Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis

BACKGROUND: To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. METHODS: Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). RESULTS: In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. CONCLUSIONS: IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow

Polymorphisms of the BCL2 gene associated with susceptibility to tuberculosis

Although tuberculosis (TB) is a serious public health concern, we still don’t understand why only 10% of people infected will develop the disease. Apoptosis plays a role in the interaction of Mycobacterium tuberculosis (Mtb) with the human host and it may be modified by subtle alterations in the B-cell lymphoma 2 (BCL2) gene, an anti-apoptotic regulatory element. Therefore, we investigated whether there is an association between BCL2 polymorphisms and susceptibility to TB by analyzing 130 TB cases, 108 subjects with latent TB infection (LTBI), and 163 healthy controls (HC). Logistic regression was used to calculate odds ratios (ORs) and 95% confidential intervals (95% CIs) for possible associations between single nucleotide polymorphisms (SNPs) in BCL2 and the risk of tuberculosis. We found that the G allele of rs80030866 (OR=0.62, 95%CI:0.42-0.91, P=0.015), and also the G allele of rs9955190 (OR=0.58, 95%CI:0.38-0.88, P=0.011) were less frequent in the TB group compared with the LTBI group. In addition, individuals with rs2551402 CC genotype were more likely to have LTBI than those with AA genotype (OR=2.166, 95%CI:1.046-4.484, P=0.037). Our study suggests that BCL2 gene polymorphisms may be correlated with susceptibility to both TB and LTBI

Can Vascular Endothelial Growth Factor and Microvessel Density Be Used as Prognostic Biomarkers for Colorectal Cancer? A Systematic Review and Meta-Analysis

Background. Vascular endothelial growth factor (VEGF) and microvessel density (MVD) are associated with greater incidence of metastases and decreased survival. Whether they can be used as prognostic indicators of colorectal cancer (CRC) is still controversial. Methods. The authors performed a meta-analysis using the results of a literature search of databases of PubMed and EMBASE, and the references of articles included in the analysis. Meta-analysis was performed using random effects model and hazard ratios (HRs) and 95% confidence intervals (CIs) as effect measures. Results. Twenty studies contributed to the analysis of VEGF, of which 16 were used for overall survival (OS) and 9 for disease-free survival (DFS). High VEGF levels has a relationship with unfavorable survival (OS: HR = 1.98, 95% CI: 1.30–3.02; DFS: HR = 2.10, 95% CI: 1.26–3.49) and a 4.22-fold increase in the rate of distant metastases. Analysis was performed on 18 studies for MVD; the results showed that patients with high MVD expression in tumors appeared to have poorer overall survival (HR = 1.39, 95% CI: 1.22–1.58) and were at a greater risk of having unfavorable clinical characteristics related to prognosis. Corresponding results were obtained from quantitative and/or qualitative analysis of clinicopathological. Conclusions. The meta-analysis demonstrates that VEGF and MVD can be used as prognostic biomarkers for CRC patients

Integrative Analysis of Identifying Methylation-Driven Genes Signature Predicts Prognosis in Colorectal Carcinoma

BackgroundAberrant DNA methylation is a critical regulator of gene expression and plays a crucial role in the occurrence, progression, and prognosis of colorectal cancer (CRC). We aimed to identify methylation-driven genes by integrative epigenetic and transcriptomic analysis to predict the prognosis of CRC patients.MethodsMethylation-driven genes were selected for CRC using a MethylMix algorithm and LASSO regression screening strategy, and were further used to construct a prognostic risk-assessment model. The Cancer Genome Atlas (TCGA) database was obtained as the training set for both the screening of methylation-driven genes and the effect of genes signature on CRC prognosis. Then, the prognostic genes signature was validated in three independent expression arrays of CRC data from Gene Expression Omnibus (GEO).ResultsWe identified 143 methylation-driven genes, of which the combination of BATF, PHYHIPL, RBP1, and PNPLA4 expression levels was screened as a better prognostic model with the best area under the curve (AUC) (AUC = 0.876). Compared with patients in the low-risk group, CRC patients in the high-risk group had significantly poorer overall survival in the training set (HR = 2.184, 95% CI: 1.404–3.396, P < 0.001). Similar results were observed in the validation set. Moreover, VanderWeele’s mediation analysis indicated that the effect of methylation on prognosis was mediated by the levels of their expression (HRindirect = 1.473, P = 0.001, Proportion mediated, 69.10%).ConclusionsWe identified a four-gene prognostic signature by integrative analysis and developed a risk-assessment model that is significantly associated with patients’ survival. Methylation-driven genes might be a potential prognostic signature for CRC patients

Experimental Study and Comparison of Imbalance Ensemble Classifiers with Dynamic Selection Strategy

Imbalance ensemble classification is one of the most essential and practical strategies for improving decision performance in data analysis. There is a growing body of literature about ensemble techniques for imbalance learning in recent years, the various extensions of imbalanced classification methods were established from different points of view. The present study is initiated in an attempt to review the state-of-the-art ensemble classification algorithms for dealing with imbalanced datasets, offering a comprehensive analysis for incorporating the dynamic selection of base classifiers in classification. By conducting 14 existing ensemble algorithms incorporating a dynamic selection on 56 datasets, the experimental results reveal that the classical algorithm with a dynamic selection strategy deliver a practical way to improve the classification performance for both a binary class and multi-class imbalanced datasets. In addition, by combining patch learning with a dynamic selection ensemble classification, a patch-ensemble classification method is designed, which utilizes the misclassified samples to train patch classifiers for increasing the diversity of base classifiers. The experiments’ results indicate that the designed method has a certain potential for the performance of multi-class imbalanced classification

Influence of Different Rotor Teeth Shapes on the Performance of Flux Switching Permanent Magnet Machines Used for Electric Vehicles

This paper investigated a 12-slot/11-pole flux switching permanent magnet (FSPM) machine used for electric vehicles (EVs). Five novel rotor teeth shapes are proposed and researched to reduce the cogging torque and torque ripple of the FSPM machine. These rotor teeth shapes are notched teeth, stepped teeth, eccentric teeth, combination of notched and stepped teeth, and combination of notched and eccentric teeth. They are applied on the rotor and optimized, respectively. The influences of different rotor teeth shapes on cogging torque, torque ripple and electromagnetic torque are analyzed by the 2-D finite-element method (FEM). Then, the performance of FSPMs with different rotor teeth shapes are compared and evaluated comprehensively from the points of view of cogging torque, torque ripple, electromagnetic torque, flux linkage, back electromotive force (EMF), and so on. The results show that the presented rotor teeth shapes, especially the combination of stepped and notched teeth, can greatly reduce the cogging torque and torque ripple with only slight changes in the average electromagnetic torque

PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3β/β-catenin/cyclin D1 signaling pathway in ER-negative breast cancer

Abstract Background A growing amount of evidence has indicated that PSAT1 is an oncogene that plays an important role in cancer progression and metastasis. In this study, we explored the expression and function of PSAT1 in estrogen receptor (ER)-negative breast cancer. Method The expression level of PSAT1 in breast cancer tissues and cells was analyzed using real-time-PCR (RT-PCR), TCGA datasets or immunohistochemistry (IHC). The overall survival of patients with ER-negative breast cancer stratified by the PSAT1 expression levels was evaluated using Kaplan-Meier analysis. The function of PSAT1 was analyzed using a series of in vitro assays. Moreover, a nude mouse model was used to evaluate the function of PSAT1 in vivo. qRT-PCR and western blot assays were used to evaluate gene and protein expression, respectively, in the indicated cells. In addition, we demonstrated that PSAT1 was activated by ATF4 by chromatin immunoprecipitation (ChIP) assays. Results mRNA expression of PSAT1 was up-regulated in ER-negative breast cancer. A tissue microarray that included 297 specimens of ER-negative breast cancer was subjected to an immunohistochemistry assay, which demonstrated that PSAT1 was overexpressed and predicted a poor clinical outcome of patients with this disease. Our data showed that PSAT1 promoted cell proliferation and tumorigenesis in vitro and in vivo. We further found that PSAT1 induced up-regulation of cyclin D1 via the GSK3β/β-catenin pathway, which eventually led to the acceleration of cell cycle progression. Furthermore, ATF4 was also overexpressed in ER-negative breast cancers, and a positive correlation between the ATF4 and PSAT1 mRNA levels was observed in ER-negative breast cancers. We further demonstrated that knockdown of ATF4 by siRNA reduced PSAT1 expression. Finally, chromatin immunoprecipitation (ChIP) assays showed that PSAT1 was a target of ATF4. Conclusions PSAT1, which is overexpressed in ER-negative breast cancers, is activated by ATF4 and promotes cell cycle progression via regulation of the GSK3β/β-catenin/cyclin D1 pathway

Quantitative Analysis of the Proteome and the Succinylome in the Thyroid Tissue of High-Fat Diet-Induced Hypothyroxinemia in Rats

