CMOS image sensor characteristics for commercial camera phones.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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This book presents theoretical works as well as empirical studies that contrast the arguments offered by the leading, ground-breaking theories on the firm value. What variables determine the firm value? Are these determinants controllable or uncontrollable by the managers of the companies? Is the impact of corporate governance systems on the firm value symmetrical between different institutional contexts? Do the financial reports affect the value of the firm? What role does corporate social responsibility play as a determinant of the firm value? These and other questions are analyzed and scrutinized step by step throughout this book.",isbn:"978-1-78923-495-4",printIsbn:"978-1-78923-494-7",pdfIsbn:"978-1-83881-674-2",doi:"10.5772/intechopen.72333",price:119,priceEur:129,priceUsd:155,slug:"firm-value-theory-and-empirical-evidence",numberOfPages:150,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"df56274854b9ccf88ca5c4b342713671",bookSignature:"Paolo Saona Hoffmann",publishedDate:"August 1st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6725.jpg",numberOfDownloads:9679,numberOfWosCitations:3,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:10,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:20,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 15th 2017",dateEndSecondStepPublish:"December 6th 2017",dateEndThirdStepPublish:"February 4th 2018",dateEndFourthStepPublish:"April 25th 2018",dateEndFifthStepPublish:"June 24th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"201486",title:"Ph.D.",name:"Paolo",middleName:null,surname:"Saona Hoffmann",slug:"paolo-saona-hoffmann",fullName:"Paolo Saona Hoffmann",profilePictureURL:"https://mts.intechopen.com/storage/users/201486/images/6368_n.jpg",biography:"Paolo Saona is a Professor of Finance at John Cook School of Business, Saint Louis University in its campus of Madrid, Spain. He received his PhD at Universidad de Valladolid, Spain, and his MBA and BSc in Business at Universidad Austral de Chile. His research fields are international corporate finance, international corporate governance, capital structure decision, financial and regulatory systems, and banking systems. His research work has appeared in a number of international refereed scientific journals. He is a member of numerous international societies and served in the editorial board of several scientific journals. He has been awarded with research grants.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Saint Louis University",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"63",title:"Business Administration",slug:"business-management-and-economics-business-administration"}],chapters:[{id:"61748",title:"Firm Value",doi:"10.5772/intechopen.77342",slug:"firm-value",totalDownloads:1919,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The chapter explains the meaning of firms from the perspective of economic researchers in the past to the views of current dates. Traditional model of a firm’s value is linked firmly with shareholders’ value. This traditional view is used in finance and in business for many years. To enhance a firms’ value, we need to maximize shareholders’ value. According to this view, any activities in firms can increase the value of firms if it increases the value of the Shareholders. However, traditional concept of shareholders’ value as the explanation to firms’ value is challenged by a group of researchers. This group believes that value of firms should not be based on just shareholders but should include all groups of stakeholders. After giving some ideas on the meaning of firm, the corporate sustainability value of firm in terms of economics and finance is explained.",signatures:"Ravi Lonkani",downloadPdfUrl:"/chapter/pdf-download/61748",previewPdfUrl:"/chapter/pdf-preview/61748",authors:[null],corrections:null},{id:"61720",title:"Stock Price Determinants: Empirical Evidence from Muscat Securities Market, Oman",doi:"10.5772/intechopen.77343",slug:"stock-price-determinants-empirical-evidence-from-muscat-securities-market-oman",totalDownloads:1481,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Stock price is one of the main indicators for measuring firm performance and also the only factor determining shareholders’ wealth. Stock price changes are based on information related to the firm and the market as a whole. This paper is focused on the determinants of the share price of the twenty-six non-financial companies listed in Muscat Securities Market, Oman. In this study, closing annual stock price from 2011 to 2016 is the dependent variable and the firm-specific variables like firm size (logarithm of total assets), dividends payout, earning per share (EPS), debt ratio, price-earnings(PE) ratio, first lag of dependent variable(stock price) are the independent variables in the panel data regression using random effect model. There are two categories of research hypothesis: the first one is based on semi-strong form of Efficient Market Hypothesis (EMH) and second one is based on Arbitrage Pricing theory (APT). To test the second set of hypothesis, oil price, growth rate in GDP and consumer price index are considered as independent variables as they effect performance of business and so do the stock prices. EPS, debt ratio and first lag of stock prices are significant determinants of stock prices. Dividend payout, firm size and PE ratio are insignificant variables.",signatures:"Dharmendra Singh",downloadPdfUrl:"/chapter/pdf-download/61720",previewPdfUrl:"/chapter/pdf-preview/61720",authors:[null],corrections:null},{id:"60927",title:"Effect of Free Float Ratio on the Behavior of Shares Valuation in Companies Listed in Latin American Capital Market",doi:"10.5772/intechopen.76421",slug:"effect-of-free-float-ratio-on-the-behavior-of-shares-valuation-in-companies-listed-in-latin-american",totalDownloads:1485,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Free float is generally defined as the number of outstanding shares minus the number of shares that are restricted from trading. This restriction comes from the fact that these shares belong strategic investors who do not usually negotiate their holdings. The ownership structure of the capital of each company can condition share’s prices and trading volume. The objective of this chapter is to identify if there is a relationship between floating capital ratio and volumes operated, volatility of prices and performance of the shares. The data analyzed correspond to Latin American companies listed in Argentina, Brazil, Chile, Peru and Colombia at the end of 2016. The applied statistical methodology is a simple linear regression. As a result of the study, it is observed that, in Peru and Colombia, greater floating capital affects the equity’ retorn in the market. The contribution of this research is the analysis of the free float impact on the explained variables in stock markets of Latin American countries. This study presents two limitations; the use of data from a cross-sectional sample and the number of companies that formed the sample.",signatures:"Tolosa Leticia Eva and Nicolas María Claudia",downloadPdfUrl:"/chapter/pdf-download/60927",previewPdfUrl:"/chapter/pdf-preview/60927",authors:[null],corrections:null},{id:"60266",title:"Ask of National Pension Service for Higher Dividend and Firm Value: Evidence from Korea",doi:"10.5772/intechopen.75578",slug:"ask-of-national-pension-service-for-higher-dividend-and-firm-value-evidence-from-korea",totalDownloads:958,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, we examine the effect of ask of Korea’s National Pension Service for higher dividend on the firm value. There is a conflicting view on the dividend pressure of the National Pension Service. First, the dividend pressure of the National Pension Service contributes not only to reducing the agency problem, which is a disadvantage for Korean companies’ ownership management, but also to reducing the Korea discount, which is a low dividend. The other hand, it is the so-called pension socialism that National Pension Service engages in the dividend policy which is the essence of corporate management with a high stake. This study is conducted on Korean listed companies from 2011 to 2016 and has constructed a test sample using propensity score matching. The results show that the dividend pressure of National Pension Service doesn’t have a significant effect on the firm value. This study is expected to provide useful information for pension funds to exercise voting rights. Also, this study is expected to provide further evidence of a study that verifies the relationship between dividend and firm value by examining the effect of external pressures on dividend policy on firm value.",signatures:"Jung Hee Noh",downloadPdfUrl:"/chapter/pdf-download/60266",previewPdfUrl:"/chapter/pdf-preview/60266",authors:[null],corrections:null},{id:"60903",title:"Can Corporate Social Responsibility Fill Institutional Voids?",doi:"10.5772/intechopen.76164",slug:"can-corporate-social-responsibility-fill-institutional-voids-",totalDownloads:1182,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"We conduct empirical analysis on the relation between firm value and corporate social responsibility (CSR) using 134,823 observations of 2542 firms across 44 countries from 2009 to 2014. We find that the firm value is positively related to the overall CSR score of the firm. At a more granular level, we find that good environmental score is positively related to the firm value and good social and governance scores are negatively related to the firm value. Since these firms operate in different institutional frameworks, we explore whether the institutional voids—the absence of institutions or intermediaries that are instrumental in supporting business operations in a country—may result in greater firm valuation for its CSR and vice versa. Our results show that firms’ environmental scores and social scores receive higher valuation in countries with weaker institutions. Overall, our findings suggest that CSR creates value for firms by filling institutional voids in their home country.",signatures:"Swee-Sum Lam, Weina Zhang and Christopher Yuen Kwong Chien",downloadPdfUrl:"/chapter/pdf-download/60903",previewPdfUrl:"/chapter/pdf-preview/60903",authors:[null],corrections:null},{id:"60650",title:"Corporate Social Responsibility and Firm Value: Recent Developments",doi:"10.5772/intechopen.76160",slug:"corporate-social-responsibility-and-firm-value-recent-developments",totalDownloads:1613,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"We provide a synthesized introduction to recent findings in the link between corporate social responsibility and firm value. The focus is on how and why profit-maximizing firms engage in socially responsible actions, and how such activities can increase product demand and shareholder value. Recent studies in empirical evidences, theoretical models, and trends in practice are discussed. This chapter is not intended to be a comprehensive survey but rather an introduction to bring future research interest in this field. Empirical studies show evidences of a positive impact of corporate giving on indicators of firm value such as shareholder value and financial performance. Theoretical models provide mechanisms and economic foundations for the demand increase leading to profits in different market structures. Socially responsible actions can be induced by external activists for fear of boycotts. Investors may prefer to hold shares of responsible firms when corporate giving can substitute for personal giving. A public good may be produced jointly with a private good. Models of general industry equilibrium find that demand increases due to the public good may come from the endogenous market effect. Companies in industries with entry barriers make the top list of corporate giving. Using examples in the pharmaceutical, finance, and high-tech industries, we discuss how corporate social responsibility is conducted in practice.",signatures:"Fan-chin Kung and Nicholas G. Rupp",downloadPdfUrl:"/chapter/pdf-download/60650",previewPdfUrl:"/chapter/pdf-preview/60650",authors:[null],corrections:null},{id:"60700",title:"Public Company Communications with Equity Investors and Firm Value",doi:"10.5772/intechopen.76171",slug:"public-company-communications-with-equity-investors-and-firm-value",totalDownloads:1041,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Corporate governance is essentially developed from the characteristics of a public company. In such a company, there is a strict division between entrepreneurship and ownership, which results with agency problem between management and stockholders in asymmetric information’s conditions. Therefore, the communication of society is with the investor’s public, which is one of the key areas of corporate governance. This is primarily related to existing and potential firm’s stockholders, who use that information for the assessment of existing, or potential investment. There are many ways of communication. Periodically, the most comprehensive is by using financial reporting. Unfortunately, today’s common financial reporting practice are not directed to existing and potential firm’s stockholders. Reporting shows business value primary as firm’s assets value and stockholders are observing assets as financial potential, and are primary interested in economic value based on expected cash flows and risk reward relationship. Because of that, there are big challenges for the improvement of financial reporting. 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These devices may include many sensors, such as global positioning system (GPS)/global navigation satellite system (GNSS) chipset, inertial measurement unit (IMU) platforms, barometer, altimeter, cameras, etc., that empower customers to plan their activities (e.g., to know the time that it is necessary to wait a train) or to share their location on social networks (e.g., Facebook) [13]. With these kind of sensors and to the rise of new positioning techniques, it is possible to obtain the position both in outdoor and in indoor scenarios. In the first case, GPS/GNSS are the most useful sensors for obtaining a fast position even if there are some problems, especially in harsh environment, due to multipath or satellite obstructions. In the second case, these sensors became useless because no satellites are visible: so, it is possible to perform positioning thanks to other sensors, such as IMUs and cameras, considering other techniques such as the image recognition‐based (IRB) or the pedestrian dead reckoning (PDR) technology.
In this chapter, we will investigate the positioning performances and methodologies in outdoor and indoor scenarios considering smartphone technology. In particular, the goal of this work is to analyze the state‐of‐the‐art of the precisions and accuracies that can be achieved with these instruments for positioning and navigation purposes, in both scenarios.
In Section 2, the analysis of the most common sensors installed into smartphones is given as well as the methodology for the determination of the smartphone’s reference system. We will discuss about the GNSS chipset (Section 2.1) available today and the positioning accuracy obtainable today with these sensors and with INS platforms (Section 2.2). Moreover a short description of cameras installed today into smartphones is done, in order to perform positioning using also images (Section 2.3).
Subsequently, in Section 3 a description of the positioning techniques obtainable today with smartphones is made and some practical examples are provided: the tests performed and the results obtained are presented, focusing the attention on outdoor (Section 3.1) and indoor (Section 3.2) scenarios.
Finally, some conclusions will be drawn in Section 4.
Many sensors are available today on smartphones: most of them are related to internal applications (proximity sensor, light sensors, etc.) while other ones (e.g., GNSS, INS, and cameras) allow to obtain a positioning. One of the biggest problems is represented by the operating system (OS) installed inside the smartphone: each OS has different ways to manage data that comes from internal sensors, not to mention the use of these data made by the apps.
While sensor availability varies from device to device, it can also vary between iOS and Android versions. The biggest changes were made in this last OS, due to several platform releases: in Android 1.5 (API Level 3) many sensors have been introduced even if some of them were not employed and not accessible before Android 2.3 (API Level 9). Similarly, in Android 2.3 (API Level 9) and Android 4.0 (API Level 14) some other sensors have been introduced and some others have been removed and replaced by newer ones.
Figure 1 shows the availability of each sensor on a platform‐by‐platform basis, considering the only four platforms that involved sensor changes.
Availability of each sensor in different Android systems (available at:
In this chapter, we focus the attention only on sensors useful for positioning: GNSS and INS chipset and cameras for images. Hereinafter, a brief description of these sensors is provided.
GPS/GNSS chipset is the most widespread sensor installed inside smartphones. There are many chipsets today available on the market, and very often each manufacturer installs few different versions of the same GNSS brand [2]. For example, Apple installs chips provided by Broadcom Corporation, while Samsung smartphones with Android OS have installed u‐blox AG chipsets. Since 2016, no GNSS raw data acquired by mobile platform such as smartphones or tables were available, but starting from 2016 it has been possible also to extract pseudoranges and carrier‐phase measurements from smartphones with Android 7.0 OS. The announcement came from Google during the I/O 2016, the 3‐day developer conference which took place from 18 to 20 May. It is a very strong innovation, destined to bring a revolution in the field of survey and geo‐localization: with these kinds of sensors, accuracies of few centimeters will be obtainable even with mobile devices. Despite that, this kind of possibility will not be analyzed in this chapter.
Inertial measurement unit platforms are increasingly being used integrated either with other instruments, typically GNSS, odometers, and magnetometers, or with storage units [34]. They then form an inertial navigation system (INS).
In general, INS instruments are comprised of three accelerometers, three gyroscopes, and three magnetometers. The characteristics of these sensors are briefly described.
Accelerometers are instruments that measure acceleration (the rate of change in velocity), and help the phone distinguish up from down.
All accelerometers have two fundamental parts:
A housing attachment to the object whose acceleration we want to measure.
A mass that, while tethered to the housing, can still move.
For example, let us assume a spring and a heavy ball. If you move the housing up, the ball lags behind stretching the spring. If we measure how much that spring stretches, we can calculate the force of gravity.
Gyroscopes are sensors that can provide orientation information as well, but with greater precision. Thanks to this particular sensor, Android’s Photo Sphere camera feature can tell how much a phone has been rotated and in which direction.
The digital compass is normally based on a sensor called magnetometer, which provides a simple orientation in relation to the Earth’s magnetic field. Consequently, every smartphone knows where is North so it can autorotate the digital maps depending on its physical orientation.
Like GPS/GNSS chipset, camera sensors are mandatory components for any kind of mass‐market communication device and in particular for smartphones. CMOS image sensor (CIS) has always been one of the most important features in our phone, so that it was able to move the market to a new category of smartphones, the so‐called camera phones. Google Pixel, Apple iPhone 7 Plus, Samsung Galaxy S7, Huawei P9, and Sony Xperia X are some of the best camera phones according to the international mobile industry congress like the International Consumer Electronics Show (CES) 2017 in Las Vegas and the Mobile World Congress (MWC) 2017 in Barcelona.
The mobile image sensing is the more direct way for the commercial user to represent the reality, to share information, and to create social interactions. For these reasons, in the last years, the CIS market has put particular emphasis on the quality of the camera modules, reaching high resolution levels, and makes them usable as low cost tools for numerous applications. Jointly with the numerous embedded sensors, like gyroscope, accelerometer, proximity sensor, GPS receiver, and Wi‐Fi connectivity, these new camera chipset have boost the effort in R&D for new kind of applications like 3D sensing technology, such as Google’s Tango, automotive self‐drive, drone product, and virtual and augmented reality. Numerous technological upgrades in chipset architecture, like backside illumination (BSI) and in‐sensors setups, like the dual camera implementation, have moved the market in favor of company rather than another. Nowadays, production and technology leader of image chipsets is Sony, covering 35% of the entire market. Sony’s sensors are mounted into numerous smartphones and tablets like the Samsung Galaxy S7, Huawei P9, Sony Xperia X, etc. After, there is Samsung (Samsung Galaxy S7, Lenovo Vibe Shot) and Omnivision (Huawei P8, Lenovo K3 Note) and, according to many CIS market research firms, all three together reach about the 70% of the world market.
CMOS stands for complementary metal‐oxide semiconductor, and it uses the same manufacturing technologies of CCDs sensors, the dominated technology till now, but needs much less power and the production is less expensive. The main advantages of CMOS imagers are that they are compatible with mainstream silicon chip technology and this allows on‐chip processing and consequently the miniaturization. With the technological development on the semiconductor industry, the gap between CCD and CMOS has narrowed and the quality of the obtained image is competitive.
A typical CMOS is an integrated circuit with an array of pixel sensors and has the following main part:
Micro lenses
Color filter
Pixel array
ADC (analog to digital converter)
Digital controller
Looking at the best camera phone of 2017, it is possible to state the specification of the camera sensors and make an overview on the best characteristics. Table 1 resumes some smartphone camera specifications.
CMOS imaging sensor characteristics | |||||||
---|---|---|---|---|---|---|---|
Smartphone | Sensor name | Size (diagonal) [mm] | dpix [µm] | CMOS technology | Sensor dimensions [mm × mm] | Image dimension [pix × pix] | MP |
Sony Exmor RS IMX378 | 7.81 | 1.55 | BSI CMOS | 6.25 | 4032 | 12.2 | |
Sony Exmor RS IMX315 | 6.15 | 1.22 | BSI CMOS | 4.92 | 4032 | 12.2 | |
Sony Exmor RS IMX* | 6.15 | n/a | n/a | n/a | n/a | 12 | |
Sony Exmor RS IMX* | 5 | n/a | n/a | n/a | n/a | 12 | |
Sony Exmor RS IMX240 | 6.83 | 1.12 | BSI CMOS | 5.95 | 5312 | 15.9 | |
Sony Exmor RS IMX260 | 7.06 | 1.4 | BSI CMOS | 5.64 | 4032 | 12.2 | |
Samsung Isocell S5K2L1 | 7.06 | 1.4 | ISOCELL | 5.64 | 4033 | 12.2 | |
Sony Exmor RS IMX286 | 6.2 | 1.25 | BSI CMOS | 4.96 | 3968 | 11.8 | |
Sony Exmor RS IMX298 | 6.4 | 1.12 | BSI CMOS | 5.16 | 4608 | 15.9 | |
Sony Exmor RS IMX300 | 7.87 | 1.08 | BSI CMOS | 6.46 | 5984 | 24.8 | |
5.96 | 5520 | 22.8 | |||||
6.46 | 5984 | 20.1 | |||||
Sony Exmor RS IMX400 | 7.73 | 1.22 | BSI CMOS | 6.17 | 5056 | 19.2 | |
Sony Exmor RS IMX234 | 6.83 | 1.12 | BSI CMOS | 5.95 | 5312 | 15.9 |
CMOS image sensor characteristics for commercial camera phones.
More details about cameras are available at the following hyperlinks:
When outdoor scenarios are considered, smartphone technology can provide positions with a quite good level of accuracy, using the assisted GPS (A‐GPS) system. Despite that, it is possible that the received GPS/GNSS signal is too noisy or not available at all, for example, if the user is in urban canyons or inside buildings: in these cases GNSS positioning is not possible.
Starting from that, many researchers have been investigating alternative solutions that consider different sensors (such as INS and images) and other technologies (e.g., Wi‐Fi, pedestrian tracking system, Bluetooth) in order to improve position accuracy and availability. A brief overview about accuracies obtainable today with a generic smartphone (chosen as representative) is made in the following subsections.
As said in Section 2.1, starting from the end of 2016, it is possible to acquire raw GNSS measurements from smartphones: the main problem is that only Android Nougat OS allows to extract these information. Thus, in this section the attention is focused only on internal solutions provided by software installed on smartphones. In order to analyze the precision obtainable today with GNSS internal chipset, some tests were performed.
The tests took place in the same places described in [11] considering two different scenarios: an open outdoor area to represent “ideal” conditions (Figure 2, left) and another area (one of the courts in Politecnico di Torino campus) with characteristics of urban canyon (Figure 2, right). The line in Figure 2 - right shows a particular track where it is possible to find an area with a limited satellite visibility (similar to urban canyon conditions) and many windows that create multipath due to their high reflectivity.
Test site and track: an open sky area (left) and an urban canyon (right).
Dynamic tests were performed in these areas by walking along the same path with the smartphones mounted on a special “two‐hands” support as shown in Figure 3. The entire data collection system includes:
The two‐hands support system developed at Politecnico di Torino.
a smartphone (a)
a 360‐degree retro‐reflector (d)
and allows to install also an external IMU platform (b) and an external GNSS antenna (c).
GNSS data positions were recorded during the surveys considering a one‐second sample rate, using a dedicated app that stores the National Marine Electronics Association (NMEA) GGA messages in an ASCII file. All results were compared with a “ground‐truth” obtained through the continuous tracking of the smartphone position with a total station, thanks to the retro‐reflector installed on the “two‐hands” support. In this way, a millimeter accuracy was obtained, considering and estimating the level‐arm offset between the instruments.
The NMEA sentences were analyzed and compared with the reference trajectories using software written in MATLAB.
The horizontal positioning errors of the representative receiver are shown in Figure 4 for the urban canyon environment.
2D performances of internal GPS sensor.
In order to have a more complete analysis from a statistical point of view, the most significant statistical parameters have been summarized in Table 2 for the urban canyon and open area test locations.
Smartphone | Mean (m) | Standard deviation (m) | ||||
---|---|---|---|---|---|---|
E | N | H | E | N | H | |
Urban canyon environment | 0.4 | −7.3 | −2.1 | 4.5 | 4.7 | 5.0 |
Open area environment | −0.5 | 1.6 | −1.9 | 2.6 | 2.5 | 4.5 |
Error statistics in urban canyon and open area environments.
As expected, then, it is generally possible to affirm that some environmental characteristics, such as obstacles, multipath effects coupled with the number of trackable satellites, play a crucial role in the accuracy determination of the smartphone positioning.
However, precision and accuracy improvements could be increased by computing a differential positioning solution, considering the raw measurements obtainable from internal sensors.
Very often in bibliography it is possible to find two different methods for GNSS + INS positioning: the loosely (LC) and the tightly (TC) coupled approaches(Figure 5).
GNSS + INS processing approaches.
In the first case (LC), the software integrates acceleration and angular velocities and updates all the state parameters. These include the positions and angular assets, but also the instrumental biases, using GNSS positions and IMU measurements.
In the latter one (TC method), the input parameters are the same, but both the GNSS (pseudoranges, carrier‐phases, Doppler) and IMU observations enter into the extended Kalman filter, each with its own rate and precision, associated with their new biases [8], in order to provide an unique solution.
Although from a computing point of view, this is a heavier process and it takes into account the use even of one or a few visible GNSS satellites, which is a typical situation of urban canyons [13]
It is important to underline that the only LC method is available today because this approach does not require the raw GNSS measurements, while for the TC is fundamental to have these observations.
Starting from this, in this subsection a brief analysis of results obtainable with GPS + INS instruments installed on smartphones is made, following the LC approach.
The tests were carried out in our campus in the same two different test sites described in the previous subsection, considering the same special support created in the Geomatics Lab at the Politecnico di Torino.
Considering the Inertial Explorer® software for postprocessing all data acquired on the field, it is possible to have an horizontal error loop equal to 4.21 m and a vertical error loop equal to 3.73 m, considering a 3‐min session duration. Obviously, the results are slightly different if different smartphones are considered but it is possible t o affirm that these values are representative for the technology available today.
The spread of smartphone devices with different embedded sensors, increased computational power and advance connectivity features, has led to the introduction into the market of numerous application services, based on the awareness of the user position, which provides information and assistance for navigation in the environment, pose estimation, tracking, and any kind of service related to the spatial context. Many location‐based services (LBS) are implemented as information systems that use as prior information the position of a mobile device [22]. The number of companies deploying LBS solution for commercial purpose reveals that location‐based solutions are finally meeting markets’ needs and soon will be implemented on mass‐market application. The principal fields of application are medical care [15], ambient assisted living [40], environmental monitoring [33], transportation [38], and marketing [1] etc.
The major part of these services requires accurate localization for people, instruments, vehicles, animals, and assets. As it is well known, the GNSS positioning provides good accuracies only in open‐sky environments. Contrariwise, when an indoor space or in an urban canyon is considered, the GNSS positioning in not possible and it is mandatory to overcome this issue considering different techniques and sensors. In recent years, some indoor location‐based services (LBSs) have been developed integrating different technologies and measurements [22], such as cameras [27], infrared (Kinect), ultrasound [20], WLAN/Wi‐Fi [6], RFID [23], mobile communication [10], and so forth are examples of the technologies that the scientific community has put at the service of indoor locations. Despite the ample panorama of solutions, mass market applications for indoor positioning require the use of embedded sensors in commercial smartphone without supplementary physical components. For this reason, major modification to the devices is forbidden and the type of technology usable in these applications is reduced. Ref. [36] has made a summary on the user requirements for mass‐market localization systems that is reported in Table 3.
All these indoor positioning systems have pros and cons that make them more useful in specific scenarios, compared to other options. One of the most useful but complex localization method is the inertial navigation system. This system is based on dead reckoning, which computes locations employing inertial measurements units installed inside the smartphone as accelerometers and gyroscope. The main advantages of a system using IMU (INS) is that nowadays, every kind of mobile device have it already implemented inside and no external infrastructure is required. Moreover, with the inertial systems, the only input information that is needed is the staring position. Without any other external information required, this technology is not affected by adverse weather conditions or by security vulnerability or jamming problems. However, these systems suffer from integration drift, making errors accumulate and therefore must be corrected by some other system. The LBSs based on the camera sensor have strong advantages and do not need to install any network of chipsets in the environment. All the primary sensors are already installed in the user device. In this case, the system could be considered low cost. Moreover, the positioning accuracy with these systems is usually more accurate in comparison to other systems. Furthermore, most of these systems based on triangulation, cannot determinate the orientation of the user, with important limitations to support many useful applications like augmented reality.
It is evident now that providing a reliable and stable position information in a complex and changing environment is a very challenging task. Sensor fusion may be an option to combine advantages of two or more different techniques (e.g., angle of arrival (AoA), time of flight (ToF), received signal straight indication (RSSI)), and technologies (e.g., GPS, Wi‐Fi, Bluetooth, camera sensors, ultrasound) and minimize the limitation. Some methods and technologies are ideal candidate to support or complete other navigation or localization systems in a multimodal approach in order to obtain an accuracy and reliability in the location information superior to that obtainable by each technique, technology, or system parameter without the use of diversity. Multimode solutions employing different sensor would not be feasible for low‐end handsets unable to connect to more than one technology or without the hardware enhancements required to apply different techniques. For these reasons, the positioning solution with smartphone technologies exploits the already embedded sensors: INS, CMOS image sensor, and Wi‐Fi.
In this chapter, we will focus on solution of image recognition‐based (IRB) technology that uses CIS as the main sensor. In particular, after a general overview on existing methods, we will investigate an innovative method of IRB location based on the image retrieval of real‐time acquired smartphone pictures with the corresponding synthetically generated 3D image or RGBD image extracted by a database. Then we will evaluate the integration of INS for a multimodal solution of the previous method for indoor navigation and finally some consideration on system using Wi‐Fi technology as the main positioning technology.
Indoor positioning and navigation by optical sensors is becoming one of the dominant techniques, able to cover a large number of fields of application at all levels of accuracy. The success of these techniques is due to the improvements and miniaturization of the CMOS sensors. Simultaneously, there has been an increase in the data transfer speed and smartphone computational capabilities, as well as a remarkable development in the field of image processing.
As seen before, the LBSs based on the camera sensor have strong advantages. First, these systems do not need to install any network of chipsets in the environment as the primary sensor (CIS) is already installed in the user device. This allows to develop a low cost service without design and implementation of onsite network. Moreover, the positioning accuracy with these systems is usually more accurate in comparison to other systems. In industrial process, for example, computer vision systems based on object detection algorithms are used in production line to track object and check the quality. These kinds of systems have accuracy around few millimeters. Of course, applications of image‐based positioning with smartphones cannot reach these levels of accuracy but can perfectly match the requirements for navigation purpose.
