Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Obrador, Brenda Wiederhold, Mark Wiederhold, Verónica Lara and Amador Santander",authors:[{id:"13436",title:"Prof.",name:"Jose Luis",middleName:null,surname:"Mosso",fullName:"Jose Luis Mosso",slug:"jose-luis-mosso"},{id:"358761",title:"Dr.",name:"Brenda",middleName:null,surname:"Wiederhold",fullName:"Brenda Wiederhold",slug:"brenda-wiederhold"},{id:"358762",title:"Dr.",name:"Mark",middleName:null,surname:"Wiederhold",fullName:"Mark Wiederhold",slug:"mark-wiederhold"},{id:"358763",title:"Dr.",name:"Gregorio T",middleName:null,surname:"Obrador",fullName:"Gregorio T Obrador",slug:"gregorio-t-obrador"},{id:"358764",title:"Dr.",name:"Verónica",middleName:null,surname:"Lara",fullName:"Verónica Lara",slug:"veronica-lara"},{id:"358765",title:"Dr.",name:"Amador",middleName:null,surname:"Santander",fullName:"Amador Santander",slug:"amador-santander"}]},{id:"39046",title:"Using Augmented Reality Cognitive Artifacts in Education and Virtual Rehabilitation",slug:"using-augmented-reality-cognitive-artifacts-in-education-and-virtual-rehabilitation",signatures:"Claudio Kirner, Christopher Shneider Cerqueira and Tereza Gonçalves Kirner",authors:[{id:"143717",title:"Prof.",name:"Claudio",middleName:null,surname:"Kirner",fullName:"Claudio Kirner",slug:"claudio-kirner"},{id:"148728",title:"Prof.",name:"Tereza",middleName:null,surname:"Kirner",fullName:"Tereza Kirner",slug:"tereza-kirner"},{id:"148729",title:"Mr.",name:"Christopher",middleName:"Shneider",surname:"Cerqueira",fullName:"Christopher Cerqueira",slug:"christopher-cerqueira"}]},{id:"39053",title:"Virtual Environments for Children and Teens",slug:"virtual-environments-for-children-and-teens",signatures:"Jamshid Beheshti",authors:[{id:"143530",title:"Prof.",name:"Jamshid",middleName:null,surname:"Beheshti",fullName:"Jamshid Beheshti",slug:"jamshid-beheshti"}]}]}],publishedBooks:[{type:"book",id:"2214",title:"Virtual Reality in Psychological, Medical and Pedagogical Applications",subtitle:null,isOpenForSubmission:!1,hash:"28049ab50a2bc84b98a9ec96724c143c",slug:"virtual-reality-in-psychological-medical-and-pedagogical-applications",bookSignature:"Christiane Eichenberg",coverURL:"https://cdn.intechopen.com/books/images_new/2214.jpg",editedByType:"Edited by",editors:[{id:"13468",title:"Dr.",name:"Christiane",surname:"Eichenberg",slug:"christiane-eichenberg",fullName:"Christiane Eichenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5326",title:"Multimedia",subtitle:null,isOpenForSubmission:!1,hash:"54e647d5941a2b75d7be01da16591dab",slug:"multimedia",bookSignature:"Kazuki Nishi",coverURL:"https://cdn.intechopen.com/books/images_new/5326.jpg",editedByType:"Edited by",editors:[{id:"4965",title:"Dr.",name:"Kazuki",surname:"Nishi",slug:"kazuki-nishi",fullName:"Kazuki Nishi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7753",title:"Interactive Multimedia",subtitle:"Multimedia Production and Digital Storytelling",isOpenForSubmission:!1,hash:"ec62348c48f21b53dc2896b6a58f81a5",slug:"interactive-multimedia-multimedia-production-and-digital-storytelling",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/7753.jpg",editedByType:"Edited by",editors:[{id:"101330",title:"Dr.",name:"Dragan",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9221",title:"Multimedia Information Retrieval",subtitle:null,isOpenForSubmission:!1,hash:"d44f176ab7139d4d3d6fc65309c77c69",slug:"multimedia-information-retrieval",bookSignature:"Eduardo Quevedo",coverURL:"https://cdn.intechopen.com/books/images_new/9221.jpg",editedByType:"Edited by",editors:[{id:"186525",title:"Dr.",name:"Eduardo",surname:"Quevedo",slug:"eduardo-quevedo",fullName:"Eduardo Quevedo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[]},onlineFirst:{chapter:{type:"chapter",id:"70843",title:"The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined",doi:"10.5772/intechopen.91002",slug:"the-link-between-environmental-toxicant-exposure-and-endometriosis-re-examined",body:'\n
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1. Introduction
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Endometriosis an estrogen dependent disease characterized by ectopic growth of endometrial glands and stroma outside of the uterine cavity. It is estimated that endometriosis may affect anywhere from 5 to 45% of all women [1]. Although retrograde menstruation has become the most widely accepted theory for the development of endometriosis [2], it cannot account for endometriosis in distant organs such as the lung and brain. Therefore, alternative explanations are sought.
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While the cause of endometriosis remains unknown, it most likely arises from a multifaceted origin involving the interaction of environment and genetics [3]. Among the different hypotheses advanced, a growing body of literature suggests that environmental factors including environmental toxicants may play a role in the pathophysiology of endometriosis. Lifestyle and medication use point to a role for environmental factors in endometriosis. While alcohol consumption and cigarette smoking have been associated with lower endometriosis risk [4], developmental exposure to diethylstilbestrol and early life exposure to soy formula as well as alcohol consumption in adulthood was linked with an increased risk of endometriosis [4, 5]. Support for an environmental toxicant influence on the development of endometriosis surged with the report of endometriosis in rhesus monkeys treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [6]. Evidence of estrogen mimicry, dysregulation of steroid signaling, and immune modulation by environmental toxicants such as the persistent organic pollutants including the polychlorinated biphenyls (PCBs), dioxins and dioxin like compounds, pesticides, plasticizers (phthalates and bisphenol A), and some metals has led some to hypothesize that human exposure to environmental toxicants may play an important role in reproductive health including endometriosis [3]. Although a recent systematic review and meta-analysis suggests a possible link between exposure to chlorinated organic chemicals and endometriosis [7], we postulate that the role of exposure to environmental toxicants in the pathophysiology of endometriosis remain uncertain.
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Potential associations between exposure to environmental toxicants and women with endometriosis have been equivocal with several finding positive associations [8, 9, 10] whereas others were unable to document an association [11, 12, 13]. Since our last review of the subject [14, 15, 16, 17] numerous studies have emerged suggesting a potential link between environmental toxicant exposure and endometriosis [7, 18]. Herein, we describe a systematic review and critical appraisal of the recent literature linking exposure to environmental toxicants and endometriosis using a modified weight-of-evidence approach to evaluate the strength of potential associations.
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2. Approach
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We conducted a systematic review of the literature between 2008 and present, to capture publications since our last review of the subject [14, 17]. An electronic search was performed using PubMed and web of science between October and November 2019. The following search terms were employed: endometriosis and environmental contaminants, environmental chemicals, environmental toxicants, endocrine disrupters, dioxins, polychlorinated biphenyls (PCBs), phthalates, bisphenol A, and metals. Inclusion criteria included biomonitoring, epidemiology studies reporting chemical concentrations in women with endometriosis compared to a reference population and associated risk. We also included articles describing experimental animal studies and in vitro experiments designed to explore the effect of chemical exposure on endometriotic lesion survival, growth, and to elucidate potential mechanisms relevant to human health. Review papers, meeting summaries, commentaries were excluded as were articles written in languages other than English. Article titles were downloaded into an Excel spreadsheet and duplicate titles excluded. Articles meeting inclusion and exclusion criteria were decided by review of article titles and abstracts by both authors. Disagreements were resolved through discussion. Articles meeting inclusion criteria were printed in full and read by both authors.
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3. Results
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Our electronic search of the literature revealed 67 articles from which four articles with duplicate titles were excluded (Figure 1). We further excluded six review articles. An additional seven articles were excluded because they either did not report chemical concentrations or associated risk for the development of endometriosis. Consequently, 50 articles were retained for full assessment. The largest group of articles addressed the association between exposure to chlorinated organic compounds including polychlorinated biphenyls (PCBs), dioxins, and dioxin-like compounds with relatively few studies exploring the link between pesticide exposure and endometriosis. Of the chemicals with comparatively short half-lives relative to the chlorinated organic compounds and potential to disrupt endocrine signaling pathways, several reports linking phthalate esters and bisphenol A with endometriosis were found in our search whereas relatively few studies involving perfluoroalkyl compounds and metals studies were found.
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Figure 1.
Flow diagram summarizing the process of candidate article title identification in our electronic literature searches (PubMed and Web of Science) conducted between January 2018 and February 2019, screening, and article selection vs. exclusion. The number of articles included vs. excluded and reasons for exclusion are indicated.
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3.1 Polychlorinated biphenyls (PCBs), dioxin and dioxin-like compounds
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PCBs are one of the most widely produced chemicals worldwide, with millions of pounds being produced globally over the last decade alone [19] for use a coolants in electrical transformers. With 209 possible congeners, PCB toxicity is dependent on chemical structure. For example, non-ortho or mono-ortho PCBs are far more toxic due to the loss of chlorine atoms on the 2,2′,6,6′ of the benzene rings [20]. Due to their diverse structures, PCBs share similar characteristics to estrogen, allowing them to have both agonistic and anti-estrogenic activity [21, 22]. PCBs have been known to disrupt several organs and tissue types throughout the human body; with particular damage to the liver, kidney, and the endocrine system [19]. Our search revealed several studies primarily focused on PCB exposure and endometriosis and additional studies that explored the link between dioxin and dioxin-like compounds and endometriosis (Table 1). Since these compounds are frequently found together in human tissues, we will discuss them together.
Increased risk of endometriosis for DL-PCB-118 (OR = 3.79; 95% CI, 1.61–8.91), NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10) were all significant in case versus controls.
PCB concentrations were higher in peritoneal fluid than serum. However, the total TEQ LOD and dioxin-like PCBs were not significantly different between women with endometriosis and the controls.
Several PCB congeners were associated with significantly lower risk (PCB 170 3rd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9) PCN196 (3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), PCB201 (2nd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; and 3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7) but not summed values (PCBs 170, 196, 201; OR = 1.3, CI 0.8–2.2) and estrogenic PCBs (OR = 1.1; 95% CI, 0.8–1.4).
Significant correlations for PCB concentrations within the three biological compartments omental versus peritoneal adipose tissue were found (p < 0.0001). 137.1 vs. 147.9 ng/g l.w. for sum of 6 NDL-PCB. Adipose vs. serum: WHO-TEQ2005 DL-PCB = 3.6 pg/g l.w., sum of 6 NDL-PCB = 81.1 ng/g l.w.
Dioxins and DL-PCBs were significantly higher in patients with deep infiltrating endometriosis; TCDD, PeCDD, PeCDF were the most significant p < 0.01 for each compound. PCB-126 (PCB-114 p < 0.05; PCB-156 p < 0.05; PCB-189 p = 0.04; PCB-126 p < 0.01).
DLC concentrations were marginally higher in patients with endometriosis (22.3±9.3 pg vs. 20.5±10.8 pg) and higher plasma levels of DLC were linked to a higher risk of endometriosis (aOR = 2.44; 95% CI 1.04–5.70; p = 0.04) adjusted for age. Moderate–severe endometriosis cases only (OR = 3.01; 95% CI 1.06–9.04; p = 0.03)
With the presence of the GSTP1 wild type genotype, medium-high levels of PCB 153, high levels of PCB 180 and total PCBS were significantly associated with endometriosis risk (OR = 6.00; 95% CI, 1.88–19.18 and OR = 9.08; 95% CI, 2.14–44.4, respectively).
