1,720,978 research outputs found
Analytical Description of Access Probability and RRA strategy for UAV-Aided Vehicular Applications
No full textLong-term prognostic potential of microRNA-150-5p in optimally treated heart failure patients with reduced ejection fraction: a pilot study
No full textBACKGROUND: In a previous study, we found that miR-150-5p was specifically downregulated in patients with advanced heart failure (HF). Here, we investigated the long-term prognostic potential of miR-150-5p. METHODS: We studied optimally-treated HF outpatients with reduced ejection fraction. The primary outcome comprised the composite of death, urgent heart transplantation (HT) and ventricular assist device (VAD) implantation within 30 months. We used recursive partitioning analysis to identify the optimal log miR-150-5p cut-off. The association of log miR-150-5p with the primary outcome was examined using Cox regression analysis. We used the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score for adjustment in multivariable analysis. Finally, we compared the global fit of three models (MAGGIC score + miR-150-5p, MAGGIC score + NT-proBNP, and NT-proBNP + miR-1505p) using Akaike Information Criterion. RESULTS: Recursive partitioning analysis identified the value of -2.22 as the optimal cut-off for log miR-150-5p. Thirtymonth survival free of urgent HT/VAD implantation was 31% among the patients with log miR-150-5p<-2.22 and 86% among those with log miR-150-5p>-2.22. Crude hazard ratio (HR) of the primary outcome for log miR-150-5p expression level <-2.22 was 6.70 (95% CI: 2.31-19.38; P<0.001). After adjusting for the MAGGIC score in multivariable analysis, the HR was 4.40 (95% CI: 1.52-12.77; P=0.006). Adding log miR-150-5p to the MAGGIC score led to an increase of 0.047 in C-index. The model combining miR-150-5p and MAGGIC score had a 73% likelihood of representing the best-fit model of those evaluated. CONCLUSIONS: Our data generate the hypothesis that miR-150-5p may represent a novel risk marker in HF with reduced ejection fraction
Should we enlarge the indication for kidney biopsy in patients with diabetes? The pro part
Full text linkDiabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted nature of renal damage, fueled by insights from histopathological investigations, offer unprecedented prospects for refining diagnostic strategies and customizing therapeutic interventions. Renal biopsies have emerged as indispensable tools for unraveling the diverse phenotypes of renal damage in diabetes. The pioneering study by Mazzucco identified three classes of renal damage in type 2 diabetes patients: classical diabetic glomerulosclerosis (DN), vascular and ischemic glomerular changes (NDRD), and other glomerulonephritides in the presence (DN + NDRD, mixed forms) or absence of DN (NDRD). The prevalence of these classes varies widely in published studies, influenced by factors such as ethnicity, geography and selection criteria for renal biopsy. Moreover, the international Renal Pathology Society consensus classification system has stratified the classical diabetic nephropathy into progressive categories of renal impairment, a breakthrough that aids in prognostication. Histopathological scrutiny, particularly the intricate correlation between glomerular and tubulointerstitial lesions, contributes profoundly to enhancing our grasp of the phenotype's heterogeneity. This amplified comprehension holds the potential to steer personalized treatment strategies. Cutting-edge interventions, encompassing sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and anti-endothelin receptor agents, are broadening the arsenal against renal injury in diabetes. When combined with the profound insights garnered from histopathological, omics, imaging and clinical data, these therapeutic avenues promise a transformative shift towards precision-driven care paradigms. Collaborative efforts uniting researchers, clinicians and patients are indispensable for propelling our knowledge of diabetic renal damage and ameliorating patient outcomes. The fusion of histopathological, omics and imaging findings into clinical decision-making harbors the potential to customize interventions and optimize care for individuals grappling with diabetes-associated renal complications. Furthermore, groundbreaking initiatives like the iBeat Study within the BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease) project (https://www.beat-dkd.eu/), elucidating distinct phenotypes of renal damage within diabetes, underscore the imperative necessity of integrating histopathological data into the broader framework of diabetic renal management
Optimizing beam selection and resource allocation in UAV-aided vehicular networks
No full textFuture mobile radio networks require a degree of flexibility that technologies like Unmanned Aerial Vehicles (UAVs) carrying Base Stations (BSs) can provide. It is expected that the lower space above cities will be populated by many different types of UAVs, such as taxis and smaller drones used for logistics or patrolling, which can be equipped with BSs to serve users on the ground, while flying for their given mission. We investigate an urban scenario with terrestrial macro BSs (MBSs) deployed, where multiple UAVs are flying on a given path. Vehicles in the area are moving while relying on network services, and MBSs alone might not serve them adequately. UAVs operate as BSs, helping the MBSs. Vehicles are assumed to be satisfied if an appropriate quality of experience (QoE) is fulfilled, that is they are able to upload a given amount of data during a given time window, continuously. We assume BSs use beamforming and a limited number of beams can be activated at the same time on UAVs. This paper proposes an optimization algorithm allowing to select the best set of beams to be activated at each UAV and the best set of resource units per vehicle, in order to maximaze the QoE. The algorithm jointly considers: i) resource management at both MBSs and UAVs; ii) traffic prioritization to attain the continuous service; iii) a limited backhaul capacity. Numerical results show the notable improvement of satisfied users when the flying BSs are present and report the impact of backhaul capacity
The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase
No full textAdenylate kinases regulate adenine nucleotide levels and are present in different intracellular compartments. These enzymes also participate in the activation of pharmacologically active nucleoside and nucleotide analogs. We have in the present study identified the ninth isoform of the adenylate kinase family of enzymes and accordingly named the protein adenylate kinase 9 (AK9). Initially a full-length cDNA of a hypothetical protein containing a predicted adenylate kinase domain was identified and subsequently cloned and expressed in Escherichia coli. The substrate specificity of the recombinant protein showed that the enzyme catalyzed the phosphorylation of AMP, dAMP, CMP and dCMP with ATP as phosphate donor, while only AMP and CMP were phosphorylated when GTP was the phosphate donor. The kinetic parameters of AK9 were determined for AMP, dAMP and CMP with ATP as phosphate donor. Interestingly, in addition to the diphosphate products, a nucleoside diphosphate kinase (NDPK) activity was also present with subsequent triphosphates formed. With ATP or GTP as phosphate donor it was possible to detect the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and UP as enzymatic products from the corresponding diphosphate substrates. A number of previously characterized adenylate kinases were also tested and found to possess a broad phosphotransferase activity similar to AK9. These enzymes are accordingly suggested to be regarded as nucleoside mono- and diphosphate kinases with catalytic activities possibly determined by local substrate concentrations. (C) 2013 Elsevier Ltd. All rights reserved
The pathological role of the ubiquitination pathway in diabetic nephropathy
No full textDiabetic nephropathy (DN) is a chronic complication of type 2 diabetes and is the most frequent form of chronic kidney disease that can lead to end-stage renal disease. Different pathways, involved in oxidative stress, inflammation, fibrosis and cell death, are responsible for the pathogenesis of DN and regulate the progression of the disease. Ubiquitination is a fundamental pathway in intracellular signaling whose role is emerging in the regulation of molecular processes responsible for several human diseases. Among the conventional ubiquitination pathway, leading to proteasomal degradation of proteins, also non-conventional ubiquitination plays an important role in the regulation of intracellular signaling. Several proteasome inhibitors have been developed and tested both in humans and in animal models and show potential as promising therapeutic approaches. In this review, we focused our attention on the role of ubiquitination pathway in the principal processes involved in the pathogenesis and progression of DN
A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications
Full text linkDiabetic nephropathy (DN), a microvascular complication occurring in approximately 20-40% of patients with type 2 diabetes mellitus (T2DM), is characterized by the progressive impairment of glomerular filtration and the development of Kimmelstiel-Wilson lesions leading to end-stage renal failure (ESRD). The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed
Extract from Asteraceae Brachylaena ramiflora induces apoptosis preferentially in mutant p53-expressing human tumor cells
No full textThe p53 tumor suppressor gene is inactivated by point mutation in a large fraction of human tumors, allowing evasion of apoptosis and tumor progression. p53 mutation is often associated with increased resistance to therapy. Pharmacological reactivation of mutant p53 is an attractive therapeutic strategy. We previously identified p53 reactivation and induction of massive apoptosis, a low-molecular weight compound that suppresses the growth of cancer cells in a mutant p53-dependent manner. Here, we report the identification and characterization of an extract from the terrestrial plant Brachylaena ramiflora (Asteraceae) that preferentially induces apoptosis in human tumor cells expressing mutant p53. Further analysis of this extract and identification of active compounds may provide novel structural scaffolds for the development of mutant p53-targeting anticancer drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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