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Lillsunde Larsson, G., Kaliff, M., Sorbe, B., Helenius, G. & Karlsson, M. G. (2018). HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma. Papillomavirus research, 6, 63-69
Open this publication in new window or tab >>HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma
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2018 (English)In: Papillomavirus research, ISSN 2405-8521, Vol. 6, p. 63-69Article in journal (Refereed) Published
Abstract [en]

Vulvar carcinoma is the fourth most common gynecological malignancy. Two separate carcinogenic pathways are suggested, where one is associated with the human papillomavirus (HPV) and HPV16 the most common genotype.

The aim of this study was to evaluate HPV-markers in a set of primary tumors, metastases and recurrent lesions of vulvar squamous cell carcinomas (VSCC). Ten HPV16-positive VSCC with metastatic regional lymph nodes, distant lymphoid/hematogenous metastases or local recurrent lesions were investigated for HPV genotype, HPV16 variant, HPV16 viral load, HPV16 integration and HPV16 E2BS3 and 4 methylation.

In all 10 analyzed case series, the same HPV genotype (HPV16), HPV16 variant and level of viral load were detected in all lesions within a patient case. Primary tumors with a high E2/E6 ratio were found to have fewer vulvar recurrences and/or metastases after diagnosis and treatment. Also, a significantly lower viral load was evident in regional lymph nodes compared to primary tumors.

The data presented strengthens the evidence for a clonal HPV-induced pathway for vulvar carcinoma.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Vulvar carcinoma, human papillomavirus, integration, metastases, recurrences, viral load
National Category
Cancer and Oncology Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:oru:diva-69992 (URN)10.1016/j.pvr.2018.10.008 (DOI)000452069800012 ()30391517 (PubMedID)2-s2.0-85056569332 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research Committee

Available from: 2018-11-07 Created: 2018-11-07 Last updated: 2022-02-11Bibliographically approved
Karlsson, J., Dreifaldt, A.-C., Bohr Mordhorst, L. & Sorbe, B. (2017). Differences in outcome for cervical cancer patients treated with or without brachytherapy. Brachytherapy, 16(1), 133-140
Open this publication in new window or tab >>Differences in outcome for cervical cancer patients treated with or without brachytherapy
2017 (English)In: Brachytherapy, ISSN 1538-4721, E-ISSN 1873-1449, Vol. 16, no 1, p. 133-140Article in journal (Refereed) Published
Abstract [en]

Purpose: To compare the clinical outcome of cervical cancer patients treated with primary radiotherapy with and without the addition of brachytherapy.

Methods and Materials: In all, 220 patients with cervical cancer stage I-IV treated between 1993 and 2009 were included. Three or five 6.0 Gy fractions of brachytherapy were given in addition to the external beam radiotherapy to 134 patients, whereas 86 patients received external beam radiotherapy alone (EBRTA). In the EBRTA group, the patients received external boost instead of brachytherapy with a total dose to the tumor of 64-72 Gy.

Results: The 5-year overall survival and cancer-specific survival rates of the complete series were 42.5% and 55.5%, respectively. The rates of primary complete remission, 5-year cancer-specific survival, and recurrence were 92.5%, 68.5%, and 31.3% for the brachytherapy group vs. 73.3%, 35.4%, and 37.2% for the EBRTA group. The survival (all types) of the patients receiving brachytherapy was significantly (p < 0.0001) better than for the patients treated with external boost, but the difference was most pronounced in FIGO stage II tumors. Higher FIGO stage, nonsquamous cell carcinoma histology, treatment with EBRTA, and lower total equal 2-Gy (EQD2) external dose were significantly associated with poorer survival, lower rate of remission, and higher recurrence rate in multivariate models.

Conclusions: Primary tumor remission rate, recurrence rate, and all types of survival rates were improved in the brachytherapy group. Brachytherapy is important to achieve sufficient doses to the periphery and central part of the tumor and should always be considered in treatment of cervical carcinomas.

