Some basic differential diagnoses of ASPS.
\r\n\tIn eukaryotic cells, the endoplasmic reticulum is an organelle adjacent to the nuclear membrane. This organelle is essential for calcium homeostasis and lipid biosynthesis and protein assembly, folding, and post-translational modification. The interplay between the endoplasmic reticulum membrane and the outer mitochondrial membrane, called mitochondria-associated endoplasmic reticulum membranes (MAMs), permits a wide range of cellular activity, including the division and fusion of mitochondria and the dynamic passage of lipids, glycogen, and calcium ions.
\r\n\tIt has been established that energy/nutrient depletion, calcium flux injury, or oxidative stress disrupt endoplasmic reticulum homeostasis and even induce accumulation of misfolded/unfolded proteins leading to endoplasmic reticulum stress. Under endoplasmic reticulum stress conditions, an adaptive mechanism of coordinated signaling pathways, defined unfolded protein response (UPR), is activated to return the endoplasmic reticulum to its healthy functioning state. The aging causes a decrease of the protective adaptive response of the UPR and an increase of the pro-apoptotic pathway together with endoplasmic reticulum ultrastructural injury. Controlling endoplasmic reticulum stress response, maintaining the appropriate endoplasmic reticulum ultrastructure and homeostasis, and retaining mitochondria interplay are crucial aspects for cellular health.
\r\n\tThis book presents a comprehensive overview of endoplasmic reticulum, including, but not limited to, endoplasmic reticulum ultrastructural anatomy, MAMs, endoplasmic reticulum stress, and their implication in health and diseases. Additionally, identifying perturbations in the endoplasmic reticulum stress response could lead to early detection of age-related disease and may help develop therapeutic approaches.
",isbn:"978-1-80356-228-5",printIsbn:"978-1-80356-227-8",pdfIsbn:"978-1-80356-229-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"5d7d49bd80f53dad3761f78de4a862c6",bookSignature:"Dr. Gaia Favero",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",keywords:"Metabolism, Aging, Neurodegenerative Diseases, Endoplasmic Reticulum, Microscopy, Metabolic Stress, Ultrastructural Anatomy, Cellular Stress, Contactology, Mitochondria, Cellular Stress, Endoplasmic Reticulum Response",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",remainingDaysToSecondStep:"14 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Human anatomy researcher involved in crucial topics on morphology, anatomy, and molecular medicine - working on innovative approaches to aging-related pathopsychological processes at the University of Brescia.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero",profilePictureURL:"https://mts.intechopen.com/storage/users/238047/images/system/238047.jpg",biography:'Dr. Gaia Favero is a prominent scientist in the field of life sciences. She is currently engaged as a researcher for the Scientific-Disciplinary Sector BIO/16 Human Anatomy at the Anatomy and Pathophysiology Division, Department of Clinical and Experimental Sciences, University of Brescia (Italy).\r\nDr. Favero focuses on aging-related morphological dysfunctions as the prelude to various pathophysiological processes in her research programs. The central hypothesis is that natural antioxidants and, in particular, melatonin may act as molecular "switches" that modulate cells and tissues by suppressing, at various levels, oxidative stress and inflammatory signalling cascades. These research approaches represent powerful tools for developing innovative preventive strategies and identifying novel prognostic biomarkers for several diseases. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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\nThe proportion of the world’s population living in cities is increasing dramatically. It is predicted that by 2030, the worldwide population of urban dwellers will be nearly 5 billion [3], and by 2050 it may reach 9 billion [4]. The increased rate of urbanization has important economic, social, and political implications: A large number of people residing in the cities can approach toward education and employment easily; they can trust the healthcare industry and can see cultural evolution. But this rapid growth of population is often integrated with communal challenges and also climate change: cities may fail to provide the basic facilities resulting in communal riots leading to inferior and undesirable living conditions. Therefore, in order to deal with the challenges of rapid urbanization, urban agriculture is in demand nowadays.
\nThe need or importance of urban agriculture is broadly discussed with the following
Today, cities consume more than two-thirds of the world’s energy and are responsible for 70% of global CO2 emissions. Recently, UA is considered to deal with the difficult situations like climate change as it plays sufficiently in greening the metros and improving the warmer city climate while encouraging the reuse of organic wastes that reduces the urban energy footprint [2].
\nThe World Meteorological Organization (WMO) suggested that more urban farming should take place as a response to climate change and as a way to build more resilient cities.
\nUA helps cities to improve the urban environment and become more resilient by [2, 6]:
UA reduces the weakness of specific urban groups and diversifies urban food sources and income opportunities of the urban poor and forms a source of innovation and learning about new strategies/technologies for land- and water-efficient food production.
UA helps in keeping the open areas covered with greeneries that might reduce the severity of the climatic conditions. UA also makes the microclimate worth living and also forbids the construction of buildings on risky areas, and by this not only flooding, landslides, and other disasters are reduced but also urban biodiversity and living conditions are improved. Such open green spaces also help to control storm water flows by allowing water storage and increased infiltration of excess storm water [7]. In these open green spaces in and around urban areas, food production can be combined with other services to city dwellers, such as agro-tourism or park and landscape maintenance, e.g., “productive parks.”
UA produces fresh green foods that reduces the green-house gas emission and also uses limited energy in the process of getting food from the farm to the plate in industrially developed countries [8].
