Neoadjuvant therapy in HER2-positive breast cancer
\r\n\tThe purpose of the book is to bring together the latest knowledge about genetic diversity by presenting the studies of some of the scientists who are engaged in development of new tools and ideas used to reveal genetic diversity, often from very different perspectives. The book should prove useful to students, researchers and experts in the area of biology, medicine and agriculture.
",isbn:"978-1-80356-945-1",printIsbn:"978-1-80356-944-4",pdfIsbn:"978-1-80356-946-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"0b1e679fcacdec2448603a66df71ccc7",bookSignature:"Prof. Mahmut Çalışkan and Dr. Sevcan Aydin",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11643.jpg",keywords:"PCR Based Methods, Protein Based Methods, Sequencing, Conservation of Genetic Resources, Natural Variation, Molecular Markers, Genetic Manipulation in Animals, Resistance to Disease, Genetic Manipulation in Plants, Use of Microorganisms in Biotechnology, Genetic Differentiation, Gene Therapy and Gene Editing",numberOfDownloads:17,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Professor of genetics and molecular biology and Head of Biotechnology division at İstanbul University in Turkey whose main research areas include plant molecular genetics, microbial biotechnology and characterization and biotechnological use of halophilic archaeal strains.",coeditorOneBiosketch:"Associate Professor of Biotechnology Division in Department of Biology at Istanbul University in Turkey whose main research areas include genetics, environmental biotechnology and bioengineering.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"51528",title:"Prof.",name:"Mahmut",middleName:null,surname:"Çalışkan",slug:"mahmut-caliskan",fullName:"Mahmut Çalışkan",profilePictureURL:"https://mts.intechopen.com/storage/users/51528/images/system/51528.png",biography:"Mahmut Çalışkan is a Professor of Genetics and Molecular Biology in the Department of Biology, Biotechnology Division, Istanbul University, Turkey. He obtained a BSc from Middle East Technical University, Ankara, and a Ph.D. from the University of Leeds, England. His main research areas include the role of germin gene products during early plant development, analysis of genetic variation, polymorphisms, and the characterization and biotechnological use of halophilic archaea.",institutionString:"Istanbul University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"8",institution:{name:"Istanbul University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:{id:"462767",title:"Dr.",name:"Sevcan",middleName:null,surname:"Aydin",slug:"sevcan-aydin",fullName:"Sevcan Aydin",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003QRfRpQAL/Profile_Picture_2022-03-24T08:49:06.jpg",biography:"Sevcan Aydın is an Associate Professor of Biotechnology Division in Department of Biology at Istanbul University in Türkiye. She obtained her bachelor's degree from Biology Department of Ege University. She obtained her Ph.D. in Biotechnology Programme of Istanbul Technical University. 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Giving chemotherapy before performing a resection of tumour was initially introduced in locally advanced breast cancer where large inoperable tumour can be converted to operable cancer.
Moreover, at the time of breast cancer diagnosed with 2 to 3 cm in size, the risk of occult metastasis either in axillary lymph node or distant micrometastasis is greater than 50% [1], [2]. There were some evidences demonstrated in animal model that after surgical removal of primary cancer, metastases might be exacerbated [3], [4]. The administration of systemic chemotherapy in this setting might be a benefit to decrease the mortality risk from systemic spreading of the disease. Therefore, control of the disease prior to surgical treatment might produce a better treatment outcome. It was debated that NAC might delay the operation. However, the result from many studies showed that during the course of NAC breast cancer rarely progressed, or if it progressed that likely reflected the aggressive tumour which did not response to chemotherapy postoperatively.
Another main benefit of NAC is monitoring response to the treatment, so as a good model for
Furthermore, increased rate of breast conserving surgery (BCS) was documented in operable breast cancer with lower risk of local recurrence, in particular when pCR was achieved [10].
Preoperative or NAC has been compared with standard adjuvant chemotherapy as the treatment of breast cancer in several phase III studies. The primary end points mainly are disease-free survival (DFS) and OS. These studies showed that using the chemotherapy preoperatively did not improve DFS and OS, compared with using the same regimen as an adjuvant treatment. A pivotal study from the National Surgical Adjuvant Breast and Bowel Project (NSABP18) [11] compared the use of neoadjuvant adriamycin plus cyclophosphamide (AC) with the same regimen administering postoperatively. With 4-cycle of neoadjuvant AC, the complete clinical response rate (cCR) and pathological complete response rate (pCR) were 36% and 13%, respectively. In primarily operable breast cancer, NAC can downstage tumor and lead to small increase of breast conserving rate (60% vs 67%, p = 0.002). Although substantial response was found with neoadjuvant approach, there was no statistically significant difference in terms of DFS and OS at a 9-year follow up [12]. Another study from the European Organization for Research and Treatment of Cancer (EORTC) compared the efficacy of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) preoperatively or postoperatively [13]. Consistent with the NSABP-B18 trial, the OS, PFS and relapse rate were similar between both groups. Also, several smaller studies exploring the benefit of NAC did not find any survival benefit for the neoadjuvant approach [13]-[15].
Recent meta-analysis addressed directly the benefit of neoadjuvant versus adjuvant chemotherapy [16]. This meta-analysis included nine randomized trials with the total of 3946 patients. There was no difference of death and disease progression. Surprisingly, the patients who received neoadjuvant treatment experienced higher local relapse (risk ratio of 1.22, p=0.015). This greater risk of local recurrence mainly occurred in the trials that the patients received radiotherapy without surgery in patients who achieved clinical complete response.
To date, the evidence-based literatures support the benefit of NAC as an approach to convert inoperable breast cancer to an operable tumor, or downstaging to increase breast conserving rate. These seems to be no difference in survival in patients with operable breast cancer whether chemotherapy is given before or after surgery.
There was no inherent reason to believe that a regimen that works postoperatively will not work preoperatively. Therefore, a standard neoadjuvant regimen is an acceptable postoperative regimen. Previously, anthracycline-based chemotherapy was approved as standard of care for adjuvant treatment of operable breast cancer. It is justified to use at least three to four cycles of anthracycline-based regimen and additional cycles may be considered to maximize response. Later, combination of taxane and anthracycline using as an adjuvant treatment has been proven to be superior to anthracycline alone and become a standard of care in node-positive and high-risk node negative breast cancer. Therefore, several clinical trials have explored the different chemotherapy combinations using as the primary systemic treatment. The best type and schedule administration of preoperative taxanes were investigated in several phase III studies.
The study of NSABP-B27 is the largest study to demonstrate the benefit of adding docetaxel to anthracycine-based regimen [17]. Over 2000 patients were randomized to receive 1) 4 cycles of preoperative AC, 2) 4 cycles of neoadjuvant AC followed by 4 cycles of docetaxel and then surgery, and 3) 4 cycles of AC followed by surgery and then 4 cycles of adjuvant docetaxel. The results showed superiority of clinical response, pCR in patients who received the addition of docetaxel preoperatively (14% vs 26%, p<0.001), but similar breast conserving rate (63% vs 62%). Furthermore, adding docetaxel either preoperatively or postoperatively modestly reduced local recurrence rate with comparable DFS and OS [6].