There are many previous research studies on indoor image‐based localization that pursue different goals and use different methods and technologies also in the function of the field of interest of the research groups. There are visual odometry approaches [19], simultaneous and location mapping (SLAM) [24], structure from motion, or investigating semantic features [29]. Some interesting work exploits the computer vision algorithm and in particular the neural network and transfer learning for visual indoor positioning and classification [35]. Some use RGB‐D images to perform object recognition [25]. On the use of a smartphone as a navigation device, some interesting research can be found in [27, 39].
As seen in bibliography, there are many LBS based on images, whose accuracies and coverage area is function of the application. Some accuracy ranges may be useful for applications in very large indoor spaces like museums or fairs, and others may require accuracies at subroom level, for example, in the field of logistics and optimization. When trying to make indoor positioning and navigation in more complex spaces with task of “search and rescue” or in construction sites, the coverage area decreases and higher accuracies are required.
A possible solution, considering all sensors which are installed into the smartphone device, is the image recognition‐based approach, where the localization of our device is based on photogrammetric principle [16]. Image recognition‐based (IRB) positioning is a good technology for smartphone indoor localization. The aim of these procedures is to match a user‐generated query image, via a mobile device, against an existing image database with position information [41].
Some test has been carried out in our campus, following the methodologies presented in [9, 28]. The use of IRB positioning in mobile applications is characterized by the availability of a single camera; under this constraint, in order to estimate the camera parameters (position and orientation), a prior knowledge of 3D environment has to be available, in the form of a database of images with associated spatial information. A Terrestrial LiDAR (Light Detection and Ranging) Survey (TLS) with an associated camera can be executed to acquire the 3D model of the environment used to generate the images database (RGB‐D images) . Once the retrieval of the reference image is completed, it is possible to extract the 3D information of the selected features from the image to estimate the external parameters (position and attitude) of the query image according to the collinearity equations (Figure 6).
The IRBL procedure.
Table 4 summarizes the accuracy results in terms of discrepancies from ground truth and estimated values, for indoor trial in case of good level of similarity between the query image and the reference one extracted out of the database.
Criteria | Criteria description | Value |
---|---|---|
Horizontal accuracy | 2D position for the detection of a shelf in a supermarket | 1 m |
Vertical accuracy | Selection of the correct floor and visualization | Floor detection |
Update rate | Minimum for navigation | 1 Hz |
Latency | Delay with which position is available to the user | None |
TTFF | Time-To-First-Fix, latency after switching on the device | Without delay |
Privacy | Maintenance of the user privacy | According to user-set policy |
Summary of requirements for mass-marked localization according to Wirola et al. [36].
Param. | ||||||
---|---|---|---|---|---|---|
|Max| | 0.164 | 0.149 | 0.063 | 0.4646 | 0.5288 | 0.2396 |
Mean | 0.018 | 0.010 | 0.015 | 0.0975 | 0.0544 | 0.0573 |
Dev. St. | 0.084 | 0.086 | 0.020 | 0.1850 | 0.1689 | 0.1022 |
Accuracy results in indoor trial for position (Δ
It is important to state that the entire procedure could be executed in real time on a commercial smartphone and could provide the device position in few seconds. This is true for one‐spot positioning task, while, when it is needed to transpose the methodology for indoor navigation, it is necessary to take into account three fundamental problems: the energy consumption, the latency of the image processing, and the Internet data consumption. Acquiring images at a given frame rate for navigation applications is a procedure that requires high wastage of energy, with a consequent problem of battery optimization. Furthermore, as each query image has to be sent to a server for image retrieval procedure, a certain amount of Internet traffic is needed. Finally, the rates of positioning information are subordinated to the latency of the entire IRB methodology.
To overcome the reduction of the frame rate and latencies compensation, inertial (INS) platforms built with MEMS (micro electro‐mechanical systems) technology can be integrated in the IRB positioning [12]. Fusing IRB position and attitude measurement with INS measurements, accelerations, and angular velocity measurements are integrated to provide real‐time relative position and relative attitude information, while inner INS variables (velocity at the starting point, accelerometer biases, and gyro drift) are estimated using absolute IRB positioning inputs (position and attitude).
When MEMS technology is used together with IRB positioning, it is important to analyze the precisions and accuracies obtainable. The procedure was tested in our campus walking in a predefined path using two different smartphones (a) mounted on a special support, as described in Figure 3.
The procedure starts with the analysis of the raw data of inertial sensors (acceleration, angular velocity, and magnitude of magnetic field), directly registered from the smartphone. It is necessary to filter these data for estimating and removing the noise. After that, it is possible to use INS raw data in real time for positioning purposes considering a Kalman filter approach in order to reduce the number of frames that can be acquired for geo‐localization. This means that it is possible to extend the time interval between two images from 2 s up to 5 s, depending on the requested accuracy.
In Table 5, we see the positioning results in terms of accuracies, considering an IBN approach. Considering an interval of 1 s between images, the mean planimetric error was 21.3 cm at 67% of reliability, while at 95% this error was 37 cm.
1 s | 2 s | 5 s | |||||||
---|---|---|---|---|---|---|---|---|---|
Mean | Percentile | Mean | Percentile | Mean | Percentile | ||||
67% | 95% | 67% | 95% | 67% | 95% | ||||
E | 0.130 | 0.148 | 0.353 | 0.387 | 0.485 | 0.960 | 1.673 | 2.221 | 4.158 |
N | 0.130 | 0.141 | 0.412 | 0.380 | 0.409 | 1.162 | 1.574 | 1.677 | 3.952 |
Results obtained with drift estimation coming from images.
When the positioning obtained with an interval of 2 s between the images is analyzed, the mean planimetric error increases to 61 cm at 67% and 1.49 m at 95%.
IBN allows to reduce to 50% the final residuals and increase the outages up to 90 s, even improving the quality of the estimated angles. At the moment, the IBN requires a server with high performance in order to obtain the solution and a well‐defined images database (DB).
Over the last decade, wireless location estimation has been an active field of research, becoming the most widespread approach for indoor localization in GNSS denied environment. A WLAN (Wireless Local Area Networks, IEEE 802.11 standard), otherwise known as Wi‐Fi (Wi‐Fi is a trademark of the Wi‐Fi Alliance), is a wireless network of devices that uses high frequency radio signal (2.4 GHz in ISM band) to transmit and receive data within a limited area. As the connection between nodes of the network maintains continuity, the communication is preserved even if one device is moving around in the limited area (50–100 m) [37]. This means that for these reasons, the WLAN technology could be used to estimate the location of a mobile device within this network. The positioning accuracy required to offer satisfactory LBSs is in the order of 1 m and a great effort is needed in R&D. The expansion of this field of research is expected to continue for years, beside numerous commercial applications, due to the fact that it is a low cost solution providing proper connectivity and high speed links. In fact, nowadays, the WLAN infrastructure is widespread in many indoor environments and it is already standardize for commercial smartphone communication.
Usually, an indoor environment is often complex, characterized by nonline‐of‐sight (NLOS) of target objects; in these situations, WLAN positioning technologies could be very helpful because they do not require the line of sight. Unfortunately, compared to IRBL procedure, WLAN positioning is affected by a large estimation error, proportional to the number, and position of nodes in the network. Others challenging issues are the power consumption and the signal attenuation.
Pros and cons of WLAN positioning are true in function of the techniques of positioning used. The most popular WLAN positioning method is based on the received signal straight indicator (RSSI) because it is easy to extract from any connected device in a Wi‐Fi network [17]. The RSSI method is based on the received signal power and on the relation between the signal attenuation and distance of the nodes. Knowing the strength of the emitted signal, the strength of the received signal, is possible to calculate its attenuation and consequently the distance between the emitter and the receiver. With these techniques, it is possible to combine different strategies for positioning, like propagation modeling, fingerprinting, cell of origin, and multilateration [30]. To obtain a most precise localization, it is necessary to combine the technique of fingerprinting [37] that consists an
Another way to locate a device in a Wi‐Fi positioning system is the cell of origin (CoO) method, with which the receiver position is made to coincide with the coordinate of the access point (AP) generating the highest RSSI value. Due to the spatial distribution of the APs in an indoor environment, this type of techniques is able to reach location with errors around 10–20 m [14].
Finally, multilateration methods, like time of arrival, time difference of arrival, angle of arrival, and so forth, are less common for WLAN positioning due to computational complexity of these kinds of measurements in mobile devices [26].
A literature review on WLAN systems for indoor positioning has been published by He et al. in 2016 [18]. There are many previous research studies on indoor Wi‐Fi localization that pursue different goals and use different methods and technologies also in the function of the field of interest of the research groups. In particular, besides the numerous interesting works on positioning and navigation on self‐made mobile devices with sensor integration, there are some researches exploiting the embedded sensors in COTS (Commercial On‐The‐Shelf) smartphone. Some interesting work exploits the integration of inertial sensor‐based positioning with Wi‐Fi capability of smartphones [7, 31]. For example, in [7] the authors propose a sensor fusion framework for combining Wi‐Fi, pedestrian dead reckoning (PDR) and landmarks. The whole system runs on a smartphone and Android app is developed for real‐time indoor localization and navigation. The established accuracy is 1 m. An interesting multimodal approach of Wi‐Fi navigation is described in [21], where PDR carried out with only low cost sensors and Wi‐Fi smartphones are issued in a cooperative positioning operation made by a certain number of participants. The size of the error becomes smaller when the number of participants rises (5 m for 50 devices). Some use GPS integration for cloud‐based LBSs [3], while other researchers introduce sensors fusion between Wi‐Fi and CIS for accurate indoor positioning [32] or for augmented reality navigation [1].
A comprehensive and complete view on indoor positioning systems implemented today, with its applications and obtainable positioning accuracies, is described in [18].