Productive reuse of waste water in UA helps to combat the freshwater crisis and also saves rivers, canals, and other water bodies from being polluted by the waste water. On the other hand, waste water as a source of irrigation might decrease the risk of water scarcity [9]. Use of urban waste water as a source of irrigation will help to adapt to risks of drought and flood. Urban waste water can be recycled for irrigation/fertilization of horticultural crops, i.e., floriculture and fruit crops, as well as for irrigation of forest plantations that provide wood for fuel.
UA contributes to enhance urban food security and nourishment of the poor class. Families that are involved in UA are exposed to better quality and variety of diet. They consume more herbs and greens than the others. Production of food by urban families can supply up to 20–60% of their total food consumption especially in green vegetables, medicinal and aromatic plants, eggs, and milk and meat from small animals. Involvement in UA may also cause better mitigation of diseases as it has better nutritional and medicinal properties in homegrown medicinal plants, it causes more physical exercise, and people do not have to depend on gifts and food aid which may enhance their self-esteem. UA also increases the accessibility of fresh and affordable food for other urban consumers, as most of the food produced by urban farmers is bartered or sold locally. UA also ensures food requirement during natural calamities and wars. In Sierra Leone, the residents devoted themselves in UA in order to meet their daily foods during the civil war that lasted for about 10 years. UA acts as a survival strategy for the refugees and helps them to live in a state of being worthy for honor [1, 2, 6].
\nThe world’s urban population is expected to reach 6–9 billion by 2050. It is estimated that poverty will progress from villages to the metro cities by 2030 as 60% of the Earth’s population will reside in the cities. Moreover, in most developing countries, urbanization has led to the growth of slum population which has almost doubled in the past 15 years [3]. Also this rapid urbanization in developing countries created difficulty in making sufficient employment opportunities creating very poor living conditions in the slum areas. The presence of UA can definitely meet the requirement of employment to some extent in the cities of developing countries. The effects of UA on poverty alleviation vary with the type of participants involved, the products produced, and the degree of market orientation, among other things. UA often plays an important role in the survival strategies of the urban dwellers, who might be benefited from UA in various ways: Firstly, when a household produces edible crops, their food expenses are reduced and they can do a huge amount of savings. Moreover, the surplus produce can be sold by them in order to make a profitable business [2, 6].
\nIn addition to climate change and urbanization, food production is confronted with decrease in productive agricultural land. Large-scale urban food production could provide opportunities and take the pressure off agricultural land. Consequently, researchers and practitioners are aiming to separate arable land from production and produce food on a larger scale in and on buildings in high-density urban areas. Scientists visualized the “edible city” and introduced the concept of continuous productive urban landscape (CPUL), recommending the coherent introduction of interlinked productive landscapes into cities as an essential element of sustainable urban infrastructure. One major challenge of urban food production is land availability and access. Principally, there might be large resources of land that could be made accessible for agricultural purposes, but for densely built-up areas and where availability of space often limits the area of production unit, no-space or low-space technologies provide opportunities for space-confined growing [5, 10, 11].
\nBesides its so many advantages, there are some
Reuse of contaminated, untreated irrigation water from urban streams gives rise to potential health risks. This can be managed through complementary health risk reduction measures as explained in the 2006 WHO guidelines for safe use of excreta and waste water.
Insufficient or improper management of livestock leads to health risks. Proper management of animals, manure, urine, and slaughterhouse procedures will reduce the rate of the associated health risks.
Intensive use of fertilizers, pesticides, and fungicides in UA may lead to residues of agrochemicals in crops or in the groundwater. The risk mainly occurs in areas with commercial urban farming. In subsistence and semicommercial urban farming, this risk is limited because the producers rarely apply agrochemicals due to poverty. They use composted organic wastes as they prefer a clean product for self-consumption.
With rapid worldwide population growth, there is scarcity of agricultural lands. It increases the demand for both more food and more land to grow food. But some entrepreneurs and farmers are beginning to find a solution to this problem, one of which can be found in the abandoned warehouses in our cities, in new buildings built on environmentally damaged lands, and even in used shipping containers from ocean transports. This solution is called vertical farming, which is an UA technology involving growing crops in controlled indoor environments, with precise light, nutrients, and temperatures.
\nIn vertical farming, growing plants are arranged in layers that may reach several stories high. Although small-scale, residential vertical gardening (including window farms) is under practice for several years, commercial-scale vertical farms have become an important topic of discussion for the past few years in the United States. This new farming technology is growing rapidly, and entrepreneurs in many cities are taking an interest in this innovative farming system [12].
\nVertical farming is gaining its importance throughout several urban cities around the world due to the beneficial role it plays in the field of agriculture. Vertical farming can reduce the transportation costs due to its adjacency to the buyer; planned production of herbs and their growing conditions can be enhanced by adjusting the temperature, humidity, lighting conditions, etc. Indoor farming in a controlled environment needs much less amount of water than outdoor farming because it involves recycling of waste water. Because of these features, vertical farming is widely implemented initially in desert and drought-stricken regions, such as some Middle Eastern countries, Africa, Israel, Japan, and the Netherlands [13].
\nIt is the predominant growing system used in vertical farms, involving growing plants in nutrient solutions that are devoid of soil. The plant roots are submerged in a nutrient solution, which is frequently examined and circulated to ensure that the correct chemical composition is maintained [12].
