\\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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Although this technique is invented more than 150 years ago, its applications are continuously very relevant and applicable for nowadays fast-growing technology. As the previous book titled "Multiplexing" published in September 2019 has been a great success and received great attention from all over the world, and more than 3200 scientists have downloaded the book, we decided to have another book with a similar approach. Here in this book, we will aim to target the most recent and relevant applications and advancements of the Multiplexing technique, from all disciplines, including Wireless Telecommunications, Internet of Things (IoT), Smart Cities, Computing and Computer Science, Machine Learning and Artificial Intelligence, COVID-19.
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Dr. Mohammady’s research interests include digital signal processing (DSP), power efficiency improvement algorithms in wireless telecommunication systems, physical layer security improvement, bandpass filter design using optimization algorithms, the Internet of Things (IoT), robotics and programmable logic control (PLC) automation systems.\nHer hobbies include illustrating, yoga, and swimming. She is skilled in communications, Arduino and Allen-Bradley automation equipment. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Also, DS individuals have a significantly higher prevalence of some oral diseases, including periodontal disease, which develops at early age and is rapidly progressive as well as oral candidosis. [8-10] On the other hand, a lower prevalence of dental caries appears to be a characteristic of DS populations, although there are some controversial results.[11-15] The alteration in oral microbiology and biochemistry of DS population will be discussed in the light of these infectious diseases.[11]
However, the oral health problems experienced in people with DS are still not fully defined, so future studies are suggested.
Bibliographic research undertaken through the MEDLINE/PubMed, Science Direct and B-on search engine as well as through the library archives of Porto University’s School of Dental Medicine between 1988 and 2014 limited to articles published in English, French, Spanish and Portuguese. In total, 63 bibliographic references were obtained according to the following factors of inclusion: articles released by Porto University’s School of Dental Medicine’s servers through SCOPUS, ISI, Cochrane and PUBMED database, articles with titles referred in the keywords mentioned above.
Patients with DS have a high prevalence of specific otorhinolaryngologic pathology, including recurrent sinusitis and chronic nasal obstruction, as a consequence of hypotonia and craniofacial malformations (Figure 1.).[16-20]
The base of the skull, the frontal bone and the paranasal sinus are significantly small, leading to a decrease in the size of the sella turcica. There’s a flattening of the cranial base as a result of vertical hypoplasia of the structures of the skull (Figure 1.).[2, 9, 17, 21]
In DS, the respiratory dysfunction is among the pathologies that cause most worries and imply serious dysfunction in the individual development, learning ability and sleep capacity, as well as having large family repercussion.
Dry skin and lips with fissures.
These problems, together with their short Eustachian tubes, predispose them to chronic media otitis with effusion and conductive hearing loss, which interferes with their language acquisition. They are also more susceptible to recurrent infections, particularly of the upper airway.[16-20]
Sleep apnea is diagnosed in more than 50% of the patients and may adversely affect behaviour, growth and neurodevelopment.[16, 20]
Another common abnormality is the dysfunction of the thyroid gland. Individuals with DS tend to present hypothyroidism and it is related to an underdevelopment of the bones and the teeth and to a delayed tooth eruption.[1, 2] The atlanto-axial joint, which is responsible for promoting communication between the first and the second vertebrae, is unstable in about 20% of the individuals.[1, 2] This defect may cause spinal cord compression during sudden movements of flexion and extension and, therefore, the dentist must be very careful while handling their necks.[1, 2]
When compared to the general population, these children have up to 20 times higher risk of developing leukaemia.[1, 2] The dentist should be alert to the presence of persistent lesions and spontaneous gingival bleeding as it may be an early sign of leukaemia.[3]
Some facial features of DS, to notice the hypotonia of facial muscles and tongue, with open mouth and tongue protrusion. Hypotonic lips, incomplete lip closure.
Mental health and behavioural problems, including attention deficit disorder, hyperactivity, obsessive-compulsive disorder and depression are common among individuals with DS.[9, 21, 22] Most of them also develop Alzheimer’s disease around the fourth or fifth decade of life.[1, 2] This degenerative disease is related to an over-expression of β-amyloid precursor protein (βAPP), which is the expression of one of the triplicated genes in DS.[1, 2, 9] The most common craniofacial features observed in children with DS are small nose, low nasal bridge, narrow, short, deep and high palate, bifid uvula, hypertrophy of the tonsils, underdeveloped jaw, cleft lip, incomplete lip closure, hypotonic lips, fissured tongue, inaccurate and slow tongue movement, anterior open bite, posterior crossbite and reductions in the maxillary arch and changes in temporary and permanent tooth eruption (Figure 2., Figure 3., Figure 4., Figure5.).[6, 7, 9, 16, 17, 20, 23, 24]
The scrotal tongue, sometimes with tongue diastasis, is often found in this syndrome.
Lateral or anterior open bite is often found and tongue interposition worsens and maintains open bite.
This hypotonicity is associated with ligament laxity, easily visible throughout the body. It induces hyper-flexible joints, which can compromise the periodontal ligaments.[20] Excess of saliva on the labial commissure is also related to the muscle hypotonicity and can lead to irritation, cracking (angular cheilitis), aphthous ulcers and infectious conditions like candidiasis.[3, 24]
According to [Oredugba (25)], 51% of class I dental malocclusion and 47% of class III among 43 individuals with DS and only 5% of class III in the control group (individuals without DS), concluding that class III has a higher incidence in DS individuals than in the general population.
[Musich (26)] and [Soares K (27)] have concluded that class III is more frequent in DS individuals. Anatomically, the facial mid-third is underdeveloped but the mandible follows normal development (pseudo-progeny). This midface dysplasia also contributes to the narrow maxilla (Figure 5., Figure 6.).[7, 11, 18, 20]
Mandible measurements are not significantly different from normal subjects. However, a transverse expansion may occur due to lingual pressure.[20, 28] This intermaxillary discrepancy prevents the optimal intercuspal position to occur, which is needed to stabilize the mandible and the hyoid bone during mastication and swallowing.[16, 20]
Natural position of the tongue, resting against the palate, creating a favourable force vector to maxillary growth; the protruded tongue and its low position, no longer exercises the vector of expansive force on the maxilla; on the other hand, the maintenance of the open mouth increases the compression.
Anterior crossbite is primarily attributed to the anteroposterior deficiency of the maxillary arch development, resulting in a crossbite of the mandible, projecting the jawbone arch towards the front of the maxilla (Figure 5., Figure 6.).[5, 6, 26-29]
Dental anomalies are very common, both in the primary and permanent teeth and occur with an incidence five times greater in DS individuals than in general population (Figure 7.).[7, 23]
Anomalies in the number (fewer), size (smaller) and morphology (crowns may also be short, small and conical) and the timing of their development (late dentition) are constant features of this syndrome.[7, 23] In the primary dentition, the most commonly absent teeth are lateral incisors, while in the permanent dentition, third molars, second premolars and lateral incisors, in this sequence, are the most frequently missing teeth (Figure 7.). [3, 7, 20]
Patients with DS have complete tooth mineralization, delayed tooth eruption (six to eighteen months) changes in the sequence of eruption (mainly of the temporary teeth), high incidence of impacted teeth (incisors and canines) and teeth agenesis. Microdontia, enamel hypoplasia, hypodontia of deciduous teeth and oligodontia are the most common dental anomalies. Structural abnormalities include taurodontia, peg-shaped teeth, fusion and germination. Canines are the most affected regarding shape and size.[3, 11, 20, 29, 30]
Delayed tooth eruption, compression and crowded teeth, microdontia, enamel hypoplasia, hypodontia of deciduous teeth and oligodontia.
