More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\n
Additionally, each book published by IntechOpen contains original content and research findings.
\\n\\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\n
Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\n
IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\n
Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n
\n\n
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1. Introduction
Melanoma is the most aggressive form of skin cancer and accounts for 4% of all skin cancers and nearly 75% of all melanoma deaths. According the National Cancer Institute, the incidence of melanoma is increasing 6-7% annually. In 2012, it is estimated that there will be 76,250 new cases of melanoma and more than 9,000 deaths. Risk factors for melanoma include one or more severe sunburns, a familial history, excessive presence of moles, and fair skin. Melanoma is unique from many cancers in that it that the tumor suppressor p53 is functional in a relatively high percentage of tumors. Despite functional p53 protein, melanoma cells evade p53-mediated apoptosis because of complex alterations in the apoptotic pathways. This chapter will discuss the aberrant apoptosis mechanisms that exist in melanoma and provide insight on to how these alterations could be therapeutically targeted.
2. P53
The tumor suppressor protein p53 has long been regarded as the guardian of the genome and is mutated in more than half of all human cancers. The functional status of p53 is of significant clinical importance because of its role in apoptosis, cell cycle arrest, and DNA repair; all cellular processes targeted by chemotherapy and radiation therapy [1]. The human p53 gene is highly conserved and consists of seven exons. The protein exists in a latent form and is activated through tetramerization, allowing p53 to then bind with high affinity to DNA. The tetramer conformation forms through interactions between regions in the C-terminus. Once activated, p53 can recognize sequence specific binding sites on target genes and stimulate their activation. p53 mutations are predominantly seen in the DNA binding domain, and very rarely occur in the oligomerization region [2]. The half-life of p53 is short and is increased acutely in response to DNA damage or changes in oxidation status. Upon activation, p53 is phosphorylated at various serine residues at the N or C terminus. The phoshorylation sites vary depending on the type of damage inflicted on the cell. Once phosphorylated, p53 acts as a transcription factor, translocating to the nucleus and binding to promoter elements of downstream target genes [3].
3. p53 and apoptosis
One of the essential roles of p53 is to maintain cellular integrity through transducing apoptosis, programmed cell death, in the event of an irreparable damage to prevent propagation of this aberrancy through uninterrupted proliferation. The mechanism of cell growth without checks and balances is the essence of malignancy; making p53 central to the governing of cell growth. Cellular damage caused by agents such as UV light, ionizing radiation, hypoxia, and oxidative stress will lead to the activation of p53, allowing for p53-dependent apoptosis to occur. The role of p53 in the mitochondrial apoptotic cascade is largely through its activities as a transcription factor for several pro-apoptotic proteins. p53 induced apoptosis can be activated via intrinsic and the extrinsic cellular pathways [4;5].
3.1. Intrinsic apoptosis
The intrinsic or mitchondrial apoptotic cascade results from genotoxic stress such as UV damage, oxidative stress, hypoxia, chemotherapy, or ionizing radiation. As depicted in Figure 1, activation of p53 from stress stimuli leads to activation of Bax and Bak. These proteins are important players in apoptosis and are members of the Bcl-2 family, which is made up of both pro and anti-apoptotic proteins. Family members are classified by structural similarity to the Bcl-2 homology (BH) domains (BH1, BH2, BH3, and BH4), as well as a transmembrane domain. The BH3 domain is referred to as the “death domain” and is the minimum requirement for the protein to have pro-apoptotic functions. Once activated, pro-apoptotic Bax and Bak lead to depoloarization of mitochondria and the release of cytochrome c, a small heme protein, which is bound loosely within the mitochondrial membrane. The pro-apoptotic functions of Bax and Bak are antagonized by the structurally similar anti-apoptotic proteins Bcl-2 and Bcl-xL. The Bcl-2 family also contains ‘BH3 only’ proteins that are exclusively pro-apoptotic and include Bax, PUMA, and Bid. Upon release, cytochrome c complexes with apoptosis protease activation factor (APAF-1) to form an apoptosome. The apoptosome then binds to inactivated pro-caspase 9, the initiating caspase. Once activated, caspase 9 goes on to cleave caspase 3, the effector caspase responsible for executing apoptosis [6-8].
3.2. Extrinsic apoptosis
Extrinsic apoptosis involves death receptor activation through activation of the TNF-R family proteins (Tumor necrosis factor receptor) including Fas, PERP, and DR5. The Fas receptor is located on the cell surface and is activated by the ligand FasL, which is largely expressed by T cells. Fas ligands, which usually exist as trimmers, bind and activate their receptors by inducing receptor trimerization. Activated receptors recruit adaptor molecules such as Fas-associating protein with death domain (FADD), which then recruit procaspase 8 to the receptor complex, where it undergoes autocatalytic activation. Activated caspase 8 activates caspase 3 through two pathways. In the more complex pathway caspase 8 activates Bcl-2 interacting protein (Bid), which interacts with Bax to promote translocation of Bax to the inner mitochondrial membrane where it triggers cytochrome c release. The released cytochrome c binds to apoptotic protease activating factor-1 (Apaf-1). As in intrinsic apoptosis, the apoptosome leads to activation of caspase 9, which is then able to cleave and activate procaspase 3, ultimately leading to DNA fragmentation [8;9]. Figure 1 depicts the intersection of intrinisic and extrinsic apoptosis and onset of extrinsic apoptosis through death receptor activation.
Figure 1.
Intersecting intrinsic and extrinsic apoptotic pathways
4. Role of p53 in melanogenesis
4.1. Tyrosinase
The role of DNA damage and DNA repair in the stimulation of melanogenesis is corroborated by the observation that activated p53 upregulates transcription of tyrosinase, the rate-limiting enzyme involved in melanin production. Tyrosinase is a glycoprotein found in the melanosomal membrane. The protein has an inner melanosomal domain, which contains a catalytic region and a short transmembrane, and a cytoplasmic domain made up of about 30 amino acids. Histidine residues present in the catalytic domain portion of tyrosinase bind copper ions needed for tyrosinase activity. Structural studies of the tyrosinase promoter region have revealed the presence of a TATA box, CAAT box, 5 AP-1 sites, 2 AP-2, 2 glucocorticoid responsive elements, 2 UV responsive elements, and 3 Oct-1 sites [10]. The role of tyrosinase in pigmentation reactions is the result of the oxidation of phenols.Tyrosinase hydroxylates tyrosine in the first step of melanogenesis.Tyrosinase then catalyzes the hydroxylation of L-tyrosinse to L-Dopa and its subsequent oxidation to dopaquinone. Dopaquinone then undergoes a series of reactions that lead to the synthesis of melanin within the melanocyte. Tyrosinase has been studied as a prognostic marker of melanoma and has been useful in staging the disease and determining prognosis [11;12]. Pathological analysis of melanoma tissue samples have shown that tyrosinase detection is 97-100% specific to melanoma versus other tumor types. Detection of tyrosinase mRNA in peripheral blood in patients with metastatic melanoma using RT-PCR has been correlated to poor survival following immunotherapy with IL-2 [12]. It has also been observed that patients with primary lesions do not show tyrosinase mRNA in peripheral blood. Tyrosinase mRNA is not observed in peripheral blood in patients with previous metastatic disease but who are currently disease free, implicating that tyrosinase could be a useful prognostic tool [13].
Figure 2.