Place, publisher, year, edition, pages
Philadelphia, USA: Elsevier, 2017
Keywords
Cervical cancer, radiotherapy, external beam radiotherapy, brachytherapy, prognosis
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:oru:diva-53486 (URN)10.1016/j.brachy.2016.09.011 (DOI)000392793900013 ()27836496 (PubMedID)2-s2.0-85009895081 (Scopus ID)
Available from: 2016-11-14 Created: 2016-11-14 Last updated: 2018-07-27Bibliographically approved
Qvick, A., Sorbe, B., Helenius, G., Karlsson, M. G. & Lillsunde Larsson, G. (2017). Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?. Medical Oncology, 34(3), Article ID 36.
Open this publication in new window or tab >>Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?
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2017 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 34, no 3, article id 36Article in journal (Refereed) Published
Abstract [en]

Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in susceptibility to cancer induced by this virus, but with contradicting results. In this study, we have investigated the prognostic value of the codon 72 polymorphism by real-time PCR (qPCR) in two cohorts of vaginal (n = 66) and vulvar (n = 123) carcinomas. In vaginal carcinoma, arginine homozygous patients were significantly associated with a higher primary cure rate (p = 0.023) but also associated with a higher recurrence rate (p = 0.073), significant at distant locations (p = 0.009). No significant differences were found in overall survival rate (p = 0.499) or cancer-specific survival rate (p = 0.222). A higher frequency of arginine homozygosity was noted in HPV-positive tumors (p = 0.190) in comparison with HPV-negative tumors. In vulvar carcinoma, the genotype homozygous for arginine was significantly associated with a larger tumor size at diagnosis in the entire cohort (p = 0.015) and a lower cancer-specific survival rate (p = 0.024) compared with heterozygous (arginine/proline) in HPV-negative tumors. Our results indicate that the relation between HPV and the p53 codon 72 polymorphism is complex and the significance and mechanisms responsible for this relationship need to be further elucidated.

Place, publisher, year, edition, pages
Heidelberg, Germany: Springer, 2017
Keywords
P53, Codon 72, Polymorphism, Vagina, Vulva, Carcinoma, HPV
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-55410 (URN)10.1007/s12032-017-0893-6 (DOI)000394277700006 ()28144815 (PubMedID)2-s2.0-85011707902 (Scopus ID)
Note

Funding Agencies:

Region Örebro County through ALF

Örebro County Council Research Committee

Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2022-09-21Bibliographically approved
Farkas, S. A., Sorbe, B. G. & Nilsson, T. K. (2017). Epigenetic changes as prognostic predictors in endometrial carcinomas. Epigenetics, 12(1), 19-26
Open this publication in new window or tab >>Epigenetic changes as prognostic predictors in endometrial carcinomas
2017 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 12, no 1, p. 19-26Article in journal (Refereed) Published
Abstract [en]

Endometrial carcinoma is one of the most frequent gynecological malignancies of the female. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide, and, therefore, the aim of this study was to identify new potential DNA methylation markers for the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n = 31 and n = 39, respectively). We identified specific DNA methylation signature in high-risk endometrial tumors, and potential molecular biomarker genes (TBX2, CHST11, and NID2) associated with unfavorable clinical predictive and prognostic factors.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
DNA methylation; endometrial cancer; FIGO grade; prognosis
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Genetics
Identifiers
urn:nbn:se:oru:diva-53666 (URN)10.1080/15592294.2016.1252891 (DOI)000394449200003 ()27874289 (PubMedID)2-s2.0-85007417723 (Scopus ID)
Funder
Swedish Research Council
Note

Funding Agencies:

Lions Cancer Foundation, Uppsala

Nyckelfonden, Örebro

Cancer-forskningsfonden, Umeå

Available from: 2016-11-28 Created: 2016-11-28 Last updated: 2020-12-01Bibliographically approved
Ranhem, C., Lillsunde-Larsson, G., Hedman, H., Lindquist, D., Karlsson, M. G., Hellström, A.-C., . . . Andersson, S. (2017). Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma. PLOS ONE, 12(8), Article ID e0183816.
Open this publication in new window or tab >>Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma
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2017 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 8, article id e0183816Article in journal (Refereed) Published
Abstract [en]

Background: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients.

Methods: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses.

Results: The majority of PVC patients (72%) had > 50% LRIG1-and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival.

Conclusion: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-61041 (URN)10.1371/journal.pone.0183816 (DOI)000408370700059 ()28841699 (PubMedID)2-s2.0-85029173894 (Scopus ID)
Funder
Swedish Cancer Society, 070623 CAN 2007/1044 11 0544 CAN 2011/471Swedish Research Council, 521-2008-2899
Note

Funding Agencies:

Karolinska Institutet Cancer Strategic Grants  5888/05-722

Stockholm County Council  20130097 

Region Örebro County  OLL-526041 

Lion's Cancer Research Foundation  

University of Umeå  

Gustaf V Jubilee Fund  154022 

Region Västmanland - Uppsala University Centre for Clinical Research Hospital of Västmanland Västerås 

Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2021-06-14Bibliographically approved
Bohr Mordhorst, L., Ahlin, C. & Sorbe, B. (2016). Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy. Oncotarget, 7(39), 63042-63053
Open this publication in new window or tab >>Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy
2016 (English)In: Oncotarget, E-ISSN 1949-2553, Vol. 7, no 39, p. 63042-63053Article in journal (Refereed) Published
Abstract [en]

Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.

