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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1. Introduction
Financial fraud committed by managers have multiplied in recent years; however, they constitute a highly delicate phenomenon in the world of finance. Each year, fraud causes significant losses to the shareholders and creditors of the targeted companies, which hinders the proper functioning of the capital markets. Fraud is generally committed by executives who are very often involved and are subject to legal action by financial market regulators.
The revelation of a fraud tarnishes the reputation of several participants in the financial markets, thereby affecting investor confidence in the market and penalizing all businesses [1]. In fact, any fraud announcement leads investors to question the competence and vigilance of financial market regulators, and even auditors, financial analysts, boards of directors, and credit rating agencies, all these actors have their share of responsibility.
In addition to the financial losses suffered by investors, other losses are added, such as the socio-economic costs related to job losses [2], and can even go as far as the disappearance of the whole entity. But the question that arises is as follows: Given the financial losses and reputation suffered, why do business leaders or entrepreneurs engage in fraud and manipulation? Can we determine the individual and organizational responsibilities that lead to fraud committed by leaders and entrepreneurs?
What tools and strategies are available to a board of directors to detect and prevent such fraudulent practices? We will try to answer these questions, by proceeding as follows: we will first carry out a synthesis of the main types of fraud committed by managers. Secondly, the motivations of the main actors and to identify the attributes, whatever it is individual or organizational likely to lead to fraud. Third, we will focus on the profile of the fraudulent leader. And finally, we will present the recommendations for the various actors responsible for the integrity of the financial markets which are the boards of directors, the regulatory bodies, the accountants, and the auditors.
2. The manager’s frauds
Fraud or embezzlement committed by business leaders can take many forms but often boil down to the following maneuvers:
misappropriation of assets;
manipulation of financial results; and
lack of disclosure, incomplete or misleading disclosure.
2.1 Misappropriation of assets
Misappropriation of assets is mainly carried out by means of the so-called related party transactions where the offending manager initiates commercial or financial transactions between the company he manages and the subsidiary companies [3]. For example, a holding company may carry out several transactions with companies or entities controlled by the members of its management team, allowing them to make significant gains. So the leaders could profit and transfer several millions to companies that they personally created. This investment strategy cannot be controlled or approved by the board of directors. Managers can therefore be led to invest even in companies in liquidation, without anyone controlling them, and the discovery by the board of this misappropriation of an unauthorized action of the funds of the company would not have heavy punishment; the offending manager will simply be dismissed.
2.2 Handling of financial statements
The manipulation of financial statements most often relates to an excessive or excessively exaggerated recognition of revenue, and an undervaluation of operating expenses or an overvaluation of assets [4]. The extent of accounting and financial manipulation by companies is difficult to pin down due to the multitude of events, prosecutions, and counter-prosecutions that have characterized this file. However, according to the information available, it generally seems difficult to verify accounting or financial information such as the increase in profits. Indeed, a swelling generally reflects the nonrecognition of certain operations or even an overvaluation of negotiable securities, tax credits receivable.
2.3 Misleading disclosure absent
When the disclosure of financial and accounting information, which should be made by the officers of the companies, is absent or misleading, the companies may be liable to fines of up to millions. What is certain, acts of fraud such as embezzlement and manipulation could not have existed if the company’s disclosure practices had been carried out in accordance with the rules and the transparency required by the regulations [5]. For example, we disclose financial information in the balance sheet which will give information on marketable securities classified as current assets. However, these securities are not really negotiable or cashable in the short term, but their recovery can be spread over several years. To detect these anomalies or to verify the authenticity of this information, it is necessary to analyze the notes of the financial statements and compare them with the balance sheets and the financial statements.
Thus, certain information disclosed may be disguised or unrealistic, especially in the case of accounting for transactions between the parent company and its subsidiaries; indeed certain transactions have not been properly accounted for and presented in its previous financial statements.
The errors that are generally made concerned mainly the following elements in previous periods:
products;
cost of goods sold;
selling fees;
general and administrative costs;
depreciation of fixed assets;
interest expense;
exceptional items;
charge of income taxes;
tax credits receivable;
production costs;
related party accounts receivable;
fixed assets; and
creditors and charges payable and income taxes receivable.
2.3.1 Consequences of reporting all of these fraud allegations
In a few months, following the announcement of various allegations of fraud and embezzlement, the action plummeted and then the company was sold. In most cases, the companies have either declared bankruptcy and been wound up or undergone a judicial restructuring where the shareholders have lost everything.
3. Why do leaders make fraud?
In addition to financial losses, leaders certainly lose their leadership positions, control of their business, and especially their reputation [6].
How did they commit the frauds they were accused of while the company was open with a board of directors made up of influential people? Why did they go down that path, risking everything they had worked for? In general, a manager or entrepreneur will engage in fraud if the organizational context is favorable to commit fraud and also if the manager displays a profile likely to commit the act of fraud.