\nUrban hydroponics is not a recent invention. The Hanging Gardens of Babylon and the Floating Gardens of the Aztecs were beautifying the cities for quite a long period of time. Also, fruits and vegetables were cultivated in those areas. Nowadays, modern cities use urban hydroponics for physical and psychological relaxation. It is also plays an important role in managing the urban environment. In areas with arid climate, it increases humidity and lowers temperatures. It also captures dust and polluted air by the foliage of the plants. It contributes to the reduction of the overall discharge of CO2, hence preventing global warming to some extent. Hydroponics gardens are usually constructed vertically because city space is limited. Apart from immediate improvement in the environmental quality, vertical farms on top of traditional buildings serve as large heat sinks that radiate heat and increase ambient air temperature; hydroponic systems thermoregulate buildings by trapping heat in the winter and cooling buildings in the summer. The air quality inside the house can also be improved by growing plants on interior walls. In some modern cities, for example in Bangkok, the concrete roads and railway overpasses are covered with hydroponically grown ornamentals. Also commercial centers are decorated with indoor hydroponics for an improved air quality inside [14].
\nThe hydroponic system is taken one step forward by another system called aquaponics which combines plants and fish in the same ecosystem. The nutrient-rich wastes produced by the indoor-grown fish serve as feed source of the plants present in the vertical farm. On the other hand, the plant filters and purifies the waste water which is then recycled into the fish tanks [12].
\nThis combination of systems is cheaper and easier as mineral nutrients are not be purchased and the plants are growing totally organically and moreover no additional expenses are required to clean the fish tanks and there is no scene of pesticides harming the fish. Thus, aquaponics is not only cost-effective but also diseases in the systems can be reduced and a very suitable urban farming technology can be formed. Canadian scientist Savidov explained that possibly the organic components in the system make the trace elements readily available to the plant for proper growth and thus recirculating aquaponic system decreases root diseases in the crop with increased crop yield from aquaponics compared with conventional hydroponics. Also fruits and vegetables grown in aquaponic system qualify for organic product certification very easily since no pesticides and fertilizers are used in this system. Some scientists are planning to construct vertical farms in skyscrapers and have created the name sky farming. Such buildings may also incorporate aquaponics to ensure a good source of fresh fish [14].
\nThis innovative indoor growing technique was first developed by the National Aeronautics and Space Administration (NASA). In the 1990s, NASA started finding efficient ways to grow plants in space and coined the term “aeroponics.” Aeroponic systems are still in a growing phase in the vertical farming world, however gaining interest gradually. It is an efficient plant-growing system in vertical farms, using up to 90% less water than other efficient hydroponic systems. Plants grown in these aeroponic systems take up more minerals and vitamins, making the plants healthier and more nutritious [12].
\nIn tropical hot and humid climate, it is difficult to grow temperate vegetables like lettuce. Geoff Wilson, an agricultural journalist and Australia’s representative of a group of 16 national organizations for an international Green Roofs organization, has reported in an article that a new aeroponic system originated in Singapore can provide a solution to this difficulty. Traditional aeroponic method involved cold nutrient mixture that used to be sprayed onto the plant roots, thereby lowering the temperature causing wilting and ultimately death of the plant. But this type of cooling is expensive, even for rich cities like Singapore. To overcome this limitation, in the year 2004, Gregory Chow, lecturer at the Ngee Ann Polytechnic of Singapore invented the air dynaponics—a much less costly way of maintaining low root-zone temperatures for commercially successful aeroponics. This system gave positive outcomes. Researchers stated that the nutrients infused with oxygen “energized” the entire root system and improved the plant top biomass. Air dynaponics uses the cooling methods of Venturi nozzle effect in an air-powered operation that lowers the temperature of the nutrient mixture and supplies air from the dissolved oxygen. In Singapore, this method is used to produce valuable greens like butterhead lettuce, Batavia lettuce, and Romaine lettuce for moneymaking purposes [14].
\nThese are the types of vertical farms constructed in abandoned buildings in urban areas. For example, Chicago’s “The Plant” vertical farm was constructed in an old pork-packing plant. Vertical farms are also constructed in new buildings. A new multistory vertical farm is built to an existing parking lot structure in downtown Jackson Hole, Wyoming. Here, vegetables are grown throughout the year in the 13,500-square-foot hydroponic greenhouse for sale to restaurants, to local grocery stores, and also directly to consumers [12].
\nThese types of vertical farms are becoming popular day by day. They use 40-foot shipping containers that carry goods around the world and house vertical farms with LED lights, drip irrigation systems, and vertically stacked shelves for growing a variety of plants. It contains computer-controlled growth management systems that allow users to examine all systems from a smartphone or computer. The three leading companies producing shipping-container vertical farms are Freight Farms, CropBox, and Growtainers [12].
\nDespommier mentioned a number of environmental and social advantages in his book called “The Vertical Farm: Feeding the World in the 21st Century.” The advantages are summarized below [15]:
Vertical farming ensures production of greens all year round in nontropical countries and is better than normal farming. Despommier stated that 1 acre of vertical farm can produce products almost equal to the amount of products produced by 30 acres of normal farmland on considering the number of crops produced each season.
Vertical farming involves reduction or abandonment of the use of herbicides and pesticides. In some cases, vertical farming uses ladybugs and other biological controls when required.
As the crops in a vertical farm are grown under a controlled environment, they are safe from extreme weather conditions such as droughts, hail, and floods.
Hydroponic growing techniques help in water conservation by using about 70% less water than normal agriculture.
