\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"1348",leadTitle:null,fullTitle:"Neuroimaging - Clinical Applications",title:"Neuroimaging",subtitle:"Clinical Applications",reviewType:"peer-reviewed",abstract:'Modern neuroimaging tools allow unprecedented opportunities for understanding brain neuroanatomy and function in health and disease. Each available technique carries with it a particular balance of strengths and limitations, such that converging evidence based on multiple methods provides the most powerful approach for advancing our knowledge in the fields of clinical and cognitive neuroscience. The scope of this book is not to provide a comprehensive overview of methods and their clinical applications but to provide a "snapshot" of current approaches using well established and newly emerging techniques.',isbn:null,printIsbn:"978-953-51-0200-7",pdfIsbn:"978-953-51-6866-9",doi:"10.5772/1814",price:159,priceEur:175,priceUsd:205,slug:"neuroimaging-clinical-applications",numberOfPages:592,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d079672454f0551916e81fc3685b846a",bookSignature:"Peter Bright",publishedDate:"March 9th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1348.jpg",numberOfDownloads:128890,numberOfWosCitations:34,numberOfCrossrefCitations:15,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:38,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:87,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 22nd 2010",dateEndSecondStepPublish:"December 20th 2010",dateEndThirdStepPublish:"April 26th 2011",dateEndFourthStepPublish:"May 26th 2011",dateEndFifthStepPublish:"July 25th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"49019",title:"Prof.",name:"Peter",middleName:null,surname:"Bright",slug:"peter-bright",fullName:"Peter Bright",profilePictureURL:"https://mts.intechopen.com/storage/users/49019/images/2330_n.jpg",biography:"Dr. Peter Bright was educated at the Universities of Surrey (BSc, 1991), Reading (MSc, 1993) and Cambridge (PhD, 1999). His research in the fields of memory and conceptual knowledge are well known. He has held research positions at the MRC Cognition and Brain Sciences Unit in Cambridge (1994-1995), King’s College London (1998-2001), and the University of Cambridge (2001-2005). He currently holds the position of Reader at Anglia Ruskin University in Cambridge (since 2005).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Anglia Ruskin University",institutionURL:null,country:{name:"United Kingdom"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1008",title:"Radiology Diagnosis",slug:"radiology-diagnosis"}],chapters:[{id:"31404",title:"Congenital Malformation of the Brain",doi:"10.5772/22936",slug:"congenital-malformations-of-the-brain",totalDownloads:17468,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Shahina Bano, Vikas Chaudhary and Sachchidanand Yadav",downloadPdfUrl:"/chapter/pdf-download/31404",previewPdfUrl:"/chapter/pdf-preview/31404",authors:[{id:"49858",title:"Dr.",name:"Shahina",surname:"Bano",slug:"shahina-bano",fullName:"Shahina Bano"},{id:"60644",title:"Dr.",name:"Vikas",surname:"Chaudhary",slug:"vikas-chaudhary",fullName:"Vikas Chaudhary"},{id:"60645",title:"Dr.",name:"Sachchidanand",surname:"Yadav",slug:"sachchidanand-yadav",fullName:"Sachchidanand Yadav"}],corrections:null},{id:"31405",title:"Neuroimaging in Inborn Errors of Metabolism",doi:"10.5772/24803",slug:"neuroimaging-in-inborn-errors-of-metabolism",totalDownloads:12356,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Carlos Casimiro, Paula Garcia, Miguel Cordeiro, Isabel Fineza, Teresa Garcia and Luísa