\r\n\tThis book will intend to look at different migrant patterns, voluntary and involuntary migration, over the last three centuries. What influenced people to leave their home countries, family, and friends and settle somewhere else? The book may include histories of the 19th century, consider tragedies and movements activated by political events in the 20th century, and/or look at recent events of the 21st century. Push and pull factors are important points. While most of us may be influenced in a negative way by the current happenings in Eastern Europe, the Russian invasion and resulting tragedies also demonstrate some very positive human traits – the preparedness of Ukraine’s surrounding countries to help those in need and to provide a safe place for the present.
\r\n\tWhether one looks at voluntary or involuntary migration into any country, after a period of adjustment, migrants do play a positive role. The research found that migrants contribute to the economy (food, shelter, employment, tax) and enrich a country’s cultural norms. Prerequisites for successful settlements are that the host society adopts a tolerant approach and that the migrants recognize the law and the language of the host country. Nothing is ever easy or without controversy, but I am a migrant (German Australian), and life in Australia has been relatively harmonious. Issues that could be considered in the book are multicultural societies (do monocultural societies still exist?) and theories of acculturation versus integration (settlement processes).
\r\n\tTwo further issues are very important in relation to human migration. There is climate change, global warming, and the environment, which clearly affect people’s movement. Small island populations are very concerned about rising sea levels. 2021 has also seen floods costing human lives: Turkey (August 2021), Brazil (December 2021), Chile (January 2021), and South India (November 2021), to name but a few. In Australia (March 2022), farms and whole townships in New South Wales and Queensland have been flooded for the second time in five years, and plans to resettle these towns are considered. Official and social media provide ample coverage of the events, which leads me to the next issue. There is today’s very important role of the media, of the official and social media. We are constantly bombarded with images of human war tragedies and flood victims. People in industrialized, western countries must be the best-informed populace. How far do the images and up-to-date TV news influence us, make us change our behavior, and perhaps even consider us more generous than we have been?
\r\n\tClimate change and the media are relatively new to the human migration debate, but both issues play important parts, and some interesting discussions are appreciated.
\r\n\t
Epigenetics is a biological system that describes phenotypes and occurs due to differential regulation of genes (as opposed to genetic mutations). Current epigenetic studies include the control of basic biological functions [1], developmental biology [2, 3], the origin of disease [4], and cancer therapeutics [5]. Investigating the regulatory mechanisms driving these results involves genome-wide mapping of chromatin accessibility and conformation, transcription factor (TF) binding, DNA methylation, and histone modifications. Leukemia oncogenesis is a result of both genetic and epigenetic factors, whereby hematopoietic pathways are disrupted and leukemia cells are able to evade lineage commitment. This interdependence between altered genes and gene regulation is critical in cancer development. Consequently, a broader understanding inclusive of genomics and epigenomics will allow for development of drug targets which may limit cancer progression, improve therapeutic response, and find novel targeted therapies.
\nMulticellular eukaryotic organisms consist of a complex variety of different cells, all containing identical genomic DNA. The ability to create such diversity from identical duplicates of DNA is attributed to differential gene expression regulation. Gene expression is as product of epigenetic regulatory systems. Differences within these regulations result in differential expressions and subsequently, cell types that differ in structure and function [6].
\nThe three-dimensional organization of DNA is central to gene expression, as it depends on physical access to the gene to be expressed. Genomic DNA is condensed and wrapped around histone proteins, forming chromatin [7]. Condensed chromatin structures inhibit gene transcription by making the gene physically inaccessible for transcriptional machinery to access (Figure 1). To unfold chromatin structure and expose the gene for transcription, endogenous mechanisms and drugs modify the histone proteins around which the DNA is bound [8, 9]. Modifications which result in gene silencing include histone deacetylation and DNA methylation. To achieve differential expression profiles between cell types, cells have different gene access profiles controlled by protein mediation, external stimuli, and development of cells [10].
\nChromatin accessibility. Chromatin accessibility modulates gene expression. Densely packed chromatin (left) is inaccessible, preventing transcription factors (TFs), CCCTC-binding factor (CTCF), and polymerases from binding and subsequent gene expression. Opened chromatin structure (right) can be accessed by TFs, CTCF, and polymerases bindings, resulting in ability for gene transcription. Opened and closed chromatin structures are regulated by the acetylation status of histone proteins. Acetylated histones provide an open chromatin structure, while deacetylated histones form a closed chromatin structure. Adapted from Shlyueva et al., 2014 [
Histone deacetylation involves the switching of histone proteins from a positive to neutral charge via the addition of an acetyl to a lysine residue within the histone tail. This change in charge will result in the DNA (negatively charged) separation from the histone due to repulsion forces of like charges. Separated DNA regions become accessible to transcriptional machinery as a result. When this mechanism is reversed and lysines are deacetylated, DNA is attracted back toward the protein, resulting in tight DNA wrapping, thus inaccessible for transcriptional machinery (Figure 2) [11]. The enzyme responsible for acetylation of histone proteins is called histone acetyltransferase (HAT), which opens the chromatin structure and allows transcription. Deacetylating enzymes which cause compacting of chromatin are called histone deacetylases (HDAC).
\nHierarchical layers of chromatin organization in mammalian cells. Adapted from Aranda et al., 2015 [
DNA methylation is another mechanism of chromatin remodeling. CpG islands are target sites in the genome for methylation by the DNA methyltransferase (DNMT) enzyme. Of the CpG sites in gene promoter regions, 70% are primary targets for methylation. DNMT prevents gene transcription via physically preventing transcription factor binding and by methylating DNA. Methylated DNA binds to methyl-CpG-binding domain (MBD) proteins that in turn recruit proteins such as histone deacetylase and other chromatin-remodeling proteins. In this new environment, chromatin becomes compact and inactive, termed heterochromatin (repressed domain in Figure 2).
\nALL population studies indicated a trend in disease peak around the age of 5, after which there is no increase in prevalence (Figure 3). Evidences suggest hematopoietic regulatory network probably most highly involved in leukemia development at their highest in children <5 years old. Case-control studies have shown that the occurrence of childhood ALL is inversely linked to the degree of exposure to infections in the first few months of life [12, 13]. This suggests that there may be certain oncogenic factors present in the early days of a child’s life that lead to the development of ALL, rather than being present later on or in adulthood. Addressing these up- and downregulations of oncogenic factors in this critical stage of hematopoiesis will provide insight into pathogenesis and progression of ALL beyond the genetic level.
\nEpigenetics is still in the early stages of investigation and translational clinical use. Primary testing in clinics focuses on cytogenic studies, categorizing disease based on genetic abnormalities and cell markers, and then treating the patient accordingly; screening gene expression to map out regulatory profiles of a tumor are less established. In acute lymphoblastic leukemia (ALL), subtypes are diagnosed based on cytogenic testing and testing for markers [14]. In vivo mouse studies, however, have indicated that in almost 75% of diagnosed cases, chromosomal changes alone are insufficient to induce ALL [15]. Investigation of genetic alterations alongside epigenetics microarrays of gene expression suggested an association between mutations and altered regulation in gene expressions during hematopoiesis in both B-ALL and T-ALL [14, 15]. Prenatal lesions and postnatal-acquired mutations have also shown impaired regulation and development of progenitor B cells or T cells [16, 17, 18]. Together, these studies suggest that it is not mutations alone that act as oncogenic drivers but also an altered gene regulatory network.