Hypothyroidism is a common disease, and its molecular mechanism still needs further investigation. Lysine succinylation is found to be involved in various metabolic processes associated with hypothyroidism. We performed quantitative analysis on lysine succinylome in thyroids of rats with hypothyroxinemia, which was induced through the administration of a high-fat diet. Overall, 129 differentially expressed proteins were quantified. Downregulated proteins were enriched in the thyroid hormone synthesis and thyroid hormone signaling pathways and were mainly localized in the mitochondria. In addition, 172 lysine succinylation sites on 104 proteins were obviously changed. Decreased succinylated proteins were involved in diverse metabolic pathways and were primarily localized in mitochondria. Finally, the mitochondrial oxygen consumption rates of human normal thyroid epithelial cells were measured to further verify the role of lysine succinylation. The mitochondrial oxygen consumption rates were markedly blunted in the cells treated with palmitic acid (all p<0.05), and the changes were reversed when the cells were treated with palmitic acid and desuccinylase inhibitor together (all p<0.05). Thus, we theorize that the thyroid differentially expressed proteins and changed succinylation levels played potential roles in the mitochondria-mediated energy metabolism in the high-fat diet-induced hypothyroxinemia rat model

Characterization of a Novel Mycovirus from the Phytopathogenic Fungus Botryosphaeria dothidea

Botryosphaeria dothidea is, globally, one of the most economically important phytopathogenic fungi worldwide, causing the canker and dieback of fruit trees. An increasing number of viruses infecting B. dothidea have lately been reported, several of which could confer hypovirulence. In this study, isolated from strain ZM170285-1 of B. dothidea, a novel double-stranded RNA (dsRNA) mycovirus, tentatively named Botryosphaeria dothidea partitivirus 2 (BdPV2), was identified well. The BdPV2 harbored three dsRNA segments (1&ndash;3) with lengths of 1751, 1568, and 1198 bp, which encoded an RNA-dependent RNA polymerase (RdRp), a capsid protein (CP), and a hypothetical protein of unknown function, respectively. BLASTp searches revealed that the predicted protein sequences of dsRNA1 and dsRNA2 had the highest identities (74.95% and 61.01%) with the corresponding dsRNAs of Penicillium stoloniferum virus S (PsV-S), whereas dsRNA3 shared the highest identity (32.95%) with the dsRNA3 of Aspergillus ochraceous virus 1 (AoV1). Phylogenetic analysis indicated that BdPV2 belonged to the Gammapartitivirus genus and Partitiviridae family. To our knowledge, this is the first report of a Gammapartitivirus in B. dothidea

Factors associated with willingness to participate in free HIV test among general residents in Heilongjiang, Northeast China

Abstract Background The human immunodeficiency virus (HIV) is spreading from high-risk groups, such as men who have sex with men (MSM) and sex workers, to the general population in China. This study examined the willingness of general residents in Heilongjiang, Northeast China, to participate in free HIV testing in the nearest health care setting, and the factors that may affect participation, including demographic characteristics, HIV-related knowledge, and stigma. Methods A cross-sectional study was conducted in Heilongjiang Province. All residents aged 15–69 years in two communities in urban areas (September 2007) and four villages in rural areas (April 2008) were recruited using stratified cluster sampling. A total of 4050 residents were interviewed using an anonymous questionnaire. Univariate and multivariate log-binomial regression were used to analyze factors affecting willingness to undergo HIV testing. Results The proportions of participants who were willing to participate in free HIV testing was 73.0% in urban residents and 78.8% in rural residents. Multivariate regression analysis among urban participants showed that greater knowledge of HIV transmission misconceptions (relative risk (RR) = 1.02, 95% confidence interval (CI): 1.00–1.04, P = 0.021) and the awareness that an apparently healthy person can be an HIV carrier (RR = 1.12, 95%CI: 1.03–1.21, P = 0.007) was significantly associated with greater willingness to participate in free HIV testing. Among rural participants, greater knowledge of HIV transmission modes (RR = 1.03, 95%CI: 1.01–1.06 P = 0.001) and the awareness that an apparently healthy person can be an HIV carrier (RR = 1.07; 95%CI: 1.01–1.13 P = 0.019) was significantly associated with greater willingness to participate. Conclusions The overall level of willingness to accept free HIV testing is high, and is higher in rural residents than in urban residents in Heilongjiang. knowledge of HIV transmission misconceptions and that an apparently healthy person can be a carrier for HIV were associated with willingness to accept free HIV testing among urban residents, while knowledge of HIV transmission modes and that an apparently healthy person can be a carrier for HIV were associated with willingness to accept free HIV testing among rural residents.</p