Multiple Imputation Based on Conditional Quantile Estimation

Multiple imputation is a simulation-based approach for the analysis of data with missing observations. It is widely utilized in many set- tings and preeminent among general approaches when the analytical method does not involve a likelihood function or this is too complex. We consider a multiple imputation method based on the estimation of conditional quantiles of missing observations given the observed data. The method does not require modeling a likelihood and has desirable features that may be useful in some practical settings. It can also be applied to impute dependent, bounded, censored and count data. In a simulation study it shows some advantage over the alternative meth- ods considered in terms of mean squared error across all scenarios except when the data arise from a normal distribution where all meth- ods considered perform equally well. We present an application to the estimation of percentiles of body mass index conditional on physical activity assessed by accelerometers

Are clusters of mental retardation correlated with clusters of developmental delay?

Mental retardation (MR) is a subset of developmental delay (DD), a broader classification of childhood disability. The purpose of this study was to determine if clusters of these two conditions were statistically significantly correlated. The residential addresses of 81,935 Medicaid insured pregnant women during each month of pregnancy were used to identify clusters of MR and DD in their children. Correlations between MR and DD were computed based on the sets of P-value surface from selected centroid points, where the P-value for cumulative relative risk of MR and DD was known. The correlations are quite small for all the 10 gestational months for which maternal addresses were available, but they are all statistically significant. This indicates MR and DD are correlated, but they are not linear. When MR was used as the centroid point to identify a cluster the only correlations that were statistically significant were for gestational month 5 and 6 with correlation 0.14 (P = 0.007) for both months. When the centroid points were selected based on the significance of risk of DD, the correlations between MR and DD are not statistically significant for any month. Correlation between MR and DD based on the sets of P-value surfaces from 4 MR clusters are significant in gestational month 5, 6 and 7 with correlation 0.17 (P = 0.047), 0.16 (P = 0.060) and 0.17 (P = 0.044), respectively. Our finding suggests that locations of high risk for the more severe condition, MR, also identify a spatial area where less severe cases of DD might be present, however the reverse is not the case

Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma

<p>Abstract</p> <p>Introduction</p> <p>The aim of the present study was to analyze the expression of matrix metalloproteinase 9 (<it>MMP9</it>) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including the survival of patients with NPC.</p> <p>Methods</p> <p>Using real-time PCR, we detected the mRNA expression of <it>MMP9 </it>in normal nasopharyngeal tissues and nasopharyngeal carcinoma (NPC) tissues. Using immunohistochemistry analysis, we analyzed <it>MMP9 </it>protein expression in clinicopathologically characterized 164 NPC cases (116 male and 48 female) with age ranging from 17 to 80 years (median = 48.4 years) and 32 normal nasopharyngeal tissues. Cases with greater than or equal to 6 and less than 6 of the score value of cytoplasmic <it>MMP9 </it>immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of <it>MMP9 </it>and clinical features was analyzed.</p> <p>Results</p> <p>The expression level of <it>MMP9 </it>mRNA was markedly greater in NPC tissues than that in the nasopharyngeal tissues. Immunohistochemical analysis revealed that the protein expression of <it>MMP9 </it>detected in NPC tissues was higher than that in the nasopharyngeal tissues (<it>P </it>= 0.004). In addition, high levels of <it>MMP9 </it>protein were positively correlated with the status of lymph node metastasis (N classification) (<it>P </it>= 0.002) and clinical stage (<it>P </it>< 0.001) of NPC patients. Patients with higher <it>MMP9 </it>expression had a significantly shorter overall survival time than did patients with low <it>MMP9 </it>expression. Multivariate analysis suggested that the level of <it>MMP9 </it>expression was an independent prognostic indicator (<it>P </it>= 0.008) for the survival of patients with NPC.</p> <p>Conclusion</p> <p>High level of <it>MMP9 </it>expression is a potential unfavorable prognostic factor for patients with NPC.</p

Elevated expression of CDK4 in lung cancer

<p/> <p>Background</p> <p>The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (<it>CDK4</it>) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of <it>CDK4</it>-mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer.</p> <p>Methods</p> <p>Using immunohistochemistry analysis, we analyzed <it>CDK4 </it>protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear <it>CDK4 </it>immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of <it>CDK4 </it>and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression.</p> <p>Results</p> <p>The expression level of <it>CDK4 </it>protein was significantly increased in lung cancer tissues compared to normal tissues (<it>P </it>< 0.001). In addition, high levels of <it>CDK4 </it>protein were positively correlated with the status of pathology classification (<it>P </it>= 0.047), lymph node metastasis (<it>P </it>= 0.007), and clinical stage (<it>P </it>= 0.004) of lung cancer patients. Patients with higher <it>CDK4 </it>expression had a markedly shorter overall survival time than patients with low <it>CDK4 </it>expression. Multivariate analysis suggested the level of <it>CDK4 </it>expression was an independent prognostic indicator (<it>P </it>< 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of <it>CDK4 </it>in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing <it>CDK4 </it>expression also significantly elevated the expression of cell cycle regulator <it>p21</it></p> <p>Conclusion</p> <p>Overexpressed <it>CDK4 </it>is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of <it>p21 </it>in lung cancer</p

Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (<it>EIF4G1</it>) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including patients' survival time.</p> <p>Methods</p> <p>Using real-time PCR, we detected the expression of <it>EIF4G1 </it>in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. <it>EIF4G1 </it>protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of <it>EIF4G1 </it>on cell invasion and tumorigenesis were investigated.</p> <p>Results</p> <p>The expression levels of <it>EIF4G1 </it>mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (<it>P </it>< 0.001). Immunohistochemical analysis revealed that the expression of <it>EIF4G1 </it>protein was higher in NPC tissues than that in the nasopharyngeal tissues (<it>P </it>< 0.001). In addition, the levels of <it>EIF4G1 </it>protein in tumors were positively correlated with tumor T classification (<it>P </it>= 0.039), lymph node involvement (N classification, <it>P </it>= 0.008), and the clinical stages (<it>P </it>= 0.003) of NPC patients. Patients with higher <it>EIF4G</it>1 expression had shorter overall survival time (<it>P </it>= 0.019). Multivariate analysis showed that <it>EIF4G1 </it>expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of <it>EIF4G1 </it>not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed <it>in vivo </it>xenograft tumor growth.</p> <p>Conclusion</p> <p>Our data suggest that <it>EIF4G1 </it>can serve as a biomarker for the prognosis of NPC patients.</p

Enhanced Acetone-Sensing Properties of PEI Thin Film by GO-NH2 Functional Groups Modification at Room Temperature

The functional groups of organic gas-sensing materials play a crucial role in adsorbing specific gas molecules, which is significant to the sensing performances of gas sensor. In this work, amido-graphene oxide (GO-NH2) loaded poly(ethyleneimine) (PEI) composite thin film (PEI/GO-NH2) with abundant amino functional groups -NH2 was successfully prepared on quartz crystal microbalance (QCM) by a combined spraying and drop coating method for acetone detection at room temperature (25°C). The morphological, spectrographic and acetone-sensing properties of composite film were investigated. The results demonstrated that a wrinkled surface morphology was formed and the ratio of nucleophilic -NH2 was increased for PEI/GO-NH2 composite film. Meanwhile, the composite film sensor possessed excellent acetone-sensing performances, and its sensitivity was about 4.2 times higher than that of pure PEI one owing to the increased -NH2 groups. This study reveals the important role of absorbing favorable functional groups and provides a novel method for the rational design and construction of acetone-sensing materials

Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated.</p> <p>Methods</p> <p>Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation.</p> <p>Conclusion</p> <p>This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.</p

Changes in quality of life and disease-related symptoms in patients with polycythemia vera receiving ruxolitinib or standard therapy

Objectives Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant. Methods In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC). Results Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores. Conclusions Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant

Genome-wide analysis of long non-coding RNAs (lncRNAs) in tea plants (Camellia sinensis) lateral roots in response to nitrogen application

Tea (Camellia sinensis) is one of the significant cash crops in China. As a leaf crop, nitrogen supply can not only increase the number of new shoots and leaves but also improve the tenderness of the former. However, a conundrum remains in science, which is the molecular mechanism of nitrogen use efficiency, especially long non-coding RNA (lncRNA). In this study, a total of 16,452 lncRNAs were identified through high-throughput sequencing analysis of lateral roots under nitrogen stress and control conditions, of which 9,451 were differentially expressed lncRNAs (DE-lncRNAs). To figure out the potential function of nitrogen-responsive lncRNAs, co-expression clustering was employed between lncRNAs and coding genes. KEGG enrichment analysis revealed nitrogen-responsive lncRNAs may involve in many biological processes such as plant hormone signal transduction, nitrogen metabolism and protein processing in endoplasmic reticulum. The expression abundance of 12 DE-lncRNAs were further verified by RT-PCR, and their expression trends were consistent with the results of RNA-seq. This study expands the research on lncRNAs in tea plants, provides a novel perspective for the potential regulation of lncRNAs on nitrogen stress, and valuable resources for further improving the nitrogen use efficiency of tea plants