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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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The multifocal, multicentric, and bilateral aspects of breast cancer (BC) are the eternal dilemma in the scientific literature. Breast cancer is the most common tumour disease and the second leading cause of death in American women, with 268,600 new cases and 41,760 deaths in 2019 [1]. The second most common malignancy in patients with breast cancer is contralateral breast cancer [2]. Presence of another focus of breast cancer, far away from the dominant mass, was described as early as 1920 by Cheatle [3]. The appearance of such non-dominant lesions in multiple ducts of a single quadrant (multifocal), or in two or more quadrants (multicentric) was further elaborated in 1957 by Qualheim and Gall [4]. Multifocal/multicentric (MF/MC) breast cancer is occurring frequently, however, its genesis is not fully understood [5].
Previous studies evaluated histological and immunohistochemical characteristics [6, 7], revealing that most multicentric breast cancers share similar features in terms of histology and immunohistochemistry, suggesting that early-stage synchronous tumours develop from one breast cancer [6]. The heterogeneity of the focus of multiple cancers [8] is understudied in the literature, with a number of studies which have evaluated histological and immunohistochemical characteristics of tumour foci in multiple cancers arriving at contradictory results and different conclusions [7, 9].
Multiple synchronous ipsilateral breast cancer (MSIBC) with heterogeneous histopathology is a controversial condition in a clinical context, which has been discussed and studied extensively in the literature, but lacking international consensus on itsdefinition and clinical treatment options. Current incidence of MSIBC is unknown, but, owing to improved sensitivity of medical imaging methods and the use of magnetic resonance imaging (MRI) for BC screening and staging, is showing increased occurrence. This heterogeneous disease requires special attention during treatment, given the fact that MSIBC is a much more aggressive condition which produces metastases in lymph nodes more frequently [10].
Based on current therapies for breast cancer, the treatment of this heterogeneous disease calls for joint decision making in a multidisciplinary team and in collaboration with an oncology council, where the pathologist, working with the other members of the team, influences the new concept of individual approach to treatment of MC/MF breast cancer patients with their data and explanations obtained through testing. A new rigorous view on genetic patterns of heterogeneity in each individual focus would present a more specific approach to treating MSIBC [11].
Multiple synchronous tumour foci in one breast are referred to as multifocal and multicentric, but without a consensus on terminology [12]. MF/MC cancer may occur due to intramammary proliferation of a single primary BC or multiple synchronous, independent primary breast cancers [5, 13]. Recently, the definition of multifocal cancer was changed. Previous definition of multiple synchronous lesions of breast cancer stated that these could be either MF or MC, depending on where the lesion was located (in the same or different quadrants). The use of breast quadrants to define and classify cancers is now considered inappropriate, since quadrants are not part of convention which correspond to the breast anatomy [14]. Pathologists define multiple simultaneous primary lesions when there are two or more tumour foci without malignant tissue between them [15].
Multifocality is usually determined microscopically, when a greater number of morphological cancer development centres are present, which is the same micromorphological unit or lobe in the breast. Radiologists do not have a more precise definition, but tumours are usually considered multifocal when the distance between the tumour masses is less than or equal to 5 cm, and multicentric when this distance is greater than 5 cm (Figure 1) [16, 17]. Given that a standardised definition is not established, multifocal and multicentric breast cancers are often grouped together as multifocal/multicentric breast cancers [18]. In histological terms, BC is defined as multiple cancer when it consists of more than one clearly distinguishable tumour foci which are separated by normal and benign breast tissue or ductal carcinoma in situ (DCIS) [19].
Images from mammograms of ILC from three different patients: (A) stellate tumour shadow of unifocal ILC from the 58 years old patient; (B) multicentric (bicentric) ILC from the 53 years old patient; (C) bilateral synchronous ILC from the 32 years old patient. In reference [
Various time intervals are used to define bilateral synchronous breast cancer (BSBC). In 1921, Kilgore defined BSBC as breast cancer where both tumours are diagnosed simultaneously [20]. Since 1921, various time intervals were introduced, ranging from one to five years [21]. A broadly accepted definition of BSBC is the one given by Hartman and co-authors in 2007 as a tumour diagnosed within 90 days after the initial mass has occurred. Although the reported time intervals vary, bilateral BCs are considered to be synchronous when contralateral BC is diagnosed within a period of three months, and as metachronous bilateral cancers (BMBC) when diagnosed more than three months after the first diagnosis [22]. Limit values used in the literature to differentiate between BSBC and BMBC range from 1 to 12 months [23]. Before a bilateral breast cancer diagnosis is confirmed, metastatic contralateral breast cancer has to be ruled out [24].
