scholarly journals Identification of the Novel Methylated Genes’ Signature to Predict Prognosis in INRG High-Risk Neuroblastomas

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhichao Liu ◽  
Changchun Li
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Test Group ◽  
Functional Enrichment ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Log Rank Test

Background. Neuroblastomas are the most frequent extracranial pediatric solid tumors. The prognosis of children with high-risk neuroblastomas has remained poor in the past decade. A powerful signature is required to identify factors associated with prognosis and improved treatment selection. Here, we identified a strong methylation signature that favored the earlier diagnosis of neuroblastoma in patients. Methods. Gene methylation (GM) data of neuroblastoma patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were analyzed using a multivariate Cox regression analysis (MCRA) and univariate Cox proportional hazards regression analysis (UCPHRA). Results. The methylated genes’ signature consisting of eight genes (NBEA, DDX28, TMED8, LOC151174, EFNB2, GHRHR, MIMT1, and SLC29A3) was selected. The signature divided patients into low- and high-risk categories, with statistically significant survival rates (median survival time: 25.08 vs. >128.80 months, log-rank test, P < 0.001 ) in the training group, and the validation of the signature’s risk stratification ability was carried out in the test group (log-rank test, P < 0.01 , median survival time: 30.48 vs. >120.36 months). The methylated genes’ signature was found to be an independent predictive factor for neuroblastoma by MCRA. Functional enrichment analysis suggested that these methylated genes were related to butanoate metabolism, beta-alanine metabolism, and glutamate metabolism, all playing different significant roles in the process of energy metabolism in neuroblastomas. Conclusions. The set of eight methylated genes could be used as a new predictive and prognostic signature for patients with INRG high-risk neuroblastomas, thus assisting in treatment, drug development, and predicting survival.

scholarly journals Clinical Characteristics and Prognosis of Renal Cell Carcinoma With Spinal Bone Metastases

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianpo Zhai ◽  
Ning Liu ◽  
Hai Wang ◽  
Guanglin Huang ◽  
Libo Man
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Visceral Metastasis ◽  
Cox Regression Analysis

BackgroundThe prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. In this study, we aimed to define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center.MethodsThe clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis, and the pathological type of BM were investigated. All patients were followed up regularly. Overall survival (OS) was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis.ResultsForty-three RCC patients with sBM were collected. sBM was found synchronously in 30 patients (70%) and metachronously in 13 patients (30%). The median survival time was 30 months in 13 patients (30%) with solitary sBM and 19 months in 30 patients (70%) with multiple sBMs (P = 0.002). Visceral metastasis occurred in 12 patients (28%) with the median survival time of 17 months, while the other 31 patients (72%) had no visceral metastasis with the median survival time of 29 months (P&lt;0.001). En-block resection was done in 10 patients with median survival time of 40.1 months. Non-en-block resection were done in 33 patients with median survival time of 19.7 months (P&lt;0.001). Multivariate COX regression analysis showed that MSKCC score, number of BM, visceral metastasis, and en-block resection are the independent prognosis factors of RCC patients with sBM.ConclusionsMSKCC risk stratification, number of sBM, visceral metastasis and en-block resection are significant prognostic factors for OS in RCC patients with spinal BM. Therefore, for selected patients who has solitary spinal BM with no visceral metastasis, en-block resection of spinal BM can potentially prolong survival and is the treatment of choice.

The CD4+/CD8+ ratio as a prognostic factor in patients with metastatic melanoma receiving chemoimmunotherapy.

1996 ◽  
Vol 14 (5) ◽  
pp. 1690-1696 ◽  
Author(s):  
M Hernberg ◽  
T Muhonen ◽  
J P Turunen ◽  
M Hahka-Kemppinen ◽  
S Pyrhönen
Keyword(s):  
Survival Time ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Median Survival Time ◽  
Lymphocyte Subsets ◽  
Objective Response ◽  
Suppressor Cells ◽  
Rank Test ◽  
Log Rank Test ◽  
Melanoma Patients

PURPOSE As reported earlier, a chemotherapy regimen that consisted of dacarbazine, vincristine, lomustine, and bleomycin (DOBC) combined with natural leukocyte interferon (IFN) has been administered with favorable results to patients with metastatic melanoma. In this study, lymphocyte subsets (CD4+ and CD8+) were analyzed before and during treatment to elucidate if alterations in the CD4+/CD8+ ratio had any prognostic value. MATERIALS AND METHODS Blood samples were systematically obtained from 54 patients with metastatic melanoma who received this chemoimmunotherapy. The frequencies of peripheral-blood lymphocyte subsets were monitored by flow cytometry using the monoclonal antibodies OKT4 (CD4+, T-helper cells) and OKT8 (CD8+, T-suppressor cells). RESULTS Twenty-seven patients had a constantly increasing ratio, while the remaining 27 patients had a fluctuating or constantly decreasing ratio. The former group had a median survival time of 11.8 months, as compared with 6.5 months for the latter (P = .008, log-rank test). This difference was generated among patients who had an objective response. Responding patients with a constantly increasing ratio had a median survival time of 21.7 months, as compared with 10.2 months for patients with no constant increase in the ratio (P = .038, log-rank test). In nonresponders, no difference in survival was observed between the two groups. CONCLUSION The monitoring of early changes in the CD4+/CD8+ ratio can provide valuable information that predicts the prognosis of metastatic melanoma patients receiving chemoimmunotherapy.

