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A pharmacovigilance study of vortioxetine based on data from the FDA adverse event reporting system
Identification of STAT3 and BIRC5 as anoikis-related biomarkers in psoriasis
The impact of exercise on skeletal muscle proteome of prediabetic subjects analyzed with data independent mass spectrometry
Abstract Physical exercise of even a moderate intensity is beneficial in both the prevention of prediabetes and management of Type 2 diabetes mellitus, as skeletal muscle is a primary tissue responsible for glucose uptake. Exercise-evoked proteomic alterations in muscle of subjects with prediabetes are of great importance for the study of relationships between insulin resistance and exercise. Although data-dependent (DDA) proteomic analysis is a cornerstone of deep proteome profiling employed in the elucidation of skeletal muscle biology, data-independent (DIA) approaches gain popularity in the studies focused on data reproducibility and throughput. We compared various ion-chromatogram libraries assembled with the use of off-line high-pH fractionation (HpH), gas-phase fractionation (GPF) and libraryless DirectDIA in LC/MS/HRMS DIA proteomic analysis of muscle from normoglycemic (NGT) and prediabetic (IGT) subjects after 3 months of supervised, mixed-mode exercise. In our hands, GPF-fractionated, hybrid DDA/DIA libraries yielded the best overall balance between the speed of preparation, data collection and protein identification among tested approaches. Analysis revealed, that despite 3-month exercise intervention skeletal muscle from IGT subjects displayed significant alterations in pathways and molecules relevant to muscle contraction, extracellular matrix composition and protein synthesis as compared to NGT counterparts. In conclusion, our study underlines the importance of the ion library assembly in the DIA analysis of clinical samples and confirms at molecular level changes connected with deficiency of muscle function in the prediabetic state.
Impact of ceftazidime avibactam on colonization by carbapenem resistant Enterobacterales during treatment of related infections
Real time blood detection in CCTV surveillance using attention enhanced InceptionV3
Integrating ecological importance and risk for restoration zoning and ecological water demand in the Shiyang river basin
Invariance of dynamo action in an early-Earth model
Study on the driving mechanisms of spatiotemporal nonstationarity of vegetation dynamics in Heilongjiang Province
Modular arene functionalization by differential 1,2-diborylation
The expression of the tight junction protein and therapeutical target Claudin 18.2 is heterogeneously distributed within esophageal and gastric adenocarcinoma
Abstract Claudin 18.2 (CLDN18.2) is a therapeutically relevant biomarker in esophageal (EAC) -and gastric adenocarcinoma (GAC). Little is known about its heterogeneity within the primary tumor and corresponding metastases and how many biopsies are needed to determine the true CLDN18.2 status of a tumor. CLDN18.2 was assessed in 1,283 patients (822 EAC, 461 GAC), using the antibody clone 43–14 A. Eight virtual endoscopic biopsies were taken from digitized whole tumor blocks. 204 of 822 EAC (24.8%) and 132 of 461 GAC (28,6%) were positive for CLDN18.2. In GAC, CLDN18.2 expression showed a trend towards less invasive growth ( p = 0.02) and less common lymph node metastasis ( p = 0.07) and was more often observed within the EBV-associated subtype ( p = 0.01). When comparing the expression in one biopsy with the whole tissue section, the sensitivity for CLDN18.2 was low (58.8%). The sensitivity increased to a maximum of 76.5% with 6 and 8 biopsies (positive likelihood ratio = 17.8). Discordant expression between primary tumor and corresponding local lymph node metastasis was observed in 18.5%. This study highlights that CLDN18.2 is a heterogeneously expressed biomarker, within the tumor tissue as well as in primary tumor and corresponding lymph node metastasis. In case of CLN18.2-negative results the representativity of the biopsies must be critically assessed and a re-biopsy might be recommendable.
Complementary MR measures of white matter and their relation to cardiovascular health and cognition
Abstract The microstructural and macrostructural integrity of white matter (WM) underpins efficient brain function, and is known to decline with age and vascular burden. Key aspects of WM health include axonal fibre density, myelination, free-water content, and the presence of tissue damage or lesions. Magnetic Resonance Imaging (MRI) offers multiple complementary sequences to non-invasively estimate these properties in vivo. For example, diffusion-weighted imaging (DWI) provides sensitive measures of microstructure, while T1-weighted and T2-weighted MRI can estimate total WM volume and hyper-intensities, and magnetisation transfer imaging (MT) and T1:T2 ratios can indicate myelin content. In this study, we leveraged all of these MRI-derived measures in a large population-based cohort (Cam-CAN) to identify latent WM factors and test how these factors relate to cardiovascular health and cognitive performance. Among 11 commonly-used WM metrics [Fractional Anisotropy (FA); Mean Signal Diffusion (MSD); Mean Signal Kurtosis (MSK); Neurite Density Index (NDI); fibre Orientation Dispersion Index (ODI); Free water volume faction (F iso ); spread of Mean Signal Diffusivity values (MSDvar); Magnetisation Transfer Ratio (MTR); T1:T2 ratio; volume of White Matter Hyper-Intensities (WMHI); White Matter Volume (WMV)], latent factor analysis showed that four factors were needed to explain 89% of the variance, which we interpreted in terms of (1) fibre density/myelination, (2) free-water / tissue damage, (3) fibre-crossing complexity and (4) microstructural complexity. These factors showed distinct effects of age and sex. To test the validity of these factors, we related them to measures of cardiovascular health and cognitive performance. Specifically, we ran path analyses linking (1) cardiovascular factors to the WM factors, and (2) the WM factors to cognitive measures. Even after adjusting for age and sex, we found that a vascular factor related to pulse pressure predicted the WM factor capturing free-water/tissue damage, and that several WM factors made unique predictions for fluid intelligence and processing speed. Our results show that there is both complementary and redundant information across common MR measures of WM, and their underlying latent factors may be useful for pinpointing the differential causes and contributions of white matter health in aging.