\nThus far, ALL oncogenic studies have reported prenatal genetic lesions and inherited genetic predisposition which neither can stand alone to account for the disease. Prenatal genetic lesions have been reported with an unknown pathogenesis [18], and only 5% of ALL patients reported with an inherited genetic predisposition such as Down’s syndrome and Bloom’s syndrome [17, 19]. Figure 4 indicates multiple genetic lesions contributing to an altered regulatory network in healthy lymphoid development toward a pathogenic ALL pathway [20, 21, 22, 23]. Incomplete evidence regarding prenatal genetic lesions in ALL supports research into the epigenetic regulatory system in the development of ALL. Prenatal genetic lesions suggest the preleukemic states. Despite studies suggesting preleukemic state in utero, other studies show that the development of ALL in monozygotic twins follows a different time course. The difference in postnatal disease progression despite an identical prenatal state suggests the role of epigenetics in ALL manifestation [24, 25, 26, 27].
\nIncidence of ALL per 100,000 populations in 2010. Source: Australian Institute of Health and Welfare (AIHW), 2014 [
B-ALL development. Multiple mutations contribute to the development of ALL. Mutations in ALL predisposing genes, e.g., IKZF1, and initiating genes, e.G., ETV6-RUNX1, and MLL rearrangement will promote ALL development. Alterations in B-cell development genes, e.G., PAX5 and IKZF1, inhibit cell maturation, resulting in the accumulation of immature cells. This alone however is not enough to cause ALL pathogenesis. Cell cycle and lymphoid lineage regulatory gene expression must also be altered to promote its survival. Further alterations may induce chemoresistance. Adapted from Mullighan, 2013 [
Since drugs target distinct cell pathways relying on gene expression, access to target genes is crucial for the treatment to work. A common ALL chemotherapy regimen of glucocorticoids relies on activation of the glucocorticoid receptor (GR), which binds to glucocorticoid-response elements (GREs) in gene promoters, to induce expression of pro-apoptotic pathways [28]. Using a DNase hypersensitivity assay (DHA) to determine chromatin accessibility [29], the majority of GR binding to GREs were identified in open chromatin [8, 30]. Thus, glucocorticoid therapy is dependent on GRE accessibility which is defined by chromatin accessibility. Resistance and patient response to such drugs is thought to be dependent on their gene accessibility profiles.
\nALL is a malignant disease in both adults and children, with mutations developing along the lymphoid lineage starting at the lymphoid progenitor cells. Normally, lymphoid cells have the potential to differentiate into B or T cells, which under oncogenic conditions give rise to either B-ALL or T-ALL [17, 21]. Hematopoietic stem cells (HSCs), in the bone marrow, are the origin of both lymphoid and myeloid lineages. The tight regulation of gene expression in HSCs determines the lineage pathway and development. During oncogenesis, molecular defects and abnormal genes regulation may alter the differentiation of HSC; these factors may also contribute to further alterations downstream in hematopoiesis [17, 31, 32, 33, 34, 35, 36]. Alterations along the lymphoid lineage result in abnormal pre-lymphoid cells called lymphoblasts; these aggressively proliferate and gradually replace the normal hematopoietic cells in the bone marrow and blood. Accumulation of lymphoblasts results in immunity retardation due to the insufficient amounts of mature lymphoid cells. Patients thus become immunocompromised and prone to various infectious diseases normally fought off by the immune system’s lymphocytes [21, 37, 38].
\nGlucocorticoids are naturally occurring steroid hormones that are widely recognized for their anti-inflammatory and immunosuppressing activities [39, 40, 41]. In leukemia, glucocorticoids are able to induce apoptosis in lymphoid cells. As such, glucocorticoid drugs such as dexamethasone and prednisolone are used as part of multi-agent chemotherapy regimens treating hematological malignancies [42, 43, 44], including ALL, chronic lymphocytic leukemia, multiple myeloma, and lymphoma. Due to pro-apoptotic pathway activation, glucocorticoids have remained the pivot point in chemotherapy treatment to combat ALL for 50 years [38, 45].
\nGlucocorticoids play a role in all three phases of treatment phases. During the remission-induction phase, glucocorticoids make up a significant portion of drug when administered in combination with vincristine and asparaginase and/or anthracycline. This initial high glucocorticoid portion aims to relieve at least 99% of the leukemic burden; the patient’s response is critical in determining the future course of treatment and determining chance of relapse and prognosis [46]. The following two chemotherapy phases are less intensive, involving re-administration of remission-induction drugs in addition to methotrexate and mercaptopurine [17]. To note, some patients do not need to be administered pulses of glucocorticoids in phases two and three of the therapy, due to patients’ contraindications [47]. This three-phase glucocorticoid regimen has seen an increase in ALL 5-year survival rate from 73–90% in the past 20 years [48], yet there still exits a subset of ALL patients who are resistant to glucocorticoids, resulting in poor prognosis.
\nGlucocorticoid mode of action involves the activation of specific cellular pathways specific in lymphoid cells to induce cell death. Depending on cell type, cell-specific chromatin conformation provides the structural framework for transcription factor (TF) binding to regulate gene transcription that determines the ability of a cell to activate a pathway [49, 50, 51]. A cell-type-specific conformation is generated [11, 52] with each type having approximately 70,000–100,000 accessible chromatin domains and a network of cell-type-specific binding of transcriptional regulators [10, 53, 54]. Glucocorticoids are able to target intracellular pathways by interacting with the glucocorticoid receptor (GR) in the cytoplasm [55, 56]. The complex then translocates into the nucleus and binds at accessible chromatin domains containing glucocorticoid-response elements (GREs) at proximal promoter regions and/or distal sites of a gene [57, 58, 59]. GR binding to GREs induces chromatin remodeling and activates gene transcription via recruitment of other transcription proteins [60, 61]. To keep gene transcription tightly regulated, GR binding is highly selective and predetermined by chromatin accessibility in different cell types [8, 62]. Currently, the GR-binding landscape in different cell subsets, as well as between glucocorticoid-sensitive and resistant leukemia subsets, is yet to be established. Understanding this epigenetic landscape is crucial in understanding patient relapse or chemoresistance. Preliminary studies have started this investigation in pediatric ALL, to understand the mechanism of drug resistance in B-ALL.
\nWhile the glucocorticoid induces apoptosis pathway is still unclear, it is a pro-apoptotic pathway exclusive to lymphoid cells despite widespread expressions of GR in most human tissues [63, 64]. Glucocorticoids are rarely efficacious in treating myeloid leukemia [65]. Due to this lymphoid-specific apoptosis pathway, it is hypothesized that glucocorticoid-sensitive cells have a distinguished chromatin structure allowing for specific GR binding at GREs that glucocorticoid-resistant lymphoids, myeloid cells, and other tissue cells do not have [8, 66–69]. Therefore, understanding the lymphocyte-specific mechanisms of glucocorticoid-induced apoptosis, as well as the development of resistance to this class of steroid hormones, is critical in optimizing glucocorticoid-based therapies in the clinic.
\nThe actions of glucocorticoids are cell type specific [65, 66, 67], although the exact molecular basis for this differential function remained elusive. While certain signaling pathways resulting from ALL oncogenes appear to interfere with glucocorticoid actions resulting in resistance, epigenetic evidence suggests that in addition to genetic alterations, epigenetic factors contribute to resistance. For instance, inhibition of GR expression or its translocation to the nucleus in vitro and in vivo models via
Lymphocyte-specific enhancers associated with glucocorticoid-induced apoptosis were identified in cell-wide studies [5, 28]. Moreover, aberrations at these enhancers were observed in glucocorticoid-resistant ALL cells. Similarly, nonlymphoid cells also exhibited inaccessible chromatin at these enhancers, providing insights into the cell-type-specific actions of glucocorticoids. A link between epigenetic differences and cell-type-specific actions of glucocorticoids are essential in the treatment determining treatment approaches for lymphoid malignancies. Lymphocyte-specific epigenetic modifications pre-determine glucocorticoid resistance in ALL and may account for the lack of glucocorticoid sensitivity in other cell types. Recent findings suggest that in glucocorticoid-sensitive cells, GR cooperates with the structural protein, CTCF, at lymphocyte-specific regulatory domains to mediate the formation of a transcriptionally active DNA loop to trigger gene transcription, which can be inhibited by increased DNA methylation in glucocorticoid-resistant ALL. By using a comprehensive map of chromatin accessibility, CTCF binding, histone modifications, and DNA methylation in normal and malignant cell types, there is evidence of regulatory heterogeneity in the epigenome of different cell types. Azacytidine, a DNA demethylating drug that is routinely used in the clinic, could partially reverse these changes and restore glucocorticoid-induced gene expression and glucocorticoid sensitivity. This indicates that reversal of epigenetic changes may lead to improvements in the use of glucocorticoids for the management of lymphoid malignancies.
\nEpigenetic drugs inhibit and manipulate different epigenetic regulators involved in histone remodeling. Drugs which target epigenetic regulators can open closed chromatin structures commonly found in chemotherapy-resistant patients. Epigenetic regulators can be divided into different categories based on their method of modification: epigenetic writers, readers, and erasers (Figure 5).
\nEpigenetic reader, writer, and eraser. Epigenetic writers such as histone acetyltransferases (HATs), histone methyltransferases (HMTs), protein arginine methyltransferases (PRMTs), and kinases lay down epigenetic marks on amino acid residues on histone tails. Epigenetic readers are proteins that contain bromodomains, chromodomains, and Tudor domains, allowing them to bind to these epigenetic marks. Epigenetic erasers such as histone deacetylases, lysine demethylases, and phosphatases catalyze the removal of epigenetic marks. Together they modulate chromatin structures and regulate various DNA-dependent biological processes such as DNA synthesis and replication. Adapted from Falkenberg and Johnstone, 2014 [
Epigenetic regulators determine gene expression, and an understanding of them allows for the development of drugs to regulate gene expression over epigenetic marks. Epigenetic writers lay down epigenetic marks on DNA or amino acid residues on histones tails [77]. Examples include histone acetyltransferases (HATs), histone methyltransferases (HMTs), and protein arginine methyltransferases (PRMTs). Drugs which target these are DNA hypomethylating agents, bromodomains, and HDAC inhibitors. Epigenetic readers are proteins that contain bromodomains, chromodomains, and Tudor domains allowing them to bind to specific epigenetic marks on chromatin. Epigenetic erasers such as histone deacetylases, lysine demethylases, and phosphatases catalyze the removal of epigenetic marks.
\nThe epigenetic drugs to be discussed are designed to target different epigenetic regulators responsible for gene silencing.
\nDuring preparation of genetic information in the S phase of the cell cycle, replication machinery is responsible for DNA replication, and DNMT functions duplicate methylation status by adding methyl groups to the DNA accordingly (Figure 6). DNMT inhibitors, azacytidine and decitabine, prevent DNMT methylation. Azacytidine and decitabine are metabolized inside cells into 5-aza-2′-deoxycytidine-triphosphate. The difference between DNMT bounding to 5-aza-2′-deoxycytidine-triphosphate and DNMT bound to cytosine is used to inhibit DNMT. As illustrated in Figure 7, DNMT reversibly binds with cytosine, which allows DNMT to be released from DNA through beta-elimination once methylation is completed. DNMT binding to 5-aza-2′-deoxycytidine-triphosphate establishes a covalent bond preventing beta-elimination; therefore, DNMT remains bond to the DNA. Subsequently, the error triggers DNA damage signaling and the trapped DNMT is degraded. As a result, methylation markers get lost during DNA replication [78]. Demethylated DNA allows for an open chromatin structure to be accessed by transcription factors induce by chemotherapeutic drugs such as glucocorticoids.
