Identifying Connectome Module Patterns via New Balanced Multi-Graph Normalized Cut.

Computational tools for the analysis of complex biological networks are lacking in human connectome research. Especially, how to discover the brain network patterns shared by a group of subjects is a challenging computational neuroscience problem. Although some single graph clustering methods can be extended to solve the multi-graph cases, the discovered network patterns are often imbalanced, e.g. isolated points. To address these problems, we propose a novel indicator constrained and balanced multi-graph normalized cut method to identify the connectome module patterns from the connectivity brain networks of the targeted subject group. We evaluated our method by analyzing the weighted fiber connectivity networks

Lower Blood Calcium Associates with Unfavorable Prognosis and Predicts for Bone Metastasis in NSCLC

Ionized calcium was involved in various cellular signal pathways,and regulates many cellular processes, including those relevant to tumorigenesis. We hypothesis that imbalance of calcium homeostasis is correlated with development of lung carcinomas. We collected the clinical data of 1084 patients with non small cell lung cancer (NSCLC) treated in Shandong Provincial Hospital, Shandong University. Logistic regression was used to determine the association between calcium levels and clinical characteristics, and COX regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. Blood electrolytes were tested before treatment; and nearly 16% patients with NSCLC were complained with decreased blood calcium, which is more frequent than that in other electrolytes. Further, Multivariate logistic regression analysis disclosed that there were significant correlation between blood calcium decrease and moderate and poor differentiation (P = 0.012, OR = 1.926 (1.203–4.219)), squamous cell carcinoma (P = 0.024, OR = 1.968(1.094–3.540)), and bone metastasis (P = 0.032, OR = 0.396(0.235–0.669)). In multivariate COX regression analysis, advanced lymph node stage and decreased blood calcium were significantly and independent, unfavorable prognostic factors (P<0.001). Finally, the Kaplan-Meier Survival curve revealed that blood calcium decrease was associated with shorter survival (Log-rank; χ2 = 26.172,P<0.001). Our finding indicates that lower blood calcium levels are associated with a higher risk of unfavorable prognosis and bone metastasis of NSCLC

Transportation Infrastructure and Digital Economy—Evidence from Chinese Cities

In this research, the influences of railways, roads, waterways, and civil aviation on the digital economy were analyzed using traffic, urban, and enterprise data in the integrated transport system. Regression was performed through the generalized spatial least square method (GS2SLS) in the empirical section to solve the endogeneity problem. It was verified that transportation infrastructure can promote the digital economy. While the development of railways, waterways, and roads is expected to rise by 1%, the digital economy will be increased by 0.0049, 0.0048, and 0.0031, respectively, and civil aviation’s effect is not significant. The robustness test results were still remarkable. From the industry level of cities, it was found that transportation infrastructure mainly promotes the development of the digital economy by upgrading the industrial structure. At the enterprise level, promoting entrepreneurship and facilitating the digital transformation of enterprises have become the main driving forces for the development of the digital economy, and strengthening labor flow is a vital promotion mechanism at the factor level of cities. In addition, a significant single-threshold effect is observed in promoting the digital economy by transportation infrastructure. In the cities that cross the threshold of the economic development level, the progress in the digital economy increases from 0.0027 and 0.0035 to 0.0059 and 0.0061 for 1% development of railways and roads; the promotion of the digital economy by transportation infrastructure is more evident in cities with a permanent-residents population of more than 3 million. Developing the digital economy and transport infrastructure is essential for economic recovery and sustainable development

Performance Optimization of High Specific Speed Centrifugal Pump Based on Orthogonal Experiment Design Method

A high specific speed centrifugal pump is used in the situation of large flow and low head. Centrifugal pump parameters need to be optimized in order to raise its head and efficiency under off-design conditions. In this study, the orthogonal experiment design method is adopted to optimize the performance of centrifugal pump basing on three parameters, namely, blade outlet width b2, blade outlet angle &beta;2 and blade wrap angle &phi;. First, the three-dimensional model of the centrifugal pump is established by CFturbo and SolidWorks. Then nine different schemes are designed by using orthogonal table, and numerical simulation is carried out in CFX15.0. The final optimized combination of parameters is b2 = 24 mm, &beta;2 = 24&deg;, &phi; = 112&deg;. Under the design condition, the head and efficiency of the optimized centrifugal pump are appropriately improved, the increments of which are 0.74 m and 0.48%, respectively. However, the efficiency considerably increases at high flow rates, with an increase of 6.9% at 1.5 Qd. The anti-cavitation performance of the optimized centrifugal pump is also better than the original pump. The results in this paper can provide references for parameter selection (b2, &beta;2, &phi;) in the centrifugal pump design

Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review

Abstract Background Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. Case description Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. Conclusions This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy

Prognostic significance of systemic inflammation-based lymphocyte- monocyte ratio in patients with lung cancer: based on a large cohort study.

Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275-1.816 for OS, and HR = 1.338, 95% CI: 1.152-1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520-2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946-3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC

Association between circulating levels of IGF-1 and IGFBP-3 and lung cancer risk: a meta-analysis.