Diogo",downloadPdfUrl:"/chapter/pdf-download/31405",previewPdfUrl:"/chapter/pdf-preview/31405",authors:[{id:"50822",title:"Prof.",name:"Luisa",surname:"Diogo",slug:"luisa-diogo",fullName:"Luisa Diogo"},{id:"59630",title:"Dr.",name:"Carlos",surname:"Casimiro",slug:"carlos-casimiro",fullName:"Carlos Casimiro"},{id:"61288",title:"Dr.",name:"Paula",surname:"Garcia",slug:"paula-garcia",fullName:"Paula Garcia"},{id:"61289",title:"Dr.",name:"Miguel",surname:"Cordeiro",slug:"miguel-cordeiro",fullName:"Miguel Cordeiro"},{id:"61290",title:"Dr.",name:"Isabel",surname:"Fineza",slug:"isabel-fineza",fullName:"Isabel Fineza"},{id:"62860",title:"Dr.",name:"Teresa",surname:"Garcia",slug:"teresa-garcia",fullName:"Teresa Garcia"}],corrections:null},{id:"31406",title:"Acquired Demyelinating Disorders of the CNS in Children",doi:"10.5772/23731",slug:"acquired-demyelinating-disorders-of-the-cns-in-children",totalDownloads:8930,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"R. 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Schneidhofer, S. Sen and N. Dörr",authors:[{id:"38255",title:"MSc",name:"Christoph",middleName:null,surname:"Schneidhofer",fullName:"Christoph Schneidhofer",slug:"christoph-schneidhofer"},{id:"38280",title:"BSc.",name:"Sedat",middleName:null,surname:"Sen",fullName:"Sedat Sen",slug:"sedat-sen"},{id:"38281",title:"Dr.",name:"Nicole",middleName:null,surname:"Dörr",fullName:"Nicole Dörr",slug:"nicole-dorr"}]}]}],publishedBooks:[{type:"book",id:"6839",title:"Anaerobic Digestion",subtitle:null,isOpenForSubmission:!1,hash:"b2f120cc045f5e705912043f9802ec7d",slug:"anaerobic-digestion",bookSignature:"J. 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Iron oxide nanoparticles usually include several phases such as magnetite (Fe3O4), maghemite (γ-Fe2O3), and ferrihydrite (Fh) [1, 2, 3]. The surface structure, crystal phase and facet, shape as well as size dependence make them have various functions [4, 5].
Due to excellent magnetic property, iron oxide nanoparticles have been broadly used in biomedical field, such as magnetic separation of biosamples (nucleic acids, proteins, cells), drug delivery, tumor hyperthermia. Among these applications, iron oxide nanoparticles are assumed as biological inert, even if they have been used as Fenton catalysts for advanced oxidation in waste treatment. In recent years, enzyme-like properties of iron oxide nanoparticles have drawn more attention. In 2007, Yan group found that these nanoparticles performed intrinsic peroxidase (POD)-like activity [6]. Since then, many nanoparticles are found with enzyme-like properties, which boost the development of nanozymes [7, 8]. In particular, iron oxide nanoparticles are found with multiple enzyme-like activities. For instance, Xiaolan Huang found that iron oxide nanoparticles exhibit phosphatase activity that can hydrolyze phosphate ester. Currently, iron oxide nanoparticles are classified as one typical nanozymes and extend their biomedical applications such as antibacterial, antiviral, antitumor, antioxidant, immune regulation.
In addition, iron oxide nanoparticles are also found in biological system, such as magnetosomes of bacteria and ferritin, which are classified as natural nanozymes. These biological iron oxide nanoparticles may be involved in metabolic processes and contribute to life evolution. Thus, the studies on enzyme-like property of iron oxide nanoparticles not only have important significance in extending their biomedical applications, but also provide clues for origin of life. In this chapter, we will summarize the cutting-edged progress in the field of iron oxide nanoparticles related to biological properties (mainly for enzyme-like catalysis) and highlight the significance of such properties in biomedicine and nanobiology.