Tyrosinase catalyzed reactions during melanogenesis
4.2. Melanogenesis
The activities of p53 as a tranducer of melanin production was further elucidated by Cui et al. A p53 consensus sequence was discovered in the proopiomelanocortin (POMC) gene promoter, establishing a line of communication between UV-induced DNA damage and the sun tan response. The binding of p53 to the POMC promoter leads to an increase in the release of POMC-derived alpha-melanocyte stimulating hormone (alpha-MSH), an important messenger inducing melanogenesis. Once released, alpha-MSH acts as a ligand for the melanocortin-1 receptor (MC1R), and binding results in the production of eumelanin [14]. Yamaguchi et al. demonstrated that within keratinocytes, melanin acts as a native sunscreen. Melanin absorbs UV light, thus protecting DNA from damage. In dark skin, which possesses higher levels of melanin, protein levels of p53 are markedly lower following exposure to UV light compared to more fair skin when p53 is highly stabilized following the same exposure. The photo absorbent property of melanin protects from DNA damage, decreasing the activation of p53 [15]. Additionally, this observation supports that p53 is central to the UV damage response through stimulation of melanogenesis as an innate means to protect skin from damage through increased pigmentation.
Figure 3.
Role of p53 in transducing melanogenesis
5. p53 in melanoma
It has been observed that the frequency of p53 mutations in melanocytic tumors ranges from 5-25%, which is considerably lower than other types of cancers. Although mutations in p53 itself remain less frequent, the functional anti-tumor properties of p53 can be repressed by many other mechanisms [16;17]. For example, p53 may be wildtype in melanoma but its repressor, MDM2, is often overexpressed, causing p53 destabilization and a decreasing in its transcriptional activities. Furthermore, the p53 upstream protein p14ARF is responsible for the regulation of MDM2; once activated, p14ARF activates p53 through inhibition of MDM2, allowing p53 to avoid proteosomal degradation and subsequent phosphorylation. Mutations or a loss of p14ARF are frequently seen in melanoma [18]. Loss of function of one or both of the p14ARF of p16INK4a proteins is thought to lead to a compensatory increase in p53 stability as melanoma progresses [19].
In normal melanocytes, the apoptotic functions of p53 are attenuated in response to UV stress in order to facilitate a longer cell life. One way this occurs is by upregulation of the p53 responsive gene GADD45a, which inhibits intrinsic apoptosis mediated through p53. It is speculated that this alteration in the apoptotic machinery that is specific to melanocytes could be the genesis of the inherent chemoresistence of melanoma [20].
5.1. MDM2
The murine double minute protein (MDM2) functions as a negative regulator of p53. Its ability to inhibit p53 is regulated by a negative feedback loop in which activated p53 leads to the transcription and translation of MDM2, which then inhibits p53 [21]. Studies conducted in mice have shown that MDM2 knockout mice are embryonic lethal in a p53-dependent manner, where incessant p53 activity causes excessive apoptosis and ultimately death. A rescue effect was observed by p53 knockout, confirming the role of MDM2 in p53 regulation [22]. MDM2 interacts with the transactivation domain of p53 via a p53-interacting domain on the N-terminus of MDM2. This binding of MDM2 to p53 prevents p53 from binding to its transcriptional co-activators and subsequently prevents p53 from activating target genes [21]. In melanoma, MDM2 has been found to be highly expressed in half of invasive primary and metastatic melanomas. Amplification of the MDM2 locus is infrequent and over-expression is the most common occurrence. In patient follow-up studies, decreased MDM2 expression was associated with higher rates of survival. It has also been observed that both MDM2 and p53 are overexpressed in patients with melanoma [23]. This could be explained by the auto-regulatory loop between p53 and MDM2. Increased expression of MDM2 is also possible due to the loss of its repressor p14ARF, a common mutation or deletion seen in melanoma [24]. Without its repressor, MDM2 is constitutively active. This could account for the apoptotic resistance observed in melanoma despite the largely wild-type status of p53.
5.2. INK4a/ARF locus
The INK4a/ARF locus contains the open reading frames of the proteins p16 INK4a and p14ARF. This locus is of particular importance in melanoma because primary melanoma tumors and nearly all melanoma cell lines carry a deletion at this locus [25]. Melanocytes have an intrinsically longer life than many other cell types in the body. The anti-proliferative properties of p53 may be attenuated in melanocytes to accommodate this longer cell life. All normal cells have a finite number of cellular divisions. After this number is reached the cells enter a phase called senescence, which is a protective cellular mechanism in cancer because it prevents aberrant cell growth. Senescence can also be triggered through tumor suppressor proteins when damage is sensed, minimizing uncontrolled cell growth and halting the path to malignancy [26]. The p16INK4a/Rb pathway as shown in Figure 4, is a key pathway for triggering cellular senescence. The loss of this pathway in melanoma is thought to contribute to the pathogenesis of melanoma. It is likely that loss of this protective cellular pathway is more damaging than the potential loss of p53, offering an explanation as to why a p53 mutation is not required for melanocytic tumorigenesis [26]. The p16INK4a protein works as a tumor suppressor by binding to the cyclin-D-dependent protein kinases Cdk4 and Cdk6, preventing them from phosphorylating Rb and preventing entrance into the cell cycle. The genes that encode for both p16INK4a and Cdk4 have be identified as melanoma susceptibility genes [27]. The CdkN2A locus encodes p16INK4a as well as the tumor suppressor p14ARF. The p14ARF gene is encoded by a different promoter through the use of alternative reading frames. Both p14ARF and p16INK4a share exons 2 and 3, while Exon 1B encodes p14 ARF and Exon 1A encodes for p16INK4a. The two share no sequence homology and are not isoforms. The main regulatory function of p14ARF is its binding to MDM2, which prevents the ubiquitination and subsequent degradation of p53 [28]. In cases of familial melanoma, either p16INK4a or both p16INK4a and p14ARF are mutated or deleted. It is rare to see mutations or deletions of p14ARF alone. Germline mutations at the p16INK4a/p14ARF locus are observed in 20-40% of familial cases of melanoma [25]. Somatic melanomas often involve mutations, deletions, or methylation of p16INK4a. Due to a shared open reading frame, up to 40% of mutations or deletions that affect p16INK4a will affect p14ARF [29]. Loss of homozygousity of the p16INK4a/p14ARF locus is observed in half of sporadic melanomas and loss of p16INK4a and p14ARF expression occurs in 50-70% of invasive melanomas [30].
Figure 4.
Gene products from the INK4a/ARF locus
5.3. APAF-1
Apoptosis protease-activating factor-1 (APAF-1) is a regulator in the intrinsic apoptosis pathway. When APAF-1 complexes with cytochome c a multimeric apoptosome is formed that recruits and activates pro-caspase 9, the initiator of the mitochondrial apoptotic cascade. Once activated, caspase 9 proceeds to activate pro-caspase 3 for the execution of apoptosis. A p53 transactivation site has been identified on APAF-1 determining that APAF-1 is a p53 responsive gene [31]. Downregulation of APAF-1 has been observed at the protein and mRNA level during melanoma progression, possibly contributing to the ability of melanoma to evade apoptosis and thus conferring chemoresistance. Noncancerous melanocytes have normal APAF-1 protein and mRNA levels. Conversely, loss of homozygousity has been detected in 42% of metastatic melanoma samples. Analysis of 19 metastatic lines revealed 10 lines with low APAF-1 staining. Other studies have demonstrated significantly higher APAF-1 staining in benign nevi compared with primary melanomas. Lower APAF-1 staining has also been associated with greater tumor thickness in primary melanocytic tumors [32;33].
5.4. Bcl-2
The proapoptotic namesake for the Bcl-2 protein family has a complicated role in melanocytes and in melanoma. Its proapoptotic role in melanocytes prevents premature cell death to allow for continued production of pigment during the long life of the melanocyte. Bcl-2 knockout studies in mice resulted in greying of the mice two weeks after birth due to melanocyte death. The prognostic role of Bcl-2 in melanocytic tumors is controversial. Some analyses have shown that melanoma primary tumors overexpressing Bcl-2 have an increased risk for invasion and are responsible for drug resistance. It has also been observed that Bcl-2 levels actually decrease in melanoma progression. Tumorigenic melanoma cells may take advantage of high endogenous Bcl-2 levels to survive under adverse environmental conditions that they may encounter during metastatic transformation and chemotherapeutic intervention [5;34].
5.5. Bax
The protein Bcl-2 associated X protein (Bax) is a pro-apoptotic Bcl-2 family member highly involved in the mitochondrial apoptotic cascade. It is a p53 target gene and in response to stress, p53 will bind to the Bax promoter leading to its transcription, making it a valuable indicator of p53 transcriptional activity as well as an indicator of intrinsic apoptosis. Bax will translocate to the inner mitochondrial membrane, facilitating the depolarization and release of cytochrome c. It has been observed that expression of Bax increases with melanoma progression, although the tumors remain largely chemoresistant. This implicates that a ratio effect is taking place; the inherent increase of Bcl-2 in melanocytes is potentially high enough to negate the increased expression of Bax, thus facilitating tumor resistance to apoptosis. An increase in Bax expression could also be a result of increased p53 stability and transcriptional activity from mutation or deletion of proteins at the INK4a/ARF locus [35;36].
5.6. PUMA
The BH3-only mitchondrial protein p53 upregulated modulator of apoptosis (PUMA) belongs to the Bcl-2 family of apoptotic regulators. The BH3 domain and its localization within the mitochondria are necessary for PUMA to induce apoptosis or decrease cell growth. Studies have not demonstrated that PUMA is post-translationally modified like other BH3 only proteins. In response to stress stimuli, PUMA is transactivated by p53 [37]. Once activated, PUMA promotes the apoptotic pathway through inhibition of the anti-apoptotic protein Bcl-2, allowing Bax and Bak to become activated and fosters cytochrome c release from the inner mitochondrial membrane to signal initiation of apoptosis. The main pro-apoptotic effect of PUMA is such that once activated by p53, it will inhibit Bcl-2 anti-apoptotic family members in order to transduce apoptosis [38]. It is possible that a loss of PUMA activity in melanoma cells could give rise to an increase in Bcl-2 activity, leading to either evasion of apoptosis by therapy or propagating transformation [39]. Complete silencing of PUMA in melanoma is not known. However, immunostaining for PUMA in benign nevi have shown increased PUMA staining in comparison to dysplastic nevi, primary melanoma, and metastatic tissues. When this data was compared to patient 5-year survival, patients exhibiting increased PUMA staining had a better prognosis and therapeutic response compared to those with little or no PUMA staining [40].
5.7. p73
The p73 protein is a p53 homolog with tumor supressor activities, but it can also demonstrate oncogenic properties, as the p73 gene can be transcribed into several different isoforms. The full length p73 (TAp73) contains a N-terminal transactivation domain, proline rich region, DNA binding domain, and C-terminal oligmerization domain. Members of the p53 family generally carry approximately 70% sequence homology to p53, primarily in the DNA binding domain. Homology in the DNA binding domain allows p73 to recognize and regulate p53 target genes. Splice variants are generated through the use of an internal promoter, the use of an alternative translation start site, or alternative splicing of the first exons. The splice variants have a truncated N-terminus and do not contain a functional DNA binding domain, resulting in a dominant negative protein with anti-apoptotic and growth promoting characteristics. These variants are referred to as delta Np73. The delta isoforms possess antagonistic properties and counteract the tumor supressor activities of TAp73.The intracellular concentration of the of the delta isoforms in relation to the concentration of TAp73 is believed to be of significance. The ratio of the delta isoforms to TAp73 levels may determine the role p73 plays in cell survival [41;42]. Loss or mutation of the p73 gene have not been determined to be major events in the development in melanoma. However, immunostaining of several of the Delta isoforms have shown increased levels of delta isoforms in metastatic melanoma, in addition to strong p73 staining. This suggests p73 may have a role as a positive regulator of tumor growth. In this situation, the ratio of the delta isoforms to TAp73 may be of importance [43]. It is important to note that the delta isoforms are markedly more stable in comparison to TA73, promoting the antagonistic effects. It has been observed that MDM2 can disrupt p73 activities through interfering with the acetyl-transferase p300/CBP. The interaction between p53 and p73 with MDM2 are similar in that they both interact with the same hydrophobic pocket of MDM2, suggests that increased MDM2 activity may decrease the actions of TAp73 as well as that of its isoforms [44].
6. p53-related targeted therapy
Targeting p53 pathways pharmacologically can serve as a very effective means of circumventing chemoresistance observed in melanoma. The use of the small molecule inhibitor nutlin-3 to inhibit MDM2 can restore the anti-tumor effects of p53. Due to the common loss of p14ARF seen in melanoma and the compensatory increase in MDM2, p53 is unable to serve as a mediator of chemosensitivity. The sequesteration of MDM2 in combination with temezolomide potentiated the effects of the drug and increased sensitivity in vivo. The use of nutlin-3 to reinstate p53 function was also shown to be successful with the topoisomerase inhibitor Topotecan [45]. It has also been suggested that the use of nutlin-3 could reverse inaction of p73 through MDM2 inactivation. Given the presence of antagonistic isoforms of p73, the presence of MDM2 could potentially be a defect to exploit in melanoma in order to cease the anti-apoptotic functions of the delta isoforms. Another possibility of therapeutic intervention is the combination of p73 antissense in order to reduce the antagonistic effects of p73 while restoring the native function of p53.
Along with the loss of the p16INK4a/p14ARF locus, an overexpression of cyclin D1 can occur in melanoma, exacerbating the lack of the G1/S cell cycle checkpoint. Sauter et. al. demonstrated that cyclin D1 antisense can work to sensitize melanoma cell lines to apoptosis. The intrinsic increase of Bcl-2 in melanoma results in apoptotic resistance and a decrease in therapeutic outcomes [46]. A study of 771 patients with advanced melanoma were treated with the Bcl-2 antisense Oblimersen in combination with Dacarbazine and had improved 24-month survival and drug response, indicating a role of Bcl-2 in chemoresistence [47].
7. Conclusion
P53-mediated signaling in melanoma provides exceptional insight into the delicate signaling interplay involved in melanoma progression. The role of p53 in the compensatory responses to the infamous deletions and mutations associated with melanocytic tumors will further elucidate mechanisms involved in tumor progression. Increased understanding of these pathways will no doubt propel development of new treatment protocols forward, resulting in new and more effective means to treat this very aggressive disease.
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Breshears and Randy Burd",authors:[{id:"157592",title:"Dr.",name:"Randy",middleName:null,surname:"Burd",fullName:"Randy Burd",slug:"randy-burd",email:"rburd@u.arizona.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Arizona",institutionURL:null,country:{name:"United States of America"}}},{id:"167484",title:"Dr.",name:"Erin",middleName:null,surname:"Mendoza",fullName:"Erin Mendoza",slug:"erin-mendoza",email:"mendo1@email.arizona.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Arizona",institutionURL:null,country:{name:"United States of America"}}},{id:"167485",title:"Dr.",name:"Nicholas",middleName:null,surname:"Panayi",fullName:"Nicholas Panayi",slug:"nicholas-panayi",email:"panayi@email.arizona.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Arizona",institutionURL:null,country:{name:"United States of America"}}},{id:"167486",title:"Mr.",name:"Elliot",middleName:null,surname:"Breshears",fullName:"Elliot Breshears",slug:"elliot-breshears",email:"esbreshears@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Arizona",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. P53",level:"1"},{id:"sec_3",title:"3. p53 and apoptosis",level:"1"},{id:"sec_3_2",title:"3.1. Intrinsic apoptosis",level:"2"},{id:"sec_4_2",title:"3.2. Extrinsic apoptosis",level:"2"},{id:"sec_6",title:"4. Role of p53 in melanogenesis",level:"1"},{id:"sec_6_2",title:"4.1. Tyrosinase",level:"2"},{id:"sec_7_2",title:"4.2. Melanogenesis",level:"2"},{id:"sec_9",title:"5. p53 in melanoma",level:"1"},{id:"sec_9_2",title:"5.1. MDM2",level:"2"},{id:"sec_10_2",title:"5.2. INK4a/ARF locus",level:"2"},{id:"sec_11_2",title:"5.3. APAF-1 ",level:"2"},{id:"sec_12_2",title:"5.4. Bcl-2",level:"2"},{id:"sec_13_2",title:"5.5. Bax",level:"2"},{id:"sec_14_2",title:"5.6. PUMA",level:"2"},{id:"sec_15_2",title:"5.7. p73",level:"2"},{id:"sec_17",title:"6. p53-related targeted therapy",level:"1"},{id:"sec_18",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Chene P. Targeting p53 in cancer. 2001 Aug.'},{id:"B2",body:'Chene P. The role of tetramerization in p53 function. Oncogene 2001 May 10;20(21):2611-7.'},{id:"B3",body:'Gu B, Zhu WG. Surf the post-translational modification network of p53 regulation. Int J Biol Sci 2012;8(5):672-84.'},{id:"B4",body:'Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis - the p53 network. J Cell Sci 2003 Oct 15;116(Pt 20):4077-85.'},{id:"B5",body:'Hussein MR, Haemel AK, Wood GS. p53-related pathways and the molecular pathogenesis of melanoma. Eur J Cancer Prev 2003 Apr;12(2):93-100.'},{id:"B6",body:'Shamas-Din A, Brahmbhatt H, Leber B, Andrews DW. BH3-only proteins: Orchestrators of apoptosis. Biochim Biophys Acta 2011 Apr;1813(4):508-20.'},{id:"B7",body:'Lindsay J, Esposti MD, Gilmore AP. Bcl-2 proteins and mitochondria--specificity in membrane targeting for death. Biochim Biophys Acta 2011 Apr;1813(4):532-9.'},{id:"B8",body:'Sayers TJ. Targeting the extrinsic apoptosis signaling pathway for cancer therapy. 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Biochem Pharmacol 2010 Sep 1;80(5):724-30.'},{id:"B45",body:'de LJ, Ly LV, Lodder K, Verlaan-de VM, Teunisse AF, Jager MJ, et al. Synergistic growth inhibition based on small-molecule p53 activation as treatment for intraocular melanoma. Oncogene 2012 Mar 1;31(9):1105-16.'},{id:"B46",body:'Sauter ER, Takemoto R, Litwin S, Herlyn M. p53 alone or in combination with antisense cyclin D1 induces apoptosis and reduces tumor size in human melanoma. Cancer Gene Ther 2002 Oct;9(10):807-12.'},{id:"B47",body:'Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006 Oct 10;24(29):4738-45.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Nicholas D. Panayi",address:null,affiliation:'
College of Medicine, University of Arizona, Tucson, AZ, USA
'},{corresp:null,contributorFullName:"Erin E. Mendoza",address:null,affiliation:'
Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA
'},{corresp:null,contributorFullName:"Elliot S. Breshears",address:null,affiliation:'
Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA
Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA
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1. Introduction
In [1] it was reported that the main reasons adolescent use social media is for information sharing, alleviating boredom, escapism, to interact socially with peers, building social capital and to receive feedback on their appearances. Therefore, adolescents’ participation in social media platforms is an important aspect for “social participation” [1, 2, 3, 4]. However, research has also shown that social media use can have an impact on the emotional state of the adolescent and the extent to which they can be influenced by peers [5]. Although, research on adolescents’ use of social media is widely reported, this research is focusing on one social media platform, YouTube. YouTube is a video sharing platform that allows content creators to share videos easily, and viewers can view most videos without subscription, registration or restriction.
According to [6] 80% of parents survey in the United States of America (USA) indicate that their children younger than 11 years of age watches videos on YouTube. According to [7] 85% of USA boys and 70% of USA girls between the ages 13 and 17 years of age use YouTube on a daily basis.
In [3] it was shown that adolescents develop a familiarity with the YouTubers (both as content creators and viewers) as they can identify with what they represent. This prolific use of YouTube by adolescents, and even pre-adolescent children, expose children to a variety of content: good and bad. Although it has been reported that adolescent do access YouTube content “for good” such as incidental learning [8], informal learning [9], dealing with anxiety [10], practicing safe sexual health [11] and to obtain information regarding medical procedures [12] to name a few, unfortunately a number of studies have reported on using YouTube “for bad”.
This chapter reports on a systematic review of literature on the negative aspects associated with YouTube, specifically concerning adolescents.
The chapter is structured as follows: Section 2 provides a description of the research methodology, Section 3 provides the data analysis and results. The results are discussed in Section 4 and the chapter is concluded in Section 5.
2. Research methodology
This study employed a systematic review of literature as the methodology. Two research platforms (ProQuest and Ebscohost) were used to access scholarly articles. The ProQuest platform included 12 databases (including ProQuest Central, Health & medical Collection, healthcare Administration database, Nursing and Allied Heath Database and Psychology Database) and the Ebscohost platform included multiple databases (including APA PscyArticles, APA PsycInfo, Family and Society Studies Worldwide, Health Source – consumer edition, Health source: Nursing/academic edition, humanities source, MEDLINE,) In both instances the search terms used were “YouTube” AND “(adolescents or teenagers)”. In both instances “YouTube” had to appear in the title of the paper and “adolescents/teenagers” needed to appear in the abstract of the paper. This search criteria ensured that the search was focused on the YouTube social media platform, with the user segment of adolescents or teenagers. The only filtered aspect was that only peer reviewed scholarly articles should be included.
The initial search with the keywords revealed 99 papers. 76 papers were excluded based on the following criteria:
Duplicate paper
Not written in English
Not focusing on “dark side” aspects
Table 1 illustrates that the final results obtained was a review of 24 papers. These 24 papers.
Platform
Initial results
Final results
ProQuest
44
6
EbscoHost
58
18
Final Total
99
24
Table 1.
Search results.
Thematic Analysis [13] was employed to analyze the content of each of the 24 papers. Phase one is concerned with the researcher familiarizing herself with the data. This was accomplished by reviewing the articles obtained in the search and applying the exclusion criteria. Phases two to five almost occurred in parallel. Phase two was concerned with coding which involves the identification of the theme addressed by the paper. Eight main themes were identified and is illustrated in Table 2. The third phase was concerned with sub-themes. For example, it emerged that YouTube videos featuring smoking also features violence and sexualized imagery. Phase four was concerned with reviewing the themes. This phase involved identifying links between sub-themes, for example it emerged that YouTube videos featuring alcohol also featured sexualized content. This is illustrated in Figure 1. Phase five was self-evident, as the eight themes that emerged was very well-defined in terms of the context in which it was presented. Phase six is concerned with the write up of the data. This was done in two phases, first by providing a short description on each of the studies and then discussing the results in Section 6.
Thematic analysis uncovered eight major themes. The themes that were uncovered are detailed in Table 2.
Figure 1 illustrate how the themes (in yellow) are connected with the sub themes (in blue). The themes and sub themes have emerged from the literature where the authors discussed the theme in terms of the sub themes. For example, Kim et al. [14] conducted a content analysis of smoking fetish videos on YouTube and discovered videos containing smoking glamourizes the activity and it also contains a lot of sexualized imagery and violence. They call for guidelines to manage videos as young children have access to videos that should have parental guidance (PG) ratings.
Likewise, YouTube videos featuring alcohol, also contained sexualized imagery, were present in a number of music videos [18] where the use of alcohol was glamourized [20] and advertised [19].
Each of these themes will be discussed below.
3.1 Smoking
Four of the twenty four articles discussed the promotion and “eroticized” nature [14] of smoking. In [14] 200 videos were sampled from 2300 videos obtained by using the search words “smoking fetish” and “smoking fetishism”. Their analysis revealed (at 4 November 2007) 2220 smoking fetish videos. Using the same search term (“smoking fetch”) it was observed by looking at the playlists only, that there are over 7000 smoking fetish videos now1. Their analysis further showed that although some content was not available for under 18-year old’s, 85.1% of the content was available to everybody. Their study further found that almost 60% of the smoking fetish videos were sexually charged with scantily clad women. They also recommended stronger rating for the videos as it contained sexuality and violence.
In [16] it was tested whether health messages that informs adolescents of the risks of smoking had an impact on their perception of smoking. Their research showed that smoking exposure to adolescents on YouTube correlates with an apparent increased prevalence of smoking.
In [15] it was investigated how tobacco was presented in music videos. The results showed that, at that time (2015), the music videos contained 203 million representations of tobacco products where adolescents were exposed four times more than adults to tobacco products per head of the UK population. The research also showed that for both alcohol and tobacco girls were more.
In [17] it was explained that adolescents perceive cigars to be less harmful than cigarettes. As a consequence, smokers remove the tobacco binder through a process known as “freaking”. The results of their multi-study indicated that adolescents participate in freaking because they believe it ‘Easier to smoke’ (54%), ‘Beliefs in reduction of health risks’ (31%), ‘Changing the burn rate’ (15%) and ‘Taste enhancement’ (12%). Study 2, which concentrated on the comments of freaking videos, indicated that adolescents were unaware or not understanding the risks associated with smoking.
3.2 Alcohol
The alcohol theme is associated with the presence or consumption of alcohol in YouTube videos. Four papers reported on the extent to which alcohol was present in YouTube videos.
Further to what was reported above, [15] also investigated how the presence of alcohol was presented in music videos. The results showed that, at that time (2015), the music videos contained 1006 million representations of alcohol products where adolescents were exposed five times higher for alcohol than for tobacco and four times higher than adults for alcohol representations per head of the UK population. Exposed than boys.
In a further study of Cranwell et al. [18] analyzed “lyrics and visual imagery” of “49 UK Top 40 songs and music videos”. They found that the presence of alcohol in music videos were often accompanied with sexualized imagery or the objectification of women., that the use of alcohol was part of the image, lifestyle and sociability of the video actors and finally the videos promoted excessive drinking with no regards to consequences. Their study concluded, with a caution to the role of advertisers play in the promotion of music video product placements. The placement of alcohol in the videos are often not in line with the “advertising codes of practice”.
Managing the advertising content on social media, has received some attention. In [19] it was investigated whether organizations conform to their digital marketing standards, even on social media. Specifically, the study focused on the extent alcohol is advertised/promoted on YouTube to viewers that are under the legal drinking age. The also, found that alcohol companies’ digital marketing is not sufficient to protect underage viewers from viewing advertisements that promotes the consumption of alcoholic beverages.
In [20] it was further reported that alcohol use was presented as a fun, social activity with underage drinkers. A content analysis on 137 YouTube videos were conducted and concluded that YouTube is an effective platform to advertise alcohol use to adolescents.
3.3 Body image/health
The body image/health theme is concerned with the way body image/health information is communicate and perceived on YouTube. Three papers reported on the dissemination of body image/health data on YouTube.
In [21] an experimental study was conducted to examine the effects of health advice on “adolescent girls’ state of self-objectification, appearance anxiety and preference on products that can be used to enhance appearance”. The study used YouTube videos to inform adolescent girls on healthy behaviors. The results from 154 adolescent girls showed that younger girls tend to self-objectify more. Furthermore, the younger adolescent girls’ self-objectification mediated the effects on appearance anxiety and the use of products to improve their appearance.
In [22] misinformation spread on YouTube regarding anorexia was investigated. Three doctors analyzed 140 videos on YouTube regarding anorexia. They classified content as “informative, pro-anorexia, or other”. It was found there were less pro-anorexia videos than informational videos creating awareness on anorexia, but pro-anorexia videos were more liked by the viewers. The researchers advocated for more awareness on truthfulness of YouTube videos, especially concerning beauty and lifestyle advice. They recommended that celebrities should be employed to create awareness of anorexia.
In [23] it was reported on adolescents accessing YouTube videos to learn about weight loss. They reported that adolescents showed negative feelings regarding body image. The exploratory research analyzed 50 videos that were identified by searching with the key word “diet”. Their analysis concluded that the videos did not show appropriate guidelines to safely lose weight as it was made by non-qualified people. They recommended that policies by government should be in place, or at least be present on the YouTube platform to guide the information being made available on YouTube.
3.4 Bullying
Bullying is concerned with the actions to cause physical or emotional harm to another party. Four papers reported on the extent of bullying content visible in YouTube videos. In [2, 31] it was identified as a common theme as part of digital vulnerabilities of adolescents. However, two papers focused exclusively on bullying.
In [24] investigated the degree to which bullying content is present on YouTube. They found that 89 videos showed violence, 38 videos presented content related to suicide. Only 56 videos were promulgating positive messages related to finding help. They concluded that professional agencies should work towards spreading messages to stop bullying behavior.
In [25] it was reported that YouTube is the most popular social networking platform among Canadian adolescents. This research reported on the analysis of 55 video logs (vlogs) about bullying. They recommended that YouTube can be used as a platform to disseminate and discuss bully behavior.
3.5 Self-harm/suicide
Self-harm/suicide theme is associated with activity to inflict injuries on themselves, or in extreme cases take their own lives. Four papers reported on these types of activities. In [32] research on the “blue whale challenge” was reported. The “blue whale challenge” encouraged adolescents to self-harm and eventually kill themselves. Through a thematic analysis of comments on 60 publicly posted YouTube videos, they learnt that although the comments were focused on raising awareness of the risks of the challenge, it might encourage vulnerable individuals to partake in the challenge. They advocated for “safe messaging guidelines” to create awareness to social media users on the risks associated with content that promote self-harm/suicide.
