The performance of COVNet as per [45].
\r\n\tDiagnosis (clinical, radiological, cytogenetic, and molecular criteria), pathogenesis (risk factors, pre-myeloma conditions, and bone marrow microenvironment), cytogenetic abnormalities and molecular profiles disease staging and risk stratification, novel therapies such as proteasome inhibitors, immunomodulatory agents as well as monoclonal antibodies, drug resistance (primary and secondary resistance as well as evolution of new genetic mutations that may be disease or therapy-related), hematopoietic stem cell transplantation (HSCT) (autologous HSCT, allogeneic HSCT, and tandem transplantation), relapsed and refractory multiple myeloma, minimal residual disease (evaluation by flow cytometry or various sequencing techniques, importance of MRD in prognosis and prediction of disease relapse), chimeric antigen receptor (CAR) T-cell therapy, infectious complications in multiple myeloma (viral infections, bacterial infections, fungal infections, disease-related infections and therapy-related infections).
\r\n\r\n\tThe book chapters will intend to be written by scientists and experts in the field from various institutions around the world.
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He is a distinguished researcher in the fields of stem cell therapies & infections in immunocompromised individuals.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"37255",title:"Dr.",name:"Khalid",middleName:"Ahmed",surname:"Al-Anazi",slug:"khalid-al-anazi",fullName:"Khalid Al-Anazi",profilePictureURL:"https://mts.intechopen.com/storage/users/37255/images/system/37255.jpg",biography:"Dr. Khalid Ahmed Al-Anazi is a consultant Hemato-Oncologist and the Chairman of the Department of Adult Hematology and Hematopoietic Stem Cell Transplantation (HSCT) at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia. \r\nHe graduated from the college of medicine, King Saud University (KSU) in Riyadh in 1986. After having his Boards in Internal Medicine, he trained in clinical hematology and HSCT at King’s College Hospital, University of London, U.K. He has 4 year experience in internal medicine and 28 year experience in adult clinical hematology and HSCT at: Riyadh Armed Forces Hospital; King Faisal Specialist Hospital and Research Centre (KFSH&RC) in Riyadh; King Khalid University Hospital (KKUH) and the College of Medicine, KSU in Riyadh; and KFSH in Dammam, Saudi Arabia. \r\nHe established the adult HSCT program at KFSH in Dammam in the year 2010. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"78155",title:"AI Modeling to Combat COVID-19 Using CT Scan Imaging Algorithms and Simulations: A Study",doi:"10.5772/intechopen.99442",slug:"ai-modeling-to-combat-covid-19-using-ct-scan-imaging-algorithms-and-simulations-a-study",body:'Today, the world is facing one of its most dangerous risks, if not the most one throughout the century. It is a pandemic that is draining the whole world’s resources and threatening the development of human civilization. The COVID-19 pandemic continues to have a devastating effect on the health and well-being of global population, caused by the infection of individuals by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. On the 30th of January 2020, the WHO declared the SARS-CoV-2 outbreak a public health emergency of international concern. On March 11th, WHO characterized COVID-19 as a pandemic. At the time of writing this manuscript (May 29, 2021), the number of infected people has surpassed 169,118,995 confirmed cases and more than 3,519,175 deaths in 223 countries [2]. The World Trade Organization has announced that the world has effectively entered a recession period. The world’s economy and many countries’ economies are in danger of collapsing. Schools in many countries are closed and students around the world are forced to stay at home [3, 4].
One of the early challenges that emerged at the beginning of the pandemic is the detection of COVID-19 cases. The most important method used for detecting COVID-19 cases is polymerase chain reaction (PCR) testing, that can detect SARSCoV-2 RNA from respiratory specimens [5]. Though PCR testing is the standard, it is a time-consuming, laborious, and complicated manual process that is in short supply [6]. Accurate and rapid diagnosis of COVID-19 suspected cases plays a crucial role in timely quarantine and medical treatment. This limitation of human expert-based diagnosis has provided a strong motivation for the use of computer simulation and modeling to improve the speed and accuracy of the detection process [7, 8]. Another related issue is the manual contouring of lung lesions which tends to be a tedious and time-consuming work, and could lead to subsequent assessment discrepancies in case of inconsistent delineation. Thus, a fast auto-contouring tool for COVID-19 infection is needed in the onsite applications for quantitative disease assessment [9].
Since the early days of this catastrophic crisis, there has been an upsurge in the exploration and use of artificial intelligence (AI), computer simulation, and data modeling and analytic tools, in a multitude of areas. AI and machine learning (ML) have demonstrated great performance in various medical fields and have proven their vital role in complicated therapeutic scenes. These systems have shown high level of accuracy in different applications, such as lung disease classification, breast cancer, skin lesion classification, identifying diabetic retinopathy, and Alzheimer [10, 11, 12].
Scientists and healthcare professionals have realized the importance of AI and imaging technologies in slowing the spread of COVID-19 at preliminary stages, and containing the virus at later stages. Currently, many AI and computer modeling systems are used in disease diagnosis, examining, identifying, and treating patients. AI-based simulations have also been employed for evaluating disease progression, economic downturn and recovery, contingency planning, demand sensing, supply chain disruptions, workforce planning, as well as for management decision-making on site openings [13]. For example, AI-based simulations were critical in integrating multiple decision-making domains (e.g., COVID-19 disease progression, government interventions, people behavior, demand sensing, supply disruptions etc.) [14].
In this paper, we provide an extensive review and a deep study on how AI and ML can help the world to deliver efficient responses and combat the COVID-19 pandemic using CT scan imaging. More specifically, we will focus on the modern algorithms in CT scan imaging that may be used for detection, quantification, and tracking of Coronavirus and study how they can differentiate Coronavirus patients from those who do not have the disease. We provide recent theoretical developments, technological advancements, and practical implementations of AI algorithms and ML techniques that uses CT imaging to suggest possible solutions in investigating diagnosis, severity level, prediction, tracking, treatments and other decision making scenarios related to COVID-19. In this regard, we explore a vast number of important studies that have been performed by various academic and research communities from numerous disciplines during the period of pandemic since the early days of 2020 up to the very recent days (May 2021). Before we further proceed, we note that many of the articles cited are still preprints at the time of writing this manuscript. Given the fast-moving nature of the crisis, we endeavored to be comprehensive of coverage. We understand that the full scientific rigor for many articles should still be assessed by the scientific community through peer-reviewed evaluation and other quality control mechanisms. However, the whole story is a striking dilemma and a big challenge to the global scientific communities. Researchers, physicians, technical-background individuals, and academics are putting all their efforts to come up with solutions and cures to this fatal disease. All of these efforts have emerged during a very short period of time, and a lot are yet to emerge in the coming few months, and possibly years.
AI is becoming one of the highest priorities for healthcare decision makers, governments, investors and innovators. An increasing number of governments have set out targets for AI in healthcare, in countries as diverse as the United States, China, Finland, Germany, and the UK, and many are investing heavily in AI-related research. The private sector is also playing a significant role, with venture capital funding for the top 50 firms in healthcare-related AI reaching $8.5 billion [15]. Though the US dominates the list of firms with highest venture capital funding in healthcare AI to date, and has the most related research studies and trials, China is emerging as the fastest growing country in this field. Europe, meanwhile, benefits from the vast depot of health data collected by national health systems and has significant strengths in terms of the number of research studies, established clusters of innovation and collaborations related to AI [16].
AI applications based on imaging, are already in use in specialties such as radiology, oncology, cardiology, neurology, pathology and ophthalmology. It is expected that more AI solutions would support the shift from hospital-based to home-based care, such as remote monitoring, AI-powered alerting systems, and virtual assistants [17, 18]. Also, AI is anticipated to be embedded more extensively in clinical workflows through the intensive engagement of professional bodies and providers. Moreover, AI solutions are expected to emerge in clinical practices based on evidence from clinical trials, with increasing focus on improved and scaled clinical decision-support tools [19]. Advances in AI mean that algorithms can generate layers of abstract features that enable computers to recognize complicated concepts (such as a diagnosis). This enables them to learn discriminative features automatically and approximate highly complex relationships [20, 21].
Neural networks have been successfully applied to many real-world problems. The most general type of neural network is Multilayer Perceptron (MLP). While MLPs can be used to effectively classify small images, they are impractical for large images. The reason for this can be explained by the fact that the implementation of a MLP would result in a huge output vector of weights for each class (size of millions). MLPs not only are computationally expensive to train (both in terms of time and memory usage), but they also have high variance due to the large number of weights [22, 23].
Convolutional Neural Networks (CNNs) have been driving the heart of computer vision in recent years. The key concept of CNNs is to find local features from an input (usually an image) at higher layers and combine them into more multifaceted features at lower layers [24, 25]. CNNs are very good in extracting patterns in the input image, such as lines, gradients, circles, or even eyes and faces. It is this property that makes CNNs so powerful for computer vision. Unlike earlier computer vision algorithms, CNNs can operate directly on a raw image and do not need any preprocessing. In the medical field, CNNs are used to improve image quality in low-light images from a high-speed video endoscopy [26] and is also applied to recognize the nature of pulmonary nodules via CT images and the identification of pediatric pneumonia via chest X-ray images [27].
A CNN comprises several layers where each neuron of a subsequent higher layer connects to a subset of neurons in the previous lower layer. This permits the receptive field of a neuron of a higher layer to cover a greater part of images compared to that of a lower layer. The higher layer is capable to learn more abstract features of images than the lower layer by considering the spatial relationships between different receptive fields. It should be noted that CNNs significantly reduce the number of weights, and in turn reduce the variance. Like MLPs, CNNs use fully connected (FC) layers and non-linearities, but they introduce two new types of layers: convolutional and pooling layers. A convolutional layer takes a W × H × D dimensional input “I” and convolves it with a w × h × D dimensional filter (or kernel) G. The weights of the filter can be hand designed, but in the context of machine learning they are automatically tuned, just like the way weights of an FC layer are tuned. In line with convolutional layers where reducing the number of weights in neural networks reduces the variance, pooling layers directly reduce the number of neurons in neural networks. The sole purpose of a pooling layer is to downsample (also known as pool, gather, consolidate) the previous layer, by sliding a fixed window across a layer and choosing one value that effectively “represents” all of the units captured by the window. There are two common implementations of pooling. In max-pooling, the representative value just becomes the largest of all the units in the window, while in average-pooling, the representative value is the average of all the units in the window. In practice, pooling layers are stridden across the image with the stride equal to the size of the pooling layer. None of these properties actually involve any weights, unlike fully connected and convolutional layers.
Medical imaging is a useful supplement to reverse transcription polymerase chain reaction (RT-PCR) testing for the confirmation of COVID-19. Researchers have found that CT images of COVID-19 patients exhibit typical imaging characteristics. During the last year, studies have shown that typical chest CT patterns of COVID-19 viral pneumonia include multifocal bilateral peripheral ground-glass areas associated with subsegmental patchy consolidations, mostly subpleural, and predominantly involving lower lung lobes and posterior segments [28, 29, 30, 31, 32]. In more detail, chest CT images of COVID-19 patients could be evaluated using the following characteristics [33, 34, 35, 36, 37, 38, 39, 40]:
presence of ground-glass opacities (GGOs)
laterality of GGO and consolidation
presence of nodules
presence of pleural effusion
presence of thoracic lymphadenopathy
degree of involvement of each lung lobe, in addition to the overall extent of lung involvement measured
presence of underlying lung disease such as emphysema or fibrosis
bilateral distribution
number of lobes affected where either ground-glass or consolidative opacities are present
interlobular septal thickening
presence of cavitation
bronchial wall thickening
air bronchogram
perilesional vessel diameter
lymphadenopathy
pleural pericardial effusion
GGO, which is defined as hazy increased lung attenuation with preservation of bronchial and vascular margins [41], is the most common early finding of COVID-19 on chest CT. Besides GGO, bilateral patchy shadowing is one of the most common radiologic findings on chest CT [42]. In another study containing 51 COVID-19 patients, Song et al. [43] found that disease progression can be determined by lesions with consolidation. Multiple lesions and crazy-paving pattern are also common in COVID-19 patients. The diagnosis of chest CT depending on visual diagnosis of radiologists suffers from some problems [44]. For example, chest CT contains hundreds of slices, which takes a long time to diagnose. Also, it was found that the chest CT images of some COVID-19 patients share some similar manifestations with other types of pneumonia. This could add extra challenges to inexperienced radiologists, considering that COVID-19 is a new lung disease.
