Nintedanib pharmacokinetic parameters and special considerations [4].
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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We rapidly learn to identify, characterize and eventually distinguish those who are near and dear to us. We accept face recognition later as an everyday ability. We realize the complexity of the underlying problem only when we attempt to duplicate this skill in a computer vision system. This book is arranged around a number of clustered themes covering different aspects of face recognition. The first section on Statistical Face Models and Classifiers presents reviews and refinements of some well-known statistical models. The next section presents two articles exploring the use of Infrared imaging techniques and is followed by few articles devoted to refinements of classical methods. New approaches to improve the robustness of face analysis techniques are followed by two articles dealing with real-time challenges in video sequences. 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He continued his studies at TCD and was awarded a Ph.D. in Electronic Engineering for research work in the field of Dielectric Liquids. In 1986 he was appointed to a lectureship in Electronic Engineering at the National University of Ireland Galway. He is currently vice-dean in the College of Engineering & Informatics at NUI, Galway. \r\nHis research interests include embedded systems applications, home networking, digital imaging, pattern recognition, face & fingerprint biometrics, smart grid and wired and wireless networking technologies. He was technical and conference chair of the IEEE International Conference on Consumer Electronics (ICCE) in 2010 and 2011 respectively. 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In 2013 he joined the Centre of Polymer Systems, Tomas Bata University in Zlin, the Czech Republic where was awarded PhD in Chemistry and Material Technology in 2016 defending a research work based on the encapsulation of bioactive compound in biopolymeric matrices. At the moment he is a senior researcher at the Centre of Polymer Systems in Zlin, Czech Republic, in the Bioactive Polymer group and his main attention is focused on developing innovative formulations based on polysaccharides for drug delivery applications.\nIn 2016 he joined the National Research Tomsk Polytechnic University as a Postdoctoral Research in the Department of Technology of Organic Substances and Polymer Materials and his research work mainly focused on the development of hybrid nanocarrier for drug delivery and diagnostic. In 2019 he became associate professor and member of the Research School in Chemistry & Applied Biomedical Sciences at Tomsk Polytechnic University, Russia. He is supervisor and consultant of Master and PhD students and his work is focused on the development of hydrogels for controlled delivery of bioactive compounds for application in pharmaceutical and biomedical area.\nHis primary research interest is the development of nano- and microcarrier based on biopolymer for multiple encapsulations and controlled delivery of bioactive compounds.\nHe has to his credit to 23 publications indexed in Web of Science (h-index 9) and active participation in projects financed by Czech Ministry of education, Russian Ministry of Education and European Union and author of one patent.",institutionString:"Tomas Bata University in Zlin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Tomsk Polytechnic University",institutionURL:null,country:{name:"Russia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1090",title:"Radiation Oncology",slug:"radiation-oncology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"288104",firstName:"Ivana",lastName:"Spajic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/288104/images/8497_n.jpg",email:"ivana.s@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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The wearable device market is currently having a worldwide profit of around $34 billion and is expected to reach above $50 billion by 2022 owing to wearables’ ease of use, flexibility, and convenience [4]. Real-time monitoring, operational efficiency, and fitness tracking are reported as main factors supporting the market growth of health wearable devices such as smart watches, smart glasses, and other wellness gadgets, with expected $12.1 billion world market by 2021 [5].
\nIn the past decade, the recent progress in developing wearable devices was more focused on monitoring physical parameters, such as motion, respiration rate, etc. [3, 6, 7]. Today, there is a great interest in evolving wearable sensors capable of detecting chemical markers relevant to the status of health. Different approaches have been applied by researchers to design and fabricate wearable biosensors for remote monitoring of metabolites and electrolytes in body fluids including tear, sweat, and saliva [3, 8, 9, 10]. A great example would be the development of small and reliable sensors that would allow continuous glucose monitoring in diabetic patients [11, 12]. Diabetes is a chronic disease that can significantly impact on quality of life and reduce life expectancy. However, diabetics can stay one step ahead of the disease by monitoring their blood glucose level to minimize the complication of the disease by proper administration of insulin. Currently, blood analysis is the gold standard method for measuring the level of glucose in patient’s blood. However, this technique cannot be applied without penetrating the skin, which can be painful and inconvenient, and requires user obedience. Therefore, current research focuses on the development of portable and wearable devices capable of continuous glucose sensing through noninvasive detection techniques.
\nA majority of the recent studies in this field have targeted the area of personalized medicine, endeavoring to develop miniaturized wearable devices featuring real-time glucose monitoring in diabetic patients [12, 13, 14, 15]. One great example is contact lens which is an ideal wearable device that can be worn for hours without any pain or discomfort [16]. Integration of glucose biosensors into contact lenses has recently been demonstrated by several research groups [9, 17, 18]. However, the level of glucose in tear fluid is very low (0.1–0.6 mM), requiring a high sensitivity of the sensor for picking up the signal from expected chemical reaction [3, 19]. Yao et al. [16] have fabricated a contact lens with integrated sensor for continuous tear glucose monitoring with wireless communication system over a distance of several centimeters. The sensor demonstrated a fast response of 20 s with a minimum detection of less than 0.01 mM glucose, which is 10–60 times lower than glucose level in human tear [16].
\nIn addition to glucose, lactate is an important metabolite in the human body, which gets converted into l-lactate under hypoxic condition [20]. l-Lactate levels in tear fluid is about 1–5 mmol L−1, which might increase significantly due to some heath conditions including ischemia, inadequate tissue oxygenation, stroke, and different types of cancer [21]. Thomas et al. [22] demonstrated an invasive detection of lactate in human tear by integrating an amperometric lactate sensor with Pt working (WE) and reference (RE) electrodes as well as a counter electrode (CE) as current drain, on a polymer-based contact lens, measuring lactate in situ in human tears without any need for physical sampling [22].
\nVery recently, Park et al. [17] reported a novel approach for fabricating fully transparent and stretchable smart contact lens capable of wirelessly monitoring the level of glucose in the tears of diabetic patients. Figure 1 shows the layout of fabricated devices made of glucose sensors, wireless circuit, and display pixel on soft and transparent contact lens substrate (Figure 1a and b). The circuit diagram of the device is illustrated in Figure 1a, with radio frequency antenna receiving signals from a transmitter and a rectifier converting the signals to DC (Figure 1a and c). A continuous network of ultralong Ag nanofibers was used as stretchable electrodes for the antenna and interconnects (Figure 1d). In the case of any change in the concentration of glucose in tear, the sensor resistance changes resulting in the light-emitting diode (LED) pixel turning on or off. The device was tested in vitro using a live rabbit, providing substantial finding for smart contact lenses as one of the promising wearable devices in healthcare system [17].
\n(a) (i) Schematic illustration and (ii) operation of the soft, smart contact lens and (iii) the circuit diagram of the smart contact lens system. The soft, smart contact lens is composed of (b) a hybrid substrate; (c) functional devices including rectifier, LED, and glucose sensor; and (d) a transparent, stretchable conductor for antenna and interconnects [
In addition to tear, sweat electrolyte concentrations and blood serum are related [2, 8]. As one of the most readily accessible human biofluids, a great deal of information about the human body and its physical performance could be obtained via monitoring sweat electrolyte concentrations [23, 24]. Several groups have reported the key biomarkers in human sweat (e.g., sodium level, pH change, lactate concentration) relevant to human health and well-being, for monitoring athletic performance during sporting activities [25]. Jia et al. fabricated a skin-worn tattoo-based sensor for real-time monitoring of lactate in human sweat, offering substantial benefits for biomedical as well as sport applications [25]. In another approach, Curto et al. [26] fabricated a wearable and flexible microfluidic platform capable of monitoring changes in the sweat pH in real time. Anastasova et al. [27] developed a flexible microfluidic device for real-time monitoring of metabolite such as lactate as well as electrolytes such as pH and sodium in human sweat. Recently, Gao et al. [28] developed a flexible and wearable device (Figure 2) made of arrays of sensors for real-time monitoring of heavy metals, such as Zn, Cu, and Hg in human sweat. The device fabrication method is presented in Figure 2a, showing the deposition and stripping steps on microelectrodes. The sensing mechanism was based on an electrochemical detection of targeted heavy metals through four microelectrodes, including Au and Bi working electrodes, Ag reference electrode, and an Au counter electrode (Figure 2b and c). The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application, via monitoring the level of some heavy metals in human sweat [28]. A balanced level of Zn is necessary in the human body as a low and high Zn concentration can lead to pneumonia and liver damages, respectively [29, 30]. High level of Cu in the human body can lead to several diseases including Wilson’s disease and heart, kidney, and liver failures as well as brain diseases [31, 32]. The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application [28].
\n(a) A schematic showing the concept of deposition and stripping on microelectrodes. (b) A schematic showing the composition of the microsensor array. (c) Optical image of a flexible sensor array interfacing with a flexible printed circuit connector [
Saliva, as a great diagnostic fluid, can be used in personal health devices for real-time monitoring of chemical markers including salivary lactate analysis [33]. Chai et al. developed a saliva nanosensor with a radio-frequency identification tag, integrated into dental implants for detecting cardiac biomarkers in saliva and predicting close heart attack in patients suffering from cardiovascular diseases [34]. In another approach, an instrumented mouthguard was designed and fabricated by Kim et al. [35] for measuring salivary uric acid levels which could be a biomarker for several diseases including hyperuricemia, gout, physical stress, and renal syndrome. The fabricated device showed high selectivity and sensitivity to low level of uric acid as well as great stability during a 4-h operation period [35]. Mannoor et al. [36] developed a hybrid biosensor made of graphene layers printed onto water-soluble silk, for noninvasive detection of bacteria through body fluids including sweat and saliva. This graphene/silk hybrid device illustrated an extremely high sensitivity to bacteria in body fluid with detection limits down to a single bacterium [36]. In addition, the fabricated device provided the potential users with battery-free operation and wireless communication system via radio frequency [36]. Arakawa et al. [37] designed and fabricated a salivary sensor equipped with a wireless measurement system, embedded onto a mouthguard support, featuring a high sensitivity toward detection of glucose over a range of 5–1000 μmol L−1. The device demonstrated a great stability during a 5-h real-time glucose monitoring period in an artificial saliva with a phantom jaw [37]. In a similar approach, de Castro et al. [38] developed a microfluidic paper-based device integrated into a mouthguard, for continues monitoring of glucose and nitrite in human saliva. The saliva samples were collected from periodontitis and/or diabetes patients as well as healthy individuals. The fabricated device featured a low detection limit of 27 and 7 μmol L−1 for glucose and nitrite, respectively [38].
\nIn summary, there is a great potential for micro- and nanosensors’ integration into healthcare monitoring devices, developing new technologies for noninvasive detection of diseases in the human body. Flexible wearable devices offer promising capabilities in real-time monitoring of body fluids including tear, sweat, and saliva. However, more research is required to expand the use of wearable platforms in continuous analysis of body fluids, providing reliable real-time detection of targeting ions and proteins, among other complex analytes.
\nIdiopathic pulmonary fibrosis (IPF) is a common interstitial lung disease (ILD) caused by environmental exposures, infections, or traumatic injuries and subsequent epithelial damage [1, 2]. It is characterized by fibroblast activation, followed by excessive secretion of extracellular matrix in the bronchial walls and alveolar interstitium [3]. This uncontrolled deposition leads to stiffening of lung tissue, which impairs diffusion of gases and reduces blood oxygenation [3, 4]. More prevalent among males and adults over 65 years old, it has a high incidence in North America and Europe [1]. Smoking, family history, and genetic mutations associated with telomere length maintenance have been linked to increased risk of developing IPF, as well as the history of gastroesophageal reflux disease and obstructive sleep apnea [1].
Patients typically present with chronic, progressive dyspnea, and dry cough [5]. Their history may include long-term smoke or workplace exposure such as inhalation of wood or metal particulates [6]. On physical examination, bibasilar inspiratory crackles (“velcro rales”) and finger clubbing may be seen [4, 7]. Pulmonary function tests (PFTs) usually demonstrate reduced lung capacity and reduced diffusion capacity for carbon monoxide, indicating restrictive disease and abnormal gas exchange [4, 8]. Exclusion of other interstitial lung diseases—including autoimmune diseases—is required before a diagnosis can be made. Additionally, the presence of a honeycomb fibrosis pattern on high-resolution computed tomography is necessary [4, 8]. Patients commonly have at least one comorbidity, such as chronic obstructive pulmonary disease (COPD), pulmonary hypertension, lung cancer, and diabetes mellitus [4, 8].
IPF is characterized by irreversible and potentially fatal lung deterioration [8, 9]. Patients may experience different rates of disease progression, ranging from gradual deterioration to stable periods lasting months or years. Symptoms associated with progression include worsening dyspnea, hypoxemia, and pulmonary hypertension, as well as fatal exacerbations, where respiratory function declines acutely and unpredictably [8, 9]. Although the disease course varies among patients, prognosis remain poor, with an average life expectancy of 3–5 years after diagnosis [4, 9].
Since IPF is a progressively fatal disease without remission, treatment is both urgent and necessary [10, 11]. The two medications indicated solely for treatment include the tyrosine kinase inhibitor nintedanib (Ofev®) and the anti-fibrotic agent pirfenidone (Esbriet®) [4, 12]. Both were approved in 2014 after clinical trials suggested that they halted the decline in lung function, including a decline in forced vital capacity (FVC) by 50% over a 1-year period [4, 11]. Moreover, they have been shown to be safe and effective in reducing severe respiratory episodes often seen in IPF [4].
Treatment regimens for COPD, heart disease, and smoking cessation are also recommended to reduce respiratory strain if experienced concurrently [4, 13]. Patients suffering from hypoxemia and IPF often receive supplemental oxygen [4, 14]. Pulmonary rehabilitation, physical therapy, and oxygen are all recommended to improve exercise tolerance and duration, reduce dyspnea, prevent the development of pulmonary hypertension, and improve overall lung capacity [4].
Lung transplantation remains a viable option for those who meet the criteria for the procedure [11]. It must be considered earlier in disease progression, with early evaluation to maximize eligibility [4, 11]. Past treatments like warfarin, N-acetylcysteine, prednisone, and azathioprine are no longer recommended due to an overall lack of treatment efficacy [4, 15]. Furthermore, these pharmacotherapeutic options should be avoided in IPF until high-quality randomized control trials prove efficacy since they have failed to show relevant reductive changes in FVC, adverse events, or death [16].
Though current drug therapies demonstrate a reduction in acute exacerbations due to their cytotoxic and immunosuppressive side effect profiles, non-drug measures are often considered. Unfortunately, patients opting for mechanical ventilation—often as a bridge to lung transplantation—suffer from low survival rates [17]. Poor prognostic indicators include a decline in 6-minute walk (6 MW) distance greater than 150 meters within one year, a decrease in FVC greater than 10% within 6 months, and a decline in diffusing capacity for carbon monoxide (DLCO) greater than 15% within 6 months [4].
Improvements in both quality of life and 6 MW distance can be seen in those undergoing pulmonary rehabilitation [4]. Length of survival is highly variable; patients diagnosed with mild, moderate, and severe diseases survive an average of 55.6, 38.7, and 27.4 months, respectively [4]. Ultimately, transplantation remains the only option for those with advanced IPF; those who do not undergo this procedure often have poorer outcomes [4, 12]. Approximately 66% of transplant recipients live for more than 3 years postsurgery, while 53% survive greater than 5 years [4]. Transplantation does carry certain complications such as cancer, infections, primary graft dysfunction, cytomegalovirus, and allograft rejection are all commonly seen [12]. Moreover, supplemental oxygen has been shown to improve symptom control during exercise, while lung transplantation may increase survival rates and improve patients’ overall quality of life [14].
Since drug therapy is merely supportive therapy, patients are encouraged to take alternative measures to decrease their risk, including smoking cessation, supplemental oxygen, and pulmonary rehabilitation [4]. Ongoing GERD has been thought to worsen IPF, but the use of antacids based on clinical trials remains inconclusive [4]. Although the relation of GERD to IPF is still unknown, the prevalence of GERD and erosive esophagitis are observed more commonly in patients with IPF than in the general population [18, 19].
Lastly, patients should receive pneumonia and influenza vaccinations as part of complementary therapy, though there is no proven benefit for the previously mentioned interventions [14]. Although there is no documented outcome benefit with vaccination in the IPF setting, preventing pulmonary infections is essential as extrapulmonary comorbidities through interactions with environmental factors by various mechanisms are thought to contribute to IPF [20]. Vaccinations are especially recommended for post-transplantation patients since they may be more susceptible immunologically. In outpatient settings, pulmonary hypertension should be controlled with supplemental oxygen [21]. Unless a patient participates in a clinical trial, alternative therapies should be avoided.
Although commonly used for their anti-inflammatory effects, corticosteroids do not improve clinical outcomes in IPF [14, 22]. When used as monotherapy, they show no survival benefit and actually increased risk of morbidity with long-term use [7, 14]. A regimen consisting of prednisone, azathioprine, and N-acetylcysteine (NAC) was once accepted therapy [7, 14]. However, trial data revealed that, compared to placebo, the combination increased risk of death and hospitalization [7, 14].
