Meta-Analysis of Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes and All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus

The benefit or risk of sodium glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus has not been established. We aimed to assess the comparative CV safety and mortality risk associated with the use of SGLT2 inhibitors. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were systematically searched up to January 27, 2016, to identify randomized controlled trials (RCTs) with the use of SGLT2 inhibitors of at least 24 weeks of duration. The primary outcomes included all-cause mortality and major adverse cardiovascular events. A random-effects network meta-analysis was performed to calculate the odds ratio (OR) with 95% CI. We identified 37 eligible trials involving 29,859 patients that compared 3 SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to placebo and other active antidiabetic treatments. Of all direct and indirect comparisons, only empagliflozin compared with placebo was significantly associated with lower risk of all-cause mortality (OR 0.67, 95% CI 0.56 to 0.81) and major adverse cardiovascular events (OR 0.81, 95% CI 0.70 to 0.93). However, the significant effect of empagliflozin was largely driven by one large randomized trial (EMPA-REG OUTCOME trial). Neither dapagliflozin nor canagliflozin was significantly associated with any harm. In conclusion, current RCT evidence suggests that 3 common SGLT2 inhibitors are not associated with increased risk of all-cause mortality and CV outcomes when used to treat patients with type 2 diabetes mellitus. Although empagliflozin may have a protective effect, further confirmative data from rigorous RCTs are needed

Experimental Investigation on Strength and Crack Mechanism of Rock-Like Samples with Open-Closed Cross-Flaws under Uniaxial Compression

AbstractRock masses with open-closed cross-flaws are common in nature. The open-closed cross-flaws usually control the strength of rock masses. However, studies about the influence of open-closed cross-flaws on cracking behaviors and mechanical properties of rock masses are rare. In this study, rock-like samples containing open-closed cross-flaws with different geometries were fabricated to be conducted uniaxial compressive tests. The cracks observed in the tests were classified to nine types, and two new crack modes were described and identified. Two failure modes, failure caused by tensile cracks and failure caused by the combined effect of tensile and shear cracks, were observed. The failure caused by the penetration of the rock bridge is not observed, indicating that the rock bridge is not a potential penetration path for the samples with cross-flaws. Experimental results show that, when α=0°, the peak stress decreases from 32.2 MPa to 17.0 MPa as β increases from 0° to 90°. When α=90°, the peak stress increases from 22.5 MPa to 40.0 MPa as β increases from 0° to 90°. The inclination angle of the open flaw has an obvious effect on the strength of samples. When the inclination angle of the open flaw is 0°, the peak stress is the lowest (17.0 MPa). When the inclination angle of the open flaw is 90°, the peak stress is the largest (40.0 MPa). The samples with an open flaw of large inclination angle tend to have great compressive strength. For samples with open-closed cross-flaws, the open flaw has a greater influence on the strength and failure mode than the closed flaw

Identification of H3K4me1-associated proteins at mammalian enhancers.

Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators

Associations between colorectal cancer risk and dietary intake of tomato, tomato products, and lycopene: evidence from a prospective study of 101,680 US adults

BackgroundPrevious epidemiological studies have yielded inconsistent results regarding the effects of dietary tomato, tomato products, and lycopene on the incidence of colorectal cancer (CRC), possibly due to variations in sample sizes and study designs.MethodsThe current study used multivariable Cox regression, subgroup analyses, and restricted cubic spline functions to investigate correlations between CRC incidence and mortality and raw tomato, tomato salsa, tomato juice, tomato catsup, and lycopene intake, as well as effect modifiers and nonlinear dose-response relationships in 101,680 US adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.ResultsDuring follow-up 1100 CRC cases and 443 CRC-specific deaths occurred. After adjustment for confounding variables, high consumption of tomato salsa was significantly associated with a reduced risk of CRC incidence (hazard ratio comparing the highest category with the lowest category 0.8, 95% confidence interval 0.65–0.99, p for trend = 0.039), but not with a reduced risk of CRC mortality. Raw tomatoes, tomato juice, tomato catsup, and lycopene consumption were not significantly associated with CRC incidence or CRC mortality. No potential effect modifiers or nonlinear associations were detected, indicating the robustness of the results.ConclusionIn the general US population a higher intake of tomato salsa is associated with a lower CRC incidence, suggesting that tomato salsa consumption has beneficial effects in terms of cancer prevention, but caution is warranted when interpreting these findings. Further prospective studies are needed to evaluate its potential effects in other populations

Long-term Variations of CO2 Trapped in Different Mechanisms in Deep Saline Formations: A Case Study of the Songliao Basin, China

The geological storage of CO{sub 2} in deep saline formations is increasing seen as a viable strategy to reduce the release of greenhouse gases to the atmosphere. There are numerous sedimentary basins in China, in which a number of suitable CO{sub 2} geologic reservoirs are potentially available. To identify the multi-phase processes, geochemical changes and mineral alteration, and CO{sub 2} trapping mechanisms after CO{sub 2} injection, reactive geochemical transport simulations using a simple 2D model were performed. Mineralogical composition and water chemistry from a deep saline formation of Songliao Basin were used. Results indicate that different storage forms of CO{sub 2} vary with time. In the CO{sub 2} injection period, a large amount of CO{sub 2} remains as a free supercritical phase (gas trapping), and the amount dissolved in the formation water (solubility trapping) gradually increases. Later, gas trapping decreases, solubility trapping increases significantly due to migration and diffusion of the CO{sub 2} plume, and the amount trapped by carbonate minerals increases gradually with time. The residual CO{sub 2} gas keeps dissolving into groundwater and precipitating carbonate minerals. For the Songliao Basin sandstone, variations in the reaction rate and abundance of chlorite, and plagioclase composition affect significantly the estimates of mineral alteration and CO{sub 2} storage in different trapping mechanisms. The effect of vertical permeability and residual gas saturation on the overall storage is smaller compared to the geochemical factors. However, they can affect the spatial distribution of the injected CO{sub 2} in the formations. The CO{sub 2} mineral trapping capacity could be in the order of ten kilogram per cubic meter medium for the Songliao Basin sandstone, and may be higher depending on the composition of primary aluminosilicate minerals especially the content of Ca, Mg, and Fe

OpenSARUrban: A Sentinel-1 SAR Image Dataset for Urban Interpretation

Sentinel-1 mission provides a freely accessible opportunity for urban interpretation from synthetic aperture radar (SAR) images with specific resolution, which is of paramount importance for earth observation. In parallel, with the rapid development of advanced technologies, especially deep learning, it is urgently needed to construct a large-scale SAR dataset leading urban interpretation. This paper presents OpenSARUrban: a Sentinel-1 dataset dedicated to urban interpretation from SAR images, including a well-defined hierarchical annotation scheme, the data collection, the well-established procedures for dataset construction and organizations, the properties, visualizations, and applications of this dataset. Particularly, the OpenSARUrban provides 33358 image patches of SAR urban scene, covering 21 major cities of China, including 10 different categories, 4 kinds of formats, 2 kinds of polarization modes, and owning 5 essential properties: large-scale, diversity, specificity, reliability, and sustainability. These properties guarantee the achievable of several goals for OpenSARUrban. The first is to support urban target characterization. The second is to help develop applicable and advanced algorithms for Sentinel-1 urban target classification. The dataset visualization is implemented from the perspective of manifold to give an intuitive understanding. Besides a detailed description and visualization of the dataset, we present results of some benchmark algorithms, demonstrating that this dataset is practical and challenging. Notably, developing algorithms to enhance the classification performance on the whole dataset and considering the data imbalance are especially challenging