaccine, a well-known trained immunity inducer, has shown to enhance the antibody titer and alter heterologous T cell responses against a wide range of vaccines and unrelated infections [99, 100, 101]. In different experimental models, BCG-mediated protection against viral and Plasmodium infections was abrogated in the absence of T cells. In these models, BCG vaccination has been mainly associated with modulation of CD4+ T helper (Th) 1 responses. Similar observations have been found in different clinical studies [99]. Of note, BCG vaccinated human volunteers displayed a long-lasting heterologous Th1 and Th17 response upon stimulation with unrelated pathogens and TLR-ligands [38]. To some extent, similar observations have been found in other vaccines such as diphtheria-tetanus-pertussis (DTP) or measles vaccine [99].
As said before, trained immunity properties have been recently described also for DCs. As being the most professional APCs, they emerge as crucial bridge for potentiating adaptive immune responses. In this sense, DCs with high immunostimulatory properties that enhance adaptive immune responses via IL-1β release had been described [102]. More recently, programmed memory DCs have shown to increase Th1/Th17 immunity and confer protection during cryptococcosis [46]. Finally, different polybacterial preparations of whole-cell inactivated bacteria, have shown to prime DCs and induce enhanced Th1, Th17 and IL-10 T cell responses against related and unrelated stimuli [103, 104]. This capability of modulating heterologous T cell responses by APCs have been also described to suppress pathogenic T cell immunity in experimental models of autoimmune encephalomyelitis [56].
3.2.2 Effector functions on trained innate immune cells
As noted above, a hallmark of trained innate immune cells is the enhancement of some effector functions leading to increased non-specific resistance against a variety of pathogens. In this regard, β-glucan-trained monocytes show enhanced candidacidal activity and efficiently inhibit the C. albicans outgrowth [52]. Production of reactive oxygen species (ROS) has shown to be also affected by the induction of training. Thus, BCG-trained monocytes [45], β-glucan-trained macrophages [105] or β-glucan-trained neutrophils [106] produced increased amount of ROS following different challenges. Finally, increased phagocytosis and production of microbicidal molecules have been observed in β-glucan-trained macrophages [70, 105]. Mechanisms underlying this enhanced effector function could be an intrinsic cell reprogramming as consequence of the training, as well as be supported increased expression of different PRRs and surface molecules [45, 60, 87]. Altogether, these enhanced effector responses could improve pathogen clearance by increasing host resistance.
On the other hand, a substantial part of the adaptive immune response is directed at recruiting other effector cells from the innate immune system to eventually resolve an infection. Both T helper and B responding cells release cytokines, antibodies, and other mediators that activate monocytes, macrophages, NK cells or neutrophils to clear extracellular and intracellular pathogens [107]. Multiple studies have demonstrated the importance of IFN-γ-mediated priming in the activation of macrophages [108, 109], produced by CD4+ Th1 and CD8+ T cells [107]. In this sense, it has been previously demonstrated that adaptive T cells render innate macrophage memory via IFN-γ-dependent priming [87, 89]. Furthermore, a deep crosstalk between Th17 and neutrophils have been widely demonstrated, via production of IL-17 and other related cytokines [110].
Taken into account the potential role of trained innate cells in both the induction of adaptive and effector responses, a notable amplification loop in the global immune response could be considered (Figure 1).
Figure 1.
Effect of trained immunity on ongoing immune responses. Induction of trained immunity allows trained cells to enhance adaptive immune responses and vice versa, final effector functions of trained cells can be further potentiated by enhanced adaptive responses.
4. Trained immunity-based vaccines
Based on trained immunity pillars, a next generation of anti-infectious vaccines has been postulated, coined as ‘Trained Immunity-based Vaccines’ (TIbVs). TIbVs would be conceived to confer a broad protection far beyond the antigens they contain. By proper targeting of innate immune cells to promote trained immunity, a TIbV may confer non-specific resistance to unrelated pathogens while trained immunity memory is still present, in addition to the specific response given by intrinsic antigens [39].
A bona fide TIbV would consist of two main components: the trained immunity inducer(s) and the specific antigen(s). The antigen(s) mission is to generate an adaptive (specific) immune response as any conventional vaccine. The trained immunity inducers aim to promote the training of innate immune cells. This innate immune training would confer non-specific resistance against unrelated pathogens for a window of time (months) plus an enhanced adaptive immune response to the antigens present in the vaccine itself or from other sources (e.g., coming from eventual infections or bystander pathogens) [39].
Two additional concepts arise under the TIbV umbrella: i) trained immunity-based immunostimulants (TIbIs) and ii) trained-immunity-based adjuvants (TIbAs). The former (TIbIs) would induce the training of innate immune cells, so they would be ready-to-act against upcoming infections conferring broad non-specific protection while trained immunity is present, still enhancing adaptive immune responses following any eventual natural infection. The latter (TIbAs) would enhance adaptive responses against specific antigens incorporated either to the trained inducers as in bona fide TIbVs, or in a separated but combined vaccine [39] (Figure 2).
Figure 2.
