Smart city indicators and benchmarks.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3594",leadTitle:null,fullTitle:"Sensor and Data Fusion",title:"Sensor and Data Fusion",subtitle:null,reviewType:"peer-reviewed",abstract:"Data fusion is a research area that is growing rapidly due to the fact that it provides means for combining pieces of information coming from different sources/sensors, resulting in ameliorated overall system performance (improved decision making, increased detection capabilities, diminished number of false alarms, improved reliability in various situations at hand) with respect to separate sensors/sources. 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Cities constantly compete for international investment to generate employment, revenue and funds for development, all leading to elevated energy consumption and CO2 emissions [1]. Cities also seek innovation and efficiency in reducing time, cost, and energy in delivering services: smart transportation, intelligent buildings, and smart infrastructure that would lead to low carbon city development. In fact, 80% of the world’s gross domestic product is created in cities; urban citizens earn on average three times the income of their rural counterparts; and people living in larger cities tend to have smaller energy footprints and require fewer infrastructures, consume less resources, and have higher productivity levels. A city of 8 million has 15% more productivity and 15% less infrastructure needs than two cities of 4 million each [2].
There are several urbanization models that incorporate digital technologies to address some of the urbanization and sustainability challenges. While digital cities attempt to integrate digital technology into city’s infrastructure, intelligent cities utilize digital city infrastructure to construct intelligent urban systems featuring intelligent buildings, transportation systems, hospitals, schools, public services. By the same token, smart cities deploy intelligent urban systems to support socio-economic development and improve urban quality of life [3].
Smart city initiatives seek to overcome the limitations of traditional urban development that manages infrastructure systems in silos and leverage the pervasive character of data and services offered by digital technologies, such as cloud computing, the internet of things, open and big data. As such, different stakeholders, investors and citizens work to enhance existing services and provide new services. Smart city development is highly complex, challenging and context-specific. Challenges arise from discourses of technologies and policies, failure to tackle urban sustainability challenges, and governance framework.
Over the past two decades, the concept of “smart cities” has surfaced to address the economic and social life of first worldwide cities [4]. Put simply, a smart city is a community that uses different data gathering devices to disseminate information that is used to manage services efficiently such as traffic control, power plants, water supply networks, hospitals, and other community services [5]. Within this context, citizens are very important for city’s development. To keep them engaged, real quality services have to be offered at reasonable cost.
Associated as it is with technology, the concept of “smart city” has superseded other versions: “information city”, “digital city” and the “intelligent city”. In fact, the “digital city” originates from an experiment in Amsterdam in 1994, with the aim of democratizing access to the internet. The “digital city” now refers to: a connected community that combines broadband communications infrastructure; flexible, service-oriented computing infrastructure based on open industry standards; and innovative services to meet the needs of governments and their employees, citizens and businesses [6].
Smart city has been widely studied and registered under ISO 37120 sustainable cities and communities. The indicators of smart city services and quality of life are set out in ISO 37122 and resilient city standards are prescribed in ISO 37123 (Figure 1).
Smart city indicators and standards of sustainable development.
Indicators include, inter alia, economy, education, energy, climate change, finance, governance, health, housing, waste water and water quality. In the transportation sector for instance, data mining and sensing are used to obtain real-time data for managing duration of traffic light, traffic jam and accidents. It also potentially encourages mobility sharing through car, motorcycle and bicycle (Figure 2).
Basic components of smart city.
Because energy is central to smart city and low carbon cities, this section investigates the impact of urbanization on carbon emissions focusing on residential, commercial and industrial sectors, the major components of any city’s land use. Azizalrahman and Hasyimi [7] have suggested a comparative analysis of low carbon cities in high income, upper-middle income and lower-middle income groups of countries. They have formulated an impact model of urban sector drivers on carbon emissions (USDM) to examine the relationship between urbanization, economic factors and carbon emissions and exposed urban dynamics of variables’ interaction at city level. They found that most carbon emissions originating from the residential, commercial and public sectors are strongly influenced by energy consumption. Urbanization displays an inverse function with energy consumption and a positive correlation with economy. Based on IESE Cities in Motion Index 2018 [8], the performance of top global cities are measured and ranked based on dominant sectors which promote to sustainability (Figure 3).
Significant sectors in selected global cities.
Based on their dominant characteristic, cities in lower middle-income countries have typical market towns that struggle on rapid urbanization. By contrast, cities in upper middle-income countries have typical production centres which focus on productivity. Cities in high income countries have become centres of finance and creative industries which face challenges of migrating firms to other regions (Figure 4).
Effect of carbon emissions in smart cities of high, upper-middle, and lower-middle countries.
Low carbon city and smart city are two forms of city development frameworks that purse sustainability. Low carbon city was established earlier than smart city in response to global warming and climate change. On the other hand, smart city has surfaced in the past decade to disseminate information and deploy technology solutions to improve efficiencies of city systems. Whereas low carbon city is mitigation purpose oriented, smart city is an adoption or adaptation targeted. Smart city has potentials to disseminate real data and record big data simultaneously thereby, enabling decision maker to track city system changes [9], see Figure 5.
Commonalities between smart city and low carbon city in sustainability framework.
Low carbon city framework has robust and clear targets, e.g., sulphur, nitrogen, and carbon emission levels. On the contrary, smart city has general; less specific targets that render measurement of smartness more difficult. Further, there is a widespread body of literature on low carbon city as opposed to relatively scant literature on smart cities. Some institutions have tried to develop evaluation models using sets of indicators to rank smart city performance such as smart cities ranking for Europe, world smart city government ranking, and the IESE Cities in Motion Index (CIMI) [8, 10, 11, 12].
A smart city can be viewed within the wider perspective of sustainable city. The basic sectors include, amongst other things, technology, community, economy and energy which facilitate the development of a real concept of smart city. As such it gets closer to the definition of [11] who maintain that a city is smart when governance drives investment in human capital and IT infrastructure to achieve sustainable development. The authors have constructed a fourfold framework for a typical smart city comprising technology, community, economy and energy to clearly distinguish between smart city and low carbon and sustainable cities (Figure 6).
Technology framework: ostensibly, smart cities are heavily dependent on the use of technology that is supported by technological infrastructure. These varied technologies are applied to diverse urban domains (e.g., economy, transportation, energy, environment, water management, waste disposal, education and healthcare, governance and public participation) to achieve efficiency and better management [9]. Within a Smart city context, information technology is not considered independently, but rather within wider physical and social systems that seek to deliver efficient service to people, business and government. It has become popular not only to smart cities, but also to engineering firms seeking innovation and investment opportunities for physical urban and infrastructure development.
Community framework: communities are central to city’s intelligence as exemplified by human activities, innovation and knowledge. Human and social capital drives city’s economy and technology deployment. Their power lies in effective creation of economic, cultural, social environment and formation of public opinion. Through participatory function, communities can influence policy formulation and decision making, such as redistribution of public finance and increasing the transparency of public expenditure. Representatives of cities, policy and decision makers should aim to reach consensus with the community on smart urban development [13].
Economy framework: knowledge and digital economy are essential drivers of the smart city discourse. The terms “knowledge-based economy” refer to an economy where more knowledge-intensive than labour-intensive activities take place. It played a significant role in the emergence of the idea of smart cities; it is one of the two strands of thinking that formed the current ideas about what a smart city is, how it works, and what it can do. Moreover, smart city changes people’s behaviour in purchasing from traditional to online transaction. It increases e-money usage, encourages store owners to react to this condition with some changes in their business models, etc.
Energy framework: smart cities seek to develop smart energy infrastructure, disseminate data to create efficiencies, leverage economic development, and enhance quality of life. A smart city features, inter alia, smart street lighting, intelligent buildings, smart mobility and power grid. The common thread is energy, economics and impact on cities. However, smart cities seem to have shifted attention away from environmental problems, climate change and carbon emissions to infrastructure and information usage and sharing.
Basic smart city’s sectors.
A generic framework for smart cities is proposed comprising: (1) goal, (2) conceptualization, (3) assessment, and (4) implication. This model is useful to address smart city transformation that leads to sustainability. It affords a summary of complex transformation processes that are needed for cities seeking to be smart (Figure 7).
Proposed smart city framework.
Common performance measurement methods use scoring methods which assess the current city condition. Here, the authors have used quantitative indicators used in the proposed model to create a generic framework to increase objectivity and realism. The indicators were obtained from several sources: ISO 337122, smart city in Europe, and generic model for low-carbon city [10]. The authors have initiated gathering of data for the basic sectors of the smart city: technology, community, economy and energy for which 20 key performance indicators (KPIs) were selected. For modelling purpose, the KPIs were then categorized under six urban development sectors: competitiveness, energy, mobility, urban management, urban living and waste management. The selected indicators can be seen in Figure 8.
Smart city indicators and categorization.
Quantifiable indicators under each criterion are then selected to measure smart city performance and compare it with the benchmarks [14]. Benchmark setting is important because it aims to sufficiently differentiate between cities of various performance. Benchmarks were derived from multiple sources: (1) World Bank and WHO; (2) top city performances, such as green city index; (3) International targets for developed countries set out by EU (Table 1).
Category | Indicator | Effect | Unit of measurement | Benchmark value | Source |
---|---|---|---|---|---|
Competitiveness | GDP per capita | + | $/capita | 25,616 | [15] |
Economy: services and other activity | + | % of gross value added | 60 | [16] | |
Employment in services | + | % employed | 60 | [16] | |
Energy | Carbon productivity | + | USD/ton | 8244 | [17] |
Proportion of renewable energy | + | % | 10 | [17] | |
Energy intensity | − | MJ/USD | 4 | [17] | |
Transportation | Public buses per capita | + | buses/million persons | 694 | [17] |
Rail length per capita | + | km/million persons | 40 | [17] | |
Cars per capita | − | Private cars / persons | 0.39 | [17] | |
Urban Living | Proportion of public green space | + | % | 35 | [18] |
Population density | + | People/km2 | 4236.1 | [19] | |
Solid waste generation per capita | − | Kg/capita/day | 0.8 | [20] | |
Water consumption intensity | − | L/capita/day | 102 | [21] | |
Management | Education: government expenditure | + | % of GDP | 3 | [16] |
Individuals using the internet | + | per 100 inhabitants | 70 | [16] | |
Research and development expenditure | + | % of GDP | 1.5 | [16] | |
Waste and pollution | CO2 emission per capita | + | Ton/person | 2.19 | [21] |
Share of waste collected and adequately disposed | + | % | 80 | [20] | |
Share of material recycling | + | % | 30 | [22] | |
Share of wastewater treated | + | % | 75 | [21] |
Smart city indicators and benchmarks.
A multi-criteria evaluation model has been proposed by modifying the framework of Azizalrahman and Hasyimi [23].
The equation of data normalization is set out in Eqs. (1) and (2).
where
Indicator | Unit of measurement | Formula | ||
---|---|---|---|---|
GDP Per capita | $/capita | |||
Economy: services and other activity | % of gross value added | |||
Employment in services | % employed | |||
Carbon productivity | USD/ton | |||
Proportion of renewable energy | % | |||
Energy intensity | MJ/USD | |||
Public buses per capita | buses/million persons | |||
Rail length per capita | km/million persons | |||
Cars per capita | Private cars/persons | |||
Proportion of public green space | % | … | ||
Population density | People/km2 | |||
Solid waste generation per capita | Kg/capita/day | |||
Water consumption intensity | L/capita/day | |||
Education: government expenditure | % of GDP | |||
Individuals using the internet | per 100 inhabitants | |||
Research and development expenditure | % of GDP | |||
CO2 emission per capita | Ton/person | |||
Share of waste collected and adequately disposed | % | |||
Share of material recycling | % | |||
Share of wastewater treated | % | |||
Average | … |
Proposed multi-criteria evaluation model for smart city.
For better performance presentation, the standardization by score conversion to 0–100 could be seen in Eq. (3).
Where
To obtain an average score
Smart city pathway to sustainability.
The proposed model is tested on four cities: Vienna, London, New York, and Tokyo, the result of which can be seen in Table 3. The pilot cities are selected based on the good performance in technology sector based on IESE Cities in Motion Index 2018.
Vienna | London | New York | Tokyo | |
---|---|---|---|---|
Competitiveness | 68 | 78 | 78 | 66 |
Energy | 83 | 68 | 62 | 68 |
Transportation | 83 | 84 | 79 | 75 |
Urban living | 58 | 60 | 67 | 63 |
Management | 62 | 66 | 60 | 63 |
Waste | 69 | 73 | 72 | 70 |
Average score | 71 | 71 | 70 | 68 |
Category | Smart city | Smart city | Smart city | Low carbon |
Result of smart city model on the pilot cities.
From the figure above, we can see that from four pilot cities, Vienna, London and New York are categorized as smart city. On the other side, Tokyo is low carbon city. The above scores were transformed into smart city metrics (Figure 10).
Smart city metrics.
Smart city metrics help us summarize a detailed analysis for city’s performance by sector. Through this presentation, the strength and weakness of each sector can be easily identified and promoted to achieve the desired targets. Vienna, a global tourism destination, has a very good performance in transportation and city management. Vienna has become a city of high mobility systems such as smart buses, smart ride, smart sharing, smart public transport, and eMorail to mention but a few. Moreover, Vienna has a peaceful balance between the city and green areas which account for half of the city’s total area [24]. Therefore, the city is a leading smart city.
London and New York are examples of global cities with multiple central functions and populous agglomerations. Both have a strong performance in urban competitiveness and management. As centres of global trade and economy, London and New York have focused on, amongst other things, technology, human resource development, quality of urban living, and waste management.
London proved how smart the city could be by establishing London Datastore and innovation in transportation known as Heathrow pods; building up intelligent road network; facilitating trade with digital money; and making use of new technology in reusing waste heat from underground chambers and sub-ways. London also executed the innovative program named as “Innovate18” which attempted to rejuvenate the old railway network [25].
By the same token, New York attempted to be a smart city by canvassing the concept of equitable city—a city where anyone and everyone has access to facilities justly. Being the economic hub of the world, the city is continuously engaged in delivering smart innovations. Current initiatives include reduction of greenhouse gases, fair management of water and energy, smart protection of public health increasing mortality rate and tech-based plans to make the city safer. Further, New York aims to set up strategies and policies to successfully actualise the connected devices and internet of things (IoT) [26].
Tokyo on the other hand, is categorized as a low carbon city and is being transformed to a smart city. In the last few years, Tokyo has unveiled a chain of environment friendly initiatives which include: solid waste reduction through technology, encouragement of large-scale recycling plants and rain water harvesting, rooftop planting of trees and herbs which helps in absorbing carbon dioxide, adoption of energy efficient photovoltaic solar panels, and launch of Tokyo Super Eco Town [27].
Myasthenia gravis (MG) is a clinically heterogeneous, B-cell-mediated disorder affecting the neuromuscular junction (NMJ) and is mostly caused by the abnormal production of autoantibodies against the acetylcholine receptor (AChR) located in the postsynaptic membrane [1]. MG is generally considered a prototypical autoimmune disease, since the main target of the autoimmune response in the affected patients is well known. However, it is uniquely characterized by morphological and functional thymic abnormalities (hyperplasia and thymoma), which make this organ the main site of immunological alterations leading to the disease. Indeed, if the muscle is the target organ in MG patients, the thymus is now widely accepted as the main effector organ, in which B-cell expansion, anti-AChR autosensitization, and autoimmune response arise and are perpetuated [2]. The exact mechanisms triggering and sustaining autoimmunity in MG thymus are still unknown. As with many autoimmune conditions, considerable evidence indicates a multifactorial MG pathogenesis based on complex interactions among multiple genetic and environmental factors and their interplay with the immune system [3]. Among environmental factors, viruses are the main suspects to play a role in autoimmune diseases, mainly by their ability to induce persistent or aberrant Toll-like receptor (TLR)-mediated innate immune responses, which are able to promote or favor autoimmunity in genetically susceptible individuals. In our studies, we provided evidence of dysregulated Epstein-Barr virus (EBV) infection in hyperplastic and thymomatous MG thymuses in association with TLR overexpression, thus revealing EBV as a key contributing factor to intra-thymic B-cell tolerance disruption and sustained B-cell-mediated autoimmunity in MG patients [4].
MG is an autoimmune disorder of the NMJ, leading to fluctuating weakness and fatigability of skeletal muscles, exacerbated by repetitive contraction and improved on resting. Frequently, MG starts with ocular symptoms, as diplopia and ptosis, but in 80–85% of cases, ocular disease progresses to a generalized form within the first 2–5 years from onset, involving skeletal, bulbar, or respiratory muscles [5]. Respiratory failure (myasthenic crisis) occurs in 15–20% of patients and can be observed in younger and older patients [6].
MG is a heterogeneous condition whose clinical variability allows classification of patients in distinct disease subgroups, mainly based on autoantibodies, age at onset, and thymic histology [1, 7, 8]. In more than 80% of patients, the autoimmune attack is mediated by autoantibodies against AChR, less frequently (1–5%) against the muscle-specific kinase receptor (MuSK) or the low-density lipoprotein receptor-related protein 4 (LRP4), two proteins involved in AChR clustering. In addition, autoantibodies against other NMJ components, including cortactin, agrin, titin, and ryanodine receptor (RyR), have been described, especially in late-onset or thymoma-associated disease; their presence is concomitant to anti-AChR autoantibodies and indicates more severe manifestations [7]. Around 10% of generalized (non-ocular) patients results negative for anti-AChR, anti-MuSK, or anti-LRP4 antibodies. Clinically, these seronegative patients are similar to AChR-MG patients and can show thymic hyperplastic changes [9]. The triple seronegative MG subgroup may be heterogeneous, including patients with antibodies having affinities or concentrations too low to be detected with standard routine assays, or patients with antibodies against relevant antigens not identified yet. The introduction of cell-based assays (CBAs), having increased sensitivity compared to the routine assays commonly used, has significantly increasing the chance to identify autoantibodies to low-affinity clustered AChR, MuSK, and LRP4, thus improving MG diagnosis [7, 10, 11, 12].
As mentioned above, AChR-MG is associated with thymic patho-histological changes, including follicular hyperplasia and thymoma [13, 14]. Its severity is related with the loss of AChRs on NMJ, but not with the titers of circulating autoantibodies [15]. According with age at onset, AChR-MG follows a bimodal pattern, with the first peak under 50 years (early-onset MG, EOMG), and a second peak >50 years (late-onset MG, LOMG) [16, 17]. EOMG occurs most in young women and is generally associated with thymic hyperplasia. LOMG, which usually is generalized, mainly affects men, who frequently present thymic involution. Thymoma-associated MG that presents more severe symptoms can occur at any age, though it is more frequent in the elderly myasthenic patients and is frequently associated with the presence of antibodies against RyR and titin along with anti-AChR antibodies [14, 17].
MuSK-MG patients are mainly young females and typically have severe clinical symptoms [18]. An intra-thymic pathogenesis for MuSK-MG is not considered relevant, although a recent study found hyperplasia in 23% of MG patients positive for anti-MuSK antibodies by CBA [11]. LRP4-MG is less characterized but largely overlaps with AChR-MG clinical features; typical thymic histopathology has been recorded with a sparing of thymoma, at least in the European multinational cooperative study by Zisimopoulou and colleagues [12]. Most of LRP4-MG patients present ocular or generalized mild manifestations, and about 20% have only ocular weakness for more than 2 years [12, 19].
In MG, degradation of the postsynaptic membrane results in decreased AChRs and voltage-gated sodium channels, causing a significant reduction of endplate potential and raising the firing threshold, which is required to generate an action potential. Thus, during prolonged synaptic activity, as the quantal ACh content normally runs down, the summation of endplate potentials falls below the threshold, and they can no longer trigger the action potential of muscle fibers, leading to typical muscle weakness [20]. Three mechanisms of action of anti-AChR autoantibodies can explain NMJ impairment: (1) functional AChR block due to autoantibodies binding to the ACh-binding sites; (2) cross-linking and subsequent AChR internalization due to the ability of autoantibodies to target two antigen molecules (antigenic modulation); and (3) complement pathway activation, which leads to the generation of the membrane attack complex (MAC) and hence the destruction of the postsynaptic membrane. Complement activation at NMJ is thought to be the main pathogenic mechanism of anti-AChR antibodies, which are mainly of the IgG1 and IgG3 classes and therefore can bind and activate the complement system [20].
MuSK antibodies are generally IgG4, lacking complement-fixing, and are considered functionally monovalent, being unable to induce antigenic modulation. They affect MuSK ability to maintain the correct AChR cluster at the NMJ, by inhibiting the formation of MuSK-LRP4 complex and the agrin-stimulated MuSK phosphorylation [21, 22]. In addition, anti-MuSK antibodies are able to block binding of ColQ to the NMJ, compromising agrin-mediated AChR clustering [23]. Experimentally, animals receiving repeated daily injections of MuSK-positive patients’ IgG, or actively immunized with MuSK, show impaired neuromuscular transmission, with reductions in endplate AChRs [24].
Both AChR-MG and MuSK-MG fulfill Witebsky’s criteria for autoimmune diseases [25]. LRP4-MG also seems to adhere to these criteria: mice immunized with the LRP4 extracellular domain, or with IgGs purified from LRP4-immunized rabbits, present anti-LRP4 antibodies, exhibit MG-associated symptoms and their serum is able to decrease cell surface LRP4 levels [26, 27]. Anti-LRP4 autoantibodies mainly belong to the IgG1 subclass, thus they can activate the complement system; moreover, they prevent agrin-induced MuSK activation and AChR clustering [27].
Current therapeutic approaches for MG include symptomatic treatment with cholinesterase inhibitors, non-specific immunosuppression with corticosteroids and thymectomy in selected patients. Plasmapheresis or immunoglobulins are used for acute management of severe muscular weakness [8]. New biological drugs targeting molecules involved in the specific immune-pathological mechanisms, like eculizumab, which blocks the C5 terminal complement component, and efgartigimod, a functional IgG neonatal Fc receptor blocker, are promising for more specific and effective intervention to reduce corticosteroids side effects and to treat refractory patients [8].
The thymus is a primary lymphoid organ that provides a complex environment essential for T-cell differentiation and the establishment of central tolerance. It is composed of various cell types, mainly thymocytes and thymic epithelial cells (TECs), but also myoid cells, dendritic cells (DCs), macrophages, and B-cells in a limited number. By expressing tissue-specific antigens, mainly via the transcription factor autoimmune regulator (AIRE), medullary TECs play a key role in negative selection of thymocytes. Indeed, interactions between these cells and developing thymocytes lead to the elimination of autoreactive T cells, whereas the self-tolerant T cells continue their differentiation through the different thymus compartments, to be exported to the periphery [28].
Structural and functional pathological alterations of the thymus are found in approximately 80% of AChR-MG patients with generalized disease, including thymic hyperplasia (about 70% of patients) and thymoma (10–15%); the remaining patients (10–20%) present an atrophic or involuted thymus, mainly consisting of adipose tissue with residual areas of thymic parenchyma, in some cases showing hyperplastic changes (Figure 1) [13, 29, 30]. Hyperplasia is characterized by the presence of B-lymphocyte infiltrates invading the thymic medulla, or present in expanded perivascular spaces fused with the thymic medulla. B-cell infiltrates can be scattered throughout the medullary parenchyma (diffuse hyperplasia) or be organized into ectopic B-cell germinal centers (GCs) which, together with DCs and follicular helper T (Tfh) cells, form follicles (follicular hyperplasia) [30]. GCs are microarchitectures specialized to produce high-affinity antibodies against antigens, to establish the humoral immune response [31]. They are present in secondary lymphoid organs but rarely into the thymus, implying that GC development in the thymus of MG patients is a pathological event related to autoimmunity development. Ectopic GC formation is a characteristic feature of other organs target of chronic inflammation and autoimmunity, including multiple sclerosis (MS) brain and synovia of rheumatoid arthritis (RA) patients, indicating that lymphoid neogenesis plays a relevant role in the immune-pathological process of inflammatory autoimmune conditions [31, 32, 33]. In MG, GC formation is associated with the production of high endothelial venules expressing inflammatory chemokines, that abnormally recruit peripheral immune cells into the thymus, including the chemokine ligand 21 (CCL21), a key molecule that orchestrates thymic hyperplastic changes by promoting B-cell infiltration [34]. Uniquely, MG thymic GCs are surrounded by muscle-like myoid cells expressing AChR and other muscle antigens, along with plasma cells [35], thus supporting the idea that GCs may be the site of autosensitization and autoantibody production in the thymus of MG patients.
Pathological abnormalities of myasthenia gravis thymus. Immunohistochemistry stainings showing CD20-positive B-cells in ectopic germinal centers (GCs) and lymphoid infiltrates of follicular hyperplastic (MG-FH) and diffuse hypeplastic (MG-DH) thymuses. CD20-positive B-cells are also scattered throughout the residual thymic parenchima in involuted MG thymuses characterized by abundant interlobular fat (MG-INV). CD20-positive B-cells, isolated or present as aggregates, can be detected in the cytokeratin (CK)-positive tumoral tissue of MG thymomas (MG-T).
A wealth of data indicates that MG thymus contains all the elements necessary for developing and perpetuating an AChR-specific autoimmune response: TECs and muscle-like myoid cells expressing the autoantigen, professional antigen-presenting cells, AChR-specific autoreactive T cells and B-cells, and plasma cells producing autoantibodies [30]. Indeed, transplantation of MG thymic fragments to immunodeficient mice induces the formation of anti-AChR antibodies and their deposition at the skeletal muscle endplates [36].
As regard to the autoantigen presentation, TECs express major histocompatibility (MHC) class II complex and AChR subunits, including α, β, and γ subunits [37]. Thymic myoid cells express not only AChR subunits but also a functional AChR, whose fragments can be presented to T lymphocytes by cross-presentation via DCs, since myoid cells do not express MHC class II molecules [38, 39]. Cross-presentation may be favored by a persistent autoantibody and complement-mediated attack to myoid cells, which make the levels of autoantigen more available to DCs [40, 41]. Both TECs and myoid cells respond to pro-inflammatory cytokines by increasing the expression of AChR components, mainly the α subunit, which contains the main immunogenic region, thus suggesting that inflammation in the thymic microenvironment can results in enhanced autoantigen presentation and possible autosensitization against AChR [42]. Indeed, several lines of evidence indicate that MG thymus is in a state of chronic inflammation, characterized by an overexpression of pro-inflammatory cytokines and chemokines (IL-6, CCL19, CCL21, CXCL10, CXCL11, CXCL13, and RANTES) [43]. Among cytokines, type I interferons (IFNs) and IFN-induced genes are significantly up-regulated in hyperplastic MG thymuses and have been critically involved in driving thymic events that can lead to follicular hyperplastic changes, AChR overexpression and autosensitization. In particular, IFN-β was found to increase α-AChR-specific expression in TECs, along with the expression of inflammatory chemokines (e.g., CXCL13 and CCL21), and was able to recruit T and B-cells into the thymus, as well as B-cell activating factor (BAFF), which favors B-cell survival [44]. In hyperplastic MG thymus, no changes in the frequency of CD4+ and CD8+ T cells exported to the periphery was observed, but functional defects of regulatory T cells (Tregs) were demonstrated, along with resistance of conventional T cells to the Treg immunosuppressive function, thus indicating dysregulation of immunoregulatory mechanisms [45]. Altered Treg/T effector cell balance was associated with increased expression of pro-inflammatory cytokines by MG T cells, mainly IL-17, IFN-γ, IL-21, and tumor necrosis factor α (TNF-α) [45].
Thymoma is a rare thymic epithelial tumor, associated with autoimmune and paraneoplastic syndromes. The most common thymoma-associated autoimmune disorder is MG: up to 50% of thymoma cases may develop MG, whereas 10–15% of MG patients present thymoma [46]. Histologically, thymoma is a slow growing, locally invasive tumor consisting of transformed epithelial cells surrounded by maturing polyclonal T cells. The most recent World Health Organization (WHO) classification identified five types, A, AB, B1, B2, and B3, based on the nature of the cortical or medullary epithelial cells, and on the proportion of lymphocytes, with B2 and AB being the WHO types most frequently associated with MG [47, 48]. MG associated with thymoma usually has worse prognosis, showing generalized and maximum severe symptoms [48]. Alterations typical of the thymoma microenvironment may explain the development of AChR-specific autoimmunity in thymoma patients. They include: the lack of a functional medulla expressing AIRE; the reduction, or absence, of tolerogenic myoid cells; the reduced expression of HLA class II molecules; and the failure of Treg generation, which ultimately leads to autosensitization to AChR, and other locally expressed muscle antigens, and defective negative T-cell selection [14, 49, 50]. Recently, a higher proportion of GCs was abnormally found in non-neoplastic thymic tissue adjacent to thymoma in MG patients compared to thymoma patients without MG, suggesting that B-cell dysregulation characterizes not only thymic hyperplasia but also thymoma-associated MG, and that GCs may represent a risk factor for the development of MG in thymoma patients [51].
An important evidence of the central contribution of the thymus in autoimmune response development and maintenance in MG is the ability of thymectomy to improve the disease course in non-thymomatous patients over a 2-year period after the surgery, as demonstrated by the MGTX clinical trial, and its extension study [29, 52]. Thymectomy is mandatory for thymoma patients. Its efficacy as treatment option in non-thymomatous patients is plausibly due to eradication of the site of autoimmunity, as indicated by the fact that AChR antibody titers usually fall after thymectomy, and the magnitude of this fall correlates with the proportion of GC B-cells in the removed thymus [53]. However, autoantibody titers do not always fall, suggesting other possible sites of autoantibody production in some patients [54].
Innate immunity is the first line of defense against pathogen infections. Its interplay with the adaptive-humoral immune system plays a key role in central and peripheral tolerance maintenance, and strictly depends on a fine regulation of TLRs. TLRs are a family of pattern recognition receptors (PRRs) able to recognize specific conserved microbial-derived molecular structures, thus sensing danger signals. They are expressed by a variety of cell types, but mainly by innate immune cells, such as DCs and macrophages [55]. The TLR family includes at least 11 members in humans: TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10, which are located on the cell surface and recognize microbial membrane-associated molecules (e.g., LPS, lipoprotein, and peptidoglycan); TLR3, TLR7, TLR8, TLR9, and TLR11, present on the intra-cellular endosome membranes and able to distinguish bacterial or viral nucleic acids, including ssRNA, dsRNA, and unmethylated cytosine phosphate guanine (CpG)-containing DNA [55]. Upon its own specific ligand binding, TLR dimerizes, internalizes, and interacts with the intracellular adaptor myeloid differentiation primary response gene 88 (Myd88) or with the TIR domain-containing adapter-inducing IFN-β (TRIF), which activates nuclear factor κB (NFκB) and IFN response factor transcription. The TLR signaling cascade induces the expression of pro-inflammatory agents (e.g., IFN-I, IL-6, IL-12, IL-23, and TNF-α), which in turn contribute to activate immune system cells [56]. In this way, the first function of TLRs is to set up an innate immune response to protect the organism from pathogens. However, TLRs have been implicated in several autoimmune diseases, including systemic lupus erythematosus (SLE), RA, and MS, by studies performed in humans and animal models [56, 57]. Specifically, dysregulated or persistent TLR activation has been demonstrated to contribute to autoimmunity by (i) abnormal stimulation of antigen-presenting cell maturation and increased IFN-I and pro-inflammatory cytokine production; (ii) altered balance between Treg and T helper 17 (Th17) cells; (iii) induction of co-stimulatory signals for proliferation, maturation, and survival of B-cells, which compromise B-cell tolerance; and (iv) promotion of GC formation [56, 57, 58].
In hyperplastic MG thymuses, overexpression of TLR3, TLR4, TLR7, and TLR9, in association with chronic inflammation, has been demonstrated in different studies, thus supporting the existence of a critical cross talk between innate immunity and autoimmunity in the intra-thymic MG pathogenesis [59, 60, 61, 62, 63].
Our group was the first to demonstrate a marked overexpression of TLR4 in involuted and hyperplastic MG thymuses, especially in TECs [59]. Later, we revealed that TLR4 stimulation in MG TECs was able to increase the production of Th17-related cytokines and the expression of CCL17 and CCL22, two chemokines involved in peripheral immune system cell recruitment in inflamed organs, that we found to be overexpressed in MG thymuses [60]. Moreover, by generating an in vitro imaging model based on experimental autoimmune MG co-cultures of Th1/Th17 AChR-specific T cells, naïve Tregs, DCs, and TECs, we found that TLR4 stimulation increased AChR-specific T-cell activation and impaired Treg function, thus disclosing a contribution of dysregulated TLR4 signaling to the inflammatory and autoimmune process in the MG thymic milieu [60].
Cufi and colleagues showed that also TLR3 is overexpressed in MG thymuses and demonstrated that stimulation of this TLR with its ligand poly(I:C), a synthetic analog of viral dsRNA, induced a specific up-regulation of α-AChR in TECs but not of other AChR subunits or tissue-specific antigens, via IFN-β release [61]. Of interest, another study of the same group disclosed that poly(I:C) injection in wild-type mice, in combination with LPS, that stimulates TLR4 was able to increase α-AChR thymic expression and induce thymic hyperplastic changes along with production of serum anti-AChR antibodies [62]. These mice developed MG symptoms in absence of any AChR immunization, thus supporting the idea that pathogen infections could contribute to anti-AChR sensitization and autoimmunity development via persistent or abnormal TLR stimulation [62].