\nEffect of epigenetic modification on gene expression. Activation of gene transcription needs transcription factor binding to the promoter region of the gene. Without DNA methylation, transcription factors and RNA polymerase II (RNA pol II) can bind to DNA segments; however, when methyl group is added to the DNA by DNA methyltransferase (DNMT), the methylation not only impedes the binding of transcription factors to DNA but also recruits histone deacetylase (HDAC) causing chromatin structure to become compacted, which places spatial limitation for transcription factor binding [
Reversible binding of cytosine with DNMT in DNA methylation process versus irreversible binding of 5-azacytosine with DNMT when leukemia cells were treated with azacytidine, which leads to degradation of DNMT and subsequent loss of methylation. Adapted from Stresemann and Lyko, 2008 [
Single-agent study conducted by Khaldoun Al-Romaih’s group showed that decitabine therapy had a cytotoxic effect mediated by the removal of hypomethylation of the CpG position both in vivo and in vitro. The cells treated with decitabine showed significant cell death in vitro, and six pro-apoptotic genes (GADD45A, HSPA9B, PAWR, PDCD5, NFKBIA, and TNFAIP3) were induced to ≥ twofold in vivo [79]. Combination therapy trials revealed the value of DNMT inhibition in addition to current therapeutic regimens. In one clinical trial in refractory ALL patients, decitabine combined with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) was able to achieve complete remission in patients that did not respond to hyper-CVAD treatment alone. Patient DNA analysis confirmed that the hypomethylation status in the combination treatment group was the reason for reversal of resistance [80]. A number of other clinical studies provided similar results, showing synergistic effects between hypomethylating agents and several chemotherapy agents. Agents such as prednisolone, etoposides, doxorubicin, and cytarabine were shown to increase chemosensitivity in leukemia cells [81, 82, 83, 84]. Although promising not all experimental groups responded, indicating the need for further research into the complex network of interactions.
\nAn open chromatin structure also relies on the relatively loose interactions between DNA and histone proteins. The addition of an acetyl groups to the lysine amino acids on histone proteins by histone acetyltransferases (HATs) reduces the positive charges on the histone proteins. DNA, negatively charged, is therefore less attracted to these now less positive histones, thus less tightly bound and easier for transcription factors to access [83]. Conversely, the removal of acetylation by histone deacetylase (HDAC) forms condensed heterochromatin and silences critical apoptosis gene transcriptions. HDAC inhibitors prevent this form of gene silencing and are used alongside standard chemotherapy to promote pro-apoptotic pathways.
\nHDAC enzyme family consists of Class I (HDAC1, HDAC2, HDAC3, HDAC8), Class II (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, HDAC10), Class III (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7), and Class IV (HDAC11). HDAC inhibitors are designed as either selective inhibitors or pan-inhibitors (against all types of HDAC). Evidence that some HDACs play a stronger role in cancer development and patient prognosis than others makes specific HDAC inhibitors more appealing for clinical use. A study of 94 pediatric ALL patients showed differential HDAC expressions between the T-ALL and B-ALL subtypes. For T-ALL, HDAC1 and HDAC4 showed a higher expression than in B-ALL. T-ALL patients with HDAC3 expression above the cohort median also displayed a significantly higher 5-year event-free survival (EFS). In B-ALL, HDAC5 had higher expression than in T-ALL. In both T-cell and B-cell ALL, HDAC7 and HADC9 expression levels higher than the cohort median were associated with a lower 5-year EFS [85]. These trends suggest that Class II HDACs are associated with poorer prognosis; hence, a specific inhibition of this class of HDACs is important.
\nBromodomains (BRDs) are epigenetic readers which selectively bind to acetylate lysine of histones tails, regulating gene expression [86]. Bromodomain-containing proteins that target genes are primarily cell cycle M/G1 genes in mitotic chromatin (expressed at the end or immediately after mitosis); late-phase genes were not found to be BRD4 bound. M/G1 gene expression during telophase coincides with histone H3 and H4 acetylation in those genes. BRD binding to M/G1 genes was associated with recruitment of positive transcription elongation factor b (P-TEFb), resulting in translational memory in the daughter cells [87]. BRD binds to MYC and activates enhancer-binding protein 4 (AP4) promoters. AP4 is a key mediator of mitogenicity for proto-oncogene MYC [88]. Upon AP4 activation by MYC, repressing cell cycle arrests gene
JQ1 is a BRD inhibitor which acts on the MYC-AP4 axis [89]. Direct inhibition by JQ1 of BRD binding to the MYC and AP4 promoters indirectly results in cell cycle arrest as a
Epigenetic drugs are useful in combination with cytotoxic drugs, due to their ability to allow for access to pro-apoptotic pathways, otherwise blocked by epigenetic silencing. In a subset of leukemia patients, resistance to cytotoxic drugs such as glucocorticoids and methotrexate is a result of inaction of pro-apoptotic genes. Theoretically, applying epigenetic drugs such as those mentioned above should remove the epigenetic modification such that pro-apoptotic genes may go from repression to promotion.
\nChromatin conformation and gene expression studies at the glucocorticoid-induced pro-apoptotic
Studies showed closed DNMT catalyzed chromatin structure caused by DNA methylation impedes the transcription of
Suberoylanilide hydroxamic acid (SAHA; Vorinostat) is an HDAC inhibitor shown to work synergistically with different chemotherapies. Glucocorticoid-resistant ALL cases were associated to a correlation between histone H3K9 deacetylation and pro-apoptotic gene,
Combination therapy aims to bring synergistic effects by targeting both cell death pathway (chemotherapy, e.g., glucocorticoids) and access to this pathway (epigenetic drug). Of the clinical trials underway, the use of relatively high doses of 5-azacitidine (150 mg/m2 as a continuous infusion daily × 5 days) is combined with cytarabine in patients relapsed from cytarabine alone. It was hypothesized that treatment with 5-azacitidine could induce expression of deoxycytidine kinase. Two out of the 17 patients achieved complete responses (CR). In another study, decitabine was combined with either amsacrine or idarubicin in patients with acute leukemia. CR was achieved in 36% (23 out 63) of patients, with a median disease-free survival of 8 months [82].
\nUsing a hypomethylating agent such as decitabine, glucocorticoids in resistant ALL patients had the potential to expose the pro-apoptotic gene
Knowledge of gene regulation has deepened the understanding of cellular mechanisms and disease development. In leukemia, genomic and epigenomic landscapes together provide crucial disease mechanism of pathogenicity and drug resistance [94, 95, 96]. Epigenetics is the driver of life and diversity of different organisms, and equally able to dysregulate cells and cause diseases such as leukemia. Hematopoiesis is a tightly controlled process essential for life, therefore, unless appropriately regulated, susceptible to regulatory errors as oncogenic drivers alongside mutations. Lineage-specific landscapes have been shown to be involved in hematopoiesis and leukemia evolution [51], providing a backbone for understanding targetable and non-targetable sites within different leukemic subtypes.
\nStudying a level of cell dysfunction preceding DNA mutations has allowed for understanding into pathogenesis and drug resistance which could not be correlated to DNA sequencing. Understanding resistance to chemotherapies, lowering patient prognosis, has been enlightened in epigenetic studies. For example, actions of glucocorticoids are cell type-specific and can be used in lymphocyte-specific leukemia cells to induce cell death [66, 67]. Analysis between genome-wide lymphocyte-specific open chromatin domains (LSOs) and integrated LSOs with glucocorticoid-induced RNA transcription and chromatin modulation in ALL was performed to causes glucocorticoid resistance beyond gene mutations [5]. LSOs critical for glucocorticoid-induced apoptosis were identified as well as structural protein CTCF binding in this region. These findings showed that upon GR binding to the LSO and CTCF binding, DNA would loop at the pro-apoptotic
Understanding the importance of chromatin accessibility has allowed for identification of glucocorticoid sensitivity in cells and provides promising drug response predictions. Furthermore, development of epigenetic drugs that may modify chromatin to be accessible is currently being investigated. This would allow for more effective drug treatments to disrupt the oncogenesis driven via dysregulated pathways.
