Search

PurposeTo develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions.MethodsA total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263).ResultsSix significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40).ConclusionsThe constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Abstract Background In insects, the chemosensory system is crucial in guiding their behaviors for survival. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. There is little known about the chemosensory genes in P. versicolora. Here, we conducted a transcriptome analysis of larvae heads in P. versicolora. Results In this study, 29 odorant binding proteins (OBPs), 6 chemosensory proteins (CSPs), 14 odorant receptors (ORs), 13 gustatory receptors (GRs), 8 ionotropic receptors (IRs) and 4 sensory neuron membrane proteins (SNMPs) were identified by transcriptome analysis. Compared to the previous antennae and foreleg transcriptome data in adults, 12 OBPs, 2 CSPs, 5 ORs, 4 IRs, and 7 GRs were newly identified in the larvae. Phylogenetic analyses were conducted and found a new candidate CO2 receptor (PverGR18) and a new sugar receptor (PverGR23) in the tree of GRs. Subsequently, the dynamic expression profiles of various genes were analyzed by quantitative real-time PCR. The results showed that PverOBP31, OBP34, OBP35, OBP38, and OBP40 were highly expressed in larvae, PverOBP33 and OBP37 were highly expressed in pupae, and PverCSP13 was highly expressed in eggs, respectively. Conclusions We identified a total of 74 putative chemosensory genes based on a transcriptome analysis of larvae heads in P. versicolora. This work provides new information for functional studies on the chemoreception mechanism in P. versicolora.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Objective To assess the ablative margin of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) using a three-dimensional (3D) reconstruction technique. Materials and methods We retrospectively analyzed 36 patients with stage I NSCLC lesions undergoing MWA and analyzed the relationship between minimal ablative margin and the local tumor progression (LTP) interval, the distant metastasis interval and disease-free survival (DFS). The minimal ablative margin was measured using the fusion of 3D computed tomography reconstruction technique. Results Univariate and multivariate analyses indicated that tumor size (hazard ratio [HR] = 1.91, P

Objective. To evaluate the association between neutrophil levels and all-cause mortality in geriatric hip fractures. Methods. Elderly patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between neutrophil levels and mortality. Analyses were performed using Empower Stats and R software. Results. A total of 2,589 patients were included in this study. The mean follow-up period was 38.95 months. During the study period, 875 (33.80%) patients died due to various causes. Linear multivariate Cox regression models showed that neutrophil levels were associated with mortality after adjusting for confounding factors, when neutrophil concentration increased by 1∗109/L, the mortality risk increased by 3% (HR = 1.03, 95% CI: 1.00–1.06, and P=0210). Neutrophil concentration was used as a categorical variable; we only found statistically significant differences when neutrophil levels were high (HR = 1.27, 95% CI:1.05–1.52, and P=0.0122). In addition, the results are stable in P for trend and propensity score matching sensitivity analysis. Conclusions. Neutrophil levels are associated with mortality in geriatric hip fractures and could be considered a predictor of death risk in the long-term. This study is registered with the Chinese Clinical Trial Registry (ChiCTR) as number ChiCTR2200057323.

Objective To analysis the safety and outcome of intravenous thrombolysis with recombinant tissue plasminogen activator (rt⁃PA) in patients with acute mild ischemic stroke. Methods From November 2017 to October 2018, 252 patients with acute mild ischemic stroke who were admitted into our hospital within 4.50 h after onset (84 patients in intravenous thrombolysis group, 108 patients in aspirin and clopidogrel group, and 60 patients in aspirin or clopidogrel group). The general condition, the level of high⁃sensitivity C⁃reactive protein (hs⁃CRP) and erythrocyte sedimentation (ESR) were compared among 3 groups. The modified Rankin Scale (mRS) were evaluated on 7 d after admission or at earlier discharge, and 21 and 90 d. Symptomatic intracranial hemorrhage rates were compared among 3 groups. Results There were no significant difference in general clinical data, the initial level of hs⁃CRP and ESR between the intravenous thrombolytic group and the 2 non⁃thrombolysis groups. At 7 d after admission or earlier discharge, the descending range of hs⁃CRP and ESR in 3 groups were significant (P = 0.000, for all); there were significant differences among the 3 groups (P = 0.000, for all); pairwise comparison of 3 groups showed that the levels of hs⁃CRP and ESR in intravenous thrombolytic group at 7 d were significantly lower than aspirin and/or clopidogrel group (P = 0.000, 0.000; P = 0.000, 0.010). There was no significant difference in the rate of intracranial hemorrhage between thrombolytic group and other 2 groups at 24 h after treatment [1.19% (1/84) vs. 0 (0/168); χ 2discharge, the intravenous thrombolytic group had better prognosis than aspirin and/or dopidogrel group (P = 0.043, 0.012); At 21 and 90 d, the intravenous thrombolytic group had better prognosis than aspirin or clopidogrel group (P = 0.021, 0.037); but compared with aspirin and clopidogrel group, there was no significant difference (P = 0.070, 0.053). Conclusions Patients with mild ischemic stroke, especially that may induce disability should be treated with rt⁃PA intravenous thrombolysis timely. If it impossible by any causes, aspirin and clopidogrel should be given within 24 h after onset. DOI：10.3969/j.issn.1672⁃6731.2019.12.012

In probabilistic analysis, random variables with unknown distributions are often appeared when dealing with practical engineering problem. A Hermite normal transformation model has been proposed to conduct structural reliability assessment without the exclusion of random variables with unknown probability distributions. Recently, linear moments (L-moments) are widely used due to the advantages of stability and insensitivity. In this paper, the complete expressions of the inverse transformation of L-moments Hermite (L-Hermite) model have been proposed. The criteria are proposed to derive the complete inverse transformation of performance function and the complete expressions of the inverse transformation of L-Hermite model are formulated. Moreover, a first-order reliability method for structural reliability analysis based on the proposed inverse transformation of L-Hermite model is then developed using the first four L-moments of random variables. Through the numerical examples, the proposed method is found to be efficient for normal transformations since the results of the proposed L-Hermite are in close agreement with the results of Rosenblatt transformation. Additionally, the reliability index obtained by the proposed method using the first four L-moments of random variables provides a close result to the reliability index obtained by first-order reliability method with known probability density functions in structural reliability assessment.

Plagiodera versicolora (Coleoptera: Chrysomelidae) is a worldwide leaf-eating forest pest in salicaceous trees. The forelegs play important roles in the chemoreception of insects. In this study, we conducted a transcriptome analysis of adult forelegs in P. versicolora and identified a total of 53 candidate chemosensory genes encoding 4 chemosensory proteins (CSPs), 19 odorant binding proteins (OBPs), 10 odorant receptors (ORs), 10 gustatory receptors (GRs), 6 ionotropic receptors (IRs), and 4 sensory neuron membrane proteins (SNMPs). Compared with the previous antennae transcriptome data, 1 CSP, 4 OBPs, 1 OR, 3 IRs, and 4 GRs were newly identified in the forelegs. Subsequently, the tissue expression profiles of 10 P. versicolora chemosensory genes were performed by real-time quantitative PCR. The results showed that PverOBP25, PverOBP27, and PverCSP6 were highly expressed in the antennae of both sexes. PverCSP11 and PverIR9 are predominately expressed in the forelegs than in the antennae. In addition, the expression levels of PverGR15 in female antennae and forelegs were significantly higher than those in the male antennae, implying that it may be involved in some female-specific behaviors such as oviposition site seeking. This work would greatly further the understanding of the chemoreception mechanism in P. versicolora.

Tomato flower abscission is a critical agronomic problem directly affecting yield. It often occurs in greenhouses in winter, with the weak light or hazy weather leading to insufficient photosynthates. The importance of carbohydrate availability in flower retention has been illustrated, while relatively little is understood concerning the mechanism of carbohydrate regulation on flower abscission. In the present study, we analyzed the responding pattern of nonstructural carbohydrates (NSC, including total soluble sugars and starch) and the potential sugar signal pathway involved in abscission regulation in tomato flowers under shading condition, and their correlations with flower abscission rate and abscission-related hormones. The results showed that, when plants suffer from short-term photosynthesis deficiency, starch degradation in flower organs acts as a self-protection mechanism, providing a carbon source for flower growth and temporarily alleviating the impact on flower development. Trehalose 6-phosphate (T6P) and sucrose non-fermenting-like kinase (SnRK1) signaling seems to be involved in adapting the metabolism to sugar starvation stress through regulating starch remobilization and crosstalk with IAA, ABA, and ethylene in flowers. However, a continuous limitation of assimilating supply imposed starch depletion in flowers, which caused flower abscission.

Insects can sense surrounding chemical signals by their accurate chemosensory systems. This system plays a vital role in the life history of insects. Several gene families participate in chemosensory processes, including odorant receptors (ORs), ionotropic receptors (IRs), gustatory receptors (GRs), chemosensory proteins (CSPs), odorant binding proteins (OBPs), and sensory neuron membrane proteins (SNMPs). Plagiodera versicolora (Coleoptera: Chrysomelidae), is a leaf-eating forest pest found in salicaceous trees worldwide. In this study, a transcriptome analysis of male and female adult antennae in P. versicolora individuals was conducted, which identified a total of 98 candidate chemosensory genes including 40 ORs, 7 IRs, 13 GRs, 10 CSPs, 24 OBPs, and 4 SNMPs. Subsequently, the tissue expression profiles of 15 P. versicolora OBPs (PverOBPs) and 39 ORs (PverORs) were conducted by quantitative real-time PCR. The data showed that almost all PverOBPs and PverORs were highly expressed in the male and female antennae. In addition, several OBPs and ORs (PverOBP10, PverOBP12, PverOBP18, PverOR24, and PverOR35) had higher expression levels in female antennae than those in the male antennae, indicating that these genes may be taking part in some female-specific behaviors, such as find mates, oviposition site, etc. This study deeply promotes further understanding of the chemosensory system and functional studies of the chemoreception genes in P. versicolora.

The multi-objective optimisation of high-speed rail profile with small radius curve is studied in the paper. A multi-objective mathematical model for rail profile optimisation of high-speed railway is established. The CN60 rail profile is parameterised into a series of generalised functions of design variables. In order to guarantee the smoothness of the rail profile and meet the maximum grinding depth of rail in China, the constraints are employed. The wheel-rail vertical clearance and equivalent conicity of wheelset are taken as objective functions, and a rail wear prediction programme is compiled. Contact line method is employed to complete the detection algorithm of wheel-rail contact points. Finally, NSGA-II Algorithm is adopted to solve the Pareto-optimal front of the optimisation model. A set of solutions are retrieved from the Pareto optimal front solution as the optimised profile. The optimised rail profile and the original rail profile are matched with the LMA wheel profile (a certain worn type of wheel profiles for EMU in China) respectively. It is testified that the rail profile could effectively reduce the rail wear and improve curving performance. The new method proposed in this paper can provide some reference for the optimisation design of high-speed rail profile with small radius curve. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have been performed to identify genetic variants that are associated with susceptibility to colorectal cancer. Here, the authors expand on these studies and identify a variant that regulates the expression of ETV6 and find that over-expression of ETV6 blocks cell proliferation in vitro.

Background/Aims: FOXO3a is an essential tumor suppressor that regulates the mechanisms of tumorigenesis and leukemogenesis. FOXO3a polymorphisms have not been reported previously associated with an increased risk for childhood acute lymphoblastic leukemia (ALL). In this study, the rs4946936 polymorphism located in the 3'UTR of FOXO3a was selected to evaluate its relationship with a risk for ALL in Chinese children. Methods: Questionnaires, SNaPshot genotyping, real-time PCR, cell transfection and dual luciferase reporter assays were used in this study. Results: Parental alcohol consumption and whether the child's house had been painted had significantly different distributions among the cases and controls. In addition, the C to T mutation was significantly associated with the risk for ALL. We determined that FOXO3a expression levels in patients with the CT or TT genotype were significantly higher than those of patients with the CC genotype. The T allele significantly increased the expression levels in luciferase assays and affected the binding affinity of miR-223 to the FOXO3a 3'UTR. Conclusion: Rs4946936 in FOXO3a was highly associated with an increased risk of childhood ALL in a Chinese population.

In the past decades, a good deal of studies has provided the possibility of the circulating microRNAs (miRNAs) as noninvasive biomarkers for cancer diagnosis. The aim of our study was to detect the levels of circulating miRNAs in tissues and plasmas of gastric cancer (GC) patients and evaluate their diagnostic value.Tissue samples were collected from 85 GC patients. Plasma samples were collected from 285 GC patients and 285 matched controls. Differentially expressed miRNAs were filtered with by Agilent Human miRNA Microarray and TaqMan low density array (TLDA) with pooled samples, followed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation. Receiver operating characteristic (ROC) curves were structured to evaluate the diagnostic accuracy of the miRNAs. The plasma level of miR-26a in GC patients of different clinical stages was compared.Four miRNAs (miR-26a, miR-142-3p, miR-148a, and miR-195) revealed coincidentally decreased levels in tissue and plasma of the GC patients compared with controls, and ROC curves were constructed to demonstrate that miR-26a had a highest area under the ROC curve (AUC) of 0.882. Furthermore, miR-26a was stably detected in the plasma of GC patients with different clinical characteristics.Plasma miR-26a may provide a novel and stable marker of gastric cancer.

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3'UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR = 1.84, 95% CI = 1.14 -2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR = 1.95, 95% CI = 1.04-3.67), low-risk ALL (adjusted OR = 2.09, 95% CI = 1.13-3.87), B-phenotype ALL patients (adjusted OR = 1.78, 95% CI = 1.08-2.95) and T-phenotype ALL patients (adjusted OR = 2.87, 95% CI = 1.16-7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.

BACKGROUND: A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population. METHODS: We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations. RESULTS: No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI = 0.84-1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR = 0.94, 95%CI = 0.80-1.11, P = 0.481 for colon cancer, and OR = 0.96, 95%CI = 0.82-1.13, P = 0.621 for rectum cancer). CONCLUSIONS: Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population.

PURPOSE:Recently, genetic polymorphism (rs3803662C>T) in TOX3 was reported to induce the risk of breast cancer. In this study, we hypothesized that rs3803662 could influence gastric cancer survival outcomes. METHODS:With multiplex SNaPshot method, we genotyped TOX3 rs3803662 in 880 gastric patients with surgical resection. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, Cox regression analysis models and the log-rank test. RESULTS:There was no association in the analyses of rs3803662 and survival of gastric cancer. However, the stratified analysis by histology showed that rs3803662 CT/TT genotype was associated with a significantly better survival for diffuse-type gastric cancer (log-rank p = 0.030, hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.46-0.96), than the CC genotype. In addition, this favorable effect was especially obvious among gastric cancer patients with tumor size >5 cm, T3 and T4 depth of invasion, lymph node metastasis, no drinking, no distant metastasis, no chemotherapy and gastric cardia cancer. CONCLUSIONS:TOX3 rs3803662 might play an important role in the prognostic outcome and treatment of gastric cancer, especially perhaps further help in explaining the reduced risk of death associated with diffuse-type gastric cancer.

PURPOSE: miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. EXPERIMENTAL DESIGN: We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs. RESULTS: We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein. CONCLUSIONS: Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs to regulate cell differentiation, proliferation, development, and apoptosis. The single nucleotide polymorphism (SNP) rs895819 is located at the terminal loop of pre-miR-27a. Here, we aimed to investigate whether SNP rs895819 was associated with the development of renal cell cancer (RCC) in a Chinese population. METHODS: In this case-control study, we recruited 594 RCC patients and 600 cancer-free controls with frequency matched by age and sex. We genotyped this polymorphism using the TaqMan assay and assessed the effect of this polymorphism on RCC survival. Logistic regression model was used to assess the genetic effects on the development of RCC and interactions between rs895819 polymorphism and risk factors. RESULTS: Compared with AA homozygote, individuals carrying AG/GG genotypes had a statistically significant reduced susceptibility to RCC (adjusted OR = 0.71, 95% CI = 0.56-0.90). Furthermore, AG/GG genotypes were associated with reduced RCC susceptibility in localized clinical stage (adjusted OR = 0.71, 95% CI = 0.55-0.91), and similar effects were observed in well differentiated and poorly differentiated RCC (adjusted OR = 0.71, 95% CI = 0.55-0.93 for well differentiated, adjusted OR = 0.51, 95% CI = 0.28-0.93 for poorly differentiated). We also observed that rs895819 had multiplicative interactions with age and hypertension. However, the polymorphism did not influence the survival of RCC. CONCLUSION: Our results suggest that the pre-miR-27a rs895819 polymorphism can predict RCC risk in a Chinese population. Larger population-based prospective studies should be used to validate our findings.

BACKGROUND: Alcohol dehydrogenase 1C (ADH1C) is the key enzyme catalyze oxidation of alcohol to acetaldehyde, which plays vital roles in the etiology of various cancer. To date, studies investigated the association between a functional polymorphism in ADH1C, Ile350Val (rs698), and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 35 case-control studies was performed to address this issue. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with χ2-based Q-test. RESULTS: Overall, no significant associations between ADH1C Ile350Val polymorphism and cancer risk were observed in any genetic models (P>0.05). In the stratified analyses, there was a significantly increased cancer risk among African (Val/Val vs. Ile/Ile OR = 2.19, 95% CI = 1.29-3.73, P(heterogeneity) = 0.989; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.79, 95%CI = 1.18-2.71, P(heterogeneity) = 0.761; Val/Val vs. Ile/Val + Ile/Ile: OR = 1.92, 95% CI = 1.16-3.17, P(heterogeneity) = 0.981) and Asian (Ile/Val vs. Ile/Ile: OR = 1.58, 95% CI = 1.32-1.90, P(heterogeneity) = 0.375; Val/Val vs. Ile/Ile: OR = 3.84, 95% CI = 1.74-8.49, P(heterogeneity) = 0.160; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.65, 95% CI = 1.38-1.96, P(heterogeneity) = 0.330; Val/Val vs. Ile/Val + Ile/Ile: OR = 3.54, 95% CI = 1.62-7.75, P(heterogeneity) = 0.154) studies. CONCLUSIONS: The results indicate that ADH1C Ile350Val polymorphism may contribute to cancer risk among Africans and Asians. Additional comprehensive system analyses are required to validate this association combined with other related polymorphisms.

The HOGG1 gene catalyzes the excision of modified bases and removal of DNA damage adducts. It may play an important role in the prevention of carcinogenesis. Ser³²⁶Cys polymorphism localizes in exon 7 of the hOGG1 gene. It takes the form of an amino acid substitution, from serine to cysteine, in codon 326. Several epidemiological association studies have been conducted on this polymorphism and its relationship with the risk of prostate cancer. However, results have been conflicting. To resolve this conflict, we conducted a meta-analysis on the association between this polymorphism and prostate cancer, taking into account race, country, sources of controls, and smoking status. A total of nine studies covering 2779 cases and 3484 controls were included in the current meta-analysis. Although no significant association was found between hOGG1 Ser³²⁶Cys polymorphism and prostate cancer susceptibility in the pooled analysis, individuals with Ser/Cys+Cys/Cys genotypes were found to have greater risk of prostate cancer if they were also smokers (OR = 2.66, 95% CI = 1.58-4.47) rather than non-smokers (OR = 2.18, 95% CI = 1.13-4.19), compared with those with Ser/Ser genotype. In conclusion, our meta-analysis demonstrates that hOGG1 Ser³²⁶Cys polymorphism is a risk factor for prostate cancer in smokers. Further studies are needed to confirm this relationship.

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR=1.18, 95% CI=1.03-1.34, P

Sulphate and nitrate as respiratory electron acceptors widely exist in various water bodies and are potentially harmful contaminants. In this study, we hypothesized that simultaneous removal of anodic nitrate and cathodic sulphate in a bioelectrochemical reactor (BER) can be accomplished. Results indicated that the average nitrate removal efficiency, sulphate removal efficiency, nitrite production efficiency, and ammonia production efficiency were 38.84, 22.10, 4.56 and 0.38 mg/L, respectively. Simultaneous degradation of anodic nitrate and cathodic sulphate in BER was accomplished, although the obtained results suggested that the removal efficiencies of nitrate and sulphate were not as good as those of conventional biological treatments. The existence of dominant species Pseudomonas and Azoarcus in the anode proved that nitrate was reduced by nitrate-reducing bacteria with acetate as the electron donor. In the cathode, Desulfomicrobium and Thauera were the main functional bacteria for sulphate reduction. [ABSTRACT FROM AUTHOR]

This study investigated why children reproduce and/or reconstruct text in a classroom. The focus was on social classroom variables. Results supported the prediction that students would recall text differentially according to the response interaction pattern maintained with teachers. (Author/DB)

Reports that in a low-risk reading lesson activity, individual differences among students appeared as a function of the type of verbal interaction pattern or "register" with their teacher, while in a high-risk standardized test condition, individual differences appeared as a function of reading ability. (Author/MKM)

This article showed that students demonstrate individual differences in their composition of text. It was found that noncontingent students tended to write more creative essays and used more text-creative or schema-creative propositions in composing their descriptions than did the other two register groups (imitative and contingent). (Author/GK)

The study aimed to investigate the effects of molasses on denitrification in an actual aquaculture wastewater through a set of experiments with the addition of an external C source. The difference in pollutant degradation in the aquaculture water was observed through the aerobic denitrification process in the biological aerated filter. Molasses can cause changes in the water environment and increase the bacterial metabolism when added to the reactor as a cosubstrate. High inorganic N bioremoval levels were also due to the different bacterial communities. At the phylum level, the dominant bacteria were Proteobacteria, Firmicutes and Bacteroidetes. At the genus level, molasses addition also stimulated a significant increase in the aerobic denitrifying bacteria, such as Pseudomonas, Comamonas and Zoogloea. [ABSTRACT FROM AUTHOR]

A bioelectrochemical reactor (BER) with an anaerobic biocathode was used for simultaneous heterotrophic removal of nitrate and sulphate. Different external voltages in range from 0.1 to 0.5 V were applied to investigate its effects on the degradation efficiencies, the formation of elemental sulphur and bacterial community structure. The results indicated that the effects of external voltage on the removal efficiencies of targeted pollutants were unsimilar. Chemical oxygen demand (COD) was highly affected and nitrate was the lowest affected by the variation in the external voltage. Furthermore, the removal rate of sulphate was attributed to the fact that sulphate was not affected entirely by voltage. Notably, the removal efficiency did not continuously increase with increasing voltage. The dominant genera in the reactors were Pseudomonas, Comamonas, Chryseobacterium, Stenotrophomonas, Desulfococcus and Sphingobacterium, respectively. Despite the similarities between the dominant genera, the application of external voltages resulted in variation of abundance of each microorganism in each BER. The results indicated the possible formation of elemental S during the reduction of sulphate. [ABSTRACT FROM AUTHOR]

Purpose: Automatic methods of analyzing of retinal vascular networks, such as retinal blood vessel detection, vascular network topology estimation, and arteries/veins classification are of great assistance to the ophthalmologist in terms of diagnosis and treatment of a wide spectrum of diseases. Methods: We propose a new framework for precisely segmenting retinal vasculatures, constructing retinal vascular network topology, and separating the arteries and veins. A nonlocal total variation inspired Retinex model is employed to remove the image intensity inhomogeneities and relatively poor contrast. For better generalizability and segmentation performance, a superpixel‐based line operator is proposed as to distinguish between lines and the edges, thus allowing more tolerance in the position of the respective contours. The concept of dominant sets clustering is adopted to estimate retinal vessel topology and classify the vessel network into arteries and veins. Results: The proposed segmentation method yields competitive results on three public data sets (STARE, DRIVE, and IOSTAR), and it has superior performance when compared with unsupervised segmentation methods, with accuracy of 0.954, 0.957, and 0.964, respectively. The topology estimation approach has been applied to five public databases (DRIVE,STARE, INSPIRE, IOSTAR, and VICAVR) and achieved high accuracy of 0.830, 0.910, 0.915, 0.928, and 0.889, respectively. The accuracies of arteries/veins classification based on the estimated vascular topology on three public databases (INSPIRE, DRIVE and VICAVR) are 0.90.9, 0.910, and 0.907, respectively. Conclusions: The experimental results show that the proposed framework has effectively addressed crossover problem, a bottleneck issue in segmentation and vascular topology reconstruction. The vascular topology information significantly improves the accuracy on arteries/veins classification. [ABSTRACT FROM AUTHOR]

Automated detection of vascular structures is of great importance in understanding the mechanism, diagnosis, and treatment of many vascular pathologies. However, automatic vascular detection continues to be an open issue because of difficulties posed by multiple factors, such as poor contrast, inhomogeneous backgrounds, anatomical variations, and the presence of noise during image acquisition. In this paper, we propose a novel 2-D/3-D symmetry filter to tackle these challenging issues for enhancing vessels from different imaging modalities. The proposed filter not only considers local phase features by using a quadrature filter to distinguish between lines and edges, but also uses the weighted geometric mean of the blurred and shifted responses of the quadrature filter, which allows more tolerance of vessels with irregular appearance. As a result, this filter shows a strong response to the vascular features under typical imaging conditions. Results based on eight publicly available datasets (six 2-D data sets, one 3-D data set, and one 3-D synthetic data set) demonstrate its superior performance to other state-of-the-art methods. [ABSTRACT FROM PUBLISHER]

This study was conducted to compare the clinical curative effect and acute radiation lung reactions between CyberKnife (CK) and three-dimensional conformal radiotherapy (3DCRT) treatment for inoperable stage I peripheral non-small-cell lung cancer (NSCLC). We retrospectively analyzed 68 patients with inoperable stage I peripheral NSCLC between 2012 and 2013 in our institution. The CK patients were treated with 42-60 Gy in three fractions, while the 3DCRT patients were treated with a total of 60 Gy, at 2 Gy per fraction. The patients were followed up and the clinical outcome was evaluated according to the Response Evaluation Criteria in Solid Tumours. We assessed the presence of acute radiation pneumonitis and pulmonary function status by thoracic scan and pulmonary function tests following CK and 3DCRT treatment. The binary univariate logistic regression analysis demonstrated that treatment method and forced expiratory volume in 1 sec?forced vital capacity (FEV1?FVC) prior to treatment (pre-FEV1?FVC) were the main factors affecting the risk of radiation pneumonitis. The analysis of these factors through multivariate logistic regression method demonstrated that treatment method for grade 1 and 2 [odds ratio (OR)=7.866 and 11.334, respectively) and pre-FEV1/FVC for grade 1, 2 and 3 (OR=5.062, 11.498 and 15.042, respectively) were significant factors affecting the risk of radiation pneumonitis (P<0.05). The 68 patients were divided into two subgroups using the threshold of pre-FEV1/FVC selected by the receiver operating characteristic curve. There were significant differences between the 3DCRT and CK treatment in both the pre-FEV1?FVC <68% and ≥68% subgroups for radiation pneumonitis (P=0.023 and 0.002, respectively). There was no statistically significant change in FVC, FEV1 and carbon monoxide diffusion capacity (DCLO) in the CK group, whereas there was a decrease in DCLO in the 3DCRT group. The complete remission rate was 40 vs. 34.2% at 1 year in the CK and 3DCRT groups, respectively. In conclusion, in this cohort of patients with inoperable stage I peripheral NSCLC, CK appears to be a safe and superior alternative to conventionally fractionated radiotherapy. [ABSTRACT FROM AUTHOR]

We propose a salient object detection algorithm via multi-scale analysis on superpixels. First, multi-scale segmentations of an input image are computed and represented by superpixels. In contrast to prior work, we utilize various Gaussian smoothing parameters to generate coarse or fine results, thereby facilitating the analysis of salient regions. At each scale, three essential cues from local contrast, integrity and center bias are considered within the Bayesian framework. Next, we compute saliency maps by weighted summation and normalization. The final saliency map is optimized by a guided filter which further improves the detection results. Extensive experiments on two large benchmark datasets demonstrate the proposed algorithm performs favorably against state-of-the-art methods. The proposed method achieves the highest precision value of 97.39% when evaluated on one of the most popular datasets, the ASD dataset. [ABSTRACT FROM AUTHOR]

Problem-based learning (PBL) is defined as a student-centered pedagogy which can provide learners more opportunities for application of knowledge acquired from basic science to the working situations than traditional lecture-based learning (LBL) method. In China, PBL is increasingly popular among preventive medicine educators, and multiple studies have investigated the effectiveness of PBL pedagogy in preventive medicine education. A pooled analysis based on 15 studies was performed to obtain an overall estimate of the effectiveness of PBL on learning outcomes of preventive medicine. Overall, PBL was associated with a significant increase in students' theoretical examination scores (SMD = 0.62, 95% CI = 0.41-0.83) than LBL. For the attitude- and skill-based outcomes, the pooled PBL effects were also significant among learning attitude (OR = 3.62, 95% CI = 2.40-5.16), problem solved skill (OR = 4.80, 95% CI = 2.01-11.46), self-directed learning skill (OR55.81, 95% CI53.11-10.85), and collaborative skill (OR54.21, 95% CI5 0.96-18.45). Sensitivity analysis showed that the exclusion of a single study did not influence the estimation. Our results suggest that PBL of preventive medicine education in China appears to be more effective than LBL in improving knowledge, attitude and skills. [ABSTRACT FROM AUTHOR]

The human murine double minute 2 (MDM2) is known as an oncoprotein through inhibiting P53 transcriptional activity and mediating P53 ubiquitination. Therefore, the amplification of MDM2 may attenuate the P53 pathway and promote tumorigenesis. The SNP309 T>G polymorphism (rs2279744), which is located in the intronic promoter ofMDM2 gene, was reported to contribute to the increased level of MDM2 protein. In this hospital-based case-control study, which consisted of 573 cases and 588 controls, we evaluated the association between MDM2 SNP309 and the risk of colorectal cancer (CRC) in a Chinese population by using the TaqMan method to genotype the polymorphism.Wefound that theMDM2 SNP309 polymorphism was significantly associated with CRC risk. In addition, in our meta-analysis, we found a significant association betweenMDM2 SNP309 and CRC risk among Asians, which was consistent with our results. In conclusion, we demonstrated that theMDM2 SNP309 polymorphism increased the susceptibility of CRC in Asian populations. [ABSTRACT FROM AUTHOR]

Two six-wave mixing processes are achieved simultaneously in rubidium vapor and two channels are identified. Signal competition between the two channels is observed and phase matching conditions are analyzed for the two channels. The results show that the two six-wave mixing channels correspond to two parametric processes with weak coupling and, moreover, quantum interference and phase matching conditions primarily govern the signal competition. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion induces renal tubule pyroptosis via the CHOPcaspase- 11 pathway. Am J Physiol Renal Physiol 306: F75-F84, 2014; First published October 16, 2013; doi:10.1152/ajprenal.00117.2013.--The apoptotic or necrotic death of renal tubule epithelial cells is the main pathogenesis of renal ischemia-reperfusion-induced acute kidney injury (AKI). Pyroptosis is a programmed cell death pathway that depends on the activation of the caspase cascade and IL-1 cytokine family members. However, the role of pyroptosis in AKI induced by ischemia-reperfusion remains unclear. In this study, we found that the levels of the pyroptosis-related proteins, including caspase-1, caspase- 11, and IL-1β, were significantly increased after 6 h of renal ischemiareperfusion injury (IRI) and peaked at 12 h after IRI. Enhanced pyroptosis was accompanied by elevated renal structural and functional injury. Similarly, hypoxia-reoxygenation injury (HRI) also induced pyroptosis in renal tubule epithelial NRK-52E cells, which was characterized by increased pore formation and elevated lactate dehydrogenase release. In addition, obvious upregulation of the endoplasmic reticulum (ER) stress biomarkers glucose-regulated protein 78 and C/EBP homologous protein (CHOP) preceded the incidence of pyroptosis in cells treated with IRI or HRI. Pretreatment with a low dose of tunicamycin, an inducer of ER stress, relieved IRI-induced pyroptosis and renal tissue injury. Silencing of CHOP by small interfering RNA significantly decreased HRI-induced pyroptosis of NRK-52E cells, as evidenced by reduced caspase-11 activity and IL-1β generation. Therefore, we conclude that pyroptosis of renal tubule epithelial cells is a key event during IRI and that CHOPcaspase- 11 triggered by overactivated ER stress may be an essential pathway involved in pyroptosis. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs to regulate cell differentiation, proliferation, development, and apoptosis. The single nucleotide polymorphism (SNP) rs895819 is located at the terminal loop of pre-miR- 27a. Here, we aimed to investigate whether SNP rs895819 was associated with the development of renal cell cancer (RCC) in a Chinese population. Methods: In this case-control study, we recruited 594 RCC patients and 600 cancer-free controls with frequency matched by age and sex. We genotyped this polymorphism using the TaqMan assay and assessed the effect of this polymorphism on RCC survival. Logistic regression model was used to assess the genetic effects on the development of RCC and interactions between rs895819 polymorphism and risk factors. Results: Compared with AA homozygote, individuals carrying AG/GG genotypes had a statistically significant reduced susceptibility to RCC (adjusted OR = 0.71, 95% CI = 0.56-0.90). Furthermore, AG/GG genotypes were associated with reduced RCC susceptibility in localized clinical stage (adjusted OR = 0.71, 95% CI = 0.55-0.91), and similar effects were observed in well differentiated and poorly differentiated RCC (adjusted OR = 0.71, 95% CI = 0.55-0.93 for well differentiated, adjusted OR = 0.51, 95% CI = 0.28-0.93 for poorly differentiated). We also observed that rs895819 had multiplicative interactions with age and hypertension. However, the polymorphism did not influence the survival of RCC. Conclusion: Our results suggest that the pre-miR-27a rs895819 polymorphism can predict RCC risk in a Chinese population. Larger population-based prospective studies should be used to validate our findings. [ABSTRACT FROM AUTHOR]

The HOGG1 gene catalyzes the excision of modified bases and removal of DNA damage adducts. It may play an important role in the prevention of carcinogenesis. Ser326Cys polymorphism localizes in exon 7 of the hOGG1 gene. It takes the form of an amino acid substitution, from serine to cysteine, in codon 326. Several epidemiological association studies have been conducted on this polymorphism and its relationship with the risk of prostate cancer. However, results have been conflicting. To resolve this conflict, we conducted a meta-analysis on the association between this polymorphism and prostate cancer, taking into account race, country, sources of controls, and smoking status. A total of nine studies covering 2779 cases and 3484 controls were included in the current meta-analysis. Although no significant association was found between hOGG1 Ser326Cys polymorphism and prostate cancer susceptibility in the pooled analysis, individuals with Ser/ Cys+Cys/Cys genotypes were found to have greater risk of prostate cancer if they were also smokers (OR = 2.66, 95% CI = 1.5824.47) rather than non-smokers (OR = 2.18, 95% CI = 1.1324.19), compared with those with Ser/Ser genotype. In conclusion, our meta-analysis demonstrates that hOGG1 Ser326Cys polymorphism is a risk factor for prostate cancer in smokers. Further studies are needed to confirm this relationship. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The −174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between −174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between −174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR = 4.33, 95% CI: 1.93-9.71 for CC vs. GC, OR = 2.81, 95% CI: 1.39-5.68 for CC vs. GG, and OR = 2.19, 95% CI: 1.32-3.64 for CC vs. GG/GC), and among Asians (OR = 2.08, 95% CI: 1.07-4.06 for CC vs. GG, and OR = 2.20, 95% CI: 1.02-4.74 for CC vs. GG/GC) and Africans (OR = 1.61, 95% CI: 1.07-2.42 for GC vs. GG). This meta-analysis showed the evidence that the −174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, perferably prospective studies are needed to confirm this relationship. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor receptor 4 (FGFR4) displays multiple biological activities, including mitogenic and angiogenic activity, and plays important roles in the etiology and progression of prostate cancer. Gly388Arg polymorphism in FGFR4 gene has been reported to be involved in prostate cancer incidence and aggressiveness in several studies. To derive a more precise estimation of the relationship, a meta-analysis was performed. Methods: Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results: The Arg388 allele increased prostate cancer risk compared with Gly388 allele (OR = 1.17, 95% CI = 1.07- 1.29). When stratified by race, there was a significantly increased prostate cancer risk in Asian and Caucasian populations. Moreover, prostate cancer patients with Arg/Arg genotype had a 1.34-fold increased risk of advanced prostate cancer (95% CI: 1.03-1.74) compared with those with Gly/Gly+Gly/Arg genotype. Conclusion: This meta-analysis showed the evidence that FGFR4 Gly388Arg polymorphism was associated with an increased risk of prostate cancer development and progression, suggesting that FGFR4 Gly388Arg polymorphism could be a marker for prostate cancer development and progression. [ABSTRACT FROM AUTHOR]

The potentially functional polymorphism, rs763110 (−844C>T), in the promoter region of the FAS ligand (FASL) gene, has been implicated in cancer risk, but individually published studies show inconclusive results. To derive a more precise estimation of the association between the FASL rs763110 and risk of cancer, we performed a meta-analysis of 19 published studies that included 11 105 cancer cases and 11 372 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Overall, the rs763110 CT and TT variant genotypes were associated with a significantly reduced cancer risk of all cancer types in different genetic models (homozygote comparison: OR=0.80, 95% CI: 0.68–0.95, Pheterogeneity=0.001; heterozygote comparison: OR=0.82, 95% CI: 0.72–0.95, Pheterogeneity<0.001; dominant model comparison: OR=0.82, 95% CI: 0.71–0.94, Pheterogeneity<0.001; and recessive model comparison: OR=0.88, 95% CI: 0.81–0.96, Pheterogeneity=0.074). In the stratified analyses, the risk remained for studies of the smoking-related cancers and Asian populations, or population-based studies in all the genetic models. Although some modest bias could not be eliminated, this meta-analysis suggests that the FASL rs763110 T allele has a possible protective effect on cancer risk. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) is a multifunctional growth factor that plays important roles in many biological processes, whereas RUNX3 is a target of TGF-β-mediated tumor suppressor pathway. In humans, RUNX3 inactivation may lead to the cancer development, including bladder cancer. To determine whether the RUNX3 polymorphisms are associated with risk of bladder cancer, we conducted a case–control study of 368 bladder cancer patients and 368 cancer-free controls to assess the associations between the RUNX3 tagging single-nucleotide polymorphisms (tSNPs) and bladder cancer risk. In the single-locus analysis, we found a significantly increased risk of bladder cancer associated with the SNP7 rs760805 AA genotype (adjusted odds ratio = 1.97, 95% confidence interval = 1.44–2.69), compared with the AT/TT genotype. Haplotype-based association analysis revealed that the increased risk of bladder cancer was significantly associated with two haplotypes TATCCCAAAA (2.37, 1.16–4.83) and AGCTTGAGAG (2.70, 1.08–6.72) that included the rs760805 A allele. Multifactor dimensionality reduction (MDR) analysis identified a significant more than multiplicative interaction between the SNP7 rs760805 AA and smoking and an additive interaction between the SNP3 rs11249206 TT and smoking on bladder cancer risk. The SNP3 rs11249206, SNP5 rs1395621, SNP7 rs760805, SNP8 rs2236852 and the trichotomized cumulative smoking were the five factors best predicted by the MDR models. When the variables were combined and dichotomized and fitted into the MDR model, the subjects carrying the combined risk stratum had a significantly increased risk for bladder cancer (6.37, 4.57–8.87, P = 7.03 × 10−28). These results suggested that the genetic variants in RUNX3 may modulate the risk of bladder cancer. [ABSTRACT FROM AUTHOR]

Some species have evolved the ability to use the sense of hearing to modify existing vocalizations, or even create new ones, which enlarges their repertoires and results in complex communication systems. 1 This ability corresponds to various forms of vocal production learning that are all possessed by humans and independently displayed by distantly related vertebrates. 1,2,3,4,5,6,7 Among mammals, a few species, including the Egyptian fruit bat, 8,9,10 would possess such vocal production learning abilities. 7 Yet the necessity of an intact auditory system for the development of the Egyptian fruit bat typical vocal repertoire has not been tested. Furthermore, a systematic causal examination of learned and innate aspects of the entire repertoire has never been performed in any vocal learner. Here we addressed these gaps by eliminating pups' sense of hearing at birth and assessing its effects on vocal production in adulthood. The deafening treatment enabled us to both causally test these bats' vocal learning ability and discern learned from innate aspects of their vocalizations. Leveraging wireless individual audio recordings from freely interacting adults, we show that a subset of the Egyptian fruit bat vocal repertoire necessitates auditory feedback. Intriguingly, these affected vocalizations belong to different acoustic groups in the vocal repertoire of males and females. These findings open the possibilities for targeted studies of the mammalian neural circuits that enable sexually dimorphic forms of vocal learning. [Display omitted] • Kanamycin treatment successfully suppresses hearing in Egyptian fruit bat pups • Some vocalizations are learned through the sense of hearing; the majority are innate • Males learn to control both the pitch and the frequency filtering of learned calls • Vocal production is sexually dimorphic in Egyptian fruit bats Elie et al. causally demonstrated which vocalizations of the Egyptian fruit bat vocal repertoire depend on an intact auditory system for their typical development. They also found that vocal production learning is sexually dimorphic in this bat species. [ABSTRACT FROM AUTHOR]

The article presents a study related to the remote modulation of Long non-coding RNA (lncRNA) Gastric Cancer Low-Expressed Transcript (GCLET) by risk variant at 16p13 underlying genetic susceptibility to gastric cancer. It mentions that rs3850997 exerted an allele-specific long-range regulatory effect on GCLET by affecting the binding affinity of CCCTC-Binding Factor (CTCF).