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关键词： Drug Safety and Pharmacovigilance   Pharmacology/Toxicology  

摘要： Introduction An increased risk of myopathy due to a potential interaction between sodium glucose co-transporter-2 inhibitors (SGLT-2i) and HMG-CoA reductase inhibitors (statins) has been suggested by case reports. Objective We aimed to assess if the reporting of myopathy is disproportionally higher among people using both SGLT-2i and statins compared to using either SGLT-2i or statins alone. Methods We conducted a disproportionality analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). We included reports with at least one antihyperglycemic agent. We compared the proportion of myopathy cases to non-cases between those not using SGLT-2i or statins, using SGLT-2i only, statins only, or both. We calculated the reporting odds ratio and 95% confidence interval. We further stratified by individual SGLT-2i and selected statins (rosuvastatin or atorvastatin). Results We included 688,388 reports with at least one antihyperglycemic agent recorded, of which 9.80% had at least one SGLT-2i agent. Among all included reports, there were a total of 2202 myopathy cases with the majority, 61.26%, occurring among those using statins alone and only 2.72% of myopathy cases were among those using both SGLT-2i and statins together. Reporting of myopathy was not disproportionally higher among those reporting the use of SGLT-2i with statins (reporting odds ratio 2.95, 95% confidence interval 2.27-3.85) compared to statins alone (reporting odds ratio 6.41, 95% confidence interval 5.86-7.02). Conclusions Reports of myopathy were not disproportionally higher among those using SGLT-2i with statins compared to SGLT-2i or statins alone at the class level. Further observational studies may be needed to better assess this interaction at the agent level.

关键词： Differential privacy framework   multiple-strategies privacy protection   network traffic analysis   sparse tensor factorization  

摘要： Due to high capacity and fast transmission speed, 5G plays a key role in modern electronic infrastructure. Meanwhile, sparse tensor factorization (STF) is a useful tool for dimension reduction to analyze high-order, high-dimension, and sparse tensor (HOHDST) data, which is transmitted on 5G Internet-of-things (IoT). Hence, HOHDST data relies on STF to obtain complete data and discover rules for real time and accurate analysis. From another view of computation and data security, the current STF solution seeks to improve the computational efficiency but neglects privacy security of the IoT data, e.g., data analysis for network traffic monitor system. To overcome these problems, this article proposes a multiple-strategies differential privacy framework on STF (MDPSTF) for HOHDST network traffic data analysis. MDPSTF comprises three differential privacy (DP) mechanisms, i.e., epsilon- DP, concentrated DP, and local DP. Furthermore, the theoretical proof of privacy bound is presented. Hence, MDPSTF can provide general data protection for HOHDST network traffic data with high-security promise. We conduct experiments on two real network traffic datasets (Abilene and GEANT). The experimental results show that MDPSTF has high universality on the various degrees of privacy protection demands and high recovery accuracy for the HOHDST network traffic data.

关键词： hemodynamic   cerebral glioma   glioblastoma   perfusion computed tomography   MRI   perfusion MRI   cerebrovascular reactivity  

摘要： Simple Summary Diffuse gliomas, and glioblastomas, in particular, represent a diagnostic and clinical challenge. Standard neuroimaging continues to have many limitations for accurate diagnostic assessment, resection planning and treatment follow-up. The present two-review series comprehensively summarizes recent evidence on hemodynamic imaging applications in the context of diffuse cerebral glioma. Part A provides an overview of the concepts underlying hemodynamic imaging modalities and critically discusses the diffuse glioma differential diagnosis and tumor grading results reported in the literature. Diffuse gliomas are the most common primary malignant intracranial neoplasms. Aside from the challenges pertaining to their treatment-glioblastomas, in particular, have a dismal prognosis and are currently incurable-their pre-operative assessment using standard neuroimaging has several drawbacks, including broad differentials diagnosis, imprecise characterization of tumor subtype and definition of its infiltration in the surrounding brain parenchyma for accurate resection planning. As the pathophysiological alterations of tumor tissue are tightly linked to an aberrant vascularization, advanced hemodynamic imaging, in addition to other innovative approaches, has attracted considerable interest as a means to improve diffuse glioma characterization. In the present part A of our two-review series, the fundamental concepts, techniques and parameters of hemodynamic imaging are discussed in conjunction with their potential role in the differential diagnosis and grading of diffuse gliomas. In particular, recent evidence on dynamic susceptibility contrast, dynamic contrast-enhanced and arterial spin labeling magnetic resonance imaging are reviewed together with perfusion-computed tomography. While these techniques have provided encouraging results in terms of their sensitivity and specificity, the limitations deriving from a lack of standardized acquisition and processing have

摘要： Phytoplankton stand at the base of the marine food-web, and play a major role in global carbon cycling. Rising CO2 levels and temperatures are expected to enhance growth and alter carbon:nutrient stoichiometry of marine phytoplankton, with possible consequences for the functioning of marine food-webs and the oceanic carbon pump. To date, however, the consistency of phytoplankton stoichiometric responses remains unclear. We therefore performed a meta-analysis on data from experimental studies on stoichiometric responses of marine phytoplankton to elevated pCO(2) and 3-5 degrees warming under nutrient replete and limited conditions. Our results demonstrate that elevated pCO(2) increased overall phytoplankton C:N (by 4%) and C:P (by 9%) molar ratios under nutrient replete conditions, as well as phytoplankton growth rates (by 6%). Nutrient limitation amplified the CO2 effect on C:N and C:P ratios, with increases to 27% and 17%, respectively. In contrast to elevated pCO(2), warming did not consistently alter phytoplankton elemental composition. This could be attributed to species- and study-specific increases and decreases in stoichiometry in response to warming. While our observed moderate CO2-driven changes in stoichiometry are not likely to drive marked changes in food web functioning, they are in the same order of magnitude as current and projected estimations of oceanic carbon export. Therefore, our results may indicate a stoichiometric compensation mechanism for reduced oceanic carbon export due to declining primary production in the near future.

关键词： Tenacibaculum   flavobacteria   roseobacters   probiotics   aquaculture   tropodithietic acid   Phaeobacter  

摘要： Fish-pathogenic bacteria of the Tenacibaculum genus are a serious emerging concern in modern aquaculture, causing tenacibaculosis in a broad selection of cultured finfish. Data describing their virulence mechanisms are scarce and few means, antibiotic treatment aside, are available to control their proliferation in aquaculture systems. We genome sequenced a collection of 19 putative Tenacibaculum isolates from outbreaks at two aquaculture facilities and tested their susceptibility to treatment with tropodithietic acid (TDA)-producing Roseobacter group probiotics. We found that local outbreaks of Tenacibaculum can involve heterogeneous assemblages of species and strains with the capacity to produce multiple different virulence factors related to host invasion and infection. The probiotic Phaeobacter piscinae S26 proved efficient in killing pathogenic Tenacibaculum species such as T. maritimum, T. soleae, and some T. discolor strains. However, the T. mesophilum and T. gallaicum species exhibit natural tolerance toward TDA and are hence not likely to be easily killed by TDA-producing probiotics. Tolerance toward TDA in Tenacibaculum is likely involving multiple inherent physiological features pertaining to electron and proton transport, iron sequestration, and potentially also drug efflux mechanisms, since genetic determinants encoding such features were significantly associated with TDA tolerance. Collectively, our results support the use of TDA producers to prevent tenacibaculosis;however, their efficacy is likely limited to some Tenacibaculum species. IMPORTANCE A productive and sustainable aquaculture sector is needed to meet the UN sustainable development goals and supply the growing world population with high-protein food sources. A sustainable way to prevent disease outbreaks in the industry is the application of probiotic bacteria that can antagonize fish pathogens in the aquaculture systems. TDA-producing Roseobacter group probiotics have proven efficient in k

关键词： Ordinary differential equations   initial value problem   first order   constant coefficient   triangular system   explicit solution  

摘要： Algorithm 982: Explicit solutions of triangular systems of first-order linear initial-value ordinary differential equations with constant coefficients provides an explicit solution for an homogeneous system, and a brief description of how to compute a solution for the inhomogeneous case. The method described is not directly useful if the coefficient matrix is singular. This remark explains more completely how to compute the solution for the inhomogeneous case and for the singular coefficient matrix case.

关键词： anti-CD52 antibody   EAE   innate immune cells  

摘要： Anti-CD52 antibody (anti-CD52-Ab) leads to a rapid depletion of T and B cells, followed by reconstitution of immune cells with tolerogenic characteristics. However, very little is known about its effect on innate immune cells. In this study, experimental autoimmune encephalomyelitis mice were administered murine anti-CD52-Ab to investigate its effect on dendritic cells and monocytes/macrophages in the periphery lymphoid organs and the central nervous system (CNS). Our data show that blood and splenic innate immune cells exhibited significantly increased expression of MHC-II and costimulatory molecules, which was associated with increased capacity of activating antigen-specific T cells, at first day but not three weeks after five daily treatment with anti-CD52-Ab in comparison with controls. In contrast to the periphery, microglia and infiltrating macrophages in the CNS exhibited reduced expression levels of MHC-II and costimulatory molecules after antibody treatment at both time-points investigated when compared to controls. Furthermore, the transit response of peripheral innate immune cells to anti-CD52-Ab treatment was also observed in the lymphocyte-deficient SCID mice, suggesting the changes are not a direct consequence of the mass depletion of lymphocytes in the periphery. Our study demonstrates a dynamic and tissue-specific modulation of the innate immune cells in their phenotype and function following the antibody treatment. The findings of differential modulation of the microglia and infiltrating macrophages in the CNS in comparison with the innate immune cells in the peripheral organs support the CNS-specific beneficial effect of alemtuzumab treatment on inhibiting neuroinflammation in multiple sclerosis patients.

关键词： inflammation   inflammasome regulation   inflammasome adaptor protein isoforms   ASC   ASCb   protein oligomerization and self-assembly   protein NMR  

摘要： ASC is an essential adaptor of the inflammasome, a micrometer-size multiprotein complex that processes proinflammatory cytokines. Inflammasome formation depends on ASC self-association into large assemblies via homotypic interactions of its two death domains, PYD and CARD. ASCb, an alternative splicing isoform, activates the inflammasome to a lesser extent compared with ASC. Thus, it has been postulated that adaptor isoforms differentially regulate inflammasome function. At the amino acid level, ASC and ASCb differ only in the length of the linker connecting the two death domains. To understand inflammasome regulation at the molecular level, we investigated the self-association properties of ASC and ASCb using real-time NMR, dynamic light scattering (DLS), size-exclusion chromatography, and transmission electron microscopy (TEM). The NMR data indicate that ASC self association is faster than that of ASCb;a kinetic model for this oligomerization results in differing values for both the reaction order and the rate constants. Furthermore, DLS analysis indicates that ASC self-associates into more compact macrostructures compared with ASCb. Finally, TEM data show that ASCb has a reduced tendency to form densely packed filaments relative to ASC. Overall, these differences can only be explained by an effect of the linker length, as the NMR results show structural equivalence of the PYD and CARD in both proteins. The effect of linker length was corroborated by molecular docking with the procaspase-1 CARD domain. Altogether, our results indicate that ASC's faster and less polydisperse polymerization is more efficient, plausibly explaining inflammasome activation differences by ASC isoforms at the molecular level.

关键词： Differential protection   hardware-in-the-loop (HIL)   Instantaneous power   second-order transient-extracting transform (STET)   Transformer   Ultrasaturation  

摘要： A novel Instantaneous Power-based Differential Protection (IPDP) for transformers is presented in this paper. The instantaneous power, gathering the voltage and current information, discriminates between internal fault and external fault, inrush current, sympathetic inrush current, overexcitation, and ultrasaturation with and without CT (Current Transformer) saturation. The proposed method relies on the waveshape properties of the instantaneous power signal. A high-resolution time-frequency analysis (TFA) technique, namely Second-Order Transient-Extracting transform (STET), is used for the discrimination purpose. Furthermore, the STET technique results are examined in a Hardware-in-the-Loop (HIL) test using Raspberry Pi (R-Pi) to evaluate the real-time speed of the proposed algorithm. This real-time manipulation results in the internal fault and other transient phenomena distinction time to be 14 ms. The proposed method does not require transformer parameters and various operating conditions of the power system and is entirely immune against noise. The usefulness of the proposed method is evaluated through numerous simulations as well as experimental implementation. Two experimental setups are considered for ensuring the practicality of the proposed method. The first one is a laboratory setup for capturing real-world transformer internal fault and inrush current waveforms. The second one includes a relay and CT tester, namely, Vebko Amirkabir AMT105 relay tester and a laboratory CT for determining the CT saturation test.

关键词： BCC   SWE   ultrasound   Young's modulus  

摘要： The aim of this study was to assess the value of high-resolution ultrasonic quantitative parameters of shear wave elastography (SWE) in basal cell carcinoma (BCC). A total of 86 cases of BCC were enrolled as the case group, and 38 other similar skin pigmented lesions were randomly selected as the control group. Using pathological results as the gold standard, the diagnostic test method was used to evaluate the ability of high-frequency ultrasonic elastography to diagnose BCC, and the 2D ultrasonographic features, blood flow image characteristics, and SWE of BCC were summarized.