Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000538
F. Baumann, O. Bieck, M. Strunk, N. Reimer, E. Zopf, W. Bloch, S. Han
{"title":"Effects of a 6-week Hike on Physical Activity Levels, Psycholog ical Wellbeing and Quality of Life in Breast Cancer Survivors","authors":"F. Baumann, O. Bieck, M. Strunk, N. Reimer, E. Zopf, W. Bloch, S. Han","doi":"10.4172/1948-5956.1000538","DOIUrl":"https://doi.org/10.4172/1948-5956.1000538","url":null,"abstract":"","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"21 1","pages":"156-161"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73051598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000535
A. Mekuria, Abraham Degaga Abdi, K. M. Mishore
MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNAs that negatively regulate gene expression by several mechanisms. Deregulation in expression of miRNAs has been reported in the pathogenesis of cancer. Accordingly, studies identified down regulation in the expression of miRNAs having tumor suppressor role and up-regulation in the expression of oncogenic miRNAs in different types of cancer. In response to these observations currently there are ongoing efforts to develop safe and effective miRNA-based therapeutics in the hope of fighting against cancer. This paper aimed at reviewing the role of miRNAs in tumorigenesis, and strategies for therapeutic targeting of miRNAs in cancer.
{"title":"MicroRNAs as a Potential Target for Cancer Therapy","authors":"A. Mekuria, Abraham Degaga Abdi, K. M. Mishore","doi":"10.4172/1948-5956.1000535","DOIUrl":"https://doi.org/10.4172/1948-5956.1000535","url":null,"abstract":"MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNAs that negatively regulate gene expression by several mechanisms. Deregulation in expression of miRNAs has been reported in the pathogenesis of cancer. Accordingly, studies identified down regulation in the expression of miRNAs having tumor suppressor role and up-regulation in the expression of oncogenic miRNAs in different types of cancer. In response to these observations currently there are ongoing efforts to develop safe and effective miRNA-based therapeutics in the hope of fighting against cancer. This paper aimed at reviewing the role of miRNAs in tumorigenesis, and strategies for therapeutic targeting of miRNAs in cancer.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"1 1","pages":"152-161"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74464101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000537
I. Lete, M. Aguiar, Arguine Andonegui, Nagore Zeberio, M. Cuadra, J. Mendizabal, J. Gorostiaga
Introduction: The effects of early detection on treatment need to be evaluated. The objective of this study was to assess the impact of the Basque breast cancer early detection program (BCEDP) on breast cancer surgery in our hospital. Materials and Methods: A retrospective study was conducted of women who underwent surgery for breast cancer between 1 January 2015 and 31 December 2016. Participants were classified into: Group A, those referred from the screening program after routine mammography; or group B, those referred from primary care or other gynecological clinics within our health region. Results: In the study period, 630 women were diagnosed with and treated for breast cancer. Their mean age was 60.2 years (standard deviation 5.4). Out of these, 220 (35%) referred from the BCEDP formed group A, the other 410 women (65%) forming group B. Invasive cancer was diagnosed in 185 women in group A (84%) and in 370 (90.2%) in group B (p=0.02). Regarding treatment, mastectomies were carried out in 47 women (21.4%) in Group A and 225 (54.9%) in group B (p<0.001); axillary lymphadenectomies were performed in 31 women (14.1%) in Group A and 83 (20.2%) in Group B, (p=0.02); and adjuvant chemotherapy was given in 66 women (30%) in Group A and 148 (36.1%) in Group B (p<0.001). Conclusion: In our setting, breast cancer patients referred through the BCEDP have earlier stage cancer, can be expected to benefit from less radical surgery, have lower proportion of axillary lymph node involvement and require less adjuvant chemotherapy.
{"title":"Impact of a Screening Program in the Diagnosis, Surgical Treatm ent and Management of Breast Cancer","authors":"I. Lete, M. Aguiar, Arguine Andonegui, Nagore Zeberio, M. Cuadra, J. Mendizabal, J. Gorostiaga","doi":"10.4172/1948-5956.1000537","DOIUrl":"https://doi.org/10.4172/1948-5956.1000537","url":null,"abstract":"Introduction: The effects of early detection on treatment need to be evaluated. The objective of this study was to assess the impact of the Basque breast cancer early detection program (BCEDP) on breast cancer surgery in our hospital. Materials and Methods: A retrospective study was conducted of women who underwent surgery for breast cancer between 1 January 2015 and 31 December 2016. Participants were classified into: Group A, those referred from the screening program after routine mammography; or group B, those referred from primary care or other gynecological clinics within our health region. Results: In the study period, 630 women were diagnosed with and treated for breast cancer. Their mean age was 60.2 years (standard deviation 5.4). Out of these, 220 (35%) referred from the BCEDP formed group A, the other 410 women (65%) forming group B. Invasive cancer was diagnosed in 185 women in group A (84%) and in 370 (90.2%) in group B (p=0.02). Regarding treatment, mastectomies were carried out in 47 women (21.4%) in Group A and 225 (54.9%) in group B (p<0.001); axillary lymphadenectomies were performed in 31 women (14.1%) in Group A and 83 (20.2%) in Group B, (p=0.02); and adjuvant chemotherapy was given in 66 women (30%) in Group A and 148 (36.1%) in Group B (p<0.001). Conclusion: In our setting, breast cancer patients referred through the BCEDP have earlier stage cancer, can be expected to benefit from less radical surgery, have lower proportion of axillary lymph node involvement and require less adjuvant chemotherapy.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"23 1","pages":"152-155"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84556715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000542
Dieuwke Luijten, M. Vreeswijk, Ingrid Boere, J. Kroep
The use of Poly ADP-ribose polymerase (PARP) inhibitors has recently been expanded. PARP inhibitors were initially only registered for patients with BRCA mutated high-grade serous epithelial ovarian, including primary peritoneal and fallopian tube cancer (EOC). Currently, PARP inhibitors are also registered for patients with recurrent EOC who are in a complete or partial response to platinum-based chemotherapy, irrespective of their BRCA status. Current findings indicate that patients with BRCA mutations and/or a BRCA like tumour defined by a BRCAness profile, benefit the most. Combination therapies of PARP inhibitors with immunotherapy and/or angiogenesis inhibitors are fast evolving and studied from first line therapy to recurrent disease. This review summarizes the current findings, obstacles and future developments of PARP inhibitor with a focus on female cancer.
{"title":"Current and Future Developments of PARP Inhibitors in the Treat ment of Breast and Ovarian Cancer","authors":"Dieuwke Luijten, M. Vreeswijk, Ingrid Boere, J. Kroep","doi":"10.4172/1948-5956.1000542","DOIUrl":"https://doi.org/10.4172/1948-5956.1000542","url":null,"abstract":"The use of Poly ADP-ribose polymerase (PARP) inhibitors has recently been expanded. PARP inhibitors were initially only registered for patients with BRCA mutated high-grade serous epithelial ovarian, including primary peritoneal and fallopian tube cancer (EOC). Currently, PARP inhibitors are also registered for patients with recurrent EOC who are in a complete or partial response to platinum-based chemotherapy, irrespective of their BRCA status. Current findings indicate that patients with BRCA mutations and/or a BRCA like tumour defined by a BRCAness profile, benefit the most. Combination therapies of PARP inhibitors with immunotherapy and/or angiogenesis inhibitors are fast evolving and studied from first line therapy to recurrent disease. This review summarizes the current findings, obstacles and future developments of PARP inhibitor with a focus on female cancer.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"11 1 1","pages":"178-189"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79672918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000557
Kanakaiah Thota, K. Prasad, M. Rao
Objectives: The expression pattern of cytochrome P450 genes (CYPs) affected by tumorigenesis may have an important role in the progression of cancer and in the metabolism of anticancer drugs. The aim of the present study was to determine the mRNA expression pattern of two cytochrome P450 genes (CYP3A4, and CYP3A5) in breast cancer patients. Methods: Tumor samples were collected from 38 patients recently diagnosed with breast cancer along with corresponding non-malignant tissues. Quantitative polymerase chain reaction (qPCR) was used to quantify the levels of gene expression in all the samples. The association between CYPs expression and clinico-pathological parameters was also analyzed. Results: In the present study, our results showed that CYP3A5 gene expression was not significantly associated with breast cancer (p=0.14). Significant differences in CYP3A4 mRNA expression were observed between tumor tissue and the corresponding normal tissue (p<0.003). There was no statistical difference between CYP3A4 and CYP3A5 expression and clinical and pathological features. Conclusion: CYP3A4 expression has a potential role as a breast cancer prognosis marker. We conclude that increased expression levels of the examined CYP3A4 may promote breast cancer progression and also may associate with resistance to drug treatment by inactivation of anticancer drugs. Moreover, one potential therapeutic approach may be to block CYP3A4 function.
{"title":"RNA Expression of Cytochrome P450 and its Clinical Impact in Breast Cancer Patients","authors":"Kanakaiah Thota, K. Prasad, M. Rao","doi":"10.4172/1948-5956.1000557","DOIUrl":"https://doi.org/10.4172/1948-5956.1000557","url":null,"abstract":"Objectives: The expression pattern of cytochrome P450 genes (CYPs) affected by tumorigenesis may have an important role in the progression of cancer and in the metabolism of anticancer drugs. The aim of the present study was to determine the mRNA expression pattern of two cytochrome P450 genes (CYP3A4, and CYP3A5) in breast cancer patients. Methods: Tumor samples were collected from 38 patients recently diagnosed with breast cancer along with corresponding non-malignant tissues. Quantitative polymerase chain reaction (qPCR) was used to quantify the levels of gene expression in all the samples. The association between CYPs expression and clinico-pathological parameters was also analyzed. Results: In the present study, our results showed that CYP3A5 gene expression was not significantly associated with breast cancer (p=0.14). Significant differences in CYP3A4 mRNA expression were observed between tumor tissue and the corresponding normal tissue (p<0.003). There was no statistical difference between CYP3A4 and CYP3A5 expression and clinical and pathological features. Conclusion: CYP3A4 expression has a potential role as a breast cancer prognosis marker. We conclude that increased expression levels of the examined CYP3A4 may promote breast cancer progression and also may associate with resistance to drug treatment by inactivation of anticancer drugs. Moreover, one potential therapeutic approach may be to block CYP3A4 function.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81192141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000568
Y. H. A. Montenegro, A. D. Ramos, G. C. L. Silva
Yorran Hardman Araújo Montenegro1*, Anderson dos Santos Ramos2 and Geilza Carla de Lima Silva3 1Department of Biological Sciences at the State University of Paraíba, Laboratory of Genetics and Molecular Biology (LGBM), Brazil 2Department of Cellular and Molecular Biology, Federal University of Paraíba, Laboratory of Molecular Biology Applied to Health, Brazil 3Department of Applied Biology to Health, Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Brazil
Yorran Hardman Araújo黑山1*，Anderson dos Santos Ramos2和Geilza Carla de Lima Silva3 1巴西国立大学生物科学系Paraíba，巴西遗传与分子生物学实验室(LGBM) 2巴西联邦大学细胞与分子生物学学系Paraíba，巴西分子生物学应用于健康实验室3巴西伯南布哥联邦大学(UFPE)应用生物学应用于健康学系，免疫病理学实验室Keizo Asami (LIKA)巴西
{"title":"Tumor Immunology: Uncovering Relationship Between Cancer and Immune System","authors":"Y. H. A. Montenegro, A. D. Ramos, G. C. L. Silva","doi":"10.4172/1948-5956.1000568","DOIUrl":"https://doi.org/10.4172/1948-5956.1000568","url":null,"abstract":"Yorran Hardman Araújo Montenegro1*, Anderson dos Santos Ramos2 and Geilza Carla de Lima Silva3 1Department of Biological Sciences at the State University of Paraíba, Laboratory of Genetics and Molecular Biology (LGBM), Brazil 2Department of Cellular and Molecular Biology, Federal University of Paraíba, Laboratory of Molecular Biology Applied to Health, Brazil 3Department of Applied Biology to Health, Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Brazil","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81331171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000546
S. Kaur, H. Khatun, Abhishek Kumar, M. Ellis, D. Mehta, G. Guron
A 65-year-old African American female was diagnosed with laryngeal cancer (T1N2M0) in August 2015. She received platinum-based chemotherapy initially. After an initial remission patient had a systemic recurrence which was treated with Cetuximab. The patient presented to ER six hours after receiving the first dose of cetuximab with high grade fever and signs of meningeal irritation. CSF analysis showed neutrophil predominant pleocytosis with negative gram stain and culture. It was concluded that the patient had cetuximab induced aseptic meningitis. The patient was re-challenged with lower dose of cetuximab which was tolerated well. Cetuximab induced aseptic meningitis is a rare side effect reported in handful of cases.
{"title":"Cetuximab Induced Aseptic Meningitis: A Rare Side Effect","authors":"S. Kaur, H. Khatun, Abhishek Kumar, M. Ellis, D. Mehta, G. Guron","doi":"10.4172/1948-5956.1000546","DOIUrl":"https://doi.org/10.4172/1948-5956.1000546","url":null,"abstract":"A 65-year-old African American female was diagnosed with laryngeal cancer (T1N2M0) in August 2015. She received platinum-based chemotherapy initially. After an initial remission patient had a systemic recurrence which was treated with Cetuximab. The patient presented to ER six hours after receiving the first dose of cetuximab with high grade fever and signs of meningeal irritation. CSF analysis showed neutrophil predominant pleocytosis with negative gram stain and culture. It was concluded that the patient had cetuximab induced aseptic meningitis. The patient was re-challenged with lower dose of cetuximab which was tolerated well. Cetuximab induced aseptic meningitis is a rare side effect reported in handful of cases.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"11 1","pages":"211-213"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84990557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000569
Xiao-ying Zhao
{"title":"EGFR Primary T790M and L858R Double Mutation Confers Clinical Benefit to Erlotinib and Resistance to Osimertinib in One Lung Adenocarcinoma Patient: A Case Report","authors":"Xiao-ying Zhao","doi":"10.4172/1948-5956.1000569","DOIUrl":"https://doi.org/10.4172/1948-5956.1000569","url":null,"abstract":"","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91076666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/1948-5956.1000562
I. Rivas, Jose A. Silva, Gagmar Alfonso, Helga Candanedo, Y. Cuervo, Braulio F. Mestre, J. R. M. Cabello, J. Lence, Martha Lugoyo, E. Sanz
Objective: Antioxidant supplements seem to reduce toxicity associated with radiotherapy (RT) and chemotherapy (CT) in patients with head and neck (H&N) cancers. Ocoxin-Viusid (OV) has recognized antioxidant, immunostimulant, and anti-tumor effects. Our study was aimed to evaluate the efficacy and safety of OV in patients with H&N tumors during treatment with RT and CT. Methods: A total of 60 patients with a diagnosis of H&N carcinoma and indication of radiotherapy concurrent with chemotherapy were included in a phase II, randomized, prospective, controlled, double-blind study with two treatment arms: RT+CT+Placebo (n=30) and RT+CT+OV (n=30) during one year at a tertiary referral academic center (National Institute of Oncology from Havana, Cuba) from January 2015 to January 2016, with the objective of evaluating RT-CT toxicity reduction and improving patient quality of life. Results: There was no significant difference between the two groups in regard to male predominance; median age of 60, histological diagnosis of squamous cell carcinoma of the oropharynx in locally-advanced stages. The experimental OV group obtained better results insofar as a lower number and duration of interruptions in RT and lower severity of RT-CT toxicity levels, with acceptable local tumor control and overall survival in accordance with the clinical stage of the disease. No adverse effects were recorded in relation to the OV supplement. Conclusion: Our results suggest that administration of ocoxin-viusid during radiotherapy and chemotherapy improves patient quality of life by decreasing the number and level of toxicities from these treatments without interfering with their mechanism of action.
{"title":"Oncoxin-Viusid with Radiotherapy and Chemotherapy in Patients with Head and Neck Cancer: Results from a Phase II, Randomised, Double-Blind Study","authors":"I. Rivas, Jose A. Silva, Gagmar Alfonso, Helga Candanedo, Y. Cuervo, Braulio F. Mestre, J. R. M. Cabello, J. Lence, Martha Lugoyo, E. Sanz","doi":"10.4172/1948-5956.1000562","DOIUrl":"https://doi.org/10.4172/1948-5956.1000562","url":null,"abstract":"Objective: Antioxidant supplements seem to reduce toxicity associated with radiotherapy (RT) and chemotherapy (CT) in patients with head and neck (H&N) cancers. Ocoxin-Viusid (OV) has recognized antioxidant, immunostimulant, and anti-tumor effects. Our study was aimed to evaluate the efficacy and safety of OV in patients with H&N tumors during treatment with RT and CT. Methods: A total of 60 patients with a diagnosis of H&N carcinoma and indication of radiotherapy concurrent with chemotherapy were included in a phase II, randomized, prospective, controlled, double-blind study with two treatment arms: RT+CT+Placebo (n=30) and RT+CT+OV (n=30) during one year at a tertiary referral academic center (National Institute of Oncology from Havana, Cuba) from January 2015 to January 2016, with the objective of evaluating RT-CT toxicity reduction and improving patient quality of life. Results: There was no significant difference between the two groups in regard to male predominance; median age of 60, histological diagnosis of squamous cell carcinoma of the oropharynx in locally-advanced stages. The experimental OV group obtained better results insofar as a lower number and duration of interruptions in RT and lower severity of RT-CT toxicity levels, with acceptable local tumor control and overall survival in accordance with the clinical stage of the disease. No adverse effects were recorded in relation to the OV supplement. Conclusion: Our results suggest that administration of ocoxin-viusid during radiotherapy and chemotherapy improves patient quality of life by decreasing the number and level of toxicities from these treatments without interfering with their mechanism of action.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86458855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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