In this chapter, the authors have tried to describe the positioning performances and methodologies in outdoor and indoor scenarios considering smartphone technology. In particular, the state‐of‐the‐art of smartphone technology regarding the precisions and accuracies that can be achieved with these instruments for positioning and navigation purposes has been analyzed, in both scenarios.
Even if in outdoor scenarios the obtainable accuracy is less than 5 m under open‐sky conditions considering only the GNSS sensors, in indoor environment is possible to have accuracies of 10–50 cm if some sensors, such as INS, cameras, or Wi‐Fi technology, are considered. Interesting results are obtained fusing IRB technique with MEMS technology: considering an interval of 2 s between images, the mean planimetric error is about 61 cm at 67% and 1.49 m at 95% of reliability. A possible interesting alternative for indoor positioning could be represented by the fusion of range camera and INS instruments.
This is not an exhaustive overview, also because the technology is evolving more quickly than the minds that are producing them: so this would be a starting point for future works regarding these instruments for positioning and mapping application.
Extracellular vesicles (EVs) are a collective term for tiny vesicles with a phospholipid bilayer structure that are actively secreted by cells. Almost all known cell types can be secreted. The two main categories of EVs are exosomes and microvesicles (Table 1). Exosomes (30-150 nm in diameter) are intraluminal vesicles, formed by the invagination of the multivesicular endosome membrane, and are released into the extracellular space after the multivesicular endosomes fuse with the cell membrane [1]. Microvesicles (50–1,000 nm in diameter) are a group of highly heterogeneous EVs characterized in that their origin and secretion are budding through the plasma membrane [1]. Considering the complexity of identifying its biogenesis, the size of the vesicle is the most widely used parameter for classifying EV types, and on this basis they are described as small EVs or medium and large EVs. In this article, unless otherwise specified, the term “EVs” generally refers to small EVs.
Vesicle | Size (nm) | Density (g/mL) | Origin | Markers |
---|---|---|---|---|
Exosomes | 30-150 | 1.13-1.18 | Endosomes | Tetraspanins, Alix, TSG101 |
Microvesicles | 50-1000 | 1.16-1.19 | Plasma membrane | Intergrins, Selectins, CD40 |
In recent years, people’s understanding of the biogenesis, composition, function and mechanism of EVs has continued to deepen [3, 4, 5]. Their application in clinical treatment has also attracted more and more attention. One of the most useful properties of EVs is their ability to cross barriers, such as the plasma membrane and blood/brain barrier. This makes them very suitable for delivering therapeutic molecules. With their natural source material transport properties, inherent long-term blood circulation capabilities and excellent biocompatibility, EVs can deliver a variety of chemical drugs, proteins, nucleic acids, gene drugs and other drugs. They have great potential in the field of drug carriers. CD47 is the ligand for signal regulatory protein alpha (SIRPα), and CD47-SIRPα binding initiates the ‘don’t eat me’ signal that inhibits phagocytosis. Therefore, CD47 on EVs prevents them from being engulfed by immune cells [6]. EVs are more efficient than their synthetic analog liposomes. The application of EVs as drug delivery carriers is like putting a “stealth coat” on the drug molecules, which can maximize the stability of the drugs, reduce the immune system’s clearance of them, and make “precise delivery” possible. Therefore, EVs can be described as “stealth transport aircrafts” for drugs. EVs therapy has shown great application prospects from oncology to regenerative medicine.
A number of studies have shown that EVs derived from mesenchymal stem cells (MSCs) can be used for stem cell replacement therapy [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]. In most cases, it is not clear which component of the unmodified EVs exerts curative effects. The researchers’ operations are only the separation and purification of EVs produced by therapeutic cells. The curative effects are based on the biological functions of the donor cells, such as the regulation of the immune environment, the repair of damaged cells and the promotion of angiogenesis.
At present, the most extensive research is the attempt to use stem cell-derived EVs for disease treatment. The main application ranges are to repair and regenerate tissues and organs. Such researches involve central nervous system diseases [7, 8], cardiovascular diseases [9, 10, 11, 12] and other organ damage repair and regeneration [13, 14, 15, 16, 17, 18, 19, 20, 21].
In the treatment of central nervous system disease, there is a blood-brain barrier, which often results in that drugs can not reach the diseased site and work well. Stem cells have been gradually used in the treatment of central nervous system diseases in recent years. A large number of research results have been obtained [22, 23]. However, there are still potential risks faced by direct stem cell transplantation, such as tumorigenicity, infection, transplant failure, graft versus host disease, hemorrhagic cystitis, and long-term complications [24].
The application of stem cell EVs avoids a variety of potential risks of direct stem cell transplantation. EVs have low immunogenicity and are easy to preserve and transport, showing unique advantages as a “cell-free stem cell therapy technology”. Spinal cord injury (SCI) is one of the deadliest diseases. The complex inhibitory microenvironment needs to be fully mitigated. EVs derived from MSCs have the function of microenvironmental regulation. Studies have established innovative implantation strategies using human MSC-derived EVs immobilized in peptide-modified adhesive hydrogels (Exo-pGel) [7]. Exo-pGel plays an important role in nerve recovery and urinary tissue protection by effectively reducing inflammation and oxidation [7]. In addition, small extracellular vesiclesderived from embryonic stem cells (ESC-sEVs) can significantly reduce the time-related aging of hippocampal neural stem cells (H-NSCs) through intravenous injection into vascular dementia (VD) rats. ESC-sEVs can restore the damaged proliferation and neuronal differentiation ability, and reverse cognitive impairment. The application of ESC-sEVs may be a new cell-free treatment tool for VD and other diseases related to aging [8].
Stem cells can be induced to differentiate into cardiomyocytes. Early studies believed that the transplanted stem cells can differentiate into heart cells and necrotic cells in the body to repair damaged myocardium and maintain heart function [25]. At present, a large number of preclinical studies have found that EVs derived from transplanted stem cells also have the function of myocardial repair [26, 27]. EVs mainly promote myocardial regeneration by activating cardiac precursor cells, promoting the survival and proliferation of cardiomyocytes, inhibiting their apoptosis, promoting cardiac angiogenesis, reducing infarct size and tissue fibrosis, and regulating inflammation. Extracellular vesicles secreted by cardiovascular precursor cells (hCVPC-EVs) derived from human pluripotent stem cells (hPSCs) play a role in protecting the heart in myocardial infarction by improving cardiomyocyte survival and angiogenesis [9]. Mouse ESC-derived EVs promote angiogenesis, cardiomyocyte survival and proliferation, reduce cardiac fibrosis, and improve cardiac function by carrying miR-294-3p [10]. IPSC-derived EVs inhibit cardiomyocyte apoptosis through miR-21 and miR-210 loaded, and also have a cardioprotective effect [11]. Exosomes produced by immature bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a. They can reduce the necrotic lesions of atherosclerosis [12].
With the continuous discovery of the repair and regeneration effects of stem cell EVs in brain tissue and cardiovascular tissues and organs, the application of stem cell EVs in the repair and regeneration of other tissues has also made a lot of progresses.
MSC-derived EVs reduce radiation-induced lung injury through miRNA-214-3p [13]. Replacing autologous cells with EVs derived from hair follicle papillary cell spheres can promote hair growth [14]. Human umbilical cord mesenchymal stem cell-derived exosomes (UMSC-Exo) can inhibit pyrolysis and repair muscle ischemic injury by releasing circular RNA circHIPK3 [15]. Hertwig’s EVs derived from epithelial root sheath cells promote the regeneration of dentin plasma tissue [16]. Exosomes from neural progenitor cells retain photoreceptor cells during retinal degeneration (RD) by inactivating microglia. This suggests that NPC-exos and its contents may be the mechanism of stem cell therapy to treat RD [17].
Aging is the process of cell and tissue dysfunction. Small extracellular vesicles (sEVs) isolated from primary fibroblasts from young human donors can improve certain biomarkers of cellular senescence from elderly and Hutchinson-Gilford progeria donors. Studies have shown that sEVs have GST activity to improve aging-related tissue damage [18]. In obesity diseases, EVs derived from adipocytes, as new adipokines, are related to the body’s metabolic homeostasis. EVs released from brown adipose tissue or adipose stem cells can help control the remodeling of white adipose tissue, making it brown and maintaining metabolic homeostasis. EVs have been considered as new regulators of diseases such as insulin resistance, diabetes and non-alcoholic fatty liver. The results provide new treatment strategies for obesity and metabolic diseases [19].
In addition, some reports suggest that some EVs derived from mesenchymal stem cells contain some tumor suppressor molecules. For example, it has been reported that miR-206 in exosomes derived from bone marrow mesenchymal stem cells could inhibit the progression of osteosarcoma by targeting TRA2B [20]. The exosomes derived from human umbilical cord mesenchymal stem cells deliver miRNA-375 to delay the progression of esophageal squamous cell carcinoma [21]. However, although EVs contain these small RNAs that have been reported to exert anti-cancer effects, they also contain a large number of growth factors and pro-angiogenesis factors. When these substances are transported to tumor cells by EVs, can EVs derived from MSCs still exert a tumor suppressor effect? This needs more research to prove.
At present, cell replacement therapy based on the characteristics of donor cells has been studied earlier and more frequently in the field of EVs. There is also a clearer understanding of the components that play a major role. With the continuous increase of clinical needs, people began to try to modify the surfaces and contents of EVs to adapt to more disease treatments.
Although natural EVs have been used for cell replacement therapy based on their source and achieved good results, their therapeutic range is far from meeting the current treatment needs. One of the most important therapeutic areas is the treatment of malignant tumors. The secretion ability of EVs in malignant tumor itself is enhanced and contributes to tumor progression. Considering that MSC-derived EVs generally contain high levels of growth factors and pro-angiogenic factors, most natural EVs are not suitable for tumor therapy, except that EVs derived from antigen-presenting cells can be used as tumor vaccines to activate anti-tumor immune responses [28]. Based on the biological characteristics of EVs, it has become the focus of researchers and biopharmaceutical companies to transform EVs as carriers of multiple drugs.