3.1 Fraud following the favorable organizational context
The opportunity to commit fraud arises when controls are absent or even failing. Thus, fraud will be easier to carry out since the manager will be free and without control within the company. Indeed, senior managers who can circumvent existing controls, especially if the external governance mechanisms such as regulations, or internal ones such as the board of directors, are insufficient or even ineffective [7]. When they commit fraud, the managers of a company know very well the administrative machinery and have access to data and systems, and when the latter are involved and part of the shareholders, this will make them in a position of strength, while reducing the role of the board of directors to which they belong. Managers can therefore exercise absolute control over the company. It can therefore be said that there was no counterweight to their authority within the company. For example, the CEO can be a more or less significant shareholder, which gave him an edge over the other members of the board of directors.
Another opportunity that favors fraud is the pressure geared toward high performance; this generally manifests itself during stock market bubbles. In fact, rapid deflations of stock market bubbles are very often accompanied by the manifestation of fraud committed by business managers [8]. Indeed, the stock quotes of several companies always reflect expectations of optimistic profits, which implies very high growth rates. Any profit announcement that does not meet stock market expectations will result in a sharp drop in the stock price. In this context, if the performance of the company begins to decline, the management of the company will be forced to manipulate the accounting results to ensure that the earnings per share announced meet or even exceed market expectations. Investors then imposed a stock market valuation, at an increasing, unrealistic rate, which pushes managers to fraud, by favoring accounting manipulations. Also, the stock market bubble will be liable to lead to fraud or manipulation of the financial statements if the directors have a remuneration strongly focused on the appreciation of the stock market price or focused on results or profits.
The governance role: the board of directors was composed of the different members—the founders, the directors of other partners, and the audit committee of the company.
Independent directors: board members must have experience and expertise in the areas of business of the company. They must ensure the control of management systems and the various strategic operations. It can therefore be argued that most of the information at their disposal concerning the company came from its management. The lack of expertise on the part of the board led to failure to perceive the warning signs of manipulation or embezzlement.
3.2 Is the fraudulent manager a psychopath?
In addition to the organizational context, the manager’s psychological profile can lead him to commit fraud. Indeed, some research on criminological thinking on financial fraudsters have agreed that there are psychological peculiarities specific to financial fraudsters, which are very similar to the peculiarities of the psychopath [9]. In fact, like all psychopaths, specialized fraudsters always give the image of a healthy, rational, and apparently normal personality, which would mask their true nature.
In order to recognize the psychopathic fraud leader, three aspects of the leader’s profile are typical: always having a rationalizing speech in order to justify their actions, and an arrogant attitude.
3.2.1 A rationalizing speech
The people implicated in a fraud are always able to justify their action by minimizing the extent of its serious consequences.
The fraudulent leader has the ability to rationalize bad decisions that are not even ethical.
3.2.2 Exaggerated arrogance
Fraud also has a dimension attached to the attitude of individuals. Indeed, engaging in fraud at the risk of collapsing a society reflects an attitude of trust, arrogance, and exaggerated narcissism on the part of fraudulent leaders. Such leaders will first favor a centralized decision-making process in their hands, persistence, and stubbornness to pursue their strategies. These leaders will be free from anxiety because they are convinced that ultimately their will and their decision will prevail [10]. It can therefore be said that an ambitious, arrogant, and self-confident leader always engages in fraud by never thinking that he will be caught. According to them, the controls or the people responsible for prevention or detection are of lower intelligence.
They always do so, the first successful fraud will reinforce the behavior to be pursued in this way of fraud. It will continue to make decisions unilaterally and centrally. Relations with collaborators and employees are very superficial and instrumental, the only goal being the achievement of their strategic or operational vision.
4. Role of control mechanisms
The auditors, the members of the board of directors, and the regulatory bodies play a very important role in carrying out the fraud; in fact the latter constitute the governance control mechanisms, the main role of which is prevention against any financial offense within the company [11]. What can we do about this fraudulent act? What needs to be done is great vigilance and strengthening of the following actors:
4.1 The auditors
The role of the auditors is to detect anomalies, manipulate, and prevent problems and then propose solutions. Auditors are generally retained by the board of directors. The auditors are engaged to investigate and detect fraud; they diagnose the situation of the company in order to detect fraud. Fraud is the weak point of the accounting profession, and it is the responsibility of auditors to detect fraud [12]. This is why it is very important for auditors to take a dynamic approach to fraud prevention and detection. In addition, auditors must go beyond conventional fraud, which is based on detecting the rationality of fraudulent managers, characterized by a psychological profile tempted to fraud, for generally financial reasons. The act of classic financial and accounting fraud is outdated, and the new forms of fraud have changed in nature, and therefore they must be warned in advance. Thus, the fraud has to exceed the direct money gain by the fraudulent manager, to take the form of strategic decisions, with which, the fraudulent manager will generate future profits. Therefore, the auditors must also control the strategic decision-making process of the company; this imperatively passes by the elimination of the centralization of the information held exclusively by the top executives. Finally, the auditors will have to establish fraud analysis grids to also include behavioral aspects of management during meetings with their employees.
