Search

Background: The aim of the present systematic review was to evaluate the hypothesis of an association between periodontitis and the development of cancer. Methods: Two reviewers independently screened electronic and manual sources for pertinent articles. Primary outcome measures were the occurrence of neoplasm diagnosis in exposed and non-exposed groups, reported to evaluate association between cancer and periodontitis. Results: Of the 490 initially retrieved papers 10 were included in the qualitative synthesis and eight in the quantitative synthesis; the eight papers covered six studies. Considering hazard ratios, a statistically significant association was found for all cancers studied (1.14; CI 95%: 1.04, 1.24), digestive tract cancer (1.34; CI 95%: 1.05, 1.72), pancreatic cancer (1.74; CI 95%: 1.21, 2.52), prostate cancer (1.25; CI 95%: 1.04, 1.51), breast cancer (1.11; CI 95%: 1.00, 1.23), corpus uteri cancer (2.20; CI 95%: 1.16, 4.18), lung cancer (1.24; CI 95%: 1.06, 1.45), hematological cancer (1.30; CI 95%: 1.11, 1.53), esophagus / oropharyngeal cancer pooled together (2.25; CI 95%: 1.30, 3.90) and Non-Hodgkin lymphoma (1.30; CI 95%: 1.11, 1.52). Conclusions: Despite the sparse scientific evidence and considering the low statistical power of the results, this systematic review revealed a substantial lack of studies with standardized and comparable methods to speculate about the association between periodontitis and cancer; more studies are need in order to explore further the scientific evidence of such correlation. [ABSTRACT FROM AUTHOR]

The ensemble method random forests has become a popular classification tool in bioinformatics and related fields. The out-of-bag error is an error estimation technique often used to evaluate the accuracy of a random forest and to select appropriate values for tuning parameters, such as the number of candidate predictors that are randomly drawn for a split, referred to as mtry. However, for binary classification problems with metric predictors it has been shown that the out-of-bag error can overestimate the true prediction error depending on the choices of random forests parameters. Based on simulated and real data this paper aims to identify settings for which this overestimation is likely. It is, moreover, questionable whether the out-of-bag error can be used in classification tasks for selecting tuning parameters like mtry, because the overestimation is seen to depend on the parameter mtry. The simulation-based and real-data based studies with metric predictor variables performed in this paper show that the overestimation is largest in balanced settings and in settings with few observations, a large number of predictor variables, small correlations between predictors and weak effects. There was hardly any impact of the overestimation on tuning parameter selection. However, although the prediction performance of random forests was not substantially affected when using the out-of-bag error for tuning parameter selection in the present studies, one cannot be sure that this applies to all future data. For settings with metric predictor variables it is therefore strongly recommended to use stratified subsampling with sampling fractions that are proportional to the class sizes for both tuning parameter selection and error estimation in random forests. This yielded less biased estimates of the true prediction error. In unbalanced settings, in which there is a strong interest in predicting observations from the smaller classes well, sampling the same number of observations from each class is a promising alternative. [ABSTRACT FROM AUTHOR]

Background: Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results: In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347–3.744) and MMP-7 with lowest (1.099, CI: 1.018–1.187)) pooled HRs are presented. Conclusions: The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. [ABSTRACT FROM AUTHOR]

A closer association has been found between the microRNA-146a rs2910164 polymorphism and the risk of head and neck carcinoma in some molecular epidemiological studies. Recently two meta-analyses were performed to explore the relationship between miRNA-146a polymorphisms and the susceptibility of squamous cell carcinoma of the head and neck (SCCHN); however, they yielded conflicting results in susceptibility regarding ethnic variations. Hence, the present study was performed to explain the relationship between the miRNA-146a rs2910164 polymorphism and the risk of SCCHN development of Chinese patients. We retrieved databases and screened eligible papers up to March 10, 2017 and then we extracted the essential data. The subgroup analyses were also performed based on the tumor site, region, and genotyping means. Crude odds ratios (OR) at 95% confidence intervals (CI) were chosen to describe the strength of the association. As a result, 6 publications were included in our study which involved 8 independent case-control studies. A significant association was found between miR-146a rs2910164 polymorphisms and the risk of SCCHN in Chinese patients according to the overall data [CC+CG vs. GG: OR = 1.13; 95%CI = 1.00–1.29; CC vs. GG: OR = 1.19; 95%CI = 1.03–1.38]. According to the subgroup analysis based on tumor site, the risk of cancer was significantly increased among laryngeal cancer (dominant model: OR = 1.76, 95%CI = 1.26~2.46, P = 0.001; homozygote model: OR = 1.83, 95%CI = 1.25~2.67, P = 0.002) and nasopharyngeal carcinoma (homozygote model: OR = 1.41, 95%CI = 1.05~1.90, P = 0.022). In summary, variant alleles of miR-146a rs2910164 alleles may have an association with the increased risk of SCCHN in Chinese patients, and these associations differed based on tumor site. Further studies including a larger sample size will be necessary to clarify these results. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC) by conducting a meta-analysis of 10 cohort studies. Methods: The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed. Results: The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS), nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR) 1.22; 95% confidence interval (CI) 1.08–1.38). In addition, we also found a promising increased risk for colon cancer (CC) (RR 1.30, 95% CI 1.07–1.58), but no relationship between cholecystectomy and rectum cancer (RC) (RR 1.09; 95% CI 0.89–1.34) was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC) was found (RR 1.18, 95% CI 1.11–1.26). After combining the ACC, transverse colon cancer (TCC), sigmoid colon cancer (SCC) and descending colon cancer (DCC) patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11–1.26). Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11–1.26) in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05–1.36). Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03–1.34). However, there was no relationship between gender and CC or RC. Furthermore, no publication bias was observed, and the sensitivity analysis indicated stable results. Conclusions: This meta-analysis of 10 cohort studies revealed that cholecystectomy is associated with an increased risk for CRC, CC and ACC, particularly in Western countries. No relationship between cholecystectomy and RC was observed. There was no relationship between gender and either CC or RC, but a positive relationship between female gender and CRC was observed. [ABSTRACT FROM AUTHOR]

Breast cancer is an all too common disease in women, making how to effectively predict it an active research problem. A number of statistical and machine learning techniques have been employed to develop various breast cancer prediction models. Among them, support vector machines (SVM) have been shown to outperform many related techniques. To construct the SVM classifier, it is first necessary to decide the kernel function, and different kernel functions can result in different prediction performance. However, there have been very few studies focused on examining the prediction performances of SVM based on different kernel functions. Moreover, it is unknown whether SVM classifier ensembles which have been proposed to improve the performance of single classifiers can outperform single SVM classifiers in terms of breast cancer prediction. Therefore, the aim of this paper is to fully assess the prediction performance of SVM and SVM ensembles over small and large scale breast cancer datasets. The classification accuracy, ROC, F-measure, and computational times of training SVM and SVM ensembles are compared. The experimental results show that linear kernel based SVM ensembles based on the bagging method and RBF kernel based SVM ensembles with the boosting method can be the better choices for a small scale dataset, where feature selection should be performed in the data pre-processing stage. For a large scale dataset, RBF kernel based SVM ensembles based on boosting perform better than the other classifiers. [ABSTRACT FROM AUTHOR]

Purpose: Many studies have reported that carbohydrate antigen 153 (CA153) in breast secretions (BS) can discriminate breast cancer (BC) patients from healthy individuals, indicating CA153 in BS as a potential index for BC. This meta-analysis aimed to evaluate the actual diagnostic value of CA153 in BS. Methods: Related papers were obtained from Pubmed, Embase, Scopus, Ovid, Sciverse, the Cochrane library, Chinese Biomedical literature Database (CBM), Technology of Chongqing (VIP), Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CA153 in BS for BC diagnosis were analyzed with the random effect model. SROC and the area under the curve (AUC) were applied to assess overall diagnostic efficiency. Results: This meta-analysis included five studies with a total of 329 BC patients and 381 healthy subjects. For CA153 in BS, the summary sensitivity, specificity, and DOR to diagnose BC were 0.63 (95% confidence interval (CI): 0.57∼0.68), 0.82 (95% CI: 0.78∼0.86), and 9.18 (95% CI: 4.22∼19.95), respectively. Furthermore, the AUC of BS CA153 in the diagnosis of BC was 0.8614. Conclusions: CA153 in BS is a valuable molecular marker in diagnosing BC and should be applied in standard clinical practices of BC screening upon confirmation of our findings in a larger prospective study. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone. Methods: Hazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05. Results: A total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74–0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55–0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone. Conclusion: The findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients’ characteristics important for the treatment selection criteria. [ABSTRACT FROM AUTHOR]

Background: Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. Objectives: We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. Methods: Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. Results: Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79–0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76–0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. Conclusions and Implications: The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. Systematic Review Protocol Number: CRD42015014145 [ABSTRACT FROM AUTHOR]

Distinguishing certain and uncertain information is of crucial importance both in the scientific field in the strict sense and in the popular scientific domain. In this paper, by adopting an epistemic stance perspective on certainty and uncertainty, and a mixed procedure of analysis, which combines a bottom-up and a top-down approach, we perform a comparative study (both qualitative and quantitative) of the uncertainty linguistic markers (verbs, non-verbs, modal verbs, conditional clauses, uncertain questions, epistemic future) and their scope in three different corpora: a historical corpus of 80 biomedical articles from the British Medical Journal (BMJ) 1840–2007; a corpus of 12 biomedical articles from BMJ 2013, and a contemporary corpus of 12 scientific popular articles from Discover 2013. The variables under observation are time, structure (IMRaD vs no-IMRaD) and genre (scientific vs popular articles). We apply the Generalized Linear Models analysis in order to test whether there are statistically significant differences (1) in the amount of uncertainty among the different corpora, and (2) in the categories of uncertainty markers used by writers. The results of our analysis reveal that (1) in all corpora, the percentages of uncertainty are always much lower than that of certainty; (2) uncertainty progressively diminishes over time in biomedical articles (in conjunction with their structural changes–IMRaD–and to the increase of the BMJ Impact Factor); and (3) uncertainty is slightly higher in scientific popular articles (Discover 2013) as compared to the contemporary corpus of scientific articles (BMJ 2013). Nevertheless, in all corpora, modal verbs are the most used uncertainty markers. These results suggest that not only do scientific writers prefer to communicate their uncertainty with markers of possibility rather than those of subjectivity but also that science journalists prefer using a third-person subject followed by modal verbs rather than a first-person subject followed by mental verbs such as think or believe. [ABSTRACT FROM AUTHOR]

Feature screening has become a real prerequisite for the analysis of high-dimensional genomic data, as it is effective in reducing dimensionality and removing redundant features. However, existing methods for feature screening have been mostly relying on the assumptions of linear effects and independence (or weak dependence) between features, which might be inappropriate in real practice. In this paper, we consider the problem of selecting continuous features for a categorical outcome from high-dimensional data. We propose a powerful statistical procedure that consists of two steps, a nonparametric significance test based on edge count and a multiple testing procedure with dependence adjustment for false discovery rate control. The new method presents two novelties. First, the edge-count test directly targets distributional difference between groups, therefore it is sensitive to nonlinear effects. Second, we relax the independence assumption and adapt Efron’s procedure to adjust for the dependence between features. The performance of the proposed procedure, in terms of statistical power and false discovery rate, is illustrated by simulated data. We apply the new method to three genomic datasets to identify genes associated with colon, cervical and prostate cancers. [ABSTRACT FROM AUTHOR]

High dimensional biomedical data contain tens of thousands of features, accurate and effective identification of the core features in these data can be used to assist diagnose related diseases. However, there are often a large number of irrelevant or redundant features in biomedical data, which seriously affect subsequent classification accuracy and machine learning efficiency. To solve this problem, a novel filter feature selection algorithm based on redundant removal (FSBRR) is proposed to classify high dimensional biomedical data in this paper. First of all, two redundant criteria are determined by vertical relevance (the relationship between feature and class attribute) and horizontal relevance (the relationship between feature and feature). Secondly, to quantify redundant criteria, an approximate redundancy feature framework based on mutual information (MI) is defined to remove redundant and irrelevant features. To evaluate the effectiveness of our proposed algorithm, controlled trials based on typical feature selection algorithm are conducted using three different classifiers, and the experimental results indicate that the FSBRR algorithm can effectively reduce the feature dimension and improve the classification accuracy. In addition, an experiment of small sample dataset is designed and conducted in the section of discussion and analysis to clarify the specific implementation process of FSBRR algorithm more clearly. [ABSTRACT FROM AUTHOR]

Emerging evidence has shown microRNAs (miRNAs) play an important role in human disease research. Identifying potential association among them is significant for the development of pathology, diagnose and therapy. However, only a tiny portion of all miRNA-disease pairs in the current datasets are experimentally validated. This prompts the development of high-precision computational methods to predict real interaction pairs. In this paper, we propose a new model of Logistic Model Tree for predicting miRNA-Disease Association (LMTRDA) by fusing multi-source information including miRNA sequences, miRNA functional similarity, disease semantic similarity, and known miRNA-disease associations. In particular, we introduce miRNA sequence information and extract its features using natural language processing technique for the first time in the miRNA-disease prediction model. In the cross-validation experiment, LMTRDA obtained 90.51% prediction accuracy with 92.55% sensitivity at the AUC of 90.54% on the HMDD V3.0 dataset. To further evaluate the performance of LMTRDA, we compared it with different classifier and feature descriptor models. In addition, we also validate the predictive ability of LMTRDA in human diseases including Breast Neoplasms, Breast Neoplasms and Lymphoma. As a result, 28, 27 and 26 out of the top 30 miRNAs associated with these diseases were verified by experiments in different kinds of case studies. These experimental results demonstrate that LMTRDA is a reliable model for predicting the association among miRNAs and diseases. [ABSTRACT FROM AUTHOR]

Robustly predicting outcome for cancer patients from gene expression is an important challenge on the road to better personalized treatment. Network-based outcome predictors (NOPs), which considers the cellular wiring diagram in the classification, hold much promise to improve performance, stability and interpretability of identified marker genes. Problematically, reports on the efficacy of NOPs are conflicting and for instance suggest that utilizing random networks performs on par to networks that describe biologically relevant interactions. In this paper we turn the prediction problem around: instead of using a given biological network in the NOP, we aim to identify the network of genes that truly improves outcome prediction. To this end, we propose SyNet, a gene network constructed ab initio from synergistic gene pairs derived from survival-labelled gene expression data. To obtain SyNet, we evaluate synergy for all 69 million pairwise combinations of genes resulting in a network that is specific to the dataset and phenotype under study and can be used to in a NOP model. We evaluated SyNet and 11 other networks on a compendium dataset of >4000 survival-labelled breast cancer samples. For this purpose, we used cross-study validation which more closely emulates real world application of these outcome predictors. We find that SyNet is the only network that truly improves performance, stability and interpretability in several existing NOPs. We show that SyNet overlaps significantly with existing gene networks, and can be confidently predicted (~85% AUC) from graph-topological descriptions of these networks, in particular the breast tissue-specific network. Due to its data-driven nature, SyNet is not biased to well-studied genes and thus facilitates post-hoc interpretation. We find that SyNet is highly enriched for known breast cancer genes and genes related to e.g. histological grade and tamoxifen resistance, suggestive of a role in determining breast cancer outcome. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests statins may have anti-tumor properties. Large observational studies are also consistent with improved survival and cancer-specific outcomes among cancer patients on statins. We sought to evaluate the randomized controlled trials of statins in addition to usual anti-cancer therapy. Methods: A systematic search of MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, Papers First and Clinicaltrials.gov was performed from inception through to July 4, 2017 to identify randomized clinical trials that investigated statin therapy in cancer patients. Our primary outcome was overall survival and our secondary outcome was progression-free survival. We calculated summary hazard ratio’s (HR) and 95% confidence intervals (CI) based on random-effects models using aggregate data. PROSPERO (CRD42017065503). Results: Ten studies with 1,881 individuals were included with 1,572 deaths and a median follow-up of 23 months. All trials included patients with advanced (stage 3 or higher) disease. There was minimal between-study statistical heterogeneity (I2 = 1.8%, for OS; I2 = 0%, for PFS). The pooled HR for overall survival in patients randomized to statins plus standard anti-cancer therapy versus standard therapy alone was 0.94 (95% CI, 0.85 to 1.04). In the 9 studies that reported progression-free survival (1,798 participants), the pooled HR for statin plus standard therapy versus standard therapy alone was 0.97 (95% CI, 0.87 to 1.07). Conclusions: In patients with advanced cancer and a prognosis <2 years, the addition of statins to standard anti-cancer therapy does not appear to improve overall survival or progression-free survival. Future research should assess if cancer patients with better prognosis benefit from longer-term statin therapy. [ABSTRACT FROM AUTHOR]

Background: Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer. Methods: Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted. Results: Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64–0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53–0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73–1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95). Conclusion: Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers? [ABSTRACT FROM AUTHOR]

High-throughput data generation platforms, like mass-spectrometry, microarrays, and second-generation sequencing are susceptible to batch effects due to run-to-run variation in reagents, equipment, protocols, or personnel. Currently, batch correction methods are not commonly applied to microbiome sequencing datasets. In this paper, we compare different batch-correction methods applied to microbiome case-control studies. We introduce a model-free normalization procedure where features (i.e. bacterial taxa) in case samples are converted to percentiles of the equivalent features in control samples within a study prior to pooling data across studies. We look at how this percentile-normalization method compares to traditional meta-analysis methods for combining independent p-values and to limma and ComBat, widely used batch-correction models developed for RNA microarray data. Overall, we show that percentile-normalization is a simple, non-parametric approach for correcting batch effects and improving sensitivity in case-control meta-analyses. [ABSTRACT FROM AUTHOR]

Background: Published data on the relationship between matrix metalloproteinases (MMPs) polymorphisms and ovarian cancer risk have implicated inconclusive results. To evaluate the role of MMPs polymorphisms in ovarian cancer risk, a meta-analysis and systematic review were performed. Methods: MMPs polymorphisms which could be quantitatively synthesized were involved in meta-analysis. Five comparison models (homozygote model, heterozygote model, dominant model, recessive model, additive model) were carried out, a subgroup analysis was performed to clarify heterogeneity source. The remaining polymorphisms which could not be quantitatively synthesized were involved in systematic review. Results: 10 articles with 20 studies were included in this paper. Among those studies, 8 studies involving MMP1 rs1799750 and MMP3 rs34093618 could be meta-analyzed and 12 studies involving 12 polymorphisms could not. Meta-analysis showed that no associations were found between MMP1 rs1799750 (homozygote model: OR = 0.93, 95%CI = 0.70–1.23, POR = 0.60; heterozygote model: OR = 1.09, 95%CI = 0.78–1.54, POR = 0.61; dominant model: OR = 1.02, 95%CI = 0.83–1.25, POR = 0.84; recessive model: OR = 0.95, 95%CI = 0.75–1.21, POR = 0.67; additive model: OR = 1.00, 95%CI = 0.85–1.17, POR = 0.99), MMP3 rs34093618 (homozygote model: OR = 1.25, 95%CI = 0.70–2.24, POR = 0.46; heterozygote model: OR = 1.08, 95%CI = 0.51–2.31, POR = 0.84; dominant model: OR = 0.97, 95%CI = 0.68–1.38, POR = 0.85; recessive model: OR = 1.12, 95%CI = 0.69–1.80, POR = 0.65; additive model: OR = 1.01, 95%CI = 0.79–1.31, POR = 0.91) and ovarian cancer. Furthermore, similar results were detected in subgroup analysis. The systematic review on 12 polymorphisms suggested that MMP2 C-735T, MMP7 A-181G, MMP8 rs11225395, MMP9 rs6094237, MMP12 rs2276109, MMP20 rs2292730, MMP20 rs12278250, MMP20 rs9787933 might have a potential effect on ovarian cancer risk. Conclusions: In summary, polymorphisms of MMPs might not be associated with ovarian cancer risk. However, it is necessary to conduct more larger-scale, multicenter, and high-quality studies in the future. [ABSTRACT FROM AUTHOR]

Background: The association between height and lung cancer risk has been investigated by epidemiological studies but the results are inconsistent. This meta-analysis was to evaluate whether the height is associated with lung cancer. Methods: We identified relevant articles by searching the MEDLINE and EMBASE databases, and reviewed the reference lists of selected papers. A random effect model was used to calculate summary odds ratios (OR) and relative risk (RR) with 95% confidence intervals (95% CI). Publication bias was estimated using Egger’s regression asymmetry test. Results: We included a total 16 studies (15 prospective studies and one case–control study) on adult height and lung cancer risk in the meta-analysis. Overall, per 10-cm height increases were associated with increased risk of lung cancer (RR 1.06; 95% CI 1.03–1.09, I2 = 43.6%). Conclusions: In this meta-analysis, high adult height is related to increased lung cancer risk. Well-designed, large prospective studies are required to obtain a better indication of the relationship. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) comprises a heterogenous group of tumors. Traditionally, papillary RCC (pRCC) is associated with a favorable outcome compared to clear cell RCC (ccRCC), while other series report equivalent or worse prognosis. In this paper we comparatively evaluate outcome of pRCC versus ccRCC in two large multi-institutional databases (cohort study), including distribution of pRCC subtypes 1 and 2. Retrospective data of 1,943 surgically treated pRCC patients from 17 European/ North American centers between 1984–2015 were compared to 5,600 ccRCC patients from a database comprising 11 European/ North American centers (1984–2011). Median follow-up was 64.6 months. Differences between pRCC, subtypes, and ccRCC were compared with t-tests, Chi^2-tests, and exact Fisher tests. Cancer-specific mortality was analyzed with cumulative incidence curves and Cox cause-specific hazard models. The robustness of our results was examined with sensitivity analyses. We present that cancer-specific mortality rates and variables as stage, lymph node, and distant metastasis differ significantly between groups. Furthermore, we demonstrate that patients with non-metastatic pRCC had a significantly better cancer-specific mortality (HR 0.76, p = 0.007), when compared to ccRCC. Additionally, pRCC type 2 versus ccRCC exhibited no difference in cancer-specific mortality (HR 0.9, p = 0.722), whereas pRCC type 1 versus ccRCC displayed a risk of death reduced by 69% (p = 0.044). Taken together, outcome of pRCC versus ccRCC varies significantly in non-metastatic disease. Furthermore, pRCC type 2 exhibited no difference in cancer-specific mortality, whereas pRCC type 1 displayed a significantly reduced risk of death. Consequently, there is urgent need to respect histopathological entities and their subtypes, when assigning follow-up or targeted therapy to RCC patients. [ABSTRACT FROM AUTHOR]