During the last year, AI methods and ML techniques have played a very important role in COVID-19 diagnosis in applications utilizing the CT imaging. The aim of AI techniques and ML methods was always to extract the distinguished features of COVID-19 presented in the different types of images. In this section, we review and thoroughly discuss the major works and articles that have addressed AI and ML in COVID-19 diagnosis using CT imagery. AI and deep learning methods have shown great ability to address the aforementioned problems by detecting this disease and distinguishing it from community acquired pneumonia (CAP) and other non-pneumonic lung diseases using chest CT. We explore important studies that have been performed by various academic and research communities from numerous disciplines which focus on detecting, quantifying, and tracking of Coronavirus and study how they can differentiate Coronavirus patients from those who do not have the disease.
Li et al. [45] developed a 3D deep learning framework for the detection of COVID-19, referred to as COVID-19 detection neural network (COVNet). The proposed CNN consists of a RestNet50 as the backbone, which takes a series of CT slices as the input and generates features for the corresponding slices. In more detail, it extracts visual features from volumetric chest CT scans both in 2D local and 3D global representation. The extracted features from all slices are then combined by a max-pooling operation. CAP and other non-pneumonia CT scans were included to test the robustness of the proposed model. The final feature map is fed to a fully connected layer and softmax activation function to generate a probability score for each type (COVID-19, CAP, and non-pneumonia), and produce a classification prediction. The CT scans are performed using different manufacturers with standard imaging protocols. Each volumetric scan contains 1094 CT slices with a varying slice-thickness from 0.5 mm to 3 mm. The reconstruction matrix is 512x512 pixels with in-plane pixel spatial resolution from 0.29x0.29 mm2 to 0.98x0.98 mm2. The CT scans are preprocessed and the lung region is extracted as the region of interest (ROI) using a U-net based segmentation method. Then, the image is passed to the COVNet for the predictions, as shown in Figure 1.
COVID-19 detection neural network (COVNet) architecture [
The authors have tested the system on datasets collected from six hospitals between August 2016 and February 2020. The collected datasets consisted of 4356 chest CT scans from 3322 patients. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. The COVID-19 cases were affirmed as positive by RT-PCR and were obtained from Dec 31, 2019 to Feb 17, 2020. The most shared symptoms were fever (81%) and cough (66%). Moreover, the patients were 49±15 years old and there are slightly more male patients than female (1838 vs. 1484). CT scans with multiple reconstruction kernels at the same imaging session or acquired at multiple time points were included. The final dataset consisted of 1296 (30%) scans for COVID-19, 1735 (40%) for CAP and 1325 (30%) for non-pneumonia.
For each patient, one or multiple CT scans at several time points during the course of the disease were acquired (Average CT scans per patient was 1.8, with a range from 1 to 6). The per-scan sensitivity and specificity for detecting COVID-19 in the independent test set was 114 of 127 (90% [95% confidence interval: 83%, 94%]) and 294 of 307 (96% [95% confidence interval: 93%, 98%]), respectively, with an AUC of 0.96. The details of their tests are given in Table 1.
Sensitivity % | Specificity % | AUC | |
---|---|---|---|
COVID-19 | 90 (114 of 127) | 96 (294 of 307) | 0.96 |
CAP | 87 (152 of 175) | 92 (239 of 259) | 0.95 |
Non-Pneumonia | 94 (124 of 132) | 96 (291 of 302) | 0.98 |
The performance of COVNet as per [45].
Note: Values in the parentheses are the numbers for the percentage calculations.
In another study, a weakly-supervised deep learning-based software system was developed by Zheng et al. [46] using 3D CT volumes to detect COVID-19. The authors have searched unenhanced chest CT scans of patients with suspected COVID-19 from the picture archiving and communication system of radiology department (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology). 540 patients (age of 42.5 ± 16.1 years; range 3–81 years) were enrolled into the study, including 313 patients (age, 50.7 ± 14.7 years; range 8–81 years) with clinical diagnosed COVID-19 (COVID-positive group) and 227 patients (age of 31.2 ± 10.0 years; range, 3–69 years) without COVID-19 (COVID-negative group). As shown in Figure 2, the system takes a CT volume and its 3D lung mask as input, where the 3D lung mask is generated by a pre-trained U-Net. The proposed system is divided into three stages. The first stage consists of a 3D convolution with a kernel size of 5 × 7 × 7, a batchnorm layer and a pooling layer. The second stage is composed of two 3D residual blocks. In each one of the residual block, a 3D feature map is handed into both a 3D convolution with a batchnorm layer and a shorter connection containing a 3D convolution. The third stage is a progressive classifier, which contains three 3D convolution layers and a fully-connected layer with the softmax activation function. As described in Figure 3, a U-Net is trained for lung region segmentation on the labeled training set using the ground-truth lung masks generated by an unsupervised learning method. Then, the pre-trained U-Net is used to test all CT volumes to obtain the lung masks. The lung mask is concatenated with CT volume and serves as the input of the system. The authors have used the spatially global pooling layer and the temporally global pooling layer to technically handle the weakly-supervised COVID-19 detection problem.
The architecture proposed in [
Training and testing procedures [
Furthermore, Gozes et al. [47] presented a system that exploits 2D and 3D deep learning models. Figure 4 shows a block diagram of the developed system. The system is comprised of several components and analyzes the CT case at two distinct levels:
System block diagram [
For Subsystem A, the authors used commercial off-the-shelf software that detects nodules and small opacities within a 3D lung volume. This software was developed as a solution for lung pathology detection and provides quantitative measurements (including volumetric measurements, axial measurements, calcification detection and texture characterization). For Subsystem B, the first step is the
Patient case visualization. Left: Coronal view; right: Automatically generated 3D volume map of focal opacities (green) and larger diffuse opacities (red) [
The authors have also proposed a
Multi time point tracking of disease progression [
Barstugan et al. [48] presented a classification system consisting of five different feature extraction methods followed by support vector machine (SVM). The feature extraction methods were Gray Level Co-occurrence Matrix (GLCM), Local Directional Patterns (LDP), Gray Level Run Length Matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), and Discrete Wavelet Transform (DWT). To test the proposed system, four different datasets were formed by taking patches of size 16x16, 32x32, 48x48 and 64x64 from 150 CT images belonging to 53 infected cases, from the “Societa Italiana di Radiologia Medica e Interventistica”. The samples of datasets were labeled as Coronavirus/non-Coronavirus (infected/non-infected). Table 2 shows the four different subsets created from patch regions. The authors have implemented 2-fold, 5-fold and 10-fold cross-validations during the classification process. Sensitivity, specificity, accuracy, precision, and F-score metrics were used to evaluate the classification performance. Figure 7 shows patch regions and patch samples from the four different subsets.
Subset | Patch Dimension | Number of Non-Coronavirus Patches | Number of Coronavirus Patches |
---|---|---|---|
Subset 1 | 16 × 16 | 5912 | 6940 |
Subset 2 | 32 × 32 | 942 | 1122 |
Subset 3 | 48 × 48 | 255 | 306 |
Subset 4 | 64 × 64 | 76 | 107 |
Four different subsets created from patch regions [48].
Patch regions and patch samples from the four different subsets. Sample images for infected and non-infected situations for all subsets are shown as well [
Caruso et al. [49] investigated chest CT features of patients with COVID-19 in Rome, Italy, and compared the diagnostic performance of CT with that of RT-PCR. All chest CT examinations were performed with patients in the supine position on a 128-slice CT scanner. Radiologists in consensus with thoracic imaging experience evaluated the images using a clinically available dedicated application (Thoracic VCAR, GE Medical Systems), defining patients as having positive CT findings when a diagnosis of viral pneumonia was reported. The study comprised 158 participants, of them fever was witnessed in 97 (61%) and cough and dyspnea were observed in 88 (56%) and 52 (33%), respectively. Of these patients, 62 (39%) had positive RT-PCR results and 102 (64%) had positive CT findings. Sensitivity, specificity, and accuracy of CT for COVID-19 pneumonia were 97% (60 of 62 participants), 56% (54 of 96 participants), and 72% (114 of 158 participants), respectively.
Table 3 details the CT features in participants with COVID-19 infection confirmed with RT-PCR as reported in [49]. The results presented in [49] agree with the study performed by Salehi et al. [50] of 919 patients, despite some differences. However, the population in [50] varies from the population examined in [49]. Also, Chung et al. [51] analyzed a small population consisting of 21 patients and found a very low frequency of crazy paving pattern compared with [49] (19% vs. 39%).
Furthermore, Xu et al. [52] established a model to distinguish COVID-19 from influenza-A viral pneumonia (IAVP) and healthy cases through pulmonary CT images. The authors have discussed that the RT-PCR detection of viral RNA from sputum or nasopharyngeal swab have a relatively low positive rate in the early stage. They argued that the manifestations of COVID-19 as seen through CT imaging show individual characteristics that differ from those of other types of viral pneumonia such as IAVP. The suggested model consists of multiple CNNs, where the candidate infection regions are segmented out from the pulmonary CT image set. Then, these separated images are categorized into the COVID-19, IAVP, and irrelevant to infection groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case are calculated using the Noisy-OR Bayesian function.
Figure 8 shows the whole process. As described in the figure, the CT images are first preprocessed to excavate the effective pulmonary regions. Then, a 3D CNN segmentation model is used to segment multiple candidate image cubes. After that, an image classification model is used to classify all the image patches into three kinds: COVID-19, IAVP, and irrelevant to infection. Image patches from the same group “vote” for the type and confidence score of this candidate as a whole. Finally, the Noisy-OR Bayesian function is used to calculate the overall analysis report for one CT sample. It is worth mentioning that the model uses a V-Net as the backbone feature extraction part. The authors have further discussed how the variable 3D structures of the lesion regions can aggravate the results. For example, when the border between a healthy region and the infected one becomes blurred and indistinct, it will be difficult to label pixel-level masks for lesion regions of pneumonia. As such, the model uses the RPN structure [52] to capture the region of interest with 3D bounding boxes instead of pixel-level segmented masks.
The process flow chart of [
To evaluate the system, two classification models were used, as shown in Figure 9. The first one was the ResNet model and the other was designed based on the first network structure by concatenating the location-attention mechanism in the full-connection layer to improve the overall accuracy rate. The resultant model was added to the first full-connection layer to enhance the influence of this factor on the whole network. The output of the convolution layer was flattened to a 256-dimensional feature vector and then converted into a 16-dimensional feature vector using a full-connection network. The overall accuracy rate was 86.7% in terms of all the CT cases taken together.
The network structure of ResNet-18-based classification model [
CT Feature | No. of Participants (n = 58) | Percentage |
---|---|---|
GGO | 58 | 100 |
Multilobe involvement (≥2 lobes) | 54 | 93 |
Bilateral distribution | 53 | 91 |
Posterior involvement | 54 | 93 |
GGO location (peripheral) | 52 | 89 |
Subsegmentel vessel enlargement (>3 mm) | 52 | 89 |
Consolidation | 42 | 72 |
Subsegmental | 32 | 55 |
Segmental | 10 | 17 |
Lymphadenopathy | 34 | 58 |
Bronchiectasis | 24 | 41 |
Air bronchogram | 21 | 36 |
Pulmonary nodules surrounded by GGO | 10 | 17 |
Interlobular septal thickening | 8 | 13 |
Halo sign | 7 | 12 |
Pericardial effusion | 3 | 5 |
Pleural effusion | 2 | 3 |
Bronchial wall thickening | 1 | 1 |
Cavitation | 0 | 0 |
CT features in participants with COVID-19 infection confirmed with RT-PCR [49].