Indoor farming reduces or eliminates the use of tractors and other large farm equipment that are commonly used on outdoor farms, thus reducing the burning of fossil fuel. According to Despommier, large-scale vertical farming could result in a significant reduction in air pollution and in CO2 emissions.
Vertical farming is people friendly. Some hazards that can be avoided in vertical farming are accidents while operating heavy farming equipment and exposure to harmful chemicals.
Apart from so many advantages, there are many critics of the vertical farming described by the scientists. They claimed that there are a number of problems in vertical farming. The challenges to vertical farming may be summarized as follows [13]:
Start-up costs are high in order to purchase land in central business districts.
The number of crops grown is sometimes less than rural farming.
Production volumes are also not as large as conventional farming and scaling-up may add cost and complexity.
Raising investment capitals and training a skilled workforce are also challenges in vertical farming.
Scientists explored the motivations for urban gardening in Germany by screening 657 urban gardening project websites and characterized the types of gardeners, cultivation methods, and consumer behavior. The study also highlighted the “terrabioponic smart-garden system” where the plants grow in natural soil and in organic nutrient solution, which may facilitate social transition toward bio economy [16]. Also scientists from the United Kingdom reported that vertical farming system has increased the yield of lettuce per unit area as compared to traditional horizontal hydroponics [17]. Agriculture and food production activities in the cities of Mexico can contribute in reducing carbon footprint by creating green environment and better land use [18].
\nIndia is one of the largest producers of fruits, vegetables, and many other agricultural products. In India, vertical farming has been introduced in recent times. Experts from Indian Council of Agricultural Research (ICAR) are working on the concept of “vertical farming” which can be implemented in metros like New Delhi, Mumbai, Kolkata, and Chennai [20].
\nScientists at Bidhan Chandra Krishi Viswavidyalaya in Nadia, West Bengal, had initial success on growing brinjal and tomato hydroponically on a small scale. Punjab also has succeeded in producing potato tubers through vertical farming [20].
\nIn cities like Cuttack and Nagpur, the slum dwellers performed organic farming on terrace and plots and sold the surplus products to the local markets. In Delhi, on the fertile banks of Yamuna River, extensive farming is going on in spite of the fact that farmers do not have any legal sanction to do farming there. In Hyderabad, farmers living along the banks of Musi River use water from the river for urban farming and contributed rice and vegetables to the market [21].
\nIn the urban areas of Tripura, to help the youth for income generation, a prototype model on “vertical farming system” was developed. The area of the structure was about 630 sq. ft. with two floors and two galleries. The ground floor contained two cages (50 sq. ft. each) at both corners that accommodated 100 layer chicks. The central space (140 sq. ft) housed 200 bird broiler/layer chicks per batch. Eight goats were kept on the first floor (140 sq. ft.) area. There were also 12 rabbits kept in hanging cages (4 sq. ft. each). Proper drainage facility was provided to collect wastes with storage facility where it was decomposed and used for manuring the pots. Three
Ideafarms is an Indian design-in-tech company which produces vertical farm products, and the produce is of high quality and organic and the supply is huge. A Bengaluru-based start-up company named Greenopia is selling kits with self-watering pots, enriched soil, and better quality seeds. A Mumbai-based start-up firm U-Farm Technologies is using hydroponic gardening technique to build vertical farm for an individual apartment or for a supermarket [20].
\nVertical farming is definitely a solution to critical problems in Indian farming like lack of supply of farm produce, overuse of pesticides and fertilizers, and even unemployment. But there are some challenges: The initial huge cost of infrastructure for implementing vertical farming in India is difficult. Vertical farming in India has to face other challenges like public awareness, technical knowledge, and high cost of managing and maintaining the vertical farm systems [20].
\nUrban farming, both vertical farming or farming on vacant open spaces, can be a favorable way for ensuring food security in India and around the world in the future. Although countries like Europe, the USA, and Singapore have already implemented vertical farming and are dealing with big projects for future concerns, India still has a long way to go as it is restricted to only few self-interest-driven projects. Institutional support, awareness of the benefits associated with urban agriculture, and financial and technological support from the government can only attract the city dwellers and help them to move forward with the concept of urban agriculture in India. Progressive growth of urban agriculture can act as an urban regeneration tool for the cities by providing social interaction and increasing job opportunities and environmental benefits to the urban areas across the globe. Thus, to combat the challenges associated with rapid increase in population, the topic of “urban agriculture” is being closely monitored by scientists, city planners, and the sustainable agricultural community for a better future.
\nAlveolar soft part sarcoma (ASPS) is a rare orphan malignant soft tissue tumor of uncertain cellular lineage representing 0.5–1% among soft tissue sarcomas and with a somewhat indolent yet lethal clinical course. It was first described in 1952 by Christopherson, a fellow in surgical pathology at Memorial Sloan Kettering Cancer Center, who reported 12 cases with similar clinical and pathology features [1]. It occurs mainly in adolescents and young adults between 15 and 40 years of age. For localized disease, the survival rate is 71% at 5 years and falls at 20% at 5 years for metastatic disease [2].
At diagnosis, a patient with ASPS describes a slow-growing mass in the extremities. Tumors in adults are most frequently involved located in the deep soft tissue of the lower extremities, especially the thigh and buttock [2]. This stands in contrast to the pediatric population where the tumor clearly has a predilection for the head and neck, and in particular the tongue and orbit [3]. ASPS has also been described as a rare primary lesion of the calvarium [4] and the pleura [5]. In the viscera, occurrences have been reported in such diverse anatomic sites as liver [6], lung [7], gastrointestinal tract [8], breast [9], uterine corpus [10], cervix [11], and the bladder [12]. Some deeply seated tumors may be quite large whereas those located in the head and neck area and viscera usually measure much less.