The expression of Programmed cell Death Ligand 1 (PD-L1) is observed in many malignant tumors and is associated with poor prognosis including Gastric Cancer (GC). The relationship between PD-L1 expression and prognosis, however, is controversial in GC. This paper purports to use a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in GC. For this study, the following databases were searched for articles published from June 2003 until February 2017: PubMed, EBSCO, Web of Science and Cochrane Library. The baseline information extracted were: authors, year of publication, country where the study was performed, study design, sample size, follow-up time, baseline characteristics of the study population, pathologic data, overall survival (OS). A total of 15 eligible studies covering 3291 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The analysis showed that the expression level of PD-L1 was associated with the overall survival in GC (Hazard Ratio, HR = 1.46, 95%CI = 1.08–1.98, P = 0.01, random-effect). In addition to the above, subgroup analysis showed that GC patients with deeper tumor infiltration, positive lymph-node metastasis, positive venous invasion, Epstein-Barr virus infection positive (EBV+), Microsatellite Instability (MSI) are more likely to expression PD-L1. The results of this meta-analysis suggest that GC patients, specifically EBV+ and MSI, may be prime candidates for PD-1 directed therapy. These findings support anti-PD-L1/PD-1 antibodies as a kind of immunotherapy which is promising for GC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) in the clinic is rare, and surgical treatment is currently considered the most effective treatment. However, the influence of BDTT on the prognosis of HCC patients who underwent surgery remains controversial in previous studies. Therefore, this paper uses meta-analysis method to elucidate this controversy. Methods: In this study, we conducted a literature search on databases PubMed, Embase and Web of Science from inception until September 2016. Each study was evaluated with Newcastle-Ottawa Scale (NOS). The pooled effect was calculated, and the association between BDTT and overall survival (OS) or disease-free survival (DFS) was reevaluated using meta-analysis for hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 11 studies was included containing 5295 patients. The (HR) for OS and DFS was 3.21 and 1.81, 95%CI was 2.34–4.39 and 1.17–2.78 respectively. Conclusions: The results showed that HCC patients with BDTT had a worse prognosis than those without BDTT after hepatic resection or liver transplantation (LT). [ABSTRACT FROM AUTHOR]

Background: Previous studies have noted significant gender difference in the risk of liver cancer among hepatitis B chronic infection patients. Some indicated that it might be due to lifestyle-related differences. This paper tests whether or not such a gender discrepancy among the chronic hepatitis B population is confounded by lifestyle and environment related exposures. Methods: We retrieved a sample of 1863 participants from a prospective cohort in Haimen City, China in 2003. Liver disease severity was categorized as “normal”, “mild”, “moderate”, and “severe” based on a clinical diagnosis. Lifestyle and environmental exposures were measured by questionnaires. We used factor analysis and individual variables to represent lifestyle and environmental exposures. We applied the cumulative logit models to estimate the effect of gender on liver disease severity and how it was impacted by lifestyle and environmental exposures. Results: Gender and HBeAg positivity were independent risk factors for more severe liver disease. Compared to females, males were 2.08 times as likely to develop more severe liver disease (95% CI: 1.66–2.61). Participants who were HBeAg positivite were 2.19 times (95% CI: 1.61–2.96) as likely to develop more severe liver disease compared to those who were negative. Controlling for lifestyle and environmental exposures did not change these estimations. Conclusions: Males in the HBV infected population have an increased risk of severe liver disease. This gender effect is independent of the lifestyle and environmental exposures addressed in this study. Our findings support the hypothesis that gender discrepancies in HCC risk are attributable to intrinsic differences between males and females. [ABSTRACT FROM AUTHOR]

One of the most accepted findings across psychology is that people are unrealistically optimistic in their judgments of comparative risk concerning future life events—they judge negative events as less likely to happen to themselves than to the average person. Harris and Hahn (2011), however, demonstrated how unbiased (non-optimistic) responses can result in data patterns commonly interpreted as indicative of optimism due to statistical artifacts. In the current paper, we report the results of 5 studies that control for these statistical confounds and observe no evidence for residual unrealistic optimism, even observing a ‘severity effect’ whereby severe outcomes were overestimated relative to neutral ones (Studies 3 & 4). We conclude that there is no evidence supporting an optimism interpretation of previous results using the prevalent comparison method. [ABSTRACT FROM AUTHOR]

Spatial scan statistics with circular or elliptic scanning windows are commonly used for cluster detection in various applications, such as the identification of geographical disease clusters from epidemiological data. It has been pointed out that the method may have difficulty in correctly identifying non-compact, arbitrarily shaped clusters. In this paper, we evaluated the Gini coefficient for detecting irregularly shaped clusters through a simulation study. The Gini coefficient, the use of which in spatial scan statistics was recently proposed, is a criterion measure for optimizing the maximum reported cluster size. Our simulation study results showed that using the Gini coefficient works better than the original spatial scan statistic for identifying irregularly shaped clusters, by reporting an optimized and refined collection of clusters rather than a single larger cluster. We have provided a real data example that seems to support the simulation results. We think that using the Gini coefficient in spatial scan statistics can be helpful for the detection of irregularly shaped clusters. [ABSTRACT FROM AUTHOR]

Identification of miRNA-disease association is a fundamental challenge in human health clinic. However, the known miRNA-disease associations are rare and experimental verification methods are expensive and time-consuming. Therefore, there is a strong incentive to develop computational methods. In this paper, we calculate the similarity score for each miRNAs pair by integrating miRNA functional similarity and miRNA family information. We use the disease phenotype similarity data to construct the disease similarity network. Then we introduce a new miRNA-disease association prediction method (NETwork Group Similarity, NetGS) to explore the global network similarity, capturing the relationship between the disease and other diseases, the similarity between the potential disease-related miRNA and other miRNAs. Finally based on the consistency of diffusion profiles we get the miRNA-disease association scores. NetGS is tested by the leave-one-out cross validation and achieves an AUC value of 0.8450, which improves the prediction accuracy. NetGS can also be applied to solve the new miRNA-disease association and obtain reliable accuracy. Moreover, we use NetGS to predict new causing miRNAs of three cancers including breast cancer, lung cancer and Hepatocellular cancer. And the top predictions have been confirmed in the online databases. The encouraging results indicate that NetGS might play an essential role for future scientific research. [ABSTRACT FROM AUTHOR]