A majority of published studies have reported that people with DS have lower caries rates than people without DS, although several studies found that people with and without DS share the same caries rates, and some reported higher caries rates in those with DS.[7, 13, 14, 31] The differences herein described may be related to the control group used in each study: non-related healthy individuals, healthy siblings or other cognitive impaired individuals. The most commonly used indicator of caries experience is an index comprising disease and treatment markers, the DMFT (Decayed, Missing and Filled Teeth).[11, 12, 14] This index should be analysed together with factors such as a diet, frequency of snacking, social status, oral health in close relatives, dental awareness and past dental history. In studies of
Saliva plays a crucial role in the defense against periopathogenic and cariogenic bacteria in the oral cavity and the equilibrium between demineralisation and remineralisation of enamel and dentin.[3, 12, 38] Consequently, the protective effects of salivary constituents, salivary flow rates and the salivary buffering capacity are essential.[36, 39-43] It is agreed almost universally that the salivary flow rate is significantly reduced in individuals with Down syndrome.[13, 36, 39-43] Also,
The Gingivitis and Periodontitis are the two main subgroups of periodontal diseases affecting a high percentage of the world population and is therefore a serious public health problem.[8] Dental practitioners are challenged by the high incidence of early-onset aggressive periodontal disease in DS; these patients have higher levels of periodontal pathogens and periodontitis-associated interproximal bone loss. The complex anatomy, physiology, immunology and microbiology underscore the need for further investigation in specific areas related to dental treatment of these patients.[8, 48, 49] Gingivitis and periodontal disease start early in life, and the severity of these diseases increase with age. The prevalence of periodontal disease in adolescents with DS is 30% to 40%. Consequently, a large number of young people with DS lose their permanent anterior teeth in their early teens. In individuals in their thirties, the incidence of periodontal disease rises up to nearly 100%.[8]
Bruxism is quite common in this population, initiating at very young age, and often persisting throughout life. [5] The increased frequency of bruxism in DS population is associated to chronic anxiety, underdeveloped nervous system, malocclusion and TMJ dysfunction due to hypotonicity, hyper flexibility and laxity of the supporting ligaments. Initially, it creates an erosion of the pits and fissures of the occlusal surfaces (that become smoother), enabling self-cleaning with tongue and facilitating oral hygiene. [5, 11, 14] On the other hand, it can lead to an overloading of the supporting tissues and subsequent teeth fractures. These patients should be monitored through a regular program to allow an early diagnosis of the problems related to bruxism. [5, 14] In cases where bruxism is diagnosed, it is necessary to reposition the jaw and to decrease teeth grinding. Unfortunately, patients with a severe bruxism are the ones with more neurological problems and the treatment may not be successful.[5, 52]
This section intends to guide clinicians regarding the most important preventive measures in this population and also suggest the best approaches to improve the most common oral pathologies in DS individuals.[48] In this regard, oral hygiene and habits will be discussed and specific methods such as adapted DS pacifiers and rapid maxillary expansion will be suggested. According to
Baby mouth with Down syndrome.
To improve the suction, drooling and the chewing and secondarily to help the development of the language,
After 12 months of therapy, the mean duration of the factor "closed mouth” was significantly longer (p < 0.001) and "inactive protrusion of the tongue” significantly shorter (p < 0.001) in the test group than in the control group. The results indicate that in children with Down syndrome, palatal plate therapy may be a valuable complement to a training program for improving orofacial muscle function. It may be used as a prophylactic measure of the tongue protrusion.
Undesirable effects after the insertion of the plate can occur; for example, development of active avoidance of the plate with the tongue, which results in more pronounced tongue protrusion, no clinical reaction, immediate habituation to the plate, hyper salivation or more pronounced tongue protrusion after the suspension of the treatment, even if for a short period.[57-62] All these reactions were rare, but required fitting a new plate, or suspension of the treatment.
Due to the presence of a protruding tongue and a muscular hypotonicity, these children have oral–motor problems (seen during swallowing, chewing and sucking) and are mouth breathers (exhibit open bite). The use of an adapted pacifier could prevent these problems (Figure 9).[3, 7, 11, 20]
Reflex of Weiffenbach and repositioning of the tongue by the palatal plate.
When teeth are erupting, the plate does not adhere to the palate. So, they take off the plate easily, which leads to stopping the usage of the plate for a period until the child is about 3 years old. When the device is omitted for a period of time in the early stages of treatment, it will result in a return to the pathological condition. It is important to notice that people that already use the plates on their patients, don’t refer major problems. Do not put plates if there is not a strong motivation by the parents. The motivation of the parents is fundamental.[57-62]
Examples of traditional palatine plates with tongue stimulat (a) or (in pink or in blue), and lip stimulatior(b)
Due to fear of plate swallowing and child choking, the plate developed by Castillo-Morales did not allow a prolonged use and required adult supervision [58]. Thereafter, Andrade C. et al [20, 63] developed a modified, pacifier-shaped device, that provide greater security, prolonged usage time (even at night), less concern by caregivers, and better acceptance by society. The results of its use show an improvement in aesthetics with less tongue protrusion and higher time of closed mouth when compared to the traditional Castillo-Morales plate (Figure 11., Figure 12., Figure 13.).[12, 20, 58, 63]
An alteration of the traditional plate now like a pacifier-shaped device.
Pacifier-shaped device; the results of its use show an improvement in aesthetics with less tongue protrusion and higher time of closed mouth when compared to the traditional Castillo-Morales plate.
We can place fixed appliances in preschool age, if the child is cooperative. Problems like anterior or posterior crossbites should be corrected as soon as they are found. Fixed appliances have better results because we can have a greater control of their use, which does not happen with removable appliances, which can either be used or not. We may expand the maxilla to gain more space to the tongue and in DS we prefer to do it expanding from the apical base, to obtain an orthopaedic effect. At certain ages, the effects of maxillary disjunction may be more favourable, which has to do with the overall growth of the jaws and the individual himself (Figure 13., Figure 14.). [20, 28]
Advantages of the device
Fixed appliance
Easy to clean
Acts in a short time
Does not need intense cooperation from parents or from the children.
How to remove crossbites expanding from the apical base – the occlusal radiograph shows the disjunction of the maxilla; the superior incisors separated and the palatine suture opened.
Effect of the maxillary disjunction in DS patient that presents bilateral and anterior crossbite. We open 0.3 to 0.5 mm a day, for 2 to 4 weeks.
Cutting this cycle of mouth breathing and increasing the area for nasal ventilation can provide a solution for some breathing difficulties, a reduction of tongue protrusion and drooling, as well as the high incidence of repeating respiratory infections and the high rates of compression and crossbites.[20, 28]
After the maxillary disjunction and in respect to clinical symptomatology, we may conclude:
Nasal symptomatology:
Global improvement of cases and controls, but in that the cases show up, markedly, a minor incidence of rhinorrhea: "went the first summer in that my son had the nose completely without secretions".
Otologic symptomatology:
Smaller evidence in the resolution from the serous otitis, that persisted in the cases and in the controls.
Rapid maxillary expansion produced a significant augmentation of nasal volume in children who had been treated (p<0.05) compared to the control group; these results were stable through the period of retention.
The rapid maxillary expansion (disjunction) in infants with Down syndrome:
Diminishes the number of infections of the superior airways.
Improves nasal permeability.
Improves several parameters analysed by speech therapists.
Tongue Mobility
Articulation
Intelligibility
Patient with Down syndrome that present a bilateral crossbite (photographs extra and intra - orals, models and X rays).
Rapid maxillary expansion (RME) increased space for the tongue in the oral cavity (Figure 15., Figure 16., Figure 17.). This in turn results in a reduction of tongue protrusion and drooling. These aspects, in addition to the enlargement of the maxilla, often lead to an aesthetic improvement noted by the parents of the RME children. By placing the tongue in its normal position, the speech is improved, and so the aesthetics and self-confidence of the individual, facilitating his integration in society. This procedure may be carried out concomitantly with other surgical procedures for upper airway obstruction, sleep apnea and chronic otitis media with effusion. Rapid maxillary expansions give these patients a better airway, if used (Figure 15., Figure 16., Figure 17.). It is important to make exercise routines and teach these patients to use this new airway, increasing attention and activity, and leading to a better general development, better general health and less hours of work lost by the family. The indications should be accurate. The effect is similar to the infants from the general population. The use of this device should be included in the suggestion to medical and connected Associations of parents of Down’s syndrome children.
In less than one month, they obtain an increase from the apical base sufficient for eliminating the bilateral crossbite and the compression of the maxilla; this helps to facilitate the nasal ventilation.
We should not be afraid to use facial masks or other orthodontic devices because these patients are very supportive, and we should encourage all dentists to treat these patients.
We cannot forget that all cases must have an appropriate fixed orthodontic contention, in most times for life.The orthodontic retention phase minimises unwanted dental movements and maintains the corrections, and in these cases, most of the times, a fixed contention is necessary because hypotonia and deleterious habits are very dangerous for the stability of the correction (Figure 18., Figure 19., Figure 20., Figure 21.). [20, 28]
Immediately after rapid maxillary expansion; in addition to an aesthetic improvement observed by all parents, the beneficial effects of rapid maxillary expansion include better ventilation and drainage of secretions, which lowers the upper respiratory infections such as adenoiditis, tonsillitis and otitis verifying still an improvement of sleep apnea, decreased nasal obstruction and tongue protrusion.
Facial mask may be used if necessary.
Facial mask immediately after disjunction.
DS patients cooperate with the dentist and we should not be afraid to treat these patients.
The crossbite may be present in primary dentition. If we have cooperation, we must correct the temporary teeth and not wait for the permanent teeth to get the treatment.
Patients with Down syndrome present peculiar orofacial features that, when not corrected, may interfere with their physical, psychological and social development.
Children with this syndrome have a high risk of developing malocclusion and periodontal problems, and these should be the main concerns in their treatment needs. When planning the dental treatment of patients with Down syndrome, dental practitioners should always consider their general health, in order to achieve a holistic and interdisciplinary approach. Nevertheless, there is a need to improve the oral health services available to individuals with DS, to further investigate the interrelations between all their health problems, and to provide a higher level of information to parents of DS.
The authors supported this investigation.
Glutamatergic signaling plays a critical role in the CNS function under physiological and pathophysiological states via two major types of receptor: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs) [1]. mGluRs consist of three subgroups (Group I-III), while iGluRs comprise four subgroups (AMPARs, KARs, Gluδs, and NMDARs). Among all GluRs, NMDARs play a crucial role in brain development, mediating the physiological functions, such as synaptic plasticity, learning, and memory. NMDARs are voltage-dependent glutamate- or aspartate-gated cation channels with two prerequisites for channel opening: 1) depolarization-induced unblockage of magnesium ions; 2). concomitant binding of glutamate (or aspartate) and glycine (or D-serine). When the NMDARs are either aberrantly enhanced or encumbered opening, various CNS symptoms/disorders may develop, such as depression, psychosis, and cognitive impairment.
CNS disorders still loom over many people’s health with limited effective treatment. The role of NMDARs playing in CNS disorders has been gaining attention owing to the finding of ketamine as an antidepressant [2]. This new therapeutic mechanism promotes NMDARs as an emerging therapeutic target. Ketamine, a NMDAR antagonist, exerts rapid and robust antidepressant effects in depressed patients [3]. On the contrary, a NMDAR agonist, D-serine, could alleviate schizophrenic and depressive symptoms in the clinical trial [4]. These contrary modulations on NMDAR further support the importance of NMDAR homeostasis leveraged by NMDAR modulators [5].
NMDAR modulators, with positive or negative modulation, have been designed to alleviate various symptoms of CNS through distinct mechanisms. Positive NMDAR modulators elevate NMDARs via direct and indirect approaches. Direct NMDAR enhancers fit into the glutamate site or glycine site of NMDARs, or they bind the allosteric pockets of the glutamate/glycine sites. In contrast to direct enhancement, several NMDAR enhancers improve NMDAR functions by modulating indirect pathways, for example, by inhibiting glycine transporter or D-amino acid oxidase (DAAO). Negative NMDAR modulators, on the contrary, work as competitive antagonists to directly occupy the glycine site, or bind an allosteric site (known as non-competitive antagonists), or block NMDAR channel pore (known as uncompetitive antagonists) [6]. All above modulators have shown potential for clinical use in CNS disorders but without one-size-fits-all approach.
The excitatory neurotransmission of mammalian CNS is largely dictated through glutamate and its receptors, particularly NMDAR. Because its critical roles in mediating synaptic plasticity related to learning and memory formation, the dysfunction of the NMDAR-based signaling is implicated in the neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), as described below.
AD is the most common cause of dementia to induce not only cognitive impairments in memory and thought, but also behavioral and psychiatric symptoms [7]. Current understanding to AD relies on two main histopathological abnormalities: (1) amyloid plaques composed of amyloid ß (Aß) peptides cleaved from amyloid precursor proteins in the brain tissue, and (2) the formation of intraneuronal neurofibrillary tangles due to phosphorylated and aggregated tau proteins. Although Aß and tau serve as the most discussed mechanisms through which cause AD, no effective treatment was developed successfully. Coincidently, the neurotransmitter systems, including cholinergic, adrenergic and glutamatergic pathways are considered critical in AD progression and development [8]. In this chapter, we focus on the discussion of how NMDAR involves in AD.
NMDAR is the major regulator associated with long-term synaptic plasticity. Studies have reported that AD brains contain neurotoxins consisted of soluble Aß oligomers. The binding of Aß 42 oligomers to forebrain synaptosomes is associated with post-synaptic density complexes containing NMDAR subunits NR1 and NR2B [9]. Consistently, Aß oligomers were found to ablate long-term potentiation in hippocampal brain slices and the cortices of AD brains via overactivating extrasynaptic NMDAR containing NR2B [10]. The over-activation of extrasynaptic NMDAR linked to neurodegeneration in AD has also been supported by the pharmacotherapeutic use of NMDAR inhibitor memantine [11].
Indirect modulation of NMDAR via glutamate release or glycine transporter-1 (GlyT1) are considered feasible for AD. An escalated stimulation via glutamatergic signaling causes glutamate excitotoxicity that results in damaged nerve cells, and such neuronal toxicity is coined “excitotoxicity”. In AD, glutamate uptake and recycling systems are severely impaired [12], which therefore increases glutamate availability, resulting in excessive NMDAR stimulation. Additionally, Aß peptides may increase glutamate availability by weakening glutamate uptake and recycling systems [13] that may contribute to AD pathology. On the other hand, at glutamatergic synapses, glycine is transported by GlyT1, a Na+/Cl−-dependent carrier protein playing a major role in maintaining glycine concentration below saturation at postsynaptic NMDAR, sculpturing GlyT1 as an intriguing target for NMDAR modulation.
Overall, direct and indirect NMDAR inhibition strategies through the discussed mechanisms to attenuate the overactivation of NMDA function have shown rationale for developing medicine for late-stage AD to attenuate the neuronal death.
PD, the second most common neurodegenerative disease, is a progressive disorder with symptoms of onset gradually, motor disturbances and cognitive impairment. Due to the rapidly aging population worldwide, PD also receives increasing attention from communities [14]. The pathophysiology of PD is due to the degeneration of pigmented dopaminergic neurons, resulting in functional changes to the circuitry of basal ganglia nuclei. Accordingly, levo-dopa, a precursor of dopamine, and dopamine receptor agonists have been serving as the standard treatments for PD. However, long-term use of these standard therapies contribute to the loss of efficacy and development of disfiguring motor complications [15]. Novel PD treatments based on different mechanism is long awaited.
Regulating glutamatergic receptors, particularly NMDAR, has been found to be altered in the basal ganglia of PD where NMDAR is widely expressed. Specifically, NR2B-containing NMDARs may significantly influence the PD pathology while NR2B was found to be substantially distributed in the striatum and other basal ganglia areas. An increasing body of literature has reported that not only experimental PD models but also PD patients present substantially elevated NMDA-sensitive glutamate binding in the striatum [16]. In levo-dopa-treated rodent and primate, GluN2A and the ratio of GluN2A/GluN2B are increased. The findings are also reported in PD patients [17], suggesting that attenuated NMDAR activity may help halt the progression of PD.
Alternately, reshaping synaptic connections for PD patients via brief activation of NMDAR can increase axonal growth rate and axonal branching. The brief NMDAR activation can be achieved through inhibiting GlyT1 to increase levels of extracellular glycine [18]. In addition, activating NMDAR via weak NMDAR glycine binding agonists can also achieve similar effects. This hypothesis remains to be investigated.
HD is a progressive CNS disorder due to a single defective gene on chromosome 4 that encodes the protein huntingtin. The defect is hereditary and will eventually develop symptoms in lifetime. At the beginning of symptom onset, patients often have subtle abnormalities in mood, usually followed by a lack of coordination and unsteady gaits [19].
Since the altered function of huntingtin induces neuronal cell death, research focuses on mechanisms towards regulation of such cell death. It has been revealed that the formation of the nuclear protein aggregates, oxidative stress, and mitochondrial dysfunction are associated with neuronal cell death in HD [20]. NMDARs have also been found to regulate neuronal cell death of HD, and by modulating NMDAR activity, psychotic symptoms of HD due to low NMDA function can be alleviated simultaneously. In this chapter, we focus on the discussion of NMDAR in HD.
Animal studies have shown that neuroexcitatory agonists kainic or quinolinic acids can induce lesions similar to those in HD, indicating that excitotoxicity from NMDAR over-activation could contribute to the progression of the disease [21]. Post-synaptic density protein 95 (PSD-95), a scaffolding protein, can bind huntingtin and the NR2 subunit of NMDAR. At the molecular level in HD, the presence of abnormal huntingtin protein causes the interruption of PSD-95 binding onto NMDAR. The unbinding of PSD-95 results in excitotoxicity and neuronal cell death consistent with HD [20]. Therefore, among the known mechanisms inducing HD progression, NMDAR remains a primary target to develop therapeutic intervention.
Existing high concentration of post-synaptic NMDAR in limbic structures [22] highlights the homeostasis of NMDAR activity as be of uttermost significance in behavioral regulation of the brain. The dysfunction of NMDAR can cause a variety of psychiatric disorders such as depression, schizophrenia, bipolar disorder (BD), and anxiety disorder [23].
Depression is a chronic mental disorder characterized by persistent low mood, loss of interest/pleasure, lack of appetite, sleep disturbance, low energy, and poor concentration. Depression can affect people irrespective of age, ethnicity, and gender. Major depressive disorder (MDD) is the most studied type of depression characterized by one or more major depressive events, that is, the presence of low mood and/or loss of interest for at least 14 days in company with depression symptoms. MDD leads to suicide that takes 2160 self-harm deaths per day in US [24]. Decades of research on depression have yielded several mechanisms that may explain its pathophysiology, including biogenic amine (e.g., monoamine) hypothesis, abnormal endocrine factors, genetic and environmental factors, neurogenesis, and the dysregulation of second messenger systems, which have been extensively reviewed elsewhere [25]. Among them, monoamine-based mechanisms were the most studied with successful development of antidepressants.
Although monoamine treatments are available for MDD, they have not been optimal. Currently, standard monoamine antidepressants require one month or more to exert antidepressant effects [26]. Such time lag has put MDD patients at risk of suicide and other self-harm acts. In recent decades, the NMDAR has emerged as a central player in MDD research, resulting in a paradigm shift from the monoamine-based to the NMDAR-based hypothesis. The NMDAR-based hypothesis of depression originated from early findings in the 1990’s that NMDAR antagonists exerted quick antidepressant-like action [27]. Subsequently, many studies have reported abnormal glutamate levels in frontal and occipital cortices in MDD; however, these findings infer the complex role of NMDAR in the brain of MDD patients. The regionally decreased glutamate level in the brain demonstrates an association with the pathophysiology of MDD [28]; on the contrary, the elevated glutamate levels occurs in medication-free MDD patients during an active depressive episode, in remission, and in young people [29]. Since glutamate is a major excitatory neurotransmitter dictating the neural plasticity and process of learning and memory, the alteration to NMDAR causes region-specific maladaptive neurocircuitry in depression and decreases in cognitive controls over negative emotion.
At the molecular level, postmortem brain analyses from MDD patients show alterations in the NMDAR subunit profile, such as reduced GluN2A and GluN2B subunits in locus coeruleus, and decreased GluN1 and GluN2A expression levels but no changes to those of GluN2B, GluN2C and GluN2D subunits in dorsolateral prefrontal cortex of MDD subjects [30]. Further studies have found that biologically, the activation of NMDAR requires both the binding of glycine and glutamate onto their binding sites, and therefore, modulating the release of the two amino acids into synapses are considered feasible. At glutamatergic synapses, glycine is transported by GlyT1, maintaining glycine concentration below saturation at postsynaptic NMDAR. Accordingly, GlyT1 has become an intriguing target for NMDAR activity modulation [31]. Alternatively, inhibiting glutamate levels at synapses renders reduced glutamate binding to NMDAR [32]. In summary, the above findings provide a solid basis for developing chemotherapeutics for treating MDD via modulating NMDA.
Schizophrenia is a psychotic illness presenting symptoms with processing thoughts and contents, and develops positive, negative and/or cognitive symptoms. Concurrently, depression and suicidal thoughts and attempts happen often in people suffering from schizophrenia. Because schizophrenia patients require lifelong treatment, early intervention may improve the long-term outlook. Conventional therapies for schizophrenia are developed based on a dopamine hypothesis which has been prevailing to explain symptoms associated with the positive symptoms. However, these treatments have not been optimal and often induce substantial adverse side effects [33].
Glutamate hypofunction hypothesis of schizophrenia has been supported by several lines of studies. Low level of glutamate in cerebrospinal fluid was reported in patients with schizophrenia [34]. The worsening of schizophrenic symptoms was observed in patients treated with NMDAR inhibitors such as ketamine. Healthy people administered with similar inhibitors were reported to develop symptoms of schizophrenia [35]. Building on these data, upregulating NMDA function serves as a promising target for treating schizophrenia [36].
Although NMDAR is a focus for antipsychotic drug development for schizophrenia, direct activation of the NMDAR via targeting the glutamate site is reported to cause excitotoxicity. The finding suggests the demand for targeting the glycine site as an alternative, but direct approach. To reduce glycine site vacancy, a number of studies have synthesized amino-acid derivatives to occupy it [37]. Alternatively, enhancing the glycine levels through GlyT1 inhibition has also shown promise, which is used as an adjunct to conventional therapies [38].
BD, as its name suggested, causes extremes of mood fluctuations that a person will be either in emotional highs (mania or hypomania) or lows (depression). BD is a lifelong disease that episodes of mood swings may occur infrequently or several times in a year. Typically, BD patients spend more time in depressive mood than mania or hypomania. Currently, treatments for BD are limited to symptom reduction and prevention of the occurrence of mood episodes [39].
Neuroimaging [40] and genetic findings [41] have revealed that glutamatergic abnormality is associated with the pathophysiology of BD, indicating NMDAR may play a role in the disease. The use of NMDAR inhibitor further evidences the role of NMDAR in the regulation of BD. Ketamine has shown to improve depressive symptom. One of possible mechanisms of ketamine in regulating BD symptoms is to increase presynaptic levels of glutamate which in turn binds to AMPAR instead of NMDAR. The increased ratio of AMPAR-to-NMDAR neurotransmission is implicated to induce the antidepressant effects of ketamine [42].
At the molecular level, postmortem findings suggest that BD is associated with a reduced expression of NR1 subunit in the prefrontal cortex [30]. The genetic polymorphisms in the 3’UTR region of GRIN2B gene that encodes for the NR2B subunit has been found to play a role in BD etiology, although its expression level is not significantly different from the control [43]. Together, these studies suggest NMDAR is associated with BD.
Having occasional anxiety is a normal part of life. However, intense, excessive, and persistent worries and fear about specific situation would be in the category of anxiety disorder that needs intervention. Types of anxiety disorders include panic attack, generalized anxiety disorder, and separation anxiety disorder. An anxiety patient may experience one or more of them and can experience anxiety at very young age [44].
Benzodiazepine and selective serotonin reuptake inhibitors (SSRIs) or selective serotonin-norepinephrine reuptake inhibitors (SNRIs) are recommended as first line drug treatment, because of their more favorable profile than tricyclic antidepressants and monoamine oxidase inhibitors. Nevertheless, some SNRIs are also antagonists of metabolic enzyme cytochrome P450, therefore causing drug–drug interactions [45]. In addition, discontinuation of SSRIs or SNRIs may experience withdrawal reactions [46]. These unwanted outcomes suggest an essential for developing next generation anxiolytic treatments based on novel mechanisms.
Fear often occurs together and share similar stress responses with anxiety, and therefore, both are often put into the same context when discussing the underlying mechanisms. Currently, studies have found that the neuronal modulatory systems in brain areas contributing to fear and anxiety share a high degree of overlap [47]. In particular, regulating extinction learning of fear through NMDAR within amygdala, medial prefrontal cortex, and hippocampus is considered critical among the neuronal modulatory systems [48]. Hippocampus and amygdala of the medial temporal lobe situate at the interface between cognition and emotion, which is believed to be potential sites where NMDAR inhibitors exert anxiolytic effects [49]. NMDAR regulates emotionality and cognition, and its antagonists have shown promising effects on them. In contrast to NMDAR antagonism, partial activation of NMDAR facilitates fear extinction in rodents. In clinical setting, partial agonists used as an adjuvant increase psychotherapeutic effects in patients suffering fear-related disorders [50]. These finding suggest that a balanced modulation of NMDAR activity can bring benefits for the patients with anxiety disorder.
In this section, positive NMDAR modulators for CNS disorders will be discussed (Figures 1 and 2, Table 1). To enhance NMDAR function, two approaches could achieve: direct or indirect modulation. For direct modulation, three types of enhancers are categorized according to their binding sites: glutamate site, glycine site, and allosteric site of NMDAR.
Scheme of direct agonism/antagonism via various binding sites of NMDAR. NAM, negative allosteric modulators; PAM, positive allosteric modulators.
Indirect NMDAR agonism/antagonism through activation or inhibition on diverse channels or transporters or enzymes. ASCT-1, alanine/serine/cysteine transporter-1; DAAO, D-amino acid oxidase; EAAT2, excitatory amino acid transporter-2; GlyT1, glycine transporter-1; NMDAR, N-methyl-D-aspartate receptor; SNAT2, sodium-coupled neutral amino-acid transporter-2; VGSC, voltage-gated sodium channel.
Drug | Mechanism | Disease | Study |
---|---|---|---|
glutamate site agonist | MDD | NCT03414931 NCT04637620 | |
glycine site agonist | Schizophrenia | [53] | |
glycine site agonist | Schizophrenia | [54] | |
glycine site agonist | MDD Schizophrenia | NCT04721249 NCT00322023 | |
glycine site partial agonist | AD MDD Schizophrenia BD Anxiety | [55] NCT00408031 [56] NCT01833897 NCT00515879 | |
PAM | MDD | NCT01684163 | |
PAM | MDD | NCT02067793 | |
Indirect enhancer (SNAT2 inhibitor) | PD MDD Schizophrenia BD | NCT00004826 [57] [58] [59] | |
Indirect enhancer (GlyT1 inhibitor) | AD Schizophrenia | NCT02788513 NCT02832037 | |
Indirect enhancer (GlyT1 inhibitor) | Schizophrenia | NCT01235585 | |
Indirect enhancer (GlyT1 inhibitor) | PD MDD Schizophrenia | NCT01785628 NCT00977353 [60] | |
Indirect enhancer (D-serine retention) | AD MDD Schizophrenia | [61] [62] NCT01908192 | |
glycine site antagonist | PD MDD | NCT04147949 NCT02484456 | |
NAM | AD HD | NCT00377715 NCT00497159 | |
NAM | MDD | NCT04688164 | |
NAM | MDD | NCT01941043 | |
Uncompetitive antagonist | PD HD | NCT00632762 [63] | |
Uncompetitive antagonist | AD PD MDD SchizophreniaBD Anxiety | [64] [65] [66] [67] [68] [69] | |
Uncompetitive antagonist | MDD BD | NCT04226352 [70] | |
Uncompetitive antagonist | MDD BD | NCT01882829 [71] | |
Uncompetitive antagonist | AD MDD Schizophrenia | NCT03393520 NCT02153502 NCT03896945 | |
(Axsome, | Uncompetitive antagonist | AD MDD | NCT04797715 NCT02741791 |
Uncompetitive antagonist | MDD BD Anxiety | [72] [73] [74] | |
Uncompetitive antagonist | MDD BD | [75] NCT03965871 | |
Uncompetitive antagonist | MDD | NCT04108234 | |
Uncompetitive antagonist | AD | [76] | |
Uncompetitive antagonist | MDD Anxiety | [77] NCT02243826 | |
Indirect blocker (glutamate release inhibitor) | MDD Schizophrenia BD | [78] [67] [78] | |
Indirect blocker (glutamate release inhibitor) | AD MDD BD Anxiety | [79] [52] [52] [80] | |
Indirect blocker (glutamate uptake activator) | AD Anxiety | NCT03605667 NCT03829241 |
AD, Alzheimer’s disease; BD, bipolar disorder; GlyT1, Glycine transporter-1; HD, Huntington’s disease; MDD, major depressive disorder; NAM, negative allosteric modulators; PAM, positive allosteric modulators; PD, Parkinson’s disease; SNAT2, sodium-coupled neutral amino-acid transporter-2.
Cognitive deficits occur often in elderly MDD patients, hardly to be relieved with the existing treatment. NMDA enhancement via the glutamate site has been proved to enhance cognitive functions in previous studies [81]. NMDA enhancer (NMDAE), binding the NMDAR glutamate site as an agonist, has been offered for the elderly (>55 years) and adults (18–55 years) with MDD. To testify the efficacy, safety, and the cognitive improvement of NMDAE in those patients, the NMDAE treatment results were compared with sertraline (SSRI) and placebo. The results of those clinical studies are not disclosed as of August 2021 (NCT03414931 and NCT04637620). The potential risk of this approach is the excitotoxicity caused by overactivation through the glutamate-binding site.
Another ligand binding site on NMDAR is the glycine site, which can also be targeted to modulate the NMDAR activation for the treatments of psychiatric disorders [82]. Glycine, acting as an agonist via binding the glycine site, can ameliorate negative symptoms in schizophrenia patients [53]. This preliminary finding encourages the development of other endogenous co-agonists, such as D-alanine. D-alanine, working as an add-on antipsychotic medication, improved schizophrenic symptoms without significant side effects, which further supports that the pathophysiology of schizophrenia is due to the hypofunction of NMDA neurotransmission [54]. D-serine, an NMDAR co-agonist without psychotomimetic effects, emerges as a novel glutamatergic antidepressant as an adjuvant therapy in MDD patients (NCT04721249). On the other hand, the therapeutic effects of D-serine at low dose (30 mg/kg/d) in schizophrenic patients are inconsistent. Some clinical studies showed significant improvement in positive, negative, and cognitive symptoms [83], whereas others presented no significant improvement [84]. Interestingly, high doses of D-serine (≥60 mg/kg/d) could possess consistent significant improvement in negative symptoms, strongly suggesting a therapeutic dose–response of D-serine for the treatment of schizophrenia (NCT00322023).
D-cycloserine (DCS), a partial agonist of NMDAR with agonism at low doses but antagonism at high doses depending on the intrinsic tone of NMDA function [85], exhibits controversial therapeutic effects on CNS disorders. In some AD studies, a dose as high as 100 mg/d could improve the cognitive symptoms, while a low dose of 15 mg/d could improve memory deficits [55, 86]. However, other studies presented no cognitive improvement from low (10 mg/d) to high dose (500 mg/d) in AD patients [87].
When the high dose of DCS (≥ 500 mg/d) was employed in MDD patients, depressive symptoms could be improved (NCT00408031) [88]. These observations implied that NMDAR antagonism might be a potential target for the development of novel antidepressant. The clinical studies of DCS at a dose of 50 mg/d is argumentative, some claimed to possess significant clinical improvement [89], while the others found no clinical improvement [90]. In the dose finding phase, the dose of 100 mg/d of DCS seemed to be more effective than 50 or 250 mg/d in improving schizophrenic symptoms [56]. In combination with ketamine, DCS could ameliorate depression symptoms in BD (NCT01833897). Cognitive behavioral therapy with DCS also reduced social anxiety (NCT00515879) and PTSD [91]. Overall, the dose selection of DCS determines its agonistic vs. antagonistic effects on NMDAR, hence modulating its therapeutic efficacy for a variety of CNS disorders.
Rapastinel (GLYX-13/BV-102), an amidated tetrapeptide acting as a NMDA allosteric glycine site partial agonist, is administered intravenously to treat MDD in clinical trial (NCT01684163). Rapastinel infusion achieved antidepressant effects without psychotomimetic properties and serious adverse events, therefore acquiring FDA Fast-Track and Breakthrough Therapy designations for adjunctive treatment of MDD. However, rapastinel failed to meet primary and key secondary endpoints in three acute studies (RAP-MD-01, −02, −03 by Allergan).
Apimostinel (NRX-1074), a chemical structure like rapastinel with an additional benzyl group, is administered intravenously and orally under the studies of efficacy and safety evaluation for MDD patients and healthy individuals (NCT02067793 and NCT02366364). Benefiting from its molecular weight and orally stability, apimostinel is 100-fold more potent than rapastinel and is also well tolerated without psychotomimetic symptoms [92]. The findings of the studies are not available yet.
To enhance NMDAR function, “consolidating” amino acids (e.g., glycine or D-serine, glutamate, and aspartate) in the synaptic cleft could achieve that goal. With the use of inhibitors of amino acid transporters or degrading enzymes, the concentration of those specific amino acids could sustain in the synaptic cleft to boost NMDAR function [58]. Clozapine, a modest inhibitor of sodium-coupled neutral amino acid transporter-2 (SNAT2), indirectly activates NMDAR via augmenting synaptic glycine levels. Clozapine could also improve symptoms of psychosis, tremor, and dyskinesias in PD patients (NCT00004826) [58]. In addition to reducing the risk of hospital re-admission for MDD patients, clozapine administration also demonstrated higher efficacy than quetiapine by ameliorating depressive symptoms [57]. As approved by Food and Drug Administration (FDA) of the USA, clozapine is utilized to treat treatment-resistant schizophrenia and symptoms of self-harm in patients with schizophrenia. Clozapine is also more effective than other antipsychotics in improving treatment-resistant bipolar disorder [59]. However, clozapine can cause potentially lethal agranulocytosis.
Other than SNAT2 inhibitor, GlyT1 inhibitor could also increase synaptic glycine level by blocking the GlyT1 to enhance NMDAR function. BI 425809, a selective GlyT1 inhibitor, emerges as a potential treatment of cognitive impairment of AD and schizophrenia. Although BI 425809 failed to improve cognition in AD study (NCT02788513), it improved cognition in patients with schizophrenia (NCT02832037). Bitopertin (RO-4917838), a selective and potent GlyT1 inhibitor, modulates both glutamatergic and dopaminergic neurotransmission in animal models of schizophrenia [93]. In six active treatment arms across three clinical studies, only one of them proved improvement in symptoms of schizophrenia (NCT01235585) [94]. However, the magnitude of improvement was small. Because of its strong antagonism, bitopertin induces NMDAR internalization, counter-productive to improve the NMDA function.
Sarcosine, a potent endogenous non-selective GlyT1 inhibitor, was applied in cognitive- and mood-related clinical studies. In PD patients, sarcosine improved depression and neuropsychiatric symptoms, especially in patients with mild–moderate severity (NCT01785628). Both in animal models and in depressed patients, sarcosine improved depression-like behaviors, further strengthening GlyT1 inhibitor as a novel class of promising antidepressant (NCT00977353) [31]. In most clinical studies of sarcosine in patents with schizophrenia, improvement in schizophrenic symptoms were reported [60]. However, when being adjunctive with clozapine, sarcosine could not produce improvement in schizophrenic patients [95]. This phenomenon may be explained by the “ceiling effect”: additional NMDAR activation may not be induced due to maximal NMDAR enhancement achieved by clozapine administration alone. In contrast, the combination therapy of sarcosine and sodium benzoate (a D-amino acid oxidase (DAAO) inhibitor) enhances the cognitive function of patients with schizophrenia [96].
DAAO, a flavoenzyme for D-amino acids (e.g., D-serine and D-alanine) degradation, could be strategically inhibited to increase endogenous D-serine levels at the synaptic cleft, resulting in strengthening NMDAR functions. In post-mortem studies, patients with schizophrenia possessed higher expression and activity of DAAO in the cortex and cerebellum [97]. Thus, DAAO inhibition provides a good rationale to be a novel therapeutic target for schizophrenia treatment. Sodium benzoate, a prototype competitive DAAO inhibitor, generated antipsychotic effects in the phencyclidine-induced model of schizophrenia [98]. In some clinical studies, sodium benzoate adjunctive therapy improved symptomatology of patients with schizophrenia [99], and a larger scale clinical trial is undergoing (NCT01908192). In patients with early-phase AD, sodium benzoate predominantly enhanced cognitive and universal functions [61]. Sodium benzoate may enlarge gray matter via synaptogenesis and neurogenesis in MDD treatment [62].
NMDAR antagonism has been a therapeutic strategy for a variety of CNS disorders [100]. To achieve NMDAR antagonism, several negative NMDAR modulators have been offered to treat patients with CNS disorders through distinct underlying mechanisms: direct blocking in competitive, non-competitive, and uncompetitive ways, and indirect blocking. All negative NMDAR modulators are introduced in this section (Figures 1 and 2, Table 1).
AV-101 (L-4-chlorokynurenine), a pro-drug of 7-Chlorokynurenic acid (7-CKA), is able to cross the blood–brain barrier and transform to 7-CKA in astrocytes [101]. 7-CKA is a potent and selective NMDAR glycine site antagonist [102]. In preclinical studies, AV-101 demonstrated dose-dependent antidepressant-like effects in animal models [103]. However, AV-101 monotherapy failed to produce the anti-depressant effects in the clinical study (NCT02484456) [104]. On the other hand, AV-101 treatment for patients with PD will be conducted (NCT04147949).
Dimebon (Latrepirdine), an NAM at the polyamine-binding site of NMDARs, was originally used as an antihistamine [51]. Assessed in clinical trials, dimebon significantly improved the neuropsychiatric symptoms of patients with mild-to-moderate AD (NCT00377715) [105]. In patients with HD, short-term administration of dimebon is beneficial for cognitive improvement (NCT00497159) [106]. Dextromethadone (D-methadone/REL-1017), a non-competitive NMDAR antagonist, provided antidepressant activity via mTORC1-mediated synaptic plasticity in the mPFC in animal models [107]. As dextromethadone performs as a rapid-acting treatment for depression in clinical studies (NCT03051256), it gained FDA Fast-Track designation as an adjunctive treatment for MDD. A phase III clinical trial of dextromethadone is currently ongoing (NCT04688164). Rislenemdaz (CERC-301/MK-0657), a NMDAR NR2B-selective antagonist, induced antidepressant properties in patients with treatment-resistant MDD [108]. Nevertheless, in a phase II study, no obvious antidepressant effects were produced by rislenemdaz (NCT01941043).
Amantadine, a low-affinity uncompetitive NMDAR antagonist with rapid blocking channel kinetics, could ameliorate several clinical symptoms in PD, and the long-term efficacy of chronic treatment with amantadine might improve apathy and fatigue in PD patients (NCT00632762) [109]. For Huntington chorea, amantadine treatment delivered no beneficial effects but brought subjectively better feelings to patients [63]. Memantine, an adamantane derivative like amantadine, is an uncompetitive, moderate affinity, open-channel NMDAR blocker with strong voltage dependency and rapid blocking and unblocking kinetics [110]. Despite being approved by the US FDA for treating moderate-to-severe AD with safe and well tolerated profile, the efficacy of memantine is inconsistent at best. Some studies proved the clinical improvement of memantine in patients with moderate to severe AD [64], while other studies showed little clinical benefits of memantine towards AD treatment [111]. Several clinical results of memantine treatment in PD were also contradictive [65]. In MDD and BD clinical studies, memantine failed to show antidepressant effects in patients [66, 68]. As treatment for schizophrenic symptoms, adjunct memantine uncovered a beneficial effect in ten studies, but no effects in two studies [67]. One study of memantine revealed minimal improvement in seven patients with anxiety [69].
Dextromethorphan, an uncompetitive NMDA receptor antagonist, is used as a cough suppressant with sedative and dissociative effects. In recent research, dextromethorphan and dextromethorphan-based compounds are considered as potential rapid-acting antidepressants, and therefore its therapeutic effect in MDD is evaluated in the clinical study (NCT04226352). In a BD study, dextromethorphan had no significant antidepressant effects compared with placebo group. This might be due to DRD2/ANKK1 TaqIA polymorphism [70]. Nuedexta, an FDA approved treatment for the pseudobulbar affect, was also utilized to treat MDD and BD. The purpose of adding dextromethorphan with quinidine in this combination is to inhibit the cytochrome P450 2D6 (CYP2D6) isoform, a dominant metabolic pathway of dextromethorphan, hence augmenting the bioavailability of dextromethorphan in CNS [112]. A proof-of-concept clinical trial demonstrated that after Nuedexta treatment, the response and remission rates in the patients with treatment resistant depression were 45% and 35%, respectively (NCT01882829). In a retrospective chart review, Nuedexta induced significant improvement in Clinical Global Impression (CGI) in depressed patients with treatment resistant bipolar disorder, implying its possible effectiveness in the BD treatment [71].
AVP-786, another dextromethorphan-based compound, is in conjunction with quinidine and deuterium to decrease the metabolism of dextromethorphan in the liver and hence increase its blood exposure. Following FDA Fast-Track designation for agitation in AD [113], four AD-related clinical studies of AVP-786 are underway (NCT02442765, NCT02442778, NCT02446132, and NCT03393520). In patients with MDD and schizophrenia, the efficacy, safety, and tolerability of AVP-786 were evaluated in the clinical studies (NCT02153502 and NCT03896945). AXS-05 (Axsome) is in combination with dextromethorphan and bupropion, which acts as an inhibitor of CYP2D6 to enhance the bioavailability of dextromethorphan [114]. In the AXS-05 treatment of agitation in patients with AD, the efficacy and safety of AXS-05 will be compared to placebo (NCT04797715). Three phase III clinical studies on the safety and efficacy of AXS-05 in patients with MDD were conducted without results posted to date (NCT02741791, NCT04019704, and NCT04039022).
(R,S)-Ketamine, an anesthetic and analgesic via intravenous administration, and its derivates (S)-ketamine (esketamine) and (R)-ketamine (arketamine) open a new era for glutamatergic rapid-acting antidepressant. At high doses (1-2 mg/kg), ketamine inhibits NMDAR as an uncompetitive antagonist to produce anesthesia, while at low doses, ketamine induces analgesia against both acute and chronic pain (0.25–0.5 mg/kg). Importantly, rapid-acting antidepressant effects of ketamine at moderate doses (0.5 mg/kg) have been proved in preclinical and clinical studies [3]. In most clinical studies of MDD, (R,S)-ketamine administration decreased depression severity with robust and rapid antidepressant effects [72], in accordance with studies of BD [73] and anxiolytic effects in anxiety disorders [74]. The (S+) enantiomer of ketamine was approved by FDA for adults with MDD with acute suicidal ideation or behavior. Esketamine improved depressive symptoms and delayed relapse in many studies [75], but did not demonstrate significant improvement as an adjunctive therapy with oral antidepressants in elderly patients with treatment-resistant depression [115]. In the study of treatment-resistant bipolar depression, the efficacy, safety, and pharmacokinetics of inhaled esketamine are still being evaluated (NCT03965871). Another enantiomer of ketamine, arketamine, is a less potent NMDAR uncompetitive antagonist, but displays greater and longer antidepressant effects than esketamine without psychotomimetic side effects [116]. In an open-label pilot study, intravenous arketamine generated fast-onset and sustained antidepressant effects in depressed patients [117], and the larger study is underway (NCT04108234).
Neramexane, a moderate-affinity NMDAR open-channel blocker, possesses similar kinetics and voltage-dependency to memantine. Although it was well tolerated at all administered doses in clinical studies, phase II/III clinical trials for moderate-to-severe AD yielded contradictory results [76]. Nitrous oxide, an uncompetitive NMDAR antagonist, is an inhaled anesthetic often used in obstetrics or dentistry [118]. One recently published research demonstrated that compared with 50% nitrous oxide, 25% nitrous oxide provides comparable antidepressant effects with a markedly lower rate of adverse effects [77]. Other studies are underway to evaluate the efficacy and safety of nitrous oxide in MDD (NCT03869736 and NCT03932825). Nitrous oxide acted as a pharmacologic treatment for lumbar puncture/other procedure-related anxiety (NCT02243826).
Lamotrigine, inhibiting voltage-dependent Na+, Ca2+, and K+ channels, acts as a presynaptic glutamate release inhibitor [119]. FDA approved lamotrigine for the maintenance treatment of BD. Lamotrigine failed to achieve clinical improvement in five clinical studies of MDD, while it induced higher response rate than placebo in BD studies [52]. In a comprehensive meta-analysis, lamotrigine performed better than placebo in improving unipolar and bipolar depressive symptoms [78]. Five of nine clinical trials of lamotrigine in schizophrenia revealed clinical improvement in a range of outcome measures [67].
Riluzole (BHV-0223), a glutamate release inhibitor, was approved by the US FDA for the treatment of amyotrophic lateral sclerosis. The mechanisms that reduce extracellular glutamate by riluzole includes reduced glutamate release through presynaptic inhibition of voltage-gated sodium channels (VGSCs), increased glutamate uptake by astroglial cells, and enhanced AMPA trafficking [120]. In a current clinical study of AD, riluzole decreased the reduction in cerebral glucose metabolism, a positive correlation with cognitive measures [79]. Additionally, riluzole only ameliorated depressive symptoms in one of four placebo-controlled MDD studies, and failed to reach clinical improvement in a BD study [52]. In one trial of anxiety disorders, eighty percent subjects responded positively to riluzole [80], and the following functional neuroimaging studies proved the alterations in hippocampal N-acetylaspartate (NAA) concentrations and volumes were in correlation with riluzole-induced improvement on anxiety scales [121]. Troriluzole (BHV-4157), a tripeptide prodrug conjugate of riluzole, has been developed to improve the bioavailability, safety, and dosing of riluzole. As a glutamate modulator, troriluzole decreases the level of synaptic glutamate via strengthening glutamate uptake, mainly through excitatory amino acid transporters (i.e., EAAT2) located on glial cells. Both in clinical studies of AD and anxiety, the clinical efficacy of troriluzole is under assessment (NCT03605667 and NCT03829241).
Not only does the discovery of ketamine to act as a novel rapid-acting antidepressant trigger a strong interest in developing novel NMDAR-modulating agents by a variety of proof-of-concept studies for CNS disorders, but also, after exploring the potential pathological mechanisms for the major CNS disorders as described above, the aberrant NMDAR activity shows to play a pivotal role in regulating clinical symptoms, hence facilitating the development of positive and negative NMDAR modulators against those pathological aberrances in NMDAR activity. Interestingly, but not surprisingly, monotherapy of single NMDAR modulators often failed in clinical studies, boosting the prosperity of combination treatment with multiple modulators, or even with the standard treatments, further implying the intricate mechanisms underlying the CNS pathology.
To date, numerous clinical studies of NMDAR modulators are still underway. With more successful clinical improvement by NMDAR modulators in clinical studies, the mysterious puzzles of CNS disorders could be dissolved gradually, further refining the utilization of NMDAR modulators as optimal treatment with less undesirable side effects for the sophisticated CNS disorders that involve vulnerability in NMDA homeostasis.
The authors thank Hung-Chun Liu and Cheng-Shen Lee for their assistance in preparation of the manuscript.
The corresponding author is the CEO of SyneuRx International Corp., which is developing CNS therapeutics.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
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\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. 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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Dimensional wood lumber is readily available and due to its convenient unit dimension can be packaged neatly and transported to work sites by either commercial transport or personal vehicle. The unit pieces of dimensional lumber are light and easily handled once on the work site. Design of light-framed single-family homes is typically conducted by an architect or construction contractor using prescriptive building codes. A structural engineer can assist, if needed, with design items not within the scope of the building code or if alternative design approaches are required. An owner may choose to involve the engineer to improve quality or economy of the home design. Engineers typically become involved with design items such as foundation design, steel framing design, or engineered product specification. In this chapter, the design of a typical light-framed home is discussed. 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Transportation system became part of the infrastructure due its connection between two destinations, using maritime, land, or aerial methods, creating a link for social and economic activity. Bridges are widely used to cross rivers, valleys, and roads, providing a passage with other parts of the land since ancient times to modernity. Each structure has different requirements to cover, such span clearage, traffic flow, geometry and characteristics of the place to build; therefore, a great variety of bridges can be developed. Common materials used on construction are structural steel, reinforced concrete, pre-stressed concrete, or post-tensioned concrete; depending on the structural behavior of each type of bridge, there will be a maximum clear span to cover, which depends directly on the project’s budget. There are a variety of loads and environmental conditions that the new and existing structure needs to support effectively, including dead load, traffic, rain, wind, flood, and seismic events, using effective structural design process and techniques; on the other hand, there are long-term deterioration process, such as corrosion, wear, and fatigue, which should be considered on the maintenance process, avoiding additional costs, several damages, and catastrophic failures. Prevention and control of degradation process is achieved by effective maintenance methods applying protection technology such as paints, coating and cathodic protection. The purpose of this chapter is to show a brief review of ancient and modern bridges, including the process of design, material selection, construction, and maintenance.",book:{id:"8355",slug:"infrastructure-management-and-construction",title:"Infrastructure Management and Construction",fullTitle:"Infrastructure Management and Construction"},signatures:"Arturo Gonzalez, Michael Schorr, Benjamin Valdez and Alejandro Mungaray",authors:[{id:"16436",title:"Dr.",name:"Michael",middleName:null,surname:"Schorr",slug:"michael-schorr",fullName:"Michael Schorr"},{id:"65522",title:"Dr.",name:"Benjamin",middleName:null,surname:"Valdez",slug:"benjamin-valdez",fullName:"Benjamin Valdez"},{id:"311533",title:"MSc.",name:"Arturo",middleName:null,surname:"Gonzalez",slug:"arturo-gonzalez",fullName:"Arturo Gonzalez"},{id:"311534",title:"Dr.",name:"Alejandro",middleName:null,surname:"Mungaray",slug:"alejandro-mungaray",fullName:"Alejandro Mungaray"}]},{id:"60236",title:"The Feasibility of Constructing Super-Long-Span Bridges with New Materials in 2050",slug:"the-feasibility-of-constructing-super-long-span-bridges-with-new-materials-in-2050",totalDownloads:1824,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter explores the possibility of designing and constructing a super-long-span bridge with new materials in 2050. The proposed bridge design has a total span of 4440 m with two 330-m end spans and a central span of 3780 m. The height of the two pylons is 702 m, and the deck width is 40 m. The features of this structure include the combination of a suspension bridge and cable-stayed bridge, application of carbon fibre materials, extension of deck width and pretension techniques. Linear static analysis, dynamic analysis and theoretical analysis are conducted under different loading cases. In linear static analysis, the stresses under critical load combinations are smaller than the ultimate strength of the materials. However, the maximum deflection under the dead and wind load combination exceeds the specified serviceability limit.",book:{id:"6395",slug:"bridge-engineering",title:"Bridge Engineering",fullTitle:"Bridge Engineering"},signatures:"Faham Tahmasebinia, Samad Mohammad Ebrahimzadeh\nSepasgozar, Hannah Blum, Kakarla Raghava Reddy, Fernando\nAlonso-Marroquin, Qile Gao, Yang Hu, Xu Wang and Zhongzheng\nWang",authors:[{id:"211659",title:"Dr.",name:"Faham",middleName:null,surname:"Tahmasebinia",slug:"faham-tahmasebinia",fullName:"Faham Tahmasebinia"},{id:"221172",title:"Dr.",name:"Samad M.E.",middleName:null,surname:"Sepasgozar",slug:"samad-m.e.-sepasgozar",fullName:"Samad M.E. Sepasgozar"}]},{id:"61896",title:"Children’s Playgrounds in Slovak Mass Housing Estates: History and Current Trends",slug:"children-s-playgrounds-in-slovak-mass-housing-estates-history-and-current-trends",totalDownloads:1303,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Children’s playgrounds represent an important amenity in the concepts of mass housing, The study chapter presents the unique concepts of children’s playgrounds that have been applied in the Slovak mass housing estates of the second half of the twentieth century, designed by architects and artist, and inspired by the best European experiences, for example, by the landscape design of the Stockholm School. The early inhabitants of the Slovak mass housing estates were predominantly young families with children. The residential aging of this homogenous social structure caused that during the lifespan of housing estates, the demand for playgrounds decreased, they became underused and fell into decay. Today, the social structure of mass housing estates becomes more heterogeneous, what puts new requirements on the design of open public spaces and, as well as, on the regeneration and design of children’s playgrounds, to serve the rising demands of the inhabitants and to enhance the livability of the housing estates. The study examines the current examples of the children’s playgrounds from Slovak mass housing estates, which show that nowadays the typified design of the standardized catalog type elements is used and preferred.",book:{id:"7205",slug:"housing",title:"Housing",fullTitle:"Housing"},signatures:"Katarína Kristiánová",authors:[{id:"224853",title:"Dr.",name:"Katarina",middleName:null,surname:"Kristianova",slug:"katarina-kristianova",fullName:"Katarina Kristianova"}]},{id:"66232",title:"Geotechnical Engineering Applied on Earth and Rock-Fill Dams",slug:"geotechnical-engineering-applied-on-earth-and-rock-fill-dams",totalDownloads:2299,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter presents the importance of geotechnical engineering on the site selection, design, construction, operation, and maintenance of earth-rock dams and earth structures; it emphasizes the geotechnical engineering work related to dam safety during the operation stage. Preliminary geological studies required to select the best dam site are described first. Next, the field and laboratory studies related to the curtain design and dam foundation treatment, as well as geotechnical studies required for the construction, operation, and maintenance of the dam, are discussed. Recent developments in the following three areas are also included: (a) seismic considerations for the design, construction, and maintenance of earth dams; (b) importance of water flow control through the dam embankment and dam foundation, required to avoid internal soil erosion and excessive pore pressure; and (c) dam safety in Mexico and around the world. A case history of a recent failure is used for illustration purposes. In this example, design and construction shortcomings resulted in serious damages on an earth dam. Conclusions and recommendations related to this topic are presented at the end of this chapter.",book:{id:"7587",slug:"hydraulic-structures-theory-and-applications",title:"Hydraulic Structures",fullTitle:"Hydraulic Structures - Theory and Applications"},signatures:"Raúl Flores-Berrones and Norma Patricia López-Acosta",authors:[{id:"58505",title:"Dr.",name:"Raul",middleName:null,surname:"Flores-Berrones",slug:"raul-flores-berrones",fullName:"Raul Flores-Berrones"}]}],onlineFirstChaptersFilter:{topicId:"114",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"76814",title:"Support System Design for Deep Coal Mining by Numerical Modeling and a Case Study",slug:"support-system-design-for-deep-coal-mining-by-numerical-modeling-and-a-case-study",totalDownloads:109,totalDimensionsCites:0,doi:"10.5772/intechopen.97840",abstract:"Importance of numerical modeling in mine design gained pace after modern way of approach took birth through many variants. Methods such as Continuum and Discontinuum emerge as most effective in resolving certain issues. Cases such as heterogeneity, prevailing boundary conditions in continuum case and presence of discontinuities in other have provided solutions for many causes. A suitable support system is designed for deep virgin coal mining blocks of Godavari Valley Coalfield in India. This analysis is carried out using numerical modeling technique. The results show that the stresses at an angle to the level galleries are adverse. The level gallery/dip-raise may be oriented at 200 to 400 to reduce roof problems.",book:{id:"10632",title:"Theory and Practice of Tunnel Engineering",coverURL:"https://cdn.intechopen.com/books/images_new/10632.jpg"},signatures:"Shankar Vikram, Dheeraj Kumar and Duvvuri Satya Subrahmanyam"},{id:"76633",title:"Capabilities and Challenges Using Machine Learning in Tunnelling",slug:"capabilities-and-challenges-using-machine-learning-in-tunnelling",totalDownloads:263,totalDimensionsCites:0,doi:"10.5772/intechopen.97695",abstract:"Digitalization changes the design and operational processes in tunnelling. The way of gathering geological data in the field of tunnelling, the methods of rock mass classification as well as the application of tunnel design analyses, tunnel construction processes and tunnel maintenance will be influenced by this digital transformation. The ongoing digitalization in tunnelling through applications like building information modelling and artificial intelligence, addressing a variety of difficult tasks, is moving forward. Increasing overall amounts of data (big data), combined with the ease to access strong computing powers, are leading to a sharp increase in the successful application of data analytics and techniques of artificial intelligence. Artificial Intelligence now arrives also in the fields of geotechnical engineering, tunnelling and engineering geology. The chapter focuses on the potential for machine learning methods – a branch of Artificial Intelligence - in tunnelling. Examples will show that training artificial neural networks in a supervised manner works and yields valuable information. Unsupervised machine learning approaches will be also discussed, where the final classification is not imposed upon the data, but learned from it. 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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 interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"15",type:"subseries",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 15th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:286,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/150460",hash:"",query:{},params:{id:"150460"},fullPath:"/profiles/150460",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()