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Table 1.
Summary of exposures and outcomes from biomonitoring studies designed to quantify the concentration of polychlorinated biphenyl congeners, dioxins, dioxin-like compounds (DLCs) and non-dioxin-like compounds (NDL) in women with endometriosis compared to healthy controls.
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In a pilot case–control study [24], involving 17 women (10 cases; 7 controls), superficial endometriosis was present in 90% of the cases. Of the 29 congeners measured in this study, both polychlorinated dibenzofurans (PCDFs) and dioxin-like (DL) -PCBs showed no significant difference between the case and control [24]. However, both were elevated in peritoneal fluid relative to the serum, with the reverse seen in polychlorinated dibenzo-p-dioxins (PCDDs) [24]. Both PCDDs and PCDFs in peritoneal fluid were significantly associated with an increased risk of endometriosis [24]. Although a potential association was found, the small sample size, the authors did not adjust for other factors such as age that have previously been shown to affect endometriosis risk. Hence, confidence in the findings from this pilot study is low. In contrast, results of a case–control study [23] of 158 Italian women (80 cases; 78 controls), revealed that both non-dioxin-like (NDL)-PCBs and DL-PCBs levels were significantly elevated in women with laparoscopically and histologically confirmed endometriosis. An increased risk of endometriosis was found for DL-PCBs (PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], and NDL-PCBs including PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10)). No significant associations were observed with respect to hexachlorobenzene (HCB) or to the sum of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs expressed as total toxic equivalent quotients (TEQs). PCB-101, PCB-156, and PCB-170 were all shown to be statistically elevated, with PCB-52, PCB-118, PCB-138, PCB-153, and PCB-180 showing a highly significant difference. All four stages and endometriosis implant localizations (peritoneal, deep, or ovarian) were analyzed, with no significant differences detected. However, the lack of adjustment for potential confounding and failure to account for multiple comparisons are important limitations of this study. IN another study [29], DLC concentrations were quantified in plasma samples using the dioxin-responsive chemical-activated luciferase expression bioassay (CALUX). Blood samples were collected prior to laparoscopic surgery from women with endometriosis (n = 96) and control patients with a normal pelvis (n = 106). A marginal increase in DLC compound concentrations in endometriosis patients relative to controls (22.3 ± 9.3 pg, versus 20.5 ± 10.8 pg CALUX-TEQ/g lipid) was reported [29]. After adjusting plasma concentrations for age only, an increased risk for endometriosis was demonstrated for high concentrations of DLC (OR = 2.44; 95% CI 1.04–5.70, p = 0.04) and when considering moderate to severe endometriosis (OR = 3.01; 95% CI 1.06–9.04, p = 0.03). While the authors adjusted for age, adjustment for BMI, parity, and breast feeding was not undertaken. Thus, these results although suggestive must be interpreted with caution.
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While several studies have provided evidence of a potential link significant associations between women with endometriosis and PCB levels could not be demonstrated by other investigators [25, 28, 31]. No significant association between PCBs and endometriosis risk was found in a study of 789 patients (251 cases; 538 controls); with 20 PCB congers measured in serum from surgically confirmed cases [25]. While the odds ratios (ORs) for several PCB congeners did show significant levels above and below the null; however, there was no specific pattern associated with endometriosis risk. Several PCBs were quantified in the serum of 473 women in an operative cohort (190 cases; 283 controls) and 127 patients from a general population cohort (14 cases; 113 controls), using omental fat in the operative cohort and serum in both [31]. Results were adjusted for confounding variables such as age, BMI, breast-feeding, cotinine, and lipids. Among the 35 PCB congers analyzed, geometric mean serum PCB levels were found to be inversely related in terms of risk in the operative cohort, with the opposite seen in the population cohort [31]. A similar relationship can be seen in omental fat, with sum PCB levels showing significantly higher levels in the non-endometriosis patients relative to the controls. Limitations of this study include the small number of women with endometriosis in the case population (only 11% of women had endometriosis), possible bias through the use of telephone directories, and use of controls without surgical confirmation of absence of disease suggest that results be interpreted with caution. The relationship between exposure to DLCs and deep infiltrating endometriosis (DIE) was explored in a case–control study of 30 cases and 30 controls [28]. Disease status was determined by clinical examination, magnetic resonance imaging (MRI), and transvaginal ultrasonography (TVUS), whereas the control population underwent laparoscopic surgery for adnexal benign gynecological disease. DLCs were analyzed omentum adipose tissue in both groups. The results suggest a significant increase of both dioxins and PCBs relative to the control, with the most toxic forms showing a significant difference (2,3,7,8-TCDD and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]; p < 0.01) [28]. Furthermore, 2,3,4,7,8-PeCDF was also significantly higher and four of the most toxic PCB congeners (PCB 144, 156, 189, 126) had toxic equivalence values (TEQ) that were statistically higher in DIE patients [28]. However, no differences were seen when the data were adjusted for age, breast feeding, and BMI. Limitations of this study include small sample size, and homogeneity of the sample population [28].
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A biomonitoring study conducted in France [26], measured the concentrations of PCBs in serum, peritoneal and omental adipose tissue of 113 adult French women with deep infiltrating endometriosis (DIE) (45 controls, 68 cases). There was a significant difference between omental versus peritoneal adipose tissue PCB concentrations (p < 0.0001). Similar trends were seen is peritoneal adipose tissue versus serum levels, with PCBs showing the highest level of significance in terms of concentration differences.
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Potential gene–environment interaction among women with endometriosis was explored [30]. Specifically, the relationship between glutathione transferase (GST) gene polymorphisms PCB concentrations in a study of 343 Italian women (181 cases; 162 controls). Ability glutathione enzymes to regulate oxidative free radicals and thus oxidative stress and therefore genetic polymorphisms may influence tissue capacity to manage the damaging effects oxidative stress, in turn influencing disease susceptibility. No significant difference in genotype distribution (GSTM1, GSTA1, and GSTP1) between case and control patients could be elicited [30]. However, the GSTP1 wild-type with medium-high blood levels of PCB153, high levels of PCB180, or total PCB levels, showed a significant increase in potential risk, while GSTT1 null was negatively associated with the disease [30]. The potential association between five microsatellites and 28 single nucleotide polymorphisms among 10 dioxin detoxification genes (aryl hydrocarbon receptor (AhR), AHRR, ARNT, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) was examined in 242 women (100 case; 143 control) from Japan [32]. Accounting for disease stages I-IV, BMI, and smoking, no significant association was seen between the polymorphisms and the contribution to the etiology of endometriosis. Taken together, these data suggest that genetic polymorphisms in detoxification enzymes do not modulate endometriosis risk.
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Establishing a link between exposure to environmental toxicants and endometriosis using epidemiology and biomonitoring is difficult owing to challenges in diagnosis of endometriosis [33], lengthy diagnostic delays [34], and high prevalence of endometriosis in asymptomatic women [1] and thus the potential for misclassification error is high. Therefore, animal studies have been employed to better understand the potential hazard posed between toxicant exposure and endometriosis. Developmental exposure of mice to TCDD induced a progesterone-resistant phenotype in adult animals that persisted across generations [35]. Results of this study suggest that TCDD induced activation of the aryl hydrocarbon signaling pathway induces dysregulation of expression of tissue remodeling enzymes, and contributes to the inflammatory responses, cell migration, and proliferation seen in endometriosis patients. These data are supported by prior animal studies demonstrating PCB and dioxin effects in animal models of endometriosis [36, 37, 38].
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Tissue culture studies have been employed to elucidate potentially important toxicant regulated mechanisms. PCBs have been linked to an increased estradiol synthesis and creating an inflammatory milieu through the production of interleukin (IL)-6 and IL-8 [39]. Primary cultures of endometrial stromal cells (ESCs) were treated with both DL-PCBs and NDL-PCBs. Dioxin-like CB126 treatment increased 17β-estradiol (E2) biosynthesis in a dose dependent manner. CB126 exposure also increased 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) as well as decreased methylation of the HSD17B7 promoter leading to an increase in expression. Inflammatory markers were also elevated in cultured endometrial stromal cells. Increased inflammation and E2 synthesis were demonstrated in a mouse model of endometriosis [39]. Although PCB has shown to increase E2 biosynthesis, combining 17β-Estradiol with TCDD showed a synergistic effect and induces M2 activation with macrophages co-cultured with ESCs. STAT3 and P38 phosphorylation in macrophages were also increased differentiation of M2 macrophages, leading to an inflammatory milieu [40]. Several studies also analyzed the impact of TCDD exposure on progesterone-dependent mechanisms. TCDD was found to induce cannabinoid receptor type 1 CB1-R mRNA expression in endometrial stromal cells and steroid-induced expression of the gene was inhibited. Through the use of tissue obtained from women with and without endometriosis, TCDD treatment-induced dysregulation of cannabinoid signaling, immune cell migration into the endometrium during embryo uterine attachment [41] and thus we propose could be an important mechanism in the pathophysiology of endometriosis. PCB was also seen to activate endogenous aryl hydrocarbon receptor (AhR) signaling pathway in immortalized human telomerase reverse transcriptase (hTERT) endometrial epithelial cell (hTERT-EEC), specific to time, concentration, and congener. The changes induced were modulated by changes in estrogen levels, in turn increasing cell migration by hTERT-EEC. Proteomic analysis also identified cell stress responses and metabolism markers (such as heat shock proteins (HSP) 27 and HSP 70) [42]. These proteins are both critical markers for the regulation of apoptosis and cellular stress response pathways. In another study [43] primary cultures of ESCs from both case and control patients showed that PCB-104 exposure affects cell migration, invasion and resultant gene expression. Treatments induced a significant increase in cell migration and invasion of ESCs. Enzyme-linked immunosorbent assays showed a time and dose dependent increase in matrix metalloproteinase 3 (MMP-3) and MMP-10 protein in ESCs, whereas MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not. MMP-3 contributes to the breakdown of the extracellular matrix and promotes tissue remodeling and migration [43]. The results from this study suggest that PCB-104 increased migration and invasion of ESCs through increasing MMP-3 and MMP-10 [43]. Taken together, results from tissue culture studies elucidate PCB and dioxin induced dysregulation of mechanisms potentially important in the pathophysiology of endometriosis.
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In summary, several studies demonstrated a potential association between exposure to PCBs, dioxins, and dioxin-like compounds and increased risk of endometriosis; however, important study limitations decrease confidence in these study findings. Moreover, several studies were unable to evoke evidence of an association between exposure to these toxicants. While, animal studies are few, results from these studies provide evidence of biological plausibility. Results of tissue culture studies also provide evidence that PCBs and dioxins adversely affect mechanistic pathways important in the pathophysiology of endometriosis although the effective concentrations exceed human exposure. Consequently, we suggest that there is weak evidence linking exposure to PCBs and dioxin and DL-PCBs in the pathophysiology of endometriosis.
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3.2 Pesticides
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Chlorinated organic pesticides (COPs) resist degradation in the environment, are lipophilic and thus bioaccumulate in adipose tissues, and concentrations are biomagnified with increasing trophic level. Moreover, COPs are able to travel long distances and remain stable for several decades in the environment, and thus widespread human exposure to these chemicals has frequently been documented. Despite widespread human exposure, the relationship between pesticides and endometriosis risk in general are equivocal.