Ambrisentan (Letairis®), a potent type-A selective endothelin receptor antagonist, was once thought to decrease time to disease progression [7]. However, the ARTEMIS-IPF trial examined its use in IPF patients, finding it to be ineffective and associated with increased risk of hospitalizations and disease progression [7]. The trial was eventually terminated when an interim analysis found minimal efficacy [7]. Recent guidelines no longer recommend the anticoagulant warfarin since it was associated with a higher risk of mortality compared to placebo [7, 14].
After numerous studies yielded conflicting results, new treatment options were developed, including two novel anti-fibrotic agents capable of slowing disease progression [4]. Pirfenidone and nintedanib both demonstrated a significant reduction in annual FVC decline and improved survival [7].
Nintedanib (Ofev®), an oral tyrosine kinase inhibitor, inhibits the fibroblast proliferation leading to progression of lung fibrosis [3, 4]. It may also inhibit other growth factor receptors, including tyrosine kinase vascular endothelial growth factor receptor and platelet-derived growth factor receptor [3, 4, 7]. This multi-faceted inhibition makes it a first-line agent for IPF [3, 7]. The standard dose is 150 mg twice daily taken with food to increase bioavailability [4, 7]. However, dosing can be withheld or lowered to 100 mg twice daily if side effects become intolerable [7]. Once controlled, standard dosing can be resumed [7]. If adverse reactions persist, however, discontinuation should be considered [7]. The most common side effects associated with its use include diarrhea, nausea, and vomiting [7]. Other important side effects include weight loss and drug-induced hepatotoxicity, designated by a 3–5 fold increase in AST/ALT, with or without severe liver damage. Discontinuation or dose reduction is based on the presence of severe liver damage; details relating to specific therapeutic steps can be found in Table 1. Adverse reactions should be monitored alongside signs of increased bleeding, especially in those taking anticoagulants. Arterial thromboembolic events have been noted in patients taking nintedanib, and caution should be exercised in those at high risk for cardiovascular events [4]. Basic pharmacokinetics and special population dosing can be found in Table 1 [4].
Bioavailability | 5% Increases by 20% when given with food |
---|---|
Half-life | 9.5 hours |
Protein Binding | 97.8% |
Volume of Distribution | Greater than 1000 L |
Metabolism | Hydrolytic cleavage by esterases (Major) CYP3A4 (Minor) |
Elimination | More than 90% of the dose eliminated via biliary/fecal excretion |
Drug Interactions | P-glycoprotein (P-gp), CYP3A4 inducers |
Dose Adjustments |
|
Monitoring Parameters |
|
Nintedanib pharmacokinetic parameters and special considerations [4].
Pirfenidone (Esbriet®) is an oral synthetic pyridine derivative with anti-fibrotic and anti-inflammatory properties [7, 12, 23, 24]. Its anti-fibrotic effects arise from down-regulation of transforming growth factor (TGF) β and tumor necrosis factor (TNF) α [7, 23, 25]. It may inhibit fibroblast proliferation, expression of heat-shock protein 47, and collagen synthesis as well [7, 23, 24, 25]. Clinically, pirfenidone reduces worsening of FVC and may reduce risk of hospitalization [7, 23, 26]. Several studies like CAPACITY, ASCEND and RECAP have confirmed its long-term safety, efficacy, and favorable tolerability [7, 12].
Common side effects and clinical pharmacology can be found in Table 2. Most prevalent are gastrointestinal (GI) and skin-related adverse drug effects, which generally wane after the first 6 months and do not impact a patient’s ability to continue and maintain a high-dose intensity [12]. Several side effects like fatigue, photosensitivity, and GI distress may require dose reductions [7, 12]. Fatigue, in particular, is observed within the first few weeks of treatment and may substantially affect the quality of life. It may be difficult to distinguish from the disease itself, though it can be managed by dose modifications or even discontinuation [7, 12]. Several studies have examined the importance of taking pirfenidone with food [27, 28, 30, 31] Administration after meals slows absorption and may mitigate GI side effects [7, 12, 27, 28].
Bioavailability | Unknown |
---|---|
Half-Life | 3.0 hours |
Protein binding | Mean of 50–58% at concentrations of 1–10 μg/mL. |
Volume of Distribution | Mean of 59–71 L following oral administration |
Dosage and Administration | Recommend titration to 801 mg three times daily (2403 mg/day) with food |
Metabolism and Excretion | Primarily metabolized in the liver and bio-transformed by CYP1A2 Roughly 80% dose excreted in urine as metabolite 5-carboxy-pirfenidone |
Common side effects | Nausea, rash, dyspnea, diarrhea, fatigue, bronchitis, upper respiratory tract infections, dizziness, photosensitivity |
Interactions |
|
Warnings/Precautions |
|
Monitoring Parameters |
|
Special Populations |
|
Updated practice guidelines recommend both nintedanib and pirfenidone [15]. Though both have been shown safe and effective, a lack of head-to-head trials makes it difficult to recommend one over the other [15]. The two agents have a different mechanism of action, making the prospect of combination therapy intriguing [12, 32]. However, when investigated, it was found that the combination led to greater photosensitivity and GI side effects [12, 32].
Acute exacerbations (AE) are defined as an acute downturn in blood oxygenation, increased lung attenuation per computed tomography scan, and acute worsening of dyspnea [33]. Common causes include exposure to particulate matter (PM) ≥ 2.5 μm or crocin peptide released by
Since AE mortality rates range between 60 and 80% within a 90-day period, most care is strictly palliative in nature [39]. The two primary therapies include corticosteroids like prednisone and cytotoxic medications like cyclophosphamide. However, no proven benefit for these therapies has been demonstrated [40]. In addition, mechanical ventilation should not be employed due to poor outcomes [41]. Novel therapy involving administration of polymyxin B-immobilized fiber column (PMX-DHP), originally developed to manage sepsis by removing plasma endotoxins, has shown increased effectiveness [38, 42]. One limitation of its use is it can lower white blood cell counts via absorption of neutrophils [38, 39]. It remains most effective if administered within 3–7 days of AE onset [38, 39].
The SENSCIS trial was a 52-week randomized, placebo-controlled, double-blind study examining the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD) with nintedanib [43, 44]. It was shown to decrease FVC decline rate (mL/year) within the treatment group compared to placebo [3, 43]. An annual difference of −52.4 mL/year for nintedanib versus −93.3 mL/year for placebo was shown at 52 weeks [3, 43]. The INPULSIS trial, a 52-week, randomized, double-blind, phase 3 trial, showed a similar reduction in FVC decline rate with nintedanib versus placebo [3, 45]. TOMORROW, a 52-week, randomized, double-blind, placebo-controlled, phase 2 trial—alongside INPULSIS—showed a decrease in acute exacerbations with nintedanib compared to placebo [4, 45]. The INBUILD trial, a 52-week, randomized, double-blind, placebo-controlled, parallel-group trial, examined patients with progressive fibrosing interstitial lung diseases other than IPF [3, 46]. Treatment groups received nintedanib 150 mg twice daily or placebo [3, 46]. Reduction in FVC decline rate was uniform across the five subgroups [46, 47].
Three major trials have recently examined pirfenidone, including CAPACITY 004, CAPACITY 006, and ASCEND [4, 12]. The two CAPACITY trials were run side-by-side for 72 weeks [48, 49]. CAPACITY 004 showed a significant reduction in FVC decline with pirfenidone, though only a significant difference up to week 48 was seen in CAPACITY 006 [48, 49]. The ASCEND trial, a 52-week, phase 3 trial, found that patients with a predicted FVC > 50% at baseline received benefit from pirfenidone over 1 year, reducing the rate of decline by approximately 50% [4, 49]. ASCEND also analyzed 6 MW distance [49, 50]. There was a significant difference between baseline and week 52 with the two treatments, including a 27.5% reduction in the pirfenidone group [49, 50]. Pooled population data from all three trials showed a 48% reduced risk of death at 1 year compared to placebo [48, 49].
As mentioned above, both agents have been shown safe and effective in placebo-controlled, randomized trials [51, 52, 53]. Both may slow the FVC decline rate by almost 50% over 1 year [51]. The two treatments have also demonstrated remarkable efficacy in minimizing severe respiratory hospitalizations and acute exacerbations [51, 54]. Though both agents may reduce mortality, each cost over $100,000 annually [51, 55].
Nintedanib has a unique mechanism of action compared to pirfenidone. It inhibits tyrosine kinase, an enzyme that targets growth factor (GF) pathway receptors like fibroblast GF, platelet-derived GF, and vascular endothelial GF [3, 4]. Elevated bleeding risk is seen in patients taking concomitant anticoagulation therapy [7, 15]. Patients should regularly monitor liver function and GI disturbances, including diarrhea [43, 46]. Conversely, pirfenidone inhibits collagen synthesis, downregulates TGF-β, tumor necrosis factor-α, and reduces fibroblast proliferation [7, 24, 26]. Side effects include abnormal liver function, anorexia, nausea, photosensitive rashes, and vomiting [56].
Pirfenidone comes in a 267 mg capsule, initially dosed as one capsule three times daily the first week [56, 57]. During the second week, the dose can be increased to 534 mg three times daily, and—after two weeks—it can be fully titrated to 801 mg three times (2,403 mg or nine pills per day). It is recommended that each dose be taken after a full meal to minimize GI side effects like nausea, dizziness, and vomiting [56, 57]. Patients may be treated with nintedanib first-line if intolerability to pirfenidone occurs [56, 57, 58]. The maximum recommended dose is 150 mg twice daily [58, 59].
In a 1-year evaluation of both medications, there was a slight decrease in FVC, especially in those with comorbidities, which may account for increases in hospitalization and all-cause mortality [60, 61]. In combined studies, pirfenidone displayed a slower rate of FVC decline than nintedanib, helping to explain increased hospitalizations and mortality with its use [60, 61].
Though pirfenidone is frequently associated with GI complications, diarrhea, and involuntary weight loss is more common with nintedanib [57, 58, 61]. Pirfenidone’s side effects include dyspepsia, nausea, loss of appetite, phototoxic reactions, and difficulty concentrating. Sunscreen use is recommended when taking it. Conversely, nintedanib displays less nausea but greater transaminase elevations [57, 58, 61]. Pirfenidone is older and better studied more nintedanib, which may explain why its gastrointestinal and cognitive side effects are better understood [57, 58, 61]. Phototoxicity is generally absent with nintedanib [57, 61].
Though pirfenidone and nintedanib may slow disease progression, neither will cure IPF or markedly improve current symptoms [4, 62]. Symptom management, especially cough and dyspnea, is crucial to maintaining the quality of life [4, 63]. This is somewhat challenging given the lack of clinical evidence showing improvement in such symptoms and guideline focus on lung function [4, 63].
Both agents have noteworthy side effects. Nintedanib is most frequently associated with diarrhea, nausea, vomiting, and elevated liver enzymes [62]. By comparison, pirfenidone may cause nausea, diarrhea, dyspepsia, anorexia, and gastroesophageal reflux, as well as rash, upper respiratory infections, and fatigue [62, 64].
Another significant burden of IPF is cost [4, 65]. A recent systematic review estimated its annual cost in the United States at $20,000 per patient per year, about three times greater than the national health care resource use per capita [4, 65]. Hospitalizations and acute exacerbations are key drivers of this cost, with an average cost exceeding $16,000 for each IPF-related hospitalization [4, 66]. Due to their specialty drug and brand-only status, pirfenidone and nintedanib remain extremely expensive, with costs exceeding $10,000 per month per agent [4]. However, nintedanib is associated with fewer acute exacerbations and, consequently, decreased medical costs [4, 62, 67]. A recent comparison analysis from the United Kingdom found that the two drugs were comparable in estimated cost and health-related quality of life benefit [4, 68].
It is important to remember that the INBUILD trial was not powered to provide sufficient evidence for the use of nintedanib in rarer, specific fibrosing ILD [47]. However, it can be challenging to recruit patients with these rarer disease states. The fact that nintedanib reduced the rate of disease progression (i.e., FVC decline) in a wide range of progressive fibrosing ILD suggests utility in such populations [47].
In recent decades, our understanding of IPF pathogenicity and management has improved significantly [15, 69]. However, many limitations, such as an inability to translate experimental findings in animal models to human subjects, remain a challenge [69, 70]. Current therapies like nintedanib and pirfenidone are limited to pathways involved in reducing disease progression and physiological decline in those with mild-to-moderate impairment [15, 69]. Second-line treatments capable of improving functional capacity for such patients or benefiting the severely impaired are still needed [15, 70].
Other viable agents have been recently investigated [9]. Increased concentrations of endothelin receptors have been observed in IPF lung tissue [15]. As a result, several clinically significant endothelin receptor antagonists have been previously tested, including ambrisentan, a selective type-A antagonist, and bosentan and macitentan, type-A and type-B antagonists [71, 72]. Nonetheless, recent guidelines strongly discourage the use of ambrisentan given its risk of harm and lack of benefit, along with a conditional recommendation against the use of bosentan and macitentan [15, 73].
The phosphodiesterase-5 inhibitor sildenafil has been investigated due to its role in pulmonary vasodilation and improved gas exchange [15]. Past studies and analyses reported a slight but significant improvement in the degree of dyspnea and quality of life compared to placebo [15]. However, it has failed to demonstrate improvements in mortality, acute exacerbations, and adverse events [15]. Recent guidelines discourage its use, though it continues to be investigated [15, 73].
N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, has also been examined for use in IPF [74]. A pooled analysis compared NAC monotherapy to placebo in IPF patients [15]. Ultimately, there was no significant difference in the rate of death or acute exacerbation, as well as no significant benefit in mortality, quality of life, or adverse outcomes [15]. Current guidelines strongly discourage its use in practice [15, 74].
A recent randomized clinical trial investigated imatinib mesylate (Gleevec®), a tyrosine kinase inhibitor. It showed a statistically significant increased risk of adverse events and no improvement in preventing disease progression or mortality [15, 74]. This distinct lack of benefit has led to its use being discouraged in IPF [15, 74].
Several active interventional and observational trials are currently underway. Recent novel studies suggest that genetic factors may play a crucial role in overall risk, disease progression, and therapeutic response [70, 75]. Future trials and drug development will likely focus more on genetic variation in IPF patients [70, 75].
IPF is a common ILD that is progressive and potentially fatal [4, 9]. It is characterized by decreased lung function stemming from abnormal fibrotic processes, ultimately leading to scarring tissue formation, diminished gas exchange, and reduced blood oxygenation [4, 7]. Though there is no known cause, it is more common in males and elderly patients and is associated with risk factors like smoking, environmental exposure, and multiple comorbidities [4, 9]. Due to insufficient understanding of its pathophysiological mechanisms, there are currently no therapies capable of preventing or reversing IPF [7, 9, 76]. Current management includes antifibrotic drugs like nintedanib (Ofev®) and pirfenidone (Esbriet®), which have been shown to slow lung deterioration [4, 7, 13]. Recent investigations examining nintedanib use in other ILDs with progressive phenotypes have shown favorable results, suggesting that such ILDs share similar mechanisms and may thus benefit from similar treatment [3, 77]. Imatinib mesylate (Gleevec®) is not recommended due to the increased risk of adverse events and no improvement in disease progression or mortality [17, 73]. Similarly, the use of ambrisentan (Letairis®) is discouraged due to lack of effectiveness and increased risk of hospitalization [7]. Other IPF management strategies include smoking cessation, immunization, respiratory rehabilitation, oxygen supplementation, and management of comorbidities [4, 20]. More recent approaches have targeted biological processes linked to IPF, such as aging, oxidative stress, and epithelial-to-mesenchymal cell transition (EMT) [9, 76]. Ultimately, a better understanding of its underlying mechanisms is necessary to develop more effective treatments and reduce mortality [7, 9, 76].
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His main focus now is to unravel the mechanism of drought and heat stress response in plants to tackle climate change related threats in agriculture.",institutionString:null,institution:{name:"Indian Council of Agricultural Research",country:{name:"India"}}},{id:"4782",title:"Prof.",name:"Bishnu",middleName:"P",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4782/images/system/4782.jpg",biography:"Bishnu P. Pal is Professor of Physics at Mahindra École\nCentrale Hyderabad India since July 1st 2014 after retirement\nas Professor of Physics from IIT Delhi; Ph.D.’1975 from IIT\nDelhi; Fellow of OSA and SPIE; Senior Member IEEE;\nHonorary Foreign Member Royal Norwegian Society for\nScience and Arts; Member OSA Board of Directors (2009-\n11); Distinguished Lecturer IEEE Photonics Society (2005-\n07).",institutionString:null,institution:{name:"Indian Institute of Technology Delhi",country:{name:"India"}}},{id:"69653",title:"Dr.",name:"Chusak",middleName:null,surname:"Limsakul",slug:"chusak-limsakul",fullName:"Chusak Limsakul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Prince of Songkla University",country:{name:"Thailand"}}},{id:"23804",title:"Dr.",name:"Hamzah",middleName:null,surname:"Arof",slug:"hamzah-arof",fullName:"Hamzah Arof",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/23804/images/5492_n.jpg",biography:"Hamzah Arof received his BSc from Michigan State University, and PhD from the University of Wales. 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In this chapter, I describe the similarities and differences between the naïve and primed pluripotent states as exemplified by mouse embryonic stem cells (mESCs), mouse epiblast stem cells (mEpiSCs), human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). I also review the efforts for derivation of naïve human pluripotent stem cells by manipulating culture conditions during reprogramming of somatic cells and attempts to revert primed hESCs to the naïve state. Understanding the requirements for induction and maintenance of the naïve pluripotent state will facilitate studies on early human embryonic development and understanding the mechanisms involved in X inactivation in vitro. In addition, the development of naïve hiPSCs will improve the efficiency of gene targeting for the purpose of modeling human diseases as well as for generating gene‐corrected autologous pluripotent stem cells for regenerative medicine.",book:{id:"5207",slug:"pluripotent-stem-cells-from-the-bench-to-the-clinic",title:"Pluripotent Stem Cells",fullTitle:"Pluripotent Stem Cells - From the Bench to the Clinic"},signatures:"Daman Kumari",authors:[{id:"180527",title:"Dr.",name:"Daman",middleName:null,surname:"Kumari",slug:"daman-kumari",fullName:"Daman Kumari"}]},{id:"26987",doi:"10.5772/32381",title:"Markers for Hematopoietic Stem Cells: Histories and Recent Achievements",slug:"endothelial-cell-selective-adhesion-molecule-esam-a-novel-hsc-marker",totalDownloads:7214,totalCrossrefCites:7,totalDimensionsCites:12,abstract:null,book:{id:"694",slug:"advances-in-hematopoietic-stem-cell-research",title:"Advances in Hematopoietic Stem Cell Research",fullTitle:"Advances in Hematopoietic Stem Cell Research"},signatures:"Takafumi Yokota, Kenji Oritani, Stefan Butz, Stephan Ewers, Dietmar Vestweber and Yuzuru Kanakura",authors:[{id:"91282",title:"Dr.",name:"Takafumi",middleName:null,surname:"Yokota",slug:"takafumi-yokota",fullName:"Takafumi Yokota"},{id:"97447",title:"Dr.",name:"Takao",middleName:null,surname:"Sudo",slug:"takao-sudo",fullName:"Takao Sudo"},{id:"97448",title:"Dr.",name:"Kenji",middleName:null,surname:"Oritani",slug:"kenji-oritani",fullName:"Kenji Oritani"},{id:"97450",title:"Prof.",name:"Yuzuru",middleName:null,surname:"Kanakura",slug:"yuzuru-kanakura",fullName:"Yuzuru Kanakura"}]},{id:"18217",doi:"10.5772/23755",title:"Stem Cells: General Features and Characteristics",slug:"stem-cells-general-features-and-characteristics",totalDownloads:9698,totalCrossrefCites:5,totalDimensionsCites:12,abstract:null,book:{id:"216",slug:"stem-cells-in-clinic-and-research",title:"Stem Cells in Clinic and Research",fullTitle:"Stem Cells in Clinic and Research"},signatures:"Hongxiang Hui, Yongming Tang, Min Hu and Xiaoning Zhao",authors:[{id:"53560",title:"Dr.",name:"Hongxiang",middleName:null,surname:"Hui",slug:"hongxiang-hui",fullName:"Hongxiang Hui"},{id:"59235",title:"Mr",name:"Xiaoning",middleName:null,surname:"Zhao",slug:"xiaoning-zhao",fullName:"Xiaoning Zhao"},{id:"59236",title:"Mr",name:"Yongming",middleName:null,surname:"Tang",slug:"yongming-tang",fullName:"Yongming Tang"},{id:"118970",title:"Dr.",name:"Min",middleName:null,surname:"Hu",slug:"min-hu",fullName:"Min Hu"}]}],mostDownloadedChaptersLast30Days:[{id:"18220",title:"How do Mesenchymal Stem Cells Repair?",slug:"how-do-mesenchymal-stem-cells-repair-",totalDownloads:5925,totalCrossrefCites:9,totalDimensionsCites:16,abstract:null,book:{id:"216",slug:"stem-cells-in-clinic-and-research",title:"Stem Cells in Clinic and Research",fullTitle:"Stem Cells in Clinic and Research"},signatures:"Patricia Semedo, Marina Burgos-Silva, Cassiano Donizetti-Oliveira and Niels Olsen Saraiva Camara",authors:[{id:"28751",title:"Prof.",name:"Niels",middleName:"Olsen Saraiva",surname:"Camara",slug:"niels-camara",fullName:"Niels Camara"},{id:"30464",title:"Prof.",name:"Patricia",middleName:null,surname:"Semedo",slug:"patricia-semedo",fullName:"Patricia Semedo"},{id:"30465",title:"BSc.",name:"Cassiano",middleName:null,surname:"Donizetti-Oliveira",slug:"cassiano-donizetti-oliveira",fullName:"Cassiano Donizetti-Oliveira"},{id:"30466",title:"BSc.",name:"Marina",middleName:null,surname:"Burgos-Silva",slug:"marina-burgos-silva",fullName:"Marina Burgos-Silva"}]},{id:"61053",title:"Adult Stem Cell Membrane Markers: Their Importance and Critical Role in Their Proliferation and Differentiation Potentials",slug:"adult-stem-cell-membrane-markers-their-importance-and-critical-role-in-their-proliferation-and-diffe",totalDownloads:1328,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The stem cells are part of the cells that belong to the stromal tissue. These cells remain in a quiescent state until they are activated by different factors, usually those generated by an alteration in the parenchymal tissue. These cells have characteristic membrane markers such as CD73, CD90, and CD105. Those are a receptor, which in response to their ligand induces strong changes in different metabolic pathways that lead to these cells, both to generate molecules with different activities and to leave their stationary phase to reproduce and even differentiate. This review describes the metabolic pathways dependent on these membrane markers and how they influence on parenchymal tissue and other stromal cells.",book:{id:"6658",slug:"stromal-cells-structure-function-and-therapeutic-implications",title:"Stromal Cells",fullTitle:"Stromal Cells - Structure, Function, and Therapeutic Implications"},signatures:"Maria Teresa Gonzalez Garza",authors:[{id:"181389",title:"Ph.D.",name:"Maria