Miracle-dz/UniFAR-FTUs huggingface dataset:
Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial

Importance The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, −0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, −0.18%; 95% CI, −0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57). Conclusions and Relevance In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration clinicaltrials.gov Identifier: NCT02298088
Study on Relationship among Internal Customer Orientation, Market Orientation and Organizational Performance of Theme Restaurants

This study takes theme restaurants as an example to discuss the relationship model of internal custome r orientation, market orientation and organizational performance. The results suggest that internal cust omer orientation has significant positive impact on market orientati on, which has no significant direct impact on organ izational performance, which will be significantly impacted p ositively by internal customer orientation. Researc h results can provide theme restaurants with references of promot ing internal customer orientation and market orient ation for the purpose of facilitating the organization to acquire market orientation, hence to increase organization al performance and establish competitive advantage.
Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery

Dodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine’s vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.
Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease

Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients.
Impact of Enhanced Staphylococcus DNA Extraction on Microbial Community Measures in Cystic Fibrosis Sputum

Staphylococcus aureus is a common constituent of the bacterial community inhabiting the airways of persons with cystic fibrosis (CF). Culture-independent studies have shown that this species is often present in relatively high abundance and would therefore be expected to exert a pronounced effect on measures of CF airway bacterial community structure. We investigated the impact of DNA extraction method on pyrosequencing-based measures of Staphylococcus abundance and bacterial community structure in 17 sputum samples from five CF patients. Staphylococcus was detected in fewer samples when DNA was extracted using a standard bacterial lysis method compared to when DNA was extracted using a lysis buffer amended with lysostaphin and lysozyme. The standard lysis method resulted in significantly lower measures of Staphylococcus relative abundance and higher levels of community diversity, richness, and evenness compared to the lysostaphin-lysozyme modified method. Measures of community dynamics in serial sputum samples from the same individual were nevertheless highly concordant between the two DNA extraction methods. These results illustrate the impact of DNA preparation method on measures of Staphylococcus abundance and bacterial community structures in studies of the airways microbiota in CF.
EEGNet: a compact convolutional neural network for EEG-based brain–computer interfaces

Objective. Brain–computer interfaces (BCI) enable direct communication with a computer, using neural activity as the control signal. This neural signal is generally chosen from a variety of well-studied electroencephalogram (EEG) signals. For a given BCI paradigm, feature extractors and classifiers are tailored to the distinct characteristics of its expected EEG control signal, limiting its application to that specific signal. Convolutional neural networks (CNNs), which have been used in computer vision and speech recognition to perform automatic feature extraction and classification, have successfully been applied to EEG-based BCIs; however, they have mainly been applied to single BCI paradigms and thus it remains unclear how these architectures generalize to other paradigms. Here, we ask if we can design a single CNN architecture to accurately classify EEG signals from different BCI paradigms, while simultaneously being as compact as possible. Approach. In this work we introduce EEGNet, a compact convolutional neural network for EEG-based BCIs. We introduce the use of depthwise and separable convolutions to construct an EEG-specific model which encapsulates well-known EEG feature extraction concepts for BCI. We compare EEGNet, both for within-subject and cross-subject classification, to current state-of-the-art approaches across four BCI paradigms: P300 visual-evoked potentials, error-related negativity responses (ERN), movement-related cortical potentials (MRCP), and sensory motor rhythms (SMR). Main results. We show that EEGNet generalizes across paradigms better than, and achieves comparably high performance to, the reference algorithms when only limited training data is available across all tested paradigms. In addition, we demonstrate three different approaches to visualize the contents of a trained EEGNet model to enable interpretation of the learned features. Significance. Our results suggest that EEGNet is robust enough to learn a wide variety of interpretable features over a range of BCI tasks. Our models can be found at: https://github.com/vlawhern/arl-eegmodels.
Predicting Species Diversity of Benthic Communities within Turbid Nearshore Using Full-Waveform Bathymetric LiDAR and Machine Learners

Epi-macrobenthic species richness, abundance and composition are linked with type, assemblage and structural complexity of seabed habitat within coastal ecosystems. However, the evaluation of these habitats is highly hindered by limitations related to both waterborne surveys (slow acquisition, shallow water and low reactivity) and water clarity (turbid for most coastal areas). Substratum type/diversity and bathymetric features were elucidated using a supervised method applied to airborne bathymetric LiDAR waveforms over Saint-Siméon–Bonaventure's nearshore area (Gulf of Saint-Lawrence, Québec, Canada). High-resolution underwater photographs were taken at three hundred stations across an 8-km2 study area. Seven models based upon state-of-the-art machine learning techniques such as Naïve Bayes, Regression Tree, Classification Tree, C 4.5, Random Forest, Support Vector Machine, and CN2 learners were tested for predicting eight epi-macrobenthic species diversity metrics as a function of the class number. The Random Forest outperformed other models with a three-discretized Simpson index applied to epi-macrobenthic communities, explaining 69% (Classification Accuracy) of its variability by mean bathymetry, time range and skewness derived from the LiDAR waveform. Corroborating marine ecological theory, areas with low Simpson epi-macrobenthic diversity responded to low water depths, high skewness and time range, whereas higher Simpson diversity relied upon deeper bottoms (correlated with stronger hydrodynamics) and low skewness and time range. The degree of species heterogeneity was therefore positively linked with the degree of the structural complexity of the benthic cover. This work underpins that fully exploited bathymetric LiDAR (not only bathymetrically derived by-products), coupled with proficient machine learner, is able to rapidly predict habitat characteristics at a spatial resolution relevant to epi-macrobenthos diversity, ranging from clear to turbid waters. This method might serve both to nurture marine ecological theory and to manage areas with high species heterogeneity where navigation is hazardous and water clarity opaque to passive optical sensors.
Chromatin‐bound bacterial effector ankyrin A recruits histone deacetylase 1 and modifies host gene expression

