Abstract The North American Thrombosis Forum Atrial Fibrillation Action Initiative consensus document is a comprehensive yet practical briefing document focusing on stroke and bleeding risk ...assessment in patients with atrial fibrillation, as well as recommendations regarding anticoagulation options and management. Despite the breadth of clinical trial data and guideline recommendation updates, many clinicians continue to struggle to synthesize the disparate information available. This problem slows the uptake and utilization of updated risk prediction tools and adoption of new oral anticoagulants. This document serves as a practical and educational reference for the entire medical community involved in the care of patients with atrial fibrillation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Subnanometric metal species (single atoms and clusters) have been demonstrated to be unique compared with their nanoparticulate counterparts. However, the poor stabilization of subnanometric metal ...species towards sintering at high temperature (>500 °C) under oxidative or reductive reaction conditions limits their catalytic application. Zeolites can serve as an ideal support to stabilize subnanometric metal catalysts, but it is challenging to localize subnanometric metal species on specific sites and modulate their reactivity. We have achieved a very high preference for localization of highly stable subnanometric Pt and PtSn clusters in the sinusoidal channels of purely siliceous MFI zeolite, as revealed by atomically resolved electron microscopy combining high-angle annular dark-field and integrated differential phase contrast imaging techniques. These catalysts show very high stability, selectivity and activity for the industrially important dehydrogenation of propane to form propylene. This stabilization strategy could be extended to other crystalline porous materials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mutations in the gene encoding the microtubule-severing protein spastin (spastic paraplegia 4 SPG4) cause hereditary spastic paraplegia (HSP), associated with neurodegeneration, spasticity, and motor ...impairment. Complicated forms (complicated HSP cHSP) further include cognitive deficits and dementia; however, the etiology and dysfunctional mechanisms of cHSP have remained unknown. Here, we report specific working and associative memory deficits upon spastin depletion in mice. Loss of spastin-mediated severing leads to reduced synapse numbers, accompanied by lower miniature excitatory postsynaptic current (mEPSC) frequencies. At the subcellular level, mutant neurons are characterized by longer microtubules with increased tubulin polyglutamylation levels. Notably, these conditions reduce kinesin-microtubule binding, impair the processivity of kinesin family protein (KIF) 5, and reduce the delivery of presynaptic vesicles and postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Rescue experiments confirm the specificity of these results by showing that wild-type spastin, but not the severing-deficient and disease-associated K388R mutant, normalizes the effects at the synaptic, microtubule, and transport levels. In addition, short hairpin RNA (shRNA)-mediated reduction of tubulin polyglutamylation on spastin knockout background normalizes KIF5 transport deficits and attenuates the loss of excitatory synapses. Our data provide a mechanism that connects spastin dysfunction with the regulation of kinesin-mediated cargo transport, synapse integrity, and cognition.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interspecific hybrids between S. cerevisiae × S. kudriavzevii have frequently been detected in wine and beer fermentations. Significant physiological differences among parental and hybrid strains ...under different stress conditions have been evidenced. In this study, we used comparative genome hybridization analysis to evaluate the genome composition of different S. cerevisiae × S. kudriavzevii natural hybrids isolated from wine and beer fermentations to infer their evolutionary origins and to figure out the potential role of common S. kudriavzevii gene fraction present in these hybrids.
Comparative genomic hybridization (CGH) and ploidy analyses carried out in this study confirmed the presence of individual and differential chromosomal composition patterns for most S. cerevisiae × S. kudriavzevii hybrids from beer and wine. All hybrids share a common set of depleted S. cerevisiae genes, which also are depleted or absent in the wine strains studied so far, and the presence a common set of S. kudriavzevii genes, which may be associated with their capability to grow at low temperatures. Finally, a maximum parsimony analysis of chromosomal rearrangement events, occurred in the hybrid genomes, indicated the presence of two main groups of wine hybrids and different divergent lineages of brewing strains.
Our data suggest that wine and beer S. cerevisiae × S. kudriavzevii hybrids have been originated by different rare-mating events involving a diploid wine S. cerevisiae and a haploid or diploid European S. kudriavzevii strains. Hybrids maintain several S. kudriavzevii genes involved in cold adaptation as well as those related to S. kudriavzevii mitochondrial functions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surgery is a therapeutic option for people with epilepsy whose seizures are not controlled by anti-epilepsy drugs. In pre-surgical planning, an array of data modalities, often including intra-cranial ...EEG, is used in an attempt to map regions of the brain thought to be crucial for the generation of seizures. These regions are then resected with the hope that the individual is rendered seizure free as a consequence. However, post-operative seizure freedom is currently sub-optimal, suggesting that the pre-surgical assessment may be improved by taking advantage of a mechanistic understanding of seizure generation in large brain networks. Herein we use mathematical models to uncover the relative contribution of regions of the brain to seizure generation and consequently which brain regions should be considered for resection. A critical advantage of this modeling approach is that the effect of different surgical strategies can be predicted and quantitatively compared in advance of surgery. Herein we seek to understand seizure generation in networks with different topologies and study how the removal of different nodes in these networks reduces the occurrence of seizures. Since this a computationally demanding problem, a first step for this aim is to facilitate tractability of this approach for large networks. To do this, we demonstrate that predictions arising from a neural mass model are preserved in a lower dimensional, canonical model that is quicker to simulate. We then use this simpler model to study the emergence of seizures in artificial networks with different topologies, and calculate which nodes should be removed to render the network seizure free. We find that for scale-free and rich-club networks there exist specific nodes that are critical for seizure generation and should therefore be removed, whereas for small-world networks the strategy should instead focus on removing sufficient brain tissue. We demonstrate the validity of our approach by analysing intra-cranial EEG recordings from a database comprising 16 patients who have undergone epilepsy surgery, revealing rich-club structures within the obtained functional networks. We show that the postsurgical outcome for these patients was better when a greater proportion of the rich club was removed, in agreement with our theoretical predictions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the genus Saccharomyces has been thoroughly studied, some species in the genus has not yet been accurately resolved; an example is S. bayanus, a taxon that includes genetically diverse ...lineages of pure and hybrid strains. This diversity makes the assignation and classification of strains belonging to this species unclear and controversial. They have been subdivided by some authors into two varieties (bayanus and uvarum), which have been raised to the species level by others. In this work, we evaluate the complexity of 46 different strains included in the S. bayanus taxon by means of PCR-RFLP analysis and by sequencing of 34 gene regions and one mitochondrial gene. Using the sequence data, and based on the S. bayanus var. bayanus reference strain NBRC 1948, a hypothetical pure S. bayanus was reconstructed for these genes that showed alleles with similarity values lower than 97% with the S. bayanus var. uvarum strain CBS 7001, and of 99-100% with the non S. cerevisiae portion in S. pastorianus Weihenstephan 34/70 and with the new species S. eubayanus. Among the S. bayanus strains under study, different levels of homozygosity, hybridization and introgression were found; however, no pure S. bayanus var. bayanus strain was identified. These S. bayanus hybrids can be classified into two types: homozygous (type I) and heterozygous hybrids (type II), indicating that they have been originated by different hybridization processes. Therefore, a putative evolutionary scenario involving two different hybridization events between a S. bayanus var. uvarum and unknown European S. eubayanus-like strains can be postulated to explain the genomic diversity observed in our S. bayanus var. bayanus strains.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nutritional improvements in intensive aquaculture production systems is necessary for the reduction of stress, maximum utilization of nutritional components, and expression of the genetic potential ...of fish. The objective of this study was to evaluate the hemato-immunological, and histological parameters and gut microbiota of Nile tilapia fed with the microalga Schizochytrium sp. Males of Nile tilapia were distributed among eight net cages (6 m3), and fed for 105 days with two diets: control (CON), without Schizochytrium sp., and supplemented (SUP), with 1.2% Schizochytrium sp. in the diet. The final weight, mortality, hematocrit, total erythrocyte count (RBC), hemoglobin, hematimetric indices, white blood cell count (WBC), total protein, and serum lysozyme were measured. Alterations in intestinal morphology were evaluated. The gut microbiota was evaluated with next-generation sequencing. No significant differences (p>0.05) were found in the final weight and mortality between diets. Regarding the hematological parameters, a difference (p<0.05) was detected only in RBC, with there being lower values in the SUP, although this group also showed a tendency toward having an increased mean corpuscular hemoglobin level. There were no differences (p>0.05) in total protein and serum lysozyme concentrations or in WBCs between diets, except for lymphocytes, which presented lower values (p<0.05) in the SUP, suggesting immunomodulation by the polyunsaturated fatty acids present in the microalga. There was no difference (p>0.05) in the intestinal morphology between diets. Metagenomic data indicated greater richness (represented by the Chao index) and a higher abundance of the bacterial phylum Firmicutes in the gut microbiota of the tilapia fed with the SUP diet, demonstrating that the digestion and use of the components of the microalga could influence the microbial community. The results indicated that the microalga had modulatory effects on blood cells and the intestinal microbiota, without affecting the structure and integrity of the intestinal villi.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Among patients on hemodialysis, pruritus has been associated with poorer mental and physical quality of life, sleep quality, depression, and mortality. We evaluated patients with nondialysis CKD to ...describe the prevalence of pruritus, identify associated factors, and investigate associations with patient-reported outcomes.
Using cross-sectional data from patient questionnaires in the CKD Outcomes and Practice Patterns Study (CKDopps), we asked patients with CKD stages 3-5 (nondialysis) from the United States, Brazil, and France to identify how much they were bothered by pruritus. Response options ranged from "not at all" to "extremely." Log-Poisson regression, yielding prevalence ratios, was used to evaluate associations of moderate-to-extreme pruritus with patient characteristics, CKD stage, self-reported depression symptoms, and restless sleep. Mixed linear regression was used to examine associations between pruritus and physical and mental component summary scores, with lower scores indicating poorer quality of life.
Of the 5658 CKDopps patients enrolled in the United States, Brazil, and France, 3780 (67%) answered the pruritus question. The prevalence of moderate-to-extreme pruritus was 24%, and more likely in older patients, women, and those with stage 5 CKD, lung disease, diabetes, and physician-diagnosed depression. In adjusted models, patients with moderate pruritus had physical and mental component summary scores 3.5 (95% confidence interval 95% CI, -4.6 to -2.3) and 2.3 (95% CI, -3.2 to -1.5) points lower, respectively, than patients without pruritus, and they also had a higher adjusted prevalence of patient-reported depression (prevalence ratio, 1.83; 95% CI, 1.58 to 2.11) and restless sleep (prevalence ratio, 1.69; 95% CI, 1.49 to 1.91) compared with patients without pruritus. These patient-reported outcomes were progressively worse with increasing severity of pruritus.
Our findings demonstrate high prevalence of pruritus in nondialysis CKD, as well as strong associations of pruritus with poor health-related quality of life, self-reported depression symptoms, and self-reported poor sleep.
Abstract
Diffuse ionized gas (DIG) is prevalent in star-forming galaxies. Using a sample of 365 nearly face-on star-forming galaxies observed by Mapping Nearby Galaxies at APO, we demonstrate how DIG ...in star-forming galaxies impacts the measurements of emission-line ratios, hence the interpretation of diagnostic diagrams and gas-phase metallicity measurements. At fixed metallicity, DIG-dominated low ΣHα regions display enhanced S ii/Hα, N ii/Hα, O ii/Hβ and O i/Hα. The gradients in these line ratios are determined by metallicity gradients and ΣHα. In line ratio diagnostic diagrams, contamination by DIG moves H ii regions towards composite or low-ionization nuclear emission-line region (LI(N)ER)-like regions. A harder ionizing spectrum is needed to explain DIG line ratios. Leaky H ii region models can only shift line ratios slightly relative to H ii region models, and thus fail to explain the composite/LI(N)ER line ratios displayed by DIG. Our result favours ionization by evolved stars as a major ionization source for DIG with LI(N)ER-like emission. DIG can significantly bias the measurement of gas metallicity and metallicity gradients derived using strong-line methods. Metallicities derived using N2O2 are optimal because they exhibit the smallest bias and error. Using O3N2, R
23, N2 = N ii/Hα and N2S2Hα to derive metallicities introduces bias in the derived metallicity gradients as large as the gradient itself. The strong-line method of Blanc et al. (IZI hereafter) cannot be applied to DIG to get an accurate metallicity because it currently contains only H ii region models that fail to describe the DIG.
Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation ...and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.
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