Iron oxide nanoparticles perform enzyme-like activities that can catalyze the biochemical reactions mediated by natural enzymes under mild condition. The fundamental rationale is that iron serves as critical cofactor in the active center of many natural enzymes. Currently, more than 80 types of natural enzymes are found with iron as cofactors in the form of hemin, coordinated single iron or di-iron, iron-sulfur clusters, which perform the activities ranging from oxidoreductases to nitrogenase. Since iron oxide nanoparticles are rich in ferrous and ferric iron, it is rational to speculate that these nanoparticles mimic the activities of iron-containing enzymes.
It should be noted that the structure of iron oxide nanoparticles is quite different to that of natural enzymes. It is rigid crystal structure in iron oxide nanoparticles, and the active sites may locate on the surface of the nanoparticle. Such inorganic structure endows iron oxide nanoparticles with superior stability and high activity (multiple active sites in single nanoparticle), which makes them suitable for applications under unfriendly environments for natural enzymes. Below, we will introduce the enzyme-like activities reported in the recent decade, in particular in the view of nanozymes.
In 2007, Yan group for the first time reported that ferromagnetic iron oxide (Fe3O4) nanoparticles perform intrinsic peroxidase-like activity that can catalyze colorimetric reaction in the presence of hydrogen peroxide (H2O2) under acidic condition (pH 3–6.5) (Figure 1) [6, 9]. In this reaction, H2O2 is converted to free radicals (•OH) as intermediate. The catalytic behaviors including substrates, optimal pH, and temperature of iron oxide nanoparticles are all similar as those of horseradish peroxidase (HRP). In particular, enzymatic kinetics assay showed that iron oxide nanoparticles fit Michaelis–Menten equation and follow ping-pong mechanism, which confirmed that iron oxide nanoparticles are mimic of HRP. For nanoparticles with the size at 300 nm in diameter, the catalytic efficiency of a single nanoparticle is comparable with a single HRP molecule. However, this does not mean that iron in the nanoparticle has higher activity than that in HRP. Each HRP molecule only has one active site and one iron. In contrast, there may be multiple active sites on the surface of one iron oxide nanoparticle, strongly related to crystal structures, exposed facets, defects, and chemical modifications (Figure 2).
Iron oxide nanoparticles with peroxidase-like activity catalyze colorimetric reaction mediated by HRP [
Diagrams of iron oxide slabs with different crystal structures, exposed facets, defects, and chemical modifications [
Xingfa Gao group used density functional theory calculations to investigate the peroxidase-mimetic mechanisms for a series of iron oxide nanosurfaces [10]. They proposed that the activity of these iron oxide nanoparticles mimicked that of POD by following a three-step mechanism in which chemisorption of H2O2 was absorbed onto the surface to form two hydroxyl adsorbates and two subsequent reduction processes to remove the hydroxyl groups from the surface. The POD-like catalyses of all iron oxide surfaces proceeded
Mechanism and kinetics of POD-like reactions catalyzed by iron oxides as determined from DFT calculations [
Compared with natural enzymes, iron oxide nanoparticles exhibit high stability to non-physiological conditions such as low or high temperature, acidic or basic pH, organic solvents. In addition, the peroxidase-like activity of iron oxide nanoparticles is tunable by adjusting their size, morphology, facets, defects, or surface modifications. Similar to natural enzymes, the activity of iron oxide nanoparticles also can be affected by activators or inhibitors [11]. However, the specific peroxidase-like activity of pure iron oxide nanoparticles is in the range of several U/mg, which is much lower than that of HRP with specific activity >150 U/mg [12]. To enhance the specific activity, iron oxide nanoparticles can by hybridized with other nanovectors to form nanocomplexes. Juewen Liu group used molecular imprinting to modify the surface and achieved selective catalysis for the substrates of TMB and ABTS. They found that introducing charged monomers led to nearly 100-fold specificity for the imprinted substrate over the nonimprinted compared with that of bare Fe3O4 [13].
In addition to peroxidase-like activity, iron oxide nanoparticles were found with catalase-like activity under neutral pH by Gu’s group [14]. Using electron spin resonance spectroscopy, they found that both Fe3O4 and γ-Fe2O3 nanoparticles decomposed H2O2 into hydroxyl radicals under acidic condition (pH < 6.5), showing peroxidase-like activity (Fe3O4 > γ-Fe2O3). However, H2O2 was decomposed into H2O and O2 under neutral pH (pH 7.4) condition by the two nanoparticles, demonstrating catalase-like activity. These results indicated that the enzyme-like activities of iron oxide nanoparticles are pH-dependent; that is, peroxidase-like activity is dominant at acidic pH and catalase-like activity is dominant at neutral pH (Figure 4).
ESR spectra subtraction of spin adduct DMPO/•OH [
Mover, ferrihydrite, a precursor for most iron oxides, was found with catalase-like activity by Fan’s group [15]. They found that among the 10 forms of iron oxide nanoparticles, 2-line ferrihydrite exhibited the highest catalase-like activity in the pH range of 4.0–8.7, but no peroxidase-like and superoxide dismutase-like activity. The structure-activity studies indicated that the surface iron-associated hydroxyl groups play a key role in catalase-like catalysis. Since natural catalase uses hemin as cofactor in active center, the catalase-like property of the previously mentioned iron oxide nanoparticles may be derived from the iron on the surface (Figure 5).
The structure-activity relationship of ferrihydrite nanoparticles in catalase-like catalysis [
Inspired by some natural superoxide dismutase (SOD) using iron as cofactor, iron oxide nanoparticles are expected to perform SOD-like activity that converts superoxide (O2−•) into O2 and H2O2 or H2O under basic pH (7 ~ 8). However, naked iron oxide nanoparticles exhibited quite low SOD-like activity. Gu et al. modified vitamin B2 on iron oxide nanoparticles and significantly improved the SOD-like activity, providing a reactive oxygen species (ROS)-scavenging ability [16] (Figure 6).
Modification of VB2 to improve SOD-like activity of iron oxide nanoparticles [
Inspired by some natural lipoxidase using iron as cofactor, iron oxide nanoparticles are expected to perform activity inducing lipid peroxidation. Tao Qin et al. incubated iron oxide nanoparticles with liposome at neutral and found that lipid peroxidation occurred by measuring MDA. This phenomenon was repeated using virus containing lipid envelope, which can disrupt viral integrity and degrade surface protein related to infecting host cells [17].
Of noted, although iron oxide nanoparticles exhibited four oxidoreductase-like activities [18], the catalytic efficiency of each activity is different, which may follow the order: peroxidase>catalase>SOD>lipoxidase. In addition, these activities show pH dependency. The pH range may have overlap, and thus, iron oxide nanoparticles may perform multiple activities simultaneously at a specific pH.
Beside the previously mentioned oxidoreductase-like properties, Xiao-Lan Huang discovered that iron oxide nanoparticles exhibited the activity to catalyze the hydrolysis of phosphate ester with enzyme-like kinetics [19, 20]. The iron oxide nanoparticles prepared using a dialysis membrane tube (DMT) system led to the decrease of phosphate esters such as G6P, ATP, G2P and the increase of inorganic orthophosphate (Pi), indicating a catalytic effect on the hydrolysis reaction, which is mediated by natural phosphatase such as purple acid phosphatase (PAP). The authors highlighted that along with other studies of nanozymes such as iron oxide, vanadium pentoxide, and molybdenum trioxide, the oxo-metal bond in the oxide nanoparticles may play critical role for the catalysis in the corresponding natural metalloproteins. In particular, these inorganic nanoparticles with enzyme-like properties not only challenge the traditional concept of enzymes, but also provide new insights into life origin in the early Earth environments (Figure 7) [21, 22].