Teresa",middleName:null,surname:"Gonzalez Garza",slug:"maria-teresa-gonzalez-garza",fullName:"Maria Teresa Gonzalez Garza"}]},{id:"63044",title:"Stromal-Epithelial Interactions during Mammary Gland Development",slug:"stromal-epithelial-interactions-during-mammary-gland-development",totalDownloads:1372,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"Mammary gland is an organ, which undergoes the majority of its development in the postnatal life of mammals. The complex structure of the mammary gland comprises epithelial and myoepithelial cells forming the parenchymal tissue and adipocytes, fibroblasts, vascular endothelial cells, and infiltrating immune cell composing the stromal compartment. During puberty and in adulthood, circulating hormones released from the pituitary and ovaries regulate the rate of development and functional differentiation of the mammary epithelium. In addition, growing body of evidence shows that interactions between the stromal and parenchymal compartments of the mammary gland play a crucial role in mammogenesis. This regulation takes place on a paracrine level, by locally synthesized growth factors, adipokines, and cytokines, as well as via direct cell-cell interactions. This chapter summarizes the current knowledge about the complex nature of interactions between the mammary epithelium and stroma during mammary gland development in different mammalian species.",book:{id:"6658",slug:"stromal-cells-structure-function-and-therapeutic-implications",title:"Stromal Cells",fullTitle:"Stromal Cells - Structure, Function, and Therapeutic Implications"},signatures:"Żaneta Dzięgelewska and Małgorzata Gajewska",authors:[{id:"165068",title:"Dr.",name:"Malgorzata",middleName:null,surname:"Gajewska",slug:"malgorzata-gajewska",fullName:"Malgorzata Gajewska"},{id:"249847",title:"Ms.",name:"Żaneta",middleName:null,surname:"Dzięgelewska",slug:"zaneta-dziegelewska",fullName:"Żaneta Dzięgelewska"}]},{id:"69757",title:"Flow Cytometry Applied to the Diagnosis of Primary Immunodeficiencies",slug:"flow-cytometry-applied-to-the-diagnosis-of-primary-immunodeficiencies",totalDownloads:1041,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Primary immunodeficiencies are the result of biological defects associated with functional immune abnormalities. It consists of a group of disorders showing a higher incidence and severity of infections, expression of immunological dysregulation such as inflammation and lymphoproliferation. The immunophenotyping and in vitro functional characterization of immunodeficient patients contribute, together with the clinical aspects, to define the underlying immune defect particularities. Flow cytometry applications in primary immunodeficiency assessment are multiple and include the study of a wide range of specific cell lymphocyte subpopulations. This chapter describes the main techniques used in the diagnosis of a wide variety of primary immunodeficiencies, in which intracellular proteins or activation markers involved in immunity are evaluated, as well as functional proliferation, cytokine production, phosphorylation of transcription factors, cytotoxic and degranulation capacity. Flow cytometry is a tool that allows rapid and accurate evaluation of multiple lymphocyte populations and immunological function, and this information is essential for the diagnosis and evaluation of patients with primary immunodeficiencies.",book:{id:"6913",slug:"innovations-in-cell-research-and-therapy",title:"Innovations in Cell Research and Therapy",fullTitle:"Innovations in Cell Research and Therapy"},signatures:"Mónica Martínez-Gallo and Marina García-Prat",authors:[{id:"286242",title:"Ph.D.",name:"Mónica",middleName:null,surname:"Martínez Gallo",slug:"monica-martinez-gallo",fullName:"Mónica Martínez Gallo"},{id:"286704",title:"BSc.",name:"Marina",middleName:null,surname:"García-Prat",slug:"marina-garcia-prat",fullName:"Marina García-Prat"}]},{id:"50685",title:"States of Pluripotency: Naïve and Primed Pluripotent Stem Cells",slug:"states-of-pluripotency-na-ve-and-primed-pluripotent-stem-cells",totalDownloads:4009,totalCrossrefCites:4,totalDimensionsCites:12,abstract:"Pluripotent stem cells are classified into naïve and primed based on their growth characteristics in vitro and their potential to give rise to all somatic lineages and the germ line in chimeras. In this chapter, I describe the similarities and differences between the naïve and primed pluripotent states as exemplified by mouse embryonic stem cells (mESCs), mouse epiblast stem cells (mEpiSCs), human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). I also review the efforts for derivation of naïve human pluripotent stem cells by manipulating culture conditions during reprogramming of somatic cells and attempts to revert primed hESCs to the naïve state. Understanding the requirements for induction and maintenance of the naïve pluripotent state will facilitate studies on early human embryonic development and understanding the mechanisms involved in X inactivation in vitro. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{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,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-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"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,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},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:48,paginationItems:[{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81756",title:"Alteration of Cytokines Level and Oxidative Stress Parameters in COVID-19",doi:"10.5772/intechopen.104950",signatures:"Marija Petrusevska, Emilija Atanasovska, Dragica Zendelovska, Aleksandar Eftimov and Katerina Spasovska",slug:"alteration-of-cytokines-level-and-oxidative-stress-parameters-in-covid-19",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"81681",title:"Immunomodulatory Effects of a M2-Conditioned Medium (PRS® CK STORM): Theory on the Possible Complex Mechanism of Action through Anti-Inflammatory Modulation of the TLR System and the Purinergic System",doi:"10.5772/intechopen.104486",signatures:"Juan Pedro Lapuente",slug:"immunomodulatory-effects-of-a-m2-conditioned-medium-prs-ck-storm-theory-on-the-possible-complex-mech",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science and Technology from the Department of Chemistry, National University of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013. She relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the National Institute of Fundamental Studies from April 2013 to October 2016. She was a senior lecturer on a temporary basis at the Department of Food Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is currently Deputy Principal of the Australian College of Business and Technology – Kandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI) Ambassador to Sri Lanka.",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-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"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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