BACKGROUND: The insulin-like growth factor (IGF) system was documented to play a predominant role in neoplasia. As lung cancer is one of the most malignant cancers, we conducted a meta-analysis in order to investigate the strength of association between circulating IGF-1 and IGFBP-3 levels and lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: A systematic literature search was conducted to identify all prospective case-control studies and case-control studies on circulating IGFs and IGFBPs levels. Six nested case-control studies (1 043 case subjects and 11 472 control participants) and eight case-control studies (401 case subjects and 343 control participants) were included in this meta-analysis. Pooled measure was calculated as the inverse variance-weighted mean of the natural logarithm of multivariate adjusted OR with 95% CIs for highest vs. lowest levels to assess the association of circulating IGF-1 and IGFBP-3 concentrations and lung cancer. Standard mean difference (SMD) was also calculated to indicate the difference of the circulating IGF-1 and IGFBP-3 concentrations between the lung cancer case group and the control group. Of the nested case-control studies, ORs for the highest vs. lowest levels of IGF-1 and IGFBP-3 were 1.047 (95% CI: [0.802,1.367], P = 0.736) and 0.960 (95%CI: [0.591,1.559], P = 0.868) respectively; and SMDs were -0.079 (95%CI:[ -0.169, 0.011], P = 0.086) and -0.097 (95%CI:[ -0.264,0.071], P = 0.258) for IGF-1 and IGFBP-3 respectively. As to the case-control studies, SMDs were 0.568 (95%CI:[ -0.035, 1.171], P = 0.065) and -0.780 (95%CI:[ -1.358, -0.201], P = 0.008) for IGF-1 and IGFBP-3 respectively. CONCLUSIONS/SIGNIFICANCE: Inverse association was shown between IGFBP-3 and lung cancer in the case-control studies,and the circulating level of IGFBP-3 underwent a decline during tumorogenesis and development of lung cancer, which suggested IGFBP-3 a promising candidate for the biomarker of lung cancer

Albumin and Neutrophil Combined Prognostic Grade as a New Prognostic Factor in Non-Small Cell Lung Cancer: Results from a Large Consecutive Cohort.

It has been reported nutritional status and systemic inflammation were associated with the outcome of patients with malignancies. However, the prognostic value of combination of them was really scarce, especially in non-small cell lung cancer (NSCLC). In order to find a more simple and efficient predictor, we hypothesized that pretreatment albumin and neutrophil combined prognostic grade (ANPG) could offer an improved prognostic ability in NSCLC patients.We collected pretreatment albumin and neutrophil, clinicopathological, treatment and follow-up data of 1033 consecutive NSCLC patients treated between 2006 and 2011 in this retrospective study. The ANPG was calculated according to pretreatment albumin and neutrophil levels dichotomized by the optimal cut-off values, the quartile values and the clinical reference values. Kaplan-Meier (K-M) curves and Cox proportional regression were used for survival analyses. All the data was analyzed by SPSS 20.0.According to optimal cut-off values and quartile values, significant differences were found in different pretreatment albumin, neutrophil levels and ANPG from the K-M curve (all p<0.05). Univariate analyses and multivariate analyses disclosed ANPG was a more sensitive independent predictor for both overall survival (OS) and progression free survival (PFS) than either albumin level or neutrophil level (HRs were higher for ANPG). As for clinical reference values, no significant difference of pretreatment albumin levels was found in K-M curve and univariate analyses. All three indexes lost their significance in multivariate analyses.Higher ANPG predicts worse OS and PFS in NSCLC patients independently, and it is more sensitive than hypoalbuminaemia and neutrophilia. It might be used as a reliable, convenient and more sensitive predictor to assist the identification of patients with poor prognosis and be a hierarchical factor in the future NSCLC clinical trials

An inflammation-related nomogram for predicting the survival of patients with non-small cell lung cancer after pulmonary lobectomy

Abstract Background Emerging inflammatory response biomarkers are developed to predict the survival of patients with cancer, the aim of our study is to establish an inflammation-related nomogram based on the classical predictive biomarkers to predict the survivals of patients with non-small cell lung cancer (NSCLC). Methods Nine hundred and fifty-two NSCLC patients with lung cancer surgery performed were enrolled into this study. The cutoffs of inflammatory response biomarkers were determined by Receiver operating curve (ROC). Univariate and multivariate analysis were conducted to select independent prognostic factors to develop the nomogram. Results The median follow-up time was 40.0 months (range, 1 to 92 months). The neutrophil to lymphocyte ratio (cut-off: 3.10, HR:1.648, P = 0.045) was selected to establish the nomogram which could predict the 5-year OS probability. The C-index of nomogram was 0.72 and the 5-year OS calibration curve displayed an optimal agreement between the actual observed outcomes and the predictive results. Conclusions Neutrophil to lymphocyte ratio was shown to be a valuable biomarker for predicting survival of patients with NSCLC. The addition of neutrophil to lymphocyte ratio could improve the accuracy and predictability of the nomogram in order to provide reference for clinicians to assess patient outcomes

Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP) on SCLC, and tried two drug combinations to improve CP therapy.Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies