Predicting Native Papilla Biliary Cannulation Success Using a Multinational ERCP Quality Network

Background and Objective: Success in achieving deep biliary cannulation success in native papillae is an accepted measure of competence in ERCP training and practice. This study aimed to determine the factors associated with native papilla deep biliary cannulation success, with and without precut sphincterotomy. Methods: A retrospective analysis was conducted in a prospectively collected database. The main outcome was deep biliary cannulation success, with and without precut facilitating access, in non-operated papillae. Multilevel random fixed effect multivariate model was used to control for doctor factor. Results: 13018 ERCPs were performed by 85 endoscopists between March 2007, and May 2011. Conventional (without precut) and overall (some precut assistance) cannulation rates were 89.8% and 95.6%, respectively. Precut was performed in 876 (6.7%). Conventional success was more likely in outpatients (OR 1.21), but less likely in complex contexts (OR 0.59), sicker patients (AS A grade (II, III/V: OR 0.81, 0.77)), with trainee involvement (OR 0.53), and certain indications (strictures, active pancreatitis). Overall cannulation success (some facilitated by precut) had similar associations, but was more likely with higher volume endoscopists (\u3e 239/year: OR 2.79), endoscopists with efficient fluoroscopy practice (OR 1.72), and less likely with moderate (versus deeper) sedation (OR 0.67).Conclusion: Success in deep biliary cannulation was high in this self-selected group of endoscopists, but was influenced by both patient and practitioner factors. Patient- and case-specific factors have greater impact on conventional cannulation success, but volume influences overall (including precut-assisted) success; both can be used to select appropriate cases and may help with credentialing guidelines

Formulation and Implementation of Energy Efficient Ultraviolet Curing for Photosensitive Resin-Bound Diamond Wire Saws

It is a currently dominant method to use wire saws for cutting silicon material because of its production efficiency and energy efficiency. Diamond wire saws, or fixed abrasive wire saws, have attracted much attention to researchers and engineers due to many advantages, including high cutting efficiency and low environmental pollution. This paper develops a novel diamond wire saw using ultraviolet curing technology. High-strength piano wires and polyethylene wires are selected as wire cores, and photosensitive resin is used as the binder. The problem of wire saw strength is mathematically formulated, and the effective parameters are analyzed. The surface morphology is analyzed for the developed diamond wire saw. A series of cutting experiments with different saws of varying manufacturing parameters are carried out. The slicing performance of such diamond wire saws is evaluated and compared. The experimental results show that the developed saw using the photosensitive resin has a very good performance in slicing silicon ingots. By the comparison between the developed diamond wire saw and the electroplated diamond wire saw, the surface smoothness of the workpiece is better than that by the latter

Longitudinal survey of microbiome associated with particulate matter in a megacity.

BackgroundWhile the physical and chemical properties of airborne particulate matter (PM) have been extensively studied, their associated microbiome remains largely unexplored. Here, we performed a longitudinal metagenomic survey of 106 samples of airborne PM2.5 and PM10 in Beijing over a period of 6 months in 2012 and 2013, including those from several historically severe smog events.ResultsWe observed that the microbiome composition and functional potential were conserved between PM2.5 and PM10, although considerable temporal variations existed. Among the airborne microorganisms, Propionibacterium acnes, Escherichia coli, Acinetobacter lwoffii, Lactobacillus amylovorus, and Lactobacillus reuteri dominated, along with several viral species. We further identified an extensive repertoire of genes involved in antibiotic resistance and detoxification, including transporters, transpeptidases, and thioredoxins. Sample stratification based on Air Quality Index (AQI) demonstrated that many microbial species, including those associated with human, dog, and mouse feces, exhibit AQI-dependent incidence dynamics. The phylogenetic and functional diversity of air microbiome is comparable to those of soil and water environments, as its composition likely derives from a wide variety of sources.ConclusionsAirborne particulate matter accommodates rich and dynamic microbial communities, including a range of microbial elements that are associated with potential health consequences

Fast Super-Resolution Imaging with Ultra-High Labeling Density Achieved by Joint Tagging Super-Resolution Optical Fluctuation Imaging (JT-SOFI)

Previous stochastic localization-based super-resolution techniques are largely limited by the labeling density and the fidelity to the morphology of specimen. We report on an optical super-resolution imaging scheme implementing joint tagging using multiple fluorescent blinking dyes associated with super-resolution optical fluctuation imaging (JT-SOFI), achieving ultra-high labeling density super-resolution imaging. To demonstrate the feasibility of JT-SOFI, quantum dots with different emission spectra were jointly labeled to the tubulin in COS7 cells, creating ultra-high density labeling. After analyzing and combining the fluorescence intermittency images emanating from spectrally resolved quantum dots, the microtubule networks are capable of being investigated with high fidelity and remarkably enhanced contrast at sub-diffraction resolution. The spectral separation also significantly decreased the frame number required for SOFI, enabling fast super-resolution microscopy through simultaneous data acquisition. As the joint-tagging scheme can decrease the labeling density in each spectral channel, we can faithfully reflect the continuous microtubule structure with high resolution through collection of only 100 frames per channel. The improved continuity of the microtubule structure is quantitatively validated with image skeletonization, thus demonstrating the advantage of JT-SOFI over other localization-based super-resolution methods.Comment: 19 pages, 4 figures, with S

Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

Background Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL). Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α) activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL. Methods T-ALL cell lines (Jurkat, Sup-T1) transfected with HIF-1α or Notch1 small interference RNA (siRNA) were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2) and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression. Conclusions Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation, invasion and chemoresistance in T-ALL. Pharmacological inhibitors of HIF-1α or Notch1 signalling may be attractive interventions for T-ALL treatment

Clustered Distribution of Natural Product Leads of Drugs in the Chemical Space as Influenced by the Privileged Target-Sites

10.1038/srep09325Scientific Reports

A pan-cancer analysis of enhancer expression in nearly 9000 patient samples

The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on “chromatin-state” to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers