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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6118",leadTitle:null,fullTitle:"Recurrent Neural Networks",title:"Recurrent Neural Networks",subtitle:null,reviewType:"peer-reviewed",abstract:"The concept of neural network originated from neuroscience, and one of its primitive \r\naims is to help us understand the principle of the central nerve system and related behaviors \r\nthrough mathematical modeling. The first part of the book is a collection of three \r\ncontributions dedicated to this aim. The second part of the book consists of seven chapters, all of which are about system \r\nidentification and control. The third part of the book is composed of Chapter 11 and Chapter 12, where two \r\ninteresting RNNs are discussed, respectively.The fourth part of the book comprises four chapters focusing on optimization problems. \r\nDoing optimization in a way like the central nerve systems of advanced animals including \r\nhumans is promising from some viewpoints.",isbn:null,printIsbn:"978-953-7619-08-4",pdfIsbn:"978-953-51-5795-3",doi:"10.5772/68",price:139,priceEur:155,priceUsd:179,slug:"recurrent_neural_networks",numberOfPages:402,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"50220ea2482aebdb822dfdb5d4bfd6a1",bookSignature:"Xiaolin Hu and P. 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Then I became a post-doc researcher at the Department of Computer Science and Technology, Tsinghua University. Since 2009, I have been a faculty member of this department. My current research interests include artificial neural networks and computational neuroscience.\n\nI'm a Senior Member of IEEE and an Associate Editor of IEEE Transactions on Neural Networks and Learning Systems.\n\nEducation background:\nBachelor of Automotive Engineering, Wuhan University of Technology, Wuhan, China, 2001;\nMaster of Automotive Engineering, Wuhan University of Technology, Wuhan, China, 2004;\nPh.D. in Automation and Computer-Aided Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China, 2007.\n\nSocial service\nAssociate Editor, IEEE Transactions on Neural Networks and Learning Systems\nAreas of Research Interests/ Research Projects\nArtificial Neural Networks\nComputational Neuroscience\n\nCourses\nNeural and Cognitive Computation (80240642,Graduate).\n\nResearch Projects\nNational Natural Science Foundation of China: Design of Recurrent Neural Network Groups for Optimization based on KKT Conditions (2009-2011);\nNational Natural Science Foundation of China: Deep Learning Networks based on Sparse Coding Models (2013-2016)\n\nResearch Status\nI'm working in the interaction between computer science and cognitive neuroscience.\n\nOn one hand, I'm interested in unraveling the secrets of the brain, especially the mechanisms of sensory information processing and decision making. Two main techniques I rely on are hierarchical computational models and Bayes theory. Another technique I'm now trying to use is functional magnetic resonance imaging (fMRI) combined with machine learning methods.\n\nOn the other hand, I'm interested in brain-inspired computing methods. Currently I'm trying to integrate more neuroscience knowledge into deep learning models for boosting their performances as well as efficiency for object recognition and detection. In addition, I'm involved in a neuromorphic hardware project, which aims at developing an intelligent and energy-efficient brain-like system. My previous interest is the design of recurrent neural network for solving optimization problems, which also lies in this direction. \n\nHonors And Awards\nMinistry of Education, The People's Republic of China: Neurodynamic Optimization: Models and Applications, Natural Science Award, 1st Class (2012);\n\nTsinghua University: Excellent Postdoctoral Fellow (2009);\n\nICONIP 2012: Best Paper Award (2012).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Tsinghua University",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"252215",title:"Dr.",name:"P.",middleName:null,surname:"Balasubramaniam",slug:"p.-balasubramaniam",fullName:"P. Balasubramaniam",profilePictureURL:"https://mts.intechopen.com/storage/users/252215/images/system/252215.jpg",biography:"P. 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Alan Wang and Li Li",reviewType:"peer-reviewed",authors:[null]},{id:"5959",type:"chapter",title:"The Deployment of Data Mining into Operational Business Processes",slug:"the_deployment_of_data_mining_into_operational_business_processes",totalDownloads:6289,totalCrossrefCites:7,signatures:"Rok Rupnik and Jurij Jaklič",reviewType:"peer-reviewed",authors:[null]},{id:"5960",type:"chapter",title:"Data Mining Applied to the Instrumentation Data Analysis of a Large Dam",slug:"data_mining_applied_to_the_instrumentation_data_analysis_of_a_large_dam",totalDownloads:3385,totalCrossrefCites:0,signatures:"Rosangela Villwock, Maria Teresinha Arns Steiner, Andrea Sell Dyminski and Anselmo Chaves Neto",reviewType:"peer-reviewed",authors:[null]},{id:"5961",type:"chapter",title:"A Data Mining Algorithm for Monitoring PCB Assembly Quality",slug:"a_data_mining_algorithm_for_monitoring_pcb_assembly_quality",totalDownloads:3580,totalCrossrefCites:0,signatures:"Feng Zhang",reviewType:"peer-reviewed",authors:[null]},{id:"5962",type:"chapter",title:"An Overview of Data Mining Techniques Applied to Power Systems",slug:"an_overview_of_data_mining_techniques_applied_to_power_systems",totalDownloads:6500,totalCrossrefCites:10,signatures:"Jefferson Morais, Yomara Pires, Claudomir Cardoso and Aldebaro Klautau",reviewType:"peer-reviewed",authors:[null]}]},relatedBooks:[{type:"book",id:"5687",title:"Pattern Recognition",subtitle:"Techniques, Technology and Applications",isOpenForSubmission:!1,hash:"776a1270a14ebea65bf567dd6dfea1de",slug:"pattern_recognition_techniques_technology_and_applications",bookSignature:"Peng-Yeng Yin",coverURL:"https://cdn.intechopen.com/books/images_new/5687.jpg",editedByType:"Edited by",editors:[{id:"5693",title:"Prof.",name:"Peng-Yeng",surname:"Yin",slug:"peng-yeng-yin",fullName:"Peng-Yeng Yin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"5779",title:"Local Energy Variability as a Generic Measure of Bottom-Up Salience",slug:"local_energy_variability_as_a_generic_measure_of_bottom-up_salience",signatures:"Anton Garcia-Diaz, Xose R. 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This has, in large part, been driven by a public perception that cannabis offers a safe and natural alternative to conventional anticonvulsant therapies. However, the phytocannabinoids found in the cannabis plant do offer some very unique anticonvulsant pharmacological properties that warrant further exploration.
\nIn this chapter the authors will provide a brief review of epilepsy and epileptogenesis followed by a review of how the endocannabinoid system can alter the processes involved in the propagation and suppression of epileptic seizures. This is then followed by a review of the phytocannabinoids and their anticonvulsant mechanisms of action. Finally, the authors provide a historical background on the use of cannabis to treat patients with epilepsy and a review of the most recent clinical trials.
\nEpilepsy is a chronic disease characterized by recurrent unprovoked seizures. It is defined as a disease of the brain in which the patient has either (1) two or more unprovoked seizures occurring more than 24 hours apart or (2) one unprovoked seizure and a probability of further seizures to be greater than 60% [1]. The prevalence of epilepsy worldwide is estimated to be between 4 and 10/1000 people with epilepsy accounting for up to 0.5% of the global burden of disease [2, 3]. There is significant geographic variation with prevalence rates of epilepsy prevalence rates being much higher in the developing world [4].
\nMost children and adults with epilepsy respond well to anticonvulsant therapy with approximately 50% of adults and 70% of children becoming seizure free with their first anticonvulsant medication [5, 6, 7]. Up to 30% of patients with epilepsy can be considered to be drug resistant which is defined by the International League Against Epilepsy as having failed two or more appropriate anticonvulsant treatments at an appropriate dosage [8, 9].
\nIn patients who have failed two appropriate anticonvulsants the likelihood of seizure freedom with the addition of further anticonvulsant therapies is low. Treatment options for patients with drug resistant epilepsy include further trials of anticonvulsants, resective surgery, neural pathway stimulation with receptive or vagal nerve stimulation and dietary therapies [10]. Further trials of anticonvulsants in adults will result in 16% of patients who had failed their first two medications becoming seizure free [11]. In pediatric patients while the likelihood of achieving remission for 1 year or more with further medication trials is higher at 57%, many will continue to have relapses over time [12]. Resective surgery success rates (as defined as obtaining Engel Class 1 seizure freedom) in pediatric and adult patients with surgically amenable epileptogenic lesions range from 34 to 90% depending on the nature and extent of the lesion [10, 13].
\nA full review of the processes that result in brain abnormalities causing seizures (epileptogenesis) is beyond the scope of this chapter. However, in order to understand how cannabinoids can have potential in treating epilepsy it is worth knowing the basic principles of these processes. One of the major hallmarks of epilepsy is the presence of abnormal oscillatory events within neuronal networks in the form of recurrent interictal spikes and high frequency oscillations within the epileptic zones of the patients’ brain [14]. These abnormal oscillations then result in excessive synchronous firing of neurons causing an epileptic seizure with alteration in the patient’s behavior, motor activity or sensorium. Epilepsy can result from injury (either ischemic or traumatic) to cortical brain structures or genetic, inflammatory, structural and metabolic disturbances within the brain. The main components of the development of the abnormal oscillations within neuronal networks and epileptogenesis (seizure development) are (a) neuronal hyperexcitability—the ability of neurons to generate abnormal intrinsic burst discharges (b) a loss of GABA mediated interneuron neuronal inhibition that would normally prevent these discharges from spreading to adjacent neurons and (c) neuronal hypersynchrony in which excessive synaptic enhancement of neighboring neurons through the development of excitatory pathways allows these bursts to spread in a synchronous manner within a group of neurons [15]. Neuronal hyperexcitability can arise from abnormalities in excitatory or inhibitory neurotransmitter receptors resulting in a loss of the normal balance between neuronal excitation and inhibition. Of particular interest in epileptogenesis are the excitatory glutamatergic N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors [16]. Alterations in ion channel function as is seen in the channelopathy associated epilepsies such as Dravet syndrome also lead to neuronal hyperexcitability [17].
\nThe endocannabinoid system comprises the two endogenous endocannabinoid receptors (CB1R and CB2R) their two endogenously produced endocannabinoids; anandamide (
Although CB1R is one of the most abundantly expressed GPCRs in the brain, its expression is concentrated within certain groups of neurons. For example, in the hippocampus, CB1R expression is concentrated on the axon terminals of inhibitory GABAergic CA1 region interneurons and Schaffer collaterals arising from CA3 pyramidal cells [22]. These interneurons play a key role in the formation and maintenance of normal oscillatory behavior in the hippocampus essential for memory formation [18]. The effect of stimulation of CB1R is very localized within neuronal networks both from a spatial and temporal point of view. This is achieved by the production of monoacylglycerol lipase (MAGL) by astrocytes and nerve terminals which breaks down 2-AG in the synaptic cleft. This temporal and spatial control allows for precise regulation of oscillations within neuronal networks by the endocannabinoid system [18].
\nDuring an epileptic seizure there is excessive glutamate release from presynaptic excitatory neurons. In rodent models of epilepsy this has been shown to cause increased production of both 2-AG and anandamide that in turn active CB1R on the glutamatergic axon terminals to decrease the release of further excessive glutamate. This prevents further neuronal hyperexcitability which may play a role in terminating seizures. The increased anandamide is felt to play a role in preventing seizure induced excitatory neurotoxic effects [18, 21].
\nTemporal lobe epilepsy secondary to mesial temporal sclerosis (scarring of the hippocampi) is a common cause of epilepsy in adults that is often amenable to surgical resection of the mesial temporal structures. Pathological examination of surgically resected specimens has shown alterations in expression of CB1R of neurons within the hippocampi that provide insight into how disruption of the endocannabinoid system could predispose to epileptogenesis. In resected hippocampi there is a downregulation of CB1R expression on the axon terminals of excitatory (glutamatergic) neurons within the inner molecular layer of the dentate gyrus and an upregulation of CB1R expression on inhibitory (GABAergic) axon terminals within the dentate molecular layer [18]. These changes in CB1R expression result in both a loss of the normal inhibition of excessive glutamate release and increased suppression of GABAergic activity both of which result in increased neuronal hyperexcitability and subsequent seizure generation [22]. In patients with chronic epilepsy, there is also a decrease in the amount of anandamide and 2-AG released with excessive neuronal activation further contributing to a loss of the endocannabinoid mediated inhibition of excessive neuronal activation [18].
\nThe growing body of evidence demonstrating the role the endocannabinoid system plays in the brains’ mechanisms in regulating neuronal network oscillations and preventing excessive neuronal hyperexcitability coupled with alterations in the endocannabinoid receptors seen in epileptogenic tissue make the endocannabinoid system an attractive therapeutic target in the treatment of epilepsy. Modulation of the endocannabinoid system would provide a potential novel anticonvulsant mechanism not provided by other anticonvulsant therapies.
\nThe phytocannabinoids are a class of cannabinoids that are produced by plants of the cannabis species. The phytocannabinoids are C21 aromatic compounds consisting of an aromatic isoprenyl terpenophenolic core and resorcinyl side chain. Based on the structure of the oxygen bond between the isoprenyl and resorcinyl moieties the phytocannabinoids can be placed into 6 main families. Within each family, variations of the R-chain on the resorcinyl moiety differentiate each individual cannabinoid [23]. To date, over 140 different phytocannabinoids have been identified in
Initial research focused on the anticonvulsant effects of Δ9-THC and other CB1R agonists such as anandamide. Through their activation of CB1R, anandamide and the synthetic cannabinoid WIN 55,212-2 were able to block the production of postsynaptic neuronal spiking and excitatory post synaptic potential production. Both compounds were also able to suppress the production of abnormal burst activity in neurons placed in Mg2+ depleted solution. Depletion of Mg2+ in solution allows activation of NMDA receptors at normal resting potentials without the usual prerequisite neuronal depolarization. This effect was abolished when CB1R antagonists were added, suggesting that the effect was secondary to activation of CB1R by these agents [26]. Δ9-THC is a major phytocannabinoid in
In a rat model of electrically induced limbic seizures Δ9-THC increased the threshold of electrically induced after discharges at the site of electrode implantation in the left subiculum. However, Δ9-THC increased the duration of cortically recorded after discharges in electrodes remote from the site of stimulation. This suggested that Δ9-THC may have both anticonvulsant and proconvulsant effects in focal onset epilepsies [27]. In the cobalt model of focal epilepsy in rats Δ9-THC increased the frequency of epileptic potentials at the site of the cobalt-induced lesion. This was not seen with Δ9-THC’s main metabolite 11-OH-Δ9-THC. Both Δ9-THC and 11-OH-Δ9-THC seemed to increase generalized cortical excitation as seen by the production of brief intermittent cortically recorded after discharges [27]. Similar findings were seen in a rat model using iron to induce a seizure focus. While both Δ9-THC and 11-OH-Δ9-THC both caused increased cortical excitability, only Δ9-THC provoked clinical seizures. As well, the dose of Δ9-THC required to induce seizures was much higher than that required to induce electrographic changes in keeping with cortical excitation [29]. In mice, Δ9-THC has also been shown to induce kindling of a second epileptic focus in response to both electroconvulsive therapy as well as pentylenetetrazol (PTZ) and picrotoxin induced seizures [30]. When administered to rabbits with a genetic mutation causing audiogenic seizures Δ9-THC caused signs of neurotoxicity but prevented seizures when the rabbits were stimulated with a sound stimulus above their normal seizure threshold range. Conversely, in another breed of rabbits, injection with Δ9-THC induced both neurotoxicity and behavioral seizures in a dosage dependent manner [31].
\nThe results of these studies show that Δ9-THC and its metabolites display anticonvulsant activity in animal models using seizure models with rapidly evoked tonic discharges which mimics certain types of generalized onset seizures in humans. However, in models mimicking focal onset seizures, Δ9-THC and its metabolites seem to display a proconvulsant effect. This is manifested by increasing the activity at the site of the focal lesion and increasing generalized cortical activity [27]. A proconvulsant effect is also seen in models mimicking genetic based generalized epilepsies and absence seizures. Δ9-THC and its metabolites seem to induce hypersynchrony with slowly propagating epileptic discharges [32]. While Δ9-THC showed some potential as an anticonvulsant agent the potential to increase seizure activity along with its neurotoxic and psychotropic side effect profile limited its potential benefit in patients with epilepsy.
\nCBD is a low affinity negative allosteric modulator of CB1R with no psychotropic side effects due to the fact it does not cause activation of CB1R. It modulates the influx of both Ca2+ and Na+ into neurons by binding to human T-type voltage gated Ca2+ channels, Melastatin and Vanilloid type Transient Receptor Potential membrane receptors (TRPM and TRPV) and voltage gated Na+ channels [19]. This decreases neuronal excitability in response to stimulation. CBD has also been shown to inhibit intrasynaptic re-uptake of adenosine as well as activation of neuronal Serotonin, Glycine and Vanilloid receptors [33, 34]. The anticonvulsant effect of CBD is felt to be independent of activation of the endogenous CBR pathways. While the exact mechanism of anticonvulsant activity of CBD remains uncertain it appears to have a poly-pharmacological effect on modulating neuronal excitability.
\nIn the Cobalt induced focal epilepsy rat model CBD had no effect on focal discharges at the lesion site but decreased the frequency of seizures. CBD also blocked the proconvulsant effects in of Δ9-THC [27, 35]. In the limbic seizure rat model CBD decreased the frequency, duration and amplitude of electrically induced after discharges at the site of stimulation in the left subiculum but did not prevent the spread of after discharges from the site of focal stimulation to distal electrodes. It had no apparent effect on generalized cortical excitability. This suggests that in focal models of epilepsy, CBD acts directly on the site of focal seizure onset [27].
\nOther animal studies continued to show the anticonvulsant effect of CBD in both transcorneal electroshock, drug induced and lesional epilepsies. This anticonvulsant effect was seen when a single intraperitoneal (i.p.) dose of CBD was administered alone but like Δ9-THC it also potentiated the effects of several anticonvulsant medications [33, 36, 37]. While CBD had potent anticonvulsant effect against tonic seizures its effect against clonic seizures was minimal. Consroe et al. hypothesized that this effect was due to the fact that tonic seizures are spread rapidly throughout the brain from a focal lesion via post-tetanic stimulation. Unlike Δ9-THC, CBD suppressed tetanic potentiation in isolated bullfrog ganglia [27]. This coupled with the fact that CBD is effective in preventing 3-Mercaptoproprionic acid (3-MPA) induced seizures suggested that some of the anticonvulsant effect of CBD may result from its ability to increase production of GABA in presynaptic GABAergic neurons [36]. Unlike Δ9-THC, the brain concentrations of CBD correlated well with its anticonvulsant effect in several animal models. This suggests that the anticonvulsant effect of CBD is due to the parent compound and not its metabolites [27].
\nIn summary, CBD was shown to display broad spectrum anticonvulsant activity in a wide range of animal models of epilepsy including generalized seizures caused by electroshock and GABA inhibiting drugs and focal seizures induced by placement of toxic metals on the cortex. It however had no effect on models of generalized absence seizures [38]. CBD also blocked kindling of a second epileptic focus [36]. Even at high doses it failed to cause any behavioral or cognitive side effects in test animals. This would suggest that CBD is a potent anticonvulsant with limited cognitive side effects, making it an attractive potential anticonvulsant in the pediatric population [33, 37].
\nIn addition, Δ9-THC and CBD several other cannabinoids have been evaluated for the potential anticonvulsant activity. These include ∆9-tetrahydrocannibivarin (∆9-THCV) and cannabidivarin (CBDV) which have been shown to have anticonvulsant effects. ∆9-THCV is a non-psychoactive cannabinoid that acts as a CB1R antagonist. In a Mg2+ depleted solution ∆9-THCV decreased the amplitude and duration of abnormal neuronal burst activity. ∆9-THCV potentiated the effects on neuronal bursting of both phenobarbital and valproic acid. In a PTZ rat model ∆9-THCV did not decrease the severity or duration of seizures or seizure mortality. However significantly fewer rats exposed to PTZ that were treated with ∆9-THCV displayed seizures compared to those that were given PTZ alone [39]. Like CBD, CBDV is believed to exert its effects via CB1R independent mechanisms and has limited neurotoxicity [40]. CBDV has been shown to decrease the amplitude and duration of abnormal bursting in mouse and rat hippocampal slices in in both Mg2+ depleted solution and solution to which 4-aminopyridine (4-AP) has been added. CBDV also significantly decreased the number of seizures seen in in vitro MES and audiogenic seizure models in mice and PTZ induced seizures in rats. Unlike CBD, CBDV also prolonged the latency of seizure induction in a dose dependent manner. Administration of CBDV had no effect on motor performance in mice regardless of the ode administered [41]. The terpenes, which are another class of compounds found in cannabis, also possess a wide range of pharmacological activity on the mammalian nervous system at very low concentrations. Individually, these terpenes have not been assessed in patients with epilepsy [42, 43].
\nThe combinatorial effect of the chemical components of cannabis has been postulated wherein cannabis whole plant extracts may benefit from ‘entourage’ effects to yield greater effectiveness than treatment with a purified cannabinoid [42, 44]. This is supported by preclinical studies. In the
The use of cannabis as a treatment for a variety of ailments in eastern and Mediterranean cultures over the last several millennium has been well documented [47]. The first description of the use of cannabis to treat seizures came from Dr. W. O’Shaugnessy who while working in India reported its successful use to treat seizures in an infant [48]. Following this, cannabis extracts became widely used throughout Europe and North America as an accepted treatment for epilepsy [49]. Following prohibition and with the introduction of other anticonvulsants, cannabis fell out of use as a treatment for epilepsy in western cultures.
\nDuring the mid-twentieth century, several reports on the effect of recreational cannabis consumption surfaced with contrasting effects. Several case reports described patients having decreased seizure frequency following the consumption of cannabis [50]. Cannabis consumption was also shown to be protective against first unprovoked seizures. In adult males who smoked cannabis in the last 90 days, the odds of having a first unprovoked seizure was 0.38 compared to adult males who never consumed cannabis [51]. Conversely, a patient with a history of epilepsy who had been seizure free for several months on medication was reported to have had an exacerbation of seizures following the consumption of cannabis [52].
\nIn 1978, Mechoulam et al. reported their double blinded placebo-controlled study of CBD used as an add-on therapy in patients with refractory focal onset seizures. Of the four patients who took CBD two were seizure free for the 3 months of the study while another had partial improvement. None of the five patients who took placebo had any improvement in their seizures [53]. Cunha et al. reported the results of their study investigating the potential of CBD in patients with refractory temporal lobe epilepsy. In the first phase of the study, healthy adult volunteers were randomized to receive either placebo or CBD at 3 mg/kg/day for 30 days. Of 8 volunteers receiving CBD, 2 reported somnolence otherwise no adverse effects were reported. In the second phase, 15 adult patients with drug-resistant temporal lobe epilepsy were randomized to receive either placebo or CBD (up to 300 mg/day) for a period of 18 weeks in a double-blinded manner. Four of 8 patients dosed with CBD had complete improvement while three had partial improvement. No adverse effects were noted in patients given CBD [54].
\nTwo further studies showed no significant difference in seizure reduction with the addition of CBD as an adjunctive therapy. However, in one study patients were given CBD at a dose of 300 mg/day and their plasma CBD levels were maintained at 20–30 ng/ml. Subsequently one participant who had no difference in their seizure frequency was placed on CBD at a higher dose of up to 1200 mg/day. CBD plasma levels were higher averaging 150 ng/ml. This patient had a significant decrease in their seizure frequency suggesting that higher doses of CBD (and higher plasma levels) were required for seizure control [55].
\nIn recent years there has been a public perception that cannabis is a potent, natural, and safe alternative therapy for epilepsy. This has driven the demand for and use of cannabis and its derived products to treat epilepsy especially in those patients whose seizures are medically intractable. Coupled with the media exposure showing examples of the apparent miraculous effects of CBD oil in select epileptic patients, treating physicians have struggled to balance the patient demand for cannabis products and the need for studies to determine their, efficacy, dosing, side-effect profile, and indication. To that end, there have been multiple studies, predominantly in children, looking into these clinical questions. Unfortunately, the overwhelming majority of these studies have been retrospective, unblinded, and uncontrolled resulting in their being hampered by various forms of bias and potential placebo effect. Despite the plethora of published research on this topic, questions still remain on the use of cannabis in epilepsy.
\nIn this section, we will review the limitations of the studies, the studies using artisanal and CBD enriched cannabis herbal extracts (CHE), the studies using highly purified pharmaceutical grade CBD, and a meta-analysis of the CBD studies.
\nThe widespread use of cannabis and the effect of bias are highlighted in various published surveys. McLachlan performed a survey in London, Ontario, Canada, in which more than 60% of patients declared that cannabis was effective for their seizures and stress levels [56]. Ladina et al. reported a case series of 18 patients who all found medicinal cannabis very helpful for seizure control and improvement of mood disorder [57]. By contrast, Press had reported a significant discrepancy in reported responder rate between preexisting Colorado residents and those who moved to Colorado to obtain cannabis to treat their child’s epilepsy (22 vs. 47%) suggesting there is a significant perception bias among these children’s caregivers as to the therapeutic benefits of cannabis [58]. Physician bias may also play a role as a recent survey by Mathern showed contrasting opinions about CBD between neurologists and the general public. In his study, a minority of epileptologists and general neurologists said that there were sufficient data safety (34%) and efficacy data (28%) and only 48% would advise using medical cannabis and only in severe cases of epilepsy. Conversely, nearly all patients and the general public responded that there was sufficient safety (96%) and efficacy (95%) data, and 98% would recommend cannabis in cases with severe epilepsy [59].
\nGiven the present approved indications for medical coverage, the high cost of pharmaceutical grade CBD products, and the illegal status of cannabis in some countries and US states, the overwhelming majority of patients will at this time be using CBD oil extracts or artisanal products. In many jurisdictions these products are unregulated and therefore their content and consistency are uncertain and can vary. In Australia, where medical use of cannabis is highly restricted, Suraev reported that in parents treating their children with “illicit” cannabis extracts, the majority of extract samples used by the families contained low concentrations of cannabidiol, while Δ9-THC was present in nearly every sample [60]. These findings highlighted the profound variation in the illicit cannabis extracts being used. Studies examining the use of artisanal and CBD oil extracts therefore could have had uncertain and inconsistent amounts of cannabinoids. This inconsistency in combination the inherent problems of retrospective studies, make the findings of these studies questionable; moreover, none of published studies included serum CBD levels.
\nTo date, there are few prospective, double blind, placebo-controlled studies which all only examined the use of the highly purified, pharmaceutical grade CBD (Epidiolex). None involved artisanal CBD or the CBD oil extracts.
\nWhile keeping the limitations of the studies examining artisanal and CBD oil extracts in epilepsy in mind, most of these studies did find that CBD oil extracts are effective in reducing seizures and improving quality of life.
\nTzadok reported out of 74 children being treated with a 20% CBD and 1% Δ9-THC CHE, 89% reported reduction in seizure frequency with only 43% of patients having a >50% reduction in seizures. Five patients reported aggravation of seizures leading to withdrawal from the study. Improvement in behavior and alertness, language, communication, motor skills and sleep were noted. Adverse reactions included somnolence, fatigue, gastrointestinal disturbances and irritability leading to withdrawal of cannabis use in five patients. The CBD dosing ranged from 1 to 20 mg/kg/day with 83% taking <10 mg/kg/day [61].
\nSimilarly, Porcari retrospectively studied the efficacy of artisanal CBD preparations in children with epilepsy. The study also included a subgroup comparison to determine if the addition of clobazam was related to any beneficial effects of CBD. Overall, the addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The difference in effect between CBD alone and CBD with clobazam was not statistically significant. Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. The average dose of CBD was 2.9 mg/kg/day in the CBD group and 5.8 mg/kg/day in the CBD and clobazam group [62].
\nMcCoy et al. performed a prospective open label study using a 2:100 Δ9-THC:CBD CHE in 20 children with Dravet syndrome. The dose of CBD ranged from 7 to 16 mg/kg/day (mean 13.3 mg CBD/kg/day). They reported that during the 20-week intervention period the median monthly reduction in motor seizures was 70.6%. The CHE also resulted in improvements in quality of life measures and spike index on electroencephalogram (EEG). Adverse events during the titration period included somnolence, anorexia and diarrhea [63].
\nThe Cannabinoid Research Initiative of Saskatchewan is currently conducting a Canadian, multicenter, prospective, open-label, dose-escalation phase 1 trial entitled Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E). The source of the CBD oil is consistent with a single batch of 1:20 Δ9-THC:CBD CHE used for all study participants. Concentrations of the cannabinoids in the CHE were confirmed through Health Canada Quality Assurance and Good Manufacturing Practices (GMP) certification [64]. Preliminary data showed that all 6 participants had improvements in seizure frequency, Quality of Life in Childhood Epilepsy (QOLCE) and EEG rating scores—with three participants showing continued improvements in these measures after the oil extract was discontinued. In addition, serum CBD levels suggested linear dose independent pharmacokinetics in all but one participant. In most participants, serum Δ9-THC concentrations remained lower than what would be expected to cause intoxication even at the maximum dose of oil extract. None of the participants displayed any evidence of Δ9-THC intoxication clinically throughout the study. Preliminary data suggests that an effective and well-tolerated CBD initial target dose of 5–6 mg/kg/day is effective and well tolerated when a 1:20 Δ9-THC:CBD CHE is used. In addition, the serum concentration of CBD follows dose-independent linear pharmacokinetics for most participants, although non-linear pharmacokinetics might occur but requires confirmation. Continued improvement in seizure frequency and QOLCE following the discontinuation of CHE suggest a possible enduring anticonvulsant effect [65].
\nWith the production of a highly purified, pharmaceutical grade CBD (Epidiolex), studies could now be performed with a CBD source of greater reliability. Although potential bias remained, better clinical studies had been performed.
\nDevinksy published an open label trial in patients aged 1–30 with severe, intractable, childhood-onset, drugs resistant epilepsy. All patients were receiving their regular anti-epileptic drugs. Patients were given CBD at 2–5 mg/kg/day, titrated over a period of 2 weeks till intolerance or to a maximum dose of 25 mg/kg to 50 mg/kg/day. The main objective of the study was to establish safety and tolerability of CBD and the primary end point was the median percentage in the mean monthly frequency of motor seizures at 12 weeks. This study included mainly patients with Dravet and Lennox-Gastaut syndromes. One hundred and sixty-two patients were enrolled. A significant high rate of adverse events was reported in 128 patients (79%). The most common were somnolence (n = 41 [25%]), decreased appetite (n = 31 [19%]), diarrhea (n = 31 [19%]) and fatigue (n = 21 [13%]). This high rate of side effects (many of which were seen during the titration period) suggests that too rapid a titration rate may predispose toward side effects. The median monthly frequency of motor seizures was 30·0 (IQR 11·0–96·0) at baseline and 15·8 (5·6–57·6) at 12 weeks of treatment. The median reduction in monthly motor seizures was 36·5% (IQR 0–64·7) [66].
\nFrom this same cohort, Rosenberg et al. reported that caregivers of 48 patients indicated an 8.2–9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global quality of life (QOL). Interestingly, these differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure reducing effects [67].
\nDevinsky et al. later performed a double blind, placebo-controlled trial in patients with Dravet syndrome including 120 children and young adults using Epidiolex with a CBD dosage of 20 mg/kg/day. The median frequency of convulsive seizures per month decreased from 12.4 (baseline) to 5.9 with CBD, as compared with a decrease from 14.9 (baseline) to 14.1 with placebo (adjusted median difference between cannabidiol vs. placebo was −22.8% points [CI], −41.1 to −5.4; p = 0.01). The percentage of patients who had at least a 50% reduction in convulsive seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93–4.30; p = 0.08). This study shows an overall benefit of CBD over placebo but also a large placebo effect in the control group [68].
\nAnother trial that assessed the efficacy of Epidiolex in reducing atonic seizures in patients with Lennox-Gastaut syndrome. In this double blind, placebo-controlled trial, a total of 225 patients were enrolled, 76 patients were assigned to a treatment group (20 mg/kg/day CBD) and 76 to the placebo group. The median percent reduction from baseline in monthly atonic seizure frequency during the treatment period was 41.9% in the treatment group vs. 21.8% in the placebo group. As with the other studies assessing Epidiolex, the most common adverse events among the patients in the treatment groups were somnolence, decreased appetite, and diarrhea [69].
\nA recent systematic review assessed the safety and efficacy of pharmaceutical grade CBD in pediatric onset drug resistant epilepsy with outcome measures including 50% seizure reduction, complete seizure freedom, improved QOL. A total of 36 studies were identified including 6 randomized controlled trials and 30 observational studies. Overall CBD at a dose of 20 mg/kg/day was more effective than placebo in reducing seizure frequency by 50% (Relative Risk 1.74: 1.24–2.43). For one patient to achieve a 50% reduction in seizures the number of patient needed to treat was 8. In pooled data of 17 of the observational studies CBD at 20 mg/kg/day resulted in 48.5% of patients achieving a 50% reduction in seizures (95% CI: 39.0–58.1%) while pooled data from 14 observational studies showed 8.5% of patients became seizure free (95% CI: 3.8–14.5%). Quality of life improved in 55.8% of patients (95% CI: 40.5–70.6%) while serious adverse events related to treatment with CBD was very low at 2.2% of patients (95% CI: 0.0–7.9%). From this data, the authors concluded that pharmaceutical grade CBD may reduce seizure frequency but other randomized controlled trials examining a more diverse group of epilepsy syndromes and other cannabinoids was needed [70].
\nTo date, the evidence to support the use of cannabis in adults is minimal. STAR 1 is a phase 2A, randomized, double blind, placebo-controlled study that evaluated the safety and efficacy of synthetic transdermal CBD in adult patients with focal epilepsy. In this study 174 patients were randomized to receive either 195 mg CBD, 390 mg CBD or placebo via a transdermal patch. Patients who completed the 12-week study were able to continue into the 24-month open-label extension STAR 2 study (n = 171). In as of yet published data from these trials there was an increase in efficacy of transdermal CBD over 18 months. Median percentage change in seizure rates was −25% at 3 months, −40% at 6 months, −48% at 9 months, −52% at 12 months, −57% at 15 months and −55% at 18 months. The transdermal patch was well tolerated. Serious adverse events were as follows: seizures (n = 2) and increased anxiety (n = 1); one death was reported after the 15 month visit. In addition, no significant elevations in alanine aminotransferase and aspartate aminotransferase levels >3 times upper limit of normal were seen [71].
\nIn comparing cannabis derived treatments to standard therapies, it is worthwhile to note that the STICLO group examining the effects of stiripentol in Dravet patients in a double blind randomized placebo controlled study showed that 15 (71%) patients had >50% seizure reduction (including nine free of clonic or tonic-clonic seizures) compared to only one (5%) on placebo (none were seizure free; stiripentol 95% CI 52.1–90.7 vs. placebo 0–14.6). Stiripentol’s responder rate is therefore suggested to be superior to Epidiolex with a far lower placebo responder rate [72]. Similarly, in a double-blind, randomized, placebo-controlled trial of the anti-epileptic drug rufinamide in patients with Lennox-Gastaut syndrome, the median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7 vs. 11.7%, p = 0.0015). There was also a difference (p < 0.0001) in tonic-atonic (“drop attack”) seizure frequency with rufinamide (42.5% median percentage reduction) vs. placebo (1.4% increase). These findings are comparable with the results with Epidiolex. One also has to keep in mind that the median reduction of atonic seizures in the placebo group was markedly higher with the Epidiolex study suggesting potential bias [73].
\nOf note, the results from the study by McCoy et al. and the preliminary data from CARE-E study showed a much higher responder rate than those with pharmaceutical grade CBD. This apparent superiority of a CHE containing Δ9-THC would be in keeping with the proposed entourage effect in which the various cannabinoids can act synergistically with one another [42, 44].
\nThe cannabinoids found in cannabis appear to offer a unique pharmacological mode of action in the treatment of epilepsy. This, combined with the apparent low risk of serious side effects, makes cannabis and an attractive potential option for patients with treatment resistant epilepsy.
\nCurrently, there is a large public perception that cannabis products are superior to and safer than conventional anti-epileptic medications especially in treating patients with Dravet syndrome and other pediatric onset epileptic encephalopathies. Based on interpretation of the available data, the authors feel that cannabis based therapies show promise in the treatment of children with treatment resistant epilepsies. While the studies to date assessing cannabis based therapies for the treatment of epilepsy have been encouraging, they should be interpreted with caution. At this time, the long-term adverse effects, the indicated epilepsy and seizure types suitable for treatment with cannabis, the dosing of CBD and other cannabinoids, remain unknown. Also, there is minimal data regarding the pharmacokinetics of the cannabinoids especially in children and when used in patients with multiple concomitant medications. Moreover, the existing studies are limited with the majority of them being retrospective and subject to bias, possible placebo effect, and other limitations.
\nAs such, further studies assessing the safety and efficacy of cannabis based therapies in both adults and children are urgently needed. The authors recommend that these studies start with well-designed dose finding studies that include age stratified pharmacokinetic analysis followed by larger scale clinical trials. When faced with physicians that are reluctant to authorize cannabis based products due to a lack of high quality safety and efficacy data, parents who are desperate to help their children are then forced to turn to unregulated suppliers of cannabis. This puts their children at risk of harm and themselves in legal jeopardy.
\nPurpose statement: This chapter explores the role of cannabis-based therapies in the treatment of children and adults with epilepsy.
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Cellulases are produced by a diverse array of microbes including fungi, bacteria, yeast and actinomycetes. Considerable research for understanding the mechanism of cellulases began in early 1950s because of the significant use of these enzymes in various industries. This review provides a general account structure and availability of lignocellulosic biomass, pretreatment strategies for effective digestion, cellulase producing organisms, cellulase activity assay, and enzymology of cellulose degradation. Cellulase production, optimization, purification and characterization studies in addition to the industrial application of cellulase have also been discussed. At last a brief account of present market scenario of cellulases and future prospects of the study are also taken into account.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Namita Singh, Anita Devi, Manju Bala Bishnoi, Rajneesh Jaryal, Avni Dahiya, Oleksandr Tashyrev and Vira Hovorukha",authors:[{id:"278205",title:"Prof.",name:"Namita",middleName:null,surname:"Singh",slug:"namita-singh",fullName:"Namita Singh"},{id:"282352",title:"Dr.",name:"Anita",middleName:null,surname:"Devi",slug:"anita-devi",fullName:"Anita Devi"},{id:"282353",title:"MSc.",name:"Avni",middleName:null,surname:"Dahiya",slug:"avni-dahiya",fullName:"Avni Dahiya"},{id:"282354",title:"MSc.",name:"Manju Bala",middleName:null,surname:"Bishnoi",slug:"manju-bala-bishnoi",fullName:"Manju Bala Bishnoi"},{id:"282355",title:"Dr.",name:"Oleksandr",middleName:null,surname:"Tashyrev",slug:"oleksandr-tashyrev",fullName:"Oleksandr Tashyrev"},{id:"282356",title:"Dr.",name:"Rajneesh",middleName:null,surname:"Jaryal",slug:"rajneesh-jaryal",fullName:"Rajneesh Jaryal"},{id:"282939",title:"Dr.",name:"Vira",middleName:null,surname:"Hovorukha",slug:"vira-hovorukha",fullName:"Vira Hovorukha"}]},{id:"56708",doi:"10.5772/intechopen.69096",title:"Human Development and Research-Development-Extension Relationships",slug:"human-development-and-research-development-extension-relationships",totalDownloads:1775,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Human capital is the most important strategic factor for development; as new technologies emerge, the market demand for better and healthier products and consumer demand in terms of quality and delivery time are changing. In today’s world, it becomes increasingly important to know how information can be accessed, how it is adopted, and how it can be assimilated. In this respect, each country allocates budget for training, education, and extension according to its own conditions. This budget may be intended for rural community-based social assistance, but the economic and welfare effect is essential. In this way, it is aimed to increase the living standards of the families living in the rural areas. This will naturally contribute to national income and to the prosperity of society. The subject has been discussed generally in the world, especially in the case of Turkey. According to this, all over the world, particularly in developing countries, research and extension (R&E) is very important and should be considered at least as much as research and development (R&D). However, it will be ensured that societies meet with the technology produced. For this, the development of human resources should be emphasized and a suitable atmosphere should be prepared for this widespread prosperity.",book:{id:"5819",slug:"research-and-development-evolving-trends-and-practices-towards-human-institutional-and-economic-sectors-growth",title:"Research and Development Evolving Trends and Practices",fullTitle:"Research and Development Evolving Trends and Practices - Towards Human, Institutional and Economic Sectors Growth"},signatures:"Orhan Özçatalbaş",authors:[{id:"170206",title:"Prof.",name:"Dr. Orhan",middleName:null,surname:"Özçatalbaş",slug:"dr.-orhan-ozcatalbas",fullName:"Dr. Orhan Özçatalbaş"}]},{id:"66110",doi:"10.5772/intechopen.84770",title:"Gold Recovery Process from Primary and Secondary Resources Using Bioadsorbents",slug:"gold-recovery-process-from-primary-and-secondary-resources-using-bioadsorbents",totalDownloads:2038,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Bioadsorbents were prepared in a simple manner only by treating in boiling concentrated sulfuric acid from various biomass materials such as various polysaccharides, persimmon tannin, cotton, paper and biomass wastes such as orange juice residue and microalgae residue after extracting biofuel. These bioadsorbents exhibited high selectivity only to gold over other metals and extraordinary high loading capacity for gold(III), which were elucidated to be attributable to the selective reduction of gold(III) ion to elemental gold due to its highest oxidation-reduction potential of gold(III) of metal ions, catalyzed by the surface of bioadsorbents prepared in boiling sulfuric acid. By using these biosorbents, recovery of gold from actual samples of printed circuit boards of spent mobile phones and Mongolian gold ore was investigated. Recovery of trace concentration of gold(I) from simulated spent alkaline cyanide solution was also investigated using the bioadsorbent. Application of bioadsorbents to some recovery processes of gold from cyanide solutions was proposed.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Katsutoshi Inoue, Durga Parajuli, Manju Gurung, Bimala Pangeni, Kanjana Khunathai, Keisuke Ohto and Hidetaka Kawakita",authors:[{id:"198951",title:"Prof.",name:"Keisuke",middleName:null,surname:"Ohto",slug:"keisuke-ohto",fullName:"Keisuke Ohto"},{id:"259238",title:"Dr.",name:"Hidetaka",middleName:null,surname:"Kawakita",slug:"hidetaka-kawakita",fullName:"Hidetaka Kawakita"},{id:"289372",title:"Dr.",name:"Katsutoshi",middleName:null,surname:"Inoue",slug:"katsutoshi-inoue",fullName:"Katsutoshi Inoue"},{id:"298633",title:"Dr.",name:"Bimala",middleName:null,surname:"Pangeni",slug:"bimala-pangeni",fullName:"Bimala Pangeni"},{id:"298634",title:"Dr.",name:"Manju",middleName:null,surname:"Gurung",slug:"manju-gurung",fullName:"Manju Gurung"},{id:"298635",title:"Dr.",name:"Kanjana",middleName:null,surname:"Khunathai",slug:"kanjana-khunathai",fullName:"Kanjana Khunathai"},{id:"298636",title:"Dr.",name:"Durga",middleName:null,surname:"Parajuli",slug:"durga-parajuli",fullName:"Durga Parajuli"}]},{id:"66428",doi:"10.5772/intechopen.84833",title:"Review of Biofuel Technologies in WtL and WtE",slug:"review-of-biofuel-technologies-in-wtl-and-wte",totalDownloads:1216,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Processing of biomass feedstocks to produce energy, fuels, and chemicals via a combination of different applied technologies is considered a promising pathway to achieve sustainable waste management, with many environmental and economic benefits. In this chapter, we review the current state of the main processes associated with energy recovery and biofuel production under the concept of waste biorefineries. The reviewed technologies are classified into thermochemical, biological, and chemical, including combustion, gasification, steam explosion, pyrolysis, hydrothermal liquefaction, and torrefaction; anaerobic digestion, fermentation, enzymatic treatment, and microbial electrolysis; and hydrolysis, solvent extraction, transesterification, and supercritical conversion. Their brief history, current status, and future developments are discussed within a perspective of valorization and managing of current waste streams with no solution.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Bruno B. Garcia, Gonçalo Lourinho, Paulo Brito and Pedro Romano",authors:[{id:"261653",title:"Prof.",name:"Paulo",middleName:null,surname:"Brito",slug:"paulo-brito",fullName:"Paulo Brito"},{id:"261654",title:"Prof.",name:"Pedro",middleName:null,surname:"Romano",slug:"pedro-romano",fullName:"Pedro Romano"},{id:"291751",title:"B.Sc.",name:"Bruno B.",middleName:"B",surname:"Garcia",slug:"bruno-b.-garcia",fullName:"Bruno B. 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The aim of the URBANREC project is to implement an eco-innovative, integrated system of bulky waste management and demonstrate its effectiveness in various regions of Europe. The project has received funding from the European Union. In this chapter, the LCA environmental analysis was performed for the technology of grinding bulky waste using a water jet by the Ecofrag company. The calculations were carried out using SimaPro 8.5.2.0. The LCA analysis shows that the reuse of foams and mattresses contributes to the avoidance of their targeted production, which is related with the reduction of greenhouse gas emission and consumption of fossil raw materials.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Izabela Samson-Bręk, Marta Gabryszewska, Justyna Wrzosek and Barbara Gworek",authors:[{id:"281239",title:"Dr.",name:"Izabela",middleName:null,surname:"Samson-Brek",slug:"izabela-samson-brek",fullName:"Izabela Samson-Brek"},{id:"290299",title:"Mrs.",name:"Marta",middleName:null,surname:"Gabryszewska",slug:"marta-gabryszewska",fullName:"Marta Gabryszewska"},{id:"290300",title:"Dr.",name:"Justyna",middleName:null,surname:"Wrzosek",slug:"justyna-wrzosek",fullName:"Justyna Wrzosek"},{id:"290301",title:"Prof.",name:"Barbara",middleName:null,surname:"Gworek",slug:"barbara-gworek",fullName:"Barbara Gworek"}]}],mostDownloadedChaptersLast30Days:[{id:"66110",title:"Gold Recovery Process from Primary and Secondary Resources Using Bioadsorbents",slug:"gold-recovery-process-from-primary-and-secondary-resources-using-bioadsorbents",totalDownloads:2038,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Bioadsorbents were prepared in a simple manner only by treating in boiling concentrated sulfuric acid from various biomass materials such as various polysaccharides, persimmon tannin, cotton, paper and biomass wastes such as orange juice residue and microalgae residue after extracting biofuel. These bioadsorbents exhibited high selectivity only to gold over other metals and extraordinary high loading capacity for gold(III), which were elucidated to be attributable to the selective reduction of gold(III) ion to elemental gold due to its highest oxidation-reduction potential of gold(III) of metal ions, catalyzed by the surface of bioadsorbents prepared in boiling sulfuric acid. By using these biosorbents, recovery of gold from actual samples of printed circuit boards of spent mobile phones and Mongolian gold ore was investigated. Recovery of trace concentration of gold(I) from simulated spent alkaline cyanide solution was also investigated using the bioadsorbent. 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He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. 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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"14",type:"subseries",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.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-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",slug:"christian-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",slug:"francisco-javier-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"}}}]},onlineFirstChapters:{paginationCount:26,paginationItems:[{id:"83087",title:"Role of Cellular Responses in Periodontal Tissue Destruction",doi:"10.5772/intechopen.106645",signatures:"Nam Cong-Nhat Huynh",slug:"role-of-cellular-responses-in-periodontal-tissue-destruction",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Periodontology - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11566.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"82654",title:"Atraumatic Restorative Treatment: More than a Minimally Invasive Approach?",doi:"10.5772/intechopen.105623",signatures:"Manal A. 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