\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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In many cases, models of given inverse problems can be linearized which allows the use of methods of linear algebra for their solutions. Effective tools of linear algebra in linear inverse problems are, in particular, generalized inverse matrices as one of the ways to represent (pseudo)solutions to singular (differential) matrix equations. Nowadays, the theory of generalized inverses is one of the hot topics of linear algebra in various aspects, such as elements of the ring, operators of Hilbert space, or matrices with real, complex, and quaternion entries. Matrices over quaternion algebra are also useful tools in a lot of applied inverse problems, among them in signal and color image processing, quantum physics, etc. In recent years, methods of simultaneous decompositions for tensors have been actively used in different inverse problems. In particular, a product singular value decomposition of a quaternion tensor triplet (higher-order PSVD) has various applications in digital watermarking technology. The main goals of this book are both to give the last achievements in various areas of linear algebra, such as generalized inverses and their applications in solving matrix equations and matrix minimization problems, decompositions of matrices and tensors, new developments in theories of quaternion matrices, and operators of Hilbert space, etc. It is also important to consider new applying models of inverse problems that can be linearized.
",isbn:"978-1-80355-223-1",printIsbn:"978-1-80355-222-4",pdfIsbn:"978-1-80355-224-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"778be380846c917e320eceaf5d7a5983",bookSignature:"Dr. Ivan Kyrchei",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11863.jpg",keywords:"Generalized Inverse Matrix, Singular Value Decomposition, Quaternion Matrix, Tenzor, Pseudoinverse Solution, Matrix Equation, Matrix Minimization Problem, Linear Operator Equation, Regularization Method, Tomographic Method, Iterative Reconstruction Method, Convolution",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 26th 2022",dateEndSecondStepPublish:"June 29th 2022",dateEndThirdStepPublish:"August 28th 2022",dateEndFourthStepPublish:"November 16th 2022",dateEndFifthStepPublish:"January 15th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A Leading Researcher of Pidstryhach Institute for Applied Problems in Mechanics and Mathematics of NAS, Ukraine. Dr. Kyrchei is an Editorial Board Member of the Journal ‘’Advances in Linear Algebra & Matrix Theory’’ and is a member of the International Linear Algebra Society.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"226980",title:"Dr.",name:"Ivan",middleName:null,surname:"Kyrchei",slug:"ivan-kyrchei",fullName:"Ivan Kyrchei",profilePictureURL:"https://mts.intechopen.com/storage/users/226980/images/system/226980.jpg",biography:'Ivan Kyrchei was born in 1964 in Lviv region, Ukraine. In 1992, he was awarded a Master of Science in Mathematics from Ivan Franko National University (Lviv, Ukraine). After that, he worked a high school teacher, studied in graduate school of Pidstryhach Institute for Applied Problems in Mechanics and Mathematics of NAS of Ukraine in Lviv and started his jobs in this institute in junior research positions. In 2008, he held a Doctor of Philosophy (Candidate of Science) degree from Taras Shevchenko National University of Kyiv in specialty of Algebra and the Theory of Numbers. His PhD thesis "Theory of the column and row determinants and inverse matrix over a skew field with involution" introduces and develops the theory of new column and row determinants for matrices with noncommutative entries. In 2021, he was awarded a Doctor of Physical and Mathematical Sciences degree from Institute of Mathematics of NAS of Ukraine in Kyiv. His habilitation ScD thesis " Generalized inverse matrices over the quaternion skew field and their applications" is devoted to generalized inverse matrices over the quaternion skew field, first of all to their determinantal representations, and their applications to solving quaternion matrix equations, some differential matrix equations, and problems of quaternion matrix minimizations and approximations. Now, he is working as the Leading Researcher of PIAPMM of NAS of Ukraine. In 2014, he held an academic degree of Senior Research Fellow (Algebra and the Theory of Numbers) from Ministry of Education and Science of Ukraine that is equivalent to Associate Professor. He obtained the award for significant achievements in the field of science from the Lviv Regional State Administration and Regional Council (2019, 2021). His research interests are mostly in Algebra, Linear Algebra and their Applications. He has more than 80 scientific publications, from them more than 60 are papers with the high science citation index that have been published in well-known professional scientific journals and editor\'s books. He serves also as Editorial Board Member and reviewer in several SCI-journals.',institutionString:"National Academy of Sciences of Ukraine",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Academy of Sciences of Ukraine",institutionURL:null,country:{name:"Ukraine"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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The wearable device market is currently having a worldwide profit of around $34 billion and is expected to reach above $50 billion by 2022 owing to wearables’ ease of use, flexibility, and convenience [4]. Real-time monitoring, operational efficiency, and fitness tracking are reported as main factors supporting the market growth of health wearable devices such as smart watches, smart glasses, and other wellness gadgets, with expected $12.1 billion world market by 2021 [5].
\nIn the past decade, the recent progress in developing wearable devices was more focused on monitoring physical parameters, such as motion, respiration rate, etc. [3, 6, 7]. Today, there is a great interest in evolving wearable sensors capable of detecting chemical markers relevant to the status of health. Different approaches have been applied by researchers to design and fabricate wearable biosensors for remote monitoring of metabolites and electrolytes in body fluids including tear, sweat, and saliva [3, 8, 9, 10]. A great example would be the development of small and reliable sensors that would allow continuous glucose monitoring in diabetic patients [11, 12]. Diabetes is a chronic disease that can significantly impact on quality of life and reduce life expectancy. However, diabetics can stay one step ahead of the disease by monitoring their blood glucose level to minimize the complication of the disease by proper administration of insulin. Currently, blood analysis is the gold standard method for measuring the level of glucose in patient’s blood. However, this technique cannot be applied without penetrating the skin, which can be painful and inconvenient, and requires user obedience. Therefore, current research focuses on the development of portable and wearable devices capable of continuous glucose sensing through noninvasive detection techniques.
\nA majority of the recent studies in this field have targeted the area of personalized medicine, endeavoring to develop miniaturized wearable devices featuring real-time glucose monitoring in diabetic patients [12, 13, 14, 15]. One great example is contact lens which is an ideal wearable device that can be worn for hours without any pain or discomfort [16]. Integration of glucose biosensors into contact lenses has recently been demonstrated by several research groups [9, 17, 18]. However, the level of glucose in tear fluid is very low (0.1–0.6 mM), requiring a high sensitivity of the sensor for picking up the signal from expected chemical reaction [3, 19]. Yao et al. [16] have fabricated a contact lens with integrated sensor for continuous tear glucose monitoring with wireless communication system over a distance of several centimeters. The sensor demonstrated a fast response of 20 s with a minimum detection of less than 0.01 mM glucose, which is 10–60 times lower than glucose level in human tear [16].
\nIn addition to glucose, lactate is an important metabolite in the human body, which gets converted into l-lactate under hypoxic condition [20]. l-Lactate levels in tear fluid is about 1–5 mmol L−1, which might increase significantly due to some heath conditions including ischemia, inadequate tissue oxygenation, stroke, and different types of cancer [21]. Thomas et al. [22] demonstrated an invasive detection of lactate in human tear by integrating an amperometric lactate sensor with Pt working (WE) and reference (RE) electrodes as well as a counter electrode (CE) as current drain, on a polymer-based contact lens, measuring lactate in situ in human tears without any need for physical sampling [22].
\nVery recently, Park et al. [17] reported a novel approach for fabricating fully transparent and stretchable smart contact lens capable of wirelessly monitoring the level of glucose in the tears of diabetic patients. Figure 1 shows the layout of fabricated devices made of glucose sensors, wireless circuit, and display pixel on soft and transparent contact lens substrate (Figure 1a and b). The circuit diagram of the device is illustrated in Figure 1a, with radio frequency antenna receiving signals from a transmitter and a rectifier converting the signals to DC (Figure 1a and c). A continuous network of ultralong Ag nanofibers was used as stretchable electrodes for the antenna and interconnects (Figure 1d). In the case of any change in the concentration of glucose in tear, the sensor resistance changes resulting in the light-emitting diode (LED) pixel turning on or off. The device was tested in vitro using a live rabbit, providing substantial finding for smart contact lenses as one of the promising wearable devices in healthcare system [17].