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The concentrations of six COP levels were measured with gas chromatography and electron-capture, in blood samples of laparoscopically confirmed cases of endometriosis [44]. Results showed that aromatic fungicides had a five-fold increase in risk (aOR = 5.3; 95% CI, 1.2–23.6) when comparing the highest and lowest tertile after adjusting for smoking and serum lipids [44]. Chlordane (t-nonachlor) (aOR = 4.6; 95% CI, 0.5–41.6) and HCB (aOR = 6.4; 95% CI, 1.0–42.8) showed a similar trend [44]. Aldrin, β-hexachlorocyclohexane (β-BHC) and mirex also had increased ORs; however, few women had concentrations above the limit of detection preventing further analysis. Two other studies yielded similar results. Specifically, hexachlorocyclohexane (HCH) was associated with an increased risk of endometriosis in a large study with 248 surgically confirmed endometriosis cases and 538 controls [45]. β-HCH concentrations were significantly elevated in the serum (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0–2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8–2.4), as well as for mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0–2.2). The results were adjusted for participant age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Although trends were seen throughout multiple forms of endometriosis, the strongest association was seen in women with ovarian endometriosis. Similarly, γ-hexachlorocyclohexane (γ-HCH) had a significant association with endometriosis risk (adjusted OR (AOR) for age, body mass index, breast-feeding conditional on parity, cotinine, and lipids = 1.27; 95% CI: 1.01–1.59) [31]. Although these studies provide evidence for a link between exposure to different pesticides and increased risk of endometriosis, there are several limitations to note. In particular, while the authors adjusted their data for some potential confounding variables none appeared to adjust for BMI. Moreover, since multiple pesticides were quantified in each study, correction for multiple comparisons would add confidence to the findings and exclude the potential for type I error. Furthermore, the lack of a dose–response relationship [45] suggests that chance discovery cannot be excluded.
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We found no recent animal studies and only one in vitro study was found. HCB treatment enhanced MMP-2 and MMP-9 activities in human endometrial stromal cell line T-HESC, primary cultures of Human Uterine Fibroblast (HUF), and ESCs [46]. Specifically, MMP-2 was only elevated in ESCs, whereas MMP-9 was elevated in all models. An increase in COX-2 and prostaglandin receptor-4 expression, prostaglandin E2 secretion and the c-Src kinase activation in T-HESC was also seen after HCB exposure. The results suggest that HCB may promote inflammation and invasion parameters through regulation of the AhR pathway.
\n
In summary, the epidemiological and biomonitoring studies suggest a potential association between exposure to chlorinated organic pesticides and increased risk of endometriosis; however, study limitations cannot exclude chance discovery owing to multiple comparisons, failure to adequately adjust for important confounders and lack of a dose–response relationship all weaken confidence in the link between COP exposure and endometriosis risk. A single tissue culture animal experiment conducted within the search window suggests that it is biologically plausible for COPs to promote endometriosis risk. Consequently, we suggest weak evidence linking exposure to COPs and endometriosis.
\n
\n
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3.3 Perfluoroalkyl and polyfluoroalkyl substances
\n
Perfluoroalkyl substances are a rather unique group of compounds due to their seemingly harmless properties. However, over the last decade, perfluoroalkyl and polyfluoroalkyl substances have been detected in blood and urine across the globe [47, 48]. Compromised of carbon-fluorine atoms, this extremely strong bond forms stable compounds that are used in clothing, cookware, carpets, and other common household items. Exposure to these compounds has been linked to adverse effects on metabolism, immune function, and fertility [49, 50, 51].
\n
In a case–control study [27], nine perfluorochemicals (PFCs) were measured in the blood of study participants by liquid chromatography–tandem mass spectrometry. Surgical visualization was used to confirm endometriosis in the operative population and MRI was used to confirm the absence of endometriosis in the control population. Both perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17–3.06]) and perfluorononanoic acid (PFNA) (2.20 [1.02–4.75]) were seen to be associated with endometriosis risk, where results were only moderately changed when adjusted for fecundity [27]. Patients with more severe stages of endometriosis (Stages III and IV) showed a higher concentration of perfluorooctane sulfonic acid (1.86 [1.05–3.30]) and PFOA (2.58 [1.18–5.64]) in their blood compared to controls [27]. Although this study shows a significant association between PFC exposure with an apparent dose response, there are a number of limitations to consider. First assignments of healthy study participants to the control population using MRI alone to exclude asymptomatic endometriosis cannot exclude women with endometriosis. Undiagnosed endometriosis was found in 45.3% of asymptomatic women undergoing laparoscopies for benign conditions [1] and thus the potential for misclassification error in this study weakens confidence in the purported association. Finally, circulating concentration of PFCs from the NHANES (2003–2006) study was compared in 753 women with self-reported diagnosis compared to healthy women without a diagnosis of endometriosis [52]. Results from this study showed that PFNA, PFOA, and perfluorooctane sulfonate (PFOS) were significantly higher among women with endometriosis compared to the control population. Women in the referent population of this study were significantly younger, non-Hispanic white, had more than one menstrual period in the last year and reported to be pregnant at the time of the exam. Furthermore, use of self-reported diagnosis of endometriosis may introduce group assignment bias and thus, these data must be interpreted with caution.
\n
The data linking exposure to Perfluoroalkyl substances and endometriosis are limited to the results of two biomonitoring studies. Although the results suggest that women with endometriosis have exposure to Perfluoroalkyl substances, any potential association with endometriosis is weak owing to limitations of these studies and absence of experimental animal studies or mechanistic experiments.
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3.4 Bisphenol A (BPA)
\n
A monomeric compound, bisphenol A (BPA) is used to polymerize plastics and can be found in common household items such as toilet paper, water bottles, the lining of tin cans, cash register receipts, dental sealants, and building supplies [53]. With over a million tons of BPA being used in the United States alone, BPA has become ubiquitous in the environment leading to widespread human exposure. BPA is able to bind to both estrogen receptors (Esr1 and Esr2), activate the estrogen signaling cascade and thus is considered a xenoestrogen [54]. Estrogenic capacity has led some to postulate that BPA exposure may play a role in the pathophysiology of endometriosis (Table 2).
Urinary BPA levels were found in all analyzed samples; with a statistically significant difference between patients and controls. Urinary BPA concentrations were significantly greater (p = 0.001) in women with endometriosis compared to the control group.
No statistically significant association between total urinary BPA concentrations and endometriosis overall. However, significant results were seen in urine in relation to non-ovarian pelvic endometriosis (2nd quartile vs. lowest quartile: OR = 3.0; 95% CI: 1.2–7.3 and 3rd vs. lowest quartile: OR = 3.0; 95% CI: 1.1–7.6), but not ovarian endometriosis.
BPA was found in 51.7% and BPB was found in sera 27.6% but either could not be detected in all the control cases. Suggests an association between at least one of the compound endometriosis risk.
No significant (p = 0.24) association of endometriosis with urinary BPA concentration.
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\n\n
Table 2.
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between Bisphenol A (BPA) exposure and endometriosis.
\n
A population-based case–control study [56], analyzed the urine from 143 women with confirmed or suspected endometriosis (cases) and 287 healthy controls. Urinary creatinine concentrations, age, reference year, as well as both ovarian and non-ovarian pelvic endometriosis were taken into account. Overall, the urinary BPA concentrations in cases did not differ from the control group. However, unconditional logistic regression analysis revealed that the second versus lowest quartile and third versus lowest quartile had increased adjusted odds ratio (aOR 3.0; 95% CI: 1.2–7.3 and aOR 3.0; 95% CI: 1.1–7.6) for higher BPA concentrations in women with non-ovarian pelvic endometriosis; however, there was no association between urine BPA concentrations and ovarian endometriosis. Moreover, there was no relationship between the highest urine concentrations of BPA and endometriosis overall as well as for non-ovarian pelvic endometriosis and ovarian endometriosis. Furthermore, the lack of a dose–response relationship with increasing urine concentrations of BPA weakens confidence in the potential link between BPA exposure and endometriosis risk.
\n
Results of biomonitoring studies revealed that mean BPA concentrations in the plasma of infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) combined (4.66 ± 3.52, 95% CI; 3.60–5.72 ng/ml) were significantly greater than in a control population (n = 34) of healthy fertile women (2.64 ± 3.99, 95% CI; 1.24–4.03 ng/ml) [59]. In women who reported a diagnosis of endometriosis, the mean ± (SD) concentration of BPA was 4.59 ± 1.22 ng/ml (range < LOQ – 5.31 ng/ml). Moreover, BPA concentrations were quantifiable in only 3% of study participants and comparisons with the fertile controls was not reported. Given the ubiquitous nature of BPA, the low detection frequency in this study is rather surprising and thus we interpret these findings with caution. The small sample size, self-reported diagnosis of endometriosis and associated potential for misclassification error are important limitations of this study. Results of a much larger cross-sectional study of 166 Japanese women [58], showed no significant difference in BPA levels in the urine. BPA concentrations were non-significantly (p = 0.24) greater in women with endometriosis stage 0–I (median = 0.74 μg/g after adjusting to creatinine levels), whereas women with stages II-IV endometriosis had a median concentration of 0.93 μg/g creatinine [58]. BPA levels measured in the sera from healthy fertile (n = 11) and endometriotic women (n = 58) found that both BPA and bisphenol B (BPB) levels were detectable in 51.7% and 27.6% of cases, respectively whereas the control patients showed a complete absence of both compounds [57]. Recently, urinary concentrations of BPA were significantly greater in women (n = 68) with endometriosis (1.17–12.68 pg/μl) compared to a control population (n = 60) (1.28–2.35 pg/μl) [55]. Finally, BPA has a short half-life and the measures in women with a diagnosis of endometriosis are temporally disconnected from the onset of disease which may have originated years earlier in time. The interval between onset of symptoms and diagnosis ranges from 6 to 12 years [34] and thus exposure measurements made after diagnosis are difficult to link with the development of endometriosis. Therefore, reverse causation cannot be excluded as a potential explanation for differences in circulating concentrations of the toxicants measured.
\n
In an animal study [60], BPA and bisphenol AF (BPAF) affected endometriosis lesion development in ovariectomized and hormonally intact mice specific to dose and hormonal status of the host mouse. Minced uterine tissue was injected into the peritoneal cavity of host mice. In this study, BPA treatment disrupted ovarian steroidogenic pathways resulting in lower progesterone levels and higher atretic oocyte numbers [60]. BPAF and BPA had higher epithelial proliferation scores, although this was only significant in the highest dose of 900 ppm. Both compounds mimicked estrogen, with BPAF having a stronger effect than estrogen [60]. Taken together, these data suggest that BPA and related compounds can affect mechanisms important in the pathophysiology of endometriosis. However, the concentrations of BPA needed to achieve these effects are higher than human exposure and thus are unlikely to be relevant at the concentrations of BPA measured in the general human population in contemporary studies.
\n
Results of a tissue culture experiments demonstrated that BPA treatment arrested human ESCs at the G2/M phase of the cell cycle, allowing for cell migration. Progesterone amplifying receptors such as insulin growth factor binding protein 1 and prolactin were also increased in response to BPA treatment [61]. These results suggest that BPA exposure could modulate endometrial stromal cells function; however, the effective concentrations exceed human exposure. Consequently, ambiguous study results from biomonitoring studies and lack of animal studies suggests a lack of association between BPA exposure and risk of endometriosis.
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\n
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3.5 Phthalate esters
\n
Phthalate esters are used as a softener in polyvinyl chloride plastics to make plastics flexible and can be found in products such as cosmetics, building materials, and in medical equipment such as intravenous bags, tubing and rubber stoppers in syringes and blood collection tubes. Phthalates leach from finished products leading to ubiquitous human exposure [62, 63]. Exposure to phthalate esters has been linked with decreased circulating testosterone [64] and animal experiments have shown that phthalates are competitive antagonists of the androgen receptor that displace testosterone from the receptor increasing its availability for conversion to estrogens via aromatase [65]. Therefore, it is postulated that exposure to phthalates could be associated with increased risk of endometriosis (Table 3).
Significantly higher plasma concentrations of MBzP (95% CI; 11.69–28.12 versus 3.34–8.10), BPA (95% CI; 3.60–5.72 versus 1.24–4.03), and MEHHP (95% CI; 5.10–8.43 versus 0.58–2.85).
Positive associations for MBP (OR = 1.36; 95% CI, 0.77–2.41) for the highest versus lowest three quartiles, and inverse associations for MEHP in relation to endometriosis (OR = 0.44; 95% CI, 0.19–1.02)
Greater urinary concentrations of MBzP and MEP in the urine of women with endometriosis compared to controls. Strong inverse association between urinary MEHP and endometriosis risk (aOR 0.3, 95% CI: 0.1–0.7).
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\n\n
Table 3.
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between phthalate exposure and endometriosis.
\n
A large case–control study [67], examined 626 women (495 cases; 131 controls) from 14 clinical centers. Study participants in both groups had a laparoscopy or a pelvic MRI to diagnose the presence of endometriosis. Among the 14 phthalate metabolites, mono-n-butyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate, mono (2-ethyl-5-carboxyphentyl) phthalate, mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-hydroxyhexyl) phthalate, and mono (2-ethyl-5-oxohexyl), all showed two-fold significant increase in the odds of diagnosis. Results were adjusted for age, BMI, and creatinine. Depending on the method of diagnosis, monooctyl phthalate was restricted to surgical diagnosis of endometriosis with histological confirmation, whereas mono (2-ethylhexyl) phthalate was restricted to surgical diagnosis alone. However potential limitations may arise through adding concentrations as mECPP, mEHHP, mEOHP where all are metabolites of DEHP that were elevated in the operative cohort. Yet when summing DEHP metabolites (mECPP, mCMHP, mEHHP, mEOHP, and mEHP), there is a higher odds of endometriosis in the control population cohort. A further limitation is the lack of adjustment for multiple comparisons and thus chance discovery cannot be excluded. A large study from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), examined phthalate levels in 1227 women, with a self-reported history of endometriosis and uterine leiomyomata. MEHP, monobutyl phthalate (MBP), monoethyl phthalate (MEP), and MBzP levels were measured in patients with each disease as well as patients that reported both [69]. Comparing the highest versus lowest three quartiles of urinary phthalate levels, MBP had an OR of 1.36 (95% CI, 0.77–2.41), MEHP was 0.44 (95% CI, 0.19–1.02), with no association for MEP and MBzP in endometriosis patients. Significantly higher plasma concentration of DBP which is broken down into MBP was also seen [69]. However, the use of self-reported cases may be unreliable. Contrary to the NHANES study, an increased endometriosis risk with an increase in urinary MBzP and MEP was described although the results were not significant [71]. Moreover, an inverse relationship between endometriosis risk and urinary MEHP was found (OR = 0.3; 95% CI = 0.1–0.7) and an inverse relationship was also suggested for DEHP, MEHHP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and ΣDEHP. Therefore, a compelling link between phthalate exposure and endometriosis has not been established.
\n
Results of several biomonitoring studies have documented higher concentrations of phthalate metabolites in the urine of women with endometriosis compared to a reference population. Plasma concentrations of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were recently quantified by gas chromatography–mass spectrometry in infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) and 34 fertile women without evidence of gynecological disorders [59]. Overall, the mean (± SD) concentrations (ng/ml) of MBzP (19.9 ± 27.3 95% CI;11.69–28.12) and MEHHP (6.76 ± 5.54, 95% CI; 5.10–8.43) were significantly higher in infertile women compared to fertile women (5.72 ± 6.82, 95% CI; 3.34–8.10 and 1.71 ± 3.24, 0.58–2.85; respectively), whereas no differences were detected between groups for MMP and MEHP. The mean concentrations of MBzP and MEHHP in women with endometriosis were 40.9 ± 51.4 (range < LOQ – 116.5) and 5.43 ± 5.53 ng/ml (range < LOQ – 14.76), respectively. However, only 4–5% of women with endometriosis had concentrations of MBzP and MEHHP above the LOQ . Study participants were assigned to groups based upon self-reports of gynecological diagnoses which is open to misclassification error. In addition, the small sample size overall together with the limited number of study participants with quantifiable concentrations of phthalates are important limitations of this study.
\n
Recently, differences in serum DEHP concentrations were found between women with endometriosis and control patients using high-performance liquid chromatography [66]. The mean ± SD concentration of DEHP in cases (n = 50) was 65.3 ± 21.7 ng/ml, whereas it was undetectable in the controls. Among the four stages of the disease, women with endometriosis showed a linear increase in DEHP concentration with more advanced stages, although the sample size for stage I was n = 1. Age groups did not impact DEHP serum levels. Controversy remains, as DEHP is broken down by glutathione S-transferase and P450 enzyme, which has been reported to be compromised in endometriosis patients [72]. This may explain the difference in serum concentration, as the control patients are able to metabolize DEHP into metabolites which were not recorded. A further weakness of this study is the measurement of DEHP in the serum rather than metabolites in either the serum or urine and thus the potential for sample contamination cannot be discounted.
\n
A group from Taiwan investigated the association between GSTM1 polymorphisms and phthalates in adenomyosis, leiomyoma and endometriosis [68]. Although no relationship between the gene and the disease was found, there was an increase in urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, p < 0.05) among the 28 women with endometriosis relative to the 29 controls. In a subsequent study [70], the potential relationship between polymorphisms of CYP17A1 and phthalate exposure was explored in women with leiomyoma (fibroids, n = 36), endometriosis or adenomyosis (n = 44) and healthy controls (n = 69). However, only a marginally increased level of urinary MEHP was found in patients with endometriosis or adenomyosis [70].
\n
Our search failed to identify any experimental animal studies and only two mechanistic studies were located. MMP-2 and 9 activities, cellular invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression (PAK4) were increased in endometrial stromal cell cultures exposed to DEHP [73]. All five significantly elevated markers play a role in cellular division, actin cytoskeletal dynamics, motility, cell survival, and immune defense [73, 74]. Another study found that DEHP treatment increased ESC reactive oxygen species (ROS) generation and decreased expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), heme oxygenase (HO), and catalase (CAT). p-ERK/p-p38 and NF-κB were also increased [75]. This provides a potential explanation for the decreased expression of antioxidant enzymes and increased ROS. Lastly, Esr1 expression was also increase proportional to dose [75].
\n
In summary, while several studies revealed higher phthalate esters concentrations in women with endometriosis compared to controls the results of epidemiological studies remain equivocal. Moreover, the short half-life of 5–6 h for these chemicals suggests that higher concentrations detected in women with endometriosis compared to controls may be a consequence of the disease rather than a causal factor and thus reverse causation cannot be excluded. While in vitro studies suggest that phthalate esters can adversely affect mechanisms relevant to the pathophysiology of endometriosis, the effective concentrations are beyond human exposure and thus are unlikely to be clinically important.
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3.6 Metals
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Trace metals are nearly impossible to avoid in one’s lifetime, as they are found both naturally in our bodies and are produced during industrial processes. Exposure to metals has been reported to interfere with cell proliferation, migration, cell degeneration, oxidative stress, and apoptosis, nearly all of which are properties of endometriosis [76]. Therefore, a link between circulating concentrations of metals and endometriosis has been explored by several groups.
\n
A positive relationship between lead and endometriosis (adjusted OR = 2.59, 95% CI = 1.11–6.06) was found in Asian women whereas zinc levels were inversely associated with the disease (adjusted OR = 0.39, 95% CI = 0.18–0.88) [77]. While cadmium (Cd) levels were greater in women with endometriosis, the adjusted odds ratio was not significant [77]. Furthermore, no significant relationship was found between 20 trace elements quantified in the urine and three in blood [76]. Cases were surgically confirmed, whereas the controls were confirmed for the absence of endometriosis through MRI. Contrary to the findings by [24], Cd was inversely related to endometriosis risk, while urinary chromium and copper were marginally associated with endometriosis (aOR = 1.97; 95% CI: 1.21–3.19; aOR = 2.66; 95% CI: 1.26–5.64) [76]. Comparisons for each of the metals increase the probability of chance discovery and thus any association is considered suspect.
\n
Our search of the literature failed to reveal any recent animal studies; however, a tissue culture study revealed that Cd treatment-induced higher ESC proliferation (p = 0.02) in cultures derived from eutopic endometrium of women with endometriosis compared to controls [78]. Although the mechanism was not identified, it is suggested that Cd at 10−5 M is the toxic threshold for ESCs [78], a concentration that is orders of magnitude above typical human exposure.
\n
In summary, biomonitoring studies offer weak support for a potential link between metals exposure and endometriosis. Moreover, results from a tissue culture experiment suggest that Cd can adversely affect ESC proliferation but only at concentrations far in excess of human exposure. Consequently, we consider the evidence of a link between exposure to metals and risk of endometriosis to be speculative at best.
\n
\n
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4. Future directions
\n
The current literature fails to provide compelling evidence for an association between exposure to environmental toxicants and endometriosis risk. Although current evidence is weak, involvement of environmental toxicants in the pathophysiology of endometriosis cannot be excluded. However, we propose that establishing a link between exposure to environmental toxicants and endometriosis is particularly challenging. Endometriosis is a heterogeneous disease in which peritoneal and ovarian endometriomas may arise by mechanisms that differ from DIE [79] and thus environmental interactions may be different from other forms of the disease.
\n
Absence of diagnostic tools such as a blood test for endometriosis together with normalization of pelvic pain and use of oral contraceptives among other factors leads to lengthy delays in diagnosis. Importantly, the interval between the onset and symptoms and definitive diagnosis of disease can be lengthy varying between 6 and 12 years [34]. Thus, there is a temporal disconnection between collection of biological samples for analysis and the onset of disease. Hence, the use of case–control studies may not permit convincing evidence of an association and the potential for reverse causation cannot be excluded.
\n
Identification of appropriate control groups poses an additional challenge since the prevalence of endometriosis in asymptomatic women can be high [1]. Furthermore, the hallmarks of endometriosis include chronic pelvic pain and infertility. Women dealing with chronic pain and or infertility may adopt activities or behaviors to reduce their pain or improve their chances of conceiving that diverge from the healthy fertile population and thus their exposures may be a function of disease status rather than factors contributing to the pathophysiology of endometriosis. Consequently, in the absence of clinical tools to diagnosis endometriosis, the most appropriate control group in the future may be symptomatic women undergoing laparoscopy with careful inspection of the pelvic cavity to exclude the presence of endometriosis, even though this step is admittedly imperfect [80].
\n
Epidemiological studies that adjust for potential confounders (e.g. age, BMI, parity, breast feeding, cigarette smoking, and alcohol consumption) and account for multiple comparisons could prove valuable in elucidating the role of exposure to environmental toxicants in the pathophysiology of endometriosis. Finally, it is unlikely that any group of women are exposed to a singly chemical or group of chemicals and thus quantification of chemicals from different chemical groups in a single study with an appropriate control, control for confounds and correction for multiple comparisons could prove informative.
\n
In the absences of robust epidemiological data experimental animal studies take on greater importance for establishing biological plausibility of a potential association. In general, there is a paucity of literature addressing the potential hazards of environmental toxicants in the survival and growth of endometriotic implants in animal models of endometriosis. While spontaneous endometriosis is predominately limited to humans and some non-human primates, animal xenotransplant models using dispersed cells from ectopic implants in women with endometriosis can provide valuable insight into potential chemical hazards relevant to endometriosis and mechanisms. However, dose levels used should include a concentration representative of human exposure. Similarly, tissue culture studies are essential for mechanistic insight; however, we propose that test concentrations should cover a range of doses that include concentrations below and representative of human exposure as well as high doses through to toxic levels.
\n
\n
\n
5. Summary and conclusions
\n
While in general, the epidemiological studies are judged to provide weak evidence of an association between exposure to environmental toxicants and endometriosis, a potential link cannot be excluded. Animal and cell culture models suggest biologically plausible mechanisms between the environmental toxicant exposures and endometriosis risk; however, the effective concentrations exceed human exposure levels. Consequently, we conclude that a causal relationship between exposure to any environmental toxicant and endometriosis does not currently exist, but the evidence does not allow us to exclude a potential link.
\n
\n\n',keywords:"endometriosis, endocrine disrupters, phthalates, bisphenol A, dioxin, estrogenic",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70843.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70843.xml",downloadPdfUrl:"/chapter/pdf-download/70843",previewPdfUrl:"/chapter/pdf-preview/70843",totalDownloads:824,totalViews:0,totalCrossrefCites:1,dateSubmitted:"October 22nd 2019",dateReviewed:"December 26th 2019",datePrePublished:"February 3rd 2020",datePublished:"January 14th 2021",dateFinished:"January 17th 2020",readingETA:"0",abstract:"Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants are associated with increased risk of endometriosis. Since our last review of the subject in 2008, the literature has expanded with several epidemiological and biomonitoring studies suggesting a potential association, whereas others have been unable to demonstrate a link between exposure and enhanced risk. Therefore, we carried out a systematic review and critical appraisal of the literature published over the past decade (2009–2019). The majority of studies found dealt with exposure to polychlorinated biphenyls (PCBs), dioxins, dioxin-like and non-dioxin-like compounds, bisphenol A and phthalate esters. Several studies suggest a potential association between exposure to environmental toxicants; however, important weaknesses in study design, methodology, and analysis together with many contradictory studies weaken confidence in these associations. Consequently, we conclude that despite a growing literature, evidence for an association between exposure to environmental toxicants and risk of endometriosis remains weak.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70843",risUrl:"/chapter/ris/70843",signatures:"Shay M. Freger and Warren G. Foster",book:{id:"9785",type:"book",title:"Endometriosis",subtitle:null,fullTitle:"Endometriosis",slug:"endometriosis",publishedDate:"January 14th 2021",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-465-0",printIsbn:"978-1-83962-464-3",pdfIsbn:"978-1-83962-466-7",isAvailableForWebshopOrdering:!0,editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],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. Approach",level:"1"},{id:"sec_3",title:"3. Results",level:"1"},{id:"sec_3_2",title:"3.1 Polychlorinated biphenyls (PCBs), dioxin and dioxin-like compounds",level:"2"},{id:"sec_4_2",title:"3.2 Pesticides",level:"2"},{id:"sec_5_2",title:"3.3 Perfluoroalkyl and polyfluoroalkyl substances",level:"2"},{id:"sec_6_2",title:"3.4 Bisphenol A (BPA)",level:"2"},{id:"sec_7_2",title:"3.5 Phthalate esters",level:"2"},{id:"sec_8_2",title:"3.6 Metals",level:"2"},{id:"sec_10",title:"4. Future directions",level:"1"},{id:"sec_11",title:"5. Summary and conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'\nRawson JM. Prevalence of endometriosis in asymptomatic women. The Journal of Reproductive Medicine. 1991;36:513-515\n'},{id:"B2",body:'\nSampson J. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. American Journal of Obstetrics and Gynecology. 1927;14:422-469\n'},{id:"B3",body:'\nMatta K, Ploteau S, Coumoul X, Koual M, Le Bizec B, Antignac JP. et al. Associations between exposure to organochlorine chemicals and endometriosis in experimental studies: A systematic review protocol. Environment International. 2019;124:400-407\n'},{id:"B4",body:'\nMissmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. American Journal of Epidemiology. 2004;160:784-796\n'},{id:"B5",body:'\nUpson K, Sathyanarayana S, Scholes D, Holt VL. Early-life factors and endometriosis risk. Fertility and Sterility. 2015;104:964.e965-971.e965\n'},{id:"B6",body:'\nRier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to tetrachlorodibenzo-p-dioxin. Fundamental and Applied Toxicology. 1993;21:433-441\n'},{id:"B7",body:'\nCano-Sancho G, Ploteau S, Matta K, Adoamnei E, Louis GB, Mendiola J, et al. Human epidemiological evidence about the associations between exposure to organochlorine chemicals and endometriosis: Systematic review and meta-analysis. Environment International. 2019;123:209-223\n'},{id:"B8",body:'\nLouis GM, Weiner JM, Whitcomb BW, Sperrazza R, Schisterman EF, Lobdell DT, et al. Environmental PCB exposure and risk of endometriosis. Human Reproduction. 2005;20:279-285\n'},{id:"B9",body:'\nPorpora MG, Ingelido AM, Domenico AD, Ferro A, Crobu M, Pallante D, et al. Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere. 2005;63(8):1361-1367\n'},{id:"B10",body:'\nReddy BS, Rozati R, Reddy S, Kodampur S, Reddy P, Reddy R. High plasma concentrations of polychlorinated biphenyls and phthalate esters in women with endometriosis: A prospective case control study. Fertility and Sterility. 2006;85:775-779\n'},{id:"B11",body:'\nLebel G, Dodin S, Ayotte P, Marcoux S, Ferron LA, Dewailly E. Organochlorine exposure and the risk of endometriosis. Fertility and Sterility. 1998;69:221-228\n'},{id:"B12",body:'\nPauwels A, Schepens PJC, Hooghe TD, Delbeke L, Dhont M, Brouwer A, et al. The risk if endometriosis and exposure to dioxins and polychlorinated biphenyls: A case-control study of infertile women. Human Reproduction. 2001;16:2050-2055\n'},{id:"B13",body:'\nTsukino H, Hanaoka T, Sasaki H, Motoyama H, Hiroshima M, Tanaka T, et al. Associations between serum levels of selected organochlorine compounds and endometriosis in infertile Japanese women. Environmental Research. 2005;99:118-125\n'},{id:"B14",body:'\nAnger DL, Foster WG. The link between environmental toxicant exposure and endometriosis. Frontiers in Bioscience. 2008;13:1578-1593\n'},{id:"B15",body:'\nFoster WG, Agarwal SK. Environmental contaminants and dietary factors in endometriosis. Annals of the New York Academy of Sciences. 2002;955:213-229\n'},{id:"B16",body:'\nFoster WG. Do environmental contaminants adversely affect human reproductive physiology? Journal of Obstetrics and Gynaecology Canada. 2003;25:33-44\n'},{id:"B17",body:'\nFoster WG. Endocrine toxicants including 2,3,7,8-terachlorodibenzo-p-dioxin (TCDD) and dioxin-like chemicals and endometriosis: Is there a link? Journal of Toxicology and Environmental Health. Part B, Critical Reviews. 2008;11:177-187\n'},{id:"B18",body:'\nVabre P, Gatimel N, Moreau J, Gayrard V, Picard-Hagen N, Parinaud J, et al. Environmental pollutants, a possible etiology for premature ovarian insufficiency: A narrative review of animal and human data. Environmental Health. 2017;16:37\n'},{id:"B19",body:'\nFaroon O, Ruiz P. Polychlorinated biphenyls: New evidence from the last decade. Toxicology and Industrial Health. 2016;32:1825-1847\n'},{id:"B20",body:'\nBruner-Tran KL, Osteen KG. Dioxin-like PCBs and endometriosis. Systems Biology in Reproductive Medicine. 2010;56:132-146\n'},{id:"B21",body:'\nKorach KS, Sarver P, Chae K, McLachlan JA, McKinney JD. Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: Conformationally restricted structural probes. Molecular Pharmacology. 1988;33:120-126\n'},{id:"B22",body:'\nMoore M, Mustain M, Daniel K, Chen I, Safe S, Zacharewski T, et al. Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum. Toxicology and Applied Pharmacology. 1997;142:160-168\n'},{id:"B23",body:'\nPorpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, et al. Endometriosis and organochlorinated environmental pollutants: A case-control study on Italian women of reproductive age. Environmental Health Perspectives. 2009;117:1070-1075\n'},{id:"B24",body:'\nCai LY, Izumi S, Suzuki T, Goya K, Nakamura E, Sugiyama T, et al. Dioxins in ascites and serum of women with endometriosis: A pilot study. Human Reproduction. 2010;26(1):117-126\n'},{id:"B25",body:'\nTrabert B, De Roos AJ, Schwartz SM, Peters U, Scholes D, Barr DB, et al. Non-dioxin-like polychlorinated biphenyls and risk of endometriosis. Environmental Health Perspectives. 2010;118:1280-1285\n'},{id:"B26",body:'\nPloteau S, Antignac JP, Volteau C, Marchand P, Vénisseau A, Vacher V, et al. Distribution of persistent organic pollutants in serum, omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure. Environment International. 2016;97:125-136\n'},{id:"B27",body:'\nLouis GM, Peterson CM, Chen Z, Hediger ML, Croughan MS, Sundaram R, et al. Perfluorochemicals and endometriosis: The ENDO study. Epidemiology. 2012;23:799-805\n'},{id:"B28",body:'\nMartínez-Zamora MA, Mattioli L, Parera J, Abad E, Coloma JL, van Babel B, et al. Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis. Human Reproduction. 2015;30:1059-1068\n'},{id:"B29",body:'\nSimsa P, Mihalyi A, Schoeters G, Koppen G, Kyama CM, Den Hond EM, et al. Increased exposure to dioxin-like compounds is associated with endometriosis in a case-control study in women. Reproductive Biomedicine Online. 2010;20:681-688\n'},{id:"B30",body:'\nVichi S, Medda E, Ingelido AM, Ferro A, Resta S, Porpora MG, et al. Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: A gene-environment interaction. Fertility and Sterility. 2012;97:1143-1151\n'},{id:"B31",body:'\nBuck Louis GM, Chen Z, Peterson CM, Hediger ML, Croughan MS, Sundaram R, et al. Persistent lipophilic environmental chemicals and endometriosis: The ENDO study. Environmental Health Perspectives. 2012;120:811-816\n'},{id:"B32",body:'\nMatsuzaka Y, Kikuti YY, Goya K, Suzuki T, Cai LY, Oka A, et al. Lack of an association human dioxin detoxification gene polymorphisms with endometriosis in Japanese women: Results of a pilot study. Environmental Health and Preventive Medicine. 2012;17:512-517\n'},{id:"B33",body:'\nSinaii N, Cleary SD, Younes N, Ballweg ML, Stratton P. Treatment utilization for endometriosis symptoms: A cross-sectional survey study of lifetime experience. Fertility and Sterility. 2007;87:1277-1286\n'},{id:"B34",body:'\nGreene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertility and Sterility. 2009;91:32-39\n'},{id:"B35",body:'\nBruner-Tran KL, Ding T, Osteen KG. Dioxin and endometrial progesterone resistance. Seminars in Reproductive Medicine. 2010;28:59-68\n'},{id:"B36",body:'\nBruner-Tran KL, Rier SE, Eisenberg E, Osteen KG. The potential role of environmental toxins in the pathophysiology of endometriosis. Gynecologic and Obstetric Investigation. 1999;48(Suppl 1):45-56\n'},{id:"B37",body:'\nRier SE, Tuner WE, Martin DC, Morris R, Lucier GW, Clark GC. Serum levels of TCDD and dioxin-like chemicals in rhesus monkeys chronically exposed to dioxin: Correlation of increased serum PCB levels with endometriosis. Toxicological Sciences. 2001;59:147-159\n'},{id:"B38",body:'\nYang JZ, Agarwal SK, Foster WG. Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the Cynomolgus monkey. Toxicological Sciences. 2000;56:374-381\n'},{id:"B39",body:'\nHuang Q , Chen Y, Chen Q , Zhang H, Lin Y, Zhu M, et al. Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions. Archives of Toxicology. 2017;91:1915-1924\n'},{id:"B40",body:'\nWang Y, Chen H, Wang N, Guo H, Fu Y, Xue S, et al. Combined 17β-estradiol with TCDD promotes M2 polarization of macrophages in the endometriotic milieu with aid of the interaction between endometrial stromal cells and macrophages. PLoS One. 2015;10:e0125559\n'},{id:"B41",body:'\nResuehr D, Glore DR, Taylor HS, Bruner-Tran KL, Osteen KG. Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Fertility and Sterility. 2012;98:948.e941-956.e941\n'},{id:"B42",body:'\nWilling C, Peich M, Danescu A, Kehlen A, Fowler PA, Hombach-Klonisch S. Estrogen-independent actions of environmentally relevant AHR-agonists in human endometrial epithelial cells. Molecular Human Reproduction. 2011;17:115-126\n'},{id:"B43",body:'\nHu T, Yao M, Fu X, Chen C, Wu R. Polychlorinated biphenyl 104 promotes migration of endometrial stromal cells in endometriosis. Toxicology Letters. 2018;290:19-28\n'},{id:"B44",body:'\nCooney MA, Buck Louis GM, Hediger ML, Vexler A, Kostyniak PJ. Organochlorine pesticides and endometriosis. Reproductive Toxicology. 2010;30:365-369\n'},{id:"B45",body:'\nUpson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, et al. Organochlorine pesticides and risk of endometriosis: Findings from a population-based case-control study. Environmental Health Perspectives. 2013;121:1319-1324\n'},{id:"B46",body:'\nChiappini F, Bastón JI, Vaccarezza A, Singla JJ, Pontillo C, Miret N, et al. Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by hexachlorobenzene in human endometrial stromal cells. Biochemical Pharmacology. 2016;109:91-104\n'},{id:"B47",body:'\nCalafat AM, Kuklenyik Z, Caudill SP, Reidy JA, Needham LL. Perfluorochemicals in pooled serum samples from United States residents in 2001 and 2002. Environmental Science & Technology. 2006;40:2128-2134\n'},{id:"B48",body:'\nGuruge KS, Taniyasu S, Yamashita N, Wijeratna S, Mohotti KM, Seneviratne HR, et al. Perfluorinated organic compounds in human blood serum and seminal plasma: A study of urban and rural tea worker populations in Sri Lanka. Journal of Environmental Monitoring. 2005;7:371-377\n'},{id:"B49",body:'\nBach CC, Vested A, Jørgensen KT, Bonde JP, Henriksen TB, Toft G. Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: A systematic review. Critical Reviews in Toxicology. 2016;46:735-755\n'},{id:"B50",body:'\nKielsen K, Shamim Z, Ryder LP, Nielsen F, Grandjean P, Budtz-Jørgensen E, et al. Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates. Journal of Immunotoxicology. 2016;13:270-273\n'},{id:"B51",body:'\nLiu G, Dhana K, Furtado JD, Rood J, Zong G, Liang L, et al. Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study. PLoS Medicine. 2018;15:e1002502\n'},{id:"B52",body:'\nCampbell S, Raza M, Pollack AZ. Perfluoroalkyl substances and endometriosis in us women in NHANES 2003-2006. Reproductive Toxicology. 2016;65:230-235\n'},{id:"B53",body:'\nRashtian J, Chavkin DE, Merhi Z. Water and soil pollution as determinant of water and food quality/contamination and its impact on female fertility. Reproductive Biology and Endocrinology. 2019;17:5\n'},{id:"B54",body:'\nRochester JR. Bisphenol a and human health: A review of the literature. Reproductive Toxicology. 2013;42:132-155\n'},{id:"B55",body:'\nItoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S. Urinary phthalate monoesters and endometriosis in infertile Japanese women. Science of the Total Environment. 2009;408:37-42\n'},{id:"B56",body:'\nUpson K, Sathyanarayana S, De Roos AJ, Koch HM, Scholes D, Holt VL. A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis. Human Reproduction. 2014;29:2457-2464\n'},{id:"B57",body:'\nCobellis L, Colacurci N, Trabucco E, Carpentiero C, Grumetto L. Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women. Biomedical Chromatography. 2009;23:1186-1190\n'},{id:"B58",body:'\nItoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S. Urinary bisphenol-A concentration in infertile Japanese women and its association with endometriosis: A cross-sectional study. Environmental Health and Preventive Medicine. 2007;12:258-264\n'},{id:"B59",body:'\nPednekar PP, Gajbhiye RK, Patil AD, Surve SV, Datar AG, Balsarkar GD, et al. Estimation of plasma levels of bisphenol-A & phthalates in fertile & infertile women by gas chromatography-mass spectrometry. The Indian Journal of Medical Research. 2018;148:734-742\n'},{id:"B60",body:'\nJones RL, Lang SA, Kendziorski JA, Greene AD, Burns KA. Use of a mouse model of experimentally induced endometriosis to evaluate and compare the effects of bisphenol A and bisphenol AF exposure. Environmental Health Perspectives. 2018;126:127004\n'},{id:"B61",body:'\nForte M, Mita L, Cobellis L, Merafina V, Specchio R, Rossi S, et al. Triclosan and bisphenol A affect decidualization of human endometrial stromal cells. Molecular and Cellular Endocrinology. 2016;422:74-83\n'},{id:"B62",body:'\nSilva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the national health and nutrition examination survey (NHANES) 1999-2000. Environmental Health Perspectives. 2004;112:331-338\n'},{id:"B63",body:'\nTyrrell J, Melzer D, Henley W, Galloway TS, Osborne NJ. Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010. Environment International. 2013;59:328-335\n'},{id:"B64",body:'\nMeeker JD, Ferguson KK. Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011-2012. The Journal of Clinical Endocrinology and Metabolism. 2014;99(11):4346-4352\n'},{id:"B65",body:'\nLague E, Tremblay JJ. Antagonistic effects of testosterone and the endocrine disruptor mono-(2-ethylhexyl) phthalate on INSL3 transcription in Leydig cells. Endocrinology. 2008;149:4688-4694\n'},{id:"B66",body:'\nNazir S, Usman Z, Imran M, Lone KP, Ahmad G. Women diagnosed with endometriosis show high serum levels of diethyl hexyl phthalate. Journal of Human Reproductive Sciences. 2018;11:131-136\n'},{id:"B67",body:'\nBuck Louis GM, Peterson CM, Chen Z, Croughan M, Sundaram R, Stanford J, et al. Bisphenol A and phthalates and endometriosis: The endometriosis: Natural history, diagnosis and outcomes study. Fertility and Sterility. 2013;100:162-169\n'},{id:"B68",body:'\nHuang PC, Tsai EM, Li WF, Liao PC, Chung MC, Wang YH, et al. Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis. Human Reproduction. 2010;25:986-994\n'},{id:"B69",body:'\nWeuve J, Hauser R, Calafat AM, Missmer SA, Wise LA. Association of exposure to phthalates with endometriosis and uterine leiomyomata: Findings from NHANES, 1999-2004. Environmental Health Perspectives. 2010;118:825-832\n'},{id:"B70",body:'\nHuang PC, Li WF, Liao PC, Sun CW, Tsai EM, Wang SL. Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes. Environmental Science and Pollution Research International. 2014;21:13964-13973\n'},{id:"B71",body:'\nUpson K, Sathyanarayana S, De Roos AJ, Thompson ML, Scholes D, Dills R, et al. Phthalates and risk of endometriosis. Environmental Research. 2013;126:91-97\n'},{id:"B72",body:'\nKubiszeski EH, de Medeiros SF, da Silva Seidel JA, Barbosa JS, Galera MF, Galera BB. Glutathione s-transferase M1 and T1 gene polymorphisms in Brazilian women with endometriosis. Journal of Assisted Reproduction and Genetics. 2015;32:1531-1535\n'},{id:"B73",body:'\nKim SH, Cho S, Ihm HJ, Oh YS, Heo SH, Chun S, et al. Possible role of phthalate in the pathogenesis of endometriosis: In vitro, animal, and human data. The Journal of Clinical Endocrinology and Metabolism. 2015;100:E1502-E1511\n'},{id:"B74",body:'\nDart AE, Wells CM. P21-activated kinase 4—Not just one of the PAK. European Journal of Cell Biology. 2013;92:129-138\n'},{id:"B75",body:'\nCho YJ, Park SB, Han M. Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro. Molecular and Cellular Endocrinology. 2015;407:9-17\n'},{id:"B76",body:'\nPollack AZ, Louis GM, Chen Z, Peterson CM, Sundaram R, Croughan MS, et al. Trace elements and endometriosis: The ENDO study. Reproductive Toxicology. 2013;42:41-48\n'},{id:"B77",body:'\nLai GL, Yeh CC, Yeh CY, Chen RY, Fu CL, Chen CH, et al. Decreased zinc and increased lead blood levels are associated with endometriosis in Asian women. Reproductive Toxicology. 2017;74:77-84\n'},{id:"B78",body:'\nSilva N, Tennekoon K, Senanayake H, Samarakoon S. Metalloestrogen cadmium stimulates proliferation of stromal cells derived from the eutopic endometrium of women with endometriosis. Taiwanese Journal of Obstetrics & Gynecology. 2013;52:540-545\n'},{id:"B79",body:'\nGordts S, Koninckx P, Brosens I. Pathogenesis of deep endometriosis. Fertility and Sterility. 2017;108:872.e871-885.e871\n'},{id:"B80",body:'\nWykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: A systematic quantitative review. BJOG. 2004;111:1204-1212\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Shay M. Freger",address:null,affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
'},{corresp:"yes",contributorFullName:"Warren G. Foster",address:"fosterw@mcmaster.ca",affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
'}],corrections:null},book:{id:"9785",type:"book",title:"Endometriosis",subtitle:null,fullTitle:"Endometriosis",slug:"endometriosis",publishedDate:"January 14th 2021",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-465-0",printIsbn:"978-1-83962-464-3",pdfIsbn:"978-1-83962-466-7",isAvailableForWebshopOrdering:!0,editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"255635",title:"Dr.",name:"Kashif",middleName:null,surname:"Ansari",email:"ka3787@gmail.com",fullName:"Kashif Ansari",slug:"kashif-ansari",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"2",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Southwest Petroleum University",institutionURL:null,country:{name:"China"}}},booksEdited:[],chaptersAuthored:[{id:"65693",title:"Investigation of Corrosion Inhibitors Adsorption on Metals Using Density Functional Theory and Molecular Dynamics Simulation",slug:"investigation-of-corrosion-inhibitors-adsorption-on-metals-using-density-functional-theory-and-molec",abstract:"The use of computational chemistry as a tool in the design and development of organic corrosion inhibitors has been greatly enhanced by the development of density functional theory (DFT) and Molecular dynamic simulation (MD). Experimentally corrosion inhibitor development requires lots of money and time. Thus, in the era of hardware and software development, corrosion scientist can select a potential inhibitor on the basis of theoretical analysis of molecular properties of inhibitor molecules, which have reduced the cost. DFT and MD are capable to accurately predict the inhibition characteristics of inhibitor molecules using molecular/electronic properties and reactivity indices. The purpose of this book chapter is to summarize some important features related to DFT and MD, giving a brief background to the selected DFT/MD-based chemical reactivity concepts, calculations and their applications to organic corrosion inhibitor design. The impact of this book chapter is to illustrate the enormous power of DFT and MD.",signatures:"Ambrish Singh, Kashif R. Ansari, Mumtaz A. Quraishi and Yuanhua Lin",authors:[{id:"178751",title:"Dr.",name:"Yuanhua",surname:"Lin",fullName:"Yuanhua Lin",slug:"yuanhua-lin",email:"yhlin28@163.com"},{id:"207838",title:"Prof.",name:"Mumtaz",surname:"Quraishi",fullName:"Mumtaz Quraishi",slug:"mumtaz-quraishi",email:"maquraishi.apc@itbhu.ac.in"},{id:"215348",title:"Dr.",name:"Ambrish",surname:"Singh",fullName:"Ambrish Singh",slug:"ambrish-singh",email:"vishisingh4uall@gmail.com"},{id:"255635",title:"Dr.",name:"Kashif",surname:"Ansari",fullName:"Kashif Ansari",slug:"kashif-ansari",email:"ka3787@gmail.com"}],book:{id:"7550",title:"Corrosion Inhibitors",slug:"corrosion-inhibitors",productType:{id:"1",title:"Edited Volume"}}},{id:"71994",title:"Corrosion Mitigation by Planar Benzimidazole Derivatives",slug:"corrosion-mitigation-by-planar-benzimidazole-derivatives",abstract:"The corrosion has a considerable amount of impact on the economics of every nation, and ultimately it affects the GDP. In the present era, the challenge given by corrosion can be easily mitigated using organic compounds as corrosion inhibitor in different corrosive media. The important property of an inhibitor is the presence of the metal interacting with heteroatoms and a planar structure. In this regard, benzimidazoles (BI) with a fused bicyclic ring consisting of benzene and imidazole moiety in their structural framework making them a potential candidate for anti-corrosion work. In addition to this, bezimidazole derivatives are classified as green inhibitor due to different kinds of biological activities. Their higher potency to mitigate corrosion is because of the planar molecular structure, nitrogen atom and sp2 hybridized carbon, which provide them an ability to strongly interact with the metal. The focus of this book chapter is to investigate briefly the anti-corrosion ability of benzimidazole (BI) and their derivatives as a potential corrosion inhibitor for various industrially useful metals in different aggressive media.",signatures:"Ambrish Singh, Kashif R. Ansari, Dheeraj S. Chauhan, Mumtaz A. 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As this section deals with legal issues pertaining to the rights of individual Authors and IntechOpen, for the avoidance of doubt, each category of publication is dealt with separately. Consequently, much of the information, for example definition of terms used, is repeated to ensure that there can be no misunderstanding of the policies that apply to each category.
