182 research outputs found

    Functional characterization of breast cancer using pathway profiles

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    BACKGROUND: The molecular characteristics of human diseases are often represented by a list of genes termed “signature genes”. A significant challenge facing this approach is that of reproducibility: signatures developed on a set of patients may fail to perform well on different sets of patients. As diseases are resulted from perturbed cellular functions, irrespective of the particular genes that contribute to the function, it may be more appropriate to characterize diseases based on these perturbed cellular functions. METHODS: We proposed a profile-based approach to characterize a disease using a binary vector whose elements indicate whether a given function is perturbed based on the enrichment analysis of expression data between normal and tumor tissues. Using breast cancer and its four primary clinically relevant subtypes as examples, this approach is evaluated based on the reproducibility, accuracy and resolution of the resulting pathway profiles. RESULTS: Pathway profiles for breast cancer and its subtypes are constructed based on data obtained from microarray and RNA-Seq data sets provided by The Cancer Genome Atlas (TCGA), and an additional microarray data set provided by The European Genome-phenome Archive (EGA). An average reproducibility of 68% is achieved between different data sets (TCGA microarray vs. EGA microarray data) and 67% average reproducibility is achieved between different technologies (TCGA microarray vs. TCGA RNA-Seq data). Among the enriched pathways, 74% of them are known to be associated with breast cancer or other cancers. About 40% of the identified pathways are enriched in all four subtypes, with 4, 2, 4, and 7 pathways enriched only in luminal A, luminal B, triple-negative, and HER2+ subtypes, respectively. Comparison of profiles between subtypes, as well as other diseases, shows that luminal A and luminal B subtypes are more similar to the HER2+ subtype than to the triple-negative subtype, and subtypes of breast cancer are more likely to be closer to each other than to other diseases. CONCLUSIONS: Our results demonstrate that pathway profiles can successfully characterize both common and distinct functional characteristics of four subtypes of breast cancer and other related diseases, with acceptable reproducibility, high accuracy and reasonable resolution

    The evolution of Turing Award Collaboration Network : bibliometric-level and network-level metrics

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    The year of 2017 for the 50th anniversary of the Turing Award, which represents the top-level award in the computer science field, is a milestone. We study the long-term evolution of the Turing Award Collaboration Network, and it can be considered as a microcosm of the computer science field from 1974 to 2016. First, scholars tend to publish articles by themselves at the early stages, and they began to focus on tight collaboration since the late 1980s. Second, compared with the same scale random network, although the Turing Award Collaboration Network has small-world properties, it is not a scale-free network. The reason may be that the number of collaborators per scholar is limited. It is impossible for scholars to connect to others freely (preferential attachment) as the scale-free network. Third, to measure how far a scholar is from the Turing Award, we propose a metric called the Turing Number (TN) and find that the TN decreases gradually over time. Meanwhile, we discover the phenomenon that scholars prefer to gather into groups to do research with the development of computer science. This article presents a new way to explore the evolution of academic collaboration network in the field of computer science by building and analyzing the Turing Award Collaboration Network for decades. © 2014 IEEE

    Boosting potassium-ion batteries by few-layered composite anodes prepared via solution-triggered one-step shear exfoliation

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    Earth-abundant potassium is a promising alternative to lithium in rechargeable batteries, but a pivotal limitation of potassium-ion batteries is their relatively low capacity and poor cycling stability. Here, a high-performance potassium-ion battery is achieved by employing few-layered antimony sulfide/carbon sheet composite anode fabricated via one-step high-shear exfoliation in ethanol/water solvent. Antimony sulfide with few-layered structure minimizes the volume expansion during potassiation and shortens the ion transport pathways, thus enhancing the rate capability; while carbon sheets in the composite provide electrical conductivity and maintain the electrode cycling stability by trapping the inevitable by-product, elemental sulfur. Meanwhile, the effect of the exfoliation solvent on the fabrication of two-dimensional antimony sulfide/carbon is also investigated. It is found that water facilitates the exfoliation by lower diffusion barrier along the [010] direction of antimony sulfide, while ethanol in the solvent acts as the carbon source for in situ carbonization

    Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms

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    AbstractHand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections

    In vitro anti-Helicobacter pylori activity and the underlining mechanism of an empirical herbal formula – Hezi Qingyou

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    BackgroundHelicobacter pylori (H. pylori) is thought to primarily colonize the human stomach and lead to various gastrointestinal disorders, such as gastritis and gastric cancer. Currently, main eradication treatment is triple or quadruple therapy centered on antibiotics. Due to antibiotic resistance, the eradication rate of H. pylori is decreasing gradually. Therefore, searching for anti-H. pylori drugs from herbal sources has become a strategy for the treatment. Our team proposed a Hezi Qingyou Formula (HZQYF), composed of Chebulae Fructus, Ficus hirta Vahl and Cloves, and studied its anti-H. pylori activity and mechanism.MethodsChemical components of HZQYF were studied using UHPLC–MS/MS and HPLC. Broth microdilution method and agar dilution method were used to evaluate HZQYF’s antibacterial activity. The effects of HZQYF on expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF), and flagellar genes (flaA, flaB) were explored using Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) technology. Effects on morphology and permeability of the extracellular membrane were studied using scanning electron microscopy (SEM) and N-phenylnaphthalen-1-amine (NPN) uptake. Effect on urease activity was studied using a urease kinetics analysis in vitro. Immunofluorescence staining method was used to examine the effect on adhesion. Western blot was used to examine the effect on cagA protein.ResultsMinimum inhibitory concentration (MIC) values of the formula against H. pylori clinical strains and standard strains were 80–160 μg/mL, and minimum bactericidal concentration (MBC) values were 160–320 μg/mL. The formula could down-regulate the expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF) and flagellar genes (flaA, flaB), change the morphology of H. pylori, increase its extracellular membrane permeability, and decrease its urease activity.ConclusionPresent studies confirmed that HZQYF had promising in vitro anti-H. pylori activities and demonstrated its possible mechanism of action by down-regulating the bacterial adhesion, urease, and flagellar gene expression, which provided scientific bases for further clinical investigations

    Impact of automatic acquisition of key clinical information on the accuracy of electrocardiogram interpretation: a cross-sectional study

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    Background: The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. Methods: Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. Results: The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. Conclusion: Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors

    Evaluation of Hybrid VMAT Advantages and Robustness Considering Setup Errors Using Surface Guided Dose Accumulation for Internal Lymph Mammary Nodes Irradiation of Postmastectomy Radiotherapy

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    ObjectivesSetup error is a key factor affecting postmastectomy radiotherapy (PMRT) and irradiation of the internal mammary lymph nodes is the most investigated aspect for PMRT patients. In this study, we evaluated the robustness, radiobiological, and dosimetric benefits of the hybrid volumetric modulated arc therapy (H-VMAT) planning technique based on the setup error in dose accumulation using a surface-guided system for radiation therapy.MethodsWe retrospectively selected 32 patients treated by a radiation oncologist and evaluated the clinical target volume (CTV), including internal lymph node irradiation (IMNIs), and considered the planning target volume (PTV) margin to be 5 mm. Three different planning techniques were evaluated: tangential-VMAT (T-VMAT), intensity-modulated radiation therapy (IMRT), and H-VMAT. The interfraction and intrafraction setup errors were analyzed in each field and the accumulated dose was evaluated as the patients underwent daily surface-guided monitoring. These parameters were included while evaluating CTV coverage, the dose required for the left anterior descending artery (LAD) and the left ventricle (LV), the normal tissue complication probability (NTCP) for the heart and lungs, and the second cancer complication probability (SCCP) for contralateral breast (CB).ResultsWhen the setup error was accounted for dose accumulation, T-VMAT (95.51%) and H-VMAT (95.48%) had a higher CTV coverage than IMRT (91.25%). In the NTCP for the heart, H-VMAT (0.04%) was higher than T-VMAT (0.01%) and lower than IMRT (0.2%). However, the SCCP (1.05%) of CB using H-VMAT was lower than that using T-VMAT (2%) as well as delivery efficiency. And T-VMAT (3.72) and IMRT (10.5).had higher plan complexity than H-VMAT (3.71).ConclusionsIn this study, based on the dose accumulation of setup error for patients with left-sided PMRT with IMNI, we found that the H-VMAT technique was superior for achieving an optimum balance between target coverage, OAR dose, complication probability, plan robustness, and complexity
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