\n(a) (i) Schematic illustration and (ii) operation of the soft, smart contact lens and (iii) the circuit diagram of the smart contact lens system. The soft, smart contact lens is composed of (b) a hybrid substrate; (c) functional devices including rectifier, LED, and glucose sensor; and (d) a transparent, stretchable conductor for antenna and interconnects [
In addition to tear, sweat electrolyte concentrations and blood serum are related [2, 8]. As one of the most readily accessible human biofluids, a great deal of information about the human body and its physical performance could be obtained via monitoring sweat electrolyte concentrations [23, 24]. Several groups have reported the key biomarkers in human sweat (e.g., sodium level, pH change, lactate concentration) relevant to human health and well-being, for monitoring athletic performance during sporting activities [25]. Jia et al. fabricated a skin-worn tattoo-based sensor for real-time monitoring of lactate in human sweat, offering substantial benefits for biomedical as well as sport applications [25]. In another approach, Curto et al. [26] fabricated a wearable and flexible microfluidic platform capable of monitoring changes in the sweat pH in real time. Anastasova et al. [27] developed a flexible microfluidic device for real-time monitoring of metabolite such as lactate as well as electrolytes such as pH and sodium in human sweat. Recently, Gao et al. [28] developed a flexible and wearable device (Figure 2) made of arrays of sensors for real-time monitoring of heavy metals, such as Zn, Cu, and Hg in human sweat. The device fabrication method is presented in Figure 2a, showing the deposition and stripping steps on microelectrodes. The sensing mechanism was based on an electrochemical detection of targeted heavy metals through four microelectrodes, including Au and Bi working electrodes, Ag reference electrode, and an Au counter electrode (Figure 2b and c). The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application, via monitoring the level of some heavy metals in human sweat [28]. A balanced level of Zn is necessary in the human body as a low and high Zn concentration can lead to pneumonia and liver damages, respectively [29, 30]. High level of Cu in the human body can lead to several diseases including Wilson’s disease and heart, kidney, and liver failures as well as brain diseases [31, 32]. The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application [28].
\n(a) A schematic showing the concept of deposition and stripping on microelectrodes. (b) A schematic showing the composition of the microsensor array. (c) Optical image of a flexible sensor array interfacing with a flexible printed circuit connector [
Saliva, as a great diagnostic fluid, can be used in personal health devices for real-time monitoring of chemical markers including salivary lactate analysis [33]. Chai et al. developed a saliva nanosensor with a radio-frequency identification tag, integrated into dental implants for detecting cardiac biomarkers in saliva and predicting close heart attack in patients suffering from cardiovascular diseases [34]. In another approach, an instrumented mouthguard was designed and fabricated by Kim et al. [35] for measuring salivary uric acid levels which could be a biomarker for several diseases including hyperuricemia, gout, physical stress, and renal syndrome. The fabricated device showed high selectivity and sensitivity to low level of uric acid as well as great stability during a 4-h operation period [35]. Mannoor et al. [36] developed a hybrid biosensor made of graphene layers printed onto water-soluble silk, for noninvasive detection of bacteria through body fluids including sweat and saliva. This graphene/silk hybrid device illustrated an extremely high sensitivity to bacteria in body fluid with detection limits down to a single bacterium [36]. In addition, the fabricated device provided the potential users with battery-free operation and wireless communication system via radio frequency [36]. Arakawa et al. [37] designed and fabricated a salivary sensor equipped with a wireless measurement system, embedded onto a mouthguard support, featuring a high sensitivity toward detection of glucose over a range of 5–1000 μmol L−1. The device demonstrated a great stability during a 5-h real-time glucose monitoring period in an artificial saliva with a phantom jaw [37]. In a similar approach, de Castro et al. [38] developed a microfluidic paper-based device integrated into a mouthguard, for continues monitoring of glucose and nitrite in human saliva. The saliva samples were collected from periodontitis and/or diabetes patients as well as healthy individuals. The fabricated device featured a low detection limit of 27 and 7 μmol L−1 for glucose and nitrite, respectively [38].
\nIn summary, there is a great potential for micro- and nanosensors’ integration into healthcare monitoring devices, developing new technologies for noninvasive detection of diseases in the human body. Flexible wearable devices offer promising capabilities in real-time monitoring of body fluids including tear, sweat, and saliva. However, more research is required to expand the use of wearable platforms in continuous analysis of body fluids, providing reliable real-time detection of targeting ions and proteins, among other complex analytes.
\nOral cancer is a type of head and neck cancer (HNC), which encompasses a wide range of tumour types that arise from a variety of anatomic structures, including the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx. Squamous cell carcinomas (OSCCs) account for over 90% of these malignancies histopathologically, with over 50% occurring in the oral cavity [1]. Tobacco usage (smoked or chewed), arecanut, excessive alcohol use, and/or human papillomavirus (HPV) infection are the most major and well-established risk factors associated with this neoplasm [2, 3, 4].
Cancer is a major public health concern around the world. According to the International Agency for Research on Cancer’s GLOBOCAN project, there were approximately 14.1 million newly diagnosed cancer cases and 8.2 million deaths worldwide in 2012.Oral cancer is one of the most common cancers worldwide, accounting for 2% of all cancer cases and having a nearly 50% mortality rate [5]. Oral and pharyngeal tumours are the sixth most common cancer worldwide [6]. Internationally, South Asian countries such as Sri Lanka, India, and Taiwan have the highest rates of oral cancer, which can be attributed to high rates of cigarette smoking and areca nut use in these countries [7].
Despite technological advancements and improvements in OSCC diagnosis and treatment modalities, the 5-year survival rate remains low, hovering around 50–60%, ranging from 80% for stage I cancers to 40% for stage IV cancers. This disparity can be explained by the delay in diagnosis as well as the relatively high tumour recurrence rates found in these patients. In general, only one-third of OSCC patients have the disease in its early stages at the time of diagnosis (I and II) [8].
Treatment strategies for OSCC differ depending on the stage of the disease at the time of diagnosis. Patients with localised disease are typically treated with surgery and/or radiotherapy, which results in a high chance of long-term survival but significant morbidity. Chemotherapy and radiotherapy and recently immunotherapy are the mainstays of treatment for metastatic OSCC [9]. Despite advances in understanding the pathobiological mechanisms of OSCC, the prognosis has not improved over the last few decades. This is largely due to the high morbidity and mortality rates associated with local and regional OSCC recurrences. The clinical challenge remains in detecting regional metastasis accurately and efficiently treating second primary OSCC and recurrent tumours [10].
The practise of medicine is still primarily empirical today, with doctors relying on pattern matching to make diagnoses based on a patient’s medical history, physical examination, and test data. As a result, a prescribed treatment is frequently dependent on a physician’s previous experience with patients with comparable symptoms. As a result, the best drug may be given for a “typical patient” with a certain condition. The treatment decisions are made through trial and error, and patients may experience unforeseen adverse effects or poor or no efficacy for a medicine that theoretically works in some people with that disease [11].
Traditional therapeutic procedures have a poor prognosis and are associated with negative side effects. Immunotherapy adoption has moved the field of cancer treatment toward the concept of precision and personalised medicine (PPM), which tailors’ treatments to each individual. For cancer treatment, there are two options: the traditional approach and the PPM model. The fundamental distinctions between the classic cancer treatment approach and the developing precision and personalised medicine (PPM) concept are compared. Traditionally, cancer has been treated with “one-size-fits-all” treatments including chemotherapy, radiation, and surgical tumour removal. These treatments have a wide range of efficacy in different people, and they frequently destroy healthy, noncancerous organs and tissues. Individualised therapy customised to specific tissues, gene alterations, and personal characteristics relevant to each unique case of cancer characterise the PPM approach [12].
This article discusses the role of precision medicine in OC prevention, detection, and management by reviewing our understanding of OC from both genetic and OMICS perspectives.
Traditionally Surgery, Radiotherapy and chemotherapy have been used in the treatment of OC. Some people will only need one treatment, but most people will need a combination of medicines to combat cancer’s resistance. When there are solid tumours that have not metastasized and are in easily accessible places of the body, surgery can be utilised; nevertheless, many cancers do metastasis, necessitating more harsh therapies such as radiotherapy and chemotherapy. High doses of radiation and medicines are used in these methods to kill cancer cells and shrink tumours, but they often inflict additional damage to healthy cells [13]. It is stated that the given class of cancer medications is projected to be useless in up to 75% of patients The success of these treatments is influenced by a variety of factors, including the type, stage, and location of the cancer, as well as the patient’s age and overall condition. This shows that before choosing a cancer treatment, various personal aspects should be examined [14]. Over the last decade, it has been increasingly obvious that no two patients’ malignancies are exactly the same, and therefore generic treatments like chemotherapy and radiation may have varying outcomes. This standard cancer treatment strategy is extremely simple, resulting in ineffective, expensive treatments and unwanted side effects for patients [15]. It is well understood that a treatment’s response varies across the variability of a population, including good and poor responders. Variables such as genetic predisposition, cohort heterogeneity, ethnicity, slow vs. quick metabolizers, epigenetic factors, and early vs. late stage of disease affect patient and therapy response. These variables influence whether or not a person will respond well to a certain treatment [11].
Immunotherapy, which uses a patient’s own immune system to combat cancer, is another type of cancer treatment that has cleared the way for more specific and successful treatments. Monoclonal antibodies (mAbs), checkpoint inhibitors, cytokines, vaccinations, and adoptive cell transfer, most notably in the form of haematopoietic stem cell transplants (HSCTs) and chimeric antigen receptor (CAR) T-cell therapies, are examples of immunotherapy treatments [16]. Targeted therapeutics, such as cetuximab (monoclonal epidermal growth factor receptor [EGFR] antibody), bevacizumab (monoclonal vascular endothelial growth factor [VEGF] antibody), and mechanistic target of rapamycin (mTOR) inhibitors, have recently been introduced into treatment regimens or ongoing clinical trials to improve survival rate and reduce toxicity. With the advancement of immunotherapy, the Food and Drug Administration (FDA) has approved monoclonal antibodies that target programmed cell death protein-1 (PD-1), a receptor of the immune escape pathway, such as nivolumab and pembrolizumab, for recurrent and/or metastatic head and neck SCC [9]. Immunotherapy adoption has moved the field of cancer treatment toward the concept of personalised precision medicine (PPM), which tailors’ treatments to each individual.
The purpose of PPM is to allow doctors to forecast the best course of action for a patient promptly, effectively, and precisely. Clinicians will require tools that are both compatible with their clinical workflow and cost-effective in order to achieve this. These techniques can make managing the biological complexity that underpins human diseases a lot easier. A PPM ecosystem is under constant development to enable the creation and refining of such tools, and it is the solution to the problem. Precision medicine emphasises the need of combining established clinical indicators with molecular profiling to provide diagnostic, prognostic, and therapeutic techniques tailored to the individual needs of each patient group. For the optimal utilisation of the PM ecosystem, accurate data interpretation is required. The PM ecosystem brings together omics and clinical data to solve problems [11].
A move from empirical treatment to PPM is now possible thanks to increased usage of Biomarkers and companion diagnostics (CDX) (the right medicine, for the right patient, at the right dose, at the right time) [17]. PPM is a more effective model that is ready to disrupt the “one size fits all” approach. Based on the measurement and manipulation of essential patient genetic and omic data, this perspective promotes the creation of customised treatments for each individual subtype of cancer (transcriptomics, metabolomics, proteomics, etc.) [12].
Based on the definition provided by the National Cancer Institute, Personalised Precision Medicine, (PPM) is “an approach to patient care that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease.”
Patients with a cancer are enrolled randomly to prevent bias in traditional drug development, employing a “all comers” method with the assumption that the enrolled patients are nearly homogeneous. The purpose of random enrollment is to guarantee that the general population is well represented. In practise, we never conduct clinical trials on patients who are randomly chosen; instead, we apply various forms of enrichments to patients’ enrolment by using particular inclusion and exclusion criteria. Despite all of the efforts to enrich the community, the population that is ultimately chosen for the study can be quite diverse in terms of drug-metabolising capacity, environmental factors (e.g., nutrition, smoking habits, lifestyle, etc.), prior medication(s) exposure, and an individual’s genetic and epigenetic make-up are all factors to consider. BMs are being used to better define molecular, genetic, and environmental changes. Drug developers have been studying the epigenetic makeup of patients and attempting to take a more objective stance.
Patient stratification is used to distinguish between likely responders and non-responders. When compared to randomly selected individuals, prospective stratification can result in a smaller and shorter clinical study. At a bare minimum, stratification can expedite approval for medication candidates targeted at a subset of patients while providing room for additional testing and market development in the more heterogeneous patient group. In the best-case scenario, it can reveal an effective therapeutic agent that would otherwise be lost in the noise generated by non-responders, as was the case with trastuzumab and gefitinib. This will not only decrease the duration of the clinical trial but will also be cost effective [18].
Scientists were able to read and understand an individual’s genetic code, as well as detect hereditary predispositions to particular diseases, when the Human Genome Project (HGP) was completed. This watershed moment shifted the focus of health care from reactive to proactive. Scientists are currently striving to gain a detailed understanding of the body’s function at numerous omics levels, as well as characterise how environmental exposures alter genetic predispositions. When all of this data is combined, scientists and doctors will be able to better anticipate how patients will respond to a particular treatment. CDx assays patients for genetic features that determine whether or not they will respond to a specific medication. This technique has the potential to have a significant impact on the patient’s care. The transformation from a clinician choosing a generic medicine that is more or less experimental for the patient to one that effectively addresses the disease with PPM is the revolution [12].
Acquiring PPM data
Developing a PPM therapy
Predictive BM for immunotherapy differs from typical BM used for targeted therapies in the case of cancer immunotherapy. Because of the complexity of the tumour microenvironment (TME), immune response, and molecular profiling, a more holistic approach is required than using a single analyte BM [3]. To address this issue, researchers have developed a multiplexing strategy, in which numerous BMs are used to provide more precise patient stratification. Histological analysis now includes concomitant analysis of immuno-oncology BMs, such as PD-L1 and immune cell infiltrates (Figure 1), as well as more comprehensive immune and tumour-related pathways (Figure 2) (the “Cancer Immunogram”). Multiplexed immunoprofiling, which generates a comprehensive biomarker collection that may be associated with clinical parameters, is critical for the effectiveness of PM in cancer immunotherapy [21, 22].
Critical checkpoints for host and tumour profiling. A multiplexed biomarker approach is highly integrative and includes both tumour- and immune-related parameters assessed with both molecular and image-based methods for individualised prediction of immunotherapy response. Byassessing patient samples continuously one can collect a dynamic data on tissue-based parameters, such as immune cell infiltration and expressionof immune checkpoints, and pathology methods. These parameters are equally suited for data integration with molecular parameters. TILs: Tumour-infiltrating lymphocytes. PD-L1: Programmed cell death-ligand 1. Immunoscore: A prognostic tool for quantification of in situ immune cell infiltrates. Immunocompetence: body’s ability to produce a normal immune response following exposure to an antigen (tumour drawing has been adapted from [
The cancer immunogram. The schema depicts the seven parameters that characterise aspects of cancer-immune interactions for which biomarkers have been identified or are plausible. Italics represent those potential biomarkers for the different parameters (adapted from [
A specific gene or mutation must be linked to a clinical result before a PPM treatment can be created and utilised in patients. This is a significant endeavour; discovering a therapeutically relevant phenotype or polymorphism might take years of research involving many scientists. Furthermore, determining which polymorphisms cause patients to have a good or negative therapy response necessitates additional research. Sequencing DNA from a large number of people is the first step in deciphering the genetic code. This phase is becoming easier with the improvement of sequencing technologies. The most difficult issues are in interpreting these massive data sets, which is where bioinformatics comes in.
Without the enormous achievement of sequencing the human genome, the discipline of PPM would not exist. From 1990 until 2003, the HGP took 13 years to complete. The International Human Genome Sequencing Consortium (IHGSC), which includes over 200 collaborators from 19 nations, was tasked with discovering new knowledge regarding the structure and organisation of the genome. The human genome has around 20,500 genes, and any two persons share 99.99 percent of their genome, implying that genetic individuality can be identified only in the remaining 0.01 percent. Long repeat sequences were also discovered in the genome, and single-base changes (single nucleotide polymorphisms [SNPs]) were found to have the potential to be distinct disease indicators. The use of bacterial artificial chromosomes (BAC) and Sanger sequencing aided in the early data collection. BAC vectors helped with the first stage of genome sequencing by determining the chromosomal location of DNA fragments recovered from a sample. Sanger sequencing, on the other hand, allowed for exact base-by-base identification of a DNA fragment. These approaches were expensive and inefficient, despite their importance in early sequencing attempts [23]. Next Generation Sequencing Technologies (NGSTs)23 have evolved as a result of years of research and development to solve these difficulties. NGSTs are a cost-effective addition to the BAC and Sanger sequencing technologies, allowing for high-dimensional and parallel sequencing [24].
Whole-genome sequencing and whole-exome sequencing are examples of genomics-related technology. There are a variety of commercial technologies for detecting gene mutations, SNPs, and copy number changes. The Cancer Genome Atlas (TCGA) is a joint project of the National Cancer Institute (NCI) and the National Human Genome Research Institute that began in 2005. In thirty-three kinds of cancer, including head and neck SCC, the TCGA has created complete, multidimensional maps of important genetic alterations. Oral and oropharyngeal SCC has two different subgroups, according to thorough genetic profiling: HPV-negative cancers that commonly develop in the oral cavity and lips; and HPV negative cancers of the oral cavity and lips in particular. The molecular changes in these two subgroups of SCC correspond to their clinical behaviour and patient prognosis. The TCGA database demonstrated that the vast majority of HPV negative OSCCs have TP53 loss-of-function mutations and CDKN2A inactivation, which is consistent with previous findings. In addition, HPV negative OSCC showed a high amount of heterogeneity, according to integrated genomic analysis [25, 26]. Whole-exome sequencing, a transcriptomics approach for sequencing all of a genome’s expressed genes, revealed new mutations that had been missed in prior studies (known as the exome. NOTCH1 mutations were found in around 15% of the patients, while mutations and focal copies of NOTCH1 were found in about 15% of the cases. NOTCH1 mutations were found in about 15% of cases, and NOTCH2/3 mutations and localised copy-number changes were found in another 11% of OSCC cases [27, 28].
OSCC’s incredible diversity exemplifies how precision medicine may actually help patients and enhance medical care. The Pan Cancer Analysis of Whole Genomes project (PCAWG) is now steered to reveal noncoding driver mutations, such as alternative promoter usage, splicing, expression, editing, fusion, allele specific expression, and nonsynonymous variants, as it progresses from whole-exome sequencing to whole-genome sequencing [29]. MiRNAs and long noncoding RNAs (lncRNAs) are two types of noncoding transcripts. These noncoding transcripts, including miRNAs and long noncoding RNAs (lncRNAs), have a lot of potential for clinical research [30, 31].
While genomic data is crucial for establishing a full understanding of disease progression and therapeutic effects in physiological systems, intermediate omics levels such as the transcriptome, proteome, and metabolome are used to bridge the gap between genotypic effect and phenotypic event.
The transcriptome is the total mRNA within an individual or sample. Microarray and RNA sequencing (RNA-Seq) are two modern high-throughput sequencing approaches for collecting transcriptome data. Microarray analysis measures the amount of hybridization between a sample and corresponding probe to determine mRNA expression. The quantity of fluorescence seen within each well of the array corresponding to a given probe indicates the abundance of gene expression within a sample. Microarray analysis is constrained by the fact that designing probes requires prior knowledge of the gene’s sequence. This approach is similar to Sanger sequencing in that it determines the mRNA sequence by adding fluorescently tagged nucleotide bases one by one. During each loop, fluorescent pictures are recorded, and their analysis shows the exact sequence as well as its expression level. Microarray analysis takes less time to prepare samples than RNA-Seq, although RNA-Seq does not require prior knowledge of gene sequences and may handle fewer samples. Both technologies have tremendous throughput capacities, but microarray has a higher cost-value at the moment [32, 33].
Genomic profiling enables modern medication development, which often includes either microarray analysis or RNA-Seq for transcriptome profiling. Both microarray and RNA-Seq analyses allow for the identification of disease phenotype and medication effect within a system (single cell or bigger), which is crucial for the development of genome-specific therapeutics. Although RNA-Seq looks to be more advantageous for discovering novel genomic medication effects and disease characteristics, microarray analyses are less expensive and have more standardised techniques. In general, RNA-Seq results are better for clinical research since they have a lower signal-to-noise ratio than microarray results. Furthermore, as compared to microarray approaches, RNA-Seq results can be obtained from smaller sample quantities — nanogram versus microgram masses, respectively. As NGSTs become more widely used in clinical diagnostics, RNA-Seq methods are expected to become more standardised, eventually replacing microarray diagnostics [33, 34].
With transcriptomics technology, extensive attempts have been made to define OSCC at the molecular level. Reliable biomarkers are necessary to ease the prediction of clinical outcome and evaluate therapy efficacy in order to optimise therapeutic regimens for the management of OSCC. Dysregulation of several pathways (e.g., mRNA processing, cytoskeletal organisation, metabolic processes, cell cycle regulation, and apoptosis) was discovered when assessing a cohort of OSCC transcriptomes [35]. OSCC has also been recommended for molecular characterisation, similar to lung SCC [36]. Dysregulation of the KEAP1/ NFE2L2 oxidative stress pathway is one of the signalling pathways that has been impacted, SOX2 and TP63 lineage markers, as well as PIK3CA and EGFR mutations, were used differently. Different activation patterns of the EGFR pathway are linked to clinically diverse behaviours [37]. A molecular signature has also been proposed to help with OSCC treatment planning by predicting the existence of lymph node metastases using the primary tumour at the time of diagnosis [38]. Furthermore, microarray results demonstrated BGH3, MMP9, and PDIA3 upregulation in more than 80% of OSCC tumours, implying the relevance of ECM-cell receptor interactions in OSCC progression [39]. These transcriptional markers may be useful in the development of customised therapy regimens for the treatment of OSCC in the future.
The term “proteomics” refers to the process of identifying and cataloguing all proteins in a biological system, as well as their relationships. Protein structure, quantities, and cellular localizations, protein–protein interactions, and protein production and breakdown rates are all revealed by proteomic analysis. This data is utilised to figure out how the proteome changes throughout various biological activities and to spot disease patterns. Data on post-transcriptional alterations, or the quantity of proteins in a tissue, may be useful for illness diagnosis, progression, and treatment in the case of PPM. Mass spectrometry (MS) has been the primary instrument for gathering proteomic data for the past two decades, particularly to assess protein expression, identify protein modification sites, and analyse protein–protein interactions [40, 41].
The cellular abundance of proteins is primarily controlled by the quantity of translation, according to a landmark study published in 2011 that measured absolute mRNA and protein abundance and turnover using parallel metabolic pulse labelling [42]. Despite the fact that mRNA and protein levels are related to some extent, genome-wide protein abundance remains an important metric in determining cellular state and function. Intracellular and secreted proteins in body fluid specimens (e.g., serum, plasma, urine, and saliva) can be investigated using high-throughput total and phosphorylated protein analysis [43]. Alterations in protein expression in cell metabolism, adhesion, motility, and signal transduction have been discovered using proteomic analysis combined with in situ hybridization or immunohistochemistry [44, 45]. Promising results have been seen in studies. Outcomes of salivary or serum proteomics in identifying OSCC and normal samples Analyses with a sensitivity and specificity of up to 90% [46, 47].
The identification and analysis of metabolites, which are small-molecule intermediate products in metabolic reactions, is referred to as metabolomics. Because metabolites reflect both hereditary and environmental factors, a comprehensive metabolic examination is typically referred to as a “functional readout” of the current status of the organic system. The Human Metabolome Database (HMDB) is a freely accessible web resource that contains complete information on the human metabolome. The human metabolome is made up of peptides, lipids, amino acids, nucleic acids, carbohydrates, organic acids, biogenic amines, vitamins, minerals, and other tiny molecules found in the human body. The overall number of metabolites in HMDB 4.0 has increased dramatically from 40 153 in HMDB 3.0 to 114 100 in HMDB 4.0. This equates to approximately a fivefold increase [48].
In the context of PPM, metabolomic data could provide insight into an individual’s unique physical reaction to a medicine, a technique known as metabolomics [49]. Currently, metabolomic studies of biofluids and tissues have aided in the development of PPM methods by discovering illness biomarkers that have the potential to aid doctors in diagnosis and early treatment. Because metabolites, unlike most proteins, travel throughout the body and appear in easily accessible biofluids like blood and urine one of the primary clinical advantages of metabolomics is that measurements may be conducted noninvasively [50]. Nuclear magnetic resonance (NMR) spectroscopy was commonly employed to identify metabolites in the early days of metabolomics research, but over the last decade, there has been a big movement toward MS, which offers superior resolution and sensitivity to small concentrations [51, 52].