Belfiore et al. [53] presented a practice of a good tool for radiologists (Thoracic VCAR) that can be used in COVID-19 diagnosis. Thoracic VCAR offers quantitative measurements of the lung involvement. Further, it can generate a clear, fast and concise report that communicates vital medical information to referring physicians. In the post-processing phase, the software can recognize the ground glass and differentiate it from consolidation and quantifies them as a percentage with respect to the healthy parenchyma. This information is useful for evaluating regression or progression disease in response to drug therapy as well as evaluating the effectiveness of pronation maneuvers for alveolar recruitment in ICU patients. The authors in [53] have discussed the importance of such high-resolution CT (HRCT) technique in investigating the patients with suspicion COVID-19 pneumonia. They have argued that the HRCT is a very accurate technique in identifying pathognomic findings of interstitial pneumonia as ground glass areas, crazy paving, nodules and consolidations, mono- or bilateral, patchy or multifocal, central and/or peripheral distribution, declivous or nondeclivous. As per the discussion, during the follow-up, HRCT examination can quantify the course of the disease and evaluate the effectiveness of the experimental trial and the patient’s prognosis.
In [54], Mei et al. have also used AI algorithms to integrate chest CT findings with clinical symptoms, exposure history and laboratory testing to rapidly diagnose patients who are positive for COVID-19. Among a total of 905 patients tested by real-time RT–PCR test, 419 (46.3%) tested positive for SARS-CoV-2. In this study, the dataset included patients aged from 1 to 91 years (with mean of 40.7 year and standard deviation of 6.5 years) where 488 of the patients were men and 417 were women. All scans were acquired using a standard chest CT protocol and were reconstructed using the multiple kernels and displayed with a lung window. Clinical information included travel and exposure history, leukocyte counts (including absolute neutrophil number, percentage neutrophils, absolute lymphocyte number and percentage lymphocytes), symptomatology (presence of fever, cough and sputum), patient age and patient sex. More specifically, the authors developed a CNN to learn the imaging characteristics of patients on the initial CT scan. They used multilayer perceptron classifiers to classify patients with COVID-19 according to the radiological data and clinical information.
Of the 134 positive cases in the test set, 90 were correctly categorized by both the joint model and the senior thoracic radiologist and 33 were classified differently. Of the 33 patients, 23 were correctly classified as positive by the joint model, but were misclassified by the senior thoracic radiologist. Ten patients were classified as negative by the joint model, but correctly diagnosed by the senior thoracic radiologist. Eleven patients were misclassified by both the joint model and the senior thoracic radiologist. Of the 145 patients negative for COVID-19 in the test set, 113 were correctly classified by both the joint model and the senior thoracic radiologist. Thirty-two out of 145 were classified differently by the joint model and the senior thoracic radiologist. Seven were correctly classified as negative by the joint model, but were diagnosed as positive by the senior thoracic radiologist. Twenty-three were classified as positive by the joint model, but correctly diagnosed as negative by the senior thoracic radiologist. Two patients were misclassified by both the joint model and the senior thoracic radiologist. As discussed in [54], patient’s age, presence of exposure to SARS-CoV-2, presence of fever, cough, cough with sputum, and white blood cell counts are significant features associated with SARS-CoV-2 status. However, it should be pointed out that difficulties on model training have been witnessed due to the limited sample size.
Moreover, Fei et al. [55] developed a deep learning-based system for automatic segmentation of lung and infection sites using chest CT. Likewise, Xiaowei et al. [56] distinguished COVID-19 pneumonia and Influenza-A viral pneumonia from healthy cases. Further, Shuai et al. [57] developed a system to extract the graphical features in order to provide a clinical diagnosis before pathogenic testing and thus save critical time. Also, Zheng et al. [58] developed a model for automatic detection using 3D CT volumes. Bai et al. [59] established and evaluated an AI system for differentiating COVID-19 and other pneumonia from chest CT to assess radiologist performance. As they have discussed, distinguishing COVID-19 from normal lung or other lung diseases, such as cancer from chest CT, may be straightforward. However, a major difficulty in controlling the current pandemic is making out subtle radiologic differences between COVID-19 and pneumonia of other origins. A total of 521 patients with positive RT-PCR results for COVID-19 and abnormal chest CT findings were retrospectively identified from 10 hospitals. A total of 665 patients with non–COVID-19 pneumonia and definite evidence of pneumonia from chest CT were retrospectively selected from three hospitals.
Further, the authors have performed data augmentation dynamically during training and included flips, scaling, rotations, random brightness and contrast manipulations, random noise, and blurring. Training was performed for 20 epochs, where each epoch was defined as 16000 slices. A classification model was trained to distinguish between slices with and those without pneumonia-like findings (both COVID-19 and non–COVID-19). In more technical details, the EfficientNet B4 architecture was used for the pneumonia classification task. Each slice was stacked to three channels as the input of EfficientNet that used pretrained weights on ImageNet. EfficientNets with dense top fully connected layers were used. There were four fully connected layers of 256, 128, 64, and 32 neurons, respectively. Also, a fully connected layer with 16 neurons with batch normalization and a classification layer with sigmoid activation were added at the end of EfficientNet. Then, the slices were pooled using a two-layer fully connected neural network to make predictions at the patient level. Figure 10 shows the proposed classification neural network model, while Figure 11 demonstrates the model’s flowchart.
Classification neural network model proposed by [
The flowchart showing the AI model used to distinguish COVID-19 from non–COVID-19 pneumonia. (PR AUC = precision recall area under curve, ROC AUC = receiver operator characteristics area under the curve) [
Kumar et al. [60] proposed a framework that collects a big amount of data from various hospitals and trains a deep learning model over a decentralized network using the most recent information related to COVID-19 patients based on CT slices. The authors suggested the integration of blockchain and federated-learning technology that allow the collection of data from different hospitals without the leakage of data; a step that adds the necessary privacy to the model. They employed Google’s Inception V3 network for feature extraction and tested various learning models (VGG, DenseNet, AlexNet, MobileNet, ResNet, and Capsule Network) in order to recognize the patterns from lung screening. They found that Capsule network achieved the best performance when compared to other learning models. Figure 12 shows the suggested model in [60].
COVID-19 model suggested by [
The Capsule network contains four layers: i) Convolutional layer, ii) Hidden layer, iii) PrimaryCaps layer, and iv) DigitCaps layer. A capsule is made when input features are in the lower layer. Each layer of the Capsule Network contains many capsules. To train it, the activation layer represents the parameters of the entity and computes the length of the Capsule network to re-compute the scores of the feature part. The capsule acts as a neuron. Capsule networks tend to describe an image at a component level and associate a vector with each component. The probability of the existence of a component is represented by the vectors lengths.
In federated learning, the hospitals keep their data private and share only the weights and gradients while blockchain technology is used to distribute the data securely among the hospitals. Federated learning was proposed by McMahan et al. [61] to learn from the shared model while protecting the privacy of data. In this context, the federated learning is used to secure data and aggregate the parameters from multiple organizations. As argued by the authors, since the volume of data is big, placing them on the blockchain directly with its limited storage space will be very expensive and resource-intensive. As such, a special data manipulation is needed. So, the hospital needs to store a transaction in the block to verify the ownership. The hospital data include the data type and size. It is noteworthy that federated learning does not affect the accuracy but it adds the privacy while sharing the data. Some selected 3D samples from the dataset are shown in Figure 13. The authors have claimed that the system sensitivity is 0.96, and its precision is 0.83. However, its specificity was not very attractive.
Selected samples from [
A simple 2D deep learning framework was developed in [62] to diagnose COVID-19 pneumonia based on a single chest CT image using transfer learning. For training and testing, the authors collected 3993 chest CT images of patients with COVID-19 pneumonia, other pneumonia and nonpneumonia diseases. These CT images were split into a training set and a testing set at a ratio of 8:2. After a simple preprocessing stage, three channels (256 × 256 × 3 pixels) were arranged in the input layer and fed into the pretrained model layers. In the pretrained model layers, the authors included one of these four models (VGG16, ResNet-50, Inception-v3, and Xception). Each model comprises two parts: a convolutional base and a classifier. The convolutional base is composed of a stack of convolutional and pooling layers to generate features from the images. The role of the classifier is to categorize the image based on the extracted features. The activations from the pretrained model layers were fed into the additional layers. In the additional layers, the activations were first flattened and connected to two fully connected layers: one consisted of 32 nodes, and the other consisted of three nodes. Subsequently, the activations from the second fully connected layer were fed into a SoftMax layer, which provided the probability for each of the classes (COVID-19, other pneumonia, and nonpneumonia). However, the study has several limitations as well. First, the testing dataset was obtained from the same sources as the training data set. This may raise issues of generalizability and overfitting of the models. Indeed, the authors have mentioned that the detection accuracy decreased when datasets from other published papers were used.
Song et al. [63] first extracted the main regions of the lungs and filled the blank of lung segmentation with the lung itself to avoid noise caused by different lung contours. Then, they extracted the top-K details in the CT images and obtained image-level predictions. Finally, the image-level predictions were combined to attain patient-level diagnoses. In the testing set, the model achieved an AUC of 0.95 and sensitivity of 0.96. In [64], Jin et al. built a method to accelerate the diagnosis speed. This model was trained using 312 images. Yet, it achieved a comparable performance with experienced radiologists. Among 1255 independent testing cases, the proposed deep-learning model achieved an accuracy of 94.98%, an AUC of 97.91%, a sensitivity of 94.06% and a specificity of 95.47%.
Zheng et al. [65] used U-Net to segment the lung area automatically, and then used 3DResNet for classification. As they have discussed, infectious areas can be distributed in many locations in the lungs, and automatic infectious area detection may not guarantee very high precision. Consequently, using the whole lung for classification is more convenient in practice. In [66], 3506 patients (468 with COVID-19, 1551 with CAP, and 1303 with non-pneumonia) were used to train and test another deep-learning model. The authors first used U-net to extract the whole lung region as an ROI. Afterwards, 2D RestNet50 was used for classifying COVID-19. Since each CT scanning includes multiple 2D image slices, the features in the last layer of ResNet50 were max pooled and combined for prediction. The model achieved an AUC of 0.96 in classifying COVID-19 from CAP and other pneumonia. Moreover, Shi et al. [67] included 1658 patients with COVID-19 and 1027 patients with CAP for classification. They first used VBNet to segment the infected areas, bilateral lungs, 5 lung lobes, and 18 lung pulmonary areas. Then, hand-crafted features such as location specific features, infection size, and radiomic features were extracted, and least absolute shrinkage and selection operator (LASSO) was used for feature selection. The method reached sensitivity of 0.9, specificity of 0.8, and accuracy of 0.88.
Further, Dong et al. [68] reviewed the use of various imaging characteristics and computing models that have been applied for the management of COVID-19. Specifically, they have quantitatively analyzed the use of imaging data for detection and treatment by means of CT, positron emission tomography - CT (PET/CT), lung ultrasound, and magnetic resonance imaging (MRI). PET is a sensitive but invasive imaging method that plays an important role in evaluating inflammatory and infectious pulmonary diseases, monitoring disease progression and treatment effect, and improving patient management. It is worth mentioning that lung ultrasound is a non-invasive, radiation-free, and portable imaging method that allows for an initial bedside screening of low-risk patients, diagnosis of suspected cases in the emergency room setting, prognostic stratification, and monitoring of the changes in pneumonia [69, 70].