Most diseases have characteristic down-regulation of small RNA expression. Small RNA is the main content of extracellular vesicles, the most abundant and the most easily carried component. Therefore, EVs can be used to carry and deliver small RNA and other gene therapy systems. This section will discuss the progress of engineered EVs to deliver nucleic acid drugs and the strategies of drug loading and targeting.
There are three main problems in the development of nucleic acid drugs: the instability of nucleic acid molecules in the body, potential side effects and difficulties in drug delivery systems. The most important one is the development of delivery systems. Because a good drug delivery system can improve drug stability and target cell absorption efficiency, and can reduce its side effects. At present, the commonly used delivery vehicles in the field of nucleic acid drugs are mainly adeno-associated virus (AAV) and liposomal nanoparticles (LNPs). A small number of companies also use lentivirus (LV) and exosomes as delivery vehicles.
The packaging capacity of AAV is small (≤5kb). AAV will be used more than once in patients for therapeutic purposes and the second use will cause the body to produce a strong immune response. The safety of LNPs is relatively high, and the carrier capacity and delivery efficiency can meet the current demand for drug carriers. However, the organ selectivity of LNPs is still relatively limited. The main delivery area is concentrated in the liver, and the delivery efficiency to other tissues and organs is relatively low.
EVs are now candidate carriers for nucleic acid drugs by virtue of their advantages. The red blood cell extracellular vesicles (RBCEVs) have a large loading capacity (≤11kb), can be loaded with many types (including DNA, mRNA, antisense oligonucleotides, siRNA and other nucleic acid types), and contain very little nucleic acid. The advantages make them high-quality natural blank nucleic acid carriers. RBCEVs can be delivered to many different organs and tissues. In mouse experiments, the delivery effects of lung, liver, kidney, bone tissue, immune cells, etc. are all obvious [29]. Moreover, the raw materials used to produce RBCEVs are mainly blood from type O blood donors. This means large quantities of raw materials are readily available, and costs are controllable. Carmine Therapeutics focuses on the research and development of nucleic acid delivery technology using RBCEVs as carriers.
In addition, researchers are also committed to modifying the surfaces of EVs to improve their targeting. Many results show that this strategy can indeed improve the therapeutic effect of engineered EVs [30, 31, 32, 33].
The researchers combined ligand-coupled superparamagnetic nanoparticles with specific membrane proteins of blood exosomes to achieve the separation, purification and tumor targeting of exosomes [30]. The chemotherapy drug doxorubicin (Dox) and the cholesterol-modified single-stranded miRNA-21 inhibitor (chol-miR21i) were co-loaded onto the exosomes. Then the cationic endolysin peptide was absorbed on the negatively charged membrane surface of exosomes to promote the cytoplasmic release of the packaged cargo (Figure 1). The research results showed that these effectively released drugs and RNA simultaneously interfered with nuclear DNA activity and down-regulated the expression of oncogenes, thereby significantly inhibiting tumor growth and reducing side effects [30].
Schematic representation of engineered blood exosomes for effective gene/chemo combined antitumor therapy [
Chimeric antigen receptors (CAR) are cell surface receptors that recognize specific proteins (antigens). Tumor cells express their specific antigens. Modification of EVs surfaces with CAR targeting tumor antigens enables EVs to target tumors for drug delivery. Modified EVs with CAR can serve as a biosafety delivery platform for the CRISPR/Cas9 system to improve their tumor selectivity. Compared with unmodified EVs, CAR-EVs accumulate rapidly in tumors and effectively release the CRISPR/Cas9 system targeting MYC oncogenes in vitro and in vivo [31].
Rabies virus glycoprotein (RVG) is neurogenic. At present, it has become the most active guide molecule for brain targeted drugs. Lysosomal-associated membrane glycoprotein 2b (Lamp2b) is the membrane surface protein of EVs. RVG fused with Lamp2b is located on the surface of the EV to achieve brain targeting. Engineered Lamp2b-RVG-circSCMH1-extracellular vesicles (Lamp2b-RVG-circSCMH1-EVs) can selectively deliver circSCMH1 to the brain. The treatment can improve the functional recovery of mice and monkeys after stroke [32].
In addition, EVs without modification for targeting have also shown certain curative effects. The miR-214 inhibitor was transfected into HEK293T cells. Their exosomes Exo-anti-214 can reverse the resistance of gastric cancer to DDP [33]. HEK293T cells were transfected with HGF siRNA and their exosomes were harvested. In vivo and in vitro experiments have shown that exosomes loaded with HGF siRNA can inhibit the proliferation and migration of cancer cells and vascular cells [33].
Methods of loading nucleic acids into EVs include: chemical reagent transfection, electroporation transfection, transfection of donor cells, protein and characteristic sequence targeting methods. The application scope and advantages and disadvantages of different methods are shown in Table 2.
Methods | Application scope | Merit and demerit | References |
---|---|---|---|
Chemical reagent transfection | Broad-spectrum. | Easy to operate, but EVs should be purified before and after transfection. | [34] |
Electroporation transfection | The most commonly used method, but not for miRNA, shRNA, mRNA containing chemical modification. | Easy to operate, but EVs should be purified before and after transfection. | [35] |
Transfection of donor cells | Broad spectrum, but not for biotoxic molecules. | Purify EVs after transfection, but the effect of the transfected molecule on the donor cell should be taken into account (e.g. biotoxicity). | [33, 36, 37] |
Protein and characteristic sequence targeting | mRNA and miRNA. | High specificity of loading, but the therapeutic molecules will be modified. Whether this will affect the efficacy remains to be determined. | [38, 39] |
Methods of loading nucleic acid drugs into engineered EVs.
The use of proteins that can bind to specific RNA sequences (Figure 2) or the conservative sequences of Exosome-enriched RNAs (eRNAs) to achieve active packaging is a promising direction. The researchers used the specificity of protein binding to the RNA sequence to develop EXOtic devices for mRNA delivery [38]. Archaeal ribosomal protein L7Ae specifically binds to the C/Dbox RNA structure [40, 41, 42]. Based on this, L7Ae was conjugated to the C-terminus of CD63. C/D box was inserted into the 3′-untranslated region (3′-UTR) of the reporter gene. Therefore, the mRNA encoding the reporter protein could be well incorporated into exosomes via the interaction between L7Ae and the C/D box in the 3′-UTR. Exosomes containing the RNA packaging device (CD63-L7Ae), targeting module (RVG-Lamp2b to target CHRNA7), cytosolic delivery helper (Cx43 S368A) and mRNA (nluc-C/Dbox) were efficiently produced from exosome producer cells by the exosome production booster. The engineered exosomes were delivered to target cells and the mRNA was delivered into the target cell cytosol with the help of the cytosolic delivery helper. Finally, protein encoded in the mRNA was expressed in the target cells [38] (Figure 2). In the future, researchers need to obtain more specific RNA sequence binding proteins and conserved sequences of eRNAs through bioinformatics analysis.
EXOtic devices for mRNA delivery. A schematic illustration of the EXOtic devices [
The lack of protein and malfunction are important causes of many diseases. For example, the occurrence of malignant tumors is related to the lack of certain tumor suppressor factors and malfunctions. Therefore, increasing the corresponding protein level is one of the ways to treat diseases. Considering the risk of genome changes, researchers aim to deliver therapeutic protein molecules to the lesion through effective drug delivery vehicles. This section will introduce the use of EVs to transport protein molecules for the prevention and treatment of tumors, immune diseases, cardiovascular diseases, atherosclerosis, myocardial infarction and other diseases.
Compared with the previous small molecule compound drugs, protein drugs have the characteristics of high activity, strong specificity, low toxicity, clear biological functions, and are beneficial to clinical application. However, protein drugs are unstable in the internal and external environments, and may undergo a variety of complex chemical degradation and physical changes, such as aggregation, precipitation, racemization, hydrolysis, and deamidation. Protein drugs have short half-life, high clearance rate, large molecular weight, poor permeability, susceptibility to the destruction of enzymes, bacteria and body fluids in the receptor, and low bioavailability of non-injection administration. These problems greatly limit the use of protein drugs. Although researchers have improved the stability and absorption efficiency of protein drugs through methods such as PEG modification, microsphere sustained release, and liposome embedding, they still look forward to the emergence of better drug carriers. The application of EVs has brought dawn to this field.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. Delivery of TRAIL through EVs can efficiently induce cancer cell apoptosis. When combined with dinaciclib, they inhibit the growth of drug-resistant tumors [43]. Immunosuppressive drugs must be taken after organ transplantation, but long-term use of these drugs increases the risk of infection and other serious diseases. Using bioengineering methods, researchers prepared exosome-like nanovesicles (NV) displaying the dual target cargo of PD-L1/CTLA-4. These NVs enhanced the PD-L1/PD-1 and CTLA-4/CD80 immunosuppressive pathways and could be used as prospective immunosuppressive agents in organ transplantation [44]. Using extracellular nanovesicles to package CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping can avoid off-target mutagenesis and immunogenicity. And this method can achieve effective genome editing in a variety of cell types that are difficult to transfect, including human induced pluripotent stem cells (iPS), neurons and myoblasts [45]. Catalase could be loaded into exosomes by incubating at room temperature, saponins penetrating the membrane, repeated freezing and thawing and mechanical extrusion for the treatment of Parkinson’s disease (PD) [46].