Preferential sites of metastatic sites are lung, bone, and frequently the brain. Metastases have been reported even 15 years after primary tumor diagnosis [2].
ASPS consists of nests of large rounded cells sometimes associated with characteristic crystalloids and embedded in a finely capillarized stromal background. The molecular genetics aspect involves the recurrent unbalanced translocation der(17)t(X;17)(p11;q25) [13]. The female predominance could theoretically be based on the statistical observation that the risk of a translocation involving the X chromosome present in two copies is greater in women [14]. No differentiation lineage is established according to the WHO classification of soft tissue tumors [15] although as is well-known differentiation patterns are the basis of most of the histopathological classifications of sarcomas.
After the original description of the lesion, one of the prevailing hypotheses, now totally abandoned, concerned its alleged myogenic phenotype which had fueled the unresolved question of its histogenesis. Masson had first numbered this tumor among muscle lesions [16]. Much data then seemed to uphold striated muscle differentiation based on different observations. Immunohistochemistry and immunofluorescent techniques showed cytoplasmic expression of muscle-associated proteins, such as desmin, muscle-specific actin, MM isozyme of creatine kinase [17, 18, 19, 20, 21, 22, 23, 24, 25], and nuclear expression of the skeletal muscle-specific regulatory protein MyoD1 [23]. The myogenic hypothesis was ultimately set aside for the following reasons. Desmin is not considered a reliable marker of skeletal muscle tissue differentiation and can be found expressed as well in smooth muscle proliferation, rhabdoid tumors, Ewing sarcoma, or neuroblastoma [26]. As for the nucleophosphoproteins MyoD1 and myogenin, no subsequent studies confirmed positivity. In the 12 cases reported by Wang et al. [27] and the 19 cases reported by Gomez [28] et al. immunohistochemical nuclear expression was completely absent. These authors observed nonspecific granular cytoplasmic staining linked to aberrant cross-reactions with unrelated antigens. In their studies, western blotting failed to highlight the 45-kd band of MyoD1, and MyoD1 transcript has not been detected by northern blot analysis [20]. Neither had ultrastructural myofilaments been observed in alveolar soft part sarcoma [27, 29]. The ultrastructure of the crystalloids supposedly composed of Z-band tropomyosin B, similar to rod structures seen in rhabdomyoma [30] seemed to favor muscle differentiation but new data demonstrated the absence of tropomyosin [31]. Some subsequent gene expression profiling studies momentarily revived the concept of muscle cell differentiation with the identification of differentially expressed genes [32, 33]. But later studies failed to validate these findings [34].
One report of expression profiling analysis suggested a neural differentiation because of marked expression of the transcription factor PAX6, an activator of neural genes [35, 36]. Curiously a neural crest origin had already been speculated [37].
DeSchryver-Kecskemeti et al. described ASPS as “malignant angioreninoma.” Indeed fluorescein-tagged antirenin antibodies in tumor cell were detected [38]. However, patient arterial hypertension was missing, and no tumor renin secretion (whether active or inactive) was biochemically revealed [31]. ASPS had also been labeled, albeit incorrectly as “malignant myoblastoma,” “granular cell myoblastoma,” “malignant granular cell myoblastoma” [39, 40, 41], or as “malignant tumor of the non-chromaffin paraganglia” [42].
When excised, ASPS has a soft consistency with encapsulated borders. The cut surface has a white to yellow–brownish color tinged with hemorrhagic spilling or central necrosis in large tumors (Figure 1a).
ASPS : gross pathology (cut surface) (a), typical cytoarchitectural features (b-j) and TFE3 immunohistochemical nuclear staining (k).
ASPS shows a distinctive recognizable morphology in most cases with nests or trabeculae (Figure 1b,c, and e) of large epithelioid round cells displaying an alveolar (Figure 1d) and sometimes dyscohesive appearance (Figure 1d and h). The stroma has a delicate vasculature with frequent lymphovascular invasions (Figure 1j). Typical cytoarchitectural aspects include individual monomorphic tumor cells with an abundant granular eosinophilic or clear glycogen-rich cytoplasm, sharp cytoplasmic borders, no striations, and an eccentric vesicular nucleus containing a prominent central nucleolus. In some cases, sheets of contiguous tumor cells may appear solid (Figure 1f and g), a finding more conspicuous in children. Cells can be multinucleated (Figure 1h). Mitoses are few and necrosis rare. Other possible aspects are nuclear pseudoinclusions, cystic or myxoid changes, stromal sclerosis, calcification, and chronic inflammatory infiltrate [2, 13, 42, 43, 44, 45, 46, 47, 48, 49, 50]. Rarely, some tumors display a high mitotic rate, polymorphism, spindling, and xanthomatous changes [9].
Special stains, such as periodic acid-Schiff with diastase can highlight crystalloids, rod-like or rhomboid diastase-resistant membrane-bound intracytoplasmic crystalline formations originally noted by Masson [16] (Figure 1i—arrows). Ladanyi et al. were able to conclude that these are complexes of monocarboxylate transporter 1 (MCT1) interacting with a CD 147, a chaperone protein [51]. Their microscopic detection may be time-consuming and inconclusive. Some cases show simply a granular substance instead of crystals which could be a pre-crystalline formation of the MCTI-CD147 complex [51].