Also, Jin et al. [71] presented their experience in building and deploying an AI system that analyzes CT images and detects COVID-19 pneumonia features. They obtained the image samples from five different hospitals with 11 different models of CT equipment to increase the model’s generalization ability. The combined “segmentation - classification” model pipeline, can highlight the lesion regions in addition to the screening result. The model pipeline is divided into two stages: 3D segmentation and classification. The pipeline leverages a model library that contains different segmentation models such as FCN-8 s, U-Net, V-Net, and 3D U-Net++, as well as the classification models like dual path network (DPN-92), Inception-v3, ResNet-50, and Attention ResNet-50. As for the training set, in addition to the positive cases, they assembled a set of negative images of inflammatory and neoplastic pulmonary diseases, such as lobar pneumonia, lobster pneumonia, and old lesions. Their aim was enabling the model to learn different COVID-19 features from various resources. Using 1136 training cases (723 positives for COVID-19), they were able to achieve a sensitivity of 0.974 and a specificity of 0.922 on the test set. Further, the system achieved an AUC of 0.991. According to the authors, the system is in use in 16 hospitals and has a daily capacity of over 1300 screenings. Similarly, Jin et al. [72] performed an extensive statistical analysis on CT images diagnosed by COVID-19.
They evaluated the system on a large dataset with more than 10000 CT volumes from COVID-19, influenza-A/B, non-viral CAP and non-pneumonia subjects. Figure 14 shows the workflow of the suggested system. The system consists of five key parts: (1) lung segmentation network, (2) slice diagnosis network, (3) COVID-infectious slice locating network, (4) visualization module for interpreting the vital region, and (5) image phenotype analysis module for features explanation. CT volumes were divided into different cohorts. The authors claimed that the system achieved an AUC of 97.81% on a test set of 3199 scans.
The workflow of the AI system suggested in [
Jin et al. [73] drafted a guideline according to the guidelines methodology and general rules of WHO in relation to CT imaging. This guideline includes the epidemiological characteristics, disease screening, diagnosis, treatment, and nosocomial infection prevention. In this regard, the authors have discussed that the imaging findings vary with the patient’s age, immunity status, disease stage at the time of scanning, underlying diseases, and drug interventions. The imaging features of lesions show: (1) dominant distribution (mainly subpleural, along the bronchial vascular bundles), (2) quantity (often more than three or more lesions, occasional single or double lesions), (3) shape (patchy, large block, nodular, lumpy, honeycomb-like or grid-like, cord-like, etc.), (4) density (mostly uneven, a paving stones-like change mixed with ground glass density and interlobular septal thickening, consolidation and thickened bronchial wall, etc.), and (5) concomitant signs variations (air-bronchogram, rare pleural effusion and mediastinal lymph nodes enlargement, etc.).
In addition, Chen et al. [74] constructed a system based on deep learning for detecting COVID-19 pneumonia from high resolution CT. For model development and validation, 46096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University were retrospectively collected and processed. Twenty-seven consecutive patients who underwent CT scans were prospectively collected to evaluate and compare the efficiency of radiologists against COVID-19 pneumonia with that of the model. The authors have first filtered the images where 35355 images were selected and split into training and testing datasets. In more detail, the authors implemented UNet++ being a well-known architecture for medical image segmentation. They trained UNet++ to extract valid areas in CT images using 289 randomly selected CT images and tested it on other 600 randomly selected CT images. The training images were labeled with the smallest rectangle containing all valid areas. With the raw CT scan images taken as the input, and the labeled map from the expert as the output, UNet++ was used to train in an image-to-image manner. The model successfully extracted valid areas in 600 images from the testing set with an accuracy of 100%. Based on system performance, the authors constructed a cloud-based platform to provide a worldwide assistance for detecting COVID-19 pneumonia [75].
In [76], Vinod and Prabaharan have elaborated a methodology that helps identifying COVID-19 infected people among the normal individuals by utilizing CT scan. The image diagnosis tool utilizes decision tree classifier for finding Coronavirus infected person. The percentage accuracy of an image was analyzed in terms of precision, recall score and F1 score. Moreover, Gieraerts et al. [77] hypothesized that the use of semi-automated AI may allow for more accurate patient detection. They assessed COVID-19 patients who underwent chest CT by conventional visual and AI-based quantification of lung injury. They also studied the impact of chest CT variability in determining the potential response to novel antiviral therapies. In their study, 250 consecutive patients with clinical suspicion of COVID-19 pneumonia were tested with both RT-PCR and CT within a 2-hour interval of hospital admission. Epidemiological, demographic, clinical, and laboratory data at admission were obtained from the electronic patient management system.
In Zhang et al. [78], 4695 manually annotated CT slices were used to build seven classes, including background, lung field, consolidation, ground-glass opacity, pulmonary fibrosis, interstitial thickening, and pleural effusion. After a comparison between different semantic segmentation approaches, the authors selected DeepLabv3 as the segmentation detection backbone. The diagnostic system was based on a neural network fed by the lung-lesion maps. The results showed a COVID-19 diagnostic accuracy of 92.49% when tested on 260 subjects. In Bai et al. [79], a direct classification of COVID-19 specific pneumonia versus other etiologies was performed using an EfficientNet B5 network followed by a two-layer fully connected network to pool the information from multiple slices and provide a patient-level diagnosis. This system yielded 96% accuracy on a testing set of 119 subjects compared to an average accuracy of 85% for six radiologists.
Also, Ying et al. [80] used 2D slices including lung regions segmented by OpenCV. Fifteen slices of complete lungs were derived from each 3D chest CT images, and each 2D slice was used as the input to the system. A pretrained ResNet-50 was used and the Feature Pyramid Network (FPN) was added to extract the top-K details from each image. An attention module was coupled to learn the important details. Chest CT images from 88 patients with COVID-19, 101 patients with bacterial pneumonia, and 86 healthy persons were used. The model achieved an accuracy of 86% for pneumonia classification (COVID-19 or bacterial pneumonia), and an accuracy of 94% for pneumonia diagnosis (COVID-19 or healthy). Wang et al. [81] used 1065 chest CT scan images of COVID-19 patients to build a classifier using InceptionNet. They reported an accuracy of 89.5%, a specificity of 0.88, and a sensitivity of 0.87. In [82], different deep learning approaches (VGG16, InceptionResNetV2, ResNet50, VGG19, MobilenetV2, and NasNetMobile) have been modified and tested on 400 CT scan images. The results have shown that NasNetMobile outperformed all other models in terms of accuracy (81.5% –95.2%). On the other hand, Mucahid et al. [83] used classical feature extraction techniques for COVID-19 detection. For example, they have implemented gray level co-occurrence matrices (GLCM), local directional pattern (LDP), gray-level run length matrix (GLRLM), and discrete wavelet transform (DWT). They reported an accuracy of 99.68% in the best configuration settings.
Modegh et al. [84] proposed a system to distinguish healthy people, patients with COVID-19, and patients with other pneumonia diseases from axial lung CT-scan images. The general workflow for the proposed model is shown in Figure 15. The Ground Glass Opacity Axial (GGOA) CT-scan images are preprocessed and the lobes of the lungs are detected and extracted from the axial slices. The images of the left and right lobes of all the slices are then fed into two deep CNNs, one for calculating the probability of being diseased versus healthy, and the other for calculating the probability of diagnosis to be COVID-19 versus other diseases. In addition, the system detects the infected areas in the lung images. At the end, the probabilities assigned to the lobes are aggregated to make a final decision.
The general workflow for the interpretable COVID-19 detection proposed in [
Figure 16 shows the model used for calculating the probability of each slice lobe being infected. The model was evaluated on a dataset of 3359 samples from 6 different medical centers and achieved sensitivities of 97.8% and 98.2%, and specificities of 87% and 81% in distinguishing normal cases from the diseased and COVID-19 from other diseases, respectively. Authors in [85] examined the effect of generalizability of the deep learning models, given the heterogeneous factors in training datasets such as patient demographics and pre-existing clinical conditions. The examination was done by evaluating the classification models trained to identify COVID-19 positive patients on 3D CT datasets from different countries: UT Southwestern (UTSW), CC-CCII Dataset (China), COVID-CTset (Iran), and MosMedData (Russia). The data were divided into two classes: COVID-19 positive and COVID-19 negative patients. The models trained on a single dataset achieved accuracy/AUC values of 0.87/0.826 (UTSW), 0.97/0.988 (CC-CCCI), and 0.86/0.873 (COVID-CTset) when evaluated on their own dataset.
The deep model used for calculating the probability of each slice lobe [
In addition, Shah et al. [86] developed a deep learning network (CTnet-10) for COVID-19 classification. The model is fed with an input image of size 128 × 128 × 3. It passes through two convolutional blocks of dimensions 126 × 126 × 32, 124 × 124 × 32 respectively. Then it passes through a max-pooling of dimension 62 × 62 × 32 followed by two convolutional layers of dimensions 60 × 60 × 32, 58 × 58 × 32 respectively. Then, it is passed through a pooling layer of dimension 29 × 29 × 32, a flattened layer of 26912 neurons, and dropout layers of 256 neurons. After that, it is passed through a dense layer of a single neuron, where the CT scan image is classified as COVID-19 positive or negative. The system achieved an accuracy of 82.1%. The CTnet-10 model architecture is shown in Figure 17.
CTnet-10 model architecture [
VB-Net, a deep learning network, was developed by Shan et al. [87] to quantify longitudinal changes in the follow-up CT scans of COVID-19 patients, and to explore the quantitative lesion distribution. VB-Net is a modified 3D CNN that consists of two paths. The first is a contracting path including down-sampling and convolution operations to extract global image features. The second is an expansive path including up-sampling and convolution operations to integrate fine-grained image features. Compared with V-Net, the VB-Net is much faster. The system not only performs auto-contouring of infection regions, but also accurately estimates their shapes, volumes and percentage of infection (POI) in CT scans. In addition, it measures the severity of COVID-19 and the distribution of infection within the lung. The accurate segmentation provides quantitative information that is necessary to track disease progression and analyze longitude changes of COVID-19 during the entire treatment period. After segmentation, various metrics are computed to quantify the infection, including the volumes of infection in the whole lung, and the volumes of infection in each lobe and each bronchopulmonary segment.
The system was trained using 249 COVID- 19 patients, and validated using 300 new COVID-19 patients. To accelerate the manual delineation of CT images for training, a human-in-the-loop (HITL) strategy (shown in Figure 18) was adopted to assist radiologists to refine automatic annotation of each case. To evaluate the performance of the system, the Dice similarity coefficient, the differences of volume and the POI were calculated between the automatic and the manual segmentation results on the validation set. The system yielded a Dice similarity coefficient of 91.6% and a mean POI estimation error of 0.3% for the whole lung on the validation dataset. Moreover, the proposed HITL strategy reduced the delineation time to 4 minutes after 3 iterations of model updating, compared to the cases of fully manual delineation that often take 1 to 5 hours. Figure 19 shows the pipeline for quantifying COVID-19 infection, whereas Figure 20 shows typical infection segmentation results of CT scans for three COVID-19 patients.
The human-in-the-loop workflow [
The proposed pipeline for quantifying COVID-19 infection [
Typical infection segmentation results of CT scans for three COVID-19 patients. Rows 1–3: Early, progressive and severe stages. Columns 1–3: CT image, CT images overlaid with segmentation, and 3D surface rendering of segmented infections [
The specific nature of COVID-19 pandemic requires strong coordination of connected data, people, and systems to facilitate worldwide collaboration in fighting against it. From this study, we notice that healthcare stakeholders are not using the same systems, data formats, or standards. This can obstruct the ability to identify the possible trends of solutions to the pandemic related challenges and develop interventions among the associated efforts. Public health researchers, epidemiologists, and government officials need to be connected via integrated systems with connected data to understand the evolving pandemic better and make collective decisions on addressing this crisis. An important key action that needs to be taken to ensure best possible fight of the current (or even future) pandemic(s) is to catalyze scaling up the implementation of AI and ML in health sector.
Our study specifically suggests the following important issues that need to be addressed intensely and more efficiently:
Due to the low contrast of the infection regions in some images and large variation of both shape and position across different patients, delineating the infection regions from the chest images is very challenging [88, 89]. Researchers are challenged to investigate AI techniques that may help in this direction.
Although CT provides rich pathological information, it was noticed that in some cases only qualitative evaluation has been provided and precise changes across follow-up CT scans are often ignored. Actually, contouring infection regions in the Chest CT is necessary for quantitative assessment [90, 91]. As such, more investigation is required in this area.
Quantifying imaging metrics and correlating them with syndromes, epidemiology, and treatment responses is essential and could further reveal insights about imaging markers and findings toward improved diagnosis and treatment for COVID-19 [92, 93].
Some segmentation models were trained using imperfect ground-truth data. This could be improved by using 3D segmentation networks and adopting precise ground-truth annotated by experts [94, 95].
The images in some datasets were acquired from different devices. This situation makes the classification process a kind of challenging. This could be explained by the fact that some gray-levels in one image represent certain Coronavirus infected levels, and the same gray-levels in another image may represent different levels (may lead to different decisions) [96, 97].
Some systems were developed to quantify infections only, and it may not be applicable for quantifying other pneumonia, for example bacterial pneumonia [98, 99].
Many datasets were collected in one center, which may not be representative of all COVID-19 patients in other geographic areas. The generalization of the deep learning system needs to be further validated on multi-center datasets [100].
Experimental evidence is presented on datasets of hundreds (maybe thousands). However, the need is to go to real world settings, in which databases consist of hundreds of thousands and even more cases, with large variability [101].
The COVID-19 is a disease that has spread all over the world. This work attempted to provide a detailed study on how the AI and ML can help in various domains related to COVID-19, specifically in the area of disease diagnosis using CT imagery. In pursuing so, we considered, examined, discussed, and analyzed comprehensive studies and detailed researches proposed by intellectuals and researchers from various scientific communities and international academic institutions. Deep learning techniques and algorithms have shown immense appearances and implementations in different domains and COVID-19 related applications.
AI solutions have the potential to detect and analyze any abnormalities in health conditions in general, and related to COVID-19 in particular. The study has demonstrated that AI solutions can assist in differentiating Coronavirus patients from those who do not have the disease and can provide support in tracking disease progression. AI technology can potentially support radiologists in the triage, quantification, and trend analysis of data. For example, if the developed technique suggests a significantly increased likelihood of disease, then the case can be flagged for further review by a radiologist or clinician for possible treatment/quarantine. Moreover, AI technology can provide a consistent method for rapid evaluation of high volumes of diagnostic that can reliably exclude images which are negative for findings associated with COVID-19. This decreases the volume of cases passing through to the radiologist without overlooking positive cases. Using AI solutions, progression and regression of positive findings could be monitored more quantitatively and regularly. This could lead to more effective identification and containment of early cases. The study also discovered that a critical existing impediment to effective AI implementation is the lack of COVID-19-related clinical data that can be maintained and processed into easily accessible databases. Integrating COVID-19-related clinical data with existing biobanks, as well as pre-existing patient data, could help bioinformaticians and computational scientists develop a faster and more practical way to useful data-mining.
It is our hypothesis that AI and ML tools can leverage the ability to modify and adapt existing models and combine them with initial clinical understanding to address COVID-19 challenges and the new emerging strains or mutations of the virus. Researchers and scientists are hoping to speed up the development of extremely precise and useful AI, ML, and deep learning technologies to combat COVID-19. If our societies could not reach the best expected AI solutions during this pandemic, we strongly anticipate that AI technology will be of greater help with the next pandemic.
The author would like to express his gratitude and grateful appreciation to the Kuwait Foundation for the Advancement of Sciences (KFAS) for financially supporting this project. The project was fully funded by KFAS under project code: PN20-13NH-03.
Plant foods contain vitamins, phytosterols, sulfur compounds, carotenoids and organic acids that are healthy for human. However, the most effective protective agents are phenolic compounds that are secondary metabolites found in fruits, vegetables, and cereals. It is known that 100 g of apples, pears and cherries fruit contain 200–300 mg of polyphenols [1, 2, 3, 4]. Grapes are rich in phenols. 10% of the total phenolic compounds of grapes are contained in the pulp, 60–65% in the seeds, and 20–35% in the peel. The content of phenolic compounds in grapes depends on the plant variety, climatic and other geographical conditions, as well as the degree of maturity [5]. These healthy components are stored in drinks made from grapes. When grape wine is produced, almost 63% of all phenolic substances from grape seeds and berry peel are extracted into wine. So provided that the optimal dose is consumed, wine can be considered one of the most effective natural remedies.
It is important that in the process of obtaining wort (fermentation) and maturation of wine, phenolic compounds undergo structural changes, which determines characteristics of the drink. The most intense reactions during the maturation of wine are the polymerization and oxidation of catechins. The products of these reactions give a pleasant taste and golden-brown color of different intensity of wine, so that aged wines are easy to distinguish from young [6, 7].
Another group of substances that are extracted into wine during fermentation is procyanidins. Procyanidins are contained mainly in grape seeds, so they are virtually absent in grape juice. Initially, the wort contains a small amount of procyanidins, as these substances started to extract from the seeds during fermentation when the alcohol content is 6%. As the alcohol concentration increases during fermentation, procyanidins are extracted into the wine. Young wine rich in procyanidins has a tart taste. In the aging process procyanidins react with each other and form longer polymers - condensed tannins. As the wine ages, these chains become very long and difficult to dissolve, so they precipitate [6, 7, 8].
Because grape peel and seeds float on the surface, the more often they are immersed in the fermenting wort, the process of extraction of procyanidins better proceed. After fermentation, many wines also insist on the pomance to enhance the color, taste and extract the tannins. Therefore, the highest content of procyanidins and tannins is characteristic of wines that have been infused for three weeks or more. Thus, the consumption of grapes, grape juice and wine has different effects on the body [6].
Numerous researchers pay much attention to the study of the effects of red wine consumption on the organism since the discovery of the “French paradox”. Although the father of medicine Hippocrates emphasized the benefits of “moderate wine consumption” [9]. As a result of large-scale studies involving almost 300 thousand people, it was shown that the consumption of 150–400 ml of dry red wine daily significantly reduces the risk of cardiovascular and neurological pathologies, diabetes, many types of cancer, and dysfunction of gastrointestinal tract. These positive effects are associated with the action of grape wine polyphenols [10]. Despite this, the molecular mechanisms of the protective action of wine remain insufficiently studied.
The pharmacological, medical, and biochemical properties of phenols are widely studied. Antioxidant, vasodilating, anti-oncological, anti-inflammatory, immunostimulatory, anti-allergic, antiviral and estrogenic effects are shown. Wine polyphenols inhibit phospholipase A2, cyclooxygenase, lipoxygenase, glutathione reductase, and xanthine oxidase, and chelate metal ions [9, 11, 12, 13, 14, 15, 16].
In cells incubated with phenols, the expression of genes encoding proteins involved in antioxidant detoxification is induced. These genes are regulated by a specific enhancer, the antioxidant response element (ARE). Red wine polyphenols can alter Nitric oxide synthase (NOS) activity due to the effect on cellular concentration of Ca2+ and the phosphorylation of key proteins of the phosphatidylinositol-3′ kinase/Akt pathway after short incubation with cells. After long-term incubation, polyphenols alter NOS activity by regulating the expression of the genes of the constitutive isoforms of NOS enzyme [12, 17, 19, 20].
Most dietary polyphenols are absorbed in the intestine by passive transport, intensively metabolized in the small and large intestine and liver, where they are converted into metabolites with higher antioxidant and estrogenic activity. Sulfated, glucuronidated, and methylated polyphenols were found in blood plasma. Moreover, a large part of polyphenols undergo hydrolysis and degradation under the action of intestinal microflora to simple phenolic compounds [12, 14, 16, 21, 23]. Metabolites of polyphenols circulate in the blood in a protein-bound form, in particular with albumin, which plays an important role in regulating the bioavailability of polyphenols. The affinity of polyphenols to albumin varies depending on their chemical structure. Albumin binding determines the rate at which metabolites are delivered to cells and tissues or excreted. The accumulation of polyphenols in tissues is the most important stage of polyphenol metabolism because it preserves the necessary concentration for the biological effects of polyphenols. Polyphenols easily penetrate tissues, especially the intestines and liver. Polyphenols excretion and their derivatives occur in urine and bile. In this case, large conjugated metabolites are more likely to be excreted in the bile, while small conjugates, such as monosulfate, are preferably excreted in the urine. The amount of metabolites excreted in the urine correlates with the maximum concentration in plasma [24].
Phenols include more than 8000 natural compounds. Their molecule contains phenol (aromatic ring with at least one hydroxyl group). Phenols are classified into polyphenols and simple phenols, depending on the number of phenolic rings in their molecules. Simple phenols include phenolic acids. The group of polyphenols, i.e. phenols that contain at least two phenolic rings, includes flavonoids, stilbenes, and tannins (containing three or more phenolic rings) [11, 13, 14, 15, 16, 18, 24].
Flavonoids are a large group of low molecular weight polyphenolic compounds. According to the degree of oxidation of the pyranose ring, hydroxylation of the nucleus and properties of the substituent at the third Carbon atom, flavonoids are divided into subclasses: flavones, isoflavones, flavanols (catechins), flavonols, flavanones, anthocyanins and proanthocyanidins [11, 14, 24, 25, 26].
Flavonoids have a vasodilating effect. They cause vascular smooth muscle relaxation, probably mediated by inhibition of protein kinase C or decreased Ca2+ uptake by cells [14].
Flavan-3-ols, in particular (−) - epicatechins, (+) - catechins, gallates, and products of their methylation, decarboxylation, and dehydroxylation, as well as quercetin (3,5,7,3′,4′-pentahydroxyflavone), activate antioxidant enzymes. Herewith, quercetin is effective at lower concentrations (5–20 μМ) than catechins (500 μМ - 1 mM) [27].
Catechins affect cell apoptosis by altering the expression of antiapoptotic or proapoptotic genes. Epicatechins inhibit apoptosis by activating genes of Bcl family proteins and inhibiting caspase-6 activity and Bax, Bad, and Mdm2 gene expression. These compounds also ensure cell survival by activating protein kinase C. It should be noted that at low concentrations flavan-3-ols have an antiapoptotic effect, and at high concentrations (50–500 mM) they promote cell death by the mechanism of apoptosis [28].
Grape wine anthocyanins (malvidin, delphinidin, peonidin, petunidin, and cyanidin) are most often identified in the glycosylated form. It has long been thought that glycosylation is the only pathway for anthocyanin metabolism, but glucuronides and sulfates of these polyphenols have recently been identified [2]. Plasma concentrations of anthocyanins are too low to capture reactive oxygen species (ROS) and reactive nitrogen species (RNS). But anthocyanins are potent antioxidants because they can affect NO content and its stable metabolites. Consumption of 16–500 μM of anthocyanins reduces NO production by more than 50%, mainly due to inhibition of inducible NOS. In this case, anthocyanins do not cause cytotoxicity [3]. Like other flavonoids, anthocyanins and anthocyanidins poses antioxidant properties. Anthocyanins act as donors of electron or to transfer a hydrogen atom of hydroxyl groups to free radicals [29]. Isolated anthocyanins and a suspension of flavonoids enriched with anthocyanins prevent the disruption of DNA molecule, the development of hormone-dependent pathologies (affect estrogen secretion), regulate immune response by preventing excessive production of cytokines [30]. Anthocyanins exhibit also an anti-inflammatory activity by inhibiting transcription factor NF-κβ. The content of several NF-κβ-dependent chemokines, cytokines, and inflammatory mediators decreases in the plasma and monocytes of healthy people after consumption of anthocyanins [30, 31].