Surface modification of EVs carrying protein drugs can greatly improve their targeting. In the study of stroke, nerve growth factor (NGF) exerts various neuroprotective functions after ischemia. NGF was loaded into EVs with RVG peptide modification on the surface. Through systemic administration, NGF was effectively delivered to the ischemic cortex. The delivered NGF reduced inflammation by remodeling microglia polarization, promoted cell survival, and increased the number of neuroblast marker doublecortin-positive cells. The results of the study indicated the potential therapeutic effect of NGF@Exo (RVG) on stroke [47]. In addition, integrin αVβ5 exhibits tropism for the liver while integrin α6Vβ4 and integrin α6β1 target lung [48, 49]. The iRGD specifically recognizes αV integrins on the surface of tumor cells [50]. RVG and c(RGDyK) peptides target brain tissue [51]. Klotho protein has the property of binding to circulating endothelial progenitor cells (EPCs) [52]. And chimeric antigen receptor (CAR) targeting specific tumor antigens and so on. These guiding molecules are utilized either by fusion with EVs membrane surface proteins (such as Lamp2b, VSVG, CD63, and other transmembrane proteins, etc.), or by chemical cross-linking on the surface of EVs to achieve the EVs targeting modification. Liu et al. summarized the surface modification strategies to improve the targeting of EVs (Figure 3) [53]. In addition, EVs derived from antigen-presenting cells with tumor antigens can be used as tumor vaccines to activate anti-tumor immune responses.
Design strategies for therapeutic exosome targeting [
How to load protein drugs into EVs? There are currently the following strategies:
Transfect donor cells with plasmids carrying the gene of interest. The cell will synthesize the target protein. These proteins are then secreted into EVs through a natural packaging process. Subsequent separation and purification of EVs in the cell culture supernatant is sufficient [54]. Although this method seems simple and easy to implement, cytotoxicity, mixed interactions and impaired biological responses will provide great obstacles to the production of EVs. And the loading efficiency of the target protein is relatively low. Therefore, researchers have carried out various attempts to specifically load target proteins into EVs. For example, the fusion of therapeutic proteins with the constituent proteins of EVs and the specific modification of therapeutic proteins.
The therapeutic proteins are fused with the constituent proteins of EVs. Then they will be distributed into EVs mediated by the constituent proteins. This method can improve the specificity of protein loading into EVs. The fused constituent proteins of EVs that have been tried include: CD63, Nef [55], vesicular stomatitis virus glycoprotein (VSVG) [56], apolipoprotein E (ApoE) [57], lysosome-associated membrane glycoprotein 2 (LAMP2B) [58], etc.
In addition, based on the idea of fusion proteins, researchers have developed a conditional loading method called “exosomes for protein loading via optically reversible protein-protein interaction (EXPLORs)” [59]. The principle is to couple the exosomal membrane protein CD9 with CIBN, and CRY 2 with the therapeutic protein. After light excitation, CIBN and CRY2 interact, and the therapeutic protein can be loaded into EVs through “photoreversible protein-protein interaction” [59].
All in all, the fusion expression of therapeutic proteins with the constituent proteins of EVs can indeed increase the enrichment level of therapeutic proteins in EVs. However, whether the fusion protein affects the uptake and function of the therapeutic protein by the recipient cells needs to be verified. Therefore, exploring the fusion of peptides that can play a sorting role with therapeutic proteins and minimize the impact on protein functions will become one of the research hotspots in the field of engineered EVs.
Currently, known protein modifications that can target therapeutic proteins into EVs mainly include two types. One is ubiquitination modification. The fusion of ubiquitin to the C-terminus of therapeutic protein can make the concentration of the fused therapeutic protein in EVs increased by nearly 10 times [60]. The other is to fuse the N-terminus of the therapeutic protein with a palmitoylated or myristoylated peptide, which can further increase the therapeutic protein in EVs [61]. However, it is still unknown whether the modification of proteins, especially ubiquitination, will cause the degradation of the therapeutic protein by the proteasome and affect its function in the recipient cell.
Expression of therapeutic protein in donor cells, combined with mechanical methods that pass through different pores, can produce small vesicles containing the therapeutic proteins [46, 62]. In addition, there are methods such as incubation at room temperature, permeabilization with saponin, freeze-thaw cycles and sonication, [46]. There are two main problems with engineered EVs obtained by mechanical methods. One is that the technical requirements for the separation and purification of EVs are relatively high. The second is the maintenance of the integrity and biological activity of EVs. The composition of EVs actively produced by cells is different from the composition of mechanically produced EVs. The difference may affect the efficacy of engineered EVs. In the future application research of EVs, these two problems need to be solved and proved urgently.
So, what are the possible development directions for the existing cytotoxicity and the interaction of biological functions? The expression of tumor suppressor protein molecules may cause cytotoxicity to donor cells, which is not conducive to the production of EVs. If an inducible expression system is established, the coding DNA containing the inducible promoter is introduced into the donor cell to make the donor cell produce EVs containing the coding DNA, which will avoid cytotoxicity to the donor cell. Then prepare EVs containing small molecules that induce DNA expression. The two types of EVs can be used in combination to express tumor suppressor molecules in target cells. It can play a therapeutic role without affecting the production efficiency of EVs. The dual targeting of the two EVs will greatly reduce the impact of engineered EVs on non-targeted tissues. Because single-component EVs are randomly engulfed by cells and will not affect the cells. This may become one of the follow-up development directions in this field.
Chemotherapeutics and traditional Chinese medicine ingredients with anticancer effects are often used in the clinical treatment of a variety of malignant tumors. However, their toxic, side effects and short half-life limit their efficacy. The packaging and transportation with EVs will improve the targeting of chemotherapeutic drugs, increase the uptake efficiency of tumor cells, promote drug stability, reduce the use concentration, and reduce toxic side effects on other organs and normal tissues [63].
The hydrophobic drug curcumin could be packaged into exosomes by direct mixing for tumor treatment [64]. Paclitaxel (PTX) was loaded into EVs secreted by macrophages by different methods such as room temperature incubation, electroporation and sonication. Studies have found that ultrasound treatment increases the load of EVs on drug molecules and the sustained release [65]. Small compounds can also be naturally secreted into EVs by incubating with donor cells. Incubation with paclitaxel make mesenchymal stromal cells produce microvesicles containing paclitaxel [66]. Injecting methotrexate-containing plasma membrane microvesicles (MTX-TMP) from apoptotic human tumor cells into the bile duct lumen of extrahepatic CCA patients could mobilize and activate neutrophils, and relieve the bile duct obstruction in 25% of patients, almost no adverse reactions [67].
At present, small molecule drugs are often loaded into EVs by passive loading methods, such as direct mixing, incubation, ultrasonic treatment, vortexing, saponin permeation, repeated freezing and thawing, and mechanical extrusion. The disadvantages of these methods have always existed, that is, the loss and quality reduction of EVs caused by multiple purifications. In addition, long-term in vitro processing and the physical and chemical properties of drug molecules will also affect the biological activity and stability of EVs. Therefore, before EVs can be widely used in treatment, the storage methods and stability factors of EVs are also worthy of research.
Why are EVs a “stealth cap” for drugs? Because we know viruses to use them exactly like this. In nature, viruses “hijack” EVs to secrete and infect other cells. This method helps to provide a “cover” for the virus to prevent the virus from being cleared by the immune system or neutralized by antibodies, such as the infection process of HAV, HBV and HCV.
In gene therapy, currently widely used adeno-associated virus (AAV), oncolytic adenovirus (OAV) and lentivirus (LV) mediated gene therapy can cause the body’s immune response. After the same kind of AAV is used once, the body will produce a strong immune response, making the second injection ineffective. If EVs encapsulate viral particles to mediate their delivery, perhaps the therapeutic effect will be better.
Studies have shown that AAV isolated from conditioned media could bind to exosomes (exo-AAV) [68]. Compared with conventional AAV, exo-AAV was more resistant to neutralizing antibodies. After systemic injection in mice, compared with conventional AAV, exo-AAV delivered genes to the brain more efficiently at low vector doses. Importantly, no cytotoxicity was found in exo-AAV transduced cells. This may make exo-AAV widely used as a neuroscience research tool [68]. Compared with non-targeted modified EV-AAV, the expression of brain-targeting peptides on the surfaces of EVs can significantly enhance transduction [69].
In gene therapy of ophthalmic diseases, transferring genes to the retina is challenging. Because it requires a carrier system to overcome physical and biochemical barriers to enter and spread throughout the retinal tissue. After the exo-AAV was injected into the vitreous cavity (IVT), it was found that the expression of exo-AAV was better than the traditional AAV. Exo-AAV exhibited a deeper penetration in the retina, effectively reaching the inner core and outer plexus, and to a lesser extent the outer nuclear layer. Exo-AAV is a reliable mouse retina gene delivery tool. Its simplicity of production and isolation makes it widely used in basic eye research [70].
Due to the low efficiency of gene delivery to the inner ear sensory hair cells. AAV is not so advanced in the field of gene therapy for hearing impairment. Studies have shown that Exo-AAV1-GFP is more effective than traditional AAV1-GFP, whether injected in mouse cochlear explants in vitro or directly injected into the cochlea in vivo. Exo-AAV was not toxic in the body. Exo-AAV1 gene therapy partially rescued the hearing in a mouse model of hereditary deafness. It was a powerful hair cell gene delivery system that could be used for gene therapy of deafness [71].
Oncolytic viruses show unique anti-cancer mechanisms in cancer treatment. Chemotherapeutic drugs combined with oncolytic viruses showed stronger cytotoxicity and oncolytic effects. Someone has studied the systemic delivery of oncolytic adenovirus and paclitaxel encapsulated by EVs. The results have shown that this combination therapy enhanced anticancer effects in lung cancer models both in vitro and in vivo. EVs play a key role in the effective transmission of oncolytic viruses and chemotherapeutic drugs [72].
EVs currently used for therapeutic research are mainly derived from the following sources: mesenchymal stem cells (MSCs), dendritic cells (DCs), tumor cells, red blood cells, macrophages and plants. EVs from different sources have different biological characteristics. Materials should be selected according to the purpose of treatment. The characteristics, advantages and disadvantages of EVs from different sources will be described below.
The MSCs involved in the study of EVs include adipose-derived MSCs, bone marrow MSCs, progenitor cells from different tissues, and so on. MSCs can be extracted from the patient’s bone marrow, fat, or other tissues. EVs derived from MSCs are very attractive. Because they have anti-inflammatory, anti-apoptotic and anti-microbial capability, and promote angiogenesis and the repair and regeneration of damaged tissues. As mentioned above, EVs derived from MSCs have been widely used in the treatment of central nervous system diseases, cardiovascular diseases, bone and cartilage damage repair and regeneration, wound repair, and other organ damage repair and regeneration [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21].
One potential source of therapeutic EVs is immature dendritic cells (imDCs). EVs secreted by imDCs lack surface markers such as CD40, CD86, MHC-I and MHC-II. Therefore, they have low immunogenicity. They can be isolated from CD34+ cells from the patient’s peripheral blood. It is one of the preferred sources of therapeutic EVs.
The use of EVs derived from tumor cells to deliver drugs and vaccines for immunotherapy is very promising. Tumor EVs can deliver antigens to dendritic cells, thereby inducing T cell-mediated immune responses to tumor cells [73]. As tumor-derived EVs specifically express Tetraspanins, they can target different tissues. This makes it possible to use tumor-derived EVs for tumor-targeting and selective drug delivery [74]. However, tumor-derived EVs also have many potential risks. Due to the presence of Tetraspanins, Urokinase plasminogen activator, Cathepsin D, Vimentin and other molecules derived from the surface of tumor cells [75, 76], they may promote tumor proliferation and metastasis, and Immunosuppressive effect [77, 78, 79].
Blood EVs mainly secreted by reticulocytes (RTC) are a potential source of safe and sufficient EVs. Because they integrate various membrane proteins including Transferrin (Tf) receptors, but they do not have any immune and cancer stimulating activity [30]. Red blood cell EVs (RBCEV) also have the following advantages: large load; low self-nucleic acid content (red blood cells without nucleus and mitochondria); they can be delivered to a variety of different organs and tissues; large quantities of raw materials and easily available (the raw materials for producing RBCEVs are mainly O-type Blood of blood donors). Using blood EVs as carriers can efficiently target tumors to co-deliver chemotherapeutics and nucleic acid drugs. Significant tumor growth inhibitory effects were observed in tumor-bearing mice. There were no obvious side effects [30].
Macrophages are an important immune cell in the antigen-presenting cell family. EVs derived from immune cells can mimic immune cells to target tumor cells. Macrophage EVs can transfer miRNAs or proteins to tumor cells, mediate tumor cell resistance to chemotherapy, promote cell invasion and other regulatory effects. Therefore, in the study of tumor treatment of EVs, in addition to using the targeting properties of macrophages-derived EVs, the influence of their contents must also be considered. It has been reported that the contents of EVs derived from macrophages can be removed. Then the EVs were used to carry chemotherapeutic drugs to achieve targeted therapy of triple-negative breast cancer [80].
Based on reliable sources and safety, fruits and plants have been used as alternative sources for the isolation of EVs for clinical use [81]. Plant-derived EVs have similar structural characteristics to animal cell-derived EVs. EVs from different plant sources have the physiological functions of the plant from which they are derived. For example, lemon-derived EVs have certain anti-cancer effects. Some researchers have tried to isolate lemon-derived EVs (LDEVs) for the treatment of gastric cancer. LDEVs caused s-phase arrest of gastric cancer cell cycle and induced cell apoptosis. LDEVs could be retained in the organs of the gastrointestinal tract and had strong anti-tumor activity against gastric cancer [82]. The isolated plant EVs can also be used after being engineered. Some researchers isolated EVs from grapefruit, modified the EVs in a targeted manner, and then loaded the anti-tumor drugs doxorubicin and curcumin. These modified EVs could target inflammatory tumors and have anti-inflammatory effects in mouse models [83].
Plant-derived EVs have a wide range of sources, are safe and non-toxic, have low immunogenicity, low cost, and are edible. They have great clinical application potential as edible chemotherapeutic drug carriers.
So far, no EVs drugs have entered the clinic. Codiak BioSciences, a leading company in the development of engineered EVs as a new type of biopharmaceutical, uses its proprietary engEx platform to engineer EVs with different characteristics, load them with various types of therapeutic molecules and change their orientation, so that they can reach specific cellular targets. Recently, Evox Therapeutics Ltd. and Eli Lilly and Co. reached a cooperation agreement to apply its exosome technology to the system to deliver RNA interference and antisense oligonucleotide drugs to the central nervous system, treating five unspecified Neurological diseases. Carmine Therapeutics is also a gene therapy company based on EVs, established in 2019. Carmine’s REGENT technology platform focuses on using red blood cell extracellular vesicles (RBCEV) as drug delivery vehicles. Mantra Bio also joined the emerging group of exosome drug development companies. With the deepening of research, more and more companies will join the field of EVs treatment.
The Severe Acute Respiratory Syndrome (which first appeared in December 2019) related to the new coronavirus (COVID-19) has rapidly developed into a pandemic, and the morbidity and mortality rates are increasing worldwide. COVID-19 respiratory tract infection is characterized by an imbalanced immune response, leading to an increased possibility of severe respiratory disease and multiple organ disease.
Because EVs derived from MSCs have anti-inflammatory, anti-apoptotic and anti-microbial capability, promote angiogenesis and the repair and regeneration of damaged tissues. In related lung disease models, including acute lung injury and sepsis, systemic administration of MSC-EVs preparations can modulate immune responses. In a mouse model of pneumonia induced by Escherichia coli, it was found that MSC-EVs administration could enhance the phagocytosis of bacteria. In the pig model, MSC-EVs could reduce influenza virus-induced acute lung injury by inhibiting influenza virus replication. In other disease models, the disease alleviation effect of MSC-EVs on the inflammatory immune response has also been observed. It is speculated that they may also have anti-COVID-19 efficacy. In cell therapy research for COVID-19, some registered clinical trials have turned their targets to EVs in the conditioned medium of MSCs. MSC-EVs can be administered intravenously (ChiCTR2000030484) or by inhalation (NCT04276987, ChiCTR2000030261).
However, before using MSC-EVs for COVID-19 patients, many other issues should be considered, such as the huge heterogeneity of MSC-EVs composition and source. In fact, comparing MSC-EVs harvested from the conditioned medium of bone marrow MSCs derived from different donors, there are significant differences in cytokine content and different therapeutic effects. In addition to immune regulation, MSC-EVs can also control other biological processes and may cause unpredictable side effects. For example, increasing the risk of thrombosis.
In short, in order to reduce the risk of potential life-threatening side effects, International Society for Extracellular Vesicles (ISEV) and International Society for Cell and Gene Therapy (ISCT) strongly require that the clinical data from reasonable clinical trial should be carefully weighed. The EV preparations with good characteristics and produced under strict GMP conditions and appropriate regulatory supervision could be used. Any application of EVs should be carefully evaluated [84].
The potential application of EVs in new diagnostic and therapeutic strategies has attracted increasing attention. However, due to the inherent complex biogenesis of EVs and their huge heterogeneity in size, composition and source, the research of EVs still faces huge challenges. It is necessary to establish a standardized method to solve the heterogeneity of EVs and the analysis of pre-processing and analysis of sources of variability in the study of EVs. The quality standards, extraction specifications and especially the stability of preparation conditions for therapeutic EVs also need to be clarified.
In addition, the diversity and uncertainty of EVs content are also issues that need to be considered in the application. Before metastasis, malignant tumor cells use EVs to modify the microenvironment of the organ targeted by cancer metastasis, making it a suitable “soil” for tumor cell growth. The contents of EVs secreted by most tumor cells play a role in promoting tumor metastasis and progression. As mentioned earlier in this article, macrophage EVs can transfer miRNAs and proteins to tumor cells, mediate tumor cell resistance to chemotherapy, promote cell invasion and other regulatory effects. Therefore, if EVs from such sources are used as drug carriers, it is particularly important to first remove the adverse effects of their contents.
As an important medium of intercellular communication, EVs play an important physiological function and are also involved in the occurrence and development of a variety of diseases. In recent years, there have been numerous studies on the treatment of related diseases with EVs from different cell sources, and EV has shown its unique advantages in drug transportation. EVs are similar to natural liposomes, which can enhance the function of EVs to treat specific diseases through targeting modification and delivery of functional active substances and other technical modifications according to the characteristics of different diseases. EVs with improved function have shown obvious advantages in the treatment of tumors and difficult diseases of central nervous system. However, the clinical application of EVs technology is still in its infancy, and the challenges it faces are accompanied by the possibility of numerous new discoveries and new technologies. We expect that with the continuous in-depth research, EVs as a new drug carrier in the treatment of a variety of diseases will bring more and greater surprises.
This work was supported by the National Key R&D Program of China (2018YFA0900900), and the National Natural Science Foundation of China (81773251 and 81702735).
Ove Odredbe i uvjeti ističu pravila i regulacije u svezi korištenja IntechOpenove stranice www.intechopen.com i svih poddomena u vlasništvu IntechOpena, tvrtke sa sjedištem u 5 Princes Gate Court, London, SW7 2QJ, Ujedinjeno Kraljevstvo.
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\\n\\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
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\\n\\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
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\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\nSve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
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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. 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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. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null}]},{type:"book",id:"9963",title:"Advances and Applications in Deep Learning",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9963.jpg",slug:"advances-and-applications-in-deep-learning",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"0d51ba46f22e55cb89140f60d86a071e",volumeInSeries:4,fullTitle:"Advances and Applications in Deep Learning",editors:[{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. 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Ribeiro-Barros",profilePictureURL:"https://mts.intechopen.com/storage/users/171036/images/system/171036.jpg",institutionString:"University of Lisbon",institution:{name:"University of Lisbon",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Sustainable Economy and Fair Society",value:91,count:1}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:1}],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:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",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:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health Production",scope:"\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
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