\nThis is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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\n\nPlease complete the publishing proposal form. The completed form should serve as an overview of your future Compacts, Monograph or Edited Book. Once submitted, your publishing proposal will be sent for evaluation, and a notice of acceptance or rejection will be sent within 10 to 30 working days from the date of submission.
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He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"38",type:"subseries",title:"Pollution",keywords:"Human Activity, Pollutants, Reduced Risks, Population Growth, Waste Disposal, Remediation, Clean Environment",scope:"\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11966,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,series:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713"},editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",slug:"meng-chuan-ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",slug:"olga-anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},onlineFirstChapters:{paginationCount:0,paginationItems:[]},publishedBooks:{paginationCount:7,paginationItems:[{type:"book",id:"7102",title:"Pneumonia",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7102.jpg",slug:"pneumonia",publishedDate:"May 11th 2022",editedByType:"Edited by",bookSignature:"Nima Rezaei",hash:"9fd70142814192dcec58a176749f1b60",volumeInSeries:13,fullTitle:"Pneumonia",editors:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9615",title:"Chikungunya Virus",subtitle:"A Growing Global Public Health Threat",coverURL:"https://cdn.intechopen.com/books/images_new/9615.jpg",slug:"chikungunya-virus-a-growing-global-public-health-threat",publishedDate:"February 9th 2022",editedByType:"Edited by",bookSignature:"Jean Engohang-Ndong",hash:"c960d94a63867dd12a8ab15176a3ff06",volumeInSeries:12,fullTitle:"Chikungunya Virus - A Growing Global Public Health Threat",editors:[{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",institutionString:"Kent State University",institution:{name:"Kent State University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9619",title:"Epstein-Barr Virus",subtitle:"New Trends",coverURL:"https://cdn.intechopen.com/books/images_new/9619.jpg",slug:"epstein-barr-virus-new-trends",publishedDate:"December 22nd 2021",editedByType:"Edited by",bookSignature:"Emmanuel Drouet",hash:"a2128c53becb6064589570cbe8d976f8",volumeInSeries:11,fullTitle:"Epstein-Barr Virus - New Trends",editors:[{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",institutionString:null,institution:{name:"Grenoble Alpes University",institutionURL:null,country:{name:"France"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9613",title:"Dengue Fever in a One Health Perspective",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9613.jpg",slug:"dengue-fever-in-a-one-health-perspective",publishedDate:"October 28th 2020",editedByType:"Edited by",bookSignature:"Márcia Aparecida Sperança",hash:"77ecce8195c11092230b4156df6d83ff",volumeInSeries:7,fullTitle:"Dengue Fever in a One Health Perspective",editors:[{id:"176579",title:"Dr.",name:"Márcia Aparecida",middleName:null,surname:"Sperança",slug:"marcia-aparecida-speranca",fullName:"Márcia Aparecida Sperança",profilePictureURL:"https://mts.intechopen.com/storage/users/176579/images/system/176579.jpg",institutionString:null,institution:{name:"Universidade Federal do ABC",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7887",title:"Hepatitis B and C",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7887.jpg",slug:"hepatitis-b-and-c",publishedDate:"April 8th 2020",editedByType:"Edited by",bookSignature:"Luis Rodrigo",hash:"8dd6dab483cf505d83caddaeaf497f2c",volumeInSeries:5,fullTitle:"Hepatitis B and C",editors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo",profilePictureURL:"https://mts.intechopen.com/storage/users/73208/images/system/73208.jpg",institutionString:"University of Oviedo",institution:{name:"University of Oviedo",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. 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