Control of host epigenetics is becoming evident as a mechanism by which symbionts and pathogens survive. Anaplasma phagocytophilum, an obligate intracellular bacterium, down‐regulates multiple host defence genes where histone deacetylase 1 (HDAC1) binds and histone 3 is deacetylated at their promoters, including the NADPH oxidase component, CYBB. How HDAC1 is targeted to defence gene promoters is unknown. Ankyrin A (AnkA), an A. phagocytophilum type IV secretion system effector, enters the granulocyte nucleus, binds stretches of AT‐rich DNA and alters transcription of antimicrobial defence genes, including down‐regulation of CYBB. Here we found AnkA binds to a predicted matrix attachment region in the proximal CYBB promoter. Using the CYBB promoter as a model of cis‐gene silencing, we interrogated the mechanism of AnkA‐mediated CYBB repression. The N‐terminus of AnkA was critical for nuclear localization, the central ANK repeats and C‐terminus were important for DNA binding, and most promoter activity localized to the central ANK repeats. Furthermore, a direct interaction between AnkA and HDAC1 was detected at the CYBB promoter, and was critical for AnkA‐mediated CYBB repression. This novel microbial manipulation of host chromatin and gene expression provides important evidence of the direct effects that prokaryotic nuclear effectors can exert over host transcription and function.
High Order Discrete Approximations to Mayer's Problems for Linear Systems

This paper presents a discretization scheme for Mayer's type optimal control problems of linear systems. The scheme is based on second order Volterra--Fliess approximations, and on an augmentation of the control variable in a control set of higher dimension. Compared with the existing results, it has the advantage of providing a higher order accuracy, which may make it more efficient when aiming for a certain precision. Error estimations (depending on the controllability index of the system at the solution) are proved by using a recent result about stability of the optimal solution with respect to disturbances. Numerical results are provided which show the sharpness of the error estimations.
The Exiguobacterium sibiricum 255-15 GtfC Enzyme Represents a Novel Glycoside Hydrolase 70 Subfamily of 4,6-α-Glucanotransferase Enzymes

ABSTRACT The glycoside hydrolase 70 (GH70) family originally was established for glucansucrase enzymes found solely in lactic acid bacteria synthesizing α-glucan polysaccharides from sucrose (e.g., GtfA). In recent years, we have characterized GtfB and related Lactobacillus enzymes as 4,6-α-glucanotransferase enzymes. These GtfB-type enzymes constitute the first GH70 subfamily of enzymes that are unable to act on sucrose as a substrate but are active with maltodextrins and starch, cleave α1→4 linkages, and synthesize linear α1→6-glucan chains. The GtfB disproportionating type of activity results in the conversion of malto-oligosaccharides into isomalto/malto-polysaccharides with a relatively high percentage of α1→6 linkages. This paper reports the identification of the members of a second GH70 subfamily (designated GtfC enzymes) and the characterization of the Exiguobacterium sibiricum 255-15 GtfC enzyme, which is also inactive with sucrose and displays 4,6-α-glucanotransferase activity with malto-oligosaccharides. GtfC differs from GtfB in synthesizing isomalto/malto-oligosaccharides. Biochemically, the GtfB- and GtfC-type enzymes are related, but phylogenetically, they clearly constitute different GH70 subfamilies, displaying only 30% sequence identity. Whereas the GtfB-type enzyme largely has the same domain order as glucansucrases (with α-amylase domains A, B, and C plus domains IV and V), this GtfC-type enzyme differs in the order of these domains and completely lacks domain V. In GtfC, the sequence of conserved regions I to IV of clan GH-H is identical to that in GH13 (I-II-III-IV) but different from that in GH70 (II-III-IV-I because of a circular permutation of the (β/α)8 barrel. The GtfC 4,6-α-glucanotransferase enzymes thus represent structurally and functionally very interesting evolutionary intermediates between α-amylase and glucansucrase enzymes.
Chinook salmon (Oncorhynchus tshawytscha) and rainbow trout (Oncorhynchus mykiss) exposed to copper: Neurophysiological and histological effects on the olfactory system

Olfactory epithelial structure and olfactory bulb neurophysiological responses were measured in chinook salmon and rainbow trout in response to 25 to 300 μg copper (Cu)/L. Using confocal laser scanning microscopy, the number of olfactory receptors was significantly reduced in chinook salmon exposed to ≥0 μg Cu/L and in rainbow trout exposed to ≥200 μg Cu/L for 1 h. The number of receptors was significantly reduced in both species following exposure to 25 μg Cu/L for 4 h. Transmission electron microscopy of olfactory epithelial tissue indicated that the loss of receptors was from cellular necrosis. Olfactory bulb electroencephalogram (EEG) responses to 10−3 M L‐serine were initially reduced by all Cu concentrations but were virtually eliminated in chinook salmon exposed to ≥50 μg Cu/L and in rainbow trout exposed to ≥200 μg Cu/L within 1 h of exposure. Following Cu exposure, EEG response recovery rates were slower in fish exposed to higher Cu concentrations. The higher sensitivity of the chinook salmon olfactory system to Cu‐induced histological damage and neurophysiological impairment parallels the relative species sensitivity observed in behavioral avoidance experiments. This difference in species sensitivity may reduce the survival and reproductive potential of chinook salmon compared with that of rainbow trout in Cu‐contaminated waters.
Prevalence and Intensity of Clonorchis sinensis Metacercariae in Freshwater Fish from Wicheon Stream in Gunwi-gun, Gyeongsangbuk-do, Korea

The infection status of Clonorchis sinensis metacercariae (CsMc) was examined in freshwater fish from a highly prevalent site, Wicheon (a branch of Nakdong-gang), which is located in Gunwi-gun, Gyeongsangbuk-do, the Republic of Korea. Total 1,162 fish in 32 species were examined by the artificial digestion method through 6 years. CsMc were detected in 720 (67.5%) out of 1,067 fish (26 spp.) and their density was 610 per fish infected. In the susceptible gobioninid fish group, i.e., Pungtungia herzi, Squalidus gracilis majimae, Squalidus japonicus coreanus, Sarcocheilichthys variegatus wakiyae and Pseudorasbora parva, all of 323 fish were infected with an average of 1,310 CsMc. Total 23 (95.8%) gobioninid fish, i.e., Pseudogobio esocinus, Abbottina springeri, Hemibarbus longirostris, Microphysogobio koreensis, and Microphysogobio jeoni, were infected with 127 CsMc in average. In the acheilognathinid fish (bitterlings) group, the prevalence was 77.0%, and the density was 50 CsMc per fish infected. In the rasborinid fish (chubs) group, i.e., Zacco platypus, Zacco temminckii, Zacco koreanus, and Opsariichthys uncirostris amurensis, 147 (36.5%) out of 403 fish examined were infected with 15 CsMc in average. The susceptibility indices of CsMc were 412 in the overall positive fish group, 1,310 in the gobioninid group-1, 122 in the gobioninid group-2, 38.5 in the acheilognathinid group, and 5.5 in the rasborinid fish group. Conclusively, it was confirmed that CsMc are highly prevalent in fish from Wicheon, and their infection tendency varied according to the subfamily groups in Cyprinidae fish hosts.
Effect of floorball training on blood lipids, body composition, muscle strength, and functional capacity of elderly men

Floorball training consists of intense repeated exercise and may offer a motivating and social stimulating team activity in elderly individuals. However, the effect of floorball training in elderly adults on physiological adaptations important for health is not known. Thus, this study examined the effect of floorball training on blood lipids, muscle strength, body composition, and functional capacity of men aged 65–76 years. Thirty‐nine recreational active men were randomized into a floorball group (FG; n = 22) or petanque group (PG; n = 17), in which training was performed 1 h twice a week for 12 weeks. In FG and PG, average heart rate (HR) during training was 80% and 57%, respectively, of maximal HR. In FG, plasma low‐density lipoprotein (LDL) cholesterol and triglycerides were 11% and 8% lower (P < 0.05), respectively. Insulin resistance determined by homeostatic model assessment (HOMA‐IR) was reduced (P < 0.05) by 18%. HR during submaximal cycling was 5% lower (P < 0.05), and maximal voluntary contraction force was 8% higher (P < 0.05). Total and visceral fat content was lowered (P < 0.05) by 5% and 14%, respectively, HR at rest was 8% lower (P < 0.05) and performance in four different functional capacity tests were better (P < 0.05) after compared to before the training period. No changes were observed in PG. In conclusion, 12 weeks of floorball training resulted in a number of favorable effects important for health and functional capacity, suggesting that floorball training can be used as a health‐promoting activity in elderly men.
Exposures to Conditioned Flavours with Different Hedonic Values Induce Contrasted Behavioural and Brain Responses in Pigs

This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d.) infusions of 15% glucose (FGlu), lithium chloride (FLiCl), or saline (control treatment, FNaCl). One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three 18FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the FLiCl than the FNaCl or FGlu meals. During the two-choice tests performed one and five weeks later, the FNaCl and FGlu foods were significantly preferred over the FLICl food even in the absence of i.d. infusions. Surprisingly, the FNaCl food was also preferred over the FGlu food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake.