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70 (95% CI 1.67-1.73); I 2 = 0%; P less then 0.00001], and changes in body weight [MD -1.43 (95% CI -2.15 to -0.72); I 2 = 84%; P less then 0.0001) from baseline. However, empagliflozin did not show a better change in the 6-min walk test (6MWT) [MD 34.06 (95% CI -29.75-97.88); I 2 = 97%; P = 0.30] or NT-proBNP [MD -98.36 (95% CI, -225.83-29.11); I 2 = 68%; P = 0.13] from baseline. Conclusion The findings suggest that empagliflozin was effective in reducing a composite of cardiovascular death or hospitalization for worsening heart failure. Further well-designed RCTs are needed to evaluate the long-term effect of empagliflozin in patients with HF. PROSPERO CRD42021231712.NOTCH intercellular signaling mediates the communications between adjacent cells involved in multiple biological processes essential for tissue morphogenesis and homeostasis. The NOTCH1 mutations are the first identified human genetic variants that cause congenital bicuspid aortic valve (BAV) and calcific aortic valve disease (CAVD). Genetic variants affecting other genes in the NOTCH signaling pathway may also contribute to the development of BAV and the pathogenesis of CAVD. While CAVD occurs commonly in the elderly population with tri-leaflet aortic valve, patients with BAV have a high risk of developing CAVD at a young age. This observation indicates an important role of NOTCH signaling in the postnatal homeostasis of the aortic valve, in addition to its prenatal functions during aortic valve development. Over the last decade, animal studies, especially with the mouse models, have revealed detailed information in the developmental etiology of congenital aortic valve defects. In this review, we will discuss the molecular and cellular aspects of aortic valve development and examine the embryonic pathogenesis of BAV. We will focus our discussions on the NOTCH signaling during the endocardial-to-mesenchymal transformation (EMT) and the post-EMT remodeling of the aortic valve. We will further examine the involvement of the NOTCH mutations in the postnatal development of CAVD. We will emphasize the deleterious impact of the embryonic valve defects on the homeostatic mechanisms of the adult aortic valve for the purpose of identifying the potential therapeutic targets for disease intervention.Background Traditionally, the only effective treatment for aortic stenosis was surgical aortic valve replacement (SAVR). Transcatheter aortic valve replacement (TAVR) was approved in the United States in late 2011 and provided a critical alternative therapy. Our aims were to investigate the trends in the utilization of SAVR in the early vs. late TAVR era and to assess SAVR and TAVR outcomes. Methods Using the 2011-2017 National Inpatient Sample database, we identified hospitalizations for patients with a most responsible diagnosis of aortic stenosis during which an aortic valve replacement (AVR) was performed, either SAVR or TAVR. selleckchem Patients' sociodemographic and clinical characteristics, procedure complications, length of stay, and mortality were analyzed. Multivariable analyses were performed to identify predictors of in-hospital mortality. Piecewise regression analyses were performed to assess temporal trends in SAVR and TAVR utilization. Results A total of 542,734 AVR procedures were analyzed. The utilization of SAVR was steady until 2014 with a significant downward trend in the following years 2015-2017 (P = 0.026). In contrast, a steady upward trend was observed in the TAVR procedure with a significant increase during the years 2015-2017 (P = 0.006). Higher in-hospital mortality was observed in SAVR patients. The mortality rate declined from 2011 to 2017 in a significantly higher proportion in the TAVR compared with the SAVR group. Conclusion Utilization of SAVR showed a downward trend during the late TAVR era (2015-2017), and TAVR utilization demonstrated a steady upward trend during the years 2011-2017. Higher in-hospital mortality was recorded in patients who underwent SAVR.Objective Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues. Approach and Results Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression. link2 Conclusions Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species.Background This study compared differences in the risk factors and clinical outcomes of primary percutaneous coronary intervention (PCI) in type 2 diabetes mellitus (DM) and non-DM patients with de novo lesions (DNLs) and late or very late stent thrombosis (LST/VLST). Methods We used angiography to screen 4,151 patients with acute coronary syndrome for DNL and LST/VLST lesions. Overall, 3,941 patients were included in the analysis and were allocated to the DM (n = 1,286) or non-DM (n = 2,665) group at admission. The primary endpoint was a composite of major adverse cardiovascular events (MACEs), defined as death, myocardial infarction, revascularization, and ischemic stroke, within a median follow-up period of 698 days. Results In the group with a total white blood cell count >10 × 109/L (P = 0.004), a neutral granular cell count >7 × 109/L (P = 0.030), and neutrophil-lymphocyte ratio >1.5 (P = 0.041), revascularization was better for DNL than for LST/VLST lesions. link3 Among DM patients with DNLs, each unit increlevel, the risk of MACEs increased by 59.7% (HR, 1.597; 95% CI, 1.110-2.295; P = 0.041). Conclusion Following successful primary PCI, the measurement of baseline and peak D-dimer values may help identify individuals at high cardiovascular risk. This suggests a potential benefit of lowering D-dimer levels among T2DM patients with DNL. Furthermore, age and the peak D-dimer values may facilitate the risk stratification of T2DM patients with LST/VLST.This article provides a theory for provably safe and computationally efficient distributed constrained control, and describes an application to a swarm of nano-quadrotors with limited on-board hardware and subject to multiple state and input constraints. We provide a formal extension of the explicit reference governor framework to address the case of distributed systems. The efficacy, robustness, and scalability of the proposed theory is demonstrated by an extensive experimental validation campaign and a comparative simulation study on single and multiple nano-quadrotors. The control strategy is implemented in real-time on-board palm-sized unmanned erial vehicles, and achieves safe swarm coordination without relying on any offline trajectory computations.Facilitating navigation in pedestrian environments is critical for enabling people who are blind and visually impaired (BVI) to achieve independent mobility. A deep reinforcement learning (DRL)-based assistive guiding robot with ultrawide-bandwidth (UWB) beacons that can navigate through routes with designated waypoints was designed in this study. Typically, a simultaneous localization and mapping (SLAM) framework is used to estimate the robot pose and navigational goal; however, SLAM frameworks are vulnerable in certain dynamic environments. The proposed navigation method is a learning approach based on state-of-the-art DRL and can effectively avoid obstacles. When used with UWB beacons, the proposed strategy is suitable for environments with dynamic pedestrians. We also designed a handle device with an audio interface that enables BVI users to interact with the guiding robot through intuitive feedback. The UWB beacons were installed with an audio interface to obtain environmental information. The on-handle and on-beacon verbal feedback provides points of interests and turn-by-turn information to BVI users. BVI users were recruited in this study to conduct navigation tasks in different scenarios. A route was designed in a simulated ward to represent daily activities. In real-world situations, SLAM-based state estimation might be affected by dynamic obstacles, and the visual-based trail may suffer from occlusions from pedestrians or other obstacles. The proposed system successfully navigated through environments with dynamic pedestrians, in which systems based on existing SLAM algorithms have failed.Reliable and robust fruit-detection algorithms in nonstructural environments are essential for the efficient use of harvesting robots. The pose of fruits is crucial to guide robots to approach target fruits for collision-free picking. To achieve accurate picking, this study investigates an approach to detect fruit and estimate its pose. First, the state-of-the-art mask region convolutional neural network (Mask R-CNN) is deployed to segment binocular images to output the mask image of the target fruit. Next, a grape point cloud extracted from the images was filtered and denoised to obtain an accurate grape point cloud. Finally, the accurate grape point cloud was used with the RANSAC algorithm for grape cylinder model fitting, and the axis of the cylinder model was used to estimate the pose of the grape. A dataset was acquired in a vineyard to evaluate the performance of the proposed approach in a nonstructural environment. The fruit detection results of 210 test images show that the average precision, recall, and intersection over union (IOU) are 89.53, 95.33, and 82.00%, respectively. The detection and point cloud segmentation for each grape took approximately 1.7 s. The demonstrated performance of the developed method indicates that it can be applied to grape-harvesting robots.During the COVID-19 pandemic, the higher susceptibility of post-stroke patients to infection calls for extra safety precautions. Despite the imposed restrictions, early neurorehabilitation cannot be postponed due to its paramount importance for improving motor and functional recovery chances. Utilizing accessible state-of-the-art technologies, home-based rehabilitation devices are proposed as a sustainable solution in the current crisis. In this paper, a comprehensive review on developed home-based rehabilitation technologies of the last 10 years (2011-2020), categorizing them into upper and lower limb devices and considering both commercialized and state-of-the-art realms. Mechatronic, control, and software aspects of the system are discussed to provide a classified roadmap for home-based systems development. Subsequently, a conceptual framework on the development of smart and intelligent community-based home rehabilitation systems based on novel mechatronic technologies is proposed. In this framework, each rehabilitation device acts as an agent in the network, using the internet of things (IoT) technologies, which facilitates learning from the recorded data of the other agents, as well as the tele-supervision of the treatment by an expert.