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All Works published on the IntechOpen platform and in print are licensed under a Creative Commons Attribution 3.0 Unported and Creative Commons 4.0 International License, a license which allows for the broadest possible reuse of published material.
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DISCLAIMER: Neither the CC BY 3.0 license, CC BY 4.0, nor any other license IntechOpen currently uses or has used before, applies to figures and tables reproduced from other works, as they may be subject to different terms of reuse. In such cases, if the copyright holder is not noted in the source of a figure or table, it is the responsibility of the User to investigate and determine the exact copyright status of any information utilised. Users requiring assistance in that regard are welcome to send an inquiry to permissions@intechopen.com.
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All rights to Books and Journals and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
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The copyright to Books, Journals and other compilations is subject to separate copyright from those that exist in the included Works.
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All Book cover design elements, as well as Video image graphics are subject to copyright by IntechOpen.
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Every reproduction of a front cover image must be accompanied by an appropriate Copyright Notice displayed adjacent to the image. The exact Copyright Notice depends on who the Author of a particular cover image is. Users wishing to reproduce cover images should contact permissions@intechopen.com.
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All software used on the IntechOpen platform, any used during the publishing process, and the copyright in the code constituting such software, is the property of IntechOpen or its software suppliers. As such, it may not be downloaded or copied without permission.
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All content included on IntechOpen Websites not forming part of contributed materials (such as text, images, logos, graphics, design elements, videos, sounds, pictures, trademarks, etc.), are subject to copyright and are property of, or licensed to, IntechOpen. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance of the content on this site is strictly prohibited.
Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
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IntechOpen only publishes manuscripts for which it has publishing rights. This is governed by a publication agreement between the Author and IntechOpen. This agreement is accepted by the Author when the manuscript is submitted and deals with both the rights of the publisher and Author, as well as any obligations concerning a particular manuscript. However, in accepting this agreement, Authors continue to retain significant rights to use and share their publications.
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HOW COPYRIGHT WORKS WITH OPEN ACCESS LICENSES?
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By accepting the agreement terms Authors retain their copyright on their Work but grant broad publishing and distribution rights to the publisher.
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Depending on the type of publication (Chapter or Long Form Monograph/Compacts; see definitions below), IntechOpen applies a Creative Commons license to the publication, allowing readers to use and share it freely.
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IntechOpen makes the publication available online under an appropriate license.
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Agreement samples are listed here for the convenience of prospective Authors:
The following definitions apply in this Copyright Policy:
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Author - in order to be identified as an Author, three criteria must be met: (i) Substantial contribution to the conception or design of the Work, or the acquisition, analysis, or interpretation of data for the Work; (ii) Participation in drafting or revising the Work; (iii) Approval of the final version of the Work to be published.
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Monograph/Compacts - a full manuscript usually written by a single Author, including any and all text, graphics, images and/or other materials.
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Compilation - a collection of Works distributed in a Book that IntechOpen has selected, and for which the coordination of the preparation, arrangement and publication has been the responsibility of IntechOpen. Any Work included is accepted in its entirety in unmodified form and is published with one or more other contributions, each constituting a separate and independent Work, but which together are assembled into a collective whole.
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Video Lecture – an audiovisual recording of a lecture or a speech given by a Lecturer, recorded, edited, owned and published by IntechOpen.
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TERMS
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All Works published on the IntechOpen platform and in print are licensed under a Creative Commons Attribution 3.0 Unported and Creative Commons 4.0 International License, a license which allows for the broadest possible reuse of published material.
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Copyright on the individual Works belongs to the specific Author, subject to an agreement with IntechOpen. The Creative Common license is granted to all others to:
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Share — copy and redistribute the material in any medium or format
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Adapt — remix, transform, and build upon the material
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And for any purpose, provided the following conditions are met:
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An Attribution, giving appropriate credit and providing a link to the license, with an indication as to whether changes to the original were made
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A commitment not to add additional restrictions. In effect, this prohibits the application of legal conditions or technological measures that legally restrict others from doing anything that the license permits.
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All Works are published under the CC BY 3.0 and CC BY 4.0 license. However, please note that book Chapters may fall under a different CC license, depending on their publication date as indicated in the table below:
Creative Commons Attribution 3.0 Unported (CC BY 3.0)
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5 October 2011 (2011-10-05)
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The CC BY 3.0 and CC BY 4.0 license permits Works to be freely shared in any medium or format, as well as the reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as the source Work is cited and its Authors are acknowledged in the following manner:
Originally published in {full citation}. Available from: {DOI}
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Republishing – More about Attribution Policy can be found here.
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The same principles apply to Works published under the CC BY-NC-SA 3.0 license, with the caveats that (1) the content may not be used for commercial purposes, and (2) derivative works building on this content must be distributed under the same license. The restrictions contained in these license terms may, however, be waived by the copyright holder(s). Users wishing to circumvent any of the license terms are required to obtain explicit permission to do so from the copyright holder(s).
\n\n
DISCLAIMER: Neither the CC BY 3.0 license, CC BY 4.0, nor any other license IntechOpen currently uses or has used before, applies to figures and tables reproduced from other works, as they may be subject to different terms of reuse. In such cases, if the copyright holder is not noted in the source of a figure or table, it is the responsibility of the User to investigate and determine the exact copyright status of any information utilised. Users requiring assistance in that regard are welcome to send an inquiry to permissions@intechopen.com.
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All rights to Books and Journals and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
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The copyright to Books, Journals and other compilations is subject to separate copyright from those that exist in the included Works.
Copyright to the individual Works (Chapters) belongs to their specific Authors, subject to an agreement with IntechOpen and the Creative Common license granted to all others to:
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Share — copy and redistribute the material in any medium or format
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Adapt — remix, transform, and build upon the material
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There must be an Attribution, giving appropriate credit, provision of a link to the license, and indication if any changes were made.
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NonCommercial - The use of the material for commercial purposes is prohibited. Commercial rights are reserved to IntechOpen or its licensees.
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No additional restrictions that apply legal terms or technological measures that restrict others from doing anything the license permits are allowed.
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The CC BY-NC 4.0 license permits Works to be freely shared in any medium or format, as well as reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as it is not used for commercial purposes. The source Work must be cited and its Authors acknowledged in the following manner:
Originally published in {full citation}. Available from: {DOI}
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All Book cover design elements, as well as Video image graphics are subject to copyright by IntechOpen.
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Every reproduction of a front cover image must be accompanied by an appropriate Copyright Notice displayed adjacent to the image. The exact Copyright Notice depends on who the Author of a particular cover image is. Users wishing to reproduce cover images should contact permissions@intechopen.com.
Share — copy and redistribute the material in any medium or format
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Under the following terms:
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Attribution — give appropriate credit, provide a link to the license, and indicate if changes were made.
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NonCommercial use only - you may not use the material for commercial purposes. Commercial rights are reserved to IntechOpen or its licensees.
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Distribution of remixed or transformed material building on the original termed derivatives is not permitted.
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No additional restrictions — you may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
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Users wishing to repost and share the Video Lectures are welcome to do so as long as they acknowledge the source in the following manner:
Users wishing to reuse, modify, or adapt the Video Lectures in a way not permitted by the license are welcome to contact us at permissions@intechopen.com to discuss waiving particular license terms.
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All software used on the IntechOpen platform, any used during the publishing process, and the copyright in the code constituting such software, is the property of IntechOpen or its software suppliers. As such, it may not be downloaded or copied without permission.
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Unless otherwise indicated, all IntechOpen websites are the property of IntechOpen.
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All content included on IntechOpen Websites not forming part of contributed materials (such as text, images, logos, graphics, design elements, videos, sounds, pictures, trademarks, etc.), are subject to copyright and are property of, or licensed to, IntechOpen. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance of the content on this site is strictly prohibited.
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Policy last updated: 2016-06-08
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Emdad Haque and M. Salim Uddin",authors:[{id:"163390",title:"Dr.",name:"C. Emdad",middleName:null,surname:"Haque",slug:"c.-emdad-haque",fullName:"C. Emdad Haque"},{id:"168399",title:"Mr.",name:"Mohammed S",middleName:null,surname:"Uddin",slug:"mohammed-s-uddin",fullName:"Mohammed S Uddin"}]},{id:"56731",doi:"10.5772/intechopen.70351",title:"Affective Technology Acceptance Model: Extending Technology Acceptance Model with Positive and Negative Affect",slug:"affective-technology-acceptance-model-extending-technology-acceptance-model-with-positive-and-negati",totalDownloads:2395,totalCrossrefCites:8,totalDimensionsCites:15,abstract:"Research works on TAM, TAM2, TAM3 and UTAUT has always focused on cognitive aspect of technology acceptance in the past two decades. Acceptance of technologies such as eCommerce, Mobile and ERP that considered emotion and affect are still less. This creates a gap in the technology acceptance research, which consider the role of affect into technology acceptance model. This study considers the role of affect of a knowledge worker that work in Multimedia Super Corridor (MSC)-status organizations in Malaysia on their behavioural intention to use knowledge sharing tools (KS tools) in their day-to-day tasks. Hence, Affective Technology Acceptance (A.T.A) model has been proposed. The behavioural intention on the acceptance of KS tools will be hypothesize in the Affective Technology Acceptance (A.T.A) model. Positive (PA) and Negative (NA) affect as the role of affect construct were introduce in this model to investigate its influence on KS tools usefulness and ease of use among employees in Multimedia Super Corridor organizations. The findings of this study highlighted that NA has no impact on perceive usefulness. The findings also showed that PA has very significant positive influence on PU, PEOU and BI with impact on PEOU being the greatest.",book:{id:"5491",slug:"knowledge-management-strategies-and-applications",title:"Knowledge Management Strategies and Applications",fullTitle:"Knowledge Management Strategies and Applications"},signatures:"Angela Lee Siew Hoong, Lip Sam Thi and Mei-Hua Lin",authors:[{id:"190265",title:"Associate Prof.",name:"Angela",middleName:"Siew Hoong",surname:"Lee",slug:"angela-lee",fullName:"Angela Lee"},{id:"195089",title:"Prof.",name:"Lip Sam",middleName:null,surname:"Thi",slug:"lip-sam-thi",fullName:"Lip Sam Thi"},{id:"195090",title:"Prof.",name:"Mei Hua",middleName:null,surname:"Lin",slug:"mei-hua-lin",fullName:"Mei Hua Lin"}]},{id:"55633",doi:"10.5772/intechopen.68933",title:"Parental Self-efficacy in Promoting Children Care and Parenting Quality",slug:"parental-self-efficacy-in-promoting-children-care-and-parenting-quality",totalDownloads:2117,totalCrossrefCites:9,totalDimensionsCites:14,abstract:"Parental self-efficacy (PSE) emerges as a crucial variable into exploring variability in parenting quality. After introducing the link between PSE and parental competence, the role of PSE on parenting quality, its multiple influences, and transactional effects connected to contextual or cultural variables are discussed. The chapter addresses some key issues: (a) the levels of PSE measurement (i.e., domain- or task-specific approach), their interrelationship and magnitude as mutual predictors (study 1); (b) infant-caring, parent’s adjustment, and PSE development in the transition to parenthood (study 2); (c) parenting difficult children and the role of PSE as a “buffer” variable moderating the effects of negative child’s characteristics on parenting skills; and (d) PSE beliefs in family context, the relationships with other family measures (marital self-efficacy and stress), and their associations with children’s adjustments (study 3). Finally, in the study 4, PSE is presented as an outcome variable in a parent training. In all summarized studies, a special attention was devoted to father’s PSE as a specific factor affecting childrearing and parent’s well-being. As Bandura says, PSE is not a personality trait, but a learnable set of beliefs producing positive effects on parenting quality. Suggestions for family-based interventions enhancing PSE are discussed.",book:{id:"5605",slug:"parenting-empirical-advances-and-intervention-resources",title:"Parenting",fullTitle:"Parenting - Empirical Advances and Intervention Resources"},signatures:"Loredana Benedetto and Massimo Ingrassia",authors:[{id:"193200",title:"Prof.",name:"Loredana",middleName:null,surname:"Benedetto",slug:"loredana-benedetto",fullName:"Loredana Benedetto"},{id:"193901",title:"Prof.",name:"Massimo",middleName:null,surname:"Ingrassia",slug:"massimo-ingrassia",fullName:"Massimo Ingrassia"}]},{id:"60813",doi:"10.5772/intechopen.76198",title:"Crisis Management: A Historical and Conceptual Approach for a Better Understanding of Today’s Crises",slug:"crisis-management-a-historical-and-conceptual-approach-for-a-better-understanding-of-today-s-crises",totalDownloads:4713,totalCrossrefCites:9,totalDimensionsCites:12,abstract:"We argue that the basic and contemporary concepts related to crisis management, especially in the communication field, share some similarities with what was practiced in ancient civilizations such as the importance of direct contact between the leadership and the public. Other similarities include the accurate diagnosis of the real causes of the crisis, the forbiddance of the dissemination of false news and the reassurance of the public opinion that there is a solution to the crisis, a sound management decision, and a good plan for its implementation. We link the past time crises to the contemporary era, providing a comparison framework. The history of crisis tends to show us that the study of crisis management cannot be linked to a specific civilization or era, especially when humanity had witnessed multiple and complex environmental, political, economic, and military crisis. Moreover, some of the problems and complex issues in the modern era are rooted in history. Thus, many geopolitical crises nowadays are the result of old causes. The study of crisis management from an academic point of view should be a multifaceted analysis, including a historical, a cultural, and an anthropological one, which determines the course of evolution and consequences of the crisis.",book:{id:"6620",slug:"crisis-management-theory-and-practice",title:"Crisis Management",fullTitle:"Crisis Management - Theory and Practice"},signatures:"Khaled Zamoum and Tevhide Serra Gorpe",authors:[{id:"230918",title:"Prof.",name:"T. Serra",middleName:null,surname:"Gorpe",slug:"t.-serra-gorpe",fullName:"T. Serra Gorpe"},{id:"230920",title:"Dr.",name:"Khaled",middleName:null,surname:"Zamoum",slug:"khaled-zamoum",fullName:"Khaled Zamoum"}]}],mostDownloadedChaptersLast30Days:[{id:"60813",title:"Crisis Management: A Historical and Conceptual Approach for a Better Understanding of Today’s Crises",slug:"crisis-management-a-historical-and-conceptual-approach-for-a-better-understanding-of-today-s-crises",totalDownloads:4710,totalCrossrefCites:8,totalDimensionsCites:11,abstract:"We argue that the basic and contemporary concepts related to crisis management, especially in the communication field, share some similarities with what was practiced in ancient civilizations such as the importance of direct contact between the leadership and the public. Other similarities include the accurate diagnosis of the real causes of the crisis, the forbiddance of the dissemination of false news and the reassurance of the public opinion that there is a solution to the crisis, a sound management decision, and a good plan for its implementation. We link the past time crises to the contemporary era, providing a comparison framework. The history of crisis tends to show us that the study of crisis management cannot be linked to a specific civilization or era, especially when humanity had witnessed multiple and complex environmental, political, economic, and military crisis. Moreover, some of the problems and complex issues in the modern era are rooted in history. Thus, many geopolitical crises nowadays are the result of old causes. The study of crisis management from an academic point of view should be a multifaceted analysis, including a historical, a cultural, and an anthropological one, which determines the course of evolution and consequences of the crisis.",book:{id:"6620",slug:"crisis-management-theory-and-practice",title:"Crisis Management",fullTitle:"Crisis Management - Theory and Practice"},signatures:"Khaled Zamoum and Tevhide Serra Gorpe",authors:[{id:"230918",title:"Prof.",name:"T. Serra",middleName:null,surname:"Gorpe",slug:"t.-serra-gorpe",fullName:"T. Serra Gorpe"},{id:"230920",title:"Dr.",name:"Khaled",middleName:null,surname:"Zamoum",slug:"khaled-zamoum",fullName:"Khaled Zamoum"}]},{id:"44219",title:"Disaster Management Discourse in Bangladesh: A Shift from Post-Event Response to the Preparedness and Mitigation Approach Through Institutional Partnerships",slug:"disaster-management-discourse-in-bangladesh-a-shift-from-post-event-response-to-the-preparedness-and",totalDownloads:4123,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"3054",slug:"approaches-to-disaster-management-examining-the-implications-of-hazards-emergencies-and-disasters",title:"Approaches to Disaster Management",fullTitle:"Approaches to Disaster Management - Examining the Implications of Hazards, Emergencies and Disasters"},signatures:"C. Emdad Haque and M. Salim Uddin",authors:[{id:"163390",title:"Dr.",name:"C. Emdad",middleName:null,surname:"Haque",slug:"c.-emdad-haque",fullName:"C. Emdad Haque"},{id:"168399",title:"Mr.",name:"Mohammed S",middleName:null,surname:"Uddin",slug:"mohammed-s-uddin",fullName:"Mohammed S Uddin"}]},{id:"74444",title:"Flood Disaster Hazards; Causes, Impacts and Management: A State-of-the-Art Review",slug:"flood-disaster-hazards-causes-impacts-and-management-a-state-of-the-art-review",totalDownloads:784,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Floods are among disasters that cause widespread destruction to human lives, properties and the environment every year and occur at different places with varied scales across the globe. Flood disasters are caused by natural phenomena, but their occurrences and impacts have been intensified through human actions and inactions. The practice of flood disaster management have evolved over the years from traditional approaches of ad-hoc response measures to integrated approaches involving technologically advanced tools in flood disaster awareness, preparedness and response measures. This chapter proffers understanding into flood disaster awareness, preparedness and management, mitigation and adaptation strategies. Most importantly, the chapter presents a review on the relevance of modern technological tools namely Geographic Information System, Remote Sensing, Internet of Things and Big Data, that are available to flood managers, in the creation of efficient early warnings and Flood decision support systems that elevates the resilience of societies to flood disasters.",book:{id:"7712",slug:"natural-hazards-impacts-adjustments-and-resilience",title:"Natural Hazards",fullTitle:"Natural Hazards - Impacts, Adjustments and Resilience"},signatures:"Frank Jerome Glago",authors:[{id:"325046",title:"M.A.",name:"Frank Jerome",middleName:null,surname:"Glago",slug:"frank-jerome-glago",fullName:"Frank Jerome Glago"}]},{id:"59667",title:"Information Security Awareness in Public Administrations",slug:"information-security-awareness-in-public-administrations",totalDownloads:1657,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Government digital agendas worldwide go hand in hand with the digital transformation in businesses and public administrations as well as the digital changes taking place in society. Information security (IS) and awareness (ISA) must be an integrated part of these agendas. The goal of IS is to protect information of all types and origins. Here, the employees play a necessary and significant role in the success of IS, and the entire staff of an institution need to know about their specific roles and be aware of the information security management system (ISMS). As there are still fundamental strategic deficiencies in the institutions themselves, humans should not be called “the weakest link” in the security chain. Rather, sustainable awareness-raising and training for people should be established in the institutions using interactive, authentic, and game-based learning methods. Psychological studies show the great importance of emotionalization when communicating IS knowledge and the reliable exchange of experience about IS. However, in many institutions, a change in culture is becoming necessary. IS must be integrated into all (business) processes and projects, and viable safeguards must be included. This chapter summarizes the most important scientific findings and transfers them to the practice of public administrations in Germany. Moreover, it shows examples of learning methods and provides practical assistance for IS sensitization and training.",book:{id:"6689",slug:"public-management-and-administration",title:"Public Management and Administration",fullTitle:"Public Management and Administration"},signatures:"Margit Scholl",authors:[{id:"235819",title:"Dr.",name:"Margit",middleName:"C.",surname:"Scholl",slug:"margit-scholl",fullName:"Margit Scholl"}]},{id:"71351",title:"Supply Chain FMEA Risk Analysis for the Heavy Industry Sector",slug:"supply-chain-fmea-risk-analysis-for-the-heavy-industry-sector",totalDownloads:805,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The discussed problem is associated with the analysis of risk factors affecting supply chain management in the heavy industry sector based on the analysis of entities operating in this industry. During the research, several aspects of key importance in supply chain management in the heavy industry sector were identified. The use of the failure mode and effects analysis (FMEA) method in research has enabled the detection of defects in supply chain management and analysis of factors that may negatively affect the flow of goods. During the research, potential design flaws and the effect of these flaws were identified, indicating the class, cause, and occurrence.",book:{id:"9256",slug:"risk-management-and-assessment",title:"Risk Management and Assessment",fullTitle:"Risk Management and Assessment"},signatures:"Małgorzata Dendera-Gruszka and Ewa Kulińska",authors:[{id:"313072",title:"Prof.",name:"Ewa",middleName:null,surname:"Kulińska",slug:"ewa-kulinska",fullName:"Ewa Kulińska"},{id:"313373",title:"Ph.D.",name:"Małgorzata",middleName:null,surname:"Dendera-Gruszka",slug:"malgorzata-dendera-gruszka",fullName:"Małgorzata Dendera-Gruszka"}]}],onlineFirstChaptersFilter:{topicId:"272",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"July 20th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:14,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). 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Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. 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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:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. 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International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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