In electron microscopy, ASPS cells are poor in desmosomes and are lined by incomplete basement membranes in contact with capillaries [43, 47]. The cytoplasmic endoplasmic reticulum is as a rule sparse, mitochondria are numerous, and Golgi apparatus is greatly developed [43]. The latter is associated with crystalloids or pre-crystallized electron-dense granules mentioned above both of which are membrane-bound [31, 43, 47].
Immunostaining is, in most cases, unnecessary for diagnosis. Transcription factor TFE3 expression (Figure 1k) is linked to the gene fusion ASPL-TFE3 (Figure 2) but is not specific to ASPS as it can also be seen in subsets of epithelioid hemangioendotheliomas and PEComas [52], in granular cell tumor, malignant melanoma and pediatric renal cell carcinoma [53].
Fluorescent
This contrasts with sensitivity which is high (92%) Nevertheless, staining can also be weak or even absent in some cases, particularly in pre-analytically ill-prepared samples [54].
CD147/EMMPRIN, a glycoprotein of the immunoglobulin superfamily, is considered a marker of poor prognosis as well as for some authors a potential therapeutic target [54, 55]. Secreted by the cancer cells as a conjugate protein of MCT1, a lactate transporter, it induces matrix metalloproteinases production by neighboring stromal fibroblasts hence facilitating local tumor progression and ultimately metastasis [15, 54, 55]. Its expression is not limited to ASPS but has also been signaled in other lesions, such as granular cell tumor and clear cell renal cell carcinoma [54].
Diffuse cytoplasmic immunostaining with cathepsin K, a protease activated by the microphthalmia transcription factor (MITF) in osteoclasts, is fairly constant. But it is also seen in melanoma, clear cell sarcoma, granular cell tumor, and PEComa [56, 57].
Other possibly expressed markers with little significance in ASPS include desmin, actin [5, 6, 7, 8, 9, 10, 11, 12, 14], S-100 protein [21], NKIC3 [22], histiocytic marker CD68 KP1 [58], and vimentin [24]. Nuclear myogenin and MyoD1, cytokeratin, epithelial membrane antigen (EMA), chromogranin, synaptophysin, neurofilament, and glial fibrillary acidic protein (GFAP) are always negative [24, 47, 50]. The eventual clinical utility of standard immune complementary immunohistochemical tests in ASPS is yet to be determined. As mentioned earlier, lymphocytic infiltrate is rare. However, Goldberg et al. reported having identified activation of the PD-1 (programmed death-1) pathway with cell immunoreactivity for PD-L1 (PD-ligand 1) and individual CD8+ tumor-infiltrating T cells expressing PD-1 [59]. This, however, needs to be confirmed.
The unbalanced translocation der(17)t(X;17)(p11;q25) and its consequential fusion gene, a marker specific as well as sensitive [54], is the exhibited molecular label of ASPS. Cullinane et al. first reportedly identified this alteration cytogenetically [60]. This paved the way for the description of the two breakpoints on Xp11.2 and 17q25 [61] leading to the characterization of the two involved genes [14], the transcription factor TFE3 on Xp11.2 and a novel gene with no yet known function, ASPL/ASPSCR1 (alveolar soft part sarcoma locus/alveolar soft part sarcoma chromosomal region 1) on 17q25 (Figure 3a and b). In the encoded protein, there is conservation of the COOH-extremity and the DNA-binding domain of TFE3. Contrariwise its N-terminal sequences are occupied by ASPL which alters TFE3 normal activity. The oncoprotein then shifts to the nucleus where it behaves as a transcriptional driver.
Representations of TFE3 (a) and ASPL (b) genes with breakpoints indicated by arrows; bottom figures (c, d) correspond to the types 1 and 2 fusions respectively.
Two published cases show a reciprocal translocation however [14, 62]. Further, two mutually exclusive translocation variants have been identified although with no known clinical consequence at present. The ASPL gene has a unique breakpoint whereas the TFE3 gene possesses two possible breakpoints with two possible fusion types. According to Ladanyi et al., in type 1 fusion, the ASPL gene is joined in frame to TFE3 exon four (exon 3 is excluded). In type 2, it links with exon 3. Aulmann et al. [63] emphasized that under the later reference sequence (GenBank NM_006521) with a modified nomenclature (with no biological consequence) since Ladanyi’s publication [14], in type 1, the shortened ASPL gene (exons 1–7) joins directly with exon 6 of TFE3 (exon 5 is excluded) and in type 2 with exon 5 (Figure 3c and d).
Rapid diagnosis is usually achieved by fluorescent
The molecular mechanisms driven by the ASPL-TFE3 oncoprotein are not entirely known. Senescence promotion through p21 up-regulation wielding a mechanism of tumor progression by senescence-associated secretory phenotype (SASP) via proinflammatory cytokines secretion has been proposed [65, 66, 67, 68].
In gene expression profiling analysis, MET acts as a transcriptional target of the ASPL-TFE3 fusion. The latter binds to the activated promoter, induces MET tyrosine kinase autophosphorylation increasing MET protein expression in the presence of its ligand hepatocyte growth factor (HGF), and upregulates downstream signaling, to promote cell proliferation, growth, and invasion. MET appears to be a possible candidate for targeted therapy in [69, 70].
Other actions of TFE3 aim at targeting hypoxia-inducible factor (HIF-1a) which activates angiogenesis via factors, such as VEGFA, PDFG, or angiopoietin [32, 35, 71, 72, 73, 74], findings useful for antiangiogenic therapy investigations.
Further, melanoma inhibitor of apoptosis (ML-IAP), a factor of cell survival in melanoma targeted by MITF, is proven to be overexpressed in ASPS gene expression profiling [71, 75]. Both MITF and TFE3 are members of the basic helix–loop–helix leucine zipper transcription factors family and lock on to the same DNA motif, the E-box DNA consensus segment CANNTG [65, 76, 77].
CGH array studies show complex anomalies at multiple levels—gains of 1q, 8q, 16q, and Xp11-pter [78] with translocations, deletions, trisomy 12, trisomy 8, and loss of chromosome 17 after chemotherapy [79]. Updated results with high-resolution aCGH reported by Selvarajah et al. have confirmed these observations and suggested increased genomic instability in the metastatic setting with still more gains and losses [35].
Recent literature relative to immunogenicity in ASPS mentions significantly increased expression of host response factors to the lesion involving the innate activating receptors TLR2 and TLR9 [59].
In our experience, ASPS can have overlapping morphological features to some degree with other lesions of which the most frequent are listed in Table 1, but these mimics lack the specific recurrent nonreciprocal translocation found in ASPS. Key cytoarchitectural aspects, such as severe atypia, spindling, or pleomorphism generally are not in favor of ASPS. Moreover, the latter belongs to different clinical and immunohistochemical contexts. Generally, paragangliomas fit older patients [50] and are not readily observed in limbs. Unlike in ASPS, tumor cells are void of cytoplasmic glycogen. More importantly, they show neuroendocrine differentiation with the accompanying sustentacular cells being immunoreactive with anti-S-100 protein [57]. Clear cell sarcoma of soft tissue and metastatic melanoma consistently express melanocytic markers, such as HMB45 and Melan A, as well as S100 protein. Equivocally in metastatic melanoma, those antigens may be lost and like in ASPS, Cathepsin K can be immunopositive. Clear cell sarcoma of soft tissue may likewise express focally cathepsin K but harbors a reciprocal translocation t(12,22) resulting in the fusion of EWSR1-ATF1 in most cases [57]. Granular cell tumors, like in ASPS, may immunostain with TFE3 and cathepsin K but unlike ASPS they are also consistently reactive with anti-PS100, anti-SOX 10, and anti-inhibin antibodies [57, 80].
Clear cell sarcoma of soft tissue |
Metastatic melanoma |
Clear cell renal carcinoma |
Liver cell carcinoma |
Granular cell tumor |
PEComa |
Paraganglioma |
Rhabdomyosarcoma |
Some basic differential diagnoses of ASPS.
Renal cell carcinoma in children shares with ASPS the same fusion gene resulting from identical breakpoints [81, 82, 83] but here translocation is reciprocal. Reciprocity can be assessed using the right primers to the nonfunctional fusion site [72]. Contrary to ASPS, renal cell carcinomas immunostain with cytokeratin, epithelial membrane antigen (EMA), and PAX8 and do not express cathepsin K. They can harbor other fusion partners of TFE3, such as DVL2 and PRCC. These fusion genes, DVLE2-TFE3 and PRCC-TTF3 as well as the newly identified chimeric HNRNPH3-TTF3 have been detected in ASPS also [84].
Liver cell carcinoma can morphologically represent an important diagnostic pitfall, the liver being a possible primary site of ASPS. Hepatocarcinoma cells are immunopositive for hepatocyte paraffin 1 (Hep-Par1), glypican-3, and polyclonal carcinoembryonic antigen (P-CEA) [57].
Neuroendocrine or endocrine tumors, contrary to ASPS, stain with antibodies against chromogranin, synaptophysin, and CD56.
PEComas are most often located in the pelvis, gynecologic tract, and retroperitoneum. Like ASPS, a subset expresses TFE3 but with a double differentiation pattern, smooth muscle and melanocytic, staining with h-Caldesmon, HMB45, less often Melan A., all of which are negative in ASPS [85]. Adrenocortical carcinomas express Melan A or inhibin. Rhabdomyosarcomas are consistently positive for skeletal muscle differentiation markers (desmin, nuclear myogenin or MyoD1). A number of other lesions are perhaps not likely to be confused with ASPS but can nevertheless, because of their epithelioid cell morphology and abundant cytoplasm, be considered as differential diagnoses of the tumor in its less frequent solid appearance without alveolar configuration. These include epithelioid sarcoma, epithelioid angiosarcoma, epithelioid hemangioendothelioma, myoepithelioma, chordoma, meningioma, or even histiocytic sarcoma. But these present immunohistochemical and molecular profiles inconsistent with ASPS.
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The following chapter looks at typical applications, real needs of public services as well as the performance of the novel system.",book:{id:"6465",slug:"drones-applications",title:"Drones",fullTitle:"Drones - Applications"},signatures:"Marzena Półka, Szymon Ptak, Łukasz Kuziora and Aneta Kuczyńska",authors:[{id:"226977",title:"Dr.Ing.",name:"Szymon",middleName:null,surname:"Ptak",slug:"szymon-ptak",fullName:"Szymon Ptak"},{id:"240085",title:"Prof.",name:"Marzena",middleName:null,surname:"Półka",slug:"marzena-polka",fullName:"Marzena Półka"},{id:"240086",title:"MSc.",name:"Łukasz",middleName:null,surname:"Kuziora",slug:"lukasz-kuziora",fullName:"Łukasz Kuziora"},{id:"240087",title:"MSc.",name:"Aneta",middleName:null,surname:"Kuczyńska",slug:"aneta-kuczynska",fullName:"Aneta Kuczyńska"}]},{id:"58775",title:"Unmanned Aerial Systems for Magnetic Survey",slug:"unmanned-aerial-systems-for-magnetic-survey",totalDownloads:1411,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Placing a magnetometer on unmanned aerial vehicle (UAV) seems to be an easy task as the sensor is rather lightweight in comparison with other geophysical sensors. But, the realization of an unmanned aeromagnetic system (UAMS) faces multiple technical complications, and, as a result, very few of many attempts to build a UAMS have succeeded. Even less projects have produced results of real magnetic survey. Different platforms (helicopters, multirotor, and fixed wing UAVs) and different kinds of magnetometers for UAMS have different pros and cons for the purpose. For the quality of magnetic survey, the most important is the issue of a platform’s (UAV) magnetic noise and its influence on a magnetic sensor. Workbench experimental studies as well as results of magnetic surveys with multirotor UAMS in Leningrad region, Republic Sakha-Yakutia, and Kazakhstan demonstrate solutions facilitating state-of-the-art high-quality measurements of magnetic anomalies for geological, archeological, and other purposes.",book:{id:"6465",slug:"drones-applications",title:"Drones",fullTitle:"Drones - Applications"},signatures:"Sergey Cherkasov and Dmitry Kapshtan",authors:[{id:"224731",title:"Dr.",name:"Sergey",middleName:null,surname:"Cherkasov",slug:"sergey-cherkasov",fullName:"Sergey Cherkasov"},{id:"224762",title:"MSc.",name:"Dmitry",middleName:null,surname:"Kapshtan",slug:"dmitry-kapshtan",fullName:"Dmitry Kapshtan"}]},{id:"58576",title:"Generalized Control Allocation Scheme for Multirotor Type of UAVs",slug:"generalized-control-allocation-scheme-for-multirotor-type-of-uavs",totalDownloads:1319,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Unmanned aerial vehicles (UAVs) are autonomous or remotely guided aircraft, which can potentially carry out a wide range of tasks. Multirotor type of UAV has unique ability to perform vertical take-off and landing (VTOL), a stationary and low-speed flight where certain configurations can achieve very complex and precise movements. Therefore, they are suitable for performing tasks such as delivery of first aid kit, firefighting, infrastructure inspection, aerial video, and many others. In this chapter, a generalized control allocation scheme for a multirotor UAV is presented, which describes the mapping of rotor angular velocities to the control vector of the aircraft. It enables control and design of multirotor configurations with diverse geometrical arrangement and characteristics of the propulsion subsystem depending on the task, which multirotor has to carry out. The inverted scheme, which is implemented as a motor mixer, maps the control inputs into a set of aircraft actuator outputs.",book:{id:"6465",slug:"drones-applications",title:"Drones",fullTitle:"Drones - Applications"},signatures:"Denis Kotarski and Josip Kasać",authors:[{id:"222226",title:"Ph.D.",name:"Denis",middleName:null,surname:"Kotarski",slug:"denis-kotarski",fullName:"Denis Kotarski"},{id:"237976",title:"Prof.",name:"Josip",middleName:null,surname:"Kasać",slug:"josip-kasac",fullName:"Josip Kasać"}]},{id:"5966",title:"Advanced UAV Trajectory Generation: Planning and Guidance",slug:"advanced_uav_trajectory_generation__planning_and_guidance",totalDownloads:5860,totalCrossrefCites:5,totalDimensionsCites:6,abstract:null,book:{id:"3696",slug:"aerial_vehicles",title:"Aerial Vehicles",fullTitle:"Aerial Vehicles"},signatures:"Antonio Barrientos, Pedro Gutierrez and Julian Colorado",authors:null}],onlineFirstChaptersFilter:{topicId:"1251",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. 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In recent years, emerging technologies such as multi-omics, high-throughput technologies, and genome editing tools could assist plant physiologists in unraveling molecular mechanisms in specific critical pathways. The global picture of physiological processes in plants needs to be investigated continually to increase our knowledge, and the resulting technologies will benefit sustainable agriculture.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null,series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"313856",title:"Dr.",name:"Christophe",middleName:"F.E.",surname:"Hano",slug:"christophe-hano",fullName:"Christophe Hano",profilePictureURL:"https://mts.intechopen.com/storage/users/313856/images/system/313856.png",institutionString:"University of Orléans",institution:{name:"University of Orléans",institutionURL:null,country:{name:"France"}}},{id:"33993",title:"Dr.",name:"Jose Carlos",middleName:null,surname:"Jimenez-Lopez",slug:"jose-carlos-jimenez-lopez",fullName:"Jose Carlos Jimenez-Lopez",profilePictureURL:"https://mts.intechopen.com/storage/users/33993/images/system/33993.jpg",institutionString:null,institution:{name:"Spanish National Research Council",institutionURL:null,country:{name:"Spain"}}},{id:"191770",title:"Dr.",name:"Mohamed A.",middleName:null,surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. 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