Miracle-dz/UniFAR-FTUs huggingface dataset:
Demonstration of a Fair Level of Agreement Between Escalation Scores Reported by Hospital Managers and Analysis of Stress-Related Hospital Metrics

Background: The National Health System in Wales has developed a novel national electronic dashboard which reports a daily “escalation score,” reflecting management’s opinion of the pressure each hospital is facing, primarily due to unscheduled care. The aim of this study was to examine the possibility of replacing human scores with a quantitative model, based on the relationship between reported escalation scores and selected hospital metrics. Methods: Generalized linear mixed models were used to model the association between hospital metrics and escalation scores between October one year and October the next year utilizing hospital bed occupancy rate, ambulance hours lost waiting outside emergency departments, number of “boarded out” patients in the hospital, and the daily ratio of admissions to discharges in the hospital. These models were tested against a subsequent period (December unto May the following year), using three models: “general,” “hospital-specific,” and “group-specific. ” The model generated by the initial time frame was tested against data from the subsequent time frame using weighted κ. Results: Across 16 hospitals, using 3343 escalation scores, the rates of agreement and weighted κ were: general model (48.8%; 0.16), hospital-specific model (45.0%; 0.25), and group-specific model (43.1%; 0.25). A 17th small hospital was excluded due to missing data. Conclusions: This is novel research as no similar studies were identified, although the topic is important as it addresses a major current health-care challenge. Automated scores can be derived which have the advantage of being derived objectively, avoiding human inter- and intraindividual variation. Prospective testing is recommended to assess potential service planning benefit.
Viral quasispecies of hepatitis B virus in patients with YMDD mutation and lamivudine resistance may not predict the efficacy of lamivudine/adefovir rescue therapy

The association between hepatitis B virus (HBV) quasispecies (QS) and the efficacy of nucleos(t)ide analog therapy is currently not well defined, particularly in the case of lamivudine (LAM)/adefovir (ADV) combination rescue therapy for patients with chronic HBV infection (CHB) presenting with LAM resistance. In the present study, 16 CHB patients with the rtM204I/V mutation in the tyrosine-methionine-aspartate-aspartate motif of the C domain of the polymerase gene who switched to LAM/ADV treatment due to LAM resistance were assessed. HBV DNA was isolated from these patients and the reverse transcriptase (RT) region was sequenced. The QS heterogeneity and distribution was analyzed, the mutation sites were recorded and the phylogenetic trees were constructed. The results indicated that QS heterogeneity and distribution in the RT and S regions were not significantly different between responders (RS) and non-RS (NRS) at baseline (P>0.05), except for the higher frequency of a dominant strain in the RT region at the nucleotide level in the RS group (P=0.039). In addition, in NRS, no significant difference in QS heterogeneity or distribution in these regions was identified at six months vs. the baseline. Furthermore, although in the non-responder group the frequency of the LAM resistance-associated mutations (rtM204V/I) decreased at 6 months compared with the baseline, it did not disappear in any of the patients after six months of treatment. Analysis of individual patients did not indicate any consistent selection of specific HBV mutants during LAM/ADV rescue therapy. In conclusion, the baseline HBV QS within the RT and S regions may not be a valid predictor of the response to LAM/ADV rescue treatment in CHB patients with LAM resistance.
Impact of several proinflammatory and cell degradation factors in patients with aortic valve stenosis

Aortic valve (AoV) stenosis is the third most common cardiovascular disease. The pathogenesis of AoV stenosis is associated with an inflammatory process where MMPs serve important roles. The aim of the present study was to determine the association between matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and inflammatory factors, and AoV stenosis at various degrees of severity compared with the control. A total of 18 patients with mild, 19 with moderate and 15 with severe AoV stenosis were included in the present stud, and 50 individuals were enrolled in the control group. The severity of stenosis was determined by echocardiography. The expression levels of chemerin, fibroblast growth factor 21, MMP-1, −3, and −9, and TIMP-1 and −3 were analyzed by ELISA. Data were analyzed using GraphPad Prism7 software. The expression levels of MMP-1 was increased in patients with stenosis compared with the control group (P=0.0043). Distribution of the trimodal MMP-1 values was obtained in the stenosis group and monomodal in the control group. A total of 80% of patients in the stenosis group presented significantly increased expression levels of MMP-1 compared with the control group (P=0.0002). Expression of MMP-1 was significantly higher in all stenosis groups compared with the control. The highest expression level of MMP-1 appeared in patients with moderate stenosis (P<0.0001). There was no significant difference in the expression of MMP-3, MMP-9 and TIMP-1 in the aortic stenosis group, compared with the control group. A positive correlation between MMP-1 and MMP-9 expression levels was identified (r=0.37; P=0.017). The increase of MMP-1 was correlated with the increase of MMP-9, but not with the level of MMP-3. The expression levels of chemerin was significantly elevated in patients with stenosis compared with healthy patients. The highest expression levels of chemerin were determined in patients with mild (P=0.0001) and moderate (P=0.0007) stenosis and decreased with the grade of severity compared with the control group. The expression of FGF-21 was significantly different between the control and mild (P=0.013), moderate (P=0.015) and severe stenosis (P=0.003) groups. The expression levels of FGF-21 increased with the increase in severity grade, reaching the maximum for severe stenosis. The results of the present study indicated that the inflammatory process is predominantly occurring at the early, mild stage of stenosis and the most prominent extracellular matrix remodeling occurs in moderate stenosis (demonstrated by MMP-1 levels). In patients with severe stenosis, the levels of MMP-1 and chemerin (which are lower than in a case of mild or moderate stenosis) could indicate the development of calcinosis and the reduction in activity or inactivation of the inflammatory process.
Perspectives on the challenges of leadership in schools to improve student learning systems

This study is an analysis of the challenges of leaders in schools to improve learning systems, trying to do an analysis of the six aspects of analysis during the study. The main contribution of this research is related to how to deal with challenges in improving learning systems in schools that have so far faced challenges and obstacles, and these need to be analyzed and solutions. This study uses a qualitative method with a case study model, because this researcher is a case that must be disclosed and found a solution, looking at the gap between quality, performance and leadership in several schools that are the object of research and this research lasted for several years. four months (18 weeks), the time is indeed quite short, but researchers try to use this time effectively to produce something useful. In this case involving eight school leaders, as participants, the results of the application of the six aspects of indicators were able to improve teacher performance and from changes in the learning system as well. can be significantly improved as evidenced by the results of evaluating student learning, this research does indeed need to be deepened comprehensively. The author measures the success rate of these indicators by using a cluster system (individually intervening) individually either for the principal or when assessing students, so the writer can see the improvement.
Monthly sulfadoxine–pyrimethamine versus dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trial

BACKGROUND Intermittent treatment with sulfadoxine-pyrimethamine, recommended for prevention of malaria in pregnant women throughout sub-Saharan Africa, is threatened by parasite resistance. We assessed the efficacy and safety of intermittent preventive treatment with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine. METHODS We did a double-blind, randomised, controlled, superiority trial at one rural site in Uganda with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-uninfected pregnant women between 12 and 20 weeks gestation were randomly assigned (1:1) to monthly intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine. The primary endpoint was the risk of a composite adverse birth outcome defined as low birthweight, preterm birth, or small for gestational age in livebirths. Protective efficacy was defined as 1-prevalence ratio or 1-incidence rate ratio. All analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02793622. FINDINGS Between Sept 6, 2016, and May 29, 2017, 782 women were enrolled and randomly assigned to receive sulfadoxine-pyrimethamine (n=391) or dihydroartemisinin-piperaquine (n=391); 666 (85·2%) women who delivered livebirths were included in the primary analysis. There was no significant difference in the risk of our composite adverse birth outcome between the dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine treatment group (54 [16%] of 337 women vs 60 [18%] of 329 women; protective efficacy 12% [95% CI -23 to 37], p=0·45). Both drug regimens were well tolerated, with no significant differences in adverse events between the groups, with the exception of asymptomatic corrected QT interval prolongation, which was significantly higher in the dihydroartemisinin-piperaquine group (mean change 13 ms [SD 23]) than in the sulfadoxine-pyrimethamine group (mean change 0 ms [SD 23]; p<0·0001). INTERPRETATION Monthly intermittent preventive treatment with dihydroartemisinin-piperaquine was safe but did not lead to significant improvements in birth outcomes compared with sulfadoxine-pyrimethamine. FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Bill & Melinda Gates Foundation.
Autologous bone marrow stem cell therapy for patients undergoing coronary artery bypass grafting: A meta-analysis of 14 randomized controlled trials

Autologous bone marrow stem cell (BMSC) therapy is a novel option for regenerative therapy in patients with ischemic heart disease. The aim of the present meta-analysis was to evaluate the effectiveness of BMSCs combined with coronary artery bypass grafting (CABG). The PubMed, Cochrane Library, EMBASE and Web of Science databases were searched from inception to November 22, 2017 for randomized controlled trials on BMSC therapy combined with CABG. Finally, 14 trials with a total of 596 participants were included. Data were analyzed using a random-effects model. Compared with the control group, the BMSC therapy group exhibited an improvement in the left ventricular (LV) ejection fraction from baseline to follow-up [mean difference (MD)=4.36%; 95% confidence interval (CI): 1.90–6.81%; P<0.01]. Analysis of the pooled results revealed non-significant differences in the LV end-diastolic volume (MD=−6.27 ml; 95% CI: −22.34 to 9.80 ml; P=0.44), LV end-diastolic volume index (MD=−15.11 ml/m2; 95% CI: −31.53 to 1.30 ml/m2; P=0.07), LV end-systolic volume (MD=−11.52 ml; 95% CI: −26.97 to 3.93 ml; P=0.14) and LV end-systolic volume index (MD=−16.56 ml/m2; 95% CI: −37.75 to 4.63 ml/m2; P=0.13) between the BMSC and CABG alone groups. Therefore, autologous BMSC therapy for patients undergoing CABG appears to be associated with an improvement in LV function compared with CABG alone.
Particulate matter, nitrogen oxides, ozone, and select volatile organic compounds during a winter sampling period in Logan, Utah, USA

ABSTRACT Particulate matter mass (PM), trace gaseous pollutants, and select volatile organic compounds (VOCs) with meteorological variables were measured in Logan, Utah (Cache Valley), for >4 weeks during winter 2017 as part of the Utah Winter Fine Particle Study (UWFPS). Higher PM levels for short time periods and lower ozone (O3) levels were present due to meteorological and mountain valley conditions. Nitrogenous pollutants were relatively strongly correlated with PM variables. Diurnal cycles of NOx, O3, and fine PM(PM 2.5) (aerodynamic diameter <2.5 μm [PM2.5]) suggested formation from NOx. O3 levels increased from early morning into midafternoon, and NOx and PM2.5 increased throughout the morning, followed by sharp decreases. Toluene/benzene and xylenes/benzene ratios and VOC correlations with nitrogenous and PM species were indicative of local traffic sources. Wind sector comparisons suggested that pollutant levels were lower when winds were from nearby mountains to the east versus winds from northerly or southerly origins. Implications: The Cache Valley in Idaho and Utah has been designated a PM2.5 nonattainment area that has been attributed to air pollution buildup during winter stagnation events. To inform state implementation plans for PM2.5 in Cache Valley and other PM2.5 nonattainment areas in Utah, a state and multiagency federal research effort known as the UWFPS was conducted in winter 2017. As part of the UWFPS, the U.S. Environmental Protection Agency (EPA) measured ground-based PM species and their precursors, VOCs, and meteorology in Logan, Utah. Results reported here from the EPA study in Logan provide additional understanding of wintertime air pollution conditions and possible sources of PM and gaseous pollutants as well as being useful for future PM control strategies in this area.
A product review of vedolizumab in inflammatory bowel disease

ABSTRACT Vedolizumab is a monoclonal antibody to the α4β7 integrin that selectively reduces intestinal lymphocyte trafficking, thereby providing a safe and effective treatment option for patients with inflammatory bowel disease (IBD). This product review outlines the unique mechanism of vedolizumab in addition to efficacy, safety, pharmacokinetic and pharmacodynamic data from clinical trials, observational studies and meta-analyses. Vedolizumab has been shown to be effective as a first- or second-line induction and maintenance therapy in both ulcerative colitis (UC) and Crohn’s disease (CD). Prolonged induction therapy may increase efficacy, particularly in tumor necrosis factor-alpha-exposed CD patients. To date, no drug-specific safety signals have been identified. In addition to the presence of an apparent exposure-response relationship, vedolizumab has demonstrated consistent pharmacodynamic effects on α4β7, mucosal vascular addressin cell adhesion molecule 1 and other cell adhesion molecules. Future efforts should focus on identifying predictive biomarkers capable of guiding personalized IBD treatment with vedolizumab.
Antigen Targets for the Development of Immunotherapies in Leukemia

Immunotherapeutic approaches, including allogeneic stem cell transplantation and donor lymphocyte infusion, have significantly improved the prognosis of leukemia patients. Further efforts are now focusing on the development of immunotherapies that are able to target leukemic cells more specifically, comprising monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and dendritic cell- or peptide-based vaccination strategies. One main prerequisite for such antigen-specific approaches is the selection of suitable target structures on leukemic cells. In general, the targets for anti-cancer immunotherapies can be divided into two groups: (1) T-cell epitopes relying on the presentation of peptides via human leukocyte antigen (HLA) molecules and (2) surface structures, which are HLA-independently expressed on cancer cells. This review discusses the most promising tumor antigens as well as the underlying discovery and selection strategies for the development of anti-leukemia immunotherapies.
Association of Lowering Low‐Density Lipoprotein Cholesterol With Contemporary Lipid‐Lowering Therapies and Risk of Diabetes Mellitus: A Systematic Review and Meta‐Analysis

Background The relationship between lowering LDL (low‐density lipoprotein) cholesterol with contemporary lipid‐lowering therapies and incident diabetes mellitus (DM) remains uncertain. Methods and Results Thirty‐three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline, Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid‐lowering therapy. More intensive lipid‐lowering therapy was defined as the more potent pharmacological strategy (PCSK9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta‐analyses were conducted using a random‐effects model. No significant association was noted between 1‐mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid‐lowering therapy (risk ratio: 0.95; 95% CI, 0.87–1.04; P=0.30; R 2=14%) or for statins or PCSK9 inhibitors. More intensive lipid‐lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI, 1.03–1.11; P<0.001; I2=0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI, 1.05–1.15; P<0.001; I2=0%), whereas PCSK9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI, 0.93–1.07; P=0.96; I2=0%; P=0.02 for interaction). Conclusions Among intensive lipid‐lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM. The risk of incident DM was higher with statins, whereas PCSK9 inhibitors had no association with risk of incident DM.
Differential immune responses of C57BL/6 mice to infection by Salmonella enterica serovar Typhimurium strain SL1344, CVCC541 and CMCC50115

ABSTRACT With a broad range of hosts, Salmonella enterica serovar Typhimurium (S. Typhimurium) is the major cause of gastroenteritis in human beings and systemic disease in susceptible mice strains. However, different S. Typhimurium strains differ in regard to virulence and host adaptation. Here, C57BL/6 mice were infected, respectively, with different S. Typhimurium strains SL1344 (calf), CVCC541 (chicken) and CMCC50115 (mutton) to determine their virulence and host immune responses. It was found that mice were less susceptible to infection by S. Typhimurium CVCC541 and CMCC50115 strains, with lower lethality and decreased bacterial burden in liver and spleen. Besides, S. Typhimurium strains CVCC541 and CMCC50115 enhanced host innate immune responses by increased frequencies of macrophages and neutrophils 3 days after infection. But SL1344 strain evaded immune response by inducing apoptosis of macrophages. Moreover, CVCC541 could elicit adaptive immune responses of host 11 days after infection upon examination of the proliferation and activation of CD4+ T cells. In addition, 125 and 138 unique mutant coding genes, respectively, in S. Typhimurium strains CVCC541 and CMCC50115 and 78 shared mutant coding genes were annotated by genomic alignment to SL1344 genome and the signal pathways involving these genes were further analyzed. The acquired results indicate that different original S. Typhimurium strains show differential virulence and may induce diverse immune responses in the same host infected.
The Global Financial Crisis and Overweight among Children of Single Parents: A Nationwide 10-Year Birth Cohort Study in Japan

Evidence suggests that socioeconomically disadvantaged children may experience a greater increase in overweight risk during macroeconomic downturns. We examined whether inequalities in the risk of overweight between Japanese children from single- and two-parent households increased after the 2008 global financial crisis. We used data from ten waves (2001 to 2011) of a nationwide longitudinal survey following all Japanese children born within 2 weeks in 2001 (boys: n = 15,417, girls: n = 14,245). Child overweight was defined according to age- and sex-specific cut-offs for Body Mass Index (BMI). Interaction between a binary measure of crisis onset (September 2008) and single-parent status was assessed using generalized estimating equation models. Covariates included baseline household income and income loss during the crisis. Girls from single-parent households showed a greater increase in the odds of overweight after crisis onset (adjusted odds ratio (AOR), 1.23; 95% confidence interval (CI), 1.04–1.46) compared to girls from households with two parents, regardless of household financial status. A similar though statistically non-significant trend was observed among boys (AOR, 1.10; 95% CI, 0.92–1.30). Child overweight risk by single-parent status may increase during macroeconomic downturns, at least among girls. Financial aid to single-parent households may not suffice to redress this gap.
A DFT Study of Hydrogen Storage in High-Entropy Alloy TiZrHfScMo

In recent years, high-entropy alloys have been proposed as potential hydrogen storage materials. Despite a number of experimental efforts, there is a lack of theoretical understanding regarding the hydrogen absorption behavior of high-entropy alloys. In this work, the hydrogen storage properties of a new TiZrHfScMo high-entropy alloy are investigated. This material is synthesized successfully, and its structure is characterized as body-centered cubic. Based on density functional theory, the lattice constant, formation enthalpy, binding energy, and electronic properties of hydrogenated TiZrHfScMo are all calculated. The calculations reveal that the process of hydrogenation is an exothermic process, and the bonding between the hydrogen and metal elements are of covalent character. In the hydrogenated TiZrHfScMo, the Ti and Sc atoms lose electrons and Mo atoms gain electrons. As the H content increases, the bonding is weakened, and the and bonding are strengthened. Our calculations demonstrate that the TiZrHfScMo high-entropy alloy is a promising hydrogen storage material, and different alloy elements play different roles in the hydrogen absorption process.