Metabolite profiling of tissue and body fluid specimens with the purpose of biomarker discovery in OSCC research has revealed significant changes in energy metabolism pathways, according to mass spectrometry-based metabolomics analysis (eg, glycolysis and tricarboxylic acid cycle) [53]. Glycolytic metabolites (e.g., glucose) had higher amounts in OSCC patients’ serum, while specific amino acids have lower levels (ie, valine, tyrosine, serine, and methionine) [54]. In OSCC tumour tissues, however, similar metabolite expression patterns are reversed, implying that this signature panel could be used as a screening tool. Early research, on the other hand, must be backed up with well-designed tests. Lipids have also been discovered as a significant class of metabolites, and abnormal cholesterol levels in the blood have been associated to a variety of cancers [55, 56, 57]. Total lipids, cholesterol, and high-density lipoprotein levels were shown to be considerably lower in OSCC patients compared to healthy controls [58, 59]. These lipidomic observations, albeit preliminary, may indicate greater usage of novel membrane synthesis by neoplastic cells and require further exploration.
These technologies will be collectively strong, with the potential to disclose molecular mechanisms and critical signalling pathways driving the disease, thanks to the rapid development of the omics tools outlined above. Furthermore, these tools have the potential to be utilised to identify new therapeutic targets as well as biomarkers that can be used to diagnose disease Cancer diagnosis, prognosis prediction, and treatment surveillance could all benefit from this technology.
The US FDA produced the first regulatory guideline document on CDx in 2014, and it was here that this type of assay was officially defined for the first time [60]. A CDx test is an in vitro diagnostic equipment that delivers information necessary for the safe and effective use of a related therapeutic product, according to this definition. This means that testing with this sort of assay is required and must be disclosed in both the medication and CDx assay labelling. CDx devices help clinicians provide the most effective, tailored medicines for their patients. In specific sections of DNA, relevant genetic information for defining malignancies can be identified (i.e., oncogenes). Some CDx are based on these specific oncogenes and can be used to evaluate whether or not a person will respond to a certain treatment in order to avoid sequencing the entire genome and obtaining superfluous information. Each CDx is linked to a certain medicinal treatment, which is linked to a particular genetic defect for which it is most effective [61]. Within the category of CDx products, there are a range of diagnostic procedures, each with its own role. Immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and real-time quantitative PCR (RT-qPCR) are examples of these techniques [62].
After collecting the OMICS data, storage and analysis also poses a great challenge. The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA; sponsored by the National Cancer Institute and the National Human Genome Research Institute) are two large databases for oncology data. The data gateway of the International Cancer Genome Centre (ICGC) focuses on 50 tumour types and defines them on genomic, transcriptomic, and epigenomic levels across genders, mutations, tumour stage, and other factors. The TCGA portal has thorough information on genetic alterations and gene expression in 11 different types of cancer tissues and 33 different cancer subtypes. On a large number of patients, analysis is performed on high-quality tumour samples and matched normal tissue samples [63, 64].
Despite the lifestyle habits of exposure to high risk factors for oral cancer with 80% attributable risk of tobacco per se, a small proportion of the tobacco habit develop persistent premalignant lesions, and 3–8% transform to the malignant phenotype. Genomic variants, somatic mutations and epigenetic regulation play a critical role in oral cancer. SNPs are the most common genomic variants. SNPs are single base changes in a gene’s exonic coding region or non-coding intronic regions that affect gene expression and function directly or indirectly in more than 1% of an ethnic population. SNPs in intronic regions may modify the three-dimensional structure of DNA, causing changes in molecular attributes such as Gibbs free energy aectLnJ stability, as well as impacting DNA polymerase activity and transcription factor activity. Binding SNPs can be found in one or both alleles, giving rise to heterozygous or homozygous genotypes. The wild-type (WT) allele is the ancestral allele, while the SNP allele is the changed allele. In a cancer case–control group, the frequency of allelotypes and genotypes differed, indicating a link between SNPs and cancer [65].
The connection of SNPs with risk propensity or susceptibility to oral cancer has been studied in several populations. In a meta-analysis research, the authors analysed SNPs in oral cancer and identified 34 SNPs in 30 genes that are strongly linked with oral cancer [66]. SNP rs1800471 in TGF- gene, with GC genotype associated with increased risk and GG genotype with lower risk in numerous studies and populations; SNP rs1048943 in CYP1A1 gene, with AG + GG genotypes resulting in increased risk and WT AA genotype resulting in decreased risk. The GSTM1 null genotype was linked to an elevated risk, while the WT genotype was linked to a lower risk. Similarly, heterozygous genotypes of SNPs rs1800870-AG in the IL-10 gene, rs11549467-GA in the HIF gene, and rs861539-CT in the XRCC3 genes were linked to an increased risk of oral cancer, while WT genotypes were linked to a lower risk. The WT genotypes rs1801133-CC in MTHFR and rs20417-GG in COX-2, on the other hand, were related with an increased risk, while the corresponding SNP homozygous genotypes TT and CC were associated with a decreased risk [67].
SNP analysis using high-throughput genomic analysis, as reported in genome-wide association studies (GWAS), and next-generation sequencing has emerged as a strong tool for identifying susceptibility loci, allowing information on thousands of SNPs to be obtained at the same time. These platforms often work with smaller samples and are more expensive, thus they must be confirmed in larger samples using alternative technology such as nucleotide sequencing and real-time PCR.SNPs investigated in various studies contribute to increased susceptibility to oral cancer, and a panel of SNPs could be used as Predictive Biomarkers to screen high-risk individuals who are prone to oral cancer due to tobacco use, providing an objective, unbiased test assay to assess oral cancer risk in individuals [66].
Establishing the link between biological data, disease, and clinical translation is a fundamental difficulty in PPM: how can we understand the data collected to make meaningful medical decisions? In the medical field, “Big Data” refers to a larger collection of medical data encompassing the tracking of various medical indicators and biomarkers across thousands of individuals (primarily clinical and omics data). Researchers may test tissues for thousands of molecular targets using high-throughput data gathering, effectively recording the response of a complex system over time.
The reconciliation of various omics components allows for the generation of prediction models of human physiology that may be employed in experimental design and clinical trial development in the field of systems biology [68].
Systems biologists and bioinformatic scientists use statistically significant trend detection approaches to link observations to biological events and phenotypes. Multivariate decomposition techniques, predictive modelling and optimization strategies, and other statistics-based tools are examples of these. Statistically understanding Big Data trends is a separate field that is required for predictive modelling, clinical decision-making, and assistance [69].
Drug discovery techniques for a number of PPM cancer products have been developed thanks to advances in omics technologies. Circulating tumour cells (CTC) and DNA detection approaches have promise not just for early diagnosis, but also for personalised patient risk monitoring and the development of effective personalised therapy. Several other cancer medicines in development take advantage of the immune system’s particular power and specialisation to fight cancer. This has been the focus of research for almost a century, and it has evolved into a distinct discipline known as immunoengineering. The ultimate goal of this profession is to tailor a more particular and potent immune response, which can lead to a powerful and effective personalised cancer treatment [70].
CTCs and circulating tumour DNA (ctDNA), two forms of oncological biomarkers, have emerged as the face of non-invasive cancer diagnosis using “liquid biopsy” procedures. Because research has shown that tumours release both types of biomarkers into the circulation early in cancer progression, there has been a lot of focus on their use in early detection and screening. CTCs and ctDNA are likely to become more effective in risk stratification, illness monitoring, and tailored treatment selection as research progresses and technology improves [71].
230 OSCC patients at various pathological stages of the disease and treatment modes were enrolled in a cross-sectional observational study. CTCs were obtained utilising the Onco Discover liquid biopsy method, which is based on immunomagnetic CTC enumeration and has been authorised by the Drug Controller General of India. The presence of CK18 and well-defined, DAPI-stained nuclei were found in CTCs. CTC were counted and then examined for stage, extracapsular spread (ECS), lymphovascular emboli (LVE), perineural invasion (PNI), and depth of invasion, among other clinicopathological criteria (DOI). To distinguish between early and advanced stages of dialysis, CTC cut off values were obtained. CTCs in OSCC patients were found to be associated with cancer stages (clinical and pathological) and aggressive pathological characteristics. We saw a 25–50 percent increase in CTC number when aggressive clinical characteristics were present, which frequently indicate a bad prognosis. Treatment-naive patients had a reduced number of CTCs in the early stages. The number of CTCs in advanced-stage OSCC patients was 50% greater than in early-stage OSCC patients. CTC might be considered a trustworthy measure to predict the disease outcome in oral cancer due to a positive connection of CTC number with numerous pathophysiological characteristics. The presence of CTC at all stages of the disease shows that OSCC is most likely a biologically systematic disease [72].
