Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta-Analysis of Potent P2Y12-ADP Receptor Antagonist Therapy Compared to Clopidogrel Therapy in Acute Coronary Syndrome Patients with Chronic Kidney Disease

Abstract Background The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk–benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown. Objective We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS. Methods We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings. Results We included data from three sub-group analysis of randomized clinical trials and two prospective observational studies (n = 31,234). Overall, PPAs were associated with lower rates of major cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence interval [CI]: 0.79–0.99; p = 0.03), without increased bleedings (pHR = 1.10) (95% CI: 0.95–1.27; p = 0.18). In a sensitivity analysis restricted to studies enrolling invasively managed patients, the benefit of PPA on MACE was maintained (pHR = 0.85) (95% CI: 0.77–0.93; p < 0.001), including a reduction in mortality (pHR = 0.82) (95% CI: 0.7–0.96; p = 0.016). Conclusion Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.
Land surface greening suggests vigorous woody regrowth throughout European semi‐natural vegetation

The satellite record has revealed substantial land surface “greening” in the northern hemisphere over recent decades. Process‐based Earth system models (ESMs) attribute enhanced vegetation productivity (greening) to CO2 fertilisation. However, the models poorly reproduce observed spatial patterns of greening, suggesting that they ignore crucial processes. Here, we explore whether fine‐scale land cover dynamics, as modified by ecological and land‐use processes, can explain the discrepancy between models and satellite‐based estimates of greening. We used 500 m satellite‐derived Leaf Area Index (LAI) to quantify greening. We focus on semi‐natural vegetation in Europe, and distinguish between conservation areas and unprotected land. Within these ecological and land‐use categories, we then explored the relationships between vegetation change and major climatic gradients. Despite the relatively short time‐series (15 years), we found a strong overall increase in LAI (i.e., greening) across all European semi‐natural vegetation types. The spatial pattern of vegetation change identifies land‐use change, particularly land abandonment, as a major initiator of vegetation change both in‐ and outside of protected areas. The strongest LAI increases were observed in mild climates, consistent with more vigorous woody regrowth after cessation of intensive management in these environments. Surprisingly, rates of vegetation change within protected areas did not differ significantly from unprotected semi‐natural vegetation. Overall, the detected LAI increases are consistent with previous, coarser‐scale, studies. The evidence indicates that woody regrowth following land abandonment is an important driver of land surface greening throughout Europe. The results offer an explanation for the large discrepancies between ESM‐derived and satellite‐derived greening estimates and thus generate new avenues for improving the ESMs on which we rely for crucial climate forecasts.
« Immunosuppression » is Inappropriately Qualifying the Immune Status of Septic and Sirs Patients.

Immunosuppression is the most commonly used concept to qualify the immune status of patients with either sterile systemic inflammatory response syndrome (SIRS) or sepsis. In this review we attempt to demonstrate that the concept of immunosuppression is an oversimplification of the complex anti-inflammatory response that occurs in patients dealing with a severe sterile or infectious insult. Particularly, the immune status of leukocytes varies greatly depending on the compartment from where they are derived from. Furthermore, while certain functions of immune cells present in the blood stream or in the hematopoietic organs can be significantly diminished, other functions are either unchanged or even enhanced. This juxtaposition illustrates that there is no global defect. The mechanisms called reprogramming or trained innate immunity are probably aimed at preventing a generalized deleterious inflammatory reaction, and work to maintain the defense mechanisms at their due levels.
MK2 Regulates Macrophage Chemokine Activity and Recruitment to Promote Colon Tumor Growth

A major risk factor for colon cancer growth and progression is chronic inflammation. We have shown that the MAPK-activated protein kinase 2 (MK2) pathway is critical for colon tumor growth in colitis-associated and spontaneous colon cancer models. This pathway is known to regulate expression of the tumor-promoting cytokines, IL-1, IL-6, and TNF-α. However, little is known about the ability of MK2 to regulate chemokine production. This is the first study to demonstrate this pathway also regulates the chemokines, MCP-1, Mip-1α, and Mip-2α (MMM). We show that these chemokines induce tumor cell growth and invasion in vitro and that MK2 inhibition suppresses tumor cell production of chemokines and reverses the resulting pro-tumorigenic effects. Addition of MMM to colon tumors in vivo significantly enhances tumor growth in control tumors and restores tumor growth in the presence of MK2 inhibition. We also demonstrate that MK2 signaling is critical for chemokine expression and macrophage influx to the colon tumor microenvironment. MK2 signaling in macrophages was essential for inflammatory cytokine/chemokine production, whereas MK2−/− macrophages or MK2 inhibition suppressed cytokine expression. We show that addition of bone marrow-derived macrophages to the tumor microenvironment enhances tumor growth in control tumors and restores tumor growth in tumors treated with MK2 inhibitors, while addition of MK2−/− macrophages had no effect. This is the first study to demonstrate the critical role of the MK2 pathway in chemokine production, macrophage influx, macrophage function, and tumor growth.
Next Stop "NoOps": Enabling Cross-System Diagnostics Through Graph-Based Composition of Logs and Metrics

Performing diagnostics in IT systems is an increasingly complicated task, and it is not doable in satisfactory time by even the most skillful operators. Systems and their architecture change very rapidly in response to business and user demand. Many organizations see value in the maintenance and management model of NoOps that stands for No Operations. One of the implementations of this model is a system that is maintained automatically without any human intervention. The path to NoOps involves not only precise and fast diagnostics but also reusing as much knowledge as possible after the system is reconfigured or changed. The biggest challenge is to leverage knowledge on one IT system and reuse this knowledge for diagnostics of another, different system. We propose a framework of weighted graphs which can transfer knowledge, and perform high-quality diagnostics of IT systems. We encode all possible data in a graph representation of a system state and automatically calculate weights of these graphs. Then, thanks to the evaluation of similarity between graphs, we transfer knowledge about failures from one system to another and use it for diagnostics. We successfully evaluate the proposed approach on Spark, Hadoop, Kafka and Cassandra systems.
Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast

Mitochondrial synthesis of cardiolipin (CL) and phosphatidylethanolamine requires the transport of their precursors, phosphatidic acid and phosphatidylserine, respectively, to the mitochondrial inner membrane. In yeast, the Ups1–Mdm35 and Ups2–Mdm35 complexes transfer phosphatidic acid and phosphatidylserine, respectively, between the mitochondrial outer and inner membranes. Moreover, a Ups1-independent CL accumulation pathway requires several mitochondrial proteins with unknown functions including Mdm31. Here, we identified a mitochondrial porin, Por1, as a protein that interacts with both Mdm31 and Mdm35 in budding yeast (Saccharomyces cerevisiae). Depletion of the porins Por1 and Por2 destabilized Ups1 and Ups2, decreased CL levels by ∼90%, and caused loss of Ups2-dependent phosphatidylethanolamine synthesis, but did not affect Ups2-independent phosphatidylethanolamine synthesis in mitochondria. Por1 mutations that affected its interactions with Mdm31 and Mdm35, but not respiratory growth, also decreased CL levels. Using HeLa cells, we show that mammalian porins also function in mitochondrial CL metabolism. We conclude that yeast porins have specific and critical functions in mitochondrial phospholipid metabolism and that porin-mediated regulation of CL metabolism appears to be evolutionarily conserved.
Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD: A Pilot Randomized Cross-Over Study.

BACKGROUND AND OBJECTIVES We examined the effect of alkali replacement for metabolic acidosis on vascular endothelial function in patients with CKD. METHODS We performed a pilot, prospective, open-label 14-week crossover study examining the effect of oral sodium bicarbonate treatment on vascular function in 20 patients with an eGFR of 15-44 ml/min per 1.73 m2 with low serum bicarbonate levels (16-21 mEq/L). Each period was 6 weeks in duration with a 2-week washout period in between. Patients were treated to goal serum bicarbonate of ≥23 mEq/L. The primary end point was change in brachial artery flow-mediated dilation (FMD) between treatment and control conditions. Secondary end points included changes in markers of inflammation, bone turnover, mineral metabolism, and calcification. RESULTS Eighteen patients completed the study and were included in the primary efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8) ml/min per 1.73 m2, respectively. Serum bicarbonate increased significantly with sodium bicarbonate treatment (+2.7±2.9 mEq/L, P≤0.001), whereas there was no change in bicarbonate levels in the control group. FMD significantly improved after sodium bicarbonate therapy (mean±SD, FMD baseline: 4.1%±4.1%; 6 weeks: 5.2%±2.9%; P=0.04) There was no significant change in FMD in the control group (mean±SD, FMD baseline: 4.6%±3.1%; 6 weeks: 4.1%±3.4%; P=0.20). Compared with control, sodium bicarbonate treatment resulted in a significant increase in FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P=0.02). There was no significant change in bone markers or serum calcification propensity with treatment. Serum phosphorus and intact fibroblast growth factor 23 increased significantly during treatment. CONCLUSIONS Treatment of metabolic acidosis with sodium bicarbonate significantly improved vascular endothelial function in patients with stages 3b and 4 CKD.
Conv-TasNet: Surpassing Ideal Time–Frequency Magnitude Masking for Speech Separation

Single-channel, speaker-independent speech separation methods have recently seen great progress. However, the accuracy, latency, and computational cost of such methods remain insufficient. The majority of the previous methods have formulated the separation problem through the time–frequency representation of the mixed signal, which has several drawbacks, including the decoupling of the phase and magnitude of the signal, the suboptimality of time–frequency representation for speech separation, and the long latency in calculating the spectrograms. To address these shortcomings, we propose a fully convolutional time-domain audio separation network (Conv-TasNet), a deep learning framework for end-to-end time-domain speech separation. Conv-TasNet uses a linear encoder to generate a representation of the speech waveform optimized for separating individual speakers. Speaker separation is achieved by applying a set of weighting functions (masks) to the encoder output. The modified encoder representations are then inverted back to the waveforms using a linear decoder. The masks are found using a temporal convolutional network consisting of stacked one-dimensional dilated convolutional blocks, which allows the network to model the long-term dependencies of the speech signal while maintaining a small model size. The proposed Conv-TasNet system significantly outperforms previous time–frequency masking methods in separating two- and three-speaker mixtures. Additionally, Conv-TasNet surpasses several ideal time–frequency magnitude masks in two-speaker speech separation as evaluated by both objective distortion measures and subjective quality assessment by human listeners. Finally, Conv-TasNet has a significantly smaller model size and a shorter minimum latency, making it a suitable solution for both offline and real-time speech separation applications. This study, therefore, represents a major step toward the realization of speech separation systems for real-world speech processing technologies.
Psychometric Properties of the Early Feeding Skills Assessment Tool

Background: Supporting infants as they develop feeding skills is an essential component of neonatal and pediatric care. Selecting appropriate and supportive interventions begins with a thorough assessment of the infant's skills. The Early Feeding Skills (EFS) tool is a clinician-reported instrument developed to assess the emergence of early feeding skills and identify domains in need of intervention. Purpose: The purpose of this study was to identify the factor structure of the EFS and test its psychometric properties, including internal consistency reliability and construct validity. Methods: EFS-trained interprofessional clinicians in 3 settings scored 142 feeding observations of infants 33 to 50 weeks' postmenstrual age. Redundant and rarely endorsed items were removed. Factor analysis methods clustered items into subscales. Construct validity was examined through the association of the EFS with (1) concurrently scored Infant-Driven Feeding Scale-Quality (IDFS-Q), (2) infant birth risk (gestational age), and (3) maturity (postmenstrual age). Results: Principal components analysis with varimax rotation supported a 5-factor structure. The total EFS demonstrated good internal consistency reliability (Cronbach &agr;= 0.81). The total EFS score had construct validity with the IDFS-Q (r =−0.73; P < .01), and with gestational age of a subsample of premature infants (r = 0.22; P < .05). Implications for Practice: As a valid and reliable tool, the EFS can assist the interprofessional feeding team to organize feeding assessment and plan care. Implications for Research: The strong psychometric properties of the EFS support its use in future research.
Dopaminergic induction of human adipose‐derived mesenchymal stem cells is accompanied by transcriptional activation of autophagy

Neural differentiation involves drastic morphological alterations, essentially performed by a cell‐homeostasis maintaining process known as autophagy. Here, we used the cocktail of choroid plexus epithelial cell‐conditioned medium (CPEC‐CM) and 15% knockout serum (KS) to induce human adipose‐derived mesenchymal stem cells (hASCs) into tyrosine hydroxylase (TH)‐positive neuron like cells. We showed that upon this induction, autophagy pathway was transcriptionally triggered. The expression levels of autophagy markers mTOR, BECN1, and MAP1LC3 were evidently changed throughout the dopaminergic (DAergic) differentiation of hASCs, highlighting the critical role of autophagy in this process at the level of transcription.
The Epidemiology of Cholera in Zanzibar: Implications for the Zanzibar Comprehensive Cholera Elimination Plan

Abstract Background Cholera poses a public health and economic threat to Zanzibar. Detailed epidemiologic analyses are needed to inform a multisectoral cholera elimination plan currently under development. Methods We collated passive surveillance data from 1997 to 2017 and calculated the outbreak-specific and cumulative incidence of suspected cholera per shehia (neighborhood). We explored the variability in shehia-specific relative cholera risk and explored the predictive power of targeting intervention at shehias based on historical incidence. Using flexible regression models, we estimated cholera’s seasonality and the relationship between rainfall and cholera transmission. Results From 1997 and 2017, 11921 suspected cholera cases were reported across 87% of Zanzibar’s shehias, representing an average incidence rate of 4.4 per 10000/year. The geographic distribution of cases across outbreaks was variable, although a number of high-burden areas were identified. Outbreaks were highly seasonal with 2 high-risk periods corresponding to the annual rainy seasons. Conclusions Shehia-targeted interventions should be complemented with island-wide cholera prevention activities given the spatial variability in cholera risk from outbreak to outbreak. In-depth risk factor analyses should be conducted in the high-burden shehias. The seasonal nature of cholera provides annual windows of opportunity for cholera preparedness activities.
Investigating Linguistic Pattern Ordering In Hierarchical Natural Language Generation

Natural language generation (NLG) is a critical component in spoken dialogue system, which can be divided into two phases: (1) sentence planning: deciding the overall sentence structure, (2) surface realization: determining specific word forms and flattening the sentence structure into a string. With the rise of deep learning, most modern NLG models are based on a sequence-to-sequence (seq2seq) model, which basically contains an encoder-decoder structure; these NLG models generate sentences from scratch by jointly optimizing sentence planning and surface realization. However, such simple encoder-decoder architecture usually fail to generate complex and long sentences, because the decoder has difficulty learning all grammar and diction knowledge well. This paper introduces an NLG model with a hierarchical attentional decoder, where the hierarchy focuses on leveraging linguistic knowledge in a specific order. The experiments show that the proposed method significantly outperforms the traditional seq2seq model with a smaller model size, and the design of the hierarchical attentional decoder can be applied to various NLG systems. Furthermore, different generation strategies based on linguistic patterns are investigated and analyzed in order to guide future NLG research work1.
Towards Discrete Solution: A Sparse Preserving Method for Correspondence Problem

Many problems of interest in computer vision can be formulated as a problem of finding consistent correspondences between two feature sets. Feature correspondence (matching) problem with one-to-one mapping constraint is usually formulated as an Integral Quadratic Programming (IQP) problem with permutation (or orthogonal) constraint. Since it is NP-hard, relaxation models are required. One main challenge for optimizing IQP matching problem is how to incorporate the discrete one-to-one mapping (permutation) constraint in its quadratic objective optimization. In this paper, we present a new relaxation model, called Sparse Constraint Preserving Matching (SPM), for IQP matching problem. SPM is motivated by our observation that the discrete permutation constraint can be well encoded via a sparse constraint. Comparing with traditional relaxation models, SPM can incorporate the discrete one-to-one mapping constraint straightly via a sparse constraint and thus provides a tighter relaxation for original IQP matching problem. A simple yet effective update algorithm has been derived to solve the proposed SPM model. Experimental results on several feature matching tasks demonstrate the effectiveness and efficiency of SPM method.
Relative Protein Intake and Physical Function in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies

(1) Background: The present work aims to conduct a systematic review and meta-analysis of observational studies, in order to investigate the association of relative protein intake and physical function in older adults; (2) Methods: Observational studies, that investigated the association between protein intake and physical function in older adults, were retrieved from MEDLINE, SCOPUS, CINAHL, AgeLine, EMBASE, and Cochrane-CENTRAL. Two independent researchers conducted study selection and data extraction; (3) Results: Very high protein intake (≥1.2 g/kg/day) and high protein intake (≥1.0 g/kg/day) groups showed better lower limb physical functioning and walking speed (WS) performance, respectively, in comparison to individuals who present relative low protein (<0.80 g/kg/day) intake. On the other hand, relative high protein intake does not seem to propitiate a better performance on isometric handgrip (IHG) and chair rise in comparison to relative low protein intake. In addition, there were no significant differences in the physical functioning of high and middle protein intake groups; (4) Conclusions: In conclusion, findings of the present study indicate that a very high (≥1.2 g/kg/day) and high protein intake (≥1.0 g/kg/day) are associated with better lower-limb physical performance, when compared to low protein (<0.80 g/kg/day) intake, in community-dwelling older adults. These findings act as additional evidence regarding the potential need to increase protein guidelines to above the current recommendations. However, large randomized clinical trials are needed to confirm the addictive effects of high-protein diets (≥1.0 g/kg/day) in comparison to the current recommendations on physical functioning. All data are available in the Open ScienceFramework.