4.2 The board of directors
The role of the board of directors has indeed changed and has evolved in recent years, especially with acts of management fraud, which have emerged, and several practices on good governance have been introduced to better balance power within from the administration board [13]. Among these good governance practices, the following actions can be cited:
It is necessary to separate the roles between the chairman of the board of directors and the CEO.
Reduce the number of the board of directors, who hold positions within the company hold regular meetings of the board of directors, with members of management, without the presence of the CEO.
Make sure that the board can count on a roadmap and expertise in order to properly follow the actions and decisions of management.
Recruit external directors, well experienced in the field or activity of the company. During meetings of the board of directors, the following points should be raised regularly:
Update strategic action plans.
Update the succession plan.
Discuss the working atmosphere with the CEO and strengthen ties between members of the management.
The board will also have to ensure that the company works in a climate of integrity and ethics, and that its internal or external communication mechanisms are set up with the greatest transparency.
4.3 The role of financial analysts
Financial analysts play almost the same roles as members of the board of directors; they must always verify the information disclosed by companies. They must analyze the financial statements well and detect any contradictions [14].
For example, fraud can appear if the analyst observed a profit which increased over a certain period, while his cash flow generated by the operation (Cash Flow) fell during the same period, this contradiction meant that there is Something is wrong [15]. In other words, if the company posted positive cumulative profits over a period, while its operation posted negative figures over the same period, this is abnormal, since as normal, growing profit, this deficit must not exist, and must be absorbed by bank loans or new equity issues.
Thus, these contradictions, or these differences between profits and cash flows, are often the sign of accounting manipulations.
Analysts will try to answer these questions:
How is it that the profit increases while the flows are negative?
How is this drain on the company’s liquidity financed?
Is there a recovery plan?
A cash budget?
Are the assets thus acquired liquid?
Are the assets good quality?
4.4 Role of the chartered accountant: auditor or verifier
The chartered accountant is a privileged interlocutor of companies facing fraud; indeed, thanks to his skills in internal control, and his mastery of accounting procedures, his role is not negligible to fight against fraud, and notify her during her activities to her clients [5]. For the accountant, his investigative role consists in intervening within the framework of his advisory missions in the event of suspicion or fraud detected by the company. Its mission intervenes even before legal action in order to confirm or not the suspicions of fraud. In fact, its services are often requested either by the majority shareholders, or by a parent company operating with its subsidiaries, or by the company victim of a fraud committed by its senior managers.
4.5 The auditor
The auditor may also be invited to investigate if there is a suspicion of customer fraud. Their investigation missions can be either audit or judicial expertise missions, and this mainly depends on the legal aspects of their missions [16]. They must carry out their missions with objectivity and professionalism while respecting the principle of professional secrecy.
4.6 The role of regulatory authorities
The role of regulatory authorities in preventing and discovering fraud is not easy to do. Their main role is to establish the mechanisms that fight against fraud. They must manage complaints, and investigations against fraudsters, and they must ensure that the governance bodies and mechanisms of listed companies play their full role. Financial reporting must be reliable and communicated to the public on time. Establish mechanisms and apply sanctions against any natural or legal person, who tries to defraud or manipulate financial or accounting information, in order to profit personally.
5. Conclusion
The financial scandals which have appeared in recent years have placed fraud at the heart of economic and financial issues. Following this, several measures have been adopted aimed at strengthening the regulatory and legal framework such as the Sarbanes-Oxley law in the United States (July 2002) and the financial security law in France (August 2003).
At the same time, new auditing standards have been created to increase the risk of fraud being taken into account by statutory auditors: SAS 99 standards in the United States, IFA ISA 240 standard internationally transposed in France by NEP 240.
But all of this did not stop the leaders from committing the fraud. In fact, the fraud and the accounting and financial manipulations made by the senior executives of the company have affected the confidence of investors and donors toward the company and its image on the financial market.
To remedy this, financial control authorities and even government authorities have introduced a series of regulations aimed at improving corporate transparency, for example by improving the disclosure of financial information, to which companies must comply, and which they must also publish through their official documents.
The control recommendations must also relate to the risks linked to overinvestment and good governance, via better collaboration of the boards of directors with independent, external directors and above all well experienced in the field of activity of the company and especially use auditors from well-experienced accounting firms.
