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Volume 50(6); November 2016
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Reviews
Pathogenesis of Focal Segmental Glomerulosclerosis
Beom Jin Lim, Jae Won Yang, Woo Sung Do, Agnes B. Fogo
J Pathol Transl Med. 2016;50(6):405-410.   Published online October 16, 2016
DOI: https://doi.org/10.4132/jptm.2016.09.21
  • 14,457 View
  • 882 Download
  • 52 Web of Science
  • 48 Crossref
AbstractAbstract PDF
Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

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Article image
Immunohistochemistry for Pathologists: Protocols, Pitfalls, and Tips
So-Woon Kim, Jin Roh, Chan-Sik Park
J Pathol Transl Med. 2016;50(6):411-418.   Published online October 13, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.08
  • 50,873 View
  • 1,977 Download
  • 271 Web of Science
  • 261 Crossref
AbstractAbstract PDF
Immunohistochemistry (IHC) is an important auxiliary method for pathologists in routine diagnostic work as well as in basic and clinical research including exploration of biomarkers, as IHC allows confirmation of target molecule expressions in the context of microenvironment. Although there has been a considerable progress in automation and standardization of IHC, there are still many things to be considered in proper optimization and appropriate interpretation. In this review, we aim to provide possible pitfalls and useful tips for practicing pathologists and residents in pathology training. First, general procedure of IHC is summarized, followed by pitfalls and tips in each step and a summary of troubleshooting. Second, ways to an accurate interpretation of IHC are discussed, with introduction to general quantification and analysis methods. This review is not intended to provide complete information on IHC, but to be used as a basic reference for practice and publication.

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Original Articles
The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence
Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong
J Pathol Transl Med. 2016;50(6):419-425.   Published online October 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.30
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AbstractAbstract PDF
Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

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Article image
Morphological and Functional Changes in the Thyroid Follicles of the Aged Murine and Humans
Junguee Lee, Shinae Yi, Yea Eun Kang, Hyeon-Woo Kim, Kyong Hye Joung, Hae Joung Sul, Koon Soon Kim, Minho Shong
J Pathol Transl Med. 2016;50(6):426-435.   Published online October 14, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.19
  • 13,935 View
  • 418 Download
  • 35 Web of Science
  • 38 Crossref
AbstractAbstract PDF
Background
Although both thyroid histology and serum concentrations of hormones are known to change with age, only a few reports exist on the relationship between the age-related structural and functional changes of the thyroid follicles in both mice and humans. Our objectives were to investigate age-related histological changes of the thyroid follicles and to determine whether these morphological changes were associated with the functional activity of the follicles.
Methods
The thyroid glands of mice at 18 weeks and at 6, 15, and 30 months of age were histologically examined, and the serum levels of thyroid hormones were measured in 11-week-old and 20-month-old mice. Samples of human thyroid tissue from 10 women over 70 years old and 10 women between 30 and 50 years of age were analyzed in conjunction with serum thyroid hormone level.
Results
The histological and functional changes observed in the thyroid follicles of aged mice and women were as follows: variable sizing and enlargement of the follicles; increased irregularity of follicles; Sanderson’s polsters in the wall of large follicles; a large thyroglobulin (Tg) globule or numerous small fragmented Tg globules in follicular lumens; oncocytic change in follicular cells; and markedly dilated follicles empty of colloid. Serum T3 levels in 20-month-old mice and humans were unremarkable.
Conclusions
Thyroid follicles of aged mice and women show characteristic morphological changes, such as cystic atrophy, empty colloid, and Tg globules.

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Article image
Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma
Gilhyang Kim, Yul Ri Chung, Bohyun Kim, Boram Song, Kyung Chul Moon
J Pathol Transl Med. 2016;50(6):436-441.   Published online October 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.12
  • 8,978 View
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AbstractAbstract PDF
Background
Human epidermal growth factor receptor 2 (HER2) is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC) has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA) criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and compare their prognostic significance in UUTUC.
Methods
HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC) using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+) and high (2+, 3+) groups.
Results
Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001). The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004), but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161) in cancer-specific survival.
Conclusions
HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

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    Hiroshi Fukushima, Baris Turkbey, Peter A. Pinto, Aki Furusawa, Peter L. Choyke, Hisataka Kobayashi
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  • Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication
    Manuela Costantini, Carla Azzurra Amoreo, Liborio Torregrossa, Greta Alì, Enrico Munari, Carmen Jeronimo, Rui Henrique, Sara Petronilho, Umberto Capitanio, Roberta Lucianò, Nazareno Suardi, Maria Teresa Landi, Umberto Anceschi, Aldo Brassetti, Vito Michel
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Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer
Jinhyuk Choi, Chungyeul Kim, Hye Seung Lee, Yoo Jin Choi, Ha Yeon Kim, Jinhwan Lee, Hyeyoon Chang, Aeree Kim
J Pathol Transl Med. 2016;50(6):442-450.   Published online October 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.08
  • 12,592 View
  • 223 Download
  • 15 Web of Science
  • 16 Crossref
AbstractAbstract PDF
Background
Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast.
Methods
Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers.
Results
The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I2 = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity.
Conclusions
These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.