Patient-derived tumour organoids, which serve as in vitro tumour models and predictors of medication responses, are one strategy now under investigation for customised cancer treatment. In vitro cancer cell lines, patient-derived xenografts, and 3D culture models are all used in traditional cancer research and therapy. Due to the diversity and variability of the tumour microenvironment, these are restricted in their ability to precisely correlate an individual tumour’s response to a treatment. Organoids provide a more faithful depiction of this dynamic niche, and data suggests that the genetic and functional similarities between patient-derived tumour organoids and the real thing are striking [73].
Because of their low cytotoxicity, high specificity, and scalability, mAbs have proven particularly promising for cancer therapies among the numerous molecular-based approaches (e.g., small compounds, mAbs, and vaccines). mAbs are Y-shaped proteins that can attach to a specific molecular target and are created either synthetically or by B lymphocytes. mAbs are one of the most rapidly expanding immunotherapies, with over 22 FDA-approved mAb-based oncology medicines. mAb-based therapies, in contrast to standard therapies (e.g., surgery, radiation, and/or chemotherapy), are targeted to specific molecular markers expressed by a specific tumour, and so are more likely to be effective [74]. Typically, monoclonal antibodies (e.g., cetuximab) or synthetic small molecules are used to target cancer-specific cell receptors or intracellular signalling pathways (eg, gefinitib) in OC [9]. The tested drugs include, Cetuximab (Erbitux), pembrolizumab (Keytruda) and nivolumab (Opdivo).
Anti-EGFR monoclonal antibodies (mAbs) possess an antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and antitumor activity. Mice study has shown EMab-17(Anti-EGFR mAb) may be used as an antibody-based therapy for EGFR-expressing OSCC [75].
The creation of antibodies capable of blocking coinhibitory immune cell receptors, or “immune checkpoints” — T-cell surface receptors that, when activated by specific ligands, limit the T-cytotoxic cell’s immunological response — is a hopeful improvement in cancer treatment. Tumour cells tend to overexpress the ligands that activate these inhibitory receptors, allowing them to evade the immunological response of T cells and proliferate freely. Despite the fact that over two dozen individual costimulatory receptors have been identified, two of them — CTLA-4 and programmed cell death 1 (PD-1), have been the focus of antibody-based immune checkpoint blockade (ICB) treatments [76].
Most of the patients do not respond to immunotherapy especially the immune check point inhibitors (ICI). The traditional imaging methods only provide anatomic information and do not define the concrete representation of response or progression, especially pseudo-progression due to tumour infiltrating lymphocytes (TILs); and third, toxicities are a potential concern for the widespread use of immunotherapy, which is associated with an increased risk of cancer progression. As a result, a reliable and repeatable imaging approach is critical for identifying the patient group most or least likely to react to immunotherapy [77].
Molecular imaging, in combination with disease-specific imaging probes, can provide non-invasive, early, and dynamic information about the effects of immune cells or other cells in the tumour microenvironment (TME), as well as target expression and biodistribution of immunomodulatory drugs in the body, allowing clinicians to predict which patients will benefit most from immunotherapy. Furthermore, integrating immunotherapy with molecular imaging may improve cancer immunotherapy precision. Immunotherapies are classified into four major categories: Immune cell-based therapies, ICIs, tumour vaccines, and CAR-T cell therapy are all examples of this [78].
Figure 3 summarises the translation of PPM in to clinical practice.
Translation of PPM in to clinical practice.
This chapter has discussed the various aspects of PPM and the use of molecular and genetic profiling of tumours through omics technology for early diagnosis, formation of patient specific databases through next generation sequencing and tailored immunotherapy. Despite the advances in development technologies very few studies have been conducted in relation to OC and the research in this arena is in its budding stage. Future clinical trials on OC treatment should focus on translating the OMICs technology from bench to bedside with the use of biomarkers and CDx technologies. Tailored treatment therapies should be planned according to patients molecular and genetic profiling with consideration of individual factors. Pharma developers should create an effective medicine combining the traditional clinical data with a patient’s biological profile, which includes a variety of omics-based statistics. The databases can be used to gather knowledge about disease and aid in its development more precise, safer, and better-targeted medicines for a variety of diseases in patient population.
“The authors declare no conflict of interest.”
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\\n\\n\\n\\nWith the purpose of protecting our Authors' copyright and the transparent reuse of Open Access content, IntechOpen has developed an Attribution Policy for works published under Creative Commons licenses.
\\n\\n\\n\\nIntechOpen is committed to disseminating high-quality scientific research in a manner that exemplifies the best practice in scholarly publishing. IntechOpen is an official member of the Committee on Publication Ethics (COPE), which advocates the maintenance of the highest ethical standards for all parties involved in the act of publishing, including Authors, Academic Editors of the book, Peer Reviewers, the publisher and Societies, where applicable.
\\n\\nIn line with publication ethics practices recommended by COPE, ICMJE, and other similar organizations, IntechOpen's contributing Authors, Academic Editors, and Peer Reviewers are required to declare fully all possible conflicts of interest.
\\n\\n\\n\\nIntechOpen's Authorship Policy is based on ICMJE criteria for authorship. In order to be identified as an Author, the following requirements must be met:
\\n\\nAll scientific works are subject to Peer Review prior to publishing. IntechOpen is a member of the Committee on Publication Ethics (COPE) and all participating referees and Academic Editors are expected to review submitted scientific works in line with the COPE Ethical Guidelines for Peer Reviewers where applicable.
\\n\\n\\n\\nThe Internet has changed the dynamics of scholarly communication and publishing which is why we find it necessary to clearly indicate our stance on what we consider to be a published scientific work. A significant number of working papers, early drafts, and similar works in progress are shared openly online between members of the scientific community. It has become common practice for researchers to announce their work on a personal website or a blog in order to gather comments and suggestions from other researchers. Such works and online postings are ‘published’ in the sense that they are made publicly available, but this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\\n\\n\\n\\nTo identify instances of fraud and misconduct during the publishing process, IntechOpen implements a robust policy governing such occurrences. In line with our general commitment to openness, and in order to maintain the highest scientific standards, we are committed to transparency about our editorial policy regarding retractions and corrections.
\\n\\n\\n\\nWhen faced with potential misconduct, IntechOpen accepts its responsibility to maintain the integrity of the academic record. For particularly complex cases, IntechOpen might ask for the assistance of formal industry bodies or seek advice from an appropriate team of advisors.
\\n\\nIntechOpen's advisors are professionals and scholars with broad knowledge and understanding of different aspects of the scientific publishing process: editorial, authorship, and reviewing roles; publication ethics, copyright, and general legal issues; as well as bibliographic and technical standards.
\\n\\nIn order to provide us with unbiased insights, without compromising the privacy of third parties, IntechOpen presents problematic cases to its advisors in an anonymized format.
\\n\\nIntechOpen publishes books in the English language. If you are interested in the translation of Book Chapters, please check IntechOpen's Translation Policy.
\\n\\n\\n\\nIn line with the Principles of Transparency and Best Practice in Scholarly Publishing, you can access a more detailed description of IntechOpen's Advertising Policy.
\\n\\n\\n\\nAt IntechOpen we realize that exceptional circumstances can occur, resulting in a request for a refund. We will honor all justified requests in the specific instances outlined in our Refund Policy.
\\n\\n\\n\\nAll chapters will be published via IntechOpen's 'Online First' service meaning chapters will be published individually, immediately after review and before the entire book is ready for publication, allowing content to be shared, searched and cited straightaway, thereby generating early stage interest and momentum for your research
\\n\\nOnline First Chapters are considered published on the day they are posted and are citable from that date.
\\n\\nChapters will remain listed as Online First until the final versions of the books are published online. Following publication of the full monograph, Chapters will be redirected from the Online First version and will be available only through the final link of the official published page.
\\n\\nYou are invited to download, use, reproduce, make derivative works of, display, distribute and cite the Online First works. You can find "How to Cite and Reference" by following the link at the end of each online book chapter. Please be aware that it is possible that further editing and changes might be made before the final release of the book.
\\n\\nIf there are supplemental materials to the chapter, these will be published at the time the final book is published online.
\\n\\nReaders and Authors can notify us if they find any errors in the works published under Online First. All major errors will be accompanied by a separate correction notice, erratum or corrigendum (Retraction and Correction Policy.)
\\n\\nIntechOpen books are available online by accessing all published content on a chapter level.
\\n\\n\\n\\nIntechOpen publishes different types of publications.
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
\n\n\n\nWith the purpose of protecting our Authors' copyright and the transparent reuse of Open Access content, IntechOpen has developed an Attribution Policy for works published under Creative Commons licenses.
\n\n\n\nIntechOpen is committed to disseminating high-quality scientific research in a manner that exemplifies the best practice in scholarly publishing. IntechOpen is an official member of the Committee on Publication Ethics (COPE), which advocates the maintenance of the highest ethical standards for all parties involved in the act of publishing, including Authors, Academic Editors of the book, Peer Reviewers, the publisher and Societies, where applicable.
\n\nIn line with publication ethics practices recommended by COPE, ICMJE, and other similar organizations, IntechOpen's contributing Authors, Academic Editors, and Peer Reviewers are required to declare fully all possible conflicts of interest.
\n\n\n\nIntechOpen's Authorship Policy is based on ICMJE criteria for authorship. In order to be identified as an Author, the following requirements must be met:
\n\nAll scientific works are subject to Peer Review prior to publishing. IntechOpen is a member of the Committee on Publication Ethics (COPE) and all participating referees and Academic Editors are expected to review submitted scientific works in line with the COPE Ethical Guidelines for Peer Reviewers where applicable.
\n\n\n\nThe Internet has changed the dynamics of scholarly communication and publishing which is why we find it necessary to clearly indicate our stance on what we consider to be a published scientific work. A significant number of working papers, early drafts, and similar works in progress are shared openly online between members of the scientific community. It has become common practice for researchers to announce their work on a personal website or a blog in order to gather comments and suggestions from other researchers. Such works and online postings are ‘published’ in the sense that they are made publicly available, but this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\n\n\n\nTo identify instances of fraud and misconduct during the publishing process, IntechOpen implements a robust policy governing such occurrences. In line with our general commitment to openness, and in order to maintain the highest scientific standards, we are committed to transparency about our editorial policy regarding retractions and corrections.
\n\n\n\nWhen faced with potential misconduct, IntechOpen accepts its responsibility to maintain the integrity of the academic record. For particularly complex cases, IntechOpen might ask for the assistance of formal industry bodies or seek advice from an appropriate team of advisors.
\n\nIntechOpen's advisors are professionals and scholars with broad knowledge and understanding of different aspects of the scientific publishing process: editorial, authorship, and reviewing roles; publication ethics, copyright, and general legal issues; as well as bibliographic and technical standards.
\n\nIn order to provide us with unbiased insights, without compromising the privacy of third parties, IntechOpen presents problematic cases to its advisors in an anonymized format.
\n\nIntechOpen publishes books in the English language. If you are interested in the translation of Book Chapters, please check IntechOpen's Translation Policy.
\n\n\n\nIn line with the Principles of Transparency and Best Practice in Scholarly Publishing, you can access a more detailed description of IntechOpen's Advertising Policy.
\n\n\n\nAt IntechOpen we realize that exceptional circumstances can occur, resulting in a request for a refund. We will honor all justified requests in the specific instances outlined in our Refund Policy.
\n\n\n\nAll chapters will be published via IntechOpen's 'Online First' service meaning chapters will be published individually, immediately after review and before the entire book is ready for publication, allowing content to be shared, searched and cited straightaway, thereby generating early stage interest and momentum for your research
\n\nOnline First Chapters are considered published on the day they are posted and are citable from that date.
\n\nChapters will remain listed as Online First until the final versions of the books are published online. Following publication of the full monograph, Chapters will be redirected from the Online First version and will be available only through the final link of the official published page.
\n\nYou are invited to download, use, reproduce, make derivative works of, display, distribute and cite the Online First works. You can find "How to Cite and Reference" by following the link at the end of each online book chapter. Please be aware that it is possible that further editing and changes might be made before the final release of the book.
\n\nIf there are supplemental materials to the chapter, these will be published at the time the final book is published online.
\n\nReaders and Authors can notify us if they find any errors in the works published under Online First. All major errors will be accompanied by a separate correction notice, erratum or corrigendum (Retraction and Correction Policy.)
\n\nIntechOpen books are available online by accessing all published content on a chapter level.
\n\n\n\nIntechOpen publishes different types of publications.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Miller, Hayley Wright, Josie Hough and Francesco P.\nCappuccio",authors:[{id:"77507",title:"Dr.",name:"Michelle A",middleName:null,surname:"Miller",slug:"michelle-a-miller",fullName:"Michelle A Miller"}]},{id:"32269",doi:"10.5772/32991",title:"Epidemiology of Insomnia: Prevalence and Risk Factors",slug:"epidemiology-of-insomnia-prevalence-and-risk-factors",totalDownloads:4726,totalCrossrefCites:5,totalDimensionsCites:12,abstract:null,book:{id:"711",slug:"can-t-sleep-issues-of-being-an-insomniac",title:"Can't Sleep? Issues of Being an Insomniac",fullTitle:"Can't Sleep? Issues of Being an Insomniac"},signatures:"Claudia de Souza Lopes, Jaqueline Rodrigues Robaina and Lúcia Rotenberg",authors:[{id:"93493",title:"Prof.",name:"Claudia",middleName:null,surname:"Lopes",slug:"claudia-lopes",fullName:"Claudia Lopes"},{id:"95778",title:"Dr.",name:"Jaqueline",middleName:null,surname:"Robaina",slug:"jaqueline-robaina",fullName:"Jaqueline Robaina"},{id:"95790",title:"Dr.",name:"Lúcia",middleName:null,surname:"Rotenberg",slug:"lucia-rotenberg",fullName:"Lúcia Rotenberg"}]},{id:"32149",doi:"10.5772/29364",title:"Sleep and Pregnancy: Sleep Deprivation, Sleep Disturbed Breathing and Sleep Disorders in Pregnancy",slug:"sleep-and-pregnancy-sleep-deprivation-sleep-disturbed-breathing-and-sleep-disorders-in-pregnancy",totalDownloads:4026,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"993",slug:"sleep-disorders",title:"Sleep Disorders",fullTitle:"Sleep Disorders"},signatures:"Michelle A. Miller, Manisha Ahuja and Francesco P. Cappuccio",authors:[{id:"77507",title:"Dr.",name:"Michelle A",middleName:null,surname:"Miller",slug:"michelle-a-miller",fullName:"Michelle A Miller"},{id:"119883",title:"Ms.",name:"Manisha",middleName:null,surname:"Ahuja",slug:"manisha-ahuja",fullName:"Manisha Ahuja"},{id:"119885",title:"Prof.",name:"Francesco P",middleName:null,surname:"Cappuccio",slug:"francesco-p-cappuccio",fullName:"Francesco P Cappuccio"}]},{id:"65707",doi:"10.5772/intechopen.82754",title:"Sleep Physiology and Polysomnogram, Physiopathology and Symptomatology in Sleep Medicine",slug:"sleep-physiology-and-polysomnogram-physiopathology-and-symptomatology-in-sleep-medicine",totalDownloads:1252,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Over recent years, the importance of sleep physiology and pathology has been better understood in terms of correct diagnosis, treatment, prognosis and innovative research of diseases. Sleep disorders are often confused with clinical symptoms of adult and pediatric medical conditions. In medicine, electrophysiological signal recording methods are very important for establishing a correct diagnosis especially in neurological sciences. Polysomnography (PSG) is a golden standard diagnostic method that records electrophysiological signals used for sleep physiology and diseases. When the medical disciplines and diseases that make use of this diagnostic method are considered, its significance becomes clearer. For example, medical disciplines benefiting from PSG are as follows: “Clinical Physiology, Neurology, Ear Nose and Throat, Dentistry, Psychiatry, Pulmonology, Cardiology, Pediatric Neurology, Pediatric Cardiology, Internal Medicine, Neurosurgery, Endocrinology, etc.” The patient groups diagnosed with PSG are as follows: “Sleep Disordered Breathing (Central Sleep Apnea Syndrome, Obstructive Sleep Apnea Syndrome), Obesity, Morbid Obesity, REM Behavior Disorder, Restless Leg Syndrome, Rhythm Disorders, Epileptic Disorders, Insomnia, Insomnia and Headache, Hypersomnia, Narcolepsy, Secondary Hypertension, etc.” Interpretation and understanding electrophysiological signals correctly show us interactions of body systems with sleep physiology and integrated therapeutic approaches to sleep disorders. In conclusion; new approaches to sleep pathophysiology depend on a better understanding and further advancement of polysomnography.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Murat Kayabekir",authors:[{id:"265598",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Kayabekir",slug:"murat-kayabekir",fullName:"Murat Kayabekir"}]},{id:"32154",doi:"10.5772/33523",title:"Upper Airway Resistance Syndrome - A Twenty-Five Years Experience",slug:"upper-airway-resistance-syndrome-a-twenty-five-years-experience",totalDownloads:5062,totalCrossrefCites:2,totalDimensionsCites:3,abstract:null,book:{id:"993",slug:"sleep-disorders",title:"Sleep Disorders",fullTitle:"Sleep Disorders"},signatures:"Felix del Campo Matías, Tomas Ruiz Albi and Carlos Zamarrón Sanz",authors:[{id:"94382",title:"Prof.",name:"Felix",middleName:null,surname:"Del Campo",slug:"felix-del-campo",fullName:"Felix Del Campo"},{id:"95981",title:"Prof.",name:"Carlos",middleName:null,surname:"Zamarrón Sanz",slug:"carlos-zamarron-sanz",fullName:"Carlos Zamarrón Sanz"},{id:"95982",title:"Dr.",name:"Tomas",middleName:null,surname:"Ruiz Albi",slug:"tomas-ruiz-albi",fullName:"Tomas Ruiz Albi"}]}],mostDownloadedChaptersLast30Days:[{id:"65707",title:"Sleep Physiology and Polysomnogram, Physiopathology and Symptomatology in Sleep Medicine",slug:"sleep-physiology-and-polysomnogram-physiopathology-and-symptomatology-in-sleep-medicine",totalDownloads:1252,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Over recent years, the importance of sleep physiology and pathology has been better understood in terms of correct diagnosis, treatment, prognosis and innovative research of diseases. Sleep disorders are often confused with clinical symptoms of adult and pediatric medical conditions. In medicine, electrophysiological signal recording methods are very important for establishing a correct diagnosis especially in neurological sciences. Polysomnography (PSG) is a golden standard diagnostic method that records electrophysiological signals used for sleep physiology and diseases. When the medical disciplines and diseases that make use of this diagnostic method are considered, its significance becomes clearer. For example, medical disciplines benefiting from PSG are as follows: “Clinical Physiology, Neurology, Ear Nose and Throat, Dentistry, Psychiatry, Pulmonology, Cardiology, Pediatric Neurology, Pediatric Cardiology, Internal Medicine, Neurosurgery, Endocrinology, etc.” The patient groups diagnosed with PSG are as follows: “Sleep Disordered Breathing (Central Sleep Apnea Syndrome, Obstructive Sleep Apnea Syndrome), Obesity, Morbid Obesity, REM Behavior Disorder, Restless Leg Syndrome, Rhythm Disorders, Epileptic Disorders, Insomnia, Insomnia and Headache, Hypersomnia, Narcolepsy, Secondary Hypertension, etc.” Interpretation and understanding electrophysiological signals correctly show us interactions of body systems with sleep physiology and integrated therapeutic approaches to sleep disorders. In conclusion; new approaches to sleep pathophysiology depend on a better understanding and further advancement of polysomnography.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Murat Kayabekir",authors:[{id:"265598",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Kayabekir",slug:"murat-kayabekir",fullName:"Murat Kayabekir"}]},{id:"67469",title:"Sleep Disorder at High Altitude",slug:"sleep-disorder-at-high-altitude",totalDownloads:836,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"In this chapter, we discuss the occurrence, mechanism, clinical manifestations, outcomes, and managements of a commonly encountered sleep disorder of someone traveling in high altitude for working and sight-seeing. Humans ascending to altitudes above 2500 m usually suffer from substantial disturbances in sleep quality as difficulty in sleep onset, frequent awakenings, respiratory disturbance, and a feeling of drowsiness on the next day. Data obtained from polysomnographic studies demonstrated several variations of sleep architecture in those healthy subjects ascending to high altitude during sleep, including periodic breathing and decreased non-rapid eye movement deep sleep stage 3 and 4 (in new nomenclature N3), which were usually accompanied by and the lowered arterial O2 and restricted ventilation. Hypoxia is most severe during sleep and in correspondence to periodic breathing and sleep disturbance at high altitude. Poor sleep quality impairs cognition and executive abilities at high altitude though it may largely be improved after full time of acclimatization. Evidence-based choices for clinicians to treat sleep disorder at high altitude are relatively scarce at present. Supplemental oxygen and dietary nitrate are effective in alleviating nocturnal hypoxia. There is strong evidence supporting the efficacy and safety of acetazolamide and nonbenzodiazepines in minimizing periodic breathing and improving sleep quality at high altitude.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Fanyi Kong",authors:[{id:"285948",title:"Dr.",name:"Fanyi",middleName:null,surname:"Kong",slug:"fanyi-kong",fullName:"Fanyi Kong"}]},{id:"64983",title:"Cognitive Impairment and Obstructive Sleep Apnea",slug:"cognitive-impairment-and-obstructive-sleep-apnea",totalDownloads:1375,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Obstructive sleep apnea (OSA) is a frequent sleep disorder characterized by repetitive interruption of ventilation caused by partial or complete collapse of the upper airway during sleep. OSA is highly prevalent in the world and it has been associated with cardiovascular disease and cognitive impairment in children and adults. The cognitive impairment in individuals with OSA includes deficiencies in attention and constructional abilities, delayed long-term visual and verbal memory, and executive functions. Although, the pathogenesis of cognitive impairment in patients with OSA is complex and remains incompletely understood, several mechanisms, such as hypoxia, inflammation and sleep fragmentation have been proposed. The aim of this chapter is to describe some findings reported in the literature to explain the association between OSA and cognitive impairment.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Liliana Otero, María del Carmen Figueredo, Alain Riveros-Rivera and Patricia Hidalgo",authors:[{id:"273415",title:"Ph.D.",name:"Liliana",middleName:null,surname:"Otero",slug:"liliana-otero",fullName:"Liliana Otero"},{id:"280824",title:"Dr.",name:"Carmen",middleName:null,surname:"Figueredo",slug:"carmen-figueredo",fullName:"Carmen Figueredo"},{id:"283338",title:"Dr.",name:"Alain",middleName:null,surname:"Riveros",slug:"alain-riveros",fullName:"Alain Riveros"},{id:"283339",title:"Dr.",name:"Patricia",middleName:null,surname:"Hidalgo-Martinez",slug:"patricia-hidalgo-martinez",fullName:"Patricia Hidalgo-Martinez"}]},{id:"71574",title:"Surgical Treatment Options for Obstructive Sleep Apnea",slug:"surgical-treatment-options-for-obstructive-sleep-apnea",totalDownloads:774,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Given the increased prevalence of obstructive sleep apnea (OSA) multiple treatment modalities including medical and surgical have been developed. First-line therapy for most of the people with obstructive sleep apnea (OSA) consists of behavioral modification, including weight loss if appropriate, and positive airway pressure (PAP) therapy. Patients who fail or do not tolerate PAP therapy, treatment options include oral appliances and surgical therapy. Surgical therapies have variable efficacy and are very important tool on OSA management in selected patients. This chapter will review the current surgical approaches sleep specialists use when other treatment options fail to accomplish the valuable outcome.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Jimmy Hanna and Anthony Izzo",authors:[{id:"266405",title:"Dr.",name:"Anthony",middleName:null,surname:"Izzo",slug:"anthony-izzo",fullName:"Anthony Izzo"},{id:"312960",title:"Dr.",name:"Jimmy",middleName:null,surname:"Hanna",slug:"jimmy-hanna",fullName:"Jimmy Hanna"}]},{id:"46441",title:"Swallowing, Gastroesophageal Reflux and Sleep Apnea",slug:"swallowing-gastroesophageal-reflux-and-sleep-apnea",totalDownloads:2399,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"3798",slug:"sleep-and-its-disorders-affect-society",title:"Sleep and its Disorders Affect Society",fullTitle:"Sleep and its Disorders Affect Society"},signatures:"Shinji Teramoto",authors:[{id:"94615",title:"Dr.",name:"Shinji",middleName:null,surname:"Teramoto",slug:"shinji-teramoto",fullName:"Shinji Teramoto"}]}],onlineFirstChaptersFilter:{topicId:"201",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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