The active form of μ-(hydr)oxo iron bridges in purple acid phosphatase (PAP) and different iron oxide phases [
Biogenic iron oxide nanoparticles, such as magnetosome and magnetoferritin, also perform enzyme-like property. Magnetosomes are often synthesized by magnetotactic bacteria species such as Alphaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, and Nitrospira classes and the candidate phyla Latescibacteria (also known as candidate division WS3) and Omnitrophica (also known as candidate division OP3) of the Planctomycetes–Verrucomicrobia–Chlamydiae (PVC) bacterial superphylum [23]. The biogenic iron oxide nanoparticles have the single-domain size range of 35–120 nm and are covered by bacterial membranes. It was reported that magnetosomes exhibited peroxidase-like activity [24].
Magnetoferritin is caged protein with 24 subunits made up of heavy-chain ferritin (HFn) and light-chain ferritin. Ferritin is spherical, with an outer diameter of 12 nm and interior cavity diameter of 8 nm, in which iron oxide nanoparticles can be formed. It has been found that ferritins are natural nanozymes that exhibit intrinsic enzyme-like activities (e.g., ferroxidase, peroxidase) [25].
The enzyme-like properties significantly extend the application range of iron oxide nanoparticles. Most of the biomedical applications of iron oxide nanoparticles are developed based on their excellent magnetism, such as magnetic separation of proteins, nucleic acids, or cells, hyperthermia of tumor, targeted drug delivery, and MRI contrast. After the discovery of enzyme-like activities, iron oxide nanoparticles have been extensively applied in immune detection, biosensor, antitumor, antibacterial, antiviral, antioxidant, and immune regulation.
First, the peroxidase-like activity allows iron oxide nanoparticles to be applied as an HRP alternative in immunoassays or biosensors for
Second, owing to oxidoreductase-like activities, iron oxide nanoparticles perform the ability of ROS regulation, which is applied in the treatments of antitumor, antibacterial, antiviral, antioxidant. The peroxidase-like activity boosts ROS generation, which allows iron oxide nanoparticles to be used to kill bacteria [31] or tumor cells [32]. In addition, iron oxide nanoparticles perform antiviral activity by inducing lipid peroxidation in enveloped viruses and subsequently disrupt integrity of virus [17]. Besides generating ROS, iron oxide nanoparticles also can scavenge ROS by utilizing their catalase-like or SOD-like activity. Such unique property can be used for antioxidant treatments in diminishing cytotoxicity [14, 16], ischemia reperfusion of brain [33] and heart [34], neurodegeneration [35]. Recent studies demonstrate that iron oxide nanoparticles can regulate immune system to suppress tumor growth [36] or act as catalytic adjuvant to improve the immune effects of viral vaccine [37].
Besides biomedical applications, iron oxide nanoparticles also can be used with potential in other fields such as environment treatment. By utilizing peroxidase-like activity, iron oxide nanoparticles can be used to detect or degrade the pollutants in environment. For instance, hydrogen peroxide in acid rain can be detected using iron oxide nanoparticles [38]. Pollutants in wastewater, such as phenol, can be degraded by iron oxide nanoparticles [39]. Overall, the enzyme-like activities endow iron oxide nanoparticles with multifunctional property and extend their applications in many important fields.
The enzyme-like activities of iron oxide nanoparticles are a unique property for such inorganic nanomaterial. The catalytic types and efficiency are correlated with the nanostructure of iron oxide nanoparticles. Iron oxide nanoparticles act as enzyme mimics of natural enzymes whose active centers are composed of iron as a key cofactor, which not only extend their potential applications, but also indicate that inorganic nanomaterials are not biological inert but active to interact with biological system. These findings may provide a clue for the origin of life from inorganic world to organic and biological world. Though the catalytic efficiency is typically lower than their natural counterparts, iron oxide nanoparticles have high stability and can be scaled up with low cost, thus having a great potential to be used as enzyme mimics (Nanozymes) in many fields.
This work was supported by the National Natural Science Foundation of China grant (81930050).
The authors declare no conflict of interest.
Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.
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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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