The definitions of multifocality, multicentricity, and bilaterality refer primarily to the two most common types of breast cancer (ductal and lobular), but can also refer to certain lesions which occur less frequently in the breast. In terms of multifocality, between 10 and 20% of tubular carcinomas may present as multifocal [25, 26], and the identical frequency of multifocality is observed in cribriform cancers [27, 28]. A thorough sampling of large areas with high DCIS grade should be performed in order not to miss the foci of the carcinoma microinvasions (or invasions). Some reports suggested that when a microinvasive carcinoma occurs, it is likely to be multifocal [29].
Certain benign lesions, such as papilloma, are rarely multiple in nature (Figure 2). Breast lesions which often present as bilateral are DCIS [30], Paget’s disease of the nipple, radial scars and complex sclerosinglesions, gynecomastia, Burkitt lymphoma [31], while bilateral breast cancer also frequently occurs in patients with Cowden syndrome and heterozygous ATM mutation carriers (ataxia telangiectasia), as a result of submitting patients suffering from Louis–Bar syndrome to radiotherapy [31, 32, 33]. Other types of potentially bilateral-onset breast lesions are atypical ductal hyperplasia [31], phyllodes tumour [32, 34], myofibroblastoma [33], desmoidfibromatosis [35], male breast cancer [36], angiosarcoma [37, 38], liposarcoma [31], lymphoma (about 10% of the cases), pseudoangiomatous stromal hyperplasia [39], ductal adenoma in patients with Carney syndrome [40]. There are also lesions with unidentified bilaterality, some of which are ALK-negative anaplastic large cell lymphoma [31], mucosa associated lymphoid tissue lymphoma [41] and granular cell tumour [42]. Most patients with diffuse large B-cell lymphoma develop a unilateral condition, but there is a risk of relapse in the contralateral breast [43].
Multiple breast papillomas in multilocular cyst of the 52 years old patient. (A) Macroscopic appearance; (B) microscopic appearance of breast papilloma (HE x 100)(image was taken from author’s own lab).
Based on data from the literature, there is no consensus on the factors relating to the development of multicentric carcinomas [44]. MF/MC BC incidence ranges from 6 to 77% [14]. Bilateral breast cancers are responsible for 2 to 6% of all breast carcinomas [22]. Earlier studies have shown that one of the most important risk factors for MCBC is if the first occurrence is an invasive lobular carcinoma (ILC) [45]. Low-grade invasive ductal carcinomas (IDC) are not linked with the number of tumour masses in the contralateral breast. All of these observations contradict the fact that ILC is more common among patients with bilateral and multifocal BC solely due to slower growth rates [46].
There are no differences when it comes to patient age, tumour stage, or the presence of multifocal, multicentric, and bilateral ILCs [47]. Contralateral tumour incidence, in particular synchronous ILCs, is in the 5 to 19% range, which is more than invasive ductal carcinoma of no special type [45, 48, 49]. BSBC is a rare entity with an incidence between 1 and 3%. Surprisingly, there has not been an increase in the BSBC incidence since 1980. A lower incidence of metachronous bilateral breast cancer was observed, likely due to the introduction of systemic adjuvant therapy. In the study on incidence of bilateral breast cancers in Sweden, conducted by Hartman and co-authors reported that the incidence of BSBC was approximately 100 times greater than what can be explained as coincidence or a cumulative effect of exogenous carcinogens [22],
Women with MF/MC breast cancers are often of younger age at the time of diagnosis and with positive oestrogen (ER) receptors expression than women with a unifocal condition [50]. Patients with MF/MC tumours are prevalently premenopausal and with a lower body mass index [51]. Women already suffering from BC are at two to six times greater risk of developing contralateral BC compared to the risk of other women developing their first primary BC, with the risk being inversely proportional to their age at the time of initial diagnosis [45, 52]. Average time between the diagnosis of the first BC and metachronous contralateral breast cancer varies from 3.9 to 7.7 years [22, 52].
Histological subtype of invasive carcinoma did not prove to be a predictive multicentricity factor, particularly in ILC subtypes [16, 47]. Earlier studies suggest that ILCs are much more prone to multicentric growth; but when lobular carcinoma in situ (LCIS) is excluded, multicentricity is not that common [44, 53]. When compared to IDCs, ILCs are ER and progesterone (PR) positive to a larger extent, but show lower HER2 positivity with the exception of pleomorphic lobular carcinoma [31]. Women diagnosed with MF/MC BC proportionally more frequently have positive ER receptors and lower prevalence of triple-negative tumour masses. Numerous studies documented significantly higher positivity levels of ER receptors among the BRCA2 mutation carriers in comparison to BRCA1 mutation carriers. Therefore, it is highly unlikely that ER signalisation leads to MF/MC disease [54]. An extensive meta-analysis found no connection between the ER status and sporadic MF/MC breast cancers, suggesting that the ER status does not play a part in the specific development of MF/MC disease [55]. The risk of other contralateral primary breast cancers varies depending on the status of hormone receptors of the first tumour, age, race, and/or ethnic origin [56].
A certain number of earlier studies discovered a strong correlation with the lobular histology in the first primary breast carcinoma and the occurrence of bilateral breast cancer [57]. Women with primary breast cancer who have positive hormone receptors show twice the risk of developing contralateral BC, while women who have cancers with negative hormone receptors are at almost four times higher risk as compared to general population with regard to age and race. Women with primary tumours who have negative hormone receptors more frequently develop secondary tumours which have negative hormone receptors, especially if the initial diagnosis is confirmed before the age of thirty [56].
Women who have next of kin with BC are at 50% higher relative risk of developing bilateral breast cancer than women without family history of this condition [22]. When compared to non-carriers, women with BRCA1 mutations are at 4.5 times greater risk and with BRCA2 mutations at 3.4 times greater risk of bilateral breast cancer [58]. On the other hand, carriers of similar ATM gene variants have a lower risk of developing contralateral breast cancer [59]. Family history of breast carcinoma, younger age at the time of initial diagnosis, or mutation of BRCA1 and BRCA2 genes are linked to a higher risk of developing contralateral tumours, placing them in the higher risk group [45]. Higher prevalence of multifocality/multicentricity than expected occurs in women diagnosed with cancer who are BRCA2 mutation carriers [50].
Mammography and ultrasound are complementary methods for evaluating the size, spread, and the presence of multifocality in BC (Figure 1) [16, 31]. However, not all MF/MC cases will necessarily be found using these imaging modalities [60]. Radiologic BC characteristics can vary significantly. These differences often depend on the tumour grade and histological subtype. Therefore, variations in the radiologic presentation can sometimes predict the differences in the morphology and biology of the tumour. ILC often invades normal tissue without causing desmoplastic stromal response which is usually found in IDC. For this reason, ILC density is often similar to the surrounding normal fibrous and glandular tissue of the breast, which makes it inconspicuous in mammographic screening [61, 62], particularly since non-desmoplastic ILC produces metastases in axillary lymph nodes more frequently [63].
Due to the limited use of mammography in diagnosing ILC and the risks of obtaining false negative results, other methods such as sonography and MRI are used to assess the tumour dissemination [64]. Magnetic resonance imaging is more useful for diagnosing ILC, in particular multifocal lesions, although this imaging procedure may produce false positive results or overestimate the tumour stage [65, 66]. Recent literature on the role of imaging modalities in the BSBC diagnosis suggests that family history of BC, multifocal BC, or the presence of an ILC should serve as recommendations to perform an MRI with the purpose of eliminating contralateral malignancy [67].
In recent decades, pathohistology has made a huge step forward from the typical traditional documentation to the ability to modify the histochemical and immunohistochemical methods [68], which has shed new light on some pathohistological parameters and consequently led to a new approach when it comes to recognising the criteria for classifying and grading tumours. Tot et al. support that there can be two different types of multifocal invasive carcinoma: one with multiple individual invasive foci which develop from
When compared to unilateral BC, bilateral breast cancer is associated with significantly lower rate of the ductal type, with a higher histologic grade, HER2 positivity and metastases in lymph nodes, without differences relating to age, race, ER and PR status, or pathologic stage of the tumour disease (Figures 3 and 4). Synchronous breast cancer is associated with a higher rate of consistency with the ER, PR, and HER2 statuses (Figure 4) as compared to metachronous bilateral breast cancer, but without any difference regarding the histologic type or grade [70]. A high-grade malignancy and multifocal contralateral breast disease are inversely proportional [46], which is why patients with BSBC often develop slow-growing and low-grade carcinomas [71].
Macroscopic appearance of BSBC from the 36 years old patient in stage IIIA and IIB: (A) mastectomies of both breasts with associated axillary adipose tissue; (B) macroscopic examination of the tumour infiltration zone by transverse serial sections; (C) foci of the largest tumour infiltration zones and their distance from the resection margins. (image was taken from author’s own lab).
Microscopic appearance of BSBC from the 36 years old patient in stage IIIA and IIB. Strong membranous expression of HER2 in invasive and “
Greater size of the tumour masses and a larger number of the lymph nodes affected are also linked with multifocal carcinoma, both in unilateral and bilateral breast cancers [46]. In unilateral BC patients with a multifocal disease, 40% present with tumour foci that have different histopathology [5, 13, 72]. Studies analysing clonal origin of the tumour focus in multifocal BC show that at least 50 to 70% of cases with different foci are genetically related [73, 74, 75], arguing that most multifocal breast carcinomas in patients with unilateral BC originated from the same precursor cell, therefore being an intramammary spread of metastases or an
Some studies revealed that multiple synchronous ipsilateral breast cancer (MSIBC) correlates with the known risk factors, suggesting aggressive biology, such as younger age of patients, higher grade, hormone receptor status, HER2 status, lymphovascular invasion and node involvement [76, 77]. Other factors can also play a part, such as the loss of E-cadherins, causing a loss of cell-to-cell adhesion and contributing to metastatic potential. A recent study demonstrated that MSIBC had a significant downregulation of E-cadherine expression as opposed to unifocal lesions [78].
While desmoplastic stromal response is not associated with higher frequency of metastases in axillary lymph nodes [63], there is a positive correlation between the presence of metastases in axillary lymph nodes and the number of tumour foci [77]. In multiple carcinomas, between 3 and 7% of cases can present with different histologic tumour types and/or histologic tumour grades (intratumor heterogeneity) [19, 77]. Using androgen receptor tests, it was discovered that some DCIS and LCIS develop from different cell clones [79]. If we assume that pure DCIS obtains its phenotypic diversity from different cell clones or from accumulated genetic alterations of a single clone, followed by the progression of the dominant clones to invasive carcinomas, it is possible that these represent different phenotypes in multifocal/multicentric BC with a heterogeneous DCIS component [5].
If the multifocal/multicentricBC in question develops as a consequence of lymphovascular invasion, a higher risk of further metastases is probable. Higher frequencies of lymph node involvement and higher relapse rates in MF/MC BC than in other unifocal BCs support the idea that they can occur as a result of lymphovascular invasion, although a high incidence of metastases in lymph nodes in MF/MC breast carcinomas is also associated with larger tumours [80, 81]. When the tumour (T) stage is determined with the diameter of the largest lesion, multifocality and multicentricity can act as independent predictors of axillary lymph node involvement.
Heterogeneity is a well-known trait of malignancies. It can be observed in individual tumours or among primary BCs and synchronous metastases in lymph nodes. This should be particularly emphasised in the case of MSIBC with different biology and positive lymph nodes in the diagnosis. The status of axillary lymph nodes is the most important individual prognostic factor for BC patients; an accurate histological characterisation of nodal metastases can help clinicians select the most appropriate .treatment [11].
