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2021 ◽  
Vol 6 (1) ◽  
Rena Elkin ◽  
Jung Hun Oh ◽  
Ying L. Liu ◽  
Pier Selenica ◽  
Britta Weigelt ◽  

AbstractNetwork analysis methods can potentially quantify cancer aberrations in gene networks without introducing fitted parameters or variable selection. A new network curvature-based method is introduced to provide an integrated measure of variability within cancer gene networks. The method is applied to high-grade serous ovarian cancers (HGSOCs) to predict response to immune checkpoint inhibitors (ICIs) and to rank key genes associated with prognosis. Copy number alterations (CNAs) from targeted and whole-exome sequencing data were extracted for HGSOC patients (n = 45) treated with ICIs. CNAs at a gene level were represented on a protein–protein interaction network to define patient-specific networks with a fixed topology. A version of Ollivier–Ricci curvature was used to identify genes that play a potentially key role in response to immunotherapy and further to stratify patients at high risk of mortality. Overall survival (OS) was defined as the time from the start of ICI treatment to either death or last follow-up. Kaplan–Meier analysis with log-rank test was performed to assess OS between the high and low curvature classified groups. The network curvature analysis stratified patients at high risk of mortality with p = 0.00047 in Kaplan–Meier analysis in HGSOC patients receiving ICI. Genes with high curvature were in accordance with CNAs relevant to ovarian cancer. Network curvature using CNAs has the potential to be a novel predictor for OS in HGSOC patients treated with immunotherapy.

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Ruonan Liu ◽  
Yuhui Yue ◽  
Dongling Miao ◽  
Baodong Cheng

PurposeThis article will select 25 years of subdivided data to perform Kaplan–Meier survival analysis on the export trade relations of Chinese wooden flooring, use discrete-time cloglog models to analyze influencing factors, use logit and probit models to test the robustness, and try to systematically reveal the duration of China's wood flooring export trade and its influencing factors.Design/methodology/approachThis study used Kaplan–Meier survival function estimation method. In the survival analysis, survival function and hazard rate function are often used to characterize the distribution of survival time.FindingsThe continuous average export time of China's wooden flooring is relatively long, about 14 years. China's wooden flooring has a negative time dependency. After the export trade exceeds the threshold value of 15 years, the failure rate of trade greatly decreases, which has a “threshold effect.” Gravity model variables have a significant impact on the duration of China's wooden floor export.Originality/valueStudying the duration of forest products trade is of great significance for clearing deep-level trade relations and promoting sustainable development of forest products trade.

2021 ◽  
Vol 21 (1) ◽  
Saitah Bufersen ◽  
Judith Jones ◽  
Jayapriyaa Shanmugham ◽  
Tun-Yi Hsu ◽  
Sharron Rich ◽  

Abstract Background Outcome studies of nonsurgical root canal treatment (NSRCT) in permanent teeth of children are scarce. This study investigated survival and assessed the variables associated with failure of endodontically treated teeth (ETT) in 6- to 18-year-olds. Methods Records of subjects who received NSRCT at age 6–18 years at Boston University between 2007 and 2015 were assessed for the occurrence of untoward events. Kaplan–Meier survival curves were used to investigate the survival of ETT in the total sample. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated. Results The analysis included 341 patients (424 ETT). Kaplan–Meier survival curves differed according to age at treatment (log-rank P = 0.026), with survival being the lowest among the youngest age group. The estimated 5-year survival probability was 80% for 15- to 18-year-olds, 64.8% for 12- to 14-year-olds and 46.4% for 6- to 11-year-olds. Compared to age at treatment of 15–18 years, age at treatment of 6–11 years (aHR: 2.19, 95% CI 1.02–4.67) and 12–14 years (aHR: 2.02, 95% CI 1.15–3.55) was associated with an increased risk of ETT failure. In the total study sample, the estimated cumulative survival probability was 93.3% at 12 months, 88.0% at 24 months, 76.2% at 36 months, 71.0% at 48 months, and 69.1% at 60 months. Conclusions In children, ETT are more likely to survive when NSRCTs are performed at an older age.

2021 ◽  
Vol 11 (1) ◽  
I. Hadi ◽  
A. Schummer ◽  
M. Dreyling ◽  
C. Eze ◽  
R. Bodensohn ◽  

AbstractTo analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin’s lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan–Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87 months (95% CI 72–102 months). Median single dose per fraction was 2.0 Gy (range 1.5–2 Gy) and median total dose was 30.6 Gy (range 16–45 Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0 years (95% CI 8.3–19.7 years). The estimated PFS after 5 and 10 years were 73.0% and 65.5% in Kaplan–Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60 years old) had significantly superior PFS to those older than 60 years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0 Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I–II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I–II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6 months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I–II side effects recovered 3 to 6 months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy.Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19–137).

