Plasma GH as a diagnostic and prognostic biomarker in HCC without cirrhosis.

227 Background: The association between the GH/IGF-1 axis and HCC was reported in patients (pt) with underlying cirrhosis. However, there is limited information among HCC pt without (w/o) cirrhosis. We herein investigated the role of GH as a circulating biomarker for HCC diagnosis and prognosis in pt w/o cirrhosis. Methods: Under IRB approval, we prospectively enrolled 1267 newly-diagnosed HCC pt in a case control study at the MD Anderson Cancer Center (2000-2015). Controls were healthy individuals (n = 1104). Plasma GH and AFP were measured 274 HCC pt w/o cirrhosis 200 healthy controls. IGF-1 was measured in 133 and 82 pt, respectively. We classified HCC pt into higher and lower GH values (cutoff for women, 3.7 µg/L; men, > 0.9 µg/L). Results: Most pt (74%) were male, with advanced BCLC staging (C-D, 74%) and 61% were older than 60y. Baseline GH was higher in HCC w/o cirrhosis (mean 3.3 µg/L) than controls (mean 0.4 µg/) (p < .001). ROC curve was plotted to assess diagnostic role. The AUC for AFP was 82.9 (p < .001); for GH 78.2 (p < .001). When only non-cirrhotic HCC pt with early stage (CLIP 0-2) and AFP < 20 ng/m were compared to controls, the GH/IGF-1 ratio had high prediction of early stage HCC - AUC 83 (95% CI 78-89%) (p < .0001). At a specificity of 90%, sensitivity of GH/IGF ratio was 67%. In addition, among HCC w/o cirrhosis, higher GH levels correlated with presence of vascular invasion (p < .001) and thrombosis (p = .004), tumor involvement of > 50% liver (p = .003), and more advanced BCLC (p < .001) and TNM staging (p < .001). Median overall survival (months) of HCC pt w/o cirrhosis with high GH levels was 13.1 (10.8-15.4) compared to 37.4 (19.8-55.1) of pt with lower plasma GH (p < .001). Multivariate cox-regression analysis identified high GH as an independent risk factor for mortality (HR = 1.8; 95% CI, 1.3-2.4; p < .001). Conclusions: Our study demonstrates the diagnostic and prognostic role of plasma GH in non-cirrhotic HCC and identifies the GH/IGF-1 ratio as a promising diagnostic marker for early stage HCC w/o cirrhosis and low AFP; this analysis excludes the confounding effect hepatocyte impaired function by presence of cirrhosis. Further studies are warranted to assess the causes of the observed differences.

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Lymph Node Maximum Uptake of 18F-ALF-NOTA-PRGD2 II PET/CT Predicts Lung Cancer Survival

10.21203/rs.3.rs-125389/v1 ◽

2020 ◽

Author(s):

Yuchun Wei ◽

Li Ma ◽

Jinsong Zheng ◽

Yanqing Pei ◽

Xueting Qin ◽

...

Keyword(s):

Lung Cancer ◽

Cox Regression ◽

Early Stage ◽

Statistical Significance ◽

Tnm Staging ◽

Tnm Stage ◽

Receiver Operating Curve ◽

Cox Regression Analysis ◽

Pet Ct

Abstract Background:Tumor angiogenesis plays a key role in tumor growth, development, and metastasis, so the exploratory study of tumor neovascularization imaging is one of the potential methods to predict survival. This study aims to examine the predictive capacity of 18F-ALF-NOTA-PRGD2 II (denoted 18F-Alfatide II) positron emission tomography (PET)/computed tomography (CT) before antitumor therapy (ATR) in patients with lung cancer.Results The median follow-up was 31 (1.3~57.0) months. Among the patients, 6 were lost to follow-up. The overall survival (OS) and progression-free survival (PFS) were 40.0 (3.50~57.0) months and 21.30 (2.0~56.0) months, respectively. The maximum uptake values (SUVmax) of the metastatic lymph nodes (SUVLN) and tumor node metastasis (TNM) staging were significant predictors of PFS and OS (all P<0.05) in a multivariate Cox regression analysis. Statistical significance was not reached by any other variable in the multivariate analysis. Receiver operating curve (ROC) analysis for survival revealed an area under the curve of 0.93 (P<0.001) for SUVLN and 0.96 for the TNM stage (P<0.001). The SUVLN and TNM stage cutoff values were 2.50 and II, and their sensitivity, specificity and positive and negative prediction were 77.42%, 80.0% and 82.76% and 74.07%; and 87.10%, 60.0% and 72.97% and 78.95%, respectively. Patients with a lower SUVLN and early stage had a longer PFS and OS (all P<0.05).Conclusions For lung cancer, low SUVLN and an early TNM stage (≤stage II) as assessed before ATR by 18F-alfatide II PET/CT represents a favorable subgroup with increased PFS and OS.

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Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

Biomarkers in Medicine ◽

10.2217/bmm-2020-0141 ◽

2020 ◽

Vol 14 (12) ◽

pp. 1127-1137

Author(s):

Tong-Tong Zhang ◽

Yi-Qing Zhu ◽

Hong-Qing Cai ◽

Jun-Wen Zheng ◽

Jia-Jie Hao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Stage Ii ◽

Poor Prognostic Factor ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

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Trends of incidence and prognosis of primary adenocarcinoma of the bladder

Therapeutic Advances in Urology ◽

10.1177/17562872211018006 ◽

2021 ◽

Vol 13 ◽

pp. 175628722110180

Author(s):

Haowen Lu ◽

Weidong Zhu ◽

Weipu Mao ◽

Feng Zu ◽

Yali Wang ◽

...

Keyword(s):

Prediction Model ◽

Marital Status ◽

Cox Regression ◽

Tnm Staging ◽

Primary Site ◽

Primary Adenocarcinoma ◽

Cancer Specific Survival ◽

Training Cohort ◽

Cox Regression Analysis ◽

Ajcc Stage

Background: Primary adenocarcinoma of the bladder (ACB) is a rare malignant tumor of the bladder with limited understanding of its incidence and prognosis. Methods: Patients diagnosed with ACB between 2004 and 2015 were obtained from the SEER database. The incidence changes of ACB patients between 1975 and 2016 were detected by Joinpoint software. Nomograms were constructed based on the results of multivariate Cox regression analysis to predict overall survival (OS) and cancer-specific survival (CSS) in patients with ACB, and the constructed nomograms were validated. Results: The incidence of ACB was trending down from 1991 to 2016. A total of 1039 patients were included in the study and randomly assigned to the training cohort (727) and validation cohort (312). In the training cohort, multivariate Cox regression showed that age, marital status, primary site, histology type, grade, AJCC stage, T stage, SEER stage, surgery, radiotherapy, and chemotherapy were independent prognostic factors for OS, whereas these were age, marital status, primary site, histology type, grade, AJCC stage, T/N stage, SEER stage, surgery, and radiotherapy for CSS. Based on the above Cox regression results, we constructed prognostic nomograms for OS and CSS in ACB patients. The C-index of the nomogram OS was 0.773 and the C-index of CSS was 0.785, which was significantly better than the C-index of the TNM staging prediction model. The area under the curve (AUC) and net benefit of the prediction model were higher than those of the TNM staging system. In addition, the calibration curves were very close to the ideal curve, suggesting appreciable reliability of the nomograms. Conclusion: The incidence of ACB patients showed a decreasing trend in the past 25 years. We constructed a clinically useful prognostic nomogram for calculating OS and CSS of ACB patients, which can provide a personalized risk assessment for ACB patient survival.

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Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001039 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1379-1386 ◽

Cited By ~ 1

Author(s):

Rhonda Farrell ◽

Suzanne C. Dixon ◽

Jonathan Carter ◽

Penny M. Webb

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Adjuvant Treatment ◽

Cox Regression ◽

Early Stage ◽

Cox Regression Analysis ◽

Cancer Study ◽

Stage Ib ◽

Australian Cohort

ObjectiveThe role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity.Materials and MethodsFrom a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests.ResultsMedian follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001).ConclusionsIn this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

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FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer

Cancer Biomarkers ◽

10.3233/cbm-203023 ◽

2021 ◽

pp. 1-8

Author(s):

Haifeng Xia ◽

Fang Hu ◽

Liangbin Pan ◽

Chengcheng Xu ◽

Haitao Huang ◽

...

Keyword(s):

Esophageal Cancer ◽

Western Blot ◽

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Cox Regression Analysis ◽

Ec Cells ◽

And Migration ◽

Proliferation And Migration

BACKGROUND: EC (esophageal cancer) is a common cancer among people in the world. The molecular mechanism of FAM196B (family with sequence similarity 196 member B) in EC is still unclear. This article aimed to clarify the role of FAM196B in EC. METHODS: The expression of FAM196B in EC tissues was detected using qRT-PCR. The prognosis of FAM196B in EC patients was determined by log-rank kaplan-Meier survival analysis and Cox regression analysis. Furthermore, shRNA was used to knockdown the expression of FAM196B in EC cell lines. MTT, wound healing assays and western blot were used to determine the role of FAM196B in EC cells. RESULTS: In our research, we found that the expression of FAM196B was up-regulated in EC tissues. The increased expression of FAM196B was significantly correlated with differentiation, lymph node metastasis, stage, and poor survival. The proliferation and migration of EC cells were inhibited after FAM196B-shRNA transfection in vitro and vivo. The western blot result showed that FAM196B could regulate EMT. CONCLUSION: These results suggested that FAM196B severs as an oncogene and promotes cell proliferation and migration in EC. In addition, FAM196B may be a potential therapeutic target for EC patients.

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Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000376 ◽

2021 ◽

pp. 1-4

Author(s):

Tanzeel Janjua ◽

Fei Sun ◽

Katy Clarke ◽

Pete Dickinson ◽

Kevin Franks ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Early Stage ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

Early Stage Lung Cancer ◽

Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

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The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽

10.1093/neuros/nyab052 ◽

2021 ◽

Author(s):

Peng Wang ◽

Chen Luo ◽

Peng-jie Hong ◽

Wen-ting Rui ◽

Shuai Wu

Keyword(s):

Cox Regression ◽

Progression Free Survival ◽

Extent Of Resection ◽

Lower Grade ◽

Wild Type ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Lower Grade Glioma ◽

Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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The Diagnostic Role of Sputum miRNA in Non-Small Cell Lung Cancer

10.21203/rs.3.rs-62275/v1 ◽

2020 ◽

Author(s):

Zaoxiu Hu ◽

Yonghe Zhao ◽

Yanlong Yang ◽

Zhenghai Shen ◽

Yunchao Huang

Keyword(s):

Lung Cancer ◽

Diagnostic Accuracy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Stage I ◽

Small Cell Lung ◽

Diagnostic Role

Abstract Objective: Recent studies indicated sputum miRNAs may provide a promising approach for non-small cell lung cancer (NSCLC) diagnosis. But some results were still inconsistent. So, we performed meta-analysis to evaluate the diagnostic role of sputum miRNAs for the detection of NSCLC.Methods: Eligible studies that estimated the diagnostic accuracy of sputum miRNAs in NSCLC were searched in Pubmed, Embase and Web of Science and Chinese National Knowledge Infrastructure (CNKI). Data from the eligible studies were collected and pooled; sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios, weighted symmetric summary ROC curve and the area under the curve (AUC) were calculated by bi-variate random effects model. The between-study heterogeneity was evaluated by Q test and I2 statistics.Results: 30 studies from 16 articles were included for analysis. The overall analysis yielded the sensitivity of 0.77 (95% CI: 0.73–0.81) and specificity of 0.87 (95% CI: 0.83–0.90), with an area under the SROC curve (AUC) of 0.89 (95% CI: 0.86–0.91). Subgroup analysis revealed the diagnostic accuracy in multiple miRNAs studies was higher than single miRNA (the sensitivity, specifcity and an AUC of multiple miRNAs were 0.76, 0.88 and 0.90; and for single miRNA, it was 0.74, 0.74, and 0.80). The diagnostic performance in early stage NSCLC was also very high (the sensitivity, specifcity and an AUC of stage I/II was 0.76, 0.88 and 0.91; and for stage I, it was 0.79, 0.85, and 0.87). We also found miR-210, miR-21, miR-31 and miR-126-3p might serve as potential biomarkers for lung cancer.Conclusion: Sputum miRNAs was useful noninvasive biomarkers for NSCLC diagnosis.

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Incidence, Survival, and Associated Factors Estimation in Osteosarcoma Patients with Lung Metastasis: A Single-center Experience of 11 Years in Tianjin, China

10.21203/rs.3.rs-1071152/v1 ◽

2021 ◽

Author(s):

Chao Zhang ◽

Haixiao Wu ◽

Guijun Xu ◽

Wenjuan Ma ◽

Lisha Qi ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Regression Analysis ◽

Prognostic Factors ◽

Lung Metastasis ◽

Associated Factors ◽

Cox Regression ◽

Cancer Center ◽

Single Center ◽

Cox Regression Analysis

Abstract Background: Osteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis. Methods: From February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. Prognostic factors of patients with osteosarcoma were identified by the Cox proportional hazard regression analysis. Risk factor of lung metastasis in osteosarcoma were investigated by the logistic regression model. Results: A total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteo-sarcoma patients was 70.0%. Surgery, bone and lung metastasis were the significant prognostic factors in multivariable Cox regression analysis. Twenty-one (10.3%) patients showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) lung metastases during the later course. T3 stage (OR=11.415, 95%CI 1.362-95.677, P=0.025) and synchronous bone metastasis (OR=6.437, 95%CI 1.69-24.51, P=0.006) were risk factors of synchronous lung metastasis occurrence. Good necrosis (≥90%, OR=0.097, 95%CI 0.028-0.332, P=0.000) and elevated Ki-67 (≥50%, OR=4.529, 95%CI 1.241-16.524, P=0.022) were proved to be significantly associated with metachronous lung metastasis occurrence. Conclusion: The overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.

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Prognostic Significance of Sarcopenia in Patients with Unresectable Advanced Esophageal Cancer

Journal of Clinical Medicine ◽

10.3390/jcm8101647 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1647 ◽

Cited By ~ 5

Author(s):

Sachiyo Onishi ◽

Masahiro Tajika ◽

Tsutomu Tanaka ◽

Yutaka Hirayama ◽

Kazuo Hara ◽

...

Keyword(s):

Esophageal Cancer ◽

Prognostic Factor ◽

Cox Regression ◽

Prognostic Significance ◽

Japanese Patients ◽

Independent Prognostic Factor ◽

Cancer Center ◽

Advanced Esophageal Cancer ◽

Cox Regression Analysis ◽

Group 2

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04–2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.

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