Studies suggest that the tumour foci in MF and MC carcinomas may manifest clonal and behavioural heterogeneity [76], irrespective of the distance between the lesions [7], that ipsilateral foci usually have identical clonality while bilateral breast cancers vary [82], and that 25% of MC carcinomas is polyclonal [83]. The studyof Nortonand co-authors focusing on multifocal ILCs, numerous genetic copies between the foci are consistent to a high degree, suggesting clonal connection between the foci on the one side, while genetic heterogeneity was observed between the foci in patients on the other side [84]. Phenotypic differences are more common in foci (Figure 5) that are homogeneous in terms of tumour type and grade [76]. Actually, all tumour foci are considered to have the same phenotype, although genetic or phenotypic alterations may occur during the progression of the tumour [5].
Phenotypic differences in ER expression (positive nuclear staining on the right side and negative nuclear staining on the left side of tumour focus) may indicate clonal and behavioural heterogeneity of LCIS (LSAB x 200). (image was taken from author’s own lab).
It is not clear whether multifocal/multicentric BCs with different phenotypes are of independent origin due to the fact that phenotypic changes may occur during the tumour progression and dissemination [85]. A few studies, using various molecular methods, showed that bilateral breast cancers are most likely not genetically identical [86, 87]. While the presence of a different phenotype is a clear indicator of separate synchronous primary tumours, over 70% of invasive BCs classified as IDC have identical morphology, meaning that the tumours are clonally related. Using targeted gene sequencing in patients with multiple invasive ductal carcinomas of the same grade and hormone receptor status, it was determined that one third of the cases shows identical mutation profile, one third shares mutations with individual mutations in different foci suggesting identical clonal origin, and one third exhibits no common mutations. Despite common mutations not being present, common changes in copies among the lesions were found, which requires more detailed examinations with methods such as sequencing the entire genome, which would reveal common subclones with a clonal distinction in a larger number of cases [73].
The 21 gene recurrence score assay is a commercially available prognostic and predictive test that measures gene expression levels (16 cancer-related and 5 reference genes) using RT-PCR. The test generates a numeric RS on a scale of 0 to 100 to predict a ten-year risk of a distant metastasis as well as the benefit of chemotherapy in patients with an early-stage ER positive, HER2 negative breast cancer. This RS divides the patients into three risk categories: low (RS < 18), medium (RS 18 to 30), and high (RS ≥ 31). Adjuvant chemotherapy is added to endocrine therapy in patients with high RS; it is estimated that the benefit is low enough to outweigh the consequences in low RS patients [88]. The importance of genome testing for classification by risk category was recognised in the eighth edition of the AJCC Cancer Staging Manual [89], which integrates RC into BC staging. This study examines the consistency of RS in multiple synchronous ipsilateral BCs of similar histology [90].
Tsuda and Hirohashi [91]. investigated the loss of heterozygosity at 16q chromosome in multiple breast cancers and have decided to define multicentric carcinomas as those which are not related through the DCIS component and are not showing satellite nodules and can appear independently. On the other hand, Teixera et al [82], using cytogenetic analyses, concluded that the dominant origin of multiple BCs is intramammary spread from a single primary tumour, despite the fact that some cases develop as unrelated pathogenetic processes. Recently, Brommesson and co-authors compared genome similarities between synchronous multiple invasive breast cancers by means of a comparative microarray-based genome hybridisation and discovered that 5 out of 10 unilateral tumour pairs showed similar genome profiles, suggesting that some synchronous unilateral multiple tumours may have a common origin, while other develop independently [74].
Tumour classification as unifocal, MF, or MC is determined in accordance with the pathology reports. The size of the tumour is obtained from the pathology reports. In patients with MF/MC tumours, T stage is determined using two methods: diameter of the largest tumour focus (Tmax) and by adding up the largest diameters of all tumour foci that are present in the pathological sample (Tsum) [51]. AJCC TNM classification defines tumour size as a measure of the largest individual focus of MSIBC [92]. BSBC should be classified independently to permit separation of cases by histological type. (Figures 3 and 4). Some authors support the hypothesis that MSIBCs can be best described as summarised dimensions which reclassify tumours to higher stages [93].
According to the College of American Pathologists’ recommendations, when multiple synchronous ipsilateral invasive cancers of the same histology are present, the largest invasive carcinoma is used for classification and receptor evaluation [94]. The largest tumour focus is ranked as index or first-rank tumour, and other foci as second to n-rank of additional foci by descending diameter size. The number of lymph nodes affected with macrometastases (larger than 2 mm) or micrometastases (with a diameter between 2 and 0.2 mm) is also reported, as well as the total number of lymph nodes analysed [8]. When the T stage is determined based on the diameter of the largest lesion, multifocality and multicentricity are an independent predictor of axillary lymph node involvement. However, redetermining the T stage based on the sum of diameters of all foci compensates for their difference, leaving the proportion of lymph node metastases between the MC/MF and UF tumours equal [93]. These findings suggest that the increase in the lymph node involvement (or any other relation with unfavourable outcomes) is not a consequence of the common nature of the MC and MF tumours, but rather the result of underestimating the spread of the disease using current staging systems [95].
Some investigationssuggest that the sum of the largest diameters is actually greater than the overall size of the tumour mass and that a better criterion for assessing the tendency of metastasis formation is the total volume and surface area of the tumour [81]. After reclassifying the tumours according to this model, MF/MC tumours still show increased level of lymph node involvement, suggesting that the difference is not the result of the lower stage, but rather the basically more aggressive tumour biology [95].
Breast-conserving therapy is now an established alternative to radical mastectomy. When it comes to tumours with more than one lesion, suggested treatments are changing at the moment. Many authors continue to support breast-conserving surgery for MC/MF tumours [96]. Furthermore, when breast-conserving surgery is proposed as a treatment option for patients who carry BRCA2 mutations and have ER positive receptor status, the surgeons should bear in mind the increased incidence of multifocality and plan the surgical procedure accordingly, ensure that the complete excision is performed in one procedure, as well as minimise the consequences related to repeated surgery due to marginal involvement [50]. Oncoplastic surgery enables a more precise resection of the tumour mass and free resection margin as compared to standard quadrantectomy or lumpectomy [97].
Considering that the effect of partial breast radiation therapy is limited to the index quadrant, it is of paramount importance that patients with low risk of occult microscopic disease in the remaining breast tissue are selected, meaning that local control is not less important than whole-breast radiation [11]. It has been proven that whole-breast radiation after a breast-conserving surgery is more efficient against microscopic foci of BC, which is demonstrated by the fact that leaving it out increases local recurrence rate to 39.2% [98]. Patients under 45 who have BC and were treated with post-lumpectomy tangential field radiotherapy are at higher risk of developing contralateral breast cancer, in particular women with family history of BC [52, 99]. Adjuvant chemotherapy is also associated with reduced incidence (up to 20%) of contralateral breast cancer in women under 50, but not in female patients of and above this age [100]. Moreover, chemotherapy is also related with a lower risk of contralateral breast cancer for a period of up to 10 years after the initial BC diagnosis [101].
It was reported that adjuvant systemic hormone ER positive therapy reduces the incidence of contralateral breast cancer by 39 to 55%, depending on the menopausal status [100], which is why detecting limit values for the ER receptor positivity is important [102]. The analysis of the study results revealed that adjuvant chemotherapy is not effective in patients with RS < 25 and above fifty years of age. However, women under 50 with BC who have RS in the medium range between 16 and 25 can still derive some benefit from chemotherapy [103].
Certain data supports the claim that multifocality/multicentricity is not an independent prognostic factor for BC. Although it is suggested that MF/MC can predict the outcome, it is a fact that the size of the tumour bears greater significance in these patients, rather than the presence of multifocality/multicentricity itself [50]. There is controversy in the literature relating to MF/MC prognosis. The rate of locoregional recurrence has increased in some studies [104], while others found no differences [95]. A 2.75 times higher risk of cancer-related death was reported in patients with MF breast cancer, irrespective of the molecular subtype [19]. In an extensive retrospective study, Weissenbacher et al. reported a lower median global survival (OS) in MF/MC patients as compared to unifocal tumours [104]. One earlier study showed that MC disease is related to higher local recurrence rates, but not MF disease (37 and 17% respectively) [105].
Histologic grade is a well-known prognostic factor for BC, with numerous studies demonstrating a strong connection with survival rates [31, 106]. The size of the tumour has been identified long ago as an independent indicator of lower global survival [107]. Two studies monitored the relation between different methods for T staging and survival. It was discovered that MF and MC tumours larger than 2 cm are accompanied by lower global survival when compared with unifocal carcinoma, but this difference vanishes if the sum of the tumour diameters is used in staging [93]. In patients with MF/MC disease, calculating the sum of diameters of multiple foci does not add any prognostic information apart from the conventionally determined T stage on the basis of the largest diameter of the largest focus [108]. A more intensive systemic chemotherapy could potentially mask an accurate prognosis which is determined by measuring the size of the tumour. The prognosis for patients with MF/MC tumours is similar to that for patients with unifocal tumours. In higher stages, the presence of lymph node positivity and distant metastases provides more significant prognostic information, while the T-stage effect on the prognosis is of little importance [51]. Most studies found increased frequency of metastases in multiple carcinomas when compared to unifocal carcinomas [77, 104], explaining the unfavourable outcome in MSIBC patients [109].
It is difficult to assess the prognosis of bilateral breast cancer, because the outcome may not be unevenly ascribed to either the first or the second carcinoma. The survival of BSBC patients seems to depend on tumours with poorer histological characteristics [110]. Women over the age of 50 with synchronous bilateral carcinoma or women who develop contralateral breast cancer within 5 years are at two- and four-times higher risk, respectively, of dying from cancer than women with unilateral carcinoma. The prognosis for women with bilateral breast cancer that was diagnosed after 10 years from the initial carcinoma is similar to that for women with unilateral BC [22]. There is no significant difference in survival for patients with bilateral BC compared to patients with unilateral tumours. However, synchronous tumours are accompanied by lower survival compared to metachronous tumours [111]. Conversely, global survival is not different in patients with bilateral BC and those with unilateral BC [112, 113].
There is a significantly higher risk of distant metastases being present in bilateral BCs [114]. Bilateral BC is associated with lower grade of the disease, patients show an absence of distant metastases prior to developing contralateral breast cancer; more importantly, no difference in the disease-specific survival (DSS) was noticed among patients with bilateral BC and unilateral BC. Bilateral BC is associated with shorter relapse-free survival (RFS), but similar DSS when compared to unilateral BC. Furthermore, BSBC is associated with favourable RFS, but has similar DSS when compared to BMBC with respect to other clinicopathologic parameters in patients with bilateral BC [70].
The incidence of MF/MC breast cancer varies between 6 and 7%, depending on somewhat arbitrary definition of the MF/MC imaging method sensitivity and biopsy performed by the pathologist. The TNM stage does not include multifocality in the tumour classification [51]. As further progress is made in the pre-operative diagnostics, the number of identified MF and MC tumour is increasing [115]. and consequently better manuals are required for treating them [95], as well as standardised immunohistochemical procedures which would reduce the subjectivity and intralaboratory variations in the interpretation [102].
The National Comprehensive Cancer Network and American Society of Clinical Oncology recommended the use of RS as a manual for adjuvant systemic therapy in patients with ER positive, HER2 negative, lymph node-negative invasive BCs that are ≥0,5 cm in size [116, 117]. In some studies, the entity of focality was determined using histological parameters, while others use clinical and radiographic data only. Most authors do not differentiate between MF and MC tumours, and some almost universally analyse these groups together [95]. Not all patients underwent the same pre-operative radiologic assessment or surgical treatment, which may lead to inaccurate classification of the patients as having unifocal carcinomas when they actually had an unidentified MF or MC condition [76]. Oncological decisions in the systemic adjuvant therapy for BC are based on the histological criterion and immunohistochemical profile of the largest tumour focus, ignoring the smaller synchronous cancers [118, 119].
Histological characteristics of the metastases (type and grade) of axillary lymph nodes in multiple breast cancers correlate with the histological type with an unfavourable prognosis and/or highest histological grade, which may not necessarily correspond to the tumour focus of the largest diameter. For this reason, we accentuate the need to individually report on and assess every single tumour focus in multiple BCs [8]. A new classification may be required for bilateral BCs that would include the size of the tumour in both breasts [120]. TNM staging does not take the tumour biology (hormone receptor status, grade, Ki-67, genetic markers) into account. Additional studies are required about the advantage of using biomarkers to improve the accuracy of staging [51]. Despite the diameter of the largest focus being smaller than the volume of the entire tumour, the sum of diameters of all foci will be bigger than the actual tumour volume, since volume is proportional to one third of the diameter. However, using tumour diameter to assess the size is convenient in the sense of being easier to measure [81]. The use of Tsum in clinical practice may improve the current staging process and change the approach, in particular for patients with early stage of the disease [51].
There are certain limitations of the retrospective view of MF/MC breast cancer and information on macroscopic appearance which is no longer available. The status of ER/PR/HER2 is also not available for individual tumour foci, since in most cases it is not evaluated for all tumour foci, meaning that the morphological nature of the MF/MC condition in these patientscannot be reviewed. Tumour characteristics of the second largest lesion are usually not tested, since most medical centres do not routinely perform immunohistochemical staining of each focus. However, certain findings indicate that the biology of the second tumour may affect the prognosis [121], which is why it is recommended to assess tumour markers in each multiple focus [9]. For instance, if the second lesion was hormone-positive or HER2-positive and the main lesion was triple-negative, the chance to administer endocrine therapy or molecular targeted therapy may be missed. That being said, there is considerable controversy surrounding the assessment of Ki-67 in the literature and, despite the efforts to standardise it, a certain degree of subjectivity still remains. Likewise, its limit value is not generally accepted [8].
Future studies observing molecular profiles of separate tumour foci in the same breast could shed light on this matter and provide clinically relevant information for therapy manual-based decisions. Another limitation is the median monitoring of under 5 years [95] and the bias of multicentric studies [120]. Failure to factor in the heterogeneity of the focus of an additional tumour could prevent the patients from taking advantage of appropriate therapies [31, 89, 122]. Most studies are retrospective or incidental in nature, which neither compare breast-conserving surgery with mastectomy nor analyse locoregional recurrence as a primary goal in MSIBC [123].
The author declares no conflict of interest.
The Edited Volume, also known as the IntechOpen Book, is an IntechOpen pioneered publishing product. Edited Volumes make up the core of our business - and as pioneers and developers of this Open Access book publishing format, we have helped change the way scholars and scientists publish their scientific papers - as scientific chapters.
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\n\nCURRENT PROJECTS
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In many filter applications after the initial transients, the gain matrix K tends to a constant during the steady state, which points to design the filter based on constant gains alone. Such a constant gain Kalman filter (CGKF) can be designed by minimising any suitable cost function. Since there are no covariances in CGKF, only the state equations need to be propagated and updated at a measurement, thus enormously reducing the computational load. Though CGKF results may not be too close to those of RRR, they are acceptable. It accepts extremely simple models and the gains are robust in handling similar scenarios. 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Because LabVIEW includes hundreds of built-in and add-on functions you need that make it easy to create a user-friendly interface. 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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. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,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:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. 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"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. 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Her research interests include microalgal biotechnology with an emphasis on microalgae-based products.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}}]},{type:"book",id:"7953",title:"Bioluminescence",subtitle:"Analytical Applications and Basic Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7953.jpg",slug:"bioluminescence-analytical-applications-and-basic-biology",publishedDate:"September 25th 2019",editedByType:"Edited by",bookSignature:"Hirobumi Suzuki",hash:"3a8efa00b71abea11bf01973dc589979",volumeInSeries:4,fullTitle:"Bioluminescence - Analytical Applications and Basic Biology",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki",profilePictureURL:"https://mts.intechopen.com/storage/users/185746/images/system/185746.png",biography:"Dr. Hirobumi Suzuki received his Ph.D. in 1997 from Tokyo Metropolitan University, Japan, where he studied firefly phylogeny and the evolution of mating systems. He is especially interested in the genetic differentiation pattern and speciation process that correlate to the flashing pattern and mating behavior of some fireflies in Japan. He then worked for Olympus Corporation, a Japanese manufacturer of optics and imaging products, where he was involved in the development of luminescence technology and produced a bioluminescence microscope that is currently being used for gene expression analysis in chronobiology, neurobiology, and developmental biology. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. 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Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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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. 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Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation"},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Biomedical Engineering",id:"7"},selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. 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