In plants are also synthesized other phenols – non-flavonoids (phenolic acids, tannins, and stilbene), which are also present in grapes and wine.
Phenols, which include one functional group of carboxylic acid called phenolic acids. There are two groups of phenolic acids – hydroxycinnamic and hydroxybenzoic acids. To hydroxycinnamic acids belong
Gallic acid (3,4,5-trihydroxybenzoic acid) is the phenol that is best absorbed into cells and exhibits various biological properties [2, 32]. Gallic acid and its derivatives (unconjugated and conjugated 4-O-methylgallic acid, 2-O-methylgallic acid, pyrogallol, 4-O-methylpyrogallol, resorcinol) in a dose-dependent manner inhibit tyrosine kinases, inhibit P-selectin exposure on the surface of blood cells, affect the release of Ca2+ into the cytoplasm, free radicals formation and thus modify cellular signaling pathways [33, 34]. Gallic acid and (−) -epicatechins inhibit NO formation by inhibiting the formation of mRNA of iNOS in immunocompetent cells [30].
Hydroxycinnamic acids cause an increase in the activity of cellular antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) by activating the transcription of their genes [5, 35].
The family of stilbenes includes resveratrol, pterostilbene, and piceatannol, which are characterized by the presence of a double bond connecting phenolic rings [14, 24]. Resveratrol has anti-infectious, antioxidant, cardioprotective, anti-proliferative, and pro-apoptotic activities. It induces apoptosis by activating signaling pathways mediated by phosphorylation of p53 proteins, protein kinase C, MAPK or through the death receptor Fas/CD95/APO-1 [36].
Tannins are polymer compounds, divided into two groups (condensed and hydrolyzed). Condensed tannins are polymeric flavonoids. Hydrolyzed tannins include gallotannins, that are gallic acid polymers, and similar in structure esterified compounds [14]. These plant polyphenols are powerful antioxidants that protect against free radical damage and, as a result, reduce the risk of skin cancer and premature aging [15].
It is known that the consumption of white or red wine causes various effects. The reason for this is the differences in the quantity and quality of polyphenols in different varieties of grape wines. The bioavailability of phenolic compounds also plays a crucial role [18]. For example, data on the absorption and the kinetics of disproportion of quercetin indicate that a glass of red wine is a much poorer source of this compound than a cup of black tea and onions [37].
It should be taken into account that excessive consumption of wine has a toxic effect on the body. Using concentrated preparations of natural polyphenol complex of grape wine can be promising, as it will allow to obtaining the required useful dose of phenolic compounds and reduce wine consumption.
Today, a large number of methods to obtain a concentrate of phenolic compounds of grape wine have been developed. The technique of lyophilization, which consists in drying polyphenolic compounds in a vacuum with pre-freezing of wine, is most often uses in the industry. The method of isolating polyphenols through a column and their subsequent drying by spraying is quite common. Although these methods prevent the loss of phenolic compounds, however, the obtained dry preparations are poorly soluble in water, which reduces their value [38]. To obtain a polyphenol concentrate, we chose the method of evaporation of dry red grape wine, in the optimal conditions for the preservation of polyphenolic compounds present in the raw material. Obtained concentrate contained also monomeric polyphenols, which were found in wine [39].
The following substances were detected in the obtained concentrate: anthocyanins (malvidin, delphinidin, peonidin, petunidin, cyanidin), flavones (quercetin, quercitin-3-O-glycoside), flavan-3-ols ((+)-catechins, (−)-epicatechins), phenolic acids (gallic, caftaric, coutaric, syringic). This spectrum of polyphenols probably determines the antioxidant and antidiabetic properties of the obtained concentrate [40, 41].
Chronic hyperglycemia in diabetes mellitus causes chronic inflammation, which are accompanied by relapses and are difficult to treat. Diabetes mellitus causes damage, dysfunction, or insufficiency of various organs and systems, including eyes, kidneys, nervous system, heart, and blood vessels.
In recent years, there has been growing evidence that plant polyphenols, due to their biological properties, can be an unique dietary supplement and additional treatment for various aspects of diabetes. Natural polyphenols are potential multifunctional agents that reduce the risk of developing diabetes and diabetic complications [42]. Red wine polyphenols significantly increase the sensitivity of peripheral tissue cells to insulin in diabetes [25].
Decreased insulin secretion in diabetes is often combined with reduced sensitivity to this hormone in peripheral tissues. The lower sensitivity of tissues to insulin can be diagnosed using a glucose tolerance test. It allows to obtain information about the dynamics and degree of assimilation of carbohydrates and identify possible violations of this process [43, 44].
When administered polyphenol complex to animals with diabetes mellitus during 14 days, fasting blood glucose was 9.8 mmol/l (in control this index was 4.9 mmol/l). 15 min after
Hypoglycemic effects of polyphenolic compounds may be associated with inhibition of carbohydrate digestion. Polyphenols inhibit α-amylase and α-glucosidase activity, slowing glucose absorption in intestine, stimulate insulin secretion, and protect pancreatic β-cells against glucose toxicity. Polyphenols can inhibit the release of glucose by liver cells by affecting hepatic glucose homeostasis, in particular glycolysis, glycogenesis, and gluconeogenesis, which are impaired under diabetes mellitus. Polyphenols also activate insulin receptors or stimulate glucose uptake into insulin-sensitive tissues [46, 47, 48]. In addition, some polyphenols, including resveratrol and quercetin, contribute to the preservation of the integrity of pancreatic β-cells in rats with streptozotocin-induced diabetes against oxidative stress damage, thus help maintain normal insulin levels [48].
During carbohydrates metabolism glucose, fructose, or glucose-6-phosphate can non-enzymatically bound to proteins, including hemoglobin. This is a glycation reaction, the essence of which is the non-enzymatic addition of free aldehyde groups to free amino groups of proteins. Under hyperglycemia, excessive glycation is observed. The structure and function of glycated proteins change, which leads to cell damage and various diabetic complications [49, 50].
Glycated hemoglobin (HbA1c) reflects the average glucose level for the previous 2–3 months and is one of the reliable diagnostic criteria for diabetes [51]. Accordingly, this indicator has become one of the main standard methods for assessing the level of glycemia and the effectiveness of its correction, as well as the most important way of long-term metabolic control over the course of diabetes [52].
It was found that the content of glycated hemoglobin increases in the blood of rats with diabetes mellitus compared with control. In the condition of polyphenolic complex concentrate administration to animals with diabetes, we observed the normalization of glycated hemoglobin content [53]. The decrease in the level of glycated hemoglobin under the administration of polyphenolic complex to animals with diabetes mellitus indicates a stable long-term hypoglycemic effect of the studied concentrate.
Revealed properties to regulate glucose tolerance and reduce the level of glycated hemoglobin justify the possibility of using polyphenolic compounds of wine as a basis for the development of new adjuvant antidiabetic therapeutic agents or to prevent the development of diabetic complications.
Due to the peculiarities of the chemical structure, all phenols are able to neutralize the electron of free radicals and form relatively stable phenoxyl radicals and thus stop oxidative chain reactions in cells [24]. Polyphenols can scavenge ROS and RNS, lipoperoxide radicals, and can chelate metal ions such as iron and copper, which play an important role in initiating free radical reactions [15]. Thus, these compounds realize antioxidant and anti-inflammatory activity. There are data in the literature on the ability of some polyphenols to affect cellular signal transduction [30], to modulate the functioning of the endocrine system, and hence the action of hormones on various physiological processes, as these compounds react with metal ions and enzymatic cofactors [11].
It is noted that the obtained concentrate of natural polyphenol complex of red wine showed antioxidant properties, at the level of individual tissues and organs and at the level of the whole organism under low level irradiation and experimental diabetes mellitus [45, 53, 54, 55]. The use of polyphenolic complex concentrate helped to prevent the accumulation of lipoperoxidation products, which indicates the powerful antioxidant properties of polyphenolic components of red grape wine. Polyphenols react with ROS and convert them into products with much lower reactivity. It is believed that the most effective protection of the lipid bilayer is provided by more hydrophobic polyphenols. Epicatechin gallate has been shown to be soluble in the membrane lipid bilayer and is a highly effective protector under excessive lipid peroxidation [56, 57].
The level of ROS in the cell is controlled by the endogenous system of antioxidant protection. However, under pathological conditions, the production of ROS increases, and, at the same time, the mechanisms of antioxidant protection are disrupted [58, 59, 60]. Polyphenolic compounds cause a decrease of ROS level by normalizing the activities of antioxidant enzymes. The ability to affect the endogenous antioxidant system has a large number of phenolic compounds present in grape wine. In particular, flavan-3-ols, ((−) - epicatechins, (+) - catechins, gallates and products of their methylation, decarboxylation and dehydroxylation), quercetin, hydroxycinnamic acids (caftaric, coutaric and coumaric acids) activate transcription of genes of the enzymes.
It is known that red wine polyphenols increase the antioxidant capacity of plasma and other tissues of animals and humans. This effect is associated with the stimulation of the activity of superoxide dismutase, catalase and glutathione peroxidase and with an increase in the content of both reduced and oxidized glutathione [10, 14, 38, 61].
It was established a decrease of NOS total activity in peripheral blood, leukocytes, aorta and kidneys of rats after low doses irradiation on the background of polyphenolic complex concentrate consumption. The same effect was found in leukocytes, erythrocytes, pancreas and heart of rats with streptozotocin-induced diabetes mellitus [62]. It was detected a lowering in the total content of nitrites and nitrates in the case of X-ray irradiation in peripheral blood, leukocytes, aortic and renal tissues [40, 45, 63, 64, 65, 66]. Under conditions of streptozotocin-induced diabetes mellitus, it was observed a significant decrease in the content of nitrite and nitrate in leukocytes, in peritoneal macrophages and in pancreas in the case of polyphenol complex concentrate consumption.
It is known that polyphenolic compounds of grape wine have the ability to capture and neutralize NO and its metabolites. Due to this, polyphenols can also prevent the development of oxidative-nitrative stress.
Grape wine anthocyanins (malvidin, delphinidin, peonidin, petunidin and cyanidin) are potent antioxidant because they can affect NO content. One of the possible mechanisms of polyphenols influence on the level of NO is the regulation of the activity of NO synthases. It is known that phenolic compounds show diverse effects on the activity of various isoforms of the enzyme: they inhibit neuronal NOS (nNOS) and inducible NOS (iNOS) and increase the activity of endothelial NOS (eNOS). In blood cells has been detected inhibition of mRNA translation of iNOS, the synthesis of which is induced by lipopolysaccharides, interleukin-1 or tumor necrosis factor α (TNF-α) [28, 31]. Catechins scavenge NO and peroxynitrite, inhibit the activity of neuronal and inducible NOS by inhibiting the binding of nuclear factor NF-κβ to the NOS gene promoter. For example, catechins activate endothelial NOS in rats aorta by binding to the antioxidant response element (ARE) of the promoter of the eNOS gene [17, 19, 21, 28, 30, 31, 67].
