Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating miRNA levels differ with respect to carotid plaque characteristics and symptom occurrence in patients with carotid artery stenosis and provide information on future cardiovascular events

Introduction Circulating microRNAs (miRNAs) levels are potentially important biomarkers and therapeutic targets of cerebral ischemic event (CIE) in patients with internal carotid artery stenosis (ICAS). Aim This prospective study investigated associations between circulating miRNAs and symptomatic and asymptomatic ICAS, carotid plaque morphology and future cardiovascular events. Material and methods Circulating miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were analyzed in 92 consecutive patients with significant ICAS referred for revascularization. Group I comprised 65 subjects (41 males, age 69.3 ±9.7 years) with a recent CIE. Group II comprised 27 patients (15 males, age 68.2 ±8.4 years) with asymptomatic ICAS. The ICAS degree and plaque morphology was assessed by ultrasonography. The incidences of cardiovascular death (CVD), myocardial infarction (MI) and recurrent CIE (CVD/MI/CIE) were recorded prospectively (mean: 38.7 ±3.8 months). Results Groups II and I differed significantly in levels of miR-124-3p (p = 0.036), miR-133a-3p (p = 0.043) and miR-134-5p (p = 0.02). Hypoechogenic, as compared to echogenic, plaques differed in levels of miR-124-3p (p = 0.038), miR-34a-5p (p = 0.006), miR-133b (p = 0.048), miR-134-5p (p = 0.045), and miR-375 (p = 0.016), while calcified plaques differed in miR-16-5p (p = 0.023). Ulcerated plaques showed higher levels of miR-1-3p (p = 0.04) and miR-16-5p (p = 0.003), while thrombotic plaques showed lower levels of miR-1-3p (p = 0.032). CVD/MI/CIE occurred in 14 (15.5%) out of 90 follow-up patients. Multivariate Cox and ROC analysis showed associations between miR-1-3p and CVD (AUC = 0.634; HR = 4.84; 95% CI: 1.62–14.5; p = 0.005), MI (AUC = 0.743; HR = 7.8; 95% CI: 2.01–30.0; p = 0.003), and CVD/MI/CIE (AUC = 0.560; HR = 4.6; 95% CI: 1.61–13.1; p = 0.004), while miR-133b was associated with recurrent CIE (AUC = 0.581; HR = 2.25; 95% CI: 1.01–5.02; p = 0.047). Conclusions A significant difference in levels of selected miRNAs is observed in symptomatic vs. asymptomatic ICAS. Plaque morphology and structure is associated with change of miRNA levels. The expression of miR-1-3p may be a potential prognostic factor for future cardiovascular events.
The effect of metronidazole plus amoxicillin or metronidazole plus penicillin V on periodontal pathogens in an in vitro biofilm model

A combination of metronidazole (MET) and amoxicillin (AMX) is commonly used as adjunct to mechanical therapy of periodontal disease. The use of broad spectrum antibiotics such as AMX may contribute to development of antibiotic resistance. The aim was to evaluate the in vitro effect of replacing AMX with penicillin V (PV) in combination with MET on a biofilm model. A biofilm model consisting of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum was developed. The biofilms were exposed to AMX + MET and PV + MET in two different concentrations. Bacterial viability in biofilms following antibiotic exposure was assessed by viable counts and by confocal microscopy. No live colonies of P. gingivalis nor F. nucleatum were retrieved from biofilms exposed to AMX + MET or PV + MET. The amount of A. actinomycetemcomitans was 4–5 logs reduced following antibiotic treatment; no statistical significance was achieved between AMX + MET or PV + MET treated biofilms. Replacement of AMX with PV at the same concentration, in combination with MET, resulted in similar effect on bacterial viability in this in vitro model. The option of using PV + MET instead of AMX + MET deserves further investigation, as this may contribute to reduce the risk of antibiotic resistance development.
Submitted to the Annals of Statistics HIGH-DIMENSIONAL CONSISTENCY IN SCORE-BASED AND HYBRID STRUCTURE LEARNING By

Main approaches for learning Bayesian networks can be classified as constraint-based, score-based or hybrid methods. Although highdimensional consistency results are available for constraint-based methods like the PC algorithm, such results have not been proved for scorebased or hybrid methods, and most of the hybrid methods have not even shown to be consistent in the classical setting where the number of variables remains fixed and the sample size tends to infinity. In this paper, we show that consistency of hybrid methods based on greedy equivalence search (GES) can be achieved in the classical setting with adaptive restrictions on the search space that depend on the current state of the algorithm. Moreover, we prove consistency of GES and adaptively restricted GES (ARGES) in several sparse high-dimensional settings. ARGES scales well to sparse graphs with thousands of variables and our simulation study indicates that both GES and ARGES generally outperform the PC algorithm.
Overview of the BioCreative VI chemical-protein interaction Track

—Despite the considerable number of available systems that recognize automatically mentions of genes/proteins and chemicals in text, only a limited number of attempts were made so far to extract interactions between them. Most biomedical relation extraction systems focus on the extraction of protein-protein or gene/chemical-disease relations. The detection of interactions between drugs and proteins/genes is of key relevance for pharmacological and clinical research, playing an important role for drug discovery, understanding of molecular mechanism of adverse drug reactions, describing drug metabolism or drawing regulatory networks of importance for systems pharmacology. The BioCreative VI - ChemProt track represents the first attempt to promote the development of systems for extracting chemical-protein interactions (CPIs), of relevance for precision medicine as well as for drug discovery and basic biomedical research. The novel ChemProt corpus consists of text exhaustively annotated by hand with mentions of chemical compounds/drugs and genes/proteins, as well as 22 different types of compound-protein relations. To focus on a subset of important relations, 5 relation classes were used for evaluation purposes, including agonist, antagonist, inhibitor, activator and substrate/product relations. A total of 13 participating teams returned 45 runs for this track. Despite the biological complexity of the considered relation types, top-scoring teams could obtain an F-measure across relation classes of 64.10%. Performance varied depending on the relation class: for the antagonist relation class the best team obtained an F-measure of 72.56% (precision of 80.75%, recall of 65.87%) while for inhibition/down-regulation the best value was of 71.48% (with a precision of 76.51% and a recall of 67.07%).
Refractory Out of Hospital Cardiac Arrest

Refractory out of hospital cardiac arrest is a common problem that is associated with poor overall survival rates and neurological outcomes. There are various definitions that have been used but the most accepted one is cardiac arrest that requires more than 10 minutes of Cardiopulmonary Resuscitation (CPR) efforts or more than 3 defibrillation attempts. There have been different pharmacologic and non-pharmacologic therapies that were studied in these patients. None of the antiarrhythmic or vasopressor medications have been consistently shown to improve survival or neurological outcomes in this subset of patients. This has led to the introduction of various devices aimed at improving outcomes such as mechanical CPR devices, Extracorporeal Cardiopulmonary Resuscitation (ECPR), targeted temperature management and early invasive approach. There is accumulating evidence that there seems to be an improvement in outcomes when these devices are used in refractory cardiac arrest patients. But none of these devices have been shown to improve outcomes when used in isolation. This underscores the importance of systematic approach to these complex patients and using these therapies in combination. There has been a paradigm shift in the approach to these patients. Instead of repeated and prolonged CPR attempts in the field, it is suggested that these patients need to be moved to cardiac arrest centers with a mechanical CPR device in place, so a percutaneous Extracorporeal Membrane Oxygenator (ECMO) can be placed to “buy” time for other therapies such as therapeutic hypothermia and early coronary angiography followed by intervention as indicated. Careful selection of patients who might potentially benefit from this approach is critical to the success of these programs.
Prevalence of Obstructive Sleep Apnea in Children With Down Syndrome: A Meta-Analysis.

STUDY OBJECTIVES To estimate the prevalence of obstructive sleep apnea (OSA) in children with Down syndrome. METHODS Two authors independently searched databases, namely PubMed, MEDLINE, EMBASE, and the Cochrane Review database. The keywords used were "Down syndrome," "Trisomy 21," "OSA," "sleep apnea syndromes," "polysomnography" and "polygraphy. " The prevalence of OSA based on apnea-hypopnea index (AHI) greater than 1, 1.5, 2, 5, and 10 event/h was estimated using a random-effects model. Subgroup analyses were conducted for children in different countries, sample size, study year, and risk of bias. Finally, the prevalence of OSA was compared between two types of sleep studies (polysomnography versus polygraphy). RESULTS A total of 18 studies (1,200 children) were included (mean age: 7.7 years; 56% boys; mean sample size: 67 patients). Five studies had low risk of bias, and nine and four studies had moderate and high risk of bias, respectively. The OSA was evaluated through polygraphy in 2 studies, and polysomnography in 16 studies. For children who underwent polysomnography, the prevalences of OSA based on AHI > 1, 1.5, 2, 5, and 10 events/h were 69%, 76%, 75%, 50%, and 34%, respectively. Subgroup analyses revealed no significant difference among all subgroups. Meta-regression showed that AHI > 5 events/h was inversely correlated with age (P < .001). Moreover, the prevalence of OSA based on AHI > 1.5 events/h was lower in polygraphy compared with polysomnography (59% versus 76%, P = .037). CONCLUSIONS OSA is highly prevalent in children with Down syndrome. Prevalence of moderate to severe OSA is higher in younger age.
Areas prone to slow slip events impede earthquake rupture propagation and promote afterslip

Frequent slow slip events and rapid postseismic slip reveal persistent aseismic fault areas delineating future seismic ruptures. At subduction zones, transient aseismic slip occurs either as afterslip following a large earthquake or as episodic slow slip events during the interseismic period. Afterslip and slow slip events are usually considered as distinct processes occurring on separate fault areas governed by different frictional properties. Continuous GPS (Global Positioning System) measurements following the 2016 Mw (moment magnitude) 7.8 Ecuador earthquake reveal that large and rapid afterslip developed at discrete areas of the megathrust that had previously hosted slow slip events. Regardless of whether they were locked or not before the earthquake, these areas appear to persistently release stress by aseismic slip throughout the earthquake cycle and outline the seismic rupture, an observation potentially leading to a better anticipation of future large earthquakes.
Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

BACKGROUND Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP). METHODS Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high-sensitivity CRP (hsCRP). RESULTS Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001). CONCLUSIONS Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden.
The Role of Pseudomonas aeruginosa ExoY in an Acute Mouse Lung Infection Model

The effector protein Exotoxin Y (ExoY) produced by Pseudomonas aeruginosa is injected via the type III secretion system (T3SS) into host cells. ExoY acts as nucleotidyl cyclase promoting the intracellular accumulation of cyclic nucleotides. To what extent nucleotidyl cyclase activity contributes to the pathogenicity of ExoY and which mechanisms participate in the manifestation of lung infection is still unclear. Here, we used an acute airway infection model in mice to address the role of ExoY in lung infection. In infected lungs, a dose-dependent phenotype of infection with bacteria-expressing ExoY was mirrored by haemorrhage, formation of interstitial oedema in alveolar septa, and infiltration of the perivascular space with erythrocytes and neutrophilic granulocytes. Analyses of the infection process on the cellular and organismal level comparing infections with Pseudomonas aeruginosa mutants expressing either nucleotidyl cyclase-active or -inactive ExoY revealed differential cytokine secretion, increased prevalence of apoptosis, and a break of lung barrier integrity in mice infected with cyclase-active ExoY. Notably, of all measured cyclic nucleotides, only the increase of cyclic UMP in infected mouse lungs coincides temporally with the observed early pathologic changes. In summary, our results suggest that the nucleotidyl cyclase activity of ExoY can contribute to P. aeruginosa acute pathogenicity.
Differential Equations for Modeling Asynchronous Algorithms

Asynchronous stochastic gradient descent (ASGD) is a popular parallel optimization algorithm in machine learning. Most theoretical analysis on ASGD take a discrete view and prove upper bounds for their convergence rates. However, the discrete view has its intrinsic limitations: there is no characterizationof the optimization path and the proof techniques are induction-based and thus usually complicated. Inspired by the recent successful adoptions of stochastic differential equations (SDE) to the theoretical analysis of SGD, in this paper, we study the continuous approximation of ASGD by using stochastic differential delay equations (SDDE). We introduce the approximation method and study the approximation error. Then we conduct theoretical analysis on the convergence rate of ASGD algorithm based on the continuous approximation.There are two methods: moment estimation and energy function minimization can be used to analyzethe convergence rates. Moment estimation depends on the specific form of the loss function, while energy function minimization only leverages the convex property of the loss function, and does not depend on its specific form. In addition to the convergence analysis, the continuous view also helps us derive better convergence rates. All of this clearly shows the advantage of taking the continuous view in gradient descent algorithms.
Methylation of the claudin-3 promoter predicts the prognosis of advanced gastric adenocarcinoma

Claudin-3 expression is associated with gastric cancer progression, but the role of epigenetic modifications remains unclear. We investigated methylation of the claudin-3 promoter and expression profiles in gastric adenocarcinoma and their associations with clinicopathological characteristics and prognosis of the patients. A total of 122 patients with advanced gastric cancer [stage IIB-IV, with lymph node (LN) metastasis] were enrolled. Each patient provided 4 tissue samples: normal gastric epithelium, intestinal metaplasia, primary tumor and metastatic LN. Claudin-3 protein expression was examined by immunohistochemistry. Claudin-3 promoter methylation was determined by methylation-specific PCR and verified by bisulfite sequencing PCR. Claudin-3 mRNA expression was measured by real-time PCR in a subset of cases, and its correlation with protein expression was analyzed using Spearman correlation. Kaplan-Meier survival analysis was performed (log-rank test). Factors associated with survival were identified by Cox regression. The strong expression rate of claudin-3 in intestinal metaplasia, primary tumor, metastatic LN and normal gastric epithelium was 91.8, 58.2, 30.3 and 13.9%, respectively. The promoter hypermethylation rate in intestinal metaplasia, primary tumor, normal gastric epithelium and metastatic LN was 5.7, 27.9, 36.9 and 49.2%, respectively. Claudin-3 mRNA and protein expression were positively correlated (P<0.001) with normal gastric epithelium (rs=0.745), intestinal metaplasia (rs=0.876), primary gastric adenocarcinoma (rs=0.915) and metastatic LN (rs=0.819). Claudin-3 mRNA expression was negatively correlated with claudin-3 promoter methylation. Median patient survival was 38, 22 and 11 months in the hypomethylated, partially methylated and hypermethylated groups, respectively (P<0.001). Claudin-3 promoter methylation status (HR: 5.67; 95% CI: 2.27–14.17) but not claudin-3 expression was an independent predictor of survival. Claudin-3 promoter hypermethylation reduces claudin-3 expression and independently predicts poor prognosis.
Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population

Background/Aims: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the population worldwide. The aim of the present study was to investigate whether miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 polymorphisms are associated with susceptibility to RA in Egyptians and whether they influence disease severity and activity. Methods: The study was performed on 104 unrelated RA patients and 112 healthy subjects. RA patients were further subdivided into active and inactive RA groups. Polymorphisms were genotyped by using real-time polymerase chain reaction with TaqMan allelic discrimination assay. Results: Significant differences in the frequency of miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 alleles and genotypes were observed between RA patients and controls. Only CA and AA genotypes of IRAK1 rs3027898 shows a significant difference between active and inactive subgroups. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one. CG and GG genotypes of miRNA-146a rs2910164 were associated with positive erosions. CA genotype of IRAK1 rs3027898 was associated with low disease activity and negative erosions, while, the AA genotype was associated with high disease activity. CC genotype of PADI4 rs1748033 was associated with negative rheumatoid factor. Conclusion: The 4 studied SNPs were likely to play an important role in the susceptibility to RA and can influence disease severity and activity in Egyptian population.
Use of Preoperative Apparent Diffusion Coefficients to Predict Brain Tumor Grade

Introduction The apparent diffusion coefficient (ADC) sequence is based on the diffusion properties of water molecules within tissues and correlates with tissue cellularity. ADC may have a role in predicting tumor grade for gliomas, and may in turn assist in identifying tumor biopsy sites. The purpose of this investigation was to assess the competence of preoperative ADC values in predicting tumor grades. Methods This was a retrospective investigation. We calculated the ADC values in the areas of greatest restriction in solid tumor components, and we recorded the pattern of contrast enhancement. Pathology reports masked to the imaging results were reviewed independently. We calculated the differences in the mean values of different tumor grades and high-grade and low-grade gliomas. A receiver operator curve (ROC) analysis assessed the predictive potential of ADC values for low-grade gliomas. Results Forty-eight cases of glioma were included in our study. We noted a statistically significant difference in the lowest mean ADC values for the tumor regions of Grade IV lesions (333.83 ± 295.47) compared with Grade I lesions (653.20 ± 145.07). On ROC analysis, we noted an area under the curve (AUC) of 0.80 for the lowest ADC value in the whole tumor region, which was a predictor of low-grade glioma with 95 % confidence interval (CI) of 0.675-0.926. The sensitivity of the lowest ADC value was 84.5% for high-grade lesions. Conclusion Given our findings that the means of the lowest ADC value are significantly different between low and high-grade gliomas with an AUC of 0.80 for ADC as a predictor of low-grade lesions and a sensitivity of 84.5% for high-grade lesions, ADC values contain some predictive properties of tumor grading. ADC values may be a valuable parameter in the assessment and treatment of tumors.
Exploring Privilege in the Digital Divide: Implications for Theory, Policy, and Practice

Background and Objectives The digital revolution has resulted in innovative solutions and technologies that can support the well-being, independence, and health of seniors. Yet, the notion of the "digital divide" presents significant inequities in terms of who accesses and benefits from the digital landscape. To better understand the social and structural inequities of the digital divide, a realist synthesis was conducted to inform theoretical understandings of information and communication technologies (ICTs); to understand the practicalities of access and use inequities; to uncover practices that facilitate digital literacy and participation; and to recommend policies to mitigate the digital divide. Research Design and Methods A systematic search yielded 55 articles published between 2006 and 2016. Synthesis of existing knowledge, combined with user-experience elicited through a deliberative dialogue session with community stakeholders (n = 35), made visible a pattern of privilege that determined individual agency in ICT access and use. Results Though age is consistently centralized as the key determinant of the digital divide, our analyses, which encompassed both van Dijk's resources and appropriation theory and intersectionality, appraised this notion and revealed that age is not the sole determinant. Findings highlight the role of other factors that contribute to digital inequity among community-dwelling middle-aged (45-64) and older (65+) adults, including education, income, gender, and generational status. Discussion and Implications Informed by results of a realist synthesis that was guided by intersectional perspectives, a conceptual framework was developed outlining implications for theory, policy, and practice to address the wicked problem that is the digital divide.