\n',keywords:"fraud, disclosure, control mechanisms, psychopathic leader",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74186.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74186.xml",downloadPdfUrl:"/chapter/pdf-download/74186",previewPdfUrl:"/chapter/pdf-preview/74186",totalDownloads:488,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:54,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"June 25th 2020",dateReviewed:"July 27th 2020",datePrePublished:"November 24th 2020",datePublished:"March 16th 2022",dateFinished:"November 24th 2020",readingETA:"0",abstract:"The financial scandals which have appeared in recent times have placed fraud at the heart of economic and financial issues. Fraud by executives has disastrous consequences as it results in huge losses for investors and creditors, and especially for the company itself. Most of these frauds were often in the form of accounting and financial manipulation, and they have evolved to change forms. We are going to analyze the aspect of fraud, how it can appear. Then we will try to see the aspects that lead to committing fraud, which are generally an organizational framework favoring fraud, and the psychopathic personality of the fraudulent manager. And finally, we will take a closer look at the role of governance oversight mechanisms and the role they must play in fighting fraud.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74186",risUrl:"/chapter/ris/74186",book:{id:"9032",slug:"corporate-social-responsibility"},signatures:"Mohamed Bechir Chenguel",authors:[{id:"293229",title:"Dr.",name:"Mohamed Bechir",middleName:null,surname:"Chenguel",fullName:"Mohamed Bechir Chenguel",slug:"mohamed-bechir-chenguel",email:"bechir.chenguel@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/293229/images/8219_n.jpg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The manager’s frauds",level:"1"},{id:"sec_2_2",title:"2.1 Misappropriation of assets",level:"2"},{id:"sec_3_2",title:"2.2 Handling of financial statements",level:"2"},{id:"sec_4_2",title:"2.3 Misleading disclosure absent",level:"2"},{id:"sec_4_3",title:"2.3.1 Consequences of reporting all of these fraud allegations",level:"3"},{id:"sec_7",title:"3. Why do leaders make fraud?",level:"1"},{id:"sec_7_2",title:"3.1 Fraud following the favorable organizational context",level:"2"},{id:"sec_8_2",title:"3.2 Is the fraudulent manager a psychopath?",level:"2"},{id:"sec_8_3",title:"3.2.1 A rationalizing speech",level:"3"},{id:"sec_9_3",title:"3.2.2 Exaggerated arrogance",level:"3"},{id:"sec_12",title:"4. Role of control mechanisms",level:"1"},{id:"sec_12_2",title:"4.1 The auditors",level:"2"},{id:"sec_13_2",title:"4.2 The board of directors",level:"2"},{id:"sec_14_2",title:"4.3 The role of financial analysts",level:"2"},{id:"sec_15_2",title:"4.4 Role of the chartered accountant: auditor or verifier",level:"2"},{id:"sec_16_2",title:"4.5 The auditor",level:"2"},{id:"sec_17_2",title:"4.6 The role of regulatory authorities",level:"2"},{id:"sec_19",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Black WK. Une fraude presque parfaite: le pillage des caisses d’épargne américaines par leurs dirigeants. Paris: Editions Charles Léonard Mayer; 2005'},{id:"B2",body:'Bouaniche J. “L’auditeur face à la fraude interne: Malaise et technicité”, Audit, N°164, Avril. 2003. pp. 20-21'},{id:"B3",body:'Capiez A. “Entreprise: la transparence financière en question”. Revue du Financier. 2003;137-138:95-105'},{id:"B4",body:'Fogarty T, Magnan M, Markarian G, Bohdjalian S. Inside agency: The rise and fall of nortel. Journal of Business Ethics. 2009;84:165-187'},{id:"B5",body:'Debellis F, De Massis. Strategic agility and international joint ventures: The willingness-ability paradox of family firms. Journal of International Management. 2020;100739'},{id:"B6",body:'Gillett PR, Uddin N. CFO intentions of fraudulent financial reporting. Auditing: A Journal of Practice and Theory. 2005;24(1):55-75'},{id:"B7",body:'David JS, Pesch HL. Fraud dynamics and controles in organizations. Accounting, Orgazations and Society. 2013;(6-7):469-483'},{id:"B8",body:'Jensen M. Agency costs of overvalued equity. Financial Management. 2005;34(1):5-19'},{id:"B9",body:'Peltier-Rivest D. ‘Detecting Occupational Fraudin Canada: AStudy of its Victims and Perpetrators’. Austin, Texas: Association of Certified Fraud Examiners; 2007'},{id:"B10",body:'Hiller, Hambrick. Conceptualizing executive hubris: The role of (hyper) -core self evaluations in strategic decision making. Strategic Management Journal. 2005;26:297-319'},{id:"B11",body:'Salterio S. A strategy for dealing with financial reporting fraud: Fewer mandates, more auditing. Accounting Perspectives. 2008;7(2):111-123'},{id:"B12",body:'Carpenter TD, Reimers JL. Unethical and fraudulent financial reporting: Applying the theory of planned behavior. Journal of Business Ethics. 2005;60:115-129'},{id:"B13",body:'Cohen J, Ding Y, Lesage C, Stolowy H. The Role of Managers’Behaviorin Corporate Fraud. Working Paper. Boston College-HEC Paris (SSRN); 2008'},{id:"B14",body:'Efendi J, Srivastava A, Swanson E. Why do corporate managers misstate financial statements? The role of option compensation and other factors. Journal of Financial Economics. 2005;85(3):667-708'},{id:"B15",body:'Del Giudice M, Carayannis EG. The human dimension of open innovation. Management Decision. 2018'},{id:"B16",body:'Jamal K. Mandatory audit of financial reporting: A failed strategy for dealing with fraud. Accounting Perspectives. 2008;7(2):97-110'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Mohamed Bechir Chenguel",address:"bechir.chenguel@gmail.com",affiliation:'
University of Kairouan, Tunisia
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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.