This effect on NOS activity is offset by an increase in Ca2+ concentration due to release into the cytoplasm from intracellular depots or a receptor-dependent mechanism, the key event of which is an increase in guanylate cyclase activity in cells. As a result, the activity of eNOS increase, as this isoform of the enzyme is calcium-dependent [12]. A number of authors describe the ability of catechins, anthocyanins, quercetin, and other wine polyphenols to activate eNOS by phosphorylation mediated by activation of the Src/PI3′-kinase/Akt signaling pathway. This mechanism is dependent on the intracellular generation of ROS.
However, much more attention today is paid to the role of peroxynitrite (ONOO−). Peroxynitrite is a powerful prooxidant and cytotoxin, interacting with lipids, DNA and proteins in oxidation, nitration and nitrosylation reactions cause cell damage and cell death [68, 69, 70, 71, 72, 73].
Modern strategies aimed at limiting the formation of cytotoxins are the use of various herbal compounds with the ability to neutralize RNS
Our results open up prospects for the use of drugs, the main active ingredients of which are phenolic compounds, as adjuncts in complex therapy and prevention of damage to the blood system, cardiovascular and excretory systems caused by ionizing radiation. Drugs of complex action, which will inhibit the development of oxidative-nitrative stress, will be effective treatment of different diseases, including diabetes mellitus and radiation sickness.
Today there is an urgent need for effective drugs for the treatment of metabolic disorders, the etiological cause of which is a violation of the redox status of cells. A successful strategy for finding such substances is to search for them among agents of natural origin due to their lower generation of side effects and the availability in obtaining material.
One of the promising plant is yacon, which has been discovered antidiabetic and antioxidant properties [76].
Yacon (
Yacon is a perennial plant with underground tubers that are grouped in clump. Average tuber weight fluctuates from 100 to 500 g, and rarely reaches more than 1 kg [77]. Yacon root tubers have great nutritional potential due to its sweet taste and lower energy content (619–937 kJ/kg of fresh matter) provided by its 70% water composition [78].
The underground storage organs of yacon accumulate mainly low molecular mass oligomeric (GF2–GF16) inulin-type β(2 → 1) fructans (over 60% on a dry basis). The main
β(2 → 1) fructans of the inulin-type are considered to be dietary fiber or the indigestible residues of plant origin due to lack of enzymes in humans body capable to hydrolyze the β(2 → 1) bond in such compounds. Because FOS do not digest in the human gastrointestinal tract and they transported to the colon they recently been classified as prebiotics. In the colon they undergo fermentation into short-chain fatty acids (acetate, propionate, and butyrate), lactic acid, carbon dioxide, and hydrogen by selected species of gut microbiota, especially
FOS except as prebiotics can be used as non-specific immunostimulators. Mechanisms of such effect can be indirect by shifting the composition of the intestinal flora and enhanced production of immunoregulatory short-chain fatty acids. On the other hand, it was suggested that fructooligosaccharides can possess direct effects on the intestinal epithelial cells and immune cells through binding to carbohydrate receptors [82].
Other important biologically active substances in the composition of yacon root tubers are
The most abundant
From yacon tuber have been isolated 4′-hydroxyacetophenone, 4′-hydroxy-3′-(3-methylbutanoyl) acetophenone, 4′-hydroxy-3′-(3-methylbutenyl) acetophenone, and 5-acetyl-2-(1-hydroxy-1-methylethyl) benzofurane which are related antifungal
Also,
One group of compounds that can play an essential role in antioxidant and antidiabetic properties of yacon leaves is
Major unsaturated
Yacon leaves contain a wide range of
The possibilities of innovative technologies in the pharmaceutical industry make it possible to expand the range of search for effective natural substances as a form of additional or substitution therapy of different pathological conditions. Natural substances affect not only carbohydrates but also lipids metabolism, regulate water balance, and normalize the functional state of the kidneys and liver. Herbal preparations support the state of long-term compensation for diabetes mellitus. In folk medicine around the world for the treatment of diabetes, aqueous extracts of yacon are widely used.
One of the biochemical methods for diagnosing carbohydrate metabolism disorders, in particular, in diabetes mellitus, is a glucose tolerance test. This approach allows checking the dynamics and degree of glucose absorption in the body and identifying possible violations of this process. The rate of decrease in glucose levels after oral administration depends mainly on the function of the cells of the islets of Langerhans of the pancreas.
Glucose tolerance test is a convenient tool for analyzing not only changes in the efficiency of carbohydrate absorption but also can be a convenient tool for assessing the effectiveness of treatment aimed at reducing postprandial hyperglycemia. This approach is often used to assess the antidiabetic potential of medicinal plants.
A screening study showed that under conditions of glucose load in healthy animals, different parts of the aboveground part (leaves, petioles, stems) of yacon have different hypoglycemic effects. A comparative analysis of the hypoglycemic effect of aqueous extracts of the aboveground part of yacon showed that the highest and longest hypoglycemic effect after single oral administration possesses yacon leaves extract. It should be noted, that in control animals, the hypoglycemic effect was achieved at a dose of 0.07 g per kg of weight of the animal [96]. No such pronounced hypoglycemic effect was found while administering a similar dose of yacon leave extract to animals with experimental diabetes mellitus. However, increasing the dose of the extract to 0.5 g per kg of animal weight led to a significant improvement in the absorption of exogenous glucose by animals with experimental diabetes mellitus [97]. In addition to convincing data on the hypoglycemic effect of the aqueous extract of yacon leaves obtained by the glucose tolerance test, a pronounced hypoglycemic effect of this extract was also demonstrated when administered it to rats with diabetes for 14 days [98]. This study confirmed that an effective hypoglycemic effect has an aqueous extract of yacon leaves at a dose of 0.5 g per kg of body weight. When using the extract at this dose, a significant decrease in both plasma glucose and glycosylated hemoglobin was shown [98].
Some authors attribute the hypoglycemic effect of yacon leaves to the presence of a number of biologically active substances, among which polyphenols play an important role [77, 99]. Chlorogenic acid has been shown to inhibit the enzyme glucose-6-phosphatase, thus, affecting the metabolism of carbohydrates (glycolysis, glycogenolysis, and gluconeogenesis). Some studies have shown that polyphenols derived from aqueous extracts of yacon leaves inhibit alpha-amylase and sucrose. They also inhibit glucose transport through gastrointestinal cells by inhibiting the functioning of the sodium glucose co-transporter (S-GLUT-1) [86]. The yacon leaves contain enhydrin, which increases the number of β-cells and the level of insulin mRNA in the pancreatic islets of rats with streptozotocin-induced diabetes [90]. Enhydrin also inhibits α-glucosidase activity, a similar inhibitory effect possesses smallanthaditerpenic acids A, B, C, and D isolated, which are also contained in the leaves of yacon [89, 90].
The uniqueness of yacon as a source of biologically active substances for the treatment of diabetes is that their source can be not only the aboveground part of the plant but also the root tubers. A comparative analysis of the hypoglycemic effect of water extracts of yacon roots in healthy animals in a dose of 0.07 g per kg of weight of the animal suggests that a more pronounced hypoglycemic effect has an extract of yacon root tubers, while the extract of root tubers peels possess much less pronounce effect [96]. However, another study showed that a dose of 0.07 g per kg of body weight of water extract of root tubers is insufficient for hyperglycemia compensation. Only the use of the extract at a dose of 0.5 g per kg leads to significant changes in the dynamics of exogenous glucose uptake under conditions of streptozotocin-induced experimental diabetes mellitus [100]. An additional approach in the creation of drugs based on plant raw materials is their use in the form of suspensions. The advantages of this form of medicines include the production of medicines of prolonged action by regulation of duration of their action by changing in the size of medicinal raw materials particles, simultaneously usage of soluble and insoluble medicinal substances, allow mask unpleasant taste and smell of medicines. Suspensions prepared by mixing homogeneous powdered root tubers with water (at a dose of 0.5 g per kg) significantly affect the intensity of glucose uptake in animals with experimental diabetes mellitus. Interestingly, the use of surfactants to stabilize the physical properties of the suspension increases its hypoglycemic effect. Comparing all forms of yacon underground part administration, yacon root tubers when they are used in the form of stabilized suspension possesses the best hypoglycemic effect [100, 101]. Long-term use (within 14 days) of the extract and suspensions of yacon root tubers in diabetes has shown a pronounced hypoglycemic effect. The use of water extract in doses 0.07 and 0.5 g per kg of body weight causes a significant reduction of plasma glucose level. However, only the use of the extract in a higher dose caused a significant decrease in the level of glycosylated hemoglobin. Suspensions of yacon root tubers stabilized with surface-active substances of biogenic origin at fourteen days of use also caused a significant decrease in both glucose and glycosylated hemoglobin in diabetic animals. Non-stabilized form of the suspension had a less pronounced hypoglycemic effect. The authors attribute this to the fact that the addition of surfactants to the suspension increases its stability and bioavailability of biologically active substances [98].
The hypoglycemic effect of yacon root tubers is less studied. The sugar-lowering effect of this part of the plant may be due to presence in its composition a high FOS content that can change the kinetics of carbohydrates absorption. As mentioned above FOS do not decompose in the gastrointestinal tract, can absorb a great amount of exogenous glucose. High absorption ability of FOS interferes with glucose transportation into blood, which causes a decrease in the level of blood sugar after meals. The stable decrease in the level of glucose causes normalization of insulin production by pancreatic cells. Intestine microorganisms hydrolyze FOS into smaller fragments and free fructose. Short fragments of FOS molecules facilitate the transportation of glucose into the cell by inserting into the cell membrane [102]. FOS also modulates concentrations of GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1) - peptides that regulate insulin release after meals [103]. Some yacon root tubers’ hypoglycemic effect can be attributed to essential amino acid L-tryptophan. It is known that this amino acid normalizes tolerance to carbohydrates and elevates the insulin level. In hepatocytes, L-tryptophan increased activity of glucokinase, hexokinase, and glucose-6-phosphate dehydrogenase that are the key enzymes of the carbohydrate exchange [85].
Hypoglycemic effect of yacon leaves and root tubers is very valuable in the development of antidiabetic medicines in terms of counteracting the harmful effects of hyperglycemia as an etiological cause of chronic diabetic complications.
The advantages of yacon as a source for the creation of effective antidiabetic medicine is that it has a high content of antioxidant compounds. Extract of the yacon leaves possesses the free radical scavenging activity and inhibitory effects on lipid peroxidation in rat brain and liver [104, 105].
Red blood cells are one of the most suitable models for the investigation of the antioxidant effect of plant material. During their circulatory life span, erythrocytes are continuously exposed to glucose. The glucose concentration in the erythrocyte cytosol is close to that in the plasma because is ensured by passive transport through GLUT1 (insulin-independent glucose transporter) [108, 109].
Hyperglycemia induced generation of free radicals is a plausible contributing factor of lipid peroxidation the intensity of which is reliably evidenced by the level of thiobarbituric acid reactive substances (TBARS). Water extracts of
One of the mechanisms of this antioxidant effect of yacon leaves extract may be its effect on antioxidant enzymes of cells. Indeed, it was established that the administration of yacon extract to diabetic rats (at a dose of 0.07 and 0.5 g/kg) causes increased activity of SOD in a dose-dependent manner. Interestingly, the extract in a lower concentration caused a more pronounced increase in CAT activity compared to its higher dose [110]. An additional mechanism of the antioxidant effect of yacon is its ability to inhibit the synthesis of myeloperoxidase that can cause causes oxidative damage of proteins and DNA [111].
The antioxidant effect of leaves extract may be caused by the presence of phenolic compounds. Chlorogenic and caffeic acid effectively scavenge N2O3, organic free radicals, HOCl, O2•−, OH•, ONOO− and peroxyl radical. After the reaction of chlorogenic or caffeic acid with free radicals products that are formed rapidly broken down to the products which are unable to generate more free radicals. Thus, no other antioxidants are necessary for the reduction of such oxidation products [112]. Flavonoids by which leaves of yacon are rich in can reduce enhancement of transition metal oxidation by donating a H• to them, rendering them less prooxidative. In addition, flavones and some flavanones can preferentially bind metals at the 5-hydroxyl and 4-oxo groups [113].
In the condition of diabetes, yacon root tubers in the form of water extract or suspensions cause a significant reduction of TBARS and PCC levels. Water extract of root tuber at a dose of 0.5 g per kg body weight causes a remarkable increase in SOD, CAT, and glutathione peroxidase activities, while in 0.07 g per kg body weight dose its effect was less pronounced. In comparison with the water extract, the suspensions obtained from the powder of yacon root tubers caused a smaller increase in the activity of the antioxidant enzymes of erythrocytes. However, the surfactant-stabilized suspension had a slightly higher antioxidant potential compared to non-stabilized one [110].
The antioxidant potential of the root part of yacon may be due to the high content of FOS. It was confirmed the significant antioxidant activity of inulin [114]. The ability of FOS to enhance the absorption of copper can reduce the deficiency of this element under the conditions of diabetes and as a result, might be one of the reasons for increased SOD activity in diabetes animals that were treated with yacon root tuber extract and suspension [115]. Similar to the leaves, yacon root tubers contain a number of phenolic compounds that have a pronounced antioxidant effect. In addition, yacon roots contain tryptophan, an antioxidant compound that scavenged hydroxyl radicals [116].
Effect of leaves and root tubers on the state of prooxidant-antioxidant balance of red blood cells may predetermine yacon as a promising source of biologically active substances that can be used for treatment and prevention of chronic diseases involving oxidative stress, among which diabetes mellitus is present [110].
General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed.
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In the last century, knowledge of genetics and development of scientific tools have become powerful enough so that the effects of many DNA mutations could be critically studied. Coat color nomenclature varies according to countries and breed associations; in addition, many factors can modify the color of the coat, such as sun exposure, age, sex, and nutritional status of the animal. Nevertheless, horses are capable of producing only two pigments. Several genes have been indicated as putative to coat color modification, altering the basic color by dilution, redistribution, or lacking of pigments.",book:{id:"5405",slug:"trends-and-advances-in-veterinary-genetics",title:"Trends and Advances in Veterinary Genetics",fullTitle:"Trends and Advances in Veterinary Genetics"},signatures:"Adriana Pires Neves, Eduardo Brum Schwengber, Fabiola Freire\nAlbrecht, José Victor Isola and Liana de Salles van der Linden",authors:[{id:"188768",title:"Associate Prof.",name:"Adriana",middleName:null,surname:"Pires Neves",slug:"adriana-pires-neves",fullName:"Adriana Pires Neves"},{id:"188993",title:"Dr.",name:"Eduardo",middleName:null,surname:"Brun Schwengber",slug:"eduardo-brun-schwengber",fullName:"Eduardo Brun Schwengber"},{id:"188994",title:"Mrs.",name:"Fabiola",middleName:null,surname:"Freire Albrecht",slug:"fabiola-freire-albrecht",fullName:"Fabiola Freire Albrecht"},{id:"188996",title:"Ph.D. Student",name:"Liana",middleName:null,surname:"de Salles van der Linden",slug:"liana-de-salles-van-der-linden",fullName:"Liana de Salles van der Linden"},{id:"188997",title:"Mr.",name:"José Victor",middleName:null,surname:"Vieira Isola",slug:"jose-victor-vieira-isola",fullName:"José Victor Vieira Isola"}]},{id:"58461",doi:"10.5772/intechopen.72638",title:"Natural Compounds as an Alternative to Control Farm Diseases: Avian Coccidiosis",slug:"natural-compounds-as-an-alternative-to-control-farm-diseases-avian-coccidiosis",totalDownloads:2056,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Coccidiosis is one of the most aggressive and expensive parasite diseases in poultry industry worldwide. Currently, the most used control techniques are chemoprophylaxis and anticoccidial feed additives. Although there is a great variety of commercial anticoccidial drugs and vaccines in the market, there is also a significant resistance to use them in animals with human as final consumer. To date, none available product offers effective protection toward coccidiosis; however, the search for novel strategies to control this disease continues, and natural products have arisen as a potential way to cope with avian coccidiosis. In this chapter, we highlight recent advances in natural compounds, their anticoccidial properties, and mechanisms.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Mayra E. 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Here, we present some of the most recent studies about B. bovis and B. bigemina genomes where some proteins have been identified with potential to prevent infections by these parasites.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Juan Mosqueda, Diego Josimar Hernández-Silva and Mario\nHidalgo-Ruiz",authors:[{id:"220191",title:"Dr.",name:"Juan",middleName:null,surname:"Mosqueda",slug:"juan-mosqueda",fullName:"Juan Mosqueda"}]}],mostDownloadedChaptersLast30Days:[{id:"59305",title:"Avian Coccidiosis, New Strategies of Treatment",slug:"avian-coccidiosis-new-strategies-of-treatment",totalDownloads:3639,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The control of avian coccidiosis since the 1940s has been associated with the use of ionophores and chemical drugs. Recently, a significant interest in natural sources has developed due to the pressure to poultry industry to produce drug-free birds. Consequently, the search of products derived from plants and other natural sources has increased in the last years. Today, many commercial products containing essential oils, extracts, and other compounds are available. The use of these compounds of natural origin is related to an increased immune response, a body weight gain, destruction of oocyst, among other benefits. The main inconvenience of these products is the act on some species of Eimeria, but not all. This genetic variability found in the parasite makes the use of products difficult to control and treat coccidiosis. In this chapter, several proposals of treatment are presented based on the use of natural products, considering the new strategies of treatment with minimal consequences to birds.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Rosa Estela Quiroz-Castañeda",authors:[{id:"187735",title:"Dr.",name:"Rosa Estela",middleName:null,surname:"Quiroz Castañeda",slug:"rosa-estela-quiroz-castaneda",fullName:"Rosa Estela Quiroz Castañeda"}]},{id:"58604",title:"Genomics of Apicomplexa",slug:"genomics-of-apicomplexa",totalDownloads:1159,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Apicomplexa is a eukaryotic phylum of intracellular parasites with more than 6000 species. Some of these single-celled parasites are important pathogens of livestock. At present, 128 genomes of phylum Apicomplexa have been reported in the GenBank database, of which 17 genomes belong to five genera that are pathogens of farm animals: Babesia, Theileria, Eimeria, Neospora and Sarcocystis. These 17 genomes are Babesia bigemina (five chromosomes), Babesia divergens (514 contigs) and Babesia bovis (four chromosomes and one apicoplast); Theileria parva (four chromosomes and one apicoplast), Theileria annulata (four chromosomes), Theileria orientalis (four chromosomes and one apicoplast) and Theileria equi (four chromosomes and one apicoplast); Eimeria brunetti (24,647 contigs), Eimeria necatrix (4667 contigs), Eimeria tenella (12,727 contigs), Eimeria acervulina (4947 contigs), Eimeria maxima (4570 contigs), Eimeria mitis (65,610 contigs) and Eimeria praecox (53,359 contigs); Neospora caninum (14 chromosomes); and Sarcocystis neurona strains SN1 (2862 contigs) and SN3 (3191 contigs). The study of these genomes allows us to understand their mechanisms of pathogenicity and identify genes that encode proteins as a possible vaccine antigen.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Fernando Martínez-Ocampo",authors:[{id:"195818",title:"Dr.",name:"Fernando",middleName:null,surname:"Martinez",slug:"fernando-martinez",fullName:"Fernando Martinez"}]},{id:"59436",title:"Pathogenomics and Molecular Advances in Pathogen Identification",slug:"pathogenomics-and-molecular-advances-in-pathogen-identification",totalDownloads:1631,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Today exists a spread spectrum of tools to be used in pathogen identification. Traditional staining and microscopic methods as well as modern molecular methods are presented in this chapter. Pathogen identification is only the beginning to obtain information related to pathogenicity of the microorganism in the near future. Once the pathogen is identified, genome-sequencing methods will provide a significant amount of information that can be elucidated only through bioinformatics methods. In this point, pathogenomics is a powerful tool to identify potential virulence factors, pathogenicity islands, and many other genes that could be used as therapeutic targets or in vaccine development. In this chapter, we present an update of the molecular advances used to identify pathogens and to obtain information of their diversity. We also review the most recent studies on pathogenomics with a special attention on pathogens of veterinary importance.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Rosa Estela Quiroz-Castañeda",authors:[{id:"187735",title:"Dr.",name:"Rosa Estela",middleName:null,surname:"Quiroz Castañeda",slug:"rosa-estela-quiroz-castaneda",fullName:"Rosa Estela Quiroz Castañeda"}]},{id:"58730",title:"Metagenomics and Diagnosis of Zoonotic Diseases",slug:"metagenomics-and-diagnosis-of-zoonotic-diseases",totalDownloads:1774,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Zoonotic diseases represent a public health problem worldwide, since approximately 60% of human pathogens have a zoonotic origin. A variety of methodologies have been developed to diagnose zoonosis, including culture-dependent and immunological-based methods, which allow the identification of a huge range of pathogens. However, some of them are not detected easily with these approaches. Additionally, molecular tests have been developed, and they are designed to identify a single pathogen or mixtures of them. In this context, metagenomics comes as an alternative to get genome sequences of different microorganisms, which comprise a microbial community. Metagenomics have been used to characterize microbiomes and viromes, which are not cultivable under laboratory conditions. This methodology could be a powerful tool in the diagnosis of zoonotic diseases because it allows not only identification of genus and species, but also detection of some proteins in specific conditions on specific tissues, through structural and functional metagenomics, respectively.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Laura Inés Cuervo-Soto, Silvio Alejandro López-Pazos and Ramón\nAlberto Batista-García",authors:[{id:"201362",title:"Dr.",name:"Ramón Alberto",middleName:null,surname:"Batista-García",slug:"ramon-alberto-batista-garcia",fullName:"Ramón Alberto Batista-García"}]},{id:"58461",title:"Natural Compounds as an Alternative to Control Farm Diseases: Avian Coccidiosis",slug:"natural-compounds-as-an-alternative-to-control-farm-diseases-avian-coccidiosis",totalDownloads:2056,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Coccidiosis is one of the most aggressive and expensive parasite diseases in poultry industry worldwide. Currently, the most used control techniques are chemoprophylaxis and anticoccidial feed additives. Although there is a great variety of commercial anticoccidial drugs and vaccines in the market, there is also a significant resistance to use them in animals with human as final consumer. To date, none available product offers effective protection toward coccidiosis; however, the search for novel strategies to control this disease continues, and natural products have arisen as a potential way to cope with avian coccidiosis. In this chapter, we highlight recent advances in natural compounds, their anticoccidial properties, and mechanisms.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Mayra E. Cobaxin-Cárdenas",authors:[{id:"223051",title:"Dr.",name:"Mayra E.",middleName:null,surname:"Cobaxin-Cárdenas",slug:"mayra-e.-cobaxin-cardenas",fullName:"Mayra E. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81557",title:"Object Tracking Using Adapted Optical Flow",doi:"10.5772/intechopen.102863",signatures:"Ronaldo Ferreira, Joaquim José de Castro Ferreira and António José Ribeiro Neves",slug:"object-tracking-using-adapted-optical-flow",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Information Extraction and Object Tracking in Digital Video",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",subseries:{id:"24",title:"Computer Vision"}}},{id:"81558",title:"Thresholding Image Techniques for Plant Segmentation",doi:"10.5772/intechopen.104587",signatures:"Miguel Ángel Castillo-Martínez, Francisco Javier Gallegos-Funes, Blanca E. Carvajal-Gámez, Guillermo Urriolagoitia-Sosa and Alberto J. 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Science",value:19,count:5}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:3},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:1},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:302,paginationItems:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been in