scholarly journals Clinical characteristics and prognosis of renal cell carcinoma with spinal bone metastases

2019 ◽  
Author(s):  
Jianpo Zhai ◽  
Ning Liu ◽  
Hai Wang ◽  
Haidong Wang ◽  
Guanglin Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Visceral Metastasis ◽  
Cox Regression Analysis

Abstract Background: The prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. To define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center. Methods: The clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis and the pathological type of BM were investigated. All patients were followed up regularly. OS was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis. Results: 22 RCC patients with sBM were collected. sBM was found synchronously in 15 patients (68.2%) and metachronously in 7 patients (31.8%) . The median survival time was 30 months in 7 patients (31.8%) with solitary sBM and 19 months in 15 patients (68.2%) with multiple sBMs. Visceral metastasis occurred in 6 patients (27.3%)with the median survival time of 17 months, while the other 16 patients (72.7%) had no visceral metastasis with the median survival time of 29 months ( P =0.006). Enblock resection was done in 7 patients with median survival time of 34 months. Non-Enblock resection were done in 15 patients with median survival time of 18 months( P =0.006). Multivariate COX regression analysis showed that visceral metastasis and Enblock resection are the independent prognostic factors of RCC with sBM. Conclusions: No visceral metastasis, En-block resection are good prognostic factors for RCC with sBM. Therefore En-block resection of sBM is recommended for RCC without visceral metastasis.

scholarly journals Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1076 ◽  
Author(s):  
Shigeo Shimose ◽  
Takumi Kawaguchi ◽  
Hideki Iwamoto ◽  
Masatoshi Tanaka ◽  
Ken Miyazaki ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Nutritional Status ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Rank Test ◽  
Multicenter Cohort Study ◽  
The Impact ◽  
Conut Score

We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan–Meier method and analyzed using the log–rank test. Independent factors for OS were albumin–bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58–5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin–bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.

scholarly journals Identification of an eight-gene signature for survival prediction for patients with hepatocellular carcinoma based on integrated bioinformatics analysis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6548 ◽  
Author(s):  
Guo-jie Qiao ◽  
Liang Chen ◽  
Jin-cai Wu ◽  
Zhou-ri Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Bioinformatics Analysis ◽  
Gene Signature ◽  
Training Dataset ◽  
Rank Test ◽  
Survival Prediction ◽  
Gene Model ◽  
Cox Regression Analysis ◽  
Log Rank Test

Background Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death worldwide. Despite recent advances in imaging techniques and therapeutic intervention for HCC, the low overall 5-year survival rate of HCC patients remains unsatisfactory. This study aims to find a gene signature to predict clinical outcomes in HCC. Methods Bioinformatics analysis including Cox’s regression analysis, Kaplan-Meier (KM) and receiver operating characteristic curve (ROC) analysis and the random survival forest algorithm were performed to mine the expression profiles of 553 hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public database. Results We selected a signature comprising eight protein-coding genes (DCAF13, FAM163A, GPR18, LRP10, PVRIG, S100A9, SGCB, and TNNI3K) in the training dataset (AUC = 0.77 at five years, n = 332). The signature stratified patients into high- and low-risk groups with significantly different survival in the training dataset (median 2.20 vs. 8.93 years, log-rank test P < 0.001) and in the test dataset (median 2.68 vs. 4.24 years, log-rank test P = 0.004, n = 221, GSE14520). Further multivariate Cox regression analysis showed that the signature was an independent prognostic factor for patients with HCC. Compared with TNM stage and another reported three-gene model, the signature displayed improved survival prediction power in entire dataset (AUC signature = 0.66 vs. AUC TNM = 0.64 vs. AUC gene model = 0.60, n = 553). Stratification analysis shows that it can be used as an auxiliary marker for many traditional staging models. Conclusions We constructed an eight-gene signature that can be a novel prognostic marker to predict the survival of HCC patients.

Prognostic impact of LDH and HCG levels in marker-positive seminomas.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 392-392 ◽  
Author(s):  
Christoph Alexander Seidel ◽  
Gedske Daugaard ◽  
Tim Nestler ◽  
Alexey Tryakin ◽  
Christian Daniel Fankhauser ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Serum Levels ◽  
Rank Test ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Oncological Outcomes ◽  
Log Rank Test

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy <1.5 UNL (n=142) had a 5-year CSS (RFS) rate of 97% (88%), compared to 86% (81%) for ≥1.5 to 3 UNL (n=40), 83% (77%) for >3 to 5 UNL (n=44) and 83% (72%) for >5 UNL (n=44) (CSS p <0.001; RFS p=0.142). Concerning LDH levels post-orchiectomy this stratification was not significant but patients with LDH levels ≥3 UNL (n=77) displayed an impaired prognosis associated with a 5-year CSS (RFS) rate of 85% (79%) compared to 94% (82%) for levels <3 UNL (n=186) (CSS p=0.025; RFS p=0.447). Patients with HCG levels ≥2000 IU/l (n=17) pre- but not post-orchiectomy had a 5-year CSS (RFS) rate of 73% (60%) compared to 94% (79%) for patients with HCG levels <2000 IU/l (n=855) (CSS p=0.09; RFS p=0.04). In cox-regression analysis LDH ≥1.5 UNL (p=0.037; HR 3.32, CI95%1.08-10.26) and HCG levels ≥2000 IU/l (p=0.044; HR 3.69, 95%CI1.04-13.13) pre-orchiectomy were confirmed as prognostic factors for CSS. Conclusions: LDH levels inversely correlate with survival outcomes, suggesting ≥1.5 UNL pre- and ≥3 UNL post-orchiectomy as potential cut-off values for further risk assessment. Patients with extensive HCG elevations may represent an unfavorable subgroup concerning RFS and CSS, but only few patients were affected.

Clinical Outcome of 40 Patients with Higher-Risk Myelodysplastic Syndromes (MDS) after Treatment with Hypomethylating Agents: a Matched-Pairs Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2687-2687
Author(s):  
Kathrin Nachtkamp ◽  
Corinna Strupp ◽  
Andrea Kuendgen ◽  
Norbert Gattermann ◽  
Rainer Haas ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Survival Benefit ◽  
Low Dose ◽  
Phase Iii ◽  
Matched Pairs ◽  
Hypomethylating Agents ◽  
Kaplan Meier

Abstract Introduction: Patients with higher-risk MDS, especially those with an IPSS score of intermediate-2 or high, face a very poor prognosis with a median survival of 12 to 18 months. Allogeneic transplantation as a curative approach is an option for only a small percentage of patients. In phase-III-trials, hypomethylating agents demonstrated a survival benefit for this patient group. In order to validate the use of these compounds in clinical day-to-day practice, we analyzed 40 patients who underwent hypomethylating treatment with either decitabine or 5-azacytidine. Methods: We performed matched-pairs analyses using the Düsseldorf MDS registry (n=3288). Patients with higher-risk MDS (INT-1, INT-2, or high-risk IPSS scores) at the time of treatment with hypomethylating agents (n=40) were compared with higher-risk MDS patients who received best supportive care (BSC) only (n=120) and with higher-risk MDS patients who underwent treatment with low-dose Ara-C (n=35). Patients were matched according to age, gender, WHO type, IPSS score and date of diagnosis. Each patient in the hypomethylating cohort was matched with three patients of the BSC cohort and one patient of the low-dose ara-C cohort. For 5 patients, no adequate match partner of the low-dose ara-C cohort could be assigned. Follow-up for survival was assured by contacting our outpatient department or primary care physician. Results: The distribution of WHO types at time of diagnosis within the decitabine/5-azacytidine cohort was 10 RA/RCMD patients, 9 RAEB I, 16 RAEB II, 2 CMML I and 3 CMML II. Median age was 70 years. 10 patients belonged to the intermediate-1, 11 to the intermediate-2 and 18 patients to the high-risk group according to the IPSS score. In one patient, the IPSS score could not be assessed. All patients had progressed to at least RAEB II when treatment was initiated. 19 patients received decitabine and 21 patients were given 5-azacytidine. Median survival time in the hypomethylating cohort was 28 months, regardless of the type of hypomethylating treatment, compared with 10 months in the BSC cohort. Figure 1 shows the Kaplan Meier curve comparing 40 patients treated with hypomethylating agents with 120 patients who received BSC only (p=0.0026). Median survival time of the low-dose ara-C cohort was 20 months; although 5 patients of the hypomethylating cohort could not be assigned a match partner and therefore had to be withdrawn from the comparison with low-dose ara-C, median survival in the remaining 35 patients of the hypomethylating cohort was still 28 months. Figure 2 shows the Kaplan Meier curve comparing the hypomethylating cohort with the low-dose ara-C cohort (p=0.027). Conclusions: Our data show that higher-risk MDS patients have a substantial survival benefit from treatment with hypomethylating agents as compared to both low-dose ara-C and BSC patients. Hypomethylating agents should be considered to be the treatment of choice in higher-risk MDS patients who are not candidates for allografting. Figure Figure

scholarly journals An immune-relevant signature of nine genes as a prognostic biomarker in patients with gastric carcinoma

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 850-859
Author(s):  
Bing Wang ◽  
Yang Zhang
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Gastric Carcinoma ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Risk Group ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cox Regression Analysis

AbstractBackgroundAs one of the most common malignant tumors worldwide, the morbidity and mortality of gastric carcinoma (GC) are gradually increasing. The aim of this study was to construct a signature according to immune-relevant genes to predict the survival outcome of GC patients using The Cancer Genome Altas (TCGA).MethodsUnivariate Cox regression analysis was used to assess the relationship between immune-relevant genes regarding the prognosis of patients with GC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select prognostic immune-relevant genes and to establish the signature for the prognostic evaluation of patients with GC. Multivariate Cox regression analysis and Kaplan–Meier survival analysis were used to assess the independent prognostic ability of the immune-relevant gene signature.ResultsA total of 113 prognostic immune-relevant genes were identified using univariate Cox proportional hazards regression analysis. A signature of nine immune-relevant genes was constructed using the LASSO Cox regression. The GC samples were assigned to two groups (low- and high risk) according to the optimal cutoff value of the signature score. Compared with the patients in the high-risk group, patients in the low-risk group had a significantly better prognosis in the TCGA and GSE84437 cohorts (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the signature of nine immune-relevant genes might serve as an independent predictor of GC.ConclusionsOur results showed that the signature of nine immune-relevant genes may potentially serve as a prognostic prediction for patients with GC, which may contribute to the decision-making of personalized treatment for the patients.

scholarly journals Gene-Gene Interaction Analysis for the Survival Phenotype Based on the Kaplan-Meier Median Estimate

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Mira Park ◽  
Jung Wun Lee ◽  
Taesung Park ◽  
SeungYeoun Lee
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Interaction Analysis ◽  
Computing Time ◽  
Gene Interaction ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Kaplan Meier

In this study, we propose a simple and computationally efficient method based on the multifactor dimensional reduction algorithm to identify gene-gene interactions associated with the survival phenotype. The proposed method, referred to as KM-MDR, uses the Kaplan-Meier median survival time as a classifier. The KM-MDR method classifies multilocus genotypes into a binary attribute for high- or low-risk groups using median survival time and replaces balanced accuracy with log-rank test statistics as a score to determine the best model. Through intensive simulation studies, we compared the power of KM-MDR with that of Surv-MDR, Cox-MDR, and AFT-MDR. It was found that KM-MDR has a similar power to that of Surv-MDR, with less computing time, and has comparable power to that of Cox-MDR and AFT-MDR, even when there is a covariate effect. Furthermore, we apply KM-MDR to a real dataset of ovarian cancer patients from The Cancer Genome Atlas (TCGA).

scholarly journals Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Jing Sun ◽  
Jinfeng Liu ◽  
Dan Liu ◽  
Xiongzhi Wu
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Protein Expression ◽  
Survival Time ◽  
Signaling Pathway ◽  
Median Survival ◽  
Cox Regression ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Cox Regression Analysis

Reports increasingly suggest that Chinese herbal medicine (CHM) has been used to treat ovarian cancer (OvCa) with a good curative effect; however, the molecular mechanisms underlying CHM are still unclear. In this retrospective study, we explored CHM’s molecular targets for the treatment of OvCa based on clinical data and network pharmacology. We used the Kaplan-Meier method and Cox regression analysis to verify the survival rate of 202 patients with CHM-treated OvCa. The association between CHM and survival time was analyzed by bivariate correlation. A target network of CHM active ingredients against OvCa was established via network pharmacology. Cox regression analysis showed that CHM is an independent favorable prognostic factor. The median survival time was 91 months in the CHM group and 65 months in the non-CHM group. The survival time of FIGO stage III patients in the two groups was 91 months and 52 months, and the median survival period of FIOG stage IV patients was 60 months and 22 months, respectively ( p < 0.001 ). Correlation analysis demonstrated that 12 herbs were closely associated with prognosis, especially in regard to the long-term benefits. Bioinformatics analysis indicated that the anti-OvCa activity of these 12 herbs occurs mainly through the regulation of apoptosis-related protein expression, which promotes OvCa cell apoptosis and inhibits OvCa development. They also regulate the progress of OvCa treatment by promoting or inhibiting protein expression on the p53 signaling pathway and by inhibiting the NF-κB signaling pathway by directly inhibiting NF-κB.

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