\n
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.
\n
\n
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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.
\n
\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:"207691",title:"Dr.",name:"Mohd Ariff",middleName:null,surname:"Mohd Aifaa",email:"aifaa@uthm.edu.my",fullName:"Mohd Ariff Mohd Aifaa",slug:"mohd-ariff-mohd-aifaa",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Tun Hussein Onn University of Malaysia",institutionURL:null,country:{name:"Malaysia"}}},booksEdited:[],chaptersAuthored:[{id:"60466",title:"Harmonic Reduction of a Single-Phase Multilevel Inverter Using Genetic Algorithm and Particle Swarm Optimization",slug:"harmonic-reduction-of-a-single-phase-multilevel-inverter-using-genetic-algorithm-and-particle-swarm-",abstract:"Power inverter play an important role in power system especially with its capability on reducing system size and increase efficiently. The recent research trends of power electronic system are focusing on multilevel inverter topics in optimization on voltage output, reducing the total harmonics distortion, modulation technique, and switching configuration. The research emphasizes the optimization with a fundamental switching frequency method that is the optimized harmonic stepped waveform (OHSW) modulation method. The selective harmonic elimination (SHE) calculation has adapted with genetic algorithm (GA) and particle swarm optimization (PSO) in order to speed up the calculation. Both bioinspired algorithms are compared in terms of total harmonic distortion (THD) and selective harmonic elimination for both equal and unequal sources. The overall result showed that both algorithms have high accuracy in solving the nonlinear equation. However, the genetic algorithm showed better output quality in terms of selective harmonic elimination which overall no exceeding 0.4%. Particle swarm optimization shows strength in finding the best total harmonic distortion where in seven-level cascaded H-bridge multilevel inverter (m=0.8) shows 6.8% only as compared to genetic algorithm. Simulation for three-level, five-level, and seven-level for each multilevel inverter at different circumferences had been done in this research. The result draws out a conclusion where the possibility of having a filterless high-efficient inverter can be achieved.",signatures:"Hui Hwang Goh, Chin Wan Ling, Kai Chen Goh, Qing Shi Chua, Sy Yi\nSim and Mohd Ariff Mohd Aifaa",authors:[{id:"207686",title:"Dr.",name:"Hui Hwang",surname:"Goh",fullName:"Hui Hwang Goh",slug:"hui-hwang-goh",email:"jonathanhhgoh@gmail.com"},{id:"207687",title:"MSc.",name:"Chin Wan",surname:"Ling",fullName:"Chin Wan Ling",slug:"chin-wan-ling",email:"lingchinwan@yahoo.com"},{id:"207688",title:"Dr.",name:"Kai Chen",surname:"Goh",fullName:"Kai Chen Goh",slug:"kai-chen-goh",email:"kaichen@uthm.edu.my"},{id:"207689",title:"MSc.",name:"Qing Shi",surname:"Chua",fullName:"Qing Shi Chua",slug:"qing-shi-chua",email:"qingshi89@gmail.com"},{id:"207690",title:"Dr.",name:"Sy Yi",surname:"Sim",fullName:"Sy Yi Sim",slug:"sy-yi-sim",email:"sysim@uthm.edu.my"},{id:"207691",title:"Dr.",name:"Mohd Ariff",surname:"Mohd Aifaa",fullName:"Mohd Ariff Mohd Aifaa",slug:"mohd-ariff-mohd-aifaa",email:"aifaa@uthm.edu.my"}],book:{id:"6173",title:"Compendium of New Techniques in Harmonic Analysis",slug:"compendium-of-new-techniques-in-harmonic-analysis",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"15058",title:"Prof.",name:"G. 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His current research\ninterests include antenna engineering, computational electromagnetics, evolutionary optimization, temporal arrays, and meta and frequency selective structures\nin electromagnetic engineering. 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The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
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Permanent and unrestricted online access to your work
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Open Access Funding
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Indexing and listing across major repositories, see details ...
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Dissemination and Promotion
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Proven world leader in Open Access book publishing with over 10 years experience
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Most competitive prices in the market
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As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
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The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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1,400 GBP Chapter - Edited Volume
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850 GBP Chapter - Book Series Topic (Annual Volume)
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During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
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Services included are:
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An online manuscript tracking system to facilitate your work
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Personal contact and support throughout the publishing process from your dedicated Author Service Manager
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Discoverability - electronic citation and linking via DOI
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Permanent and unrestricted online access to your work
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What isn't covered by the Open Access Publishing Fee?
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If your manuscript:
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Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
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If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
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Open Access Funding
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To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+5,700 OA books published
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Most competitive prices in the market
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Fully compliant with OA funding requirements
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Optimized processes that assure your research is made available to the scientific community without delay
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Personal support during every step of the publication process
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+184,650 citations in Web of Science databases
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Currently strongest OA platform with over 175 million downloads
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Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",book:{id:"5963",slug:"functional-food-improve-health-through-adequate-food",title:"Functional Food",fullTitle:"Functional Food - Improve Health through Adequate Food"},signatures:"Yvonne Maphosa and Victoria A. 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The main global health organizations have incorporated patient safety in their review of work practices. The data provided by the medical laboratories have a direct impact on patient safety and a fault in any of processes such as strategic, operational and support, could affect it. To provide appreciate and reliable data to the physicians, it is important to emphasize the need to design risk management plan in the laboratory. Failure Mode and Effect Analysis (FMEA) is an efficient technique for error detection and reduction. Technical Committee of the International Organization for Standardization (ISO) licensed a technical specification for medical laboratories suggesting FMEA as a method for prospective risk analysis of high-risk processes. FMEA model helps to identify quality failures, their effects and risks with their reduction/elimination, which depends on severity, probability and detection. Applying FMEA in clinical approaches can lead to a significant reduction of the risk priority number (RPN).",book:{id:"9808",slug:"contemporary-topics-in-patient-safety-volume-1",title:"Contemporary Topics in Patient Safety",fullTitle:"Contemporary Topics in Patient Safety - Volume 1"},signatures:"Hoda Sabati, Amin Mohsenzadeh and Nooshin Khelghati",authors:[{id:"340486",title:"M.Sc.",name:"Hoda",middleName:null,surname:"Sabati",slug:"hoda-sabati",fullName:"Hoda Sabati"},{id:"348872",title:"M.Sc.",name:"Amin",middleName:null,surname:"Mohsenzadeh",slug:"amin-mohsenzadeh",fullName:"Amin Mohsenzadeh"},{id:"348874",title:"MSc.",name:"Nooshin",middleName:null,surname:"Khelghati",slug:"nooshin-khelghati",fullName:"Nooshin Khelghati"}]},{id:"69876",title:"Leadership Styles in Nursing",slug:"leadership-styles-in-nursing",totalDownloads:3157,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Recent developments in the field of management-organization and organizational behavior and new concepts have also led to the emergence of new leadership styles in leadership. Leadership in health services is important for following innovations and adapting to current situations. Nurses working together with other health personnel in hospitals providing health services constitute an important group in leadership. Nursing, which is a key force for patient safety and safe care, is a human-centered profession, and therefore leadership is a key skill for nurses at all levels. The leadership styles of nurse managers are believed to be an important determinant of job satisfaction and persistence of nurses. The need for nurses with leadership skills and the need for nurses to develop their leadership skills are increasing day by day. There are several leadership styles defined in nursing literature. These leadership styles are examined under the titles of relational leadership style, transformational leadership, resonant leadership, emotional intelligence leadership, and participatory leadership. The task-focused leadership style is explored under the headings of transactional and autocratic leadership, laissez-faire leadership, and instrumental leadership.",book:{id:"9047",slug:"nursing-new-perspectives",title:"Nursing",fullTitle:"Nursing - New Perspectives"},signatures:"Serpil Çelik Durmuş and Kamile Kırca",authors:null},{id:"58916",title:"Factors Affecting the Attitudes of Women toward Family