A randomized clinical trial testing the effectiveness of an adapted online HIV/AIDS prevention intervention among Latino men
Tailoring color and antibacterial properties of cotton fabric materials using gold nanoparticles synthesized from Mangifera indica peel extract
Runaway resorption of microcracks contributes to age-related hip-fracture patients
Abstract Microdefects, including microcracks and resorption trenches, may be important contributors to bone fragility. 3D microdefect morphology was imaged using synchrotron micro-CT to develop a classification system for investigating the relationship with bone mechanics and hip-fractures. Femoral heads from ageing hip-fracture patients ( n = 5, 74–82 years) were compared to ageing non-fracture controls ( n = 5, 72–84 years). Two trabecular cores were prepared from the chiasma; one was imaged using synchrotron micro-CT to measure microdefects and one was mechanically tested to measure tensile strength. Morphological and mechanical data were compared and correlated using Mann Whitney U test and Pearson’s rank correlation. All the procedures performed were in accordance with the ethical standards of the Imperial College Tissue Bank (R13004) and the 1984 Declaration of Helsinki. Microdefects varied and were classified into four categories based on shape and measurable parameters. Hip-fracture donors exhibited significantly higher density of all microdefects ( p < 0.05). Microdefect volume was strongly negatively correlated with ultimate tensile strength ( p < 0.05) and stiffness ( p < 0.05). Microdefects might contribute to loss of bone strength and fragility fracture via runaway resorption. Microcracks could promote focussed osteoclastic resorption and the formation of resorption pits which create stress risers leading to the re-formation of microcracks under continued load. CT-based classification methods should be used to explore the complex interaction between microdefects, metabolism, and bone fracture mechanics.
Analysis, design and control of A high step-up three level Quasi-Z-Source PWM DC-DC converter for photovoltaic applications:
Multi-level probabilistic computing: application to the multiway number partitioning problems
Metabolomics and network analysis reveal the mechanism of Salvia miltiorrhiza bunge extract in ameliorating cognitive dysfunction in sleep-deprived rats
Multidisciplinary 3D geological-petrophysical reservoir characterization of Abu Sennan Field, Abu Gharadig Basin, Egypt
Abstract Reservoir heterogeneity within the Cretaceous Abu Roash and Bahariya formations of the Abu Sennan Field (Western Desert, Egypt) presents a significant challenge to hydrocarbon prospect evaluation. This study applies an integrated approach combining well logs from four wells, core analysis, and 2D seismic data to assess reservoir quality and structural framework. The workflow includes: (1) petrophysical evaluation to quantify shale volume (Vsh), effective porosity (ϕe), and hydrocarbon saturation (Sh) across five reservoir intervals—Abu Roash C (net pay 1–32.5 m, Vsh 29–35%, ϕe 19–29%, Sh 52–67%), Abu Roash D (7–10.5 m, Vsh 2–13%, ϕe 17–23%, Sh 60–90%), Abu Roash E (3.4–48.6 m, Vsh 20–30%, ϕe 18–24%, Sh 62–76%), Abu Roash G (3–12.5 m, Vsh 11–18%, ϕe 22–24%, Sh 58–73%), and Bahariya (2.5–52.5 m, Vsh 17–27%, ϕe 15–26%, Sh 46–77%); (2) seismic interpretation identifying a NW–SE-trending horst structure bounded by E–W and NNW–SSE fault systems, which compartmentalize the reservoirs; and (3) 3D static modeling to visualize the distribution of facies, porosity, and saturation. The results highlight the AR-D-01 structural closure within the Abu Roash D member as a high-potential prospect, featuring dissolution-enhanced vuggy porosity (ϕe 17–24%) and elevated hydrocarbon saturation (Sₕ 60–90%) corroborated by depth structure maps and petrophysical property models. Overall, the study demonstrates that fault-controlled diagenesis improves reservoir quality in grainstone facies, offering a reliable framework for targeted hydrocarbon exploration in heterogeneous systems.