Place, publisher, year, edition, pages
Orchard Park, USA: Impact Journals LLC, 2016
Keywords
APC, Wnt signaling pathway, cervical carcinoma, β-catenin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-56900 (URN)10.18632/oncotarget.11642 (DOI)000387167800018 ()27577083 (PubMedID)2-s2.0-84994045434 (Scopus ID)
Available from: 2017-03-29 Created: 2017-03-29 Last updated: 2024-01-17Bibliographically approved
Graflund, M., Sorbe, B., Sigurdardóttir, S. & Karlsson, M. G. (2014). HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas. International Journal of Gynecological Cancer, 14(5), 896-902
Open this publication in new window or tab >>HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas
2014 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 14, no 5, p. 896-902Article in journal (Refereed) Published
Abstract [en]

The present study was designed to analyze the relationship of human papillomavirus (HPV)-DNA, microvessel density, and their impact on clinical outcome in early cervical carcinoma. HPV-DNA was evaluated in 171 cases of cervical carcinoma treated from 1965 to 1990. In 110 cases, the analyses could be performed. A polymerase chain reaction technique was used on paraffin-embedded specimens obtained before the start of therapy. HPV-DNA of any type was detected in 78% (86/110) of all evaluable tumors. HPV16 was the predominant type and was detected in 56% (62/110), HPV18 in 8% (9/110), and HPV35 in 21% (23/110). Patients with tumors containing HPV16 or HPV18 were significantly (P = 0.011) younger than patients with tumors not containing either of these two subtypes. Vascular space invasion and lymph node metastases were observed more frequently in tumors expressing HPV16 and HPV18 (P = 0.002, P = 0.047) than in tumors negative for these HPV strains. Tumors containing HPV16 and HPV18 were significantly (P = 0.012) larger and more frequently (P = 0.005) associated with higher FIGO stages. The cancer-specific survival rate was lower for patients with HPV16- and HPV18-positive tumors, but the difference was not statistically significant. The microvessel density was a non-significant prognostic factor. The overall 5-year survival rate of the complete series was 91%. It was concluded that HPV-DNA was a prognostic factor in early-stage cervical cancer and was associated with the age of the patient, vascular space invasion, lymph node metastases, tumor size, and FIGO stage.

Place, publisher, year, edition, pages
Malden, USA: Blackwell Publishing, 2014
Keywords
Cervical cancer, HPV, prognostic factors, vascular space invasion
National Category
Cancer and Oncology Clinical Laboratory Medicine
Identifiers
urn:nbn:se:oru:diva-49506 (URN)10.1111/j.1048-891X.2004.014527.x (DOI)000223822000024 ()15361201 (PubMedID)2-s2.0-4544356428 (Scopus ID)
Available from: 2016-03-27 Created: 2016-03-25 Last updated: 2017-11-30Bibliographically approved
Ekwall, E., Ternestedt, B.-M., Sorbe, B. & Sunvisson, H. (2014). Lived experiences of women with recurring ovarian cancer. European Journal of Oncology Nursing, 18(1), 104-109
Open this publication in new window or tab >>Lived experiences of women with recurring ovarian cancer
2014 (English)In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 18, no 1, p. 104-109Article in journal (Refereed) Published
Abstract [en]

Background: Women with recurring ovarian cancer are living longer, due to advances in treatment options. They are now often outpatients, experiencing rapid encounters on treatment days. Whether this shift in care meets women’s needs has been scarcely explored scientifically.

Purpose of the study: This study aimed to illuminate the phenomenon of living with recurring ovarian cancer as experienced by women in that condition.

Methods and sample: A descriptive phenomenological method was used. Eight open-ended interviews with four women were performed approximately three and five years after the first recurrence of ovarian cancer. During these years the women had repeated clinically and radiologically verified recurrence requiring chemotherapy.

Key results:The phenomenon of living with recurring ovarian cancer meant that the women felt forced to pay attention to the failing body in order to avoid a potential breakdown. The growing limitation of their intermittent strength meant that strength had to be captured and protected. Sharing their lives with others was difficult, due to the different living conditions. The women found no space to mediate their experiences, either in close relationships or with health care professionals. But, the circumstances they lived under also generated a gratitude for the unexpected extra time.

Conclusions: The findings revealed that the four women were grateful to live a while longer, but needed to share their state of being. The findings are indeed directed to health care professionals, who need to provide a more patient-centred care to meet the women’s needs.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Phenomenology, Recurring ovarian cancer, Outpatient chemotherapy
National Category
Cancer and Oncology Nursing
Research subject
Nursing Science; Oncology
Identifiers
urn:nbn:se:oru:diva-31895 (URN)10.1016/j.ejon.2013.08.002 (DOI)000331859800017 ()24054734 (PubMedID)2-s2.0-84893669145 (Scopus ID)
Available from: 2013-10-11 Created: 2013-10-11 Last updated: 2021-04-12Bibliographically approved
Lillsunde-Larsson, G., Helenius, G., Sorbe, B. & Karlsson, M. G. (2014). Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas. PLOS ONE, 9(11), Article ID e112839.
Open this publication in new window or tab >>Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas
2014 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 11, article id e112839Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.

Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.

Results: Vaginal tumors were found to have a higher viral load (p=0.024) compared to vulvar tumors but a high copy number (> median value, 15 000) as well as high methylation (> 50%) was significantly (p=0.010 and p=0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150 000 copies not highly methylated (n=25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n=6, 11.1%); (3) tumors with viral DNA fully integrated (n=11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium-or unmethylated (< 50%) and having a high viral load (> total mean value 150 000; n=12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.

Conclusion: HPV16-related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-related parameters were found to be of clinical importance in the vulvar series only.

Place, publisher, year, edition, pages
Public Library Science, 2014
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-42542 (URN)10.1371/journal.pone.0112839 (DOI)000347709300111 ()2-s2.0-84911948854 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research Committee OLL-324811 OLL-259341

Available from: 2015-02-09 Created: 2015-02-09 Last updated: 2021-06-14Bibliographically approved
Isaksson, H. S., Sorbe, B. & Nilsson, T. K. (2014). Whole genome expression profiling of blood cells in ovarian cancer patients: prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14 genes. Oncotarget, 5(12), 4040-4049
Open this publication in new window or tab >>Whole genome expression profiling of blood cells in ovarian cancer patients: prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14 genes
2014 (English)In: Oncotarget, E-ISSN 1949-2553, Vol. 5, no 12, p. 4040-4049Article in journal (Refereed) Published
Abstract [en]

Ovarian cancer patients with different tumor stages and cell differentiation might be distinguished from each other by gene expression profiles in whole blood cell mRNA by the Affymetrix Human Gene 1.0 ST Array. We also examined if there is any association with other clinical variables, response to therapy, and residual tumor burden after surgery. Patients were divided into two groups, one with poor prognosis, advanced stage and poorly differentiated tumors (n = 22), and one group with good prognosis, early stage and well-to medium differentiated tumors (n = 11). Six genes were found to be differentially expressed: the PDIA3, LYAR, NOP14, NCALD and MTSS1 genes were down-regulated and the CYP1B1 gene expression was up-regulated in the poor prognosis group, all with p value <0.05, adjusted for mass comparison. In survival analyses, CYP1B1, MTSS1, NCALD and NOP14 remained significantly different (p<0.05). Patient groups did not differ in any transcript related to acute phase or immune responses. This minimal gene expression signature of prognostic ovarian cancer-related genes opens up an avenue for more practicable monitoring of ovarian cancer patients by simple peripheral blood tests, which may evolve into a tool to guide selection of curative and postoperative supportive therapies.

Place, publisher, year, edition, pages
Impact press, 2014
Keywords
ovarian cancer, whole genome profiling, prognosis, mRNA, NCALD, MTSS1, PDA3, CYP1B1, NOP14, LYAR
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-36179 (URN)10.18632/oncotarget.1938 (DOI)000339055200007 ()24961659 (PubMedID)2-s2.0-84905090787 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro County Council

Foundation for Gynecological Oncology, Örebro

Lions' Cancer Research Foundation, Uppsala-Örebro

Available from: 2014-09-02 Created: 2014-08-28 Last updated: 2024-01-17Bibliographically approved
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