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    G. M. Volgareva
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    Chia-Hsin Liu, Chi-You Liao, Ming-Hsin Yeh, James Cheng-Chung Wei
    Healthcare.2022; 10(11): 2235.     CrossRef
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    Erik Kudela, Eva Kudelova, Erik Kozubík, Tomas Rokos, Terezia Pribulova, Veronika Holubekova, Kamil Biringer
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    Nabila El-Sheikh, Nahla O Mousa, Amany M Tawfeik, Alaa M Saleh, Iman Elshikh, Mohamed Deyab, Faten Ragheb, Manar M Moneer, Ahmed Kawashti, Ahmed Osman, Mohamed Elrefaei
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    Hua Guo, Juan P. Idrovo, Jin Cao, Sudarshana Roychoudhury, Pooja Navale, Louis J. Auguste, Tawfiqul Bhuiya, Silvat Sheikh-Fayyaz
    Clinical Breast Cancer.2021; 21(6): e638.     CrossRef
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    Rancés Blanco, Diego Carrillo-Beltrán, Juan P. Muñoz, Alejandro H. Corvalán, Gloria M. Calaf, Francisco Aguayo
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    Geilson Gomes de Oliveira, Ana Katherine Gonçalves, José Eleutério, Luiz Gonzaga Porto Pinheiro
    Breast Disease.2021; 41(1): 123.     CrossRef
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    Fatih Levent Balci, Cihan Uras, Sheldon Marc Feldman
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    Erik Kudela, Marcela Nachajova, Jan Danko
    The Breast Journal.2019; 25(5): 1053.     CrossRef
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    Maryam Kazemi Aghdam, Seyed Alireza Nadji, Azadeh Alvandimanesh, Maliheh Khoddami, Yassaman Khademi
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Does Polymerase Chain Reaction of Tissue Specimens Aid in the Diagnosis of Tuberculosis?
Yoo Jin Lee, Seojin Kim, Youngjin Kang, Jiyoon Jung, Eunjung Lee, Joo-Young Kim, Jeong Hyeon Lee, Youngseok Lee, Yang-seok Chae, Chul Hwan Kim
J Pathol Transl Med. 2016;50(6):451-458.   Published online October 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.04
  • 10,856 View
  • 241 Download
  • 6 Web of Science
  • 9 Crossref
AbstractAbstract PDF
Background
Mycobacterial culture is the gold standard test for diagnosing tuberculosis (TB), but it is time-consuming. Polymerase chain reaction (PCR) is a highly sensitive and specific method that can reduce the time required for diagnosis. The diagnostic efficacy of PCR differs, so this study determined the actual sensitivity of TB-PCR in tissue specimens.
Methods
We retrospectively reviewed 574 cases. The results of the nested PCR of the IS6110 gene, mycobacterial culture, TB-specific antigen-induced interferon-γ release assay (IGRA), acid-fast bacilli (AFB) staining, and histological findings were evaluated.
Results
The positivity rates were 17.6% for PCR, 3.3% for the AFB stain, 22.2% for mycobacterial culture, and 55.4% for IGRA. PCR had a low sensitivity (51.1%) and a high specificity (86.3%) based on the culture results of other studies. The sensitivity was higher (65.5%) in cases with necrotizing granuloma but showed the highest sensitivity (66.7%) in those with necrosis only. The concordance rate between the methods indicated that PCR was the best method compared to mycobacterial culture, and the concordance rate increased for the methods using positive result for PCR or histologic features.
Conclusions
PCR of tissue specimens is a good alternative to detect tuberculosis, but it may not be as sensitive as previously suggested. Its reliability may also be influenced by some histological features. Our data showed a higher sensitivity when specimens contained necrosis, which indicated that only specimens with necrosis should be used for PCR to detect tuberculosis.

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CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance
Kyung-Ju Kim, Hee Jung Kwon, Min Chong Kim, Young Kyung Bae
J Pathol Transl Med. 2016;50(6):459-468.   Published online October 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.10.02
  • 8,952 View
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AbstractAbstract PDF
Background
CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression.
Methods
The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression.
Results
High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan- Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054).
Conclusions
High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs.

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Case Studies
Article image
A Case of Malignant PEComa of the Uterus Associated with Intramural Leiomyoma and Endometrial Carcinoma
Yoo Jin Choi, Jin Hwa Hong, Aeree Kim, Hankyeom Kim, Hyeyoon Chang
J Pathol Transl Med. 2016;50(6):469-473.   Published online July 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.04.20
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  • 201 Download
  • 8 Web of Science
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AbstractAbstract PDF
Perivascular epithelioid cell tumors (PEComas) refers to a family of mesenchymal neoplasms composed of angiomyolipomas, clear cell “sugar” tumors of the lung, and lymphangioleiomyomatoses. These tumors have a distinctive and common component of perivascular epithelioid cells that show an association with blood vessel walls and immunohistochemically display myomelanocytic differentiation. The unique neoplasms have been shown to have an expanded range through a variety of case reports, including visceral, intra-abdominal, soft tissue, and bone tumors. The retroperitoneum, abdominopelvic region, and uterus have been reported to be the most common sites. Most PEComas follow a benign course. However, reports of malignant PEComas are increasing. Many papers have described uterine PEComas, but to our knowledge, there have not yet been any reports of a malignant PEComa arising concomitant with another epithelial tumor and mesenchymal tumor. We report herein the case of a 67-year-old woman who experienced a malignant uterine PEComa infiltrating a preexisting intramural leiomyoma with synchronous well differentiated endometrial carcinoma and multiple liver and lung metastases.

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  • Metastasis of Clear Cell Renal Cell Carcinoma to Uterine Leiomyoma: First Case Report and Review of Literature
    Sarvenaz Karamooz, Paula D. Binsol, Jaya Ruth Asirvatham, Anjali Pargaonkar
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    Weiwei Shan, Yue Shi, Qin Zhu, Bingyi Yang, Liying Xie, Bing Li, Chengcheng Ning, Qiaoying Lv, Yali Cheng, Bingying Xie, Mingzhu Bai, Yuhui Xu, Xiaojun Chen, Xuezhen Luo
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    Jennifer A. Bennett, Ana C. Braga, Andre Pinto, Koen Van de Vijver, Kristine Cornejo, Anna Pesci, Lei Zhang, Vicente Morales-Oyarvide, Takako Kiyokawa, Gian Franco Zannoni, Joseph Carlson, Tomas Slavik, Carmen Tornos, Cristina R. Antonescu, Esther Oliva
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A Case of Giant Colonic Muco-submucosal Elongated Polyps Associated with Intussusception
Joo Heon Kim, Seung Yun Lee, Je Ho Jang, Hyun Young Han, Dong Wook Kang
J Pathol Transl Med. 2016;50(6):474-478.   Published online May 23, 2016
DOI: https://doi.org/10.4132/jptm.2016.04.27
  • 9,543 View
  • 128 Download
  • 5 Web of Science
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AbstractAbstract PDF
Colonic muco-submucosal elongated polyp (CMSEP), a newly categorized non-neoplastic colorectal polyp, is a pedunculated and elongated polyp composed of normal mucosal and submucosal layers without any proper muscle layer. We herein report a giant variant of CMSEP associated with intussusception in the rectosigmoid colon, with a review of the literature. A 48-year-old woman underwent a laparoscopic low anterior resection due to multiple large submucosal polypoid masses associated with intussusception. Grossly, the colonic masses were multiple pedunculated polyps with a long stalk and branches ranging in size from a few millimeters to 14.0 cm in length. Microscopically, there was no evidence of hyperplasia, atypia, or active inflammation in the mucosa. The submucosal layers were composed of edematous and fibrotic stroma with fat tissue, dilated vessels, and lymphoid follicles.

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    Atsuki Taniguchi, Izuru Endo, Takeyoshi Nishiyama, Nobuyuki Watanabe, Osamu Yoshida, Hiroaki Asano, Masatoshi Kubo, Tetsunobu Udaka
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Brief Case Reports
Primary Follicular Lymphoma of the Duodenum: A Case Report
Jin Roh, Jooryung Huh, Chan-Sik Park
J Pathol Transl Med. 2016;50(6):479-481.   Published online May 9, 2016
DOI: https://doi.org/10.4132/jptm.2016.01.27
  • 9,718 View
  • 138 Download
  • 1 Web of Science
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PDF

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Goblet Cell Carcinoid of the Rectum in a Patient with Neurofibromatosis Type 1
Youngjin Kang, Jung-Woo Choi, Younghye Kim, Hwa Eun Oh, Ju-Han Lee, Young-Sik Kim
J Pathol Transl Med. 2016;50(6):482-485.   Published online May 29, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.27
  • 9,398 View
  • 137 Download
  • 6 Web of Science
  • 5 Crossref
PDF

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