In the Aberdeen trial, the locally-advanced breast cancer patients were initially treated with 4 cycles of the combination of cyclophosphamide, vincristine, adriamycin and prednisolone (CVAP). The patients who had response to CVAP were randomized to receive another 4 cycles of CVAP or 4 cycles of docetaxel. Among total 162 patients, 66 percent experienced clinical response following the CVAP. Of these, changing to docetaxel provided much better response rate (85% vs 64%, p=0.03), pCR rate (31% vs 15%, p=0.06) and 5-year survival rate (97% vs 78%, p=0.04) [18] .
Numerous trials have addressed to answer how best to incorporate taxane to anthracycline-based regimen. The German Preoperative Adriamycin and Docetaxel study II (GEPAR-DUO) [19] and the Arbeitsgemeinschaft Gastroenterologische Onkologie (AGO) study [20] explored whether using taxane sequentially or concurrently with anthracycline is the best approach. Both studies demonstrate significantly higher pCR and breast conserving rate in sequential arm. However, it is impossible to demonstrate that the better outcome of sequential arm is a result of sequential use itself or the higher cumulative dose of chemotherapy and longer duration of treatment with sequential administration. Another randomized study compared the efficacy of paclitaxel administered either weekly or every 3 weeks schedules, followed by the combination of 5-FU, adriamycin and cyclophosphamide (FAC). Weekly schedule associated with better pCR and also breast conserving rates [21].
Taken together, these data support the sequential use of anthracycline and taxane as the neoadjuvant treatment in both locally advanced and operable breast cancer. However, the usage of taxane in low-risk patients or ER-positive patients may provide minimal benefit outrage of the risk of adverse effect. Optimizing chemotherapy regimen should be considered individually based on reliable prognostic factor, patient’s status and their preference after discussing of the risk and benefit of the treatment.
The patients who achieve poor response to initial neoadjuvant chemotherapy, i.e non-responder, have a worse prognosis. Modification of chemotherapy after observing poor response has not resulted in better outcome [22], [24]. In the German Preoperative Adriamycin and Docetaxel Study III (GEPAR-TRIO) study [22], the breast cancer patients who had poor response to 2 cycles of neoadjuvant docetaxel, adriamycin and cyclophosphamide (TAC) were randomized to receive another 4 cycles of TAC or alter to 4 cycles of vinorelbine plus capecitabine (NX). The results showed no difference in terms of breast conserving rate, clinical and pathological response. On the other hand, in the Aberdeen trial, the patients who received docetaxel after achieving poor respond to 4 cycles of cyclophosphamide, vincristine, doxorubicin and prednisolone (CVAP) ultimately had substantial overall response rate (66%) [25]. On the basis of limited benefit to neoadjuvant chemotherapy in non-responders, adjuvant therapy such as hormonal treatment as well as targeted therapy is considered as the standard treatment to improve outcome [26].
Overexpression of human epidermal growth factor receptor (HER2) is found in approximate 20-30 percent of breast cancer. Trastuzumab, a humanized antibody against HER2, combined with chemotherapy improved survival in metastatic HER2-positive breast cancer [27]. Moreover, 1-year of adjuvant trastuzumab has been established as standard treatment in HER2-positive breast cancer based on improvement of overall survival in several studies [28], [29]. With the promising activity of trastuzumab, its combination with neoadjuvant chemotherapy to enhance response has been proposed. There were several small phase II trials explored different combination of preoperative trastuzumab and chemotherapy. The pCR rate ranged from 12-45% [30], [31]. To date, there was a randomized controlled trial evaluated the efficacy of preoperative trastuzumab combined with anthracycline-based chemotherapy [32]. The stage II and III HER2-positive breast cancer patients were treated with 4 cycles of paclitaxel followed by 4 cycles of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) with or without trastuzumab. The patients in trastuzumab arm had significantly higher pCR rate (65% vs 26%, p=0.016), but no difference in breast conserving rate. There was no incidence of clinical congestive heart failure. However, this study does not demonstrate whether preoperative trastuzumab impact survival compared to using trastuzumab postoperatively. Risk of cardiotoxicity and benefit of improving response are needed to be discussed individually.
Recently, there are several clinical trials comparing the efficacy of emerging anti-HER2, lapatinib and pertuzumab, as its efficacy using with chemotherapy or the addition to trastuzumab. The GeparQuinto trial compared the efficacy of lapatinib and trastuzumab, both concurrently with chemotherapy in operable HER2-positive breast cancer [33]. The pCR rate was significantly higher with the treatment of trastuzumab plus chemotherapy (30% vs 22%, p=0.04). However, breast conserving rate was not different and long-term outcomes are awaited. With the hypothesis of using dual anti-HER2 might inhibit HER2 receptor more efficiently, the clinical trials exploring the efficacy of dual anti-HER2, as neoadjuvant therapy in HER2-positive breast cancer were developed. Dual anti-HER2, eg. Lapatinib or pertuzumab plus trastuzumab, did increase pCR rate, but did not increase breast conserving rate compared to the patients who received trastuzumab plus chemotherapy. The studies of HER2-targeted therapy combined with chemotherapy as neoadjuvant setting in HER2-positive breast cancer are summarized in Table 1.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Buzdar A et al*[32] | \n\t\t\t42 | \n\t\t\t3wPx4->FECx4 Same CMT+H | \n\t26 65 | \n\t53 57 | \n
NOAH*[34] | \n\t235 | \n\tCMT CMT+H 1 year | \n\t20 39 | \n\tNA | \n
Neosphere*[7] | \n\t417 | \n\tD+T D+T+P T+P D+P | \n\t29 46 17 24 | \n\tNA | \n
Neoaltto*[35] | \n\t455 | \n\tL->wP T->wP L+H->wP | \n25 30 51 | \n31 28 26 | \n
GeparQuinto*[33] | \n\t620 | \n\tECx4->Dx4+H ECx4->Dx4+L | \n30 22 | \n63 59 | \n
Neoadjuvant therapy in HER2-positive breast cancer
Abbrevations: N, number of patients; BCS, breast conserving rate; 3wP, Paclitaxel every 3 weeks; FEC, 5-FU+epirubicin+cyclophosphamide;H, Trastuzumab; CMT, chemotherapy; D, docetaxel; P, pertuzumab; L, lapatinib; wP, weekly paclitaxel; EC, epirubicin+cyclophosphamide; NA, not available; *The studies that reported significant different of pCR rate and breast conserving rate.
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, was shown to improve response rate and progression-free survival when added to chemotherapy in metastatic HER2-negative breast cancer patients [36], [37]. Two recent phase III trials [38], [39] determined whether the addition of bevacizumab to chemotherapy would increase pCR rate in HER2-negative operable breast cancer. Both studies confirmed that bevacizumab did increase pCR rate. However, there was a controversial result whether which specific subgroups would gain benefit from bevacizumab. It was claimed that bevacizumab added benefit in terms of pCR in only triple-negative patients from GeparQuinto trial [39], whereas only patients with positive estrogen receptor from the NSABP-B40 trial had higher pCR rate following bevacizumab treatment [38]. Because of contradictory results of these trials with premature long-term data as well as economic argument, therefore, bevacizumab is not recommended for neoadjuvant treatment in non-metastatic HER2-negative breast cancer.
Endocrine therapy has been used as a standard treatment in metastatic ER-positive breast cancer with the objective response of 30-40 percent. Because of low profile of toxicity, it is commonly used as the first option in low-risk metastatic breast cancer, ie asymptomatic, long disease-free interval and limited metastatic disease. Conversely, neoadjuvant endocrine therapy is not recommended as a standard of care because of its lower response rate compared with response rate in the study of neoadjuvant chemotherapy. The small studies reported response rate of 0-2 percent following tamoxifen [40], [41] and 2-3 percent after aromatase inhibitor treatment [40], [42]. The studies of neoadjuvant endocrine therapy are summarized in Table 2.
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Eiermann et al*[43] | \n\t\t337 | \n\t\tLetrozole Tamoxifen | \n\t\t55 36 | \n\t\t45 35 | \n\t
Smith et al [44] | \n\t\t330 | \n\t\tAnastrozole Tamoxifen Combine | \n\t\t37 36 39 | \n\t\t46 22 26 | \n\t
Ellis et al*[40] | \n\t\t324 | \n\t\tLetrozole Tamoxifen | \n\t\t60 41 | \n\t\t48 36 | \n\t
Randomized trials comparing different neoadjuvant endocrine therapy
Abbreviations; N, number of patients; ORR, overall response rate; BCS, breast conserving surgery rate; *The randomized studies with the significant difference of overall response rate and breast conserving rate.
Although the objective response of primary endocrine treatment is not promising, endocrine therapy remains a reasonable option in selected ER-positive breast cancer patients, for instance, the elderly patients who are not suitable for chemotherapy, or has organ function impairment, or desires to avoid adverse effect from chemotherapy. According to a randomized study comparing the efficacy of neoadjuvant chemotherapy and aromatase inhibitor in postmenopausal ER-positive breast cancer patients, clinical response and pCR were not significantly different [45] . However, possibility of breast conserving surgery following primary endocrine treatment is still infrequent.
With the rationale of the superiority of aromatase inhibitor to tamoxifen in metastatic setting of postmenopausal woman with breast cancer, the study of aromatase inhibitor in neoadjuvant setting compared to tamoxifen has been performed. Several studies showed higher overall response rate and also breast conserving rate with aromatase inhibitor [40], [43], [44] .
At present, there are no data available about neoadjuvant endocrine therapy in premenopausal woman.
Although, recent chemotherapeutic regimen for NAC treatment in breast cancer containing anthracycline followed sequentially by a taxane can produces the good clinical response rates [46]. A cPR is still less than 30% [46], [47]. However, these chemotherapeutic agents are associated with significant morbidity. Therefore, the main benefit would be maximum if it were possible to identify patients who are most likely to benefit from NAC before or shortly after commencing the treatment. Recently, various biotechnologies, including both imaging and biomolecular platforms, have been investigated in order to find novel biomarkers or tests to predict responses to NAC. These technologies include molecular imaging, PET-CT, scintigraphy, genomics and proteomic platforms [48]. However, there is not any promising result demonstrated so far.
Amongst the above technologies, the most recent and feasible is the use of magnetic resonance imaging (MRI) as a early predictor of response to NAC. In a recent systematic review study, where dynamic contrast enhanced (DCE) MRI performed pre and after 1-2 cycles of NAC were compared, good sensitivity and specificity in predicting response to NAC was demonstrated, depending on various MRI parameters used for interpretation. Substantial reductions in tumour volumecould be accurate parameters in discriminating responders and non-responders after 1-2 cycles of NAC [49].
PET-CT using 18 F-FDG seemed to be a good technology in predicting response to NAC due to its combination of anatomical and functional characteristics of cancer cells. However, in a small study comparing ability of PET-CT, MRI and ultrasonography in predicting response to NAC, MRI was superior to PET-CT and ultrasonography [50].
With the rationale of NAC in term of controlling distant or micrometastasis, NAC should be a good approach in breast cancer for both early and locally advanced disease. However, in some early breast cancer, addition of chemotherapy might be an overtreatment with more harmful than useful. Evidence from various clinical studies confirmed the benefit of NAC by avoiding mastectomy in some responders. In the recent day, therefore, use of NAC is the treatment of choice for locally advanced or some early breast cancer. Combination of NAC and other targeted therapy such as trastuzumab have given even better outcome. Finally, further research is still required in order to predict response to NAC as early as possible so that patient who would not respond well to NAC could be identified early and would allow seeking for the other treatment.
Pneumothorax (PNX) is an abnormal collection of air in the pleural space. It is defined as primary spontaneous pneumothorax (PSP) or secondary, based on age, causes, and the requirement of different management [1].
A PSP usually occurs following the rupture of subvisceral pleural blebs and its cause is unknown. Most frequently, patients are males, healthy teenagers or young adults, and smokers [2].
Instead, a spontaneous secondary pneumothorax (SPS) is often associated with a known lung disease and the main cause is a chronic obstructive pulmonary disease (COPD). Other causes are, for instance, idiopathic fibrosis, acquired immunodeficiency syndrome (AIDS), and neoplastic disease. Secondary pneumothorax (SP) could also occur after a chest trauma (post-traumatic pneumothorax) or after invasive procedures (iatrogenic). A specific subgroup is represented by the catamenial pneumothorax, as discussed further on.
The annual incidence of SPS is in general 26 cases per 100.000 and it is more common in men with a 3:1 ratio. It is mainly observed in patients aged 50–60 years old [3, 4].
In general, symptoms include chest pain and shortness of breath, but symptoms could differ according to the cause of pneumothorax [5].
In the following chapter, all the aspects related to a secondary pneumothorax are described.
The annual incidence of an SP is approximately 6.3 cases per 100.000 in men and 2 cases per 100.000 in women, every year [3].
A SP may occur:
in the presence of pre-existing lung diseases, like COPD, infections (e.g., tuberculosis, necrotizing pneumonia, and pneumocystis carinii), inflammatory disease (e.g., rheumatoid arthritis, polymyositis and dermatomyositis, and systemic sclerosis);
in the presence of neoplastic disease (e.g., primary lung cancer, sarcoma metastases, and malignant pleural mesothelioma);
as a consequence of a chest trauma;
as a complication of medical or surgical procedures (iatrogenic pneumothorax); or
concomitant to other pre-existing pathologies (e.g., catamenial pneumothorax) [6].
Moreover, compared to a primary pneumothorax, SP afflicts patients with a known history of lung disease. For such reasons, an SP:
is less tolerated by patients because of a co-existing lung disease;
is generally characterized by the presence of a persistent air leak that does not tend to resolve spontaneously, requiring an active intervention; and
oxygen could be required to promote air reabsorption, especially in the case of subcutaneous emphysema.
Generally, the management of such patients is complex and the treatment requires a chest tube insertion, prolonged hospitalization, and consideration for a surgical procedure to induce pleurodesis.
The main cause of SP is COPD, with an incidence of 26 cases per 100.000 patients per year [7]; COPD is one of the three main causes of death in the world and one of the main causes of chronic disease [8].
Based on computed tomography (CT) images, COPD may be divided into:
emphysema- and airway-dominant COPD: SP generally occurs as a consequence of bullae disruptions (Figure 1);
nonemphysematous COPD.
Emphysema dominant COPD.
According to the GOLD guideline [9], COPD severity depends on pulmonary function, evaluated by means of a spirometry. The risk of an SP is higher in patients affected by severe COPD. Patients with FEV1 < 1 L and/or a FEV1/FVC < 40% are deemed at high-risk [10], with a common observance of severe hypoxemia associated with hypercapnia in case of pneumothorax [8].
The development of a secondary pneumothorax in COPD patients is a parameter of high mortality and, in fact, it has been demonstrated that each SP event increases fourfold the chances of death in such patients [11].
When a pneumothorax occurs in a COPD patient with a low respiratory function, it is common to observe severe hypoxemia caused by a lower ventilation-perfusion (V/Q) rate, which is capable to determine an incremented shunt that is directly proportional to the PNX size. Compensatory hypercapnia is often associated [8].
For such reasons, an SP onset in COPD patients is generally associated with a rapidly progressive dyspnea and pleuritic chest pain where a prompt management is mandatory.
Generally, COPD patients present with hyperinflated lungs and abnormal lung auscultation. A reduced or absent vesicular murmur associated with symptoms such as shortness of breath, low saturation, and hyperventilation should easily guide to diagnose a PNX.
A chest X-ray is mandatory to assess the presence of a PNX, which usually appears as a complete collapse of the lung. Seldomly, a subcutaneous emphysema may occur, concealing the PNX at the chest X-ray (Figure 2).
Massive subcutaneous emphysema. Red arrow to indicate the small size SP.
Generally, at chest X-ray, bullous lesions have a concave appearance while a pneumothorax has a concave profile (Figure 3).
The different appearance between an SP and bullae. Image a: a secondary pneumothorax in a COPD patient. At the chest X-ray, a pneumothorax has a concave profile. Image b: bulls lesion has a concave appearance.
In COPD patients, however, a CT scan is useful to better analyze the pneumothorax size and the severity of the lung disease. Moreover, The CT scan can help in distinguishing a big bulla from a true PNX. This may not be an easy task; however, if a bulla is detected, a chest tube is not always indicated, or if it is, it should be carefully placed under CT guidance, in order to avoid an iatrogenic rupture of the bulla determining a complex PNX, which potentially requires a surgical treatment.
It is important to remember that due to the underlying pathology and the low functional reserve, these patients could become suddenly critical in case of a PNX and should therefore be treated accordingly. For the same reason, even if the PNX is correctly treated by means of a chest drain, these patients still remain at a higher risk of death. Death causes are, in fact, associated with the onset of an acute or late respiratory failure [12, 13], or with a higher risk of developing sepsis as a consequence of pneumonia or empyema due to the pneumothorax management (i.e., chest tube and/or pleurodesis) [14].
Any noxa capable to affect the integrity of the visceral pleura and reduce the lung elasticity could be a cause of a secondary pneumothorax and therefore, a secondary pneumothorax may be diagnosed in the process of:
Infection: tuberculosis, necrotizing pneumonia, and
Interstitial diseases: cystic fibrosis, acute severe asthma. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrosing lung disease of unknown etiology. The rates of pneumothorax range from 2 to 20% in patients with IPF, becoming the second cause of SP after chronic obstructive pulmonary disease (COPD) [15].
Inflammatory or connective-related diseases: such as rheumatoid arthritis, polymyositis, dermatomyositis, systemic sclerosis, Marfan’s syndrome, and Ehlers-Danlos syndrome.
Pneumothorax caused by tubercular infection.
Acquired immunodeficiency syndrome (AIDS) could be another cause of SP, likely related to an increased risk of developing cystic lesions in the sub-pleural space [16].
As in the case of primary pneumothorax, the treatment goals should aim at:
evacuating the pleural cavity from the air to restore the normal intrapleural negative pressure;
obtaining lung re-expansion and pleural apposition;
reducing the risk of recurrence.
According to the BTS guidelines, a secondary pneumothorax that occurred in a known diseased lung requires the insertion of a small-bore chest tube to drain the air in the pleural space [17].
Pneumothorax aspiration, which finds a treatment indication in the primary spontaneous pneumothorax, has a high-risk of failure, but it may be taken into account in the case of symptomatic patients with a small pneumothorax. A persistent air leak can be managed conservatively obtaining a complete resolution [17].
A talc slurry pleurodesis could be a nonsurgical therapeutic management option to be considered for persistent air leak in patients deemed unfit for surgery. According to the American College of Chest Physicians (ACCP) consensus, a talc slurry pleurodesis through the chest tube is indicated to avoid recurrence after the first episode [14].
By contrast, the BTS guidelines suggest pleurodesis in case of a recurrent SP or in case of a persistent air leak, which in COPD patients may resolve in a long time compared to non-COPD patients [18]. Surgery is an option in SP, but COPD patients may not be deemed fit enough for surgery because of their clinical status. A prerequisite for talc pleurodesis is a complete or major re-expansion of the lung. In case of partially expanded or nonexpandable lungs, other options should be advocated, such as permanent drains connected to a Heimlich valve. Furthermore, prior to proceeding to talc pleurodesis, the increased risk of a pulmonary restrictive dysfunction secondary to talc insufflation should be well pondered and discussed interdisciplinary.
Contrarily to the ACCP guidelines that suggest medical thoracoscopy or VATS as the first choice to perform talc pleurodesis, because of their lower morbidity, the BTS guidelines consider an open approach (thoracotomy) as the procedure of choice, limiting VATS procedures to unfit patients [17].
Furthermore, in nonsurgical patients with a persistent air leak a talc slurry via chest tube should be taken into consideration.
The 2021 GOLD guidelines consider as the main surgical option in high-grade COPD [9]:
lung volume reduction surgery (LVRS);
bullectomy/blebectomy, which are associated with an improvement of dyspnea and lung function;
lung transplantation: in very high-risk patients, with progressive COPD. Inclusion criteria are exacerbations associated with hypercapnia (pCO2 ≥ 50 mmHg), pulmonary hypertension, FEV1 < 20%, and/or a diffusing capacity for carbon monoxide (Dlco <20%) [9].