Planning",slug:"factors-affecting-the-attitudes-of-women-toward-family-planning",totalDownloads:8548,totalCrossrefCites:9,totalDimensionsCites:18,abstract:"Everyone has the right to decide on the number and timing of children without discrimination, violence and oppression, to have the necessary information and facilities for it, to access sexual and reproductive health services at the highest standard. Deficient or incorrect family planning methods, wrong attitudes and behaviors toward the methods and consequent unplanned pregnancies, increased maternal and infant mortality rates are the main health problems in most countries. Individuals’ learning modern family planning methods and having positive attitude for these methods may increase the usage of these methods and contributes the formation of healthy communities. It is considered important to examine the current attitudes and determinants in order to spread the choice of effective method.",book:{id:"6142",slug:"family-planning",title:"Family Planning",fullTitle:"Family Planning"},signatures:"Nazli Sensoy, Yasemin Korkut, Selcuk Akturan, Mehmet Yilmaz,\nCanan Tuz and Bilge Tuncel",authors:[{id:"216377",title:"Prof.",name:"Nazli",middleName:null,surname:"Sensoy",slug:"nazli-sensoy",fullName:"Nazli Sensoy"},{id:"216589",title:"Dr.",name:"Yasemin",middleName:null,surname:"Korkut",slug:"yasemin-korkut",fullName:"Yasemin Korkut"},{id:"216595",title:"Dr.",name:"Selcuk",middleName:null,surname:"Akturan",slug:"selcuk-akturan",fullName:"Selcuk Akturan"},{id:"216596",title:"Dr.",name:"Canan",middleName:null,surname:"Tuz",slug:"canan-tuz",fullName:"Canan Tuz"},{id:"216598",title:"Dr.",name:"Bilge",middleName:null,surname:"Tuncel",slug:"bilge-tuncel",fullName:"Bilge Tuncel"},{id:"216599",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yilmaz",slug:"mehmet-yilmaz",fullName:"Mehmet Yilmaz"}]},{id:"69631",title:"Cultural Practices and Health Consequences: Health or Habits, the Choice Is Ours",slug:"cultural-practices-and-health-consequences-health-or-habits-the-choice-is-ours",totalDownloads:902,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human beings are social animals with an innate desire to conform to socially accepted norms and values. Over periods of time, some of these norms become standards that all members of the community are expected to adhere to. Deviance from these standards is seen as absurd, wrong, or frankly abnormal. However, many of these cultural mores have no scientific basis and, some of them actually promote behaviors with negative health consequences. This chapter examines the cultural practices of some communities in Africa and their health consequences and, explores ways to address the challenges.",book:{id:"9138",slug:"public-health-in-developing-countries-challenges-and-opportunities",title:"Public Health in Developing Countries",fullTitle:"Public Health in Developing Countries - Challenges and Opportunities"},signatures:"Radiance Ogundipe",authors:[{id:"302308",title:"Dr.",name:"Radiance",middleName:null,surname:"Ogundipe",slug:"radiance-ogundipe",fullName:"Radiance Ogundipe"}]},{id:"55808",title:"The Role of Legumes in Human Nutrition",slug:"the-role-of-legumes-in-human-nutrition",totalDownloads:5433,totalCrossrefCites:63,totalDimensionsCites:109,abstract:"Legumes are valued worldwide as a sustainable and inexpensive meat alternative and are considered the second most important food source after cereals. Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",book:{id:"5963",slug:"functional-food-improve-health-through-adequate-food",title:"Functional Food",fullTitle:"Functional Food - Improve Health through Adequate Food"},signatures:"Yvonne Maphosa and Victoria A. 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The uniqueness of an individual is one in two nonillion, octillion, septillion, sextillion, quintillion, quadrillion, trillion, billion, million and thousand. Individuals are indefinitely unique.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Zouhair O. Amarin"},{id:"81930",title:"Smoking and Its Consequences on Male and Female Reproductive Health",slug:"smoking-and-its-consequences-on-male-and-female-reproductive-health",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104941",abstract:"Smoking contributes to the death of around one in 10 adults worldwide. Specifically, cigarettes are known to contain around 4000 toxins and chemicals that are hazardous in nature. The negative effects of smoking on human health and interest in smoking-related diseases have a long history. Among these concerns are the harmful effects of smoking on reproductive health. Thirteen percent of female infertility is due to smoking. Female smoking can lead to gamete mutagenesis, early loss of reproductive function, and thus advance the time to menopause. It has been also associated with ectopic pregnancy and spontaneous abortion. Even when it comes to assisted reproductive technologies cycles, smokers require more cycles, almost double the number of cycles needed to conceive as non-smokers. Male smoking is shown to be correlated with poorer semen parameters and sperm DNA fragmentation. Not only active smokers but also passive smokers, when excessively exposed to smoking, can have reproductive problems comparable to those seen in smokers. In this book chapter, we will approach the effect of tobacco, especially tobacco smoking, on male and female reproductive health. This aims to take a preventive approach to infertility by discouraging smoking and helping to eliminate exposure to tobacco smoke in both women and men.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Amor Houda, Jankowski Peter Michael, Micu Romeo and Hammadeh Mohamad Eid"},{id:"81468",title:"The Knowledge and Use of Intra-Uterine Device by Women Attending Ante-Natal Clinic at Enugu State Teaching Hospital, Parklane",slug:"the-knowledge-and-use-of-intra-uterine-device-by-women-attending-ante-natal-clinic-at-enugu-state-te",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.104097",abstract:"Intrauterine contraception has been recognized globally as one of the modern long-term reversible contraceptive methods suitable for women of all reproductive ages. It represents the most cost-effective method for preventing unwanted pregnancies, scientifically proven for its safety, efficacy and cost-effectiveness and is known to last longer in preventing pregnancy than other methods. This study assessed the knowledge of mothers attending ESUT teaching hospital, Parklane on intrauterine contraceptive device, the use as well as the common side effects experienced by the users. A descriptive survey research design was used to sample 175 mothers. A structured researcher developed questionnaire was used for data collection. The findings revealed that more than half of the respondents have good knowledge of intrauterine device but only 23 (14%) respondents make use of it. The commonly experienced side effects identified were irregular bleeding (75%) and vaginal discharge (62.5%). Although, the respondents had good knowledge of intrauterine device, their uptake of the method was poor. Therefore, there is a need to improve contraceptive counseling to ensure that women understand the relative effectiveness of IUDS. The study also recommended the need for better education for both clients and providers to improve the accessibility and acceptability of intrauterine device.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Chukwuasokam Caleb Aniechi and Uloma Cynthia Ezuma"},{id:"81003",title:"Perspective Chapter: Modern Birth Control Methods",slug:"perspective-chapter-modern-birth-control-methods",totalDownloads:42,totalDimensionsCites:0,doi:"10.5772/intechopen.103858",abstract:"This chapter focuses on various modern birth control methods, including combined oral contraceptives, progestogen-only pills, progestogen-only injectables, progestogen-only implants, intrauterine devices, barrier contraceptives, and emergency contraceptive pills. Each contraceptive method is covered in detail, including mechanism of action, effectiveness, health benefits, advantages, disadvantages, risks, and side-effects.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Rahma Al Kindi, Asma Al Salmani, Rahma Al Hadhrami, Sanaa Al Sumri and Hana Al Sumri"},{id:"80084",title:"Contraceptive Implants",slug:"contraceptive-implants",totalDownloads:174,totalDimensionsCites:0,doi:"10.5772/intechopen.101999",abstract:"Contraceptive implants or implantable contraceptive are five subdermal implants, rods the size of pencil lead that are embedded just under the skin on the inside of the upper arm. The rods contain etonogestrel, the metabolite of desogestrel, an equivalent progestin. Implants are often used during breastfeeding without an impact on milk production. It was identified that age does not affect the use of contraceptive implants but educational status is significant to its usage; there is an association between the age at first birth and the use of contraceptive implants; the number of liveborn children has a significant impact or influence on the use of implants; etc. This chapter focuses on types of contraceptive implants and its mechanism of action; global statistics on contraceptive implants; side effects; health benefits and positive characteristics of contraceptive implants; those who can and cannot use contraceptive implants; reasons women are not interested in contraceptive implants and factors influencing its usage.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Paul Hassan Ilegbusi"}],onlineFirstChaptersTotal:5},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). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. 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. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:16,paginationItems:[{id:"82135",title:"Carotenoids in Cassava (Manihot esculenta Crantz)",doi:"10.5772/intechopen.105210",signatures:"Lovina I. Udoh, Josephine U. Agogbua, Eberechi R. Keyagha and Itorobong I. 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Heshmati",slug:"comparative-senescence-and-lifespan",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hassan M.",surname:"Heshmati"}],book:{title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",doi:"10.5772/intechopen.105052",signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81723",title:"Peroxisomal Modulation as Therapeutic Alternative for Tackling Multiple Cancers",doi:"10.5772/intechopen.104873",signatures:"Shazia Usmani, Shadma Wahab, Abdul Hafeez, Shabana Khatoon and Syed Misbahul Hasan",slug:"peroxisomal-modulation-as-therapeutic-alternative-for-tackling-multiple-cancers",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}}]},overviewPagePublishedBooks:{paginationCount:14,paginationItems:[{type:"book",id:"7264",title:"Calcium and Signal Transduction",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7264.jpg",slug:"calcium-and-signal-transduction",publishedDate:"October 24th 2018",editedByType:"Edited by",bookSignature:"John N. Buchholz and Erik J. Behringer",hash:"e373a3d1123dbd45fddf75d90e3e7c38",volumeInSeries:1,fullTitle:"Calcium and Signal Transduction",editors:[{id:"89438",title:"Dr.",name:"John N.",middleName:null,surname:"Buchholz",slug:"john-n.-buchholz",fullName:"John N. Buchholz",profilePictureURL:"https://mts.intechopen.com/storage/users/89438/images/6463_n.jpg",biography:"Full Professor and Vice Chair, Division of Pharmacology, Loma Linda University, School of Medicine. He received his B.S. Degree in Biology at La Sierra University, Riverside California (1980) and a PhD in Pharmacology from Loma Linda University School of Medicine (1988). Post-Doctoral Fellow at University of California, Irvine, College of Medicine 1989-1992 with a focus on autonomic nerve function in blood vessels and the impact of aging on the function of these nerves and overall blood vessel function. Twenty years of research funding and served on NIH R01 review panels, Editor-In-Chief of Edorium Journal of Aging Research. Serves as a peer reviewer for biomedical journals. Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. 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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. 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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. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. 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. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. 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. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). 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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