The maximal information coefficient (MIC) captures dependences between paired variables, including both functional and non-functional relationships. In this paper, we develop a new method, ChiMIC, to calculate the MIC values. The ChiMIC algorithm uses the chi-square test to terminate grid optimization and then removes the restriction of maximal grid size limitation of original ApproxMaxMI algorithm. Computational experiments show that ChiMIC algorithm can maintain same MIC values for noiseless functional relationships, but gives much smaller MIC values for independent variables. For noise functional relationship, the ChiMIC algorithm can reach the optimal partition much faster. Furthermore, the MCN values based on MIC calculated by ChiMIC can capture the complexity of functional relationships in a better way, and the statistical powers of MIC calculated by ChiMIC are higher than those calculated by ApproxMaxMI. Moreover, the computational costs of ChiMIC are much less than those of ApproxMaxMI. We apply the MIC values tofeature selection and obtain better classification accuracy using features selected by the MIC values from ChiMIC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Current studies give us inconsistent results regarding the association of neoplasms and zinc(II) serum and tissues concentrations. The results of to-date studies using meta-analysis are summarized in this paper. Methods: Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL were searched. Articles were reviewed by two evaluators; quality was assessed by Newcastle-Ottawa scale; meta-analysis was performed including meta-regression and publication bias analysis. Results: Analysis was performed on 114 case control, cohort and cross-sectional studies of 22737 participants. Decreased serum zinc level was found in patients with lung (effect size = −1.04), head and neck (effect size = −1.43), breast (effect size = −0.93), liver (effect size = −2.29), stomach (effect size = −1.59), and prostate (effect size = −1.36) cancers; elevation was not proven in any tumor. More specific zinc patterns are evident at tissue level, showing increase in breast cancer tissue (effect size = 1.80) and decrease in prostatic (effect size = −3.90), liver (effect size = −8.26), lung (effect size = −3.12), and thyroid cancer (effect size = −2.84). The rest of the included tumors brought ambiguous results, both in serum and tissue zinc levels across the studies. The association between zinc level and stage or grade of tumor has not been revealed by meta-regression. Conclusion: This study provides evidence on cancer-specific tissue zinc level alteration. Although serum zinc decrease was associated with most tumors mentioned herein, further – prospective - studies are needed. [ABSTRACT FROM AUTHOR]

Background: Some authors have studied the relationship between the presence of polyps, adenomas and cancers of upper gastrointestinal tract (stomach and duodenum) and risk of colorectal polyps and neoplasms; however, the results are controversial, which may be due to study sample size, populations, design, clinical features, and so on. No meta-analysis, which can be generalized to a larger population and could provide a quantitative pooled risk estimate of the relationship, of this issue existed so far. Methods: We performed a meta-analysis to evaluate risk of colorectal polyps or neoplasms in patients with polyps, adenomas or cancers in upper gastrointestinal tract comparing with controls. A search was conducted through PubMed, EMBASE, reference lists of potentially relevant papers, and practice guidelines up to 27 November 2013 without languages restriction. Odd ratios (ORs) were pooled using random-effects models. Results: The search yielded 3 prospective and 21 retrospective case-control studies (n = 37152 participants). The principal findings included: (1) OR for colorectal polyps was 1.15 (95% CI, 1.04–1.26) in the gastric polyps group comparing with control groups; (2) Patients with gastric polyps and neoplasms have higher risk (OR, 1.31 [95% CI, 1.06–1.62], and 1.72 [95% CI, 1.42–2.09], respectively) of colorectal neoplasms comparing with their controls; and (3) Positive association was found between the presence of colorectal neoplasms and sporadic duodenal neoplasms (OR, 2.59; 95% CI, 1.64–4.11). Conclusions: Findings from present meta-analysis of 24 case-control studies suggest that the prevalence of colorectal polyps was higher in patients with gastric polyps than in those without gastric polyps, and the risk of colorectal neoplasms increases significantly in patients with gastric polyps, neoplasms, and duodenal neoplasms. Therefore, screening colonoscopy should be considered for patients with upper gastrointestinal polyps and neoplasms. [ABSTRACT FROM AUTHOR]

Context: Magnetic resonance imaging (MRI) is currently the most accurate imaging modality to assess local prostate cancer stage. Despite a growing body of evidence, incorporation of MRI images into decision-making process concerning surgical template of radical prostatectomy, is complex and still poorly understood. Objective: We sought to determine the value of MRI in preoperative planning before radical prostatectomy. Materials and methods: Systematic search through electronic PubMed, EMBASE, and Cochrane databases from 2000 up to April 2018 was performed. Only studies that used preoperative MRI in decision-making process regarding extension of resection in patients with prostate cancer, in whom radical prostatectomy was an initial form of treatment were included into analysis. Their quality was scored by Risk Of Bias In Non-Randomized Studies of Interventions system. Meta-analysis was performed to calculate the weighted summary proportion under the fixed or random effects model as appropriate and pooled effects were depicted on forest plots. Results: The results showed that the preoperative MRI led to the modification of initial surgical template in one third of cases (35%). This occurred increasingly with the rising prostate cancer-risk category: 28%, 33%, 52% in low-, intermediate- and high-risk group, respectively. Modification of neurovascular bundle-sparing surgery based on MRI appeared to have no impact on the positive surgical margin rate. The decision based on MRI was correct on average in 77% of cases and differed across prostate cancer-risk categories: 63%, 75% and 91% in low-, intermediate- and high-risk group, accordingly. Conclusions: In summary, MRI has a considerable impact on the decision-making process regarding the extent of resection during radical prostatectomy. Adaptation of MRI images by operating surgeons has at worst no significant impact on surgical margin status, however its ability to decrease the positive surgical margin rates remains unconfirmed. [ABSTRACT FROM AUTHOR]

Genetic risk prediction is an important goal in human genetics research and precision medicine. Accurate prediction models will have great impacts on both disease prevention and early treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome wide association studies (GWAS), genetic risk prediction accuracy remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes in the presence of linkage disequilibrium. In this paper, we introduce AnnoPred, a principled framework that leverages diverse types of genomic and epigenomic functional annotations in genetic risk prediction for complex diseases. AnnoPred is trained using GWAS summary statistics in a Bayesian framework in which we explicitly model various functional annotations and allow for linkage disequilibrium estimated from reference genotype data. Compared with state-of-the-art risk prediction methods, AnnoPred achieves consistently improved prediction accuracy in both extensive simulations and real data. [ABSTRACT FROM AUTHOR]

Background: LncRNA CCAT1 is significantly overexpressed in various types of cancers, suggesting that it might be associated with prognosis and clinicopathological features in patients with cancer. Methods: A comprehensive search was performed in Pubmed, Web of Science, OVID and CNKI databases. We also retrieved articles from other sources, such as retrieving from the reference lists of relevant articles. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value. Results: A total of 1587 patients from 11 eligible studies were included in the meta-analysis. The results showed that high expression level of CCAT1 was significantly associated with shorter overall survival in cancer patients (HR 2.335, 95% CI:1.551–3.517); in the subgroup analysis, region (China or UK), sample size (more or less than 100), type of cancer (digestive or non-digestive disease) and paper quality (score more or less than 7) did not alter the association between CCAT1 expression and cancer prognosis but preoperative treatment did. And CCAT1 expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.195, 95%CI:1.316–3.664) using Cox multivariate analyses. The clinicopathological parameters analysis further showed that increased expression level of CCAT1 was correlated with tumor size, lymph node metastasis, TNM stage, distant metastasis, microvascular invasion and capsular formation in relevant cancers. Conclusions: The meta-analysis results from present study suggested that increased expression level of CCAT1 was associated with poor prognosis and can serve as an independent biomarker. And the expression level of CCAT1 was associated with clinicopathological features in relevant cancers. [ABSTRACT FROM AUTHOR]

miRNAs are small non-coding RNAs that regulate gene expression by binding to the 3′-UTR of genes. Many recent studies have reported that miRNAs play important biological roles by regulating specific mRNAs or genes. Many sequence-based target prediction algorithms have been developed to predict miRNA targets. However, these methods are not designed for condition-specific target predictions and produce many false positives; thus, expression-based target prediction algorithms have been developed for condition-specific target predictions. A typical strategy to utilize expression data is to leverage the negative control roles of miRNAs on genes. To control false positives, a stringent cutoff value is typically set, but in this case, these methods tend to reject many true target relationships, i.e., false negatives. To overcome these limitations, additional information should be utilized. The literature is probably the best resource that we can utilize. Recent literature mining systems compile millions of articles with experiments designed for specific biological questions, and the systems provide a function to search for specific information. To utilize the literature information, we used a literature mining system, BEST, that automatically extracts information from the literature in PubMed and that allows the user to perform searches of the literature with any English words. By integrating omics data analysis methods and BEST, we developed Context-MMIA, a miRNA-mRNA target prediction method that combines expression data analysis results and the literature information extracted based on the user-specified context. In the pathway enrichment analysis using genes included in the top 200 miRNA-targets, Context-MMIA outperformed the four existing target prediction methods that we tested. In another test on whether prediction methods can re-produce experimentally validated target relationships, Context-MMIA outperformed the four existing target prediction methods. In summary, Context-MMIA allows the user to specify a context of the experimental data to predict miRNA targets, and we believe that Context-MMIA is very useful for predicting condition-specific miRNA targets. [ABSTRACT FROM AUTHOR]

Background: In this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC. Methods: Literature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes. Results: In this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79–4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer. Conclusion: The meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Pleural fluid homocysteine (HCY) can be useful for diagnosis of malignant pleural effusion (MPE). There are no published studies comparing the diagnostic accuracy of HCY with other tumour markers in pleural fluid for diagnosis of MPE. The aim was to compare the accuracy of HCY with that of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA19.9 and CA125 in pleural fluid and to develop a probabilistic model using these biomarkers to differentiate benign (BPE) from MPE. Methods: Patients with pleural effusion were randomly included. HCY, CEA, CA15.3, CEA19.9 and CA125 were quantified in pleural fluid. Patients were classified into two groups: MPE or BPE. By applying logistic regression analysis, a multivariate probabilistic model was developed using pleural fluid biomarkers. The diagnostic accuracy was determined by receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Results: Population of study comprised 133 patients (72 males and 61 females) aged between 1 and 96 years (median = 70 years), 81 BPE and 52 MPE. The logistic regression analysis included HCY (p<0.0001) and CEA (p = 0.0022) in the probabilistic model and excluded the other tumour markers. The probabilistic model was: HCY+CEA = Probability(%) = 100×(1+e-z)-1, where Z = 0.5471×[HCY]+0.3846×[CEA]–8.2671. The AUCs were 0.606, 0.703, 0.778, 0.800, 0.846 and 0.948 for CA125, CA19.9, CEA, CA15.3, HCY and HCY+CEA, respectively. Conclusions: Pleural fluid HCY has higher accuracy for diagnosis of MPE than CEA, CA15.3, CA19.9 and CA125. The combination of HCY and CEA concentrations in pleural fluid significantly improves the diagnostic accuracy of the test. [ABSTRACT FROM AUTHOR]

Background: Hydronephrosis is a common finding in patients with bladder cancer. The aim of the study was to appraise the prognostic value of preoperative hydronephrosis in bladder cancer patients undergoing radical cystectomy. Methods: We conducted a literature search using PubMed and Embase databases in Aug 2018. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effects models. The primary endpoint was overall survival (OS). Secondary endpoints were cancer-specific survival (CSS) and recurrence-free survival (RFS). Results: Overall, 13 studies published between 2008 and 2018 including 4,820 patients were selected for the meta-analysis. The age of bladder cancer patients ranged from 27 to 90.4 years, and the overall proportion of males was 72.5%. Preoperative hydronephrosis was reported in 27.4% of patients. The pooled HR was statistically significant for OS (HR, 1.36; 95% CI [1.20–1.55]) and CSS (HR, 1.64; 95% CI [1.33–2.02]), with no heterogeneity among the enrolled studies. Patients with bilateral hydronephrosis showed a poorer CSS compared to those with no hydronephrosis (HR 5.43, 95% CI [3.14–9.40]). However, there was no difference in CSS between no hydronephrosis and unilateral hydronephrosis groups (HR 1.35, 95% CI [0.84–2.14]). Despite a tendency towards poorer RFS (HR, 1.27; 95% CI [0.96–1.96]), the results demonstrated no significant association between presence of preoperative hydronephrosis and RFS after radical cystectomy. Conclusion: This meta-analysis indicates that preoperative hydronephrosis is significantly associated with poorer OS and CSS after radical cystectomy for patients with bladder cancer. Preoperative hydronephrosis has a stronger effect on CSS in patients with bilateral hydronephrosis. The presence of preoperative hydronephrosis not only predicts prognosis, but may also help to identify patients who benefit the most from neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The narrative surrounding the management of potentially resectable pancreatic cancer is complex. Surgical resection is the only potentially curative treatment. However resection rates are low, the risk of operative morbidity and mortality are high, and survival outcomes remain poor. The aim of this study was to create a prognostic Bayesian network that pre-operatively makes personalized predictions of post-resection survival time of 12months or less and also performs post-operative prognostic updating. Methods: A Bayesian network was created by synthesizing data from PubMed post-resection survival analysis studies through a two-stage weighting process. Input variables included: inflammatory markers, tumour factors, tumour markers, patient factors and, if applicable, response to neoadjuvant treatment for pre-operative predictions. Prognostic updating was performed by inclusion of post-operative input variables including: pathology results and adjuvant therapy. Results: 77 studies (n = 31,214) were used to create the Bayesian network, which was validated against a prospectively maintained tertiary referral centre database (n = 387). For pre-operative predictions an Area Under the Curve (AUC) of 0.7 (P value: 0.001; 95% CI 0.589–0.801) was achieved accepting up to 4 missing data-points in the dataset. For prognostic updating an AUC 0.8 (P value: 0.000; 95% CI:0.710–0.870) was achieved when validated against a dataset with up to 6 missing pre-operative, and 0 missing post-operative data-points. This dropped to AUC: 0.7 (P value: 0.000; 95% CI:0.667–0.818) when the post-operative validation dataset had up to 2 missing data-points. Conclusion: This Bayesian network is currently unique in the way it utilizes PubMed and patient level data to translate the existing empirical evidence surrounding potentially resectable pancreatic cancer to make personalized prognostic predictions. We believe such a tool is vital in facilitating better shared decision-making in clinical practice and could be further developed to offer a vehicle for delivering personalized precision medicine in the future. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that D-dimer levels are significantly correlated with the differential diagnosis and clinicopathological features of breast cancer. However, the results are currently limited and controversial. Therefore, we performed this meta-analysis to evaluate the relationship between D-dimer levels and breast cancer. Materials and methods: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang databases were searched to find studies that assessed the association of D-dimer with clinicopathological features of breast cancer and its usefulness in aiding with differential diagnosis. The standardized mean difference (SMD) was applied as the correlation measure. Results: A total of 1244 patients with breast cancer from 15 eligible studies were included in the meta-analysis. D-dimer levels were higher in the breast cancer group than in the benign (SMD = 1.02; 95% confidence interval [CI] = 0.53–1.52) and healthy (SMD = 1.27; 95% CI = 0.85–1.68) control groups. In addition, elevated D-dimer levels were associated with progesterone receptor-negative tumors (SMD = -0.25; 95% CI = -0.44–-0.05). Similarly, there was a significant correlation between D-dimer levels and tumor node metastasis staging (n = 11, SMD = 0.82; 95% CI = 0.57–1.06) and lymph node involvement (n = 8, SMD = 0.79; 95% CI = 0.50–1.09). In contrast, other clinicopathological factors, including estrogen receptor expression and human epidermal growth factor receptor 2 expression, were not associated with D-dimer levels. Conclusion: The results of this meta-analysis indicate that plasma D-dimer levels can be used as an important reference for the early identification and staging of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Randomized clinical trials compare participants receiving an experimental intervention to participants receiving standard of care (SOC). If one could predict the outcome for participants receiving SOC, a trial could be designed where all participants received the experimental intervention, with the observed outcome of the experimental group compared to the prediction for those individuals. Methods: We used the CancerMath calculator to predict outcomes for participants in two large clinical trials of adjuvant chemotherapy for breast cancer: NSABPB15 and CALGB9344. NSABPB15 was the training set, and we used the modified algorithm to predict outcomes for two groups from CALGB9344: one which received standard of care (SOC) chemotherapy and one which received paclitaxel in addition. We made a prediction for each individual CALGB9344 participant, assuming each received only SOC. Results: The predicted outcome for the group which received only SOC matched what was observed in the CALGB9344 trial. In contrast, the predicted outcome for the group also receiving paclitaxel was significantly worse than what was observed for this group. This matches the conclusion of CALGB9344 that adding paclitaxel to SOC improves survival. Conclusion: This project proves that a statistical model can predict the outcome of clinical trial participants treated with SOC. In some circumstances, a predictive model could be used instead of a control arm, allowing all participants to receive experimental treatment. Predictive models for cancer and other diseases could be constructed using the vast amount of outcomes data available to the federal government, and made available for public use. [ABSTRACT FROM AUTHOR]

In transcriptomics, micro RNAs (miRNAs) has gained much interest especially as potential disease indicators. However, apart from holding a great promise related to their clinical application, a lot of inconsistent results have been published. Our aim was to compare the miRNA expression levels in ovarian cancer and healthy subjects using the Bayesian multilevel model and to assess their potential usefulness in diagnosis. We have analyzed a case-control observational data on expression profiling of 49 preselected miRNA-based ovarian cancer indicators in 119 controls and 59 patients. A Bayesian multilevel model was used to characterize the effect of disease on miRNA levels controlling for differences in age and body weight. The difference between the miRNA level and health status of the patient on the scale of the data variability were discussed in the context of their potential usefulness in diagnosis. Additionally, the cross-validated area under the ROC curve (AUC) was used to assess the expected out-of-sample discrimination index of a different sets of miRNAs. The proposed model allowed us to describe the set of miRNA levels in patients and controls. Three highly correlated miRNAs: miR-101-3p, miR-142-5p, miR-148a-3p rank the highest with almost identical effect sizes that ranges from 0.45 to 1.0. For those miRNAs the credible interval for AUC ranged from 0.63 to 0.67 indicating their limited discrimination potential. A little benefit in adding information from other miRNAs was observed. There were several miRNAs in the dataset (miR-604, hsa-miR-221-5p) for which inferences were uncertain. For those miRNAs more experimental effort is needed to fully assess their effect in the context of new hits discovery and usefulness as disease indicators. The proposed multilevel Bayesian model can be used to characterize the panel of miRNA profile and to assess the difference in expression levels between healthy and cancer individuals. [ABSTRACT FROM AUTHOR]

Spatial scan statistics are widely used for cluster detection analysis in geographical disease surveillance. While this method has been developed for various types of data such as binary, count, and continuous data, spatial scan statistics for matched case-control data, which often arise in spatial epidemiology, have not been considered. We propose spatial scan statistics for matched case-control data. The proposed test statistics consider the correlations between matched pairs. We evaluate the statistical power and cluster detection accuracy of the proposed methods through simulations compared to the Bernoulli-based method. We illustrate the proposed methods using a real data example. The simulation study clearly revealed that the proposed methods had higher power and higher accuracy for detecting spatial clusters for matched case-control data than the Bernoulli-based spatial scan statistic. The cluster detection result of the real data example also appeared to reflect a higher power of the proposed methods. The proposed methods are very useful for spatial cluster detection for matched case-control data. [ABSTRACT FROM AUTHOR]

Objective: We performed a meta-analysis to evaluate the diagnostic value of positron emission tomography/computed tomography (PET/CT) in the detection of para-aortic lymph node metastasis in cervical cancer. Methods: We searched the PubMed, Embase, Web of Science, Cochrane Library, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases in all languages from their inception to September 2018. Stat15.0 software was used to obtain pooled estimates of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) as well as a summary receiver operating characteristic (SROC) curves. Deek‘s funnel plot was used to assess publication bias. QUADAS-2 was used to evaluate the quality of the studies. The protocol for this meta-analysis is registered in PROSPERO (CRD42019115330). Results: We obtained 14 studies, and the pooled estimates for sensitivity and specificity of PET/CT were 0.71 (95% confidence interval (CI) = 0.54–0.83) and 0.97 (95% CI = 0.93–0.98), respectively. Pooled PLR and NLR were 21.53 and 0.30, respectively. The diagnostic odds ratio (DOR) was70.59, and the area under the curve (AUC) was 0.95. Conclusion: PET/CT is an effective and important imaging method for the diagnosis of para-aortic lymph node metastasis in early cervical cancer. [ABSTRACT FROM AUTHOR]

Health disparities are commonplace and of broad interest to policy makers, but are also challenging to measure and communicate. The Health Disparity Calculator software (HD*Calc, v1.2.4) offers Monte Carlo simulation (MCS)-based confidence interval (CI) estimation of eleven disparity measures. The MCS approach provides accurate CI estimation, except when data are scarce (e.g., rare cancers). To address sparse data challenges to CI estimation, we propose two solutions: 1) employing the gamma distribution in the MCS and 2) utilizing a zero-inflated Poisson estimate for Poisson sampling in simulation experiments. We evaluate each solution through simulation studies using female breast, female brain, lung, and cervical cancer data from the Surveillance, Epidemiology, and End Results (SEER) program. We compare the coverage probabilities (CPs) of eleven health disparity measures based on simulated datasets. The truncated normal distribution implemented in the MCS with the standard Poisson samples (the default setting of HD*Calc) leads to less-than-optimal coverage probabilities (<95%). When both the gamma distribution and the estimated mean from the zero-inflated Poisson are used for the MCS, the coverage probabilities are close to the nominal level of 95%. Simulation studies also demonstrate that collapsing age categories for better CI estimation is not a pragmatic solution. [ABSTRACT FROM AUTHOR]

Objective: To investigate morbidity for patients after the primary surgical management of cervical cancer in low and middle-income countries (LMIC). Methods: The Pubmed, Cochrane, the Cochrane Central Register of Controlled Trials, Embase, LILACS and CINAHL were searched for published studies from 1st Jan 2000 to 30th June 2017 reporting outcomes of surgical management of cervical cancer in LMIC. Random-effects meta-analytical models were used to calculate pooled estimates of surgical complications including blood transfusions, ureteric, bladder, bowel, vascular and nerve injury, fistulae and thromboembolic events. Secondary outcomes included five-year progression free (PFS) and overall survival (OS). Findings: Data were available for 46 studies, including 10,847 patients from 11 middle income countries. Pooled estimates were: blood transfusion 29% (95%CI 0.19–0.41, P = 0.00, I2 = 97.81), nerve injury 1% (95%CI 0.00–0.03, I2 77.80, P = 0.00), bowel injury, 0.5% (95%CI 0.01–0.01, I2 = 0.00, P = 0.77), bladder injury 1% (95%CI 0.01–0.02, P = 0.10, I2 = 32.2), ureteric injury 1% (95%CI 0.01–0.01, I2 0.00, P = 0.64), vascular injury 2% (95% CI 0.01–0.03, I2 60.22, P = 0.00), fistula 2% (95%CI 0.01–0.03, I2 = 77.32, P = 0.00,), pulmonary embolism 0.4% (95%CI 0.00–0.01, I2 26.69, P = 0.25), and infection 8% (95%CI 0.04–0.12, I2 95.72, P = 0.00). 5-year PFS was 83% for laparotomy, 84% for laparoscopy and OS was 85% for laparotomy cases and 80% for laparoscopy. Conclusion: This is the first systematic review and meta-analysis of surgical morbidity in cervical cancer in LMIC, which highlights the limitations of the current data and provides a benchmark for future health services research and policy implementation. [ABSTRACT FROM AUTHOR]

Backgrounds: Serum C-reactive protein (CRP) level has been shown to be a predictor of survival for multiple cancer types. The aim of this study was to evaluate whether pretreatment serum CRP level could serve as a reliable independent prognostic indicator for survival in patients with soft tissue sarcoma (STS). Methods: A detailed literature search was conducted in Medline, Embase and Cochrane for relevant research publications written in English. Patients’ clinical characteristics, outcomes of disease-specific survival (DSS) and disease/recurrence free survival (DFS/RFS) were extracted. Only the results of multivariate survival analysis were recruited in our analysis. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the prognostic role of CRP. This study was registered on PROPERO and the registration number is CRD42018104802. Results: Nine articles containing 1655 patients were identified as eligible studies. The random effects model showed that elevated CRP level was significantly correlated with poor DSS (HR = 2.08; 95% CI: 1.33–3.24; p < 0.001). After excluding the heterogeneous study, the fixed effects model showed that elevated CRP level was firmly correlated with poor DSS (HR = 2.36; 95% CI: 1.84–3.03; p < 0.001). The fixed effects model revealed that elevated CRP level was significantly correlated with poor DFS (HR = 1.78; 95% CI: 1.39–2.30; p < 0.001) among studies have more than 100 samples. Conclusion: The results of this meta-analysis suggest that elevated pretreatment serum CRP level could serve as an independent risk factor for poor DSS and DFS/RFS in STS patents. [ABSTRACT FROM AUTHOR]

Glioblastomas are the most common primary brain tumours. They are known for their highly aggressive growth and invasion, leading to short survival times. Treatments for glioblastomas commonly involve a combination of surgical intervention, chemotherapy, and external beam radiation therapy (XRT). Previous works have not only successfully modelled the natural growth of glioblastomas in vivo, but also show potential for the prediction of response to radiation prior to treatment. This suggests that the efficacy of XRT can be optimized before treatment in order to yield longer survival times. However, while current efforts focus on optimal scheduling of radiotherapy treatment, they do not include a similarly sophisticated spatial optimization. In an effort to improve XRT, we present a method for the spatial optimization of radiation profiles. We expand upon previous results in the general problem and examine the more physically reasonable cases of 1-step and 2-step radiation profiles during the first and second XRT fractions. The results show that by including spatial optimization in XRT, while retaining a constant prescribed total dose amount, we are able to increase the total cell kill from the clinically-applied uniform case. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the rate of discordance of epidermal growth factor receptor (EGFR) mutation between primary lung tumor and paired distant metastases in non-small-cell lung cancer (NSCLC). Methods: We performed a meta-analysis of 17 studies (518 cases) assessing discordance rates of EGFR mutation in primary tumors and paired distant metastases. We performed subgroup analyses based on EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system (CNS) or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis (synchronous or metachronous). Results: The overall discordance rate in EGFR mutation was low at 10.36% (95% CI = 4.23% to 18.79%) and varied widely between studies (I2 = 83.18%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001). Subgroup analyses did not demonstrate any significant effect modification on the discordance rates by the EGFR mutation status in primary lung tumor, methods of testing and timing of metastasis. Conclusion: The overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases. Future studies assessing the impact of EGFR mutation discordance on treatment outcomes are required. [ABSTRACT FROM AUTHOR]

Objective: An early onset of menarche and, later, menopause are well-established risk factors for the development of breast cancer and endometrial cancer. Although the largest GWASs have identified 389 independent signals for age at menarche (AAM) and 44 regions for age at menopause (ANM), GWAS can only identify the associations between variants and traits. The aim of this study was to identify genes whose expression levels were associated with AAM or ANM due to pleiotropy or causality by integrating GWAS data with genome-wide expression quantitative trait loci (eQTLs) data. We also aimed to identify the pleiotropic genes that influenced both phenotypes. Method: We employed GWAS data of AAM and ANM and genome-wide eQTL data from whole blood. The summary data-based Mendelian randomization method was used to prioritize the associated genes for further study. The colocalization analysis was used to identify the pleiotropic genes associated with both phenotypes. Results: We identified 31 genes whose expression was associated with AAM and 24 genes whose expression was associated with ANM due to pleiotropy or causality. Two pleiotropic genes were identified to be associated with both phenotypes. Conclusion: The results point out the most possible genes which were responsible for the association. Our study prioritizes the associated genes for further functional mechanistic study of AAM and ANM and illustrates the benefit of integrating different omics data into the study of complex traits. [ABSTRACT FROM AUTHOR]

Background: Recent literature has suggested that tumor sidedness in colorectal cancer (CRC) is an independent prognostic and potentially predictive marker of survival. The aims of the study were to determine the prognostic significance of tumor sidedness in colorectal cancer patients undergoing primary tumor resection and to assess associated tumor biology. Methods: A total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012 were analyzed for association with tumor biologic factors and with overall survival. Metastatic patients were excluded from analysis. Results: Left sided CRCs were associated with a number of additional key prognostic markers including BRAFV600E wildtype status (P<0.001), mismatch repair proficiency (p<0.001), absence of peritumoral lymphocytic response (p = 0.001), high lymphocyte-to-monocyte ratio (p<0.001) and low neutrophil-to-lymphocyte ratio (p<0.001). In primary analysis with 3067 patients, there was no statistical difference in sidedness in the univariate analysis (p = 0.291). Three further subgroup analyses were performed. In the first subgroup, only stage III patients were analyzed. In the second, patients with mismatch repair deficiency were removed. In the third, additional clinicopathologic variables known to be independently prognostic were added into analysis. In all three subgroup analyses tumor sidedness was not an independent prognostic marker. Conclusions: Tumor sidedness was not an independent prognostic marker of CRC. However, right sided CRCs were associated with several key independent prognostic markers supporting a hypothesis that tumor sidedness is a surrogate for other biomarkers. [ABSTRACT FROM AUTHOR]