Along with TLR3 and TLR4, TLR7 and TLR9 have also been implicated in the intra-thymic pathological events leading to MG. Indeed, we recently revealed a significant TLR7 and TLR9 up-regulation in both involuted and hyperplastic MG thymuses compared to normal thymuses, with the two receptors being mainly expressed in B-cells, TECs, plasmacytoid DCs, and macrophages [63]. TLR7 was also enhanced in thymic myeloid DCs and its transcriptional levels positively correlated with those of IFN-β [63]. Interestingly, as described in the following paragraphs, the two receptors were markedly expressed in B-cells and plasma cells positive for EBV proteins, indicating EBV as contributing environmental factor implicated in dysregulated TLR activation in MG thymuses.
Of interest, due to the key contribution of TLRs to chronic inflammation and immune system dysregulation, their pathways are rapidly emerging as attractive targets for therapeutic strategies able to mitigate or inhibit autoimmune processes [64].
EBV is the main virus suspected to play a role in autoimmune diseases due to its unique ability to infect, activate, and immortalize B-cells, allowing them to evade immune surveillance, at the same time, promoting inflammatory state via TLR-mediated innate immune responses [65, 66].
EBV is a DNA virus of the herpes virus family transmitted through saliva exchange and infecting approximately 95% of the world’s population [65]. EBV primary infection mostly occurs during childhood and shows mild symptoms or more frequently none. However, in adolescence or adulthood, EBV causes infectious mononucleosis in 30–70% of cases, with up to 20% of B-cells being infected [67]. After resolution of primary infection, EBV persists lifelong in the host in rare circulating memory B-cells. In the latent state, it is not detectable by immune system and its genome circularizes and replicates together with the host’s chromosomal DNA, resulting in a restricted expression of a maximum of nine viral genes: the EBV nuclear antigens (EBNA1, −2, −3A, -3B, and -3C), the leader protein (LP), and the latent membrane proteins (LMP1, −2A, and -2B). Different expression patterns of EBV latent genes determine the occurrence of EBV latency types I, II, or III, each type being associated with distinct EBV-related diseases [65, 68, 69, 70]. EBV-encoded small nuclear RNA (EBER) 1 and 2 as well as EBNA1 are expressed in all the latency types [65]. EBNA2 is expressed during latency type III (known as growth program), typical of newly infected naïve B-cells, lymphoproliferative disorders, and mononucleosis [68, 69, 70, 71]. LMP1 and LMP2A, key proteins that rescue infected B-cells from apoptosis, act as functional homologs of CD40 and B-cell receptor (BCR) and are expressed during latency III and II (known as default program), with type II being observed in memory B-cells and GC cells, Hodgkin and non-Hodgkin lymphoma, and nasopharyngeal carcinoma [65, 68]. Finally, latency I (known as true latency) is characterized by EBNA1 and EBER expression only; it is typically observed in rare peripheral blood memory B-cells and is associated with Burkitt’s lymphoma [65, 68].
The exact mechanism waking up lytic EBV activities is not clear, but it seems to be the result of dynamic interactions between the host’s immune response and the infection state. When infected B-cells differentiate into plasma cells, the promoter of early lytic genes can be reactivated, driving expression of numerous proteins involved in viral activities (i.e., BSLF1, BALF2, BBLF4, and BALF5) [65]. Two genes, BZLF1 and BRLF1, which encode viral transcription factors, orchestrate the transition from viral latency to lytic infection [69]. New virions primarily infect B-cells, and the viral entry is mediated by viral gp350 protein binding to CD21 [70].
Uniquely, EBV ensures early mechanisms of immune evasion, such as the inhibition of IFN pathways, through a viral IL-10 homolog, the suppression of cytotoxic T-cell responses and the down-regulation of MHC class I and II expression. Moreover, some of the viral proteins are anti-apoptotic, including the early antigen restricted (EA/R), which is a Bcl2 viral homolog that protects infected B-cells from apoptosis and immortalize them [71]. Several mature EBV miRNAs also contribute to immune system alterations in the host by modulating expression of genes involved in immune recognition, antigen presentation and cellular migration, such as miR-BHRF1–3, which regulates IFN-inducible T-cell-attracting chemokine CXCL-11 expression, or miR-BART20-5p and miR-BART8, which affect the IFN-γ signal transduction pathway [72].
Despite it is innocuous in most cases, EBV has true pathogenic potential due to persistent latent infection with periodic reactivations. Disruption of the virus-host balance in susceptible individuals can favor autoimmunity or the abovementioned B-cell malignancies [68, 73]. Among autoimmune diseases, EBV has been associated with MS, SLE, and RA by a number of sero-epidemiological and immunological studies [65, 68, 73]. Moreover, EBV persistence and reactivation have been demonstrated in ectopic B-cell follicles detected in MS brains [74], in the Sjögren’s Syndrome salivary glands [75], and in synovia from RA patients [76], suggesting that EBV might be a common pathogenic feature of autoimmune conditions characterized by B-cell activation and lymphoid neogenesis.
Several mechanisms have been described to explain how viruses may rise an autoimmune response, including molecular mimicry and immune system general activation via TLRs. Molecular mimicry is due to T-cell Receptor (TCR) and BCR recognition flexibility, so that a microbial peptides, structurally similar to a self-peptide, may trigger the autoimmune response [77]. As regard to EBV, EBV-encoded proteins, such as BZLF1, share regions with the host transcription factors of the fos/jun family and host ankyrin proteins, which anchor the cytoskeleton and regulate host transcription factors, including NF-kB, which is critically involved in the immune response [78]. Quantitative and qualitative differences in CD4+ T-cell response to EBNA1 have been described in MS patients [79], and a small percentage of EBNA1-specific T-cell clones cross-recognize myelin-derived epitopes [80]. A further well-characterized example of molecular mimicry between EBV and host proteins is the similarity of regions of EBNA1 with ribonuclear protein Smith (Sm) antigen or the Ro self-protein in SLE [81]. There are also several examples of molecular mimicry relevant for RA, related to aminoacid motif sharing between HLA-DRB1 and EBV gp110, cytokeratin and type II collagen, and citrullinated human fibrin and a citrullinated EBNA1 form [82].
Another hypothesis of virus-induced autoimmunity is bystander activation, in which viruses act as super-antigens that promote general activation of the immune system; in this context, specialized antigen presenting cells present self-antigens, obtained by inflamed tissue destruction or by the uptake of local dying cells, to autoreactive T cells [77]. In MS, bystander activation may result in central nervous system damage by CD8+ T-cell cytotoxicity and EBER-induced IFN-α production via innate immune response, both described in post-mortem brain tissue from MS patients [74, 83]. EBV can promote inflammation in the infected organs by innate immune system activation, through release of molecules able to activate diverse TLRs and type I IFN production [66, 84]. The EBV envelope protein gp350 stimulates TLR2, whereas EBERs bind TLR3; moreover, EBV RNA and DNA can activate pathways mediated by TLR7 and TLR9 [66]. Thus, EBV ability to stimulate persistent TLR signaling may also contribute to disrupt immune system balance, favoring chronic inflammation and autoimmunity.
Evidence of chronic inflammation, GC formation, and TLR overexpression in MG thymus, along with data demonstrating a role of TLRs in inducing anti-AChR autoimmunity and MG symptoms in mice, pointed out the idea that MG pathogenesis could be associated with viral infections [43, 59, 60, 61, 62, 63].
Based on the hypothesis that active EBV infection may be a common pathogenic event of organs site of autoimmunity, in our previous studies we searched for the expression of EBV markers in the thymus of MG patients. Of interest, we provided the first demonstration of EBV presence in both hyperplastic and thymoma MG thymuses, but not in normal thymuses and non-MG thymomas, obtaining results indicative of a contribution of the virus to B-cell dysregulation, TLR overexpression and B-cell-mediated autoimmunity in MG [4, 63, 85, 86, 87].
Earlier serological studies to associate MG with EBV produced contrasting results. One of them underlined no significant difference in incidence or antibody titers to EBV, cytomegalovirus, herpes simplex type 1 and other virus, in 104 MG patients compared to age-matched healthy controls, weakening the virus hypothesis in MG pathogenesis [88]. More recently, Bhibhatbhan and colleagues reported a case of young woman with abrupt onset of both MuSK-MG and type I diabetes mellitus, following infectious mononucleosis, bringing attention back to EBV in MG [89]. Few years after, according with a possible association between MG and EBV, Csuka and collaborators discovered a strong association between EOMG and high anti-EBNA1 IgG serum concentration in EOMG patients [90]. Despite these results were conflicting, our recent pathological findings, which are deeply described below, allowed us to include MG among the autoimmune diseases critically associated with EBV.
To our knowledge, the earliest study attesting EBV presence in MG thymuses was performed by McGuire and colleagues, who found EBV DNA in thymuses of 2/4 MG patients with thymic hyperplasia, and 2/2 patients with thymoma [91]. Before that, several attempts were made for identifying or isolating viruses from homogenates or cell suspensions of MG thymuses, but without success [92, 93]. However, these initial studies used techniques, and tissue storage methods, that cannot be considered sufficiently sensitive or optimal today.
Based on data showing EBV reactivation in intra-meningeal B-cell follicles in MS patients [74], our group decided to check for signs of EBV infection in MG thymuses (n = 17), both hyperplastic (follicular and diffuse) and involuted thymuses by using a combination of techniques, including in situ hybridization (ISH) to detect EBERs, immunohistochemistry (IHC) for latent and lytic EBV antigens, real-time PCR for viral DNA (LMP1 gene), and nested PCR for viral transcripts. As controls, normal thymuses (n = 6) from adult cardiopathic donors without autoimmune diseases were analyzed [85]. Interestingly, all MG, but not normal thymuses, resulted positive for EBV latency and lytic markers, strongly indicating EBV persistence and reactivation as a common feature of MG patients’ thymuses (Figure 2). In details, by ISH, variable number of EBERs-positive cells was detected in medullary infiltrates of all the MG thymuses analyzed, particularly in GCs of hyperplastic MG thymuses. Accordingly, IHC results showed expression of EBV latency proteins EBNA2, LMP1, and LMP2A in cells scattered throughout the thymic medulla and in GCs. The early BFRF1 and BMRF1, and the late p160 and gp350/220 lytic phase EBV proteins were also found in most MG thymuses, but not in control tissues, indicating EBV reactivation. Double immunofluorescence and confocal microscopy then revealed that latently infected cells were diffuse infiltrating and GC B-cells, whereas plasma blasts, mainly located around GCs, were positive for the lytic markers [85]. By PCR approaches, latent EBNA1 and LMP2A transcripts, and the early BZLF1 lytic transcript, along with EBV DNA, were detected in MG thymuses, but not in normal thymuses, thus confirming the active EBV infection. Due to the EBV properties to activate and immortalize B-cells, our findings thus suggested a critical contribution of the virus to intra-thymic B-cell dysfunction and B-cell-mediated autoimmunity in MG patients [85].
Detection of EBV markers in follicular hyperplastic MG thymus (MG-FH), and MG thymoma (MG-T), but not in non-MG thymoma (No MG-T) and normal thymus. Representative images of immunohistochemistry and immunofluorescence stainings showing: EBER-positive cells and cells positive for latent LMP2A and lytic BMRF1 proteins in MG-FH; latent EBNA1-positive cells and CD20-positive B-cells expressing LMP1 in MG thymomas; absence of EBNA1-positive and LMP2A-positive cells in No MG-T; absence of LMP1-positive cells in normal thymuses.
In a following study, we extended the analysis of EBV to additional MG thymuses (n = 19). Real-time PCR for EBV DNA (
In contrast to our outcomes, Meyer and colleagues [94] and Kakalacheva and colleagues [95] reported absence or very low presence of EBV in MG thymuses. The first group performed ISH on formalin-fixed, paraffin-embedded MG thymic tissues (n = 44) and did not observe EBER-positive cells, likewise on cases of Hashimoto thyroiditis (n = 25), except for an isolate case in which rare EBER-positive lymphocytes were detected. Moreover, EBNA1 or BZLF1-positive cells were absent in MG thymuses or Hashimoto thyroiditis by IHC, whereas in infectious mononucleosis rare scattered positive cells were detected [94]. Kakalacheva
To better understand the EBV role in MG pathogenesis, we recently investigated the potential cross talk between TLRs and EBV in rising or sustaining self-reactivity. In details, since EBV molecules (EBERs, EBV DNA) are known to activate TLR7 and TLR9, and considering that these two receptors have super-addictive effects on EBV-induced B-cell activation and transformation process [66, 97], we analyzed their expression in EBV-positive MG and EBV-negative normal thymuses. We revealed an increased percentage of proliferating B-cells positive for EBV markers, and overexpressing TLR7 and TLR9, in EBV-positive hyperplastic MG thymuses compared to controls [63]. Our overall data thus indicated for the first time that aberrant EBV-driven TLR7 and TLR9 signaling in MG thymuses might contribute to abnormal B-cell activation and proliferation, in turn promoting or perpetuating B-cell-mediated autoimmunity in MG patients.
Since the 1980s, the involvement of EBV in thymoma, associated or not with MG, has long been investigated. However, data obtained by the different studies were contrasting: (i) McGuire et al. found EBV DNA in three thymomas, of which two were from MG patients [91]; (ii) absence of EBV in thymic epithelial tumors was reported by Inghirami
Recently, by combining ISH, IHC and molecular techniques, our group demonstrated the presence of latency EBV markers in MG-associated thymomas, but only rarely in thymomas from patients without MG [87]. Specifically, by real-time PCR we showed a significantly higher frequency of EBV DNA and EBER1 detection in MG (53.8% and 84.6%) than non-MG (21.4%) thymomas, with the higher viral load and EBER1 levels being mainly observed in B2 and B2-mixed tumors, the WHO subtypes most frequently associated with MG. These data were in contrast with data on EBV DNA from Cufi and colleagues [102], likely because of the different sensitivity of the protocol used for the viral genome detection.
We then confirmed our molecular results by ISH, which showed the presence of cells positive for EBERs in MG, but not in non-MG thymomas [87]. Latent EBNA2 and late gp350/220 lytic transcripts were undetectable in all thymomas, except one, as well as the early lytic transcript BZLF1, thus revealing that early infection and EBV reactivation are very rare event in thymomas. By IHC analysis, we confirmed EBV persistence in MG thymomas, but not in thymomas without MG, and identified the phenotype of EBV-positive cells, that were B-cells positive for the EBV latency proteins EBNA1, LMP1, and LMP2, diffused throughout the MG neoplastic tissues (Figure 2). Based on the EBV gene expression pattern, we suggested EBV latency type II in MG thymomas. Due to the absence of EBV in thymic epithelial cells, these results thus revealed an association of EBV with B-cell-mediated autoimmunity in MG associated with thymoma, rather than with thymic neoplastic transformation [87]. We also found higher TLR3 transcriptional levels in MG than non-MG thymomas. Transcriptional levels of this receptor positively correlate with EBER1 levels, supporting a possible role for EBER1 in inducing persistent TLR3 signaling pathways in thymoma from MG patients [87]. Due to the previously described role of TLR3 in triggering an anti-AChR autoimmune response [62], our findings strengthened the idea of a critical contribution of EBV to B-cell-mediated autoimmunity via TLR3 in these pathological tissues. Indeed, the activation of EBV-driven TLR3 signaling may well contribute to create an altered tumor microenvironment, which supports the recruitment of peripheral B-cells, and thus B-cell dysregulation and tolerance disruption.
EBV has been associated with several autoimmune diseases by sero-epidemiological and immunological data. Our findings revealed for the first time a contribution of EBV to the intra-thymic MG pathogenesis, thus allowing to include MG among the autoimmune conditions associated with the virus. Based on our results and literature data, we postulate that, in the context of a genetically susceptible background, EBV persistence and reactivation into the thymus may favor B-cell dysregulation, TLR over-stimulation, inflammation, and B-cell-mediated autoimmune response to AChR, which can be perpetuated in the periphery. Further advancement in the knowledge of the exact involvement of EBV and TLRs in MG pathogenesis could set the basis for novel investigations aimed at developing innovative therapeutic applications targeting EBV-positive cells, TLRs, or components of their signaling pathways to counteract autoimmunity in MG and potentially other EBV-associated autoimmune diseases.
The authors wish to thank Dr. Francesca Aloisi and Dr. Barbara Serafini of the Department of Cell Biology and Neuroscience at the Istituto Superiore di Sanità (Rome, Italy) for the key contribution to the studies on EBV in MG thymuses. The authors also thank the neurologists and biologists of the Neurology IV Unit—Neuroimmunology and Neuromuscular Disease at the Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta (Milan, Italy), for their participation in various aspects of these studies, and the Italian Association of Myasthenia Gravis (A.I.M., Associazione Italiana Miastenia e Malattie Immunodegerative—Amici del Besta Onlus) for their kind support to the research activity. The research activity was supported by the Italian Ministry of Health (GR-2013- 02358564 and annual research funding).
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This chapter thus briefly discusses different biological methods, specially biofilm technologies, the development of biofilms on different filter media, factors affecting their development as well as their structure and function. It also tackles various conventional and modern molecular techniques for detailed exploration of the composition, diversity and dynamics of biofilms. These data are crucial to improve the performance, robustness and stability of biofilm-based wastewater treatment technologies.",book:{id:"5197",slug:"microbial-biofilms-importance-and-applications",title:"Microbial Biofilms",fullTitle:"Microbial Biofilms - Importance and Applications"},signatures:"Shama Sehar and Iffat Naz",authors:[{id:"180364",title:"Dr.",name:"Iffat",middleName:null,surname:"Naz",slug:"iffat-naz",fullName:"Iffat Naz"},{id:"183345",title:"Dr.",name:"Shama",middleName:null,surname:"Sehar",slug:"shama-sehar",fullName:"Shama Sehar"}]},{id:"49246",doi:"10.5772/61300",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4671,totalCrossrefCites:25,totalDimensionsCites:57,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]}],mostDownloadedChaptersLast30Days:[{id:"65613",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9161,totalCrossrefCites:13,totalDimensionsCites:21,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"62553",title:"Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance",slug:"antibiotic-use-in-poultry-production-and-its-effects-on-bacterial-resistance",totalDownloads:7230,totalCrossrefCites:43,totalDimensionsCites:86,abstract:"A surge in the development and spread of antibiotic resistance has become a major cause for concern. Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"65914",title:"Introductory Chapter: The Action Mechanisms of Antibiotics and Antibiotic Resistance",slug:"introductory-chapter-the-action-mechanisms-of-antibiotics-and-antibiotic-resistance",totalDownloads:4358,totalCrossrefCites:6,totalDimensionsCites:9,abstract:null,book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu, Nesrin Gareayaghi and Bekir S. Kocazeybek",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"},{id:"248288",title:"Prof.",name:"Bekir",middleName:null,surname:"Kocazeybek",slug:"bekir-kocazeybek",fullName:"Bekir Kocazeybek"},{id:"406463",title:"Dr.",name:"Nesrin",middleName:null,surname:"Gareayaghi",slug:"nesrin-gareayaghi",fullName:"Nesrin Gareayaghi"}]},{id:"50992",title:"Probiotics: A Comprehensive Review of Their Classification, Mode of Action and Role in Human Nutrition",slug:"probiotics-a-comprehensive-review-of-their-classification-mode-of-action-and-role-in-human-nutrition",totalDownloads:5380,totalCrossrefCites:15,totalDimensionsCites:27,abstract:"Probiotics are live microorganisms that live in gastrointestinal (GI) tract and are beneficial for their hosts and prevent certain diseases. In this chapter, after a complete introduction to probiotics, definition, mechanism of action, and their classification, currently used organisms will be discussed in detail. Moreover, different kinds of nutritional synthetic products of probiotics along with their safety and drug interaction will be noticed. This chapter mentions all clinical trial studies that have been done to evaluate probiotic efficacy with a focus on gastrointestinal diseases.",book:{id:"5193",slug:"probiotics-and-prebiotics-in-human-nutrition-and-health",title:"Probiotics and Prebiotics in Human Nutrition and Health",fullTitle:"Probiotics and Prebiotics in Human Nutrition and Health"},signatures:"Amirreza Khalighi, Reza Behdani and Shabnam Kouhestani",authors:[{id:"179560",title:"Dr.",name:"Amirreza",middleName:null,surname:"Khalighi",slug:"amirreza-khalighi",fullName:"Amirreza Khalighi"},{id:"185238",title:"Dr.",name:"Reza",middleName:null,surname:"Behdani",slug:"reza-behdani",fullName:"Reza Behdani"},{id:"185239",title:"Dr.",name:"Shabnam",middleName:null,surname:"Kouhestani",slug:"shabnam-kouhestani",fullName:"Shabnam Kouhestani"}]},{id:"56849",title:"Physiology and Pathology of Innate Immune Response Against Pathogens",slug:"physiology-and-pathology-of-innate-immune-response-against-pathogens",totalDownloads:6143,totalCrossrefCites:21,totalDimensionsCites:28,abstract:"Pathogen infections are recognized by the immune system, which consists of two types of responses: an innate immune response and an antigen-specific adaptive immune response. The innate response is characterized by being the first line of defense that occurs rapidly in which leukocytes such as neutrophils, monocytes, macrophages, eosinophils, mast cells, dendritic cells, etc., are involved. These cells recognize the pathogen-associated molecular patterns (PAMPs), which have been evolutionarily conserved by the diversity of microorganisms that infect humans. Recognition of these pathogen-associated molecular patterns occurs through pattern recognition receptors such as Toll-like receptors and some other intracellular receptors such as nucleotide oligomerization domain (NOD), with the aim of amplifying the inflammation and activating the adaptive cellular immune response, through the antigenic presentation. In the present chapter, we will review the importance of the main components involved in the innate immune response, such as different cell types, inflammatory response, soluble immune mediators and effector mechanisms exerted by the immune response against bacteria, viruses, fungi, and parasites; all with the purpose of eliminating them and eradicating the infection of the host.",book:{id:"5975",slug:"physiology-and-pathology-of-immunology",title:"Physiology and Pathology of Immunology",fullTitle:"Physiology and Pathology of Immunology"},signatures:"José Luis Muñoz Carrillo, Flor Pamela Castro García, Oscar\nGutiérrez Coronado, María Alejandra Moreno García and Juan\nFrancisco Contreras Cordero",authors:[{id:"214236",title:"Dr.",name:"Jose Luis",middleName:null,surname:"Muñoz-Carrillo",slug:"jose-luis-munoz-carrillo",fullName:"Jose Luis Muñoz-Carrillo"},{id:"216080",title:"Dr.",name:"Alejandra",middleName:null,surname:"Moreno-García",slug:"alejandra-moreno-garcia",fullName:"Alejandra Moreno-García"},{id:"216081",title:"Dr.",name:"Oscar",middleName:null,surname:"Gutiérrez-Coronado",slug:"oscar-gutierrez-coronado",fullName:"Oscar Gutiérrez-Coronado"},{id:"216082",title:"Dr.",name:"Pamela",middleName:null,surname:"Castro-García",slug:"pamela-castro-garcia",fullName:"Pamela Castro-García"},{id:"220717",title:"Dr.",name:"Juan Francisco",middleName:null,surname:"Contreras Cordero",slug:"juan-francisco-contreras-cordero",fullName:"Juan Francisco Contreras Cordero"}]}],onlineFirstChaptersFilter:{topicId:"13",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82423",title:"Removal of Divalent Nickel from Aqueous Solution Using Blue Green Marine Algae: Adsorption Modelling and Applicability of Various Isotherm Models",slug:"removal-of-divalent-nickel-from-aqueous-solution-using-blue-green-marine-algae-adsorption-modelling-",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.103940",abstract:"The adsorption of Ni(II) onto blue green marine algae (BGMA) in batch conditions is being investigated. The highest adsorption capacity of BGMA was found to be 42.056 mg/g under ideal testing conditions, where the initial Ni(II) metal ion concentration was adjusted from 25 ppm to 250 ppm. The optimal pH, biomass loading, and agitation rate for maximum Cu(II) ion removal have been determined to be 6, 2 g and 120 rpm, respectively. For the equilibrium condition, 24 hours of contact time is allowed. At room temperature, all of the experiments are conducted. The isotherm has a L shape, based on the equilibrium experimental data. It indicates that there is no considerable competition for active sites between the solvent and Ni(II). There is no strong competition between the solvent and Ni(II) for the active sites of BGMA, indicating that there is no strong competition between the two. It also suggests that the BGMA’s Ni sorption ability is restricted (II). The experimental data is validated using multiple isotherm models, and the mechanism of adsorption is then discovered, as well as the process design parameters. The Fritz-Schlunder-V isotherm model is particularly relevant in defining the mechanism of Ni(II) adsorption under the conditions used in this study, according to modelling studies. This model’s qmax of 41.89 mg/g shows that it matches experimental data more closely.",book:{id:"11366",title:"Microalgae",coverURL:"https://cdn.intechopen.com/books/images_new/11366.jpg"},signatures:"Ramsenthil Ramadoss, Durai Gunasekaran and Dhanasekaran Subramanian"},{id:"81704",title:"Quorum Sensing Inhibition Based Drugs to Conquer Antimicrobial Resistance",slug:"quorum-sensing-inhibition-based-drugs-to-conquer-antimicrobial-resistance",totalDownloads:2,totalDimensionsCites:null,doi:"10.5772/intechopen.104125",abstract:"Quorum sensing is the cell to cell communication mechanism in microorganism through signalling molecules. Regulation of virulence factor, sporulation, proteolytic enzymes production, biofilm formation, auto-inducers, cell population density are key physiological process mediated through quorum-sensing (QS) signalling. Elevation of innate immune system and antibiotic tolerance of pathogens is highly increased with perspective of quorum-sensing (QS) activity. Development of novel drugs is highly attractive scenario against cell-cell communication of microbes. Design of synthetic drugs and natural compounds against QS signal molecules is vital combat system to attenuate microbial pathogenicity. Quorum sensing inhibitors (QSIs), quorum quenchers (QQs), efflux pump inhibitors (EPIs) act against multi-drug resistance strains (MDR) and other pathogenic microbes through regulation of auto-inducers and signal molecule with perceptive to growth arrest both in-vitro and in-vivo. QQs, QSIs and EPIs compounds has been validated with various animal models for high selection pressure on therapeutics arsenal against microbe’s growth inhibition. Promising QSI are phytochemicals and secondary metabolites includes polyacetylenes, alkaloids, polyphenols, terpenoids, quinones.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic – Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Kothandapani Sundar, Ramachandira Prabu and Gopal Jayalakshmi"},{id:"82419",title:"Effect of the Mass Distribution of ITNs in an Endemic Area with a High Entomological Index, the Case of Bandundu-City, Kwilu, DRC",slug:"effect-of-the-mass-distribution-of-itns-in-an-endemic-area-with-a-high-entomological-index-the-case-",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105021",abstract:"The bio-efficacy of Yorkol-branded ITNs collected from Bandundu-city was assessed on the Kisumu strain and wild specimens of Anopheles gambiae. The susceptibility of the wild An. gambiae s.l. was tested to select insecticides. Adult An. gambiae s.l. sampled by PSC and HLC were screened for the presence of Plasmodium falciparum. Blood samples were diagnosed by microscopy and RDTs. ITN distributed in Bandundu-city were fully effective on the Kisumu strain, but on wild An. gambiae s.l. population (22.3 ± 11.5%). Anopheles gambiae s.l. was the main vector in Bandundu. No significant difference was observed between the entomological indices before and after the deployment of nets (OR = 0.8; p = 0.39). Wild An. gambiae s.l. populations were resistant to pyrethroids and DDT, with the restoration of the susceptibility to pyrethroids post pre-exposure to PBO. Plasmodium falciparum was the main parasite species and was found alone or mixed with. P. malariae or P. ovale. The confirmation rates by microscopy and RDT were respectively 57.9% and 53.6%. Nets deployed in Bandundu-city were not effective on wild An. gambiae s.l. populations. This operational failure is likely explained by the observed resistance to pyrethroids. In the future only PBO-net should be deployed Bandundu-city.",book:{id:"11379",title:"Mosquito Research - Recent Advances in Pathogen Interactions, Immunity, and Vector Control Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11379.jpg"},signatures:"Emery Metelo-Matubi, Josue Zanga, Victoire Nsabatien, Aimé Mbala, Solange Ngamukie, Fiacre Agossa, El Hadji Amadou Niang, Jean Maniania-Nguya-Kalenga and Mulenda Basimike"},{id:"82435",title:"Vector-Parasite Interactions and Malaria Transmission",slug:"vector-parasite-interactions-and-malaria-transmission",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.105025",abstract:"Malaria remains one of the world’s most devastating vector-borne diseases. During the complex sexual development of the malaria parasite in the mosquito, it is faced with physical and physiological barriers which it must surmount before it can be transmitted to a human host. Proof-of-concept studies using RNAi have unearthed several parasite molecules which are important for countering the immunity of its vector. Understanding the counter-adaptations between the parasite and its vector could inform novel public health intervention strategies. For instance, it could guide the transgenic construction of resistant mosquitoes in which mosquito factors that restrict the parasite growth have been enhanced and/or factors promoting parasite growth deleted so as to make them refractory to malaria parasite infection. Such strategies, when deemed feasible, could be combined with conventional vector control methods as well as treatment of infection with effective malaria therapy, to actualize the malaria eradication goal.",book:{id:"11379",title:"Mosquito Research - Recent Advances in Pathogen Interactions, Immunity, and Vector Control Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11379.jpg"},signatures:"Nekpen Erhunse and Victor Okomayin"},{id:"82397",title:"Gut Microbiota Potential in Type 2 Diabetes",slug:"gut-microbiota-potential-in-type-2-diabetes",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105616",abstract:"Appropriate metabolic regulation is vital for health. Multiple factors play important roles in maintaining the metabolic system in different physiological conditions. These factors range from intestinal metabolism of food and absorption of nutrients, pancreatic hormones and their interplay under feeding and fasting, hepatic regulation of macronutrient formation and metabolism storage of macronutrients in skeletal muscles. Intestinal metabolism of ingested food and subsequent nutrient absorption depends on the symbiotic microbial community residing in the gut. The specific ratio of different microbial phyla in the gut has proved to be extremely important for the beneficial role of the gut microbiome. The importance of gut microbiome in the regulation of metabolism has been highlighted with reports of the abnormal ratio of gut microbial community resulting in different metabolic disturbances ranging from obesity to the development of diabetes mellitus. The physiological impact of insulin on the metabolic regulation of macronutrients has recently been shown to be augmented by the secondary metabolites produced by anaerobic fermentation. The current chapter aims to highlight recent findings in the regulation of extraintestinal metabolism by gut microbiome with a specific emphasis on the physiology and pathophysiology of the pancreas in health and disease.",book:{id:"11631",title:"Gut Microbiota - Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11631.jpg"},signatures:"Shahzad Irfan, Humaira Muzaffar, Haseeb Anwar and Farhat Jabeen"},{id:"82372",title:"Unlocking the Potential of Ghost Probiotics in Combating Antimicrobial Resistance",slug:"unlocking-the-potential-of-ghost-probiotics-in-combating-antimicrobial-resistance",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.104126",abstract:"Antimicrobial resistance is a global concern that requires immediate attention. Major causes of development of antimicrobial resistance in microbial cells are overuse of antimicrobials along the food chain especially in livestock, in preventing infections as well as misuse of antimicrobials by patients. Probiotics could be a viable alternative to antibiotics in the fight against antimicrobial resistance. Probiotic strains can act as a complement to antimicrobial therapy, improving antimicrobial function and enhancing immunity. However, there are safety concerns regarding the extensive use of live microbial cells especially in immunocompromised individuals; these include microbial translocation, inhibition of other beneficial microorganisms and development of antimicrobial resistance, among other concerns. Inevitably, ghost probiotics have become the favored alternative as they eliminate the safety and shelf-life problems associated with use of probiotics. Ghost probiotics are non-viable microbial cells (intact or broken) or metabolic products from microorganisms, which when administered in adequate amounts have biologic activity in the host and confer health benefits. Ghost probiotics exert biological effects similar to probiotics. However, the major drawback of using ghost probiotics is that the mechanism of action of these is currently unknown, hence more research is required and regulatory instruments are needed to assure the safety of consumers.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic – Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Abigarl Ndudzo, Sakhile Ndlovu, Nesisa Nyathi and Angela Sibanda Makuvise"}],onlineFirstChaptersTotal:97},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:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:317,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,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:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9759",title:"Vitamin E in Health and Disease",subtitle:"Interactions, Diseases and Health Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/9759.jpg",slug:"vitamin-e-in-health-and-disease-interactions-diseases-and-health-aspects",publishedDate:"October 6th 2021",editedByType:"Edited by",bookSignature:"Pınar Erkekoglu and Júlia Scherer Santos",hash:"6c3ddcc13626110de289b57f2516ac8f",volumeInSeries:22,fullTitle:"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu",profilePictureURL:"https://mts.intechopen.com/storage/users/109978/images/system/109978.jpg",institutionString:"Hacettepe University",institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:4},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:9},{group:"subseries",caption:"Chemical Biology",value:15,count:13}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:8},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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\r\n This topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
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