In [26] reference is made to another challenge, namely Tide pod, which encourages non-suicidal self-harm. The analysis of 413 YouTube videos that featured content on self-harm/suicide revealed that 80% of the videos promoted awareness regarding the risks. Other results indicated that an anlysis of the comments revealed that 2.9% of the comments encouraged suicide, 2.1% of the comments were on how to fight suicidal thoughts, 5.4% of the comments were related to the poster wanting to commit suicide and 5.8% of the comments were negative. They concluded that further research is needed to investigate the negative impact social media platforms can have on the mental health of adolescents.
In [27] the 50 most popular videos depicting self-harm was analyzed. It was revealed that 58% of the videos did not warn viewers of the potential sensitive content to be displayed. The analysis showed that 42% of the videos were portraying a neutral message with regards to self-harm, 27% of the videos discouraged self-harm. However, 23% of the videos provided “mixed messages” regarding self-harm and 7% of the videos encouraged self-harm. They concluded their research by recommending that teachers and parents need to be made aware of self-harm content on YouTube to which vulnerable adolescents can be exposed to.
In [28] 65 videos that demonstrated the asphyxiation game was analyzed. Results showed that 90% of the videos featured males. The videos demonstrated different asphyxiation techniques, including hypoxic seizures (55%) and the sleeper hold (88%). The researchers concluded that YouTube provides a platform for adolescents to view videos on choking and that continued exposure to such videos might normalize the act of choking. They advocated for increased awareness of this to alert youths to the risks associated with the choking games.
3.6 Advertising
Product advertisement on YouTube, is not always regulated by the same digital marketing guidelines as formal digital marketing platforms. Two papers spoke directly about the advertisement of products in YouTube videos.
Further to the promotion of alcohol in [19] to underage drinkers, as reported above, another paper investigated the presence of product placement in microcelebrities’ YouTube videos.
In [29] 1961 comments were analyzed and it revealed that the followers of the specific YouTube channel accepted the commercial content promoted by the star of the YouTube channel. However, they cautioned that viewers are not always aware of product placement, due to lack of transparency, and that viewers might have a skewed view of the life of microcelebrities and the extent to which their lifestyles are supported by industry.
3.7 Drugs
Three papers, [2, 30, 31] reference drugs as being a theme in YouTube videos. Although [2, 31] referenced the presence of drugs as a general theme, [30] explained in detail the effect of Salvia, a short-acting hallucinogenic drug that adolescents in the United States used. The research focused on the analysis of self-taped videos of the use of Salvia. It was reported that the onset of the drugs’ effects was quick, within 30 seconds and lasted for approximately 8 minutes. The research concluded that YouTube was an effective medium to showcase the effect of drug use.
3.8 Vulnerabilities
Through content analysis [2, 31] found that YouTube content creators focused on four major themes of: sex, bullying, pregnancy and drugs. These four themes presented the vulnerabilities adolescents are exposed through YouTube content. They concluded that the language used in the YouTube content was aimed at adolescents. Furthermore, they found that the videos that adolescents made themselves, were more often watched by other adolescents. Videos that were made by institutions to promote a certain “positive” message, were not well watched, or distributed.
4. Discussion
The analysis of the 24 articles provided eight “dark side” themes associated with YouTube content that adolescents engage with. These “dark side” themes describe the typical dangers that adolescent can be exposed to when viewing YouTube videos.
It was apparent that a number of videos featured sexualized imagery, in addition to the promotion of smoking and alcohol consumption [14, 18]. The promotion of alcohol to underage drinkers were also revealed [19, 20].
It was quite interesting to observe that the context in which smoking and alcohol was promoted was through music videos. Often in the music videos, smoking and the consumption of alcohol was perceived as fun, and socializing activities [18].
A number of papers reported that certain YouTube videos do attempt to create awareness of the risks and dangers associated with some activities promoted on YouTube [26, 32]. However, the research reported mixed results. For example, in [22] it was reported that there are fewer pro-anorexia videos observed from the sample than informational videos that caution against anorexia, however the pro-anorexia videos were more “liked” than the informational videos.
A common theme that emerged from the research was: “regulation”. In [14] it was stated that the regulation of smoking advertisements, and smoking fetishism is not sufficient. Strong regulations on advertising was also mentioned in [19]. Advertising Agencies need to be made aware, or realize that the viewers of YouTube content are becoming younger [6], and potentially more vulnerable due to the desensitizing effect of over consumption of YouTube content. The promotion of inappropriate products, such underage drinking and smoking, and the potential unawareness of a young viewer of intentional product placement [29] need to be more effectively regulated. Adolescents are greatly influenced by social media influencers [33] or microcelebrities [29] and although the intention of these influencers or microcelebrities are not always negative, they might unintentionally promote negative behavior. Furthermore, the use of “corrective messages” [16] to counteract the effect of making smoking socially acceptable. This was also advocated by [24] who argued that governmental institutions or professional organizations invest in the promulgation of “positive messages” to prevent bullying and assist adolescents who are/have been bullied.
Parents need to be aware of the availability of potentially harmful content on YouTube (also other video sharing platforms such as Tic Toc). Often, the harmful videos do not limit underage or vulnerable viewers to access the content. Although it was shown that some videos to promulgate health messages, parents need to ensure that their children do not get desensitized due to the over consumption of content. Children often do not understand the risks associated with certain “fun” activities such as freaking [17] or games [26, 32].
Adolescents’ motivation of social media use in general can provide the explanation of the impact it can have on adolescent well-being. In [1] it was shown that motivation for social media use which include passing the time or escapism are inversely related to well-being and body satisfaction and well-being respectively. Therefore, apart from the “negative message” received on social media, such as YouTube, the reason for “escaping” or “passing the time” using social media can further have a detrimental effect on adolescent well-being.
5. Conclusions
YouTube (and similar video sharing platforms) is a popular social media platform for adolescents. Although not all the content on YouTube is problematic, this research has shown that there is truly worrisome content on YouTube which adolescents, especially young adolescents have free access to. Although social media use in general need to be regulated, parents need to regulate the content that their younger adolescents consume of YouTube as the do not always understand the risks associated with the content presented. Also, due to the presentation of some content as “fun” and “sociable”, it can normalize viewers into believing that it is acceptable to partake in illustrated activities.
Apart from “being aware” of potential harmful content on YouTube which can have a detrimental impact on the well-being of adolescents, regulating authorities need to capitalize on the prolific viewership of YouTube by promoting “positive messages” on YouTube.
Furthermore, although the focus of the study was on uncovering the themes that can promulgate “negative messages”, parents, users and regulators need to be aware that the motivations of adolescents’ YouTube use might in itself be harmful to their well-being.
Due to the limited number of empirical studies conducted on the “dark themes of YouTube”, future research can be dedicated to uncovering the impact these dark themes have on the well-being of adolescents.
