SciCombinator

Discover the most talked about and latest scientific content & concepts.

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The incidence of contrast-induced acute kidney injury (CI-AKI) is particularly high in patients with severe chronic kidney disease (CKD). Novel contrast-sparing strategies are warranted to guarantee the benefit of revascularization in this challenging and growing patient population. We aimed to evaluate the feasibility of an ultra-low contrast volume percutaneous coronary intervention (ULC-PCI) protocol in patients with severe CKD.

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Dental Cone-beam computed tomography (CBCT) exposure parameters should be optimized according to patient-specific indications, mainly for children that are most vulnerable to harmful effects of ionizing radiation. The aim of this study was to determine optimized kV settings for pediatric acquisitions for a dental CBCT device.

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Zebrafish embryos and larvae have become popular vertebrate models because their body walls are transparent, which enables live imaging of target organs using fluorescent protein transgenes or dye staining. Software packages for the quantification of these fluorescent signals are available from both commercial and noncommercial sources; however, their algorithms are complicated and their resources (code) have mostly not been openly shared. In this study, we developed a simple and robust open-source software tool named “ZF-Mapper” for the quantification of the fluorescence intensity of each pixel in zebrafish images with batch image file processing capability. Using this software, we can evaluate the three-dimensional (3D) distribution of fluorescence intensity among zebrafish cells by analyzing each image pixel. We tested ZF-Mapper for the analysis of zebrafish with macrophage-specific enhanced green fluorescent protein (EGFP) and obtained results that were equivalent to those acquired using the conventional image analysis software ImageJ. We further applied ZF-Mapper to the analysis of zebrafish with cancer cell xenografts and quantified the amount of implanted melanoma cells labeled with a tdTomato red fluorescent protein in the whole body and the tail region. In addition, by combining ZF-Mapper with R freeware, we created an interactive 3D scatter plot of the fluorescence intensities of macrophage-EGFPs in zebrafish. In summary, we developed the Python-based freeware ZF-Mapper for the quantification of fluorescent signals in multiple zebrafish images, which enables fluorescence-based zebrafish screening. We provide the source code and the executable application software for Windows (.exe) and macOS (.app).

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We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.

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The rate of morphological evolution along the branches of a phylogeny varies widely [1-6]. Although such rate variation is often assumed to reflect the strength of historical natural selection resulting in adaptation [7-14], this lacks empirical and analytical evidence. One way to demonstrate a relationship between branchwise rates and adaptation would be to show that rapid rates of evolution are linked with ecological shifts or key innovations. Here, we test for this link by determining whether activity pattern, the time of day at which species are active, explains rapid bursts of evolutionary change in eye shape. Using modern approaches to identify shifts in the rate of morphological evolution [7, 13], we find that over 74% of rapid eye-shape change during mammalian evolutionary history is directly explained by distinct selection pressures acting on nocturnal, cathemeral, and diurnal species. Our results reveal how ecological changes occurring along the branches of a phylogeny can manifest in subsequent changes in the rate of morphological evolution. Although selective pressures exerted by different activity patterns have acted uniformly across all mammals, we find differences in the rate of eye-shape evolution among orders. The key to understanding this is in how ecology itself has evolved. We find heterogeneity in how activity pattern has evolved among mammals that ultimately led to differences in the rate of eye-shape evolution among species. Our approach represents an exciting new way to pinpoint factors driving adaptation, enabling a clearer understanding of the factors that drive the evolution of biological diversity.

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Grid cells fire in a triangular pattern that tessellates the environment [1]. The pattern displays a global distortion that is well described by a shearing transformation of an idealized grid [2]. However, in addition, distortions often differ across parts of the environment, suggesting that the grid interacts with the environment locally [2-5]. How this occurs is poorly understood. To further determine the nature of local distortions, we therefore analyzed the local spatial characteristics of the grid pattern. When rats ran in a large square enclosure, the grid pattern displayed several stereotypical distortions in relation to features of the environment. These distortions were stronger at edges than on open surfaces. Curved axis orientations and distortions of the grid pattern in the corners could be explained by a geometrical model where the pattern, in conjunction with being sheared, is compressed along the walls of the enclosure. The grid compression coincided with stereotypical running behavior where the animals moved faster in the areas where the grid had the most pronounced distortions. However, neither running direction nor speed influenced the distortions on a moment-to-moment basis, raising the possibility that the distortions are a learned feature.

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During visual perception, the brain enhances the representations of image regions that belong to figures and suppresses those that belong to the background. Natural images contain many regions that initially appear to be part of a figure when analyzed locally (proto-objects) but are actually part of the background if the whole image is considered. These proto-grounds must be correctly assigned to the background to allow correct shape identification and guide behavior. To understand how the brain resolves this conflict between local and global processing, we recorded neuronal activity from the primary visual cortex (V1) of macaque monkeys while they discriminated between n/u shapes that have a central proto-ground region. We studied the fine-grained spatiotemporal profile of neural activity evoked by the n/u shape and found that neural representation of the object proceeded from a coarse-to-fine resolution. Approximately 100 ms after the stimulus onset, the representation of the proto-ground region was enhanced together with the rest of the n/u surface, but after ∼115 ms, the proto-ground was suppressed back to the level of the background. Suppression of the proto-ground was only present in animals that had been trained to perform the shape-discrimination task, and it predicted the choice of the animal on a trial-by-trial basis. Attention enhanced figure-ground modulation, but it had no effect on the strength of proto-ground suppression. The results indicate that the accuracy of scene segmentation is sharpened by a suppressive process that resolves local ambiguities by assigning proto-grounds to the background.

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Drosophila Transmembrane channel-like (Tmc) is a protein that functions in larval proprioception. The closely related TMC1 protein is required for mammalian hearing and is a pore-forming subunit of the hair cell mechanotransduction channel. In hair cells, TMC1 is gated by small deflections of microvilli that produce tension on extracellular tip-links that connect adjacent villi. How Tmc might be gated in larval proprioceptors, which are neurons having a morphology that is completely distinct from hair cells, is unknown. Here, we have used high-speed confocal microscopy both to measure displacements of proprioceptive sensory dendrites during larval movement and to optically measure neural activity of the moving proprioceptors. Unexpectedly, the pattern of dendrite deformation for distinct neurons was unique and differed depending on the direction of locomotion: ddaE neuron dendrites were strongly curved by forward locomotion, while the dendrites of ddaD were more strongly deformed by backward locomotion. Furthermore, GCaMP6f calcium signals recorded in the proprioceptive neurons during locomotion indicated tuning to the direction of movement. ddaE showed strong activation during forward locomotion, while ddaD showed responses that were strongest during backward locomotion. Peripheral proprioceptive neurons in animals mutant for Tmc showed a near-complete loss of movement related calcium signals. As the strength of the responses of wild-type animals was correlated with dendrite curvature, we propose that Tmc channels may be activated by membrane curvature in dendrites that are exposed to strain. Our findings begin to explain how distinct cellular systems rely on a common molecular pathway for mechanosensory responses.

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Proprioceptors provide feedback about body position that is essential for coordinated movement. Proprioceptive sensing of the position of rigid joints has been described in detail in several systems; however, it is not known how animals with a flexible skeleton encode their body positions. Understanding how diverse larval body positions are dynamically encoded requires knowledge of proprioceptor activity patterns in vivo during natural movement. Here we used high-speed volumetric swept confocally aligned planar excitation (SCAPE) microscopy in crawling Drosophila larvae to simultaneously track the position, deformation, and intracellular calcium activity of their multidendritic proprioceptors. Most proprioceptive neurons were found to activate during segment contraction, although one subtype was activated by extension. During cycles of segment contraction and extension, different proprioceptor types exhibited sequential activity, providing a continuum of position encoding during all phases of crawling. This sequential activity was related to the dynamics of each neuron’s terminal processes, and could endow each proprioceptor with a specific role in monitoring different aspects of body-wall deformation. We demonstrate this deformation encoding both during progression of contraction waves during locomotion as well as during less stereotyped, asymmetric exploration behavior. Our results provide powerful new insights into the body-wide neuronal dynamics of the proprioceptive system in crawling Drosophila, and demonstrate the utility of our SCAPE microscopy approach for characterization of neural encoding throughout the nervous system of a freely behaving animal.

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Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria.