Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Course of Enterovirus D68 in Hospitalized Children.

BACKGROUND Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS A retrospective chart review was performed of children admitted to Children's Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records. Patients with EV-D68 were compared with children presenting simultaneously with other EV/RV. RESULTS Of 542 eligible specimens, children with EV-D68 were significantly older than children with other EV/RV (4.6 vs. 2.2 years, P < 0.001). Children with EV-D68 were more likely to have a history of asthma (38.6% vs. 30.0%, P = 0.04) or recurrent wheezing (22.1% vs. 14.8%, P = 0.04). EV-D68-positive children more commonly received supplemental oxygen (86.7% vs. 65.0%, P < 0.001), albuterol (91.2% vs. 65.5%, P < 0.001) and corticosteroids (82.9% vs. 58.6%, P < 0.001). Age ≥5 years was an independent risk factor for intensive care unit management in EV-D68-infected children. Children with a history of asthma or recurrent wheezing and EV-D68 received supplemental oxygen (92.7% vs. 82.4%, P = 0.007) and magnesium (42.7% vs. 29.7%, P = 0.03) at higher rates and more continuous albuterol (3 vs. 2 hours, P = 0.03) than those with other EV/RV. CONCLUSIONS EV-D68 causes severe disease in the pediatric population, particularly in children with a history of asthma or recurrent wheezing. EV-D68-positive children are more likely to require therapy for refractory bronchospasm and may need intensive care unit- level care.
Evolution of ST-Elevation Acute Myocardial Infarction Prevalence by Gender Assessed Age Pyramid Analysis—The Piramyd Study

Introduction: Recent studies reported a decrease in the incidence of acute myocardial infarction. This favorable evolution does not extend to young women. The interaction between gender, risk factors and myocardial infarction incidence remains controversial. Objective: To compare the evolution of the age pyramid of patients with ST-elevation myocardial infarction (STEMI) according to gender. Methods: Data from patients with STEMI managed in pre-hospital settings prospectively collected in the greater Paris area. Evolution of patient demographics and risk factors was investigated. Results: 28,249 patients with STEMI were included in the registry between 2002 and 2014, 21,883 (77%) males and 6366 (23%) females. The sex ratio did not significantly vary over the study period (p = 0.4). Median patient age was 60.1 years (51.1–73.0) and was significantly different between males and females, respectively 57.9 (50.0–68.3) vs. 72.9 years (58.3–82.2) (p = 0.0004). The median age of males significantly (p = 0.0044) increased from 57.6 (50.1–70.0) in 2002 to 58.1 years (50.5–67.8) in 2014. The median age of females significantly (p = 0.0006) decreased from 73.7 (57.9–81.8) to 69.6 years (57.0–82.4). The median gap between the age of men and women significantly (p = 0.0002) decreased, from 16.1 to 11.5 years. Prevalence of risk factors was unchanged or decreased except for hypertension which significantly increased in males. The rate of STEMI without reported risk factors increased in both males and females. Conclusion: The age of STEMI onset significantly decreased in females, whereas it significantly increased in males. The prevalence of risk factors decreased in males, whereas no significant variation was found in females.
Teachers' Perceived and Desired Roles in Nutrition Education.

BACKGROUND Elementary teachers have the potential to influence children's eating habits. This study examined teacher views and practices regarding nutrition education. METHODS An online survey was administered to K-6 teachers (N = 628) in 55 public elementary schools in a large city in the western United States. Three indices were created based on responses. Indices included: (1) attitudes and beliefs about nutrition education; (2) self-efficacy regarding nutrition education; and (3) personal health behaviors. Relationships between indices, classroom practices, and teacher characteristics were tested. Teacher comments were categorized into themes. RESULTS Most teachers agreed they can make a difference in the eating behaviors of their students (68%). Correlations between hours of nutrition taught and teachers' attitudes and beliefs (r = .37, p < .01), nutrition self-efficacy (r = .38, p < .01), and personal health practices (r = .15, p < .01) were weak, yet statistically significant. Number of years teaching was inversely related to frequency of food rewards (r = -119, p < .01). Few teachers (21%) agreed they have support to teach nutrition in the classroom. CONCLUSION Teachers understand the importance of nutrition education but provision is limited by competing demands. Teachers suggest tailored nutrition materials, qualified nutrition personnel, and school stakeholder support to promote nutrition education.
The Consistency of Visual Attention to Losses and Loss Sensitivity Across Valuation and Choice

Sensitivity to losses has been found to vary greatly across individuals. One explanation for this variability is that for some losses garner more visual attention and are subsequently given more weight in decision-making processes. In three studies we examined whether biases in visual attention toward potential losses during valuation and choice were related to loss sensitivity, as well as the valuations provided and the choices made. In all studies, we find a positive relationship between estimated loss sensitivity and attention to losses for valuation, with increased attention to losses predicting decreased valuations. For choices, however, there was no robust relationship between attention and loss sensitivity or the choices made. In addition, preferences were not strongly consistent across tasks (i.e., valuations and choices did not robustly align), nor was the distribution of attention robustly related across tasks. Study 3 involved testing across separate sessions and found significant consistency in loss sensitivity and attention to losses across sessions for both choice and valuation. In sum, it appears that loss sensitivity varies across individuals, is differentially related to attention across tasks, and shows some consistency across time. Attention to losses also shows consistency across time, and its relationship with valuations appears much more robust than with choices; patterns of results that add to research suggesting that different cognitive processes underlie valuations and choices.
Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention An Intervention Trial Evaluating Rosuvastatin)

Background— Lipoprotein(a) [Lp(a)] is a low-density lipoprotein–like particle largely independent of known risk factors and predictive of cardiovascular disease. Statins may offset the risk associated with elevated Lp(a), but it is unknown whether Lp(a) is a determinant of residual risk in the setting of low low-density lipoprotein cholesterol after potent statin therapy. Methods and Results— Baseline and on-treatment Lp(a) concentrations were assessed in 9612 multiethnic participants in the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) before and after random allocation to rosuvastatin 20 mg/d or placebo, with outcomes reported for whites (n=7746). Lp(a) concentrations (median [25th–75th percentile], in nmol/L) were highest in blacks (60 [34–100]), then Asians (38 [18–60]), Hispanics (24 [11–46]), and whites (23 [10–50]; P<0.001). Although the median change in Lp(a) with rosuvastatin and placebo was zero, rosuvastatin nonetheless resulted in a small but statistically significant positive shift in the overall Lp(a) distribution (P<0.0001). Baseline Lp(a) concentrations were associated with incident cardiovascular disease (adjusted hazard ratio per 1-SD increment in Ln[Lp(a)], 1.18; 95% confidence interval, 1.03–1.34; P=0.02). Similarly, on-statin Lp(a) concentrations were associated with residual risk of cardiovascular disease (adjusted hazard ratio, 1.27; 95% confidence interval, 1.01–1.59; P=0.04), which was independent of low-density lipoprotein cholesterol and other factors. Rosuvastatin significantly reduced incident cardiovascular disease among participants with baseline Lp(a) greater than or equal to the median (hazard ratio, 0.62; 95% confidence interval, 0.43–0.90) and Lp(a) less than the median (hazard ratio, 0.46; 95% confidence interval, 0.30–0.72), with no evidence of interaction. Similar results were obtained when analyses included nonwhites. Conclusion— Among white JUPITER participants treated with potent statin therapy, Lp(a) was a significant determinant of residual risk. The magnitude of relative risk reduction with rosuvastatin was similar among participants with high or low Lp(a). Clinical Trials Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00239681.
Metabolic regulation protects mice against Klebsiella pneumoniae lung infection

Abstract Purpose: Klebsiella pneumoniae-caused pneumonia is a risk factor for development of lung injury. However, the current clinical isolates of K. pneumoniae are mostly multidrug-resistance and thus must be addressed with new treatments. One ideal approach is to enhance the innate immunity of the infected host through metabolic modulators. Materials and Methods: We used GC/MS-based metabolomics to profile the metabolomes among Control, Dead and Survival groups. The key metabolites were administrated in mice, and the bacterial loads in lung and survival were measured. The effect of the key metabolites on macrophage phagocytosis was determined by flow cytometry. Results: Compared with the mice that compromised from K. pneumoniae lung infection, mice that survived the infection displayed the varied metabolomic profile. The differential analysis of metabolome showed D-Glucose, Glutamine, L-Serine, Myo-inositol, Ethanedioic acid and Lactic acid related to the host surviving a K. pneumoniae lung infection. Further pathway enrichment analysis proposed that valine, leucine and isoleucine biosynthesis involved in outcome of lung infection. The follow-up data showed that exogenous L-Serine, L-Valine and L-Leucine could decline the load of K. pneumoniae in infected lung and increases the mouse survival. More interestingly, L-Serine, L-Valine and L-Leucine also were able to promote macrophage phagocytosis that is the natural way to promote hosts to clear lung pathogens. Conclusions: Our study establishes a novel strategy of identifying metabolic modulator from surviving host and emphasizes the feasibility of employing the metabolic modulator as a therapy for K. pneumoniae lung infection.
Mitochondrial DNA Damage Can Promote Atherosclerosis Independently of Reactive Oxygen Species Through Effects on Smooth Muscle Cells and Monocytes and Correlates With Higher-Risk Plaques in Humans

Background— Mitochondrial DNA (mtDNA) damage occurs in both circulating cells and the vessel wall in human atherosclerosis. However, it is unclear whether mtDNA damage directly promotes atherogenesis or is a consequence of tissue damage, which cell types are involved, and whether its effects are mediated only through reactive oxygen species. Methods and Results— mtDNA damage occurred early in the vessel wall in apolipoprotein E–null (ApoE−/−) mice, before significant atherosclerosis developed. mtDNA defects were also identified in circulating monocytes and liver and were associated with mitochondrial dysfunction. To determine whether mtDNA damage directly promotes atherosclerosis, we studied ApoE−/− mice deficient for mitochondrial polymerase-&ggr; proofreading activity (polG−/−/ApoE−/−). polG−/−/ApoE−/− mice showed extensive mtDNA damage and defects in oxidative phosphorylation but no increase in reactive oxygen species. polG−/−/ApoE−/− mice showed increased atherosclerosis, associated with impaired proliferation and apoptosis of vascular smooth muscle cells, and hyperlipidemia. Transplantation with polG−/−/ApoE−/− bone marrow increased the features of plaque vulnerability, and polG−/−/ApoE−/− monocytes showed increased apoptosis and inflammatory cytokine release. To examine mtDNA damage in human atherosclerosis, we assessed mtDNA adducts in plaques and in leukocytes from patients who had undergone virtual histology intravascular ultrasound characterization of coronary plaques. Human atherosclerotic plaques showed increased mtDNA damage compared with normal vessels; in contrast, leukocyte mtDNA damage was associated with higher-risk plaques but not plaque burden. Conclusions— We show that mtDNA damage in vessel wall and circulating cells is widespread and causative and indicates higher risk in atherosclerosis. Protection against mtDNA damage and improvement of mitochondrial function are potential areas for new therapeutics.
Phosphorylation cascade regulates the formation and maturation of rotaviral replication factories

Significance Many DNA and RNA virus pathogens replicate in cytoplasmic compartments composed of viral and cellular proteins called virus factories or viroplasms. Using rotavirus (RV) as a model, we found that RV nonstructural protein NSP2 has autokinase activity. The cellular kinase CK1α additionally phosphorylates NSP2, triggering NSP2 octamers to form a lattice structure, and is required to build viroplasms. CK1α and viroplasm-specific NSP2 (vNSP2) are essential for RV nonstructural protein NSP5 hyperphosphorylation and association with vNSP2 for viroplasm formation. Protein regulation by phosphorylation is a common biological mechanism, raising the possibility that similar phosphorylation-dependent virus factory assembly mechanisms exist for other viral pathogens. The rotavirus (RV) genome is replicated and packaged into virus progeny in cytoplasmic inclusions called viroplasms, which require interactions between RV nonstructural proteins NSP2 and NSP5. How viroplasms form remains unknown. We previously found two forms of NSP2 in RV-infected cells: a cytoplasmically dispersed dNSP2, which interacts with hypophosphorylated NSP5; and a viroplasm-specific vNSP2, which interacts with hyperphosphorylated NSP5. Other studies report that CK1α, a ubiquitous cellular kinase, hyperphosphorylates NSP5, but requires NSP2 for reasons that are unclear. Here we show that silencing CK1α in cells before RV infection resulted in (i) >90% decrease in RV replication, (ii) disrupted vNSP2 and NSP5 interaction, (iii) dispersion of vNSP2 throughout the cytoplasm, and (iv) reduced vNSP2 protein levels. Together, these data indicate that CK1α directly affects NSP2. Accordingly, an in vitro kinase assay showed that CK1α phosphorylates serine 313 of NSP2 and triggers NSP2 octamers to form a lattice structure as demonstrated by crystallographic analysis. Additionally, a dual-specificity autokinase activity for NSP2 was identified and confirmed by mass spectrometry. Together, our studies show that phosphorylation of NSP2 involving CK1α controls viroplasm assembly. Considering that CK1α plays a role in the replication of other RNA viruses, similar phosphorylation-dependent mechanisms may exist for other virus pathogens that require cytoplasmic virus factories for replication.
Ingesting a 12% Carbohydrate-Electrolyte Beverage Before Each Half of a Soccer Match Simulation Facilitates Retention of Passing Performance and Improves High-Intensity Running Capacity in Academy Players.

This study investigated the influence of ingesting a 12% carbohydrate plus electrolyte (CHO-E) solution providing 60 g of carbohydrate before each half of a 90-min soccer match simulation (SMS) protocol on skill performance, sprint speed, and high-intensity running capacity. Eighteen elite academy (age: 18 ± 2 years) soccer players ingested two 250-ml doses (pre-exercise and at halftime) of a 12% CHO-E solution or electrolyte placebo administered in a double-blind randomized cross-over design. During an indoor (artificial grass pitch) SMS, dribbling, passing, and sprint performance were assessed, and blood was drawn for glucose and lactate analysis. High-intensity running capacity was assessed following the SMS. Dribbling speed/accuracy and sprint speed remained unchanged throughout the SMS. Conversely, passing accuracy for both dominant (mean percentage difference [95% confidence interval, CI]: 9 [3, 15]) and nondominant (mean percentage difference [95% CI]: 13 [6, 20]) feet was better maintained during the SMS on CHO-E (p < .05), with passing speed better maintained in the nondominant foot (mean percentage difference [95% CI]: 5.3 [0.7, 9.9], p = .032). High-intensity running capacity was greater in CHO-E versus placebo (mean percentage difference [95% CI]: 13 [6, 20], p = .010). Capillary blood glucose concentration was higher in CHO-E than placebo at halftime (CHO-E: 5.8 ± 0.5 mM vs. placebo: 4.1 ± 0.4 mM, p = .001) and following the high-intensity running capacity test (CHO-E: 4.9 ± 0.4 mM vs. placebo: 4.3 ± 0.4 mM, p = .001). Ingesting a 12% CHO-E solution before each half of a match can aid in the maintenance of soccer-specific skill performance, particularly on the nondominant foot, and improves subsequent high-intensity running capacity.
Sex Alters the MHC Class I HLA-A Association With Polyglandular Autoimmunity.

CONTEXT The major histocompatibility complex (MHC) strongly contributes to the development of polyglandular autoimmunity (PGA). OBJECTIVE To evaluate the impact of sex on human leukocyte antigen (HLA) association with PGA for the first time. DESIGN Cross-sectional immunogenetic study. SETTING Academic tertiary referral Orphan Disease Center for PGA (ORPHA 282196) and immunogenetics laboratory. SUBJECTS Patients (158) with coexistent type 1 diabetes and autoimmune thyroid disease (adult type 3 PGA, ORPHA 227982) and 479 unrelated healthy controls. INTERVENTIONS All 637 white subjects were typed for HLA-A, -B, -DRB1, -DQA1, and -DQB1 alleles at a two-field level. MAIN OUTCOME MEASURES Modification of the gene-disease association by sex. RESULTS MHC class I HLA-A association was sex related to both the total white adult type 3 PGA collective (n = 158, P = 0.0065), as well as in PGA patients with autoimmune Hashimoto thyroiditis (n = 91, P = 0.010). Compared with HLA-A*02:01, A*11:01 was over-represented in male patients, yet under-represented in women (OR 1.49, 95% CI 0.55 to 3.88 vs 0.42, 0.12 to 1.17). A*24:02 was under-represented in male but not in female patients (OR 0.37, 95% CI 0.11 to 1.04 vs 1.19, 0.65 to 2.15). With the exclusion of the five most frequent alleles (A*01:01, A*02:01, A*03:01, A*11:01, and A*24:02), the sum of all other identified alleles was under-represented in male patients (OR 0.37, 0.18 to 0.72, P = 0.0046). The strong MHC HLA-B association with PGA (P < 0.0001) was not sex related (P = 0.55). Furthermore, no interaction with sex was observed for the MHC class II HLA-DRB1, -DQA1, and -DQB1 alleles. CONCLUSION MHC class I HLA-A association with type 3 PGA is significantly affected by sex.
Sexual risk behaviour in a cohort of HIV-negative and HIV-positive Rwandan women

Abstract Here we wanted to assess whether sexual risk behaviour differs dependent by human immunodeficiency virus (HIV) status by following 100 HIV− and 137 HIV+ women recruited at two university teaching hospitals in Rwanda. Women were tested for sexually transmitted infections (STIs; trichomoniasis, syphilis, hepatitis B and C) and for reproductive tract infections (RTIs; candidiasis, bacterial vaginosis (BV)) and were interviewed at baseline and 9 months later. BV was the most prevalent infection, while syphilis was the most common STI with a 9-month incidence of 10.9% in HIV+ women. Only 24.5% of women positive for any RTI/STI contacted their health facility and got treatment. More HIV− women than HIV+ women had had more than one sexual partner and never used condoms during the follow-up period. The use of condoms was affected neither by marital status nor by concomitant STIs besides HIV. Our data highlight the importance of public education regarding condom use to protect against STIs in an era when HIV no longer is a death sentence.
Gravitational-Wave Data Analysis. Formalism and Sample Applications: The Gaussian Case

The article reviews the statistical theory of signal detection in application to analysis of deterministic gravitational-wave signals in the noise of a detector. Statistical foundations for the theory of signal detection and parameter estimation are presented. Several tools needed for both theoretical evaluation of the optimal data analysis methods and for their practical implementation are introduced. They include optimal signal-to-noise ratio, Fisher matrix, false alarm and detection probabilities, ${\mathcal F}$-statistic, template placement, and fitting factor. These tools apply to the case of signals buried in a stationary and Gaussian noise. Algorithms to efficiently implement the optimal data analysis techniques are discussed. Formulas are given for a general gravitational-wave signal that includes as special cases most of the deterministic signals of interest.
Genetic Nicotinamide N-Methyltransferase (Nnmt) Deficiency in Male Mice Improves Insulin Sensitivity in Diet-Induced Obesity but Does Not Affect Glucose Tolerance

Antisense oligonucleotide knockdown (ASO-KD) of nicotinamide N-methyltransferase (NNMT) in high-fat diet (HFD)–fed mice has been reported to reduce weight gain and plasma insulin levels and to improve glucose tolerance. Using NNMT-ASO-KD or NNMT knockout mice (NNMT−/−), we tested the hypothesis that Nnmt deletion protects against diet-induced obesity and its metabolic consequences in males and females on obesity-inducing diets. We also examined samples from a human weight reduction (WR) study for adipose NNMT (aNNMT) expression and plasma 1-methylnicotinamide (MNAM) levels. In Western diet (WD)–fed female mice, NNMT-ASO-KD reduced body weight, fat mass, and insulin level and improved glucose tolerance. Although NNMT−/− mice fed a standard diet had no obvious phenotype, NNMT−/− males fed an HFD showed strongly improved insulin sensitivity (IS). Furthermore, NNMT−/− females fed a WD showed reduced weight gain, less fat, and lower insulin levels. However, no improved glucose tolerance was observed in NNMT−/− mice. Although NNMT expression in human fat biopsy samples increased during WR, corresponding plasma MNAM levels significantly declined, suggesting that other mechanisms besides aNNMT expression modulate circulating MNAM levels during WR. In summary, upon NNMT deletion or knockdown in males and females fed different obesity-inducing diets, we observed sex- and diet-specific differences in body composition, weight, and glucose tolerance and estimates of IS.
Constrained variant detection with SPaRC: Sparsity, parental relatedness, and coverage

Structural variants (SVs) are rearrangements of DNA sequences such as inversions, deletions, insertions and translocations. The common method for detecting SVs has been to sequence data from a test genome and map it to a reference genome. More recently, DNA sequencing studies may consist of hundreds, or even thousands of individuals, some of which may be related. In order to improve our ability to identify SVs, we boost the true SV signals by simultaneously analyzing parent and child genomes. Our algorithmic formulation - SPaRC - employs realistic criteria such as sparsity of SVs, relatedness between individuals and variable sequencing coverage throughout the genome.