LVRS can improve survival in severe lung emphysema, mainly in the upper lobes localized emphysema, and low-ability exercise patients [17]. The National Emphysema Treatment Trial (NETT) identified four groups of patients [19] on the basis of their postoperative exercise tolerance and their emphysema pattern at the CT scan (Table 1).
Emphysema at CT scan | Pre-operative exercise capacity | LVRS risk of death | Survival | Post-operative exercise tolerance | Symptoms control |
---|---|---|---|---|---|
Upper lobe-predominant emphysema | Low | Lower than medical therapy | Improved | Improved within 3 years from surgery | Improved |
High | Not improved | Improved (years 1–3) | Improved (years 1–4) | ||
Non-upper lobe-predominant emphysema | Low | No effects | Not improved | No effects | |
High | Increased | Not improved | No effects | No effects |
Results in the four groups studied in the NETT trial.
The NETT demonstrated that the effects of LVRS are durable and that it is strongly recommended in upper lobe-predominant emphysema with low exercise capacity and should be considered for palliation in patients with upper lobe emphysema and high exercise capacity (Figure 5).
Results of NETT. Image D: Upper lobe–predominant emphysema with low exercise capacity group. The surgical group has a lower probability of death than the medical group.
Predominantly, the following endobronchial procedures find an indication in reducing the end-expiratory lung volume and to improve exercise tolerance:
endobronchial lung volume reduction with one-way valves (BLVR);
endobronchial coils filling;
thermal ablation.
Endobronchial valves are placed in segmental or lobar bronchi through rigid bronchoscopy, allowing peripheral lung deflation, lung volume reduction, and improvement of symptoms with an accepted mortality rate equal to 5–10% [20]. The valve mechanism does not permit air to go through the segmental or lobar bronchus during the inspiration but, instead, it allows it passage during the expiratory phase. The valves are available in multiple diameters, ranging from 4 to 8.5 mm.
In general, two main devices are available:
the “aspiration umbrella”, which is an implantable Intra-Bronchial Valve (IBV) that can be positioned via flexible bronchoscopy, leaving the umbrella shape adherent to the airway wall and limiting the airflow distally;
the Emphasis Bronchial Valve (EBV), which is able to prevent air entering in the lung during inspiration but allows outflow of air and secretion. A flexible aspiration valve is present in the endobronchial valve structure from which exhaled air and secretions can be cleared out or aspirated because of the unidirectional valve.
Both devices are inserted in the operating theater with the patient sedated and in spontaneous assisted (jet-) ventilation [21].
The VENT trial (Endobronchial Valve for Emphysema Palliation Trial) [22] is a two-arm, randomized, controlled, multi-center trial that showed a 4.3% FEV1 increase in the EBV group compared to the 2.5% in the control medical group.
However, the study shows that complications following the procedure may counterbalance the advantages of the procedure itself. In fact, on the one hand, patients may obtain an improvement in their respiratory function, and on the other hand, it may be associated with hemoptysis, pneumothorax with persistent air leak, and COPD exacerbations, which may occur more frequently in advanced, hyper-inflated emphysema patients. Moreover, as evidenced in the VENT trial, the 2-yrs mortality rate in the EBV group was 2.8% compared to no deaths in the control group, but the difference wasn’t statistically significant (p = 0.19).
Although rare findings, the main causes of SP from malignant diseases are primary cancers of the lung and pleura (e.g., mesothelioma) followed by infiltrative/metastatic pleural diseases, such as in the case of germ cell tumors, breast cancer, or osteogenic and soft tissue sarcomas metastasis [21, 22, 23].
The occurrence of an SP as the first manifestation of a lung cancer ranges between 0.03% and 0.05% and usually allows to detect the unknown presence of a lung tumor or metastasis [24] without affecting the prognosis [25, 26].
By contrast, a review published in 2010 analyzed data available in the literature concerning pneumothorax secondary to sarcoma, highlighting increased mortality in such patients compared to those without such complications [26].
Several hypotheses have been taken into account to explain the pathogenesis of pneumothorax secondary to malignant disease, which include (i) an alteration of the pleural surface following tumoral pleural infiltration; (ii) rupture of a necrotic tumoral nodule; and (iii) necrosis of subpleural metastases [27].
Moreover, adjuvant or neoadjuvant chemotherapy and/or radiotherapy treatments may alter the lung parenchymal structure. In these cases, the high-risk of infection associated with a reduced functional repair mechanism could enhance the risk of pleural alterations, possibly leading to a secondary pneumothorax. Also, a tumoral invasion of the small airways could be responsible for a distal alveolar space dilatation determining air-trapping, which may lead to rupture and pneumothorax.
The clinical presentation depends on the patients’ performance status according to their functional status and disease stage. Usually, clinical signs and symptoms are chest pain and shortness of breath.
A chest X-ray is mandatory to assess the presence of a pneumothorax, which usually appears as a complete collapse of the normal areas of the lung. A CT scan is useful to better analyze the pneumothorax size and to investigate a possible progression of disease.
Pneumothorax can be the first sign of neoplastic disease, especially when it assumes a recurrent nature in high-risk patients (heavy smokers, COPD), who will therefore undergo further investigations, which will lead to eventually diagnose the tumor.
Diagnosis and management of a secondary pneumothorax concomitant to a pulmonary neoplastic disease are the same for a pneumothorax happening in a pre-existing neoplastic condition. A chest tube is recommended according to its size and the clinical features of patients.
In case of a persistent air leak or in a recurrent pneumothorax, surgery is an option in order to investigate the causes and proceed to talc pleurodesis in case of nonoperable tumors or unfit for surgery patients. If surgery is contemplated, the surgeon may proceed to obtain a diagnosis in case this was not achieved previously, by means of pleural biopsy/wedge resection/lymph node sampling. Cases of recurrent pneumothorax as the first sign of pleural mesothelioma or sarcoma metastasis have been reported, identifying the thoracoscopic bullectomy as the key to the best diagnosis and treatment [28, 29].
Thoracic trauma is the third leading cause of death following abdominal injury and head trauma in polytrauma patients [30]. Management of chest trauma patients is complex and requires an interdisciplinary team with experience in anesthesia, critical care, and surgical disciplines, especially neurosurgery, trauma surgery, abdominal surgery, and thoracic surgery.
Blunt and penetrating chest traumas can be the cause of pneumothorax and trauma should be taken into account when discussing secondary pneumothoraces.
Thoracic trauma can be differentiated into blunt or penetrating.
Penetrating injuries, such as blade wounds and firearm injuries, are disruptive to tissue integrity. Gunshot and stabbing account for 10% and 9.5% of penetrating chest injuries, making these the most common etiology of penetrating trauma.
A blunt trauma (Figure 6) is a nonpenetrating injury of the chest. Blunt thoracic injuries are more common than penetrating injuries [30].
Pneumothorax after a barotrauma.
Blunt injuries can cause damage to organs and structures without disrupting the integrity of the tissue. Falls from a great height, motor vehicle accidents, and occupational accidents are the main mechanisms of blunt injuries [31, 32, 33].
Depending on the mechanism of injury (e.g., acceleration-deceleration and direct impacts on the chest) an SP may be detected and should be treated and investigated on the cause of its onset (rib fractures, tracheal/bronchial or esophageal disruptions, lung contusion, and lung laceration).
Particular attention is reserved for a tension pneumothorax, in which air enters the pleural space at each inspiration, while the air in the pleural space cannot escape from the pleural space due to the one-way valve mechanism. The continuous accumulation of air in the pleural space determines a lung collapse, hypoxia, tachypnea, and tachycardia, a mediastinal shift with compression of the contralateral lung and the superior vena cava (SVC), leading to respiratory distress and rapidly to respiratory failure with cardiovascular collapse.
Management of patients following major trauma should follow the standardized protocol of emergency and resuscitation advanced trauma life support guidelines (ATLS), and a primary survey of the airway, breathing, circulation, disability, and exposure (ABCDE approach) should be performed.
Particular attention is required in a tension pneumothorax because, if a prompt intervention is not carried out, can rapidly lead to death [34]. Immediate evacuation through a chest tube is mandatory as recommended by the ATLS [35].
In general, a chest tube has to be positioned in a post-traumatic pneumothorax, in order to stabilize the patient.
Once the patient is stabilized, radiological investigations, such as chest X-ray and chest CT scan are mandatory to identify the cause of pneumothorax and eventually determine the need for further treatments (surgery).
At the same time, minor blunt traumas may be cause of small pneumothoraces, which may not require a chest tube and can be treated conservatively with high flow oxygen, pain control, and repeated CXR [36].
Penetrating injuries are disruptive to tissue integrity, with direct communication between the pleural space and the external environment and they can be acutely life-threatening.
It is mandatory to know the mechanism of injury as the management may vary. For example, stab versus gunshot injury to the chest can result in different patterns of injury.
Depending on the penetrating trauma, immediate surgery may be deemed necessary and a chest tube is required to stabilize the patient for surgery (e.g., during patient transportation from the trauma site to the hospital). Frequently, when a post-traumatic pneumothorax is present it can be associated with a hemothorax [37].
Iatrogenic pneumothorax is a possible complication of several invasive procedures, such as a central venous line insertion (0.5–5%), thoracentesis (1, 5–7%), and CT-guided lung biopsy (1–6%); at times they can be associated with hemothorax (1% of all procedures) [38, 39].
In some cases, it may occur as a complication following bronchoscopic positioning of unidirectional valves in emphysematous patients [21].
The term “catamenial” derives from two Greek words meaning “pertaining to” and “monthly.”
Catamenial pneumothorax is defined as a recurrent accumulation of air in the pleural cavity in reproductive-age women.
A catamenial pneumothorax (CP) arises within 48–72 h from menstruation. It occurs in 3–6% of spontaneous pneumothoraces and most frequently involves the right side [40].
This kind of pneumothorax is, mainly, included in two syndromes:
the thoracic endometriosis syndrome (TES), which is associated with hemothorax and lung nodules. It is a rare clinical disease that sometimes is secondary to the presence of endometrial gland tissue in the lungs, pleura, diaphragm, and tracheobronchial tree [41]. TES has been reported for the first time in 1953, in a case report of a young woman that developed hemothorax. In 1958, Mauerer described recurrent pneumothoraces in association with menstruation and pelvic endometriosis [42].
the porous diaphragmatic syndrome: cases of CP without any evidence of endometrial implants, but secondary to the presence of diaphragmatic defects [43]. In rare cases, in fact, diaphragm fenestrations over the tendinous portion may be visualized during surgery and appear as orifices in the muscle, becoming the cause of pneumothorax.
The cancer antigen 125 (CA-125), a gynecological serum marker, has assumed a role in the diagnostic work-up for TES. In fact, high levels of CA-125 have been associated with recurrent SP with evidence of thoracic endometriosis, such as focal thoracic endometrial implants, during VATS procedures. On the contrary, patients without thoracoscopic evidence of endometrial disease have normal CA-125 serum level [44].
The presence of a CP is not always related to pelvic endometriosis.
In a prospective study, 32 women had a CP diagnosis, but only 2 had pelvic endometriosis associated [41].
The occurrence of PSP in women of childbearing age is not unusual and there appears to be an increased risk of recurrence during pregnancy and during parturition with potential risks to the mother and fetus.
A more recent case series and literature review have recommended the use of more modern conservative management methods for which favorable outcomes have now been experienced [17, 45]. Pneumothorax in pregnancy can be managed by simple observation, if the mother is not symptomatic, there is no fetal distress and the pneumothorax is small (<2 cm). Otherwise, aspiration can be performed, chest drain insertion being reserved for those with a persistent air leak or a greater pneumothorax.
To avoid spontaneous delivery or cesarean section, both of which have been associated with an increased risk of recurrence, the safest approach will usually be that of elective assisted delivery at or near term. Less maternal effort is required with forceps delivery, which is therefore preferable. Because of the risk of recurrence in subsequent pregnancies, a minimally invasive VATS surgical procedure should be considered few weeks from delivery. Successful pregnancies and spontaneous deliveries without pneumothorax recurrence have been reported after a VATS procedure [17, 45].
In contrast to the benign clinical course of a PSP, SP is associated with pre-existing underlying lung disease, trauma, or invasive procedures and can be a life-threatening event. Patients with pre-existing lung disease tolerate a pneumothorax less well, and the distinction between PSP and SSP should be made at the time of diagnosis to guide appropriate management. The consequences of a pneumothorax in patients with a pre-existing lung disease are significantly greater, and the management is potentially more complex than in PSP patients. Furthermore, SP is correlated to a higher morbidity and mortality compared to PSP. Differently from a PSP, where the management is well defined by different international guidelines, SP treatment may vary because of the clinical conditions, previous episodes, severity and duration of symptoms, and the presence of an underlying pulmonary disease. Its treatment will therefore vary accordingly, from observation to needle aspiration or thoracostomy tube drainage with or without pleurodesis and potentially escalating to an open thoracotomy or VATS procedures, as described in this chapter. In case of surgery in high-risk patients (e.g., COPD patients, frail patients), the risk of proceeding to surgery with the aim of resolving the underlying cause and securing the lung with adequate pleurodesis should be well pondered both from the surgical and anesthesiological point of view based onto the patients’ clinical status and consent.
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Some systems are highly affected by a small fraction of influential nodes. Number of fast and efficient spreaders in a network is much less compared to the number of ordinary members. Information about the influential spreaders is significant in the planning for the control of propagation of critical pieces of information in a social or information network. Identifying important members who act as the fastest and efficient spreaders is the focal theme of a large number of research papers. Researchers have identified approximately 10 different methods for this purpose. Degree centrality, closeness centrality, betweenness centrality, k‐core decomposition, mixed degree decomposition, improved k‐shell decomposition, etc., are some of these methods. 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Classification and prediction of decision problems can be solved with the use of a decision tree, which is a graph-based method of machine learning. In the presented approach, attribute-value system and quality function deployment (QFD) were used for decision problem analysis and training dataset preparation. 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To find out which algorithm obtains better results, there are 30 test instances used, which are grouped into 3 sets of problems according to the position of the nodes. The study begins with an economic impact analysis of the transportation sector in companies, which represents up to 20% of the final cost of the product. 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Vertex degrees deg(v) are always finite but the trees contain infinite paths (vi)i≥0. A concrete group theoretic model of the rooted in-trees T(R) is introduced by representing vertices by isomorphism classes of finite p-groups G, for a fixed prime p, and directed edges by epimorphisms π: G → πG of finite p-groups with characteristic kernels ker(π). The weight of a vertex G is realized by its nuclear rank n(G) and the weight of a directed edge π is realized by its step size s(π)=logp(#ker(π)). These invariants are essential for understanding the phenomenon of multifurcation. Pattern recognition methods are used for finding finite subgraphs which repeat indefinitely. Several periodicities admit the reduction of the complete infinite graph to finite patterns. The proof is based on infinite limit groups and successive group extensions. It is underpinned by several explicit algorithms. As a final application, it is shown that fork topologies, arising from repeated multifurcations, provide a convenient description of complex navigation paths through the trees, which are of the greatest importance for recent progress in determining p-class field towers of algebraic number fields.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Daniel C. Mayer",authors:[{id:"198580",title:"Dr.",name:"Daniel C.",middleName:null,surname:"Mayer",slug:"daniel-c.-mayer",fullName:"Daniel C. Mayer"}]},{id:"57771",doi:"10.5772/intechopen.71774",title:"Governance Modeling: Dimensionality and Conjugacy",slug:"governance-modeling-dimensionality-and-conjugacy",totalDownloads:1353,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The Q-analysis governance approach and the use of simplicial complexes—type of hypergraph—allow to introduce the formal concepts of dimension and conjugacy between the network of entities involved in governance (typically organizations) and the networks of those attributes taken into account (e.g. their competences), which offer a specific angle of analysis. The different sources of existing data (e.g. textual corpora) to feed the analysis of governance—environmental in particular—are mentioned, their reliability is briefly discussed and the required pre-processing steps are identified in the perspective of evidence-based analyses. Various indices are constructed and evaluated to characterize the context of governance as a whole, at mesoscale, or locally, i.e. at the level of each of the entities and each of the attributes considered. The analysis of ideal-type stylizing boundary cases provides useful references to the analysis of concrete systems of governance and to the interpretation of their empirically observed properties. The use of this governance modeling approach is illustrated by the analysis of a health-environment governance system in Southeast Asia, in the context of a One Health approach.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Pierre Mazzega, Claire Lajaunie and Etienne Fieux",authors:[{id:"220099",title:"Dr.",name:"Pierre",middleName:null,surname:"Mazzega",slug:"pierre-mazzega",fullName:"Pierre Mazzega"},{id:"220102",title:"Dr.",name:"Claire",middleName:null,surname:"Lajaunie",slug:"claire-lajaunie",fullName:"Claire Lajaunie"},{id:"220103",title:"Prof.",name:"Etienne",middleName:null,surname:"Fieux",slug:"etienne-fieux",fullName:"Etienne Fieux"}]}],mostDownloadedChaptersLast30Days:[{id:"55642",title:"Monophonic Distance in Graphs",slug:"monophonic-distance-in-graphs",totalDownloads:1556,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"For any two vertices u and v in a connected graph G, a u − v path is a monophonic path if it contains no chords, and the monophonic distance dm(u, v) is the length of a longest u − v monophonic path in G. For any vertex v in G, the monophonic eccentricity of v is em(v) = max {dm(u, v) : u ∈ V}. The subgraph induced by the vertices of G having minimum monophonic eccentricity is the monophonic center of G, and it is proved that every graph is the monophonic center of some graph. Also it is proved that the monophonic center of every connected graph G lies in some block of G. With regard to convexity, this monophonic distance is the basis of some detour monophonic parameters such as detour monophonic number, upper detour monophonic number, forcing detour monophonic number, etc. The concept of detour monophonic sets and detour monophonic numbers by fixing a vertex of a graph would be introduced and discussed. Various interesting results based on these parameters are also discussed in this chapter.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"P. Titus and A.P. Santhakumaran",authors:[{id:"198301",title:"Dr.",name:"P.",middleName:null,surname:"Titus",slug:"p.-titus",fullName:"P. Titus"},{id:"199035",title:"Prof.",name:"A. P.",middleName:null,surname:"Santhakumaran",slug:"a.-p.-santhakumaran",fullName:"A. P. Santhakumaran"}]},{id:"71501",title:"Accelerating DNA Computing via PLP-qPCR Answer Read out to Solve Traveling Salesman Problems",slug:"accelerating-dna-computing-via-plp-qpcr-answer-read-out-to-solve-traveling-salesman-problems",totalDownloads:824,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"An asymmetric, fully-connected 8-city traveling salesman problem (TSP) was solved by DNA computing using the ordered node pair abundance (ONPA) approach through the use of pair ligation probe quantitative real time polymerase chain reaction (PLP-qPCR). The validity of using ONPA to derive the optimal answer was confirmed by in silico computing using a reverse-engineering method to reconstruct the complete tours in the feasible answer set from the measured ONPA. The high specificity of the sequence-tagged hybridization, and ligation that results from the use of PLPs significantly increased the accuracy of answer determination in DNA computing. When combined with the high throughput efficiency of qPCR, the time required to identify the optimal answer to the TSP was reduced from days to 25 min.",book:{id:"8241",slug:"novel-trends-in-the-traveling-salesman-problem",title:"Novel Trends in the Traveling Salesman Problem",fullTitle:"Novel Trends in the Traveling Salesman Problem"},signatures:"Fusheng Xiong, Michael Kuby and Wayne D. Frasch",authors:[{id:"14757",title:"Prof.",name:"Wayne",middleName:null,surname:"Frasch",slug:"wayne-frasch",fullName:"Wayne Frasch"},{id:"317054",title:"Prof.",name:"Michael",middleName:null,surname:"Kuby",slug:"michael-kuby",fullName:"Michael Kuby"},{id:"317055",title:"Dr.",name:"Fusheng",middleName:null,surname:"Xiong",slug:"fusheng-xiong",fullName:"Fusheng Xiong"}]},{id:"57940",title:"Graph-Based Decision Making in Industry",slug:"graph-based-decision-making-in-industry",totalDownloads:1726,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Decision-making in industry can be focused on different types of problems. Classification and prediction of decision problems can be solved with the use of a decision tree, which is a graph-based method of machine learning. In the presented approach, attribute-value system and quality function deployment (QFD) were used for decision problem analysis and training dataset preparation. A decision tree was applied for generating decision rules.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Izabela Kutschenreiter-Praszkiewicz",authors:[{id:"218951",title:"Associate Prof.",name:"Izabela",middleName:null,surname:"Kutschenreiter-Praszkiewicz",slug:"izabela-kutschenreiter-praszkiewicz",fullName:"Izabela Kutschenreiter-Praszkiewicz"}]},{id:"55375",title:"An Example Usage of Graph Theory in Other Scientific Fields: On Graph Labeling, Possibilities and Role of Mind/Consciousness",slug:"an-example-usage-of-graph-theory-in-other-scientific-fields-on-graph-labeling-possibilities-and-role",totalDownloads:1831,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This paper provides insights into some aspects of the possibilities and role of mind, consciousness, and their relation to mathematical logic with the application of problem solving in the fields of psychology and graph theory. This work aims to dispel certain long-held notions of a severe psychological disorder and a well-known graph labeling conjecture. The applications of graph labelings of various types for various kinds of graphs are being discussed. Certain results in graph labelings using computer software are presented with a direction to discover more applications.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Auparajita Krishnaa",authors:[{id:"198790",title:"Dr.",name:"Auparajita",middleName:null,surname:"Krishnaa",slug:"auparajita-krishnaa",fullName:"Auparajita Krishnaa"}]},{id:"74003",title:"Introductory Chapter: Traveling Salesman Problem - An Overview",slug:"introductory-chapter-traveling-salesman-problem-an-overview",totalDownloads:536,totalCrossrefCites:1,totalDimensionsCites:1,abstract:null,book:{id:"8241",slug:"novel-trends-in-the-traveling-salesman-problem",title:"Novel Trends in the Traveling Salesman Problem",fullTitle:"Novel Trends in the Traveling Salesman Problem"},signatures:"Donald Davendra and Magdalena Bialic-Davendra",authors:[{id:"2961",title:"Prof.",name:"Donald",middleName:null,surname:"Davendra",slug:"donald-davendra",fullName:"Donald Davendra"},{id:"14638",title:"Dr.",name:"Magdalena",middleName:null,surname:"Bialic-Davendra",slug:"magdalena-bialic-davendra",fullName:"Magdalena Bialic-Davendra"}]}],onlineFirstChaptersFilter:{topicId:"1400",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,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:333,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:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,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:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Rosa María Martínez-Espinosa is a Full Professor of Biochemistry and Molecular Biology at the University of Alicante, Spain, and has been the vice president of International Relations and Development Cooperation at this university since 2010. She created the research group in applied biochemistry in 2017 (https://web.ua.es/en/appbiochem/), and from 1999 to the present has made more than 200 contributions to Spanish and international conferences. Furthermore, she has around seventy-five scientific publications in indexed journals, eighty book chapters, and one patent to her credit. Her research work focuses on microbial metabolism (particularly on extremophile microorganisms), purification and characterization of enzymes with potential industrial and biotechnological applications, protocol optimization for genetically manipulating microorganisms, gene regulation characterization, carotenoid (pigment) production, and design and development of contaminated water and soil bioremediation processes by means of microorganisms. This research has received competitive public grants from the European Commission, the Spanish Ministry of Economy and Competitiveness, the Valencia Region Government, and the University of Alicante.",institutionString:"University of Alicante",institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:45,paginationItems:[{id:"83122",title:"New Perspectives on the Application of Chito-Oligosaccharides Derived from Chitin and Chitosan: A Review",doi:"10.5772/intechopen.106501",signatures:"Paul Edgardo Regalado-Infante, Norma Gabriela Rojas-Avelizapa, Rosalía Núñez-Pastrana, Daniel Tapia-Maruri, Andrea Margarita Rivas-Castillo, Régulo Carlos Llarena-Hernández and Luz Irene Rojas-Avelizapa",slug:"new-perspectives-on-the-application-of-chito-oligosaccharides-derived-from-chitin-and-chitosan-a-rev",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chitin-Chitosan - Isolation, Properties, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11670.jpg",subseries:{id:"15",title:"Chemical Biology"}}},{id:"83015",title:"Acute Changes in Lipoprotein-Associated Oxidative Stress",doi:"10.5772/intechopen.106489",signatures:"Ngoc-Anh Le",slug:"acute-changes-in-lipoprotein-associated-oxidative-stress",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Anh",surname:"Le"}],book:{title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",subseries:{id:"15",title:"Chemical Biology"}}},{id:"83041",title:"Responses of Endoplasmic Reticulum to Plant Stress",doi:"10.5772/intechopen.106590",signatures:"Vishwa Jyoti Baruah, Bhaswati Sarmah, Manny Saluja and Elizabeth H. 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He is an IEEE Senior Member and a member of several other research organizations worldwide. His main research interests are computer vision, intelligent systems, robotics, and image and video processing. He has participated in or coordinated several research projects and received more than thirty-five awards. He has 161 publications to his credit, including books, book chapters, journal articles, and conference papers. He has vast experience as a reviewer of several journals and conferences. As a professor, Dr. Neves has supervised several Ph.D. and master’s students and was involved in more than twenty-five different courses.",institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"11317",title:"Dr.",name:"Francisco",middleName:null,surname:"Javier Gallegos-Funes",slug:"francisco-javier-gallegos-funes",fullName:"Francisco Javier Gallegos-Funes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/11317/images/system/11317.png",biography:"Francisco J. Gallegos-Funes received his Ph.D. in Communications and Electronics from the Instituto Politécnico Nacional de México (National Polytechnic Institute of Mexico) in 2003. He is currently an associate professor in the Escuela Superior de Ingeniería Mecánica y Eléctrica (Mechanical and Electrical Engineering Higher School) at the same institute. His areas of scientific interest are signal and image processing, filtering, steganography, segmentation, pattern recognition, biomedical signal processing, sensors, and real-time applications.",institutionString:"Instituto Politécnico Nacional",institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"428449",title:"Dr.",name:"Ronaldo",middleName:null,surname:"Ferreira",slug:"ronaldo-ferreira",fullName:"Ronaldo Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428449/images/21449_n.png",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. 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:"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:null,institution:null},{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:"417317",title:"Mrs.",name:"Chiedza",middleName:null,surname:"Elvina Mashiri",slug:"chiedza-elvina-mashiri",fullName:"Chiedza Elvina Mashiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"352140",title:"Dr.",name:"Edina",middleName:null,surname:"Chandiwana",slug:"edina-chandiwana",fullName:"Edina Chandiwana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"342259",title:"B.Sc.",name:"Leonard",middleName:null,surname:"Mushunje",slug:"leonard-mushunje",fullName:"Leonard Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"347042",title:"Mr.",name:"Maxwell",middleName:null,surname:"Mashasha",slug:"maxwell-mashasha",fullName:"Maxwell Mashasha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"2941",title:"Dr.",name:"Alberto J.",middleName:"Jorge",surname:"Rosales-Silva",slug:"alberto-j.-rosales-silva",fullName:"Alberto J. 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