\n',keywords:"YouTube, Adolescents, Teenagers, Risk, Vulnerabilities, Tobacco, Alcohol, Self-harm",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78470.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78470.xml",downloadPdfUrl:"/chapter/pdf-download/78470",previewPdfUrl:"/chapter/pdf-preview/78470",totalDownloads:155,totalViews:0,totalCrossrefCites:0,dateSubmitted:"March 27th 2021",dateReviewed:"August 17th 2021",datePrePublished:"September 6th 2021",datePublished:null,dateFinished:"September 6th 2021",readingETA:"0",abstract:"The prolific use of social media platforms, such as YouTube, has paved the way for the potential consumption of inappropriate content that targets the vulnerable, especially impressionable adolescents. The systematic review of literature has identified 24 papers that focused on the “dark side” of YouTube for adolescent users. The analysis showed that eight themes emerged: the glamorization of smoking, the promotion of alcohol use, videos that focused on body image/health, videos on bullying, self-harm/suicide, advertising, drugs and general vulnerabilities. The results revealed that videos that contain smoking and alcohol frequently feature sexualized imagery. Smoking videos also frequently feature violence. Smoking and alcohol are also often featured in music videos. The analysis also showed that researchers call for awareness, more strict advertising guidelines and promotion of health messages especially in terms of body image/health, self-harm/suicide and bullying. It is recommended that parents regulate the YouTube consumption of their younger adolescent children, as children do not always understand the risks associated with the content consumed, or might get desensitized against the risks associated with the content.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78470",risUrl:"/chapter/ris/78470",signatures:"Marie Hattingh",book:{id:"10671",type:"book",title:"Adolescences",subtitle:null,fullTitle:"Adolescences",slug:null,publishedDate:null,bookSignature:"Prof. Massimo Ingrassia and Prof. Loredana Benedetto",coverURL:"https://cdn.intechopen.com/books/images_new/10671.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-594-0",printIsbn:"978-1-83969-593-3",pdfIsbn:"978-1-83969-595-7",isAvailableForWebshopOrdering:!0,editors:[{id:"193901",title:"Prof.",name:"Massimo",middleName:null,surname:"Ingrassia",slug:"massimo-ingrassia",fullName:"Massimo Ingrassia"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Research methodology",level:"1"},{id:"sec_3",title:"3. Data analysis and result",level:"1"},{id:"sec_3_2",title:"3.1 Smoking",level:"2"},{id:"sec_4_2",title:"3.2 Alcohol",level:"2"},{id:"sec_5_2",title:"3.3 Body image/health",level:"2"},{id:"sec_6_2",title:"3.4 Bullying",level:"2"},{id:"sec_7_2",title:"3.5 Self-harm/suicide",level:"2"},{id:"sec_8_2",title:"3.6 Advertising",level:"2"},{id:"sec_9_2",title:"3.7 Drugs",level:"2"},{id:"sec_10_2",title:"3.8 Vulnerabilities",level:"2"},{id:"sec_12",title:"4. Discussion",level:"1"},{id:"sec_13",title:"5. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Jarman HK, Marques MD, McLean SA, et al (2021) Motivations for Social Media Use: Associations with Social Media Engagement and Body Satisfaction and Well-Being among Adolescents. 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Journal of Sexual Medicine 14:e275–e275. https://doi.org/10.1016/j.jsxm.2017.04.327'},{id:"B12",body:'Clerici CA, Veneroni L, Bisogno G, et al (2012) Videos on rhabdomyosarcoma on YouTube: an example of the availability of information on pediatric tumors on the web. Journal of pediatric hematology/oncology 34:e329–e331. https://doi.org/10.1097/MPH.0b013e31825886f8'},{id:"B13",body:'Braun V, Clarke V (2012) Thematic analysis. pp 57-71'},{id:"B14",body:'Kim K, Paek H-J, Lynn J (2010) A Content Analysis of Smoking Fetish Videos on YouTube: Regulatory Implications for Tobacco Control. Health Communication 25:97. http://dx.doi.org.uplib.idm.oclc.org/10.1080/10410230903544415'},{id:"B15",body:'Cranwell J, Opazo-Breton M, Britton J (2016) Adult and adolescent exposure to tobacco and alcohol content in contemporary YouTube music videos in Great Britain: a population estimate. Journal of Epidemiology and Community Health 70:488. http://dx.doi.org.uplib.idm.oclc.org/10.1136/jech-2015-206402'},{id:"B16",body:'Romer D, Jamieson PE, Jamieson KH, et al (2017) Counteracting the Influence of Peer Smoking on YouTube. Journal of Health Communication 22:337-345. http://dx.doi.org.uplib.idm.oclc.org/10.1080/10810730.2017.1290164'},{id:"B17",body:'Nasim A, Blank MD, Cobb CO, et al (2014) How to freak a Black & Mild: a multi-study analysis of YouTube videos illustrating cigar product modification. Health Education Research 29:41-57. https://doi.org/10.1093/her/cyt102'},{id:"B18",body:'Cranwell J, Britton J, Bains M (2017) “F*ck It! Let’s Get to Drinking--Poison our Livers!”: a Thematic Analysis of Alcohol Content in Contemporary YouTube MusicVideos. 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Journal of Medical Internet Research 15:. http://dx.doi.org.uplib.idm.oclc.org/10.2196/jmir.2237'},{id:"B23",body:'Gurgel CA, Polo GP, dos Santos MSRF, et al (2017) Videos About Diets Broadcast on Youtube: A Communication Channel Very Accessed by Adolescent. Annals of Nutrition & Metabolism 71:544'},{id:"B24",body:'Basch CH, Ruggles KV, Berdnik A, Basch CE (2017) Characteristics of the most viewed YouTube™ videos related to bullying. International Journal of Adolescent Medicine and Health 29:1872-4. http://dx.doi.org.uplib.idm.oclc.org/10.1515/ijamh-2015-0063'},{id:"B25",body:'Caron C (2017) Speaking Up About Bullying on YouTube: Teenagers’ Vlogs as Civic Engagement. Canadian Journal of Communication 42:645-668. http://dx.doi.org.uplib.idm.oclc.org/10.22230/qc2017v42n4a3156'},{id:"B26",body:'Dagar A, Falcone T (2020) High Viewership of Videos About Teenage Suicide on YouTube. Journal of the American Academy of Child & Adolescent Psychiatry 59:1-3.e1. https://doi.org/10.1016/j.jaac.2019.10.012'},{id:"B27",body:'Potera C (2011) YouTube Self-Harm Videos Under Scrutiny. AJN The American Journal of Nursing 111:20. https://doi.org/10.1097/01.NAJ.0000398530.98917.3f'},{id:"B28",body:'Linkletter M, Gordon K, Dooley J (2010) The Choking Game and YouTube: A Dangerous Combination. Clin Pediatr (Phila) 49:274-279. https://doi.org/10.1177/0009922809339203'},{id:"B29",body:'de Carvalho BJ, Marôpo L (2020) “I’m Sorry You Don’t Flag It When You Advertise”: Audience and Commercial Content on the Sofia Barbosa Youtube Channel. Comunicação e Sociedade 37:93-107. https://doi.org/10.17231/comsoc.37(2020).2394'},{id:"B30",body:'Lange JE, Daniel J, Homer K, et al (2010) Salvia divinorum: Effects and use among YouTube users. Drug & Alcohol Dependence 108:138-140. https://doi.org/10.1016/j.drugalcdep.2009.11.010'},{id:"B31",body:'Jiménez AG, Link to external site this link will open in a new window, Vozmediano MM (2020) Subject matter of videos for teens on YouTube. International Journal of Adolescence and Youth 25:63-78. http://dx.doi.org.uplib.idm.oclc.org/10.1080/02673843.2019.1590850'},{id:"B32",body:'Khasawneh A, Link to external site this link will open in a new window, Madathil KC, et al (2020) Examining the Self-Harm and Suicide Contagion Effects of the Blue Whale Challenge on YouTube and Twitter: Qualitative Study. JMIR Mental Health 7:. http://dx.doi.org.uplib.idm.oclc.org/10.2196/15973'},{id:"B33",body:'van Eldik AK, Kneer J, Lutkenhaus RO, Jansz J (2019) Urban Influencers: An Analysis of Urban Identity in YouTube Content of Local Social Media Influencers in a Super-Diverse City. Front Psychol 10:2876. https://doi.org/10.3389/fpsyg.2019.02876'}],footnotes:[{id:"fn1",explanation:"30 May 2021"}],contributors:[{corresp:"yes",contributorFullName:"Marie Hattingh",address:"marie.hattingh@up.ac.za",affiliation:'
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IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
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In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
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Does your institution already have a budget for covering Open Access publication costs?
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Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
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Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Polymorphism at the DNA level includes a wide range of variations from single base pair change, many base pairs, and repeated sequences. Genomic variability can be present in many forms, including single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs, e.g., mini- and microsatellites), transposable elements (e.g., Alu repeats), structural alterations, and copy number variations. Different forms of DNA polymorphisms can be tracked using a variety of techniques; some of these techniques include restriction fragment length polymorphisms (RFLPs) with Southern blots, polymerase chain reactions (PCRs), hybridization techniques using DNA microarray chips, and genome sequencing. During the last years, the recent advance of molecular technologies revealed new discoveries of DNA polymorphisms. DNA polymorphisms are endless, and more discoveries continue at a rapid rate. Mapping the human genome requires a set of genetic markers. DNA polymorphism serves as a genetic marker for its own location in the chromosome; thus, they are convenient for analysis and are often used as in molecular genetic studies.",book:{id:"6719",slug:"genetic-diversity-and-disease-susceptibility",title:"Genetic Diversity and Disease Susceptibility",fullTitle:"Genetic Diversity and Disease Susceptibility"},signatures:"Salwa Teama",authors:[{id:"249329",title:"Dr.",name:"Salwa",middleName:null,surname:"Teama",slug:"salwa-teama",fullName:"Salwa Teama"}]},{id:"58467",title:"Generation of Antibody Diversity",slug:"generation-of-antibody-diversity",totalDownloads:3217,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Because of the huge diversity, the immunoglobulin repertoire cannot be encoded by static genes, which would explode the genomic capacity comprising about 20,000–25,000 human genes. The immunoglobulin repertoire is provided by the process of somatic germ line recombination, which is the only controlled alteration of the genomic DNA after meiosis. It takes place in mammalian B lymphocyte (B cells) precursors in the bone marrow. The genome germ line sequence of undeveloped B cells is organized in gene segments and compromise V (variable), D (diversity), and J (joining) gene segments constituting the variable domain of the heavy chain and only V and J genes for building up the variable domain of the light chain. The rearrangement of the variable region follows a strict order. The following processes that participate in the generation of antibody diversity were summarized—allelic, combinational, and junctional diversity, pairing of IgH and IgL, and receptor editing—which all together produce the primary antigen repertoire (pre-antigen stimulation). When a B cell encounters a foreign antigen, affinity maturation and class switch are induced. Thereby the antibody repertoire increases. The resulting secondary immunoglobulin repertoire reveals in humans at least 1011 specificities for different antigens.",book:{id:"5784",slug:"antibody-engineering",title:"Antibody Engineering",fullTitle:"Antibody Engineering"},signatures:"Oliver Backhaus",authors:[{id:"177685",title:"M.Sc.",name:"Oliver",middleName:null,surname:"Backhaus",slug:"oliver-backhaus",fullName:"Oliver Backhaus"}]},{id:"61204",title:"Polymorphisms",slug:"polymorphisms",totalDownloads:2089,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"Polymorphism or variation in DNA sequence can affect individual phenotypes such as color of skin or eyes, susceptible to diseases, and respond to drug, vaccine, chemical, and pathogen. It occurs more often than mutations (frequency ≥ 1%). The common polymorphism is single nucleotide polymorphism (SNP) which is a single base change in a DNA sequence that occurs most commonly in the human genome. SNPs have been used as molecular markers in a wide range of studies. Genome-wide association studies (GWAS) searches for SNPs that occur more frequently in person with a particular disease than in person without the disease and pinpoint genes or regions that may contribute to a risk of disease. 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Modern embryology owes its initial development to the key embryo collections that began in the 19th century. The first large collection was that of Carnegie, and this was followed later by the major 7 collections. The second role of the Carnegie collection was for researchers to establish a defined set of Carnegie stages based on embryo morphological features. Today, embryos are imaged three-dimensionally (3D) by a range of imaging modalities including, magnetic resonance microscopy (MRM), episcopic fluorescence image capture (EFIC), phase-contrast X-ray computed tomography (pCT), and optical projection tomography (OPT). Historically, embryo serial images were reconstructed using wax-plate and model techniques. The above new 3D imaging techniques now allow 3D computer reconstructions, analysis, and even 3D printing. 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He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). 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He was elected a Yangtze River Scholars Distinguished Professor in 2013, a member of the International Statistical Institute (ISI) in 2016, a member of the board of the International Chinese Statistical Association (ICSA) in 2018, and a fellow of the Institute of Mathematical Statistics (IMS) in 2021. He received the ICSA Outstanding Service Award in 2018 and the National Science Foundation for Distinguished Young Scholars of China in 2012. He serves as a member of the editorial board of Statistics and Its Interface and Journal of Systems Science and Complexity. He is also a field editor for Communications in Mathematics and Statistics. His research interests include biostatistics, empirical likelihood, missing data analysis, variable selection, high-dimensional data analysis, Bayesian statistics, and data science. He has published more than 190 research papers and authored five books.",institutionString:"Yunnan University",institution:{name:"Yunnan University",country:{name:"China"}}},{id:"1177",title:"Prof.",name:"António",middleName:"J. R.",surname:"José Ribeiro Neves",slug:"antonio-jose-ribeiro-neves",fullName:"António José Ribeiro Neves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1177/images/system/1177.jpg",biography:"Prof. António J. R. Neves received a Ph.D. in Electrical Engineering from the University of Aveiro, Portugal, in 2007. Since 2002, he has been a researcher at the Institute of Electronics and Informatics Engineering of Aveiro. Since 2007, he has been an assistant professor in the Department of Electronics, Telecommunications, and Informatics, University of Aveiro. He is the director of the undergraduate course on Electrical and Computers Engineering and the vice-director of the master’s degree in Electronics and Telecommunications Engineering. He is an IEEE Senior Member and a member of several other research organizations worldwide. His main research interests are computer vision, intelligent systems, robotics, and image and video processing. He has participated in or coordinated several research projects and received more than thirty-five awards. He has 161 publications to his credit, including books, book chapters, journal articles, and conference papers. He has vast experience as a reviewer of several journals and conferences. As a professor, Dr. Neves has supervised several Ph.D. and master’s students and was involved in more than twenty-five different courses.",institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"11317",title:"Dr.",name:"Francisco",middleName:null,surname:"Javier Gallegos-Funes",slug:"francisco-javier-gallegos-funes",fullName:"Francisco Javier Gallegos-Funes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/11317/images/system/11317.png",biography:"Francisco J. Gallegos-Funes received his Ph.D. in Communications and Electronics from the Instituto Politécnico Nacional de México (National Polytechnic Institute of Mexico) in 2003. He is currently an associate professor in the Escuela Superior de Ingeniería Mecánica y Eléctrica (Mechanical and Electrical Engineering Higher School) at the same institute. His areas of scientific interest are signal and image processing, filtering, steganography, segmentation, pattern recognition, biomedical signal processing, sensors, and real-time applications.",institutionString:"Instituto Politécnico Nacional",institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"428449",title:"Dr.",name:"Ronaldo",middleName:null,surname:"Ferreira",slug:"ronaldo-ferreira",fullName:"Ronaldo Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428449/images/21449_n.png",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. 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Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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