Different possibilities of trained immunity-based vaccines (TIbVs). Under the umbrella of trained immunity-based vaccines (TIbVs) different possibilities exist depending on their design and purpose. Bona fide TIbVs are those containing both trained immunity inducers and antigens in the same vaccine as occurs in conventional vaccines with trained immunity inducing properties. These vaccines show heterologous protection in addition to the specific response to the target antigen. TIbIs are intended just to confer non-specific protection by means of trained immunity induction beyond the intrinsic antigens they may contain. TIbAs are intended to enhance the specific response of other vaccines that are administered later, once trained immunity has been induced, or specific antigens combined in the same vaccine as any other adjuvant.
Following the above features, the TIbV concept can be applied to existing anti-infectious vaccines composed of microorganisms that show heterologous protection ascribed to trained immunity.
4.1 Available vaccines with heterologous protection against viral infections
During the last decades, robust epidemiological data has demonstrated the role of certain vaccines leading to protection against heterologous infection with a high impact on overall mortality in children [111, 112, 113]. This protection could not only be explained by protection achieved by the target disease. Studies on MMR vaccination in high-income settings have also evidenced a reduction in non-target infections, particularly in respiratory infections [114]. A limitation for most of these epidemiological studies is that they do not identify the agent (viral, bacterium or parasite) responsible for the infection. These heterologous effects of certain vaccines conferring non-specific protection for a quite long time are believed to be largely due to non-specific stimulation of the innate immune system. It is not yet clear whether this is a direct reflection of trained immunity induction (i.e., acting as TIbVs) in every case. The fact that most of these vaccines use live-attenuated microorganisms, i.e., self-replicating agents, may suggest that a continuous stimulation of innate immune cells is necessary to obtain protection and/or to achieve a proper trained immunity for this purpose.
4.2 Live attenuated vaccines
4.2.1 BCG
The BCG-Denmark strain was tested in randomized-controlled trials (RCT) in infants who normally did not receive the BCG vaccine at birth. These studies carried out in Guinea-Bissau demonstrated that vaccination at birth was associated with lower neonatal mortality, especially due to neonatal sepsis, respiratory infections, and fever [111, 115]. In these lines, a meta-analysis commissioned by the WHO concluded that BCG administration during the first month of life reduces all-cause mortality by 30% [116]. In these studies authors did not discriminate the etiology of infection (bacterial vs. virus); therefore, a reduction in viral infections may explain, to some extent, this result. However, in two studied carried out in India in neonates with BCG-Russian strain no such effect was observed [117]; suggesting that different immunological effect of diverse BCG strains may account for these discrepancies. A study carried out in infants to assess the impact of BCG vaccination on the incidence of RSV infection suggested a possible protective role for BCG vaccination against acute lower respiratory tract infection [118]. Other clinical studies have provided evidence suggesting a protective role for BCG on secondary viral infections [79]. In this regard, the impact of BCG vaccination on viral infection in human healthy volunteers has been assessed using the live attenuated yellow fever vaccine (YFV) as a model of viral human infection [76]. BCG vaccination induced epigenetic reprogramming in human monocytes, and these modifications correlated with IL-1β upregulation and the reduction of viremia, all these features being the hallmarks of trained immunity [76].
Similar protective effect of BCG was observed in several studies in elderly people regarding respiratory tract infections. BCG vaccination in subjects of 60–75 years old once a month for three consecutive months resulted in reduction of acute upper respiratory tract infection, concomitant to significant increase in IFN-γ and IL-10 compared with those receiving placebo [119]. A recent randomized trial of BCG vaccination was carried out in elderly patients (age ≥ 65 years) returning home from hospital admission, these subjects are at high risk to develop infections. The BCG vaccination increased the time to first infection (primary outcome) and decreased the incidence of a new infection [120]. Besides, results demonstrated that BCG vaccination resulted in lower number of infections of all causes, especially respiratory tract infections of probable viral origin, although no discrimination was made between respiratory tract infections caused by bacteria or viruses.
BCG has also been shown to enhance the response to vaccines directed against viral infections [79]. A clinical study in healthy volunteers demonstrated that BCG administration prior to influenza vaccination increases antibody titers against the 2009 pandemic influenza A (H1N1) vaccine strain, concomitantly with an enhanced IFN-γ production to influenza antigens compared with the control group [121].
4.2.2 Influenza vaccine
The cold-adapted, live attenuated influenza vaccine (CAIV) has been shown to provide non-specific cross-protection against RSV in an experimental model of infection [122].
In a randomized pilot study conducted in healthy volunteers receiving a trivalent influenza vaccine, cytokine responses against unrelated pathogens were observed [121]. During the 2003–2004 influenza A (H3N2) outbreak, an open-labeled, nonrandomized vaccine trial was carried out in children 5 to 18 years old. Subjects received either trivalent live attenuated or inactivated influenza vaccine. Live attenuated influenza vaccine but not trivalent inactivated vaccine was effective in children administered during influenza outbreak, despite the dominant circulating influenza virus was antigenically different from the vaccine strain [123].
4.2.3 Measles vaccine
Measles vaccine (MV) is among the live vaccines that have been shown to have beneficial effects reducing all-cause mortality [124]. Randomized clinical trials and observational studies from low-income countries have concluded that measles vaccination is associated with decreased overall mortality and morbidity [100]. However, a systematic review carried out by Higgins and colleagues has pointed out that most of these studies were considered at high risk of bias [116]. Nevertheless, MV seems to induce a transient suppressive effect on both the lymphoproliferative and innate response evaluated in peripheral blood mononuclear cells (PBMCs) from children, with slight increase in innate immune response, measured by non-specific cytokine production [100]. It has been reported that following measles vaccination, the ex vivo production of both innate (IL-6 and TNF-α) and adaptive (IFN-γ and IL-2) cytokines decreases for 2 weeks, but levels of IL-2, IL-6 and IFN-γ are increased at day 30 post vaccination compared with baseline [125]. Differences in males and females have been reported, where girls seem to receive stronger beneficial effects. In this regard, a study of MV-specific innate responses following MMR vaccination found higher TNFα, IL-6 and IFN-α secretion, cytokines associated to trained immunity, in adolescent girls than boys [126].
4.2.4 Oral polio vaccine
There are currently only three countries where polio remains endemic. Thus, polio-free, high income countries are introducing the use of the inactivated polio vaccine (IPV). However, there are still many countries that use the live-attenuated oral polio vaccine (OPV). Despite current WHO policy to replace OPV by IPV, there is epidemiological evidence that supports that replacing OPV by IPV might have an impact on overall mortality [96], since OPV has shown strong non-specific beneficial effects even in settings where the incidence of the targeted infection is low. In this regard, campaigns to eliminate polio in West Africa have been associated with lower child mortality rates [127].
4.3 Inactivated vaccines
As pointed above, most of the vaccines described so far showing non-specific heterologous effects contain live-attenuated microorganisms. Nevertheless, fully inactivated bacterial vaccines have also been described conferring protection against viral infections, and some of them for a fairly long period of time. Interestingly, these vaccines are mucosal preparations that are administered daily for long periods of time (weeks/months) rather than single, or seldom, doses used in live attenuated vaccines. Thus, it seems that the much longer administration of these inactivated mucosal vaccines resembles the effect achieved by live vaccines on heterologous protection associated to trained immunity (Figure 3).
Figure 3.
Trained immunity window by self-replicating and inactivated TIbVs. Trained immunity-based vaccines (TIbVs) containing live-attenuated self-replicating microorganisms (e.g. BCG) may require fewer administrations to induce an adequate trained immunity window of sufficient intensity, quality and/or duration than vaccines with dead microorganisms. Fully-inactivated TIbVs can be enhanced to induce trained immunity with a multiple dose schedule (e.g. MV130).
4.3.1 Polybacterial whole-cell vaccines
These vaccines are used for the prevention of recurrent infections in susceptible subjects, mainly associated to the respiratory and urogenital tracts [128, 129, 130, 131, 132, 133, 134]. Since they target infections occurring in these tracts, their administration is generally through mucosal tissues to obtain a better mucosal response [135, 136].
MV130 is a sublingual vaccine used to prevent recurrent respiratory tract infections [128, 129] containing inactivated whole-cell bacteria that are common pathogens in the airways. Its ability immunomodulating DCs has been addressed experimentally in vitro and in vivo. MV130 triggers the release of cytokines ascribed to trained immunity in different setting, including TNF-α, IL-1β and IL-6 [103, 137, 138]. Sublingual immunization of mice with MV130 induces a systemic Th1/Th17 and IL-10 enhanced responses against unrelated antigens [103]. Similar enhancement was shown in patients treated with MV130 where an increased T cell response to flu antigens were described [128]. MV130 was successfully used in infants with recurrent wheezing, a condition triggered in most cases by viral infections. It is noteworthy that the protective effect was also shown 6 months after discontinuation of treatment, which points to a long-lasting effect that fits with the memory ascribed to trained immunity (Nieto et al., under review). In this regard, MV130 has been shown to induce trained immunity and to confer protection against experimental virus infections (Brandi et al., under review). Recent studies have assessed the clinical benefit of MV130 as a TIbV in the context of recurrent respiratory infections in vulnerable populations such as patients with different primary and secondary immunodeficiencies showing a reduced rate of respiratory infections [130, 139] (Ochoa-Grullón et al., in press).
4.3.2 Polybacterial lysates
Although not considered vaccines but immunostimulants, these bacterial preparations are, like MV130, used for the prevention of recurrent respiratory infections. OM-85, one of the best studied, is composed of chemically treated bacterial lysates for oral administration, acting through the gastro-intestinal mucosa. OM-85 has been shown to be effective in experimental viral infections [140] and in children with recurrent wheezing [141], a condition triggered by viruses as noted above. OM-85 stimulates the release of proinflammatory cytokines such as IL-1β, TNF-α and IL-6 by macrophages [142], typical of trained immunity induction, as well as Th1 cytokines including IFN-γ [143]. It is not known, however, the role of trained immunity in their mechanism of protection. A recent study conducted in infants, the observed protection against respiratory infections under OM-85 treatment stopped when treatment was discontinued [144], which may point against the memory ascribed to trained immunity.
4.4 The potential clinical applications of TIbVs in the context of viral outbreaks
The non-specific mechanism of TIbVs against widely differing pathogens associated to the induction of trained immunity can be exploited clinically. This makes TIbVs as a ready-to-act tool to tackle disease outbreaks from different angles where conventional specific vaccines have proven their limitations:
Newly emerging disease outbreaks, with no conventional vaccines available. Even in the presence of therapeutic options, vaccines are the best tool to prevent infections. However, even with worldwide efforts, getting a vaccine to the public takes time. In addition, side effects, dosing issues, and manufacturing problems can all cause delays [3]. Herein, using available TIbVs could mitigate the devastating consequences of emergent outbreaks by means of non-specific protection, until a suitable specific vaccine is available.
Newly emerging disease outbreaks, first coming vaccines with partial efficacy. Even if a vaccine gets available to the market, conventional strategies might raise some issues. The unpredictable identity of largely unknown emerging pathogens, the lack of appropriate experimental animal models, and the time for faster developing may give raise to an upcoming vaccine with no full efficacy [3]. On the other hand, limitations of current vaccines, such as mumps, also include a low efficacy resulting from an unacceptable drop in the immune response over time, requiring re-immunization [145]. In these contexts, the administration of a TIbV prior to the specific vaccine may enhance the response to the latter (111).
Re-emerging disease outbreaks, pathogens with high mutation rates and loss of vaccine efficacy. Mutations are the building blocks of evolution in any organism. Viruses are among the fastest evolving entities, especially RNA viruses such as influenza. Implications in conventional vaccine design are numerous, as a high mutation rate makes it hard to design a vaccine that is universally effective across many years. As a result, this makes a vaccine effective for shorter and raises the need for yearly vaccination programs [22, 146]. Since the underlying mechanism of TIbVs extend well beyond their nominal antigens and have a broad-spectrum of protection, TIbVs could overcome the troublesome of highly specific vaccines that promote antigen variant switching [147].
Disease outbreaks in vulnerable populations. During infectious disease outbreaks, vulnerable populations are usually disproportionately affected due to an interplay of immunological, epidemiological, and medical factors, which leads to sub-optimal or even under-vaccination [148]. This is well exemplified in the elderly population, where successful vaccination against important infectious pathogens which cause high morbidity and mortality represents a growing public health priority. Age-related immunosenescence and ‘inflammaging’ have been postulated as underlying mechanisms responsible for decreased response and high mortality, including during COVID-19 pandemic or influenza season [80, 149]. Therefore, more potent vaccines are needed. In this regard, the induction of trained immunity by the use of TIbVs is proposed to overcome the immune dysfunction found in these individuals [28]. Thus, elderly has been proposed as one of the groups to benefit from the use of TIbVs, including severe COVID-19 disease, with the aim of potentiating the immunogenicity of their vaccination [80]. Moreover, some types of immunodeficiencies or immunosuppression may benefit from TIbVs. These formulations, by means of tackling both branches of immunity, especially the innate compartment, may be an achievable alternative to reinforce protection or optimize immunogenicity of vaccination in this population [130, 139].
Altogether, harnessing the TIbV concept has been suggested as a crucial step in future vaccine development and implementation, because a wide range of clinical applications may benefit to some extent from their use [150].
4.5 TIbVs in the time of COVID-19
Despite the tremendous financial and scientific effort invested to rapidly obtain a prophylactic vaccine against SARS-CoV-2, only the first one has been licensed in December 2020. Although this means less than a year since the declaration of the pandemic by the WHO, which is an unprecedented achievement, in the meantime, two pandemic waves of COVID-19 and more than 1.5 million deaths have been declared worldwide. Therefore, alternative strategies have been considered to fill the gap until a safe and effective vaccine is available. As noted earlier in this chapter, TIbVs can play an important role for this purpose by increasing host resistance to other pathogens, including viruses.
A bunch of recent studies have been published supporting the role of certain vaccines, including BCG, OPV and measles, as a possible successful strategy to reduce susceptibility and severity to SARS-CoV-2 through trained immunity induction [80, 151, 152]. Thus, clinical trials are currently being conducted to find out the contribution of trained immunity as a preventive tool in the context of COVID-19 pandemics [153]. In a prospective observational trial, 255 MMR vaccinated subjects were followed searching for COVID-19 cases, thirty-six presented COVID-19 but all with a remarkable mild course [154]. Recent studies have also suggested a potential benefit of influenza vaccine on the susceptibility and the outcome of certain infections including SARS-CoV-2. In this sense, a particular attention has been focused on a high-risk population, the elderly. In a study conducted in Italy, influenza vaccination in people aged 65 and over was associated with a reduced spread and a less severe clinical expression of COVID-19 [155].
Finally, in addition to the potential role of TIbV conferring resistance against SARS-CoV-2 infection, they can eventually be used to increase efficacy of specific anti-COVID-19 vaccines, when available, especially in vulnerable population. In this sense, implications of vaccination route and mucosal immunity have also been raised as a key aspect in the development of safe and effective prophylaxis interventions against SARS-CoV-2. Most formulations in development are parentally administered; only a few COVID-19 vaccine candidates are administered by mucosal routes. Still, studies indicate that even if mucosal immunization against coronavirus does not confer sterilizing immunity, the ability to induce anti-SARS-CoV-2 IgA responses in the airways may prevent virus spread to the lung and avoid respiratory distress [156]. In this regard, mucosal TIbVs could enhance the mucosal response of specific COVID-19 vaccines acting as TIbAs by combining them as pointed above in those especially vulnerable subjects.
5. Conclusions and future perspectives
Viral outbreaks can cause epidemics and pandemics if the route of transmission allows for the rapid virus spread. Given the ease of travel and the global exchange of potential transmitting agents, these situations will be increasingly frequent in the future. Preventing the spread of a virus outbreak caused by a highly contagious agent is not easy in the absence of effective therapies or preventive measures. Although the development of effective prophylactic vaccines specific for the threatening virus is the final goal when possible, this requires a minimum time of almost a year in the best possible scenario. Meanwhile, the consequences of the spread of a deadly virus can be devastating, as it is exemplified during the COVID-19 pandemic. This scenario may also take place in the case of re-emerging viruses tackled by partial efficacious vaccines. In such situations, harnessing the heterologous non-specific protection of some existing vaccines with a known safety track record is an interesting possibility. This protection may be critical for vulnerable subjects and/or for highly exposed individuals, like healthcare workers.
Non-specific protection of some vaccines is thought to be mainly dependent on their effect on the innate immune system. Increasing evidence gathered over the past few years points that innate immune cells show memory-like features when properly activated. This memory termed “trained immunity” has been associated with the non-specific protection of vaccines. The concept of “trained immunity-based vaccine” (TIbV) has been drawn to exploit the potential of trained immunity in designing novel vaccines or to redefine bacterial-derived preparations conferring broad protection against widely differing pathogens. As trained immunity may have implications on the adaptive immune response and vice-versa, its potential to provide enhanced immune responses is quite broad whether considering natural infections or following vaccination.
Taken advantage of the current COVID-19 pandemic, a number of clinical trials have been launched with putative TIbVs in order to address protection in highly exposed subjects. The results are eagerly expected as these initiatives may be considered as a proof-of-concept supporting their use in future epidemics/pandemics to fill the gap until a specific vaccine is available. Nevertheless, as trained immunity can be achieved by different inducers, it is unlikely to obtain the same degree of protection, duration, etc. for all of them, which may also depend on the biological behavior and the route of transmission of the threatening pathogen. As in most instances rapidly spreading viruses are airborne and primarily infect the mucosa of the airway tract, induction of trained immunity at the local mucosal level can confer a more adequate protection. This may be an opportunity for mucosal TIbVs as compared to those given parenterally.
Trained immunity may justify heterologous protection of vaccines, help to explain their underlying mechanisms, open avenues for next generation of vaccines, or be proposed to tackle outbreaks by new pathogens as described here. However, this is an emerging field that requires more clinical data before being a reality in the clinical practice; not only to be used against infectious outbreaks, but to fight against recurrent infections in vulnerable subjects for whom no effective vaccines are yet available.
Conflict of interest
JLS is the founder and CEO of Inmunotek SL, Spain, a pharmaceutical company that manufactures bacterial vaccines. LC and PS-L are employees of Inmunotek.
\n',keywords:"trained immunity-based vaccines, innate immune training, pandemic, viral outbreak, BCG, MV130",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74915.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74915.xml",downloadPdfUrl:"/chapter/pdf-download/74915",previewPdfUrl:"/chapter/pdf-preview/74915",totalDownloads:326,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 13th 2020",dateReviewed:"December 24th 2020",datePrePublished:"January 23rd 2021",datePublished:"January 12th 2022",dateFinished:"January 23rd 2021",readingETA:"0",abstract:"Viral outbreaks have become significant threats to global human public health. New emerging viruses, pathogen mutations, and even the progressive loss of efficacy in some existing vaccines are behind this problem, which is amplified by the rapid virus spread given the ease of current mobility. Taking into account that these outbreaks arise in the absence of conventional effective vaccines, alternative approaches based on trained (innate) immunity are being considered. This immunity is dependent on a functional reprogramming of innate immune cells, leading to an enhanced nonspecific response towards different pathogens, including viruses. Trained immunity-based vaccines (TIbVs), defined as vaccine formulations containing trained immunity inducers, could be used during viral outbreaks to confer non-specific protection but also to enhance adaptive specific immune responses. In this chapter, we aim to illustrate how TIbVs could tackle the above-mentioned situations derived from viral outbreaks, reviewing the potential of available TIbVs in such urgent situations with a special mention to COVID-19.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74915",risUrl:"/chapter/ris/74915",signatures:"Laura Conejero, Paula Saz-Leal and José Luis Subiza",book:{id:"10470",type:"book",title:"Current Perspectives on Viral Disease Outbreaks",subtitle:"Epidemiology, Detection and Control",fullTitle:"Current Perspectives on Viral Disease Outbreaks - Epidemiology, Detection and Control",slug:"current-perspectives-on-viral-disease-outbreaks-epidemiology-detection-and-control",publishedDate:"January 12th 2022",bookSignature:"David Claborn",coverURL:"https://cdn.intechopen.com/books/images_new/10470.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83881-911-8",printIsbn:"978-1-83881-910-1",pdfIsbn:"978-1-83881-915-6",isAvailableForWebshopOrdering:!0,editors:[{id:"169536",title:"Dr.",name:"David",middleName:null,surname:"Claborn",slug:"david-claborn",fullName:"David Claborn"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"330515",title:"Dr.",name:"José Luis",middleName:"Luis",surname:"Subiza",fullName:"José Luis Subiza",slug:"jose-luis-subiza",email:"jlsubiza@inmunotek.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inmunotek (Spain)",institutionURL:null,country:{name:"Spain"}}},{id:"330517",title:"Dr.",name:"Laura",middleName:null,surname:"Conejero",fullName:"Laura Conejero",slug:"laura-conejero",email:"lconejero@inmunotek.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inmunotek (Spain)",institutionURL:null,country:{name:"Spain"}}},{id:"330518",title:"Dr.",name:"Paula",middleName:null,surname:"Saz-Leal",fullName:"Paula Saz-Leal",slug:"paula-saz-leal",email:"psaz@inmunotek.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inmunotek (Spain)",institutionURL:null,country:{name:"Spain"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Specific anti-infectious vaccines",level:"1"},{id:"sec_2_2",title:"2.1 Difficulties for novel specific vaccines in a viral outbreak situation",level:"2"},{id:"sec_4",title:"3. Trained immunity and infections",level:"1"},{id:"sec_4_2",title:"3.1 The concept",level:"2"},{id:"sec_5_2",title:"3.2 Trained immunity on ongoing immune responses",level:"2"},{id:"sec_5_3",title:"3.2.1 Effect on adaptive immunity",level:"3"},{id:"sec_6_3",title:"3.2.2 Effector functions on trained innate immune cells",level:"3"},{id:"sec_9",title:"4. Trained immunity-based vaccines",level:"1"},{id:"sec_9_2",title:"4.1 Available vaccines with heterologous protection against viral infections",level:"2"},{id:"sec_10_2",title:"4.2 Live attenuated vaccines",level:"2"},{id:"sec_10_3",title:"4.2.1 BCG",level:"3"},{id:"sec_11_3",title:"4.2.2 Influenza vaccine",level:"3"},{id:"sec_12_3",title:"4.2.3 Measles vaccine",level:"3"},{id:"sec_13_3",title:"4.2.4 Oral polio vaccine",level:"3"},{id:"sec_15_2",title:"4.3 Inactivated vaccines",level:"2"},{id:"sec_15_3",title:"4.3.1 Polybacterial whole-cell vaccines",level:"3"},{id:"sec_16_3",title:"4.3.2 Polybacterial lysates",level:"3"},{id:"sec_18_2",title:"4.4 The potential clinical applications of TIbVs in the context of viral outbreaks",level:"2"},{id:"sec_19_2",title:"4.5 TIbVs in the time of COVID-19",level:"2"},{id:"sec_21",title:"5. 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Arrutia Diez, Mucosal bacterial immunotherapy with MV130 highly reduces the need of tonsillectomy in adults with recurrent tonsillitis. Hum Vaccin Immunother, 2019. 15(9): p. 2150-2153'},{id:"B130",body:'Guevara-Hoyer, K., et al., Trained Immunity Based-Vaccines as a Prophylactic Strategy in Common Variable Immunodeficiency. A Proof of Concept Study. Biomedicines, 2020. 8(7)'},{id:"B131",body:'Nickel, J.C., Saz-Leal, P., Doiron, R.C., Could sublingual vaccination be a viable option for the prevention of recurrent urinary tract infection in Canada? A systematic review of the current literature and plans for the future. CUAJ, 2020. 14(8): p. 281-7'},{id:"B132",body:'Lorenzo-Gomez, M.F., et al., Evaluation of a therapeutic vaccine for the prevention of recurrent urinary tract infections versus prophylactic treatment with antibiotics. Int Urogynecol J, 2013. 24(1): p. 127-34'},{id:"B133",body:'Lorenzo-Gomez, M.F., et al., Comparison of sublingual therapeutic vaccine with antibiotics for the prophylaxis of recurrent urinary tract infections. Front Cell Infect Microbiol, 2015. 5: p. 50'},{id:"B134",body:'Yang, B. and S. Foley, First experience in the UK of treating women with recurrent urinary tract infections with the bacterial vaccine Uromune((R)). BJU Int, 2018. 121(2): p. 289-292'},{id:"B135",body:'Holmgren, J. and C. Czerkinsky, Mucosal immunity and vaccines. Nat Med, 2005. 11(4 Suppl): p. S45-53'},{id:"B136",body:'Kraan, H., et al., Buccal and sublingual vaccine delivery. J Control Release, 2014. 190: p. 580-92'},{id:"B137",body:'Molero-Abraham, M., et al., Human Oral Epithelial Cells Impair Bacteria-Mediated Maturation of Dendritic Cells and Render T Cells Unresponsive to Stimulation. Front Immunol, 2019. 10: p. 1434'},{id:"B138",body:'Vazquez, A., et al., Involvement of Mesenchymal Stem Cells in Oral Mucosal Bacterial Immunoterapy. Front Immunol, 2020. 11: p. 567391'},{id:"B139",body:'Sanchez Ramon, S., M. Manzanares, and G. Candelas, MUCOSAL anti-infections vaccines: Beyond conventional vaccines. Reumatol Clin, 2020. 16(1): p. 49-55'},{id:"B140",body:'Bessler, W.G., U. Vor dem Esche, and N. Masihi, The bacterial extract OM-85 BV protects mice against influenza and Salmonella infection. Int Immunopharmacol, 2010. 10(9): p. 1086-90'},{id:"B141",body:'Razi, C.H., et al., The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol, 2010. 126(4): p. 763-9'},{id:"B142",body:'Luan, H., et al., OM85-BV induced the productions of IL-1beta, IL-6, and TNF-alpha via TLR4- and TLR2-mediated ERK1/2/NF-kappaB pathway in RAW264.7 cells. J Interferon Cytokine Res, 2014. 34(7): p. 526-36'},{id:"B143",body:'Huber, M., H. Mossmann, and W.G. Bessler, Th1-orientated immunological properties of the bacterial extract OM-85-BV. Eur J Med Res, 2005. 10(5): p. 209-17'},{id:"B144",body:'Sly, P.D., et al., Primary prevention of severe lower respiratory illnesses in at-risk infants using the immunomodulator OM-85. J Allergy Clin Immunol, 2019. 144(3): p. 870-872 e11'},{id:"B145",body:'Almansour, I., Mumps Vaccines: Current Challenges and Future Prospects. Front Microbiol, 2020. 11: p. 1999'},{id:"B146",body:'Sanjuan, R., et al., Viral mutation rates. J Virol, 2010. 84(19): p. 9733-48'},{id:"B147",body:'Pichichero, M.E., Pneumococcal whole-cell and protein-based vaccines: changing the paradigm. Expert Rev Vaccines, 2017. 16(12): p. 1181-1190'},{id:"B148",body:'Doherty, M., et al., Vaccination of special populations: Protecting the vulnerable. Vaccine, 2016. 34(52): p. 6681-6690'},{id:"B149",body:'Chen, W.H., et al., Vaccination in the elderly: an immunological perspective. Trends Immunol, 2009. 30(7): p. 351-9'},{id:"B150",body:'Pasco, S.T. and J. Anguita, Lessons from Bacillus Calmette-Guerin: Harnessing Trained Immunity for Vaccine Development. Cells, 2020. 9(9)'},{id:"B151",body:'Netea, M.G., et al., Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection. Cell, 2020. 181(5): p. 969-977'},{id:"B152",body:'Wang, J., et al., The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation.AAPS PharmSciTech, 2020. 21(6): p. 225'},{id:"B153",body:'Mantovani, A. and M.G. Netea, Trained Innate Immunity, Epigenetics, and Covid-19. N Engl J Med, 2020. 383(11): p. 1078-1080'},{id:"B154",body:'Larenas-Linnemann, D.E. and F. Rodriguez-Monroy, Thirty-six COVID-19 cases preventively vaccinated with mumps-measles-rubella vaccine: All mild course. Allergy, 2020'},{id:"B155",body:'Amato, M., et al., Relationship between Influenza Vaccination Coverage Rate and COVID-19 Outbreak: An Italian Ecological Study. Vaccines (Basel), 2020. 8(3)'},{id:"B156",body:'Moreno-Fierros, L., I. Garcia-Silva, and S. Rosales-Mendoza, Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity? Expert Opin Biol Ther, 2020. 20(8): p. 831-836'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Laura Conejero",address:null,affiliation:'
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Callari, Florian Fortmann, Stefan Suck, Denis Javaux, Andreas Hasselberg and Sybert Stroeve",authors:[{id:"135235",title:"Dr.",name:"Joan",surname:"Cahill",fullName:"Joan Cahill",slug:"joan-cahill",email:"cahilljo@tcd.ie"},{id:"221073",title:"Dr.",name:"Tiziana C.",surname:"Callari",fullName:"Tiziana C. 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The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
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In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
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The IntechOpen timeline
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2004
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Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
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Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
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2005
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IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
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2006
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IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
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2008
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Downloads milestone: 200,000 downloads reached
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2009
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Publishing milestone: the first 100 Open Access STM books are published
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2010
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Downloads milestone: one million downloads reached
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IntechOpen expands its book publishing into a new field: medicine.
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2011
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Publishing milestone: More than five million downloads reached
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IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
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IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
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IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
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2012
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Publishing milestone: 10 million downloads reached
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IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
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2013
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IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
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2014
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IntechOpen turns 10, with more than 30 million downloads to date.
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IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
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2015
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Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
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Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
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40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
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Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
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2016
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IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
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2017
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Downloads milestone: IntechOpen reaches more than 100 million downloads
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Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
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In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
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The IntechOpen timeline
\n\n
2004
\n\n
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Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
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Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
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2005
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IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
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2006
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IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
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2008
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Downloads milestone: 200,000 downloads reached
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2009
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Publishing milestone: the first 100 Open Access STM books are published
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\n\n
2010
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Downloads milestone: one million downloads reached
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IntechOpen expands its book publishing into a new field: medicine.
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2011
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Publishing milestone: More than five million downloads reached
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IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
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IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
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IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
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2012
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Publishing milestone: 10 million downloads reached
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IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
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2013
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IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
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2014
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\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
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IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
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\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
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Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
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MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"26258",doi:"10.5772/28300",title:"Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke",slug:"excitotoxicity-and-oxidative-stress-in-acute-ischemic-stroke",totalDownloads:7157,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"931",slug:"acute-ischemic-stroke",title:"Acute Ischemic Stroke",fullTitle:"Acute Ischemic Stroke"},signatures:"Ramón Rama Bretón and Julio César García Rodríguez",authors:[{id:"73430",title:"Prof.",name:"Ramon",middleName:null,surname:"Rama",slug:"ramon-rama",fullName:"Ramon Rama"},{id:"124643",title:"Prof.",name:"Julio Cesar",middleName:null,surname:"García",slug:"julio-cesar-garcia",fullName:"Julio Cesar García"}]},{id:"62072",doi:"10.5772/intechopen.78695",title:"Brain-Computer Interface and Motor Imagery Training: The Role of Visual Feedback and Embodiment",slug:"brain-computer-interface-and-motor-imagery-training-the-role-of-visual-feedback-and-embodiment",totalDownloads:1439,totalCrossrefCites:13,totalDimensionsCites:23,abstract:"Controlling a brain-computer interface (BCI) is a difficult task that requires extensive training. Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"63258",title:"Anatomy and Function of the Hypothalamus",slug:"anatomy-and-function-of-the-hypothalamus",totalDownloads:4558,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hypothalamus is a small but important area of the brain formed by various nucleus and nervous fibers. Through its neuronal connections, it is involved in many complex functions of the organism such as vegetative system control, homeostasis of the organism, thermoregulation, and also in adjusting the emotional behavior. The hypothalamus is involved in different daily activities like eating or drinking, in the control of the body’s temperature and energy maintenance, and in the process of memorizing. It also modulates the endocrine system through its connections with the pituitary gland. Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"}],onlineFirstChaptersTotal:17},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"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:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:10,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,annualVolume:11975,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. 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He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain. She is a Full Professor at the Department of Medicine and Animal Surgery at the same University. She developed her research activity in the field of Endocrinology, Hematology, Biochemistry and Immunology of horses. She is a scientific reviewer of several international journals : American Journal of Obstetrics and Gynecology, Comparative Clinical Pathology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology. Since 2014, she has been the Head of the Clinical Analysis Laboratory of the Hospital Clínico Veterinario from the Faculty of Veterinary, CEU-Cardenal Herrera University.",institutionString:"CEU-Cardenal Herrera University",institution:{name:"CEU Cardinal Herrera University",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. 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Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"345713",title:"Dr.",name:"Csaba",middleName:null,surname:"Szabó",slug:"csaba-szabo",fullName:"Csaba Szabó",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"345719",title:"Mrs.",name:"Márta",middleName:null,surname:"Horváth",slug:"marta-horvath",fullName:"Márta Horváth",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"420151",title:"Prof.",name:"Novirman",middleName:null,surname:"Jamarun",slug:"novirman-jamarun",fullName:"Novirman Jamarun",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Andalas University",country:{name:"Indonesia"}}},{id:"420149",title:"Dr.",name:"Rusmana",middleName:"Wijaya Setia",surname:"Wijaya Setia Ningrat",slug:"rusmana-wijaya-setia-ningrat",fullName:"Rusmana Wijaya Setia Ningrat",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Andalas University",country:{name:"Indonesia"}}},{id:"339759",title:"Mr.",name:"Abu",middleName:null,surname:"Macavoray",slug:"abu-macavoray",fullName:"Abu Macavoray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Njala University",country:{name:"Sierra Leone"}}},{id:"339758",title:"Prof.",name:"Benjamin",middleName:null,surname:"Emikpe",slug:"benjamin-emikpe",fullName:"Benjamin Emikpe",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ibadan",country:{name:"Nigeria"}}},{id:"339760",title:"Mr.",name:"Moinina Nelphson",middleName:null,surname:"Kallon",slug:"moinina-nelphson-kallon",fullName:"Moinina Nelphson Kallon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Njala University",country:{name:"Sierra Leone"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!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. 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