2021 ◽  
Liqiang Yuan ◽  
Wei Jiang ◽  
Zhanyu Xu ◽  
Kung Deng ◽  
Yu Sun ◽  

Abstract Background: There is a high incidence of lung adenocarcinoma (LUAD). Even with surgery, targeted therapy and immunotherapy, the survival rate of LUAD patients is still low. N6-methyladenosine (m6A) and DNA methylation markers can help with the diagnosis and treatment of LUAD patients. Therefore, it is necessary to identify a novel m6A-related DNA methylation sites signature to predict the survival of patients with LUAD. Methods: In this study, we screened 15 m6A-related genes and their 217 methylation sites. RNA sequencing data of 15 genes and the clinicopathological parameters of TCGA-LUAD were obtained from the TCGA database (http://cancergenome.nih.gov/). The LUAD-DNA CpG site information was obtained from the Illumina Human Methylation 450 BeadChip (Illumina, San Diego, CA, United States). The methylation sites related to prognosis were screened using univariate COX analysis, and the independent predictors of LUAD patients were identified using multivariate COX analysis of least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Finally, a model with 5 methylation sites as the main body to predict the prognosis of OS in patients with LUAD was obtained. According to the risk grouping of the prediction model, Kaplan-Meier curve and the receiver operating characteristic (ROC) curve were performed in the test and training sets to assess the predicted capacity of the model. In addition, a nomogram constructed by combining the risk score of methylation group and other related clinicopathological factors to verify the reliability of our model.Results: We constructed a m6A-related 5-DNA methylation site model to predict OS in LUAD patients. According to the results of the Kaplan-Meier curve, both the test set and the training set, the high-risk group showed a worse prognosis. The AUCs of the 5 DNA methylation signature at 1, 5 and 10 years in test datasets were 0.730, 0.649 and 0.726, respectively, and 0.679, 0.656 and 0.732 in training datasets. Finally, we constructed a nomogram to further verify the reliability of the model.Conclusion: In this study, we analyzed the methylation sites of m6A-related genes and established a m6A-related 5-DNA methylation site model to predict OS in LUAD patients.

2021 ◽  
Vol 12 ◽  
Yi-Ran Li ◽  
Xiao-Yan Meng ◽  
Rui-Qing Zong ◽  
Fei-Xiang Wu

Objectives: Procalcitonin (PCT) has long been proved as an early diagnostic signal for postoperative outcomes. The purpose of this study is to explore the value of serum procalcitonin levels in predicting post-hepatectomy liver failure (PHLF), and further to declarethe relationship between postoperative PCT and short-term prognosis in patients after hepatectomy.Methods: Clinical data of patients with hepatocellular carcinoma (HCC) who underwent hepatectomy from June 1st, 2019 to September 31st, 2020 at Shanghai Eastern Hepatobiliary Surgery Hospital had been retrospectively analyzed. Logistic regression analysis was used to evaluate the risk factors related to PHLF. The Kaplan-Meier method was used to calculate the PHLF rate and 30-day survival after surgery.Results: A total of 885 patients with complete data were finally included in analysis, 311 of them with elevated serum PCT (≥1 ng/ml). Results of the logistic regression analysis suggested a significant association between PCT and PHLF [HR, 95%CI; 3.801 (1.825, 7.917), p < 0.001]. Other significant risk factors for PHLF included portal hypertension, portal blocking time (>30 min) and blood transfusion (>200 ml). Kaplan-Meier analysis also suggested a higher PHLF rate in elevated PCT patients [9.0% (95% CI, 7.3 to 12.8 VS. 1.9% (95% CI, 1.1–4.3)); p < 0.001]. For secondary outcomes, elevated PCT was also highly associated with postoperative sepsis, ICU admission, 30-day mortality and 3-month mortality.Conclusion: Elevated procalcitonin level in patients after hepatectomy is related to higher PHLF rate, with lower 30-day survival and poor short-term postoperative outcomes.

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Li Wang ◽  
Wenjun Zhang ◽  
Tao Yang ◽  
Le He ◽  
Yunmei Liao ◽  

Background. With the development of sequencing technology, several signatures have been reported for the prediction of prognosis in patients with hepatocellular carcinoma (HCC). However, the above signatures are characterized by cumbersome application. Therefore, the study is aimed at screening out a robust stratification system based on only one gene to guide treatment. Methods. Firstly, we used the limma package for performing differential expression analysis on 374 HCC samples, followed by Cox regression analysis on overall survival (OS) and disease-free interval (PFI). Subsequently, hub prognostic genes were found at the intersection of the above three groups. In addition, the topological degree inside the PPI network was used to screen for a unique hub gene. The rms package was used to construct two visual stratification systems for OS and PFI, and Kaplan-Meier analysis was utilized to investigate survival differences in clinical subgroups. The ssGSEA algorithm was then used to reveal the relationship between the hub gene and immune cells, immunological function, and checkpoints. In addition, we also used function annotation to explore into putative biological functions. Finally, for preliminary validation, the hub gene was knocked down in the HCC cell line. Results. We discovered 6 prognostic genes (SKA1, CDC20, AGTRAP, BIRC5, NEIL3, and CDC25C) for constructing a PPI network after investigating survival and differential expression genes. According to the topological degree, AGTRAP was chosen as the basis for the stratification system, and it was revealed to be a risk factor with an independent prognostic value in Kaplan-Meier analysis and Cox regression analysis ( P < 0.05 ). In addition, we constructed two visualized nomograms based on AGTRAP. The novel stratification system had a robust predictive value for PFI and OS in ROC analysis and calibration curve ( P < 0.05 ). Meanwhile, AGTRAP upregulation was associated with T staging, N staging, M staging, pathological stage, grade, and vascular invasion ( P < 0.05 ). Notably, AGTRAP was overexpressed in tumor tissues in all pancancers with paired samples ( P < 0.05 ). Furthermore, AGTRAP was associated with immune response and may change immune microenvironment in HCC ( P < 0.05 ). Next, gene enrichment analysis suggested that AGTRAP may be involved in the biological process, such as cotranslational protein targeting to the membrane. Finally, we identified the oncogenic effect of AGTRAP by qRT-PCR, colony formation, western blot, and CCK-8 assay ( P < 0.05 ). Conclusion. We provided robust evidences that a stratification system based on AGTRAP can guide survival prediction for HCC patients.

Zeming Liu ◽  
Di Hu ◽  
Jinpeng Li ◽  
Qing Xia ◽  
Yan Gong ◽  

BackgroundCoronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients.MethodsPatient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality.ResultsLogistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19.ConclusionElevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

2021 ◽  
Vol 11 ◽  
Jiaxing Lin ◽  
Xiao Xu ◽  
Tianren Li ◽  
Jihang Yao ◽  
Meng Yu ◽  

BackgroundBladder cancer lacks useful and robust prognostic markers to stratify patients at risk. Our study is to identify a robust prognostic marker for bladder cancer.MethodsThe transcriptome and clinical data of bladder cancer were downloaded from multiple databases. We searched for genes with robust prognosis by Kaplan-Meier analysis of the whole genome. CIBERSORT and TIMER algorithm was used to calculate the degree of immune cell infiltration.ResultsWe identified OLFML2B as a robust prognostic marker for bladder cancer in five cohorts. Kaplan-Meier analysis showed that patients with a high level of OLFML2B expression had a poor prognosis. The expression of OLFML2B increased with the increase of stage and grade. We found that patients with high expression of OLFML2B still had a poor prognosis in two small bladder cancer cohorts. OLFML2B also has the prognostic ability in ten other tumors, and the prognosis is poor in high expression. The correlation analysis between OLFML2B and immune cells showed that it was positively correlated with the degree of macrophage infiltration and highly co-expressed with tumor-associated macrophage markers. Finally, the Wound-healing assay and Colony formation assay results showed that the migration and proliferation ability of bladder cancer cell lines decreased after the knockdown of OLFML2B.ConclusionsIn summary, OLFML2B is a robust risk prognostic marker, and it can help patients with bladder cancer improve individualized treatment.

2021 ◽  
NA LI ◽  

Abstract BackgroundStudies in recent years have shown that the neutrophil-to-lymphocyte ratio (NLR) is associated with the survival and prognosis of patients with malignant tumors.However, the utility of the NLR in predicting outcomes in patients with adenoid cystic carcinoma (ACC) of the head and neck remains unclear. Here, we examined the prognostic value of the preoperative NLR in patients with ACC of the head and neck.MethodsThis study retrospectively analyzed 71 patients with a histopathological diagnosis of ACC from August 2005 to November 2020.The optimal cutoff value was obtained by receiver operating characteristic (ROC) analysis. The characteristics of the patients were evaluated using chi-squared tests.The value of the NLR used in predicting the outcomes of these patients was analyzed using Kaplan-Meier curves and Cox regression models.ResultsThe cutoff value of the NLR was 2.071. The chi-squared tests showed that a high NLR(>2.071)was associated with tumor stage and lymph node metastasis(LNM). Kaplan-Meier survival analysis showed that the NLR>2.071 group was correlated with a shorter Overall survival(P<0.05). In multivariate Cox regression analysis, high NLR (>2.071) and high age (>54 years) were independent risk factors predicting poorer outcomes in patients with ACC.ConclusionsWe suggest that the preoperative NLR is a useful biomarker for the prognosis of patients with ACC.

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