Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy, safety, and tolerability of once‐daily abediterol in patients with stable, persistent asthma: a Phase II, randomized, 7‐day, crossover study

Abediterol is a once‐daily, long‐acting β2‐adrenergic agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. We assessed the efficacy, safety, and tolerability of three dose levels of abediterol, given once daily for 7 days in patients with stable, persistent asthma. This was an ascending‐dose, three‐period incomplete crossover study design investigating three dose levels of abediterol versus placebo (EudraCT No. 2008‐003732‐38). Twenty‐eight male patients (25–59 years) were randomized to one of four treatment sequences (1:1:1:1). Follow‐up was 7 days after final treatment. Spirometry was performed regularly up to 24 h postdose Day 1, up to 36 h postdose Day 7, and at follow‐up. Vital signs, 12‐lead electrocardiogram, and clinical laboratory tests were recorded throughout. Abediterol 2.5, 5, and 10 μg provided clinically and statistically significant improvements from baseline (predose, Day 1) in trough forced expiratory volume in 1 sec (FEV1) versus placebo on Day 7 (primary endpoint) of 334, 365, and 294 mL, respectively (all P < 0.01), and peak FEV1 versus placebo on Day 7 of 364 (P < 0.001), 403 (P < 0.001), and 375 mL (P < 0.01), respectively. Days 1 and 7 area under the curve (AUC) parameters within each abediterol group were similar for AUC0–6, AUC0–12, AUC0–24, and AUC12–24, with dose‐dependent effects observed on Day 1. Abediterol (2.5–10 μg) demonstrated a good safety and tolerability profile. Abediterol 2.5, 5, and 10 μg once daily achieved statistically and clinically significant improvements in pulmonary function versus placebo over 7 days and demonstrated a safety and tolerability profile comparable with placebo.
Time Course of the Phenotype of Blood and Bone Marrow Monocytes and Macrophages in the Lung after Cigarette Smoke Exposure In Vivo

Alveolar macrophages play a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Monocytes are recruited from blood during inflammation and then mature into alveolar macrophages. The aim of this study was to investigate the effect of cigarette smoke (CS) at different times in lung macrophages and monocytes from blood and bone marrow in mice. Male mice (C57BL/6, n = 45) were divided into groups: control, CS 5 days, CS 14 days and CS 30 days. Five days’ CS exposure induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and matrix metalloproteinase (MMP)-12. After 14 days of CS exposure, neutrophil recruitment and cytokine production were greatly reduced. Moreover, chronic CS exposure led to increased recruitment of macrophages (with high expression of CD206), transforming growth factor-β (TGF-β) production as well as no detection of TNF-α, interleukin (IL)-6 and KC. CS can also change the monocyte phenotype in the blood and bone marrow, with an increase in Ly6Clow cells. These results show for the first time that CS can change not only macrophage polarization but also monocyte. These results suggest that continued recruitment of Ly6Clow monocytes may help the distinct renewing macrophage M2 population required for COPD progression.
Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: Perspectives from stem cell biology and molecular medicine

Adipose‐derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self‐repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re‐construct damaged cartilage tissue. In this article, we have reviewed the most up‐to‐date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co‐culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
Surgical treatment of infective mitral valve endocarditis: predictors of early and late outcome.

BACKGROUND AND AIMS OF THE STUDY The study aim was to review our experience in surgical treatment of infective mitral valve endocarditis, and to identify predictors of early and late outcome. METHODS Ninety-one consecutive patients (52 males, 39 females, mean age 55.6 years) underwent surgery between 1973 and 1997 for endocarditis of isolated mitral (n = 65, 71%), mitral and aortic (n = 25, 28%) and mitral, aortic and tricuspid valves (n = 1, 1%). Native valve endocarditis (NVE) was present in 60 patients (66%) and prosthetic valve endocarditis (PVE) in 31 (34%). The main indications for surgery were heart failure in 32 patients, valve dysfunction in 23, vegetations in 21, and persistent sepsis in 11. Eighty-six patients (95%) were in NYHA classes III-IV, and 58 (64%) had active culture-positive endocarditis at surgery. Mechanical valves were implanted in 73 patients and bioprosthetic valves in 13; valves were repaired in five patients. The impact of 46 parameters on early and late outcome was defined by means of univariate and multivariate statistical analysis. Follow up was complete (mean 5.5 years; range: 0-23.1 years; total 507.3 patient-years). RESULTS Operative mortality rate was 11% (n = 10). Recurrent infection was recorded in five patients (6%), and reoperation was required in eight (9%). Freedom from recurrent infection and reoperation at 10 years was 89.1% and 87.8% respectively. There were 22 late deaths, 15 from cardiac causes. Actuarial survival rates for all patients at 5, 10 and 15 years were 73.0%, 62.7% and 58.7% (for hospital survivors, the corresponding rates were 81.9%, 69.7% and 66.0%). On multiple logistic regression and Cox proportional hazards models, the following were independent predictors: preoperative pulmonary edema (p = 0.01) for operative mortality; PVE (p = 0.02) for recurrence; younger age (p = 0.02) and PVE (p = 0.02) for reoperation; male gender (p = 0.004) and longer ITU stay for survival (if all patients were included); male gender (p = 0.01) and myocardial invasion by infection (p = 0.02) for survival (if only the hospital survivors were analyzed). CONCLUSION Surgery for infective mitral valve endocarditis carries a relatively high, though acceptable, risk but provides satisfactory freedom from recurrent infection, reoperation and improved long-term survival. Analysis of these data demonstrated that the preoperative hemodynamic status was the major predictor of in-hospital outcome, PVE increased the risk for recurrent infection and reoperation, whereas male gender and myocardial invasion by the infective process critically reduced the probability of long-term survival. The type of offending pathogen, the activity of infection and the involvement of more than one valve did not appear to influence early and/or late outcome.
Complete plastid genome of Astragalus mongholicus var. nakaianus (Fabaceae)

Abstract The first complete plastid genome (plastome) of the largest angiosperm genus, Astragalus, was sequenced for the Korean endangered endemic species A. mongholicus var. nakaianus. Its genome is relatively short (123,633 bp) because it lacks an Inverted Repeat (IR) region. It comprises 110 genes, including four unique rRNAs, 30 tRNAs, and 76 protein-coding genes. Similar to other closely related plastomes, rpl22 and rps16 are absent. The putative pseudogene with abnormal stop codons is atpE. This plastome has no additional inversions when compared with highly variable plastomes from IRLC tribes Fabeae and Trifolieae. Our phylogenetic analysis confirms the non-monophyly of Galegeae.
Lack of effect of vancomycin and gentamicin on auditory function in guinea pigs

The dispositions of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph after single and multiple administrations and the effects of multiple administrations of VCM or GM alone and the combination of both drugs on auditory function were studied in male guinea pigs. The pharmacokinetic parameters of VCM and GM obtained from plasma drug concentration-time data after single and multiple (22 days) intramuscular administrations of VCM (200 mg/kg of body weight) alone and GM (50 mg/kg) alone were not significantly different from those after combined administration of VCM (200 mg/kg) and GM (50 mg/kg). There was no change in the penetration ratio of VCM and GM into perilymph between administration of VCM or GM alone and the combination of both drugs. Furthermore, the hearing threshold of guinea pigs was not affected by VCM or GM alone or the combination of both drugs within the range of therapeutic VCM and GM levels in plasma in humans.
Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

Abstract. With the recent breakthrough in genetically expressed voltage indicators (GEVIs), there has been a tremendous demand to determine the capabilities of these sensors in vivo. Novel voltage sensitive fluorescent proteins allow for direct measurement of neuron membrane potential changes through changes in fluorescence. Here, we utilized ArcLight, a recently developed GEVI, and examined the functional characteristics in the widely used mouse somatosensory whisker pathway. We measured the resulting evoked fluorescence using a wide-field microscope and a CCD camera at 200 Hz, which enabled voltage recordings over the entire cortical region with high temporal resolution. We found that ArcLight produced a fluorescent response in the S1 barrel cortex during sensory stimulation at single whisker resolution. During wide-field cortical imaging, we encountered substantial hemodynamic noise that required additional post hoc processing through noise subtraction techniques. Over a period of 28 days, we found clear and consistent ArcLight fluorescence responses to a simple sensory input. Finally, we demonstrated the use of ArcLight to resolve cortical S1 sensory responses in the awake mouse. Taken together, our results demonstrate the feasibility of ArcLight as a measurement tool for mesoscopic, chronic imaging.
Examination of momentary maintenance factors and eating disorder behaviors and cognitions using ecological momentary assessment

ABSTRACT The integrative cognitive-affective therapy (ICAT) momentary maintenance model proposes a number of situational factors that precipitate eating disorder (ED) behaviors and cognitions. The current study examines momentary situational triggers in relation to a broad range of ED symptoms in a diagnostically heterogeneous sample of individuals with ED psychopathology. In the current study, 30 women with binge eating pathology completed a 14-day ecological momentary assessment (EMA) protocol during which they responded to five random signals throughout the day. During signaled assessments, participants completed measures of self-criticism, interpersonal problems, self-regulation of binge eating, appearance concerns, and cognitive and behavioral ED symptoms. Multilevel models were used to examine prospective associations between hypothesized ICAT maintenance factors and ED symptoms. Within-subjects self-criticism prospectively predicted vomiting, restriction, preoccupation with thoughts of food, and urges to eat. Within-subjects interpersonal problems prospectively predicted vomiting, and within-subjects appearance concerns prospectively predicted preoccupation with thoughts of food. There were no significant predictors of binge eating. These results provide some support for hypothesized momentary situational triggers of ED symptoms in the momentary maintenance model of ICAT using naturalistic, momentary assessment. Specifically, it may be particularly useful for interventions such as ICAT to address momentary self-criticism when targeting a range of ED symptoms.
Studies on the Two Thymine Residues in the Catalytic Core of 10-23 DNAzyme: The Impact on the Catalysis of Their 5-Substituted Functional Groups

In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external functional groups induced new interactions within the catalytic core, resulting in both negative and positive effects on the catalytic activity of 10-23 DNAzyme, and the different linkages could be used to modulate the effect of the functional groups. The conservation of T4 and T8 could be recognized at the level of the nucleobase, but at the level of the functional group, T4 is not completely conserved. Their 5-methyl groups could be modified for a better performance in terms of the DNAzyme.
Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development

The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.
Gene Duplications at the Chemokine Locus on Mouse Chromosome 4: Multiple Strain-Specific Haplotypes and the Deletion of Secondary Lymphoid-Organ Chemokine and EBI-1 Ligand Chemokine Genes in the plt Mutation1

The murine paucity of lymph node T cell (plt) mutation leads to abnormalities in leukocyte migration and immune response. The causative defect is thought to be a loss of secondary lymphoid-organ chemokine (SLC) expression in lymphoid tissues. We now find that the plt defect is due to the loss of both SLC and EBI-1 ligand chemokine (ELC) expression in secondary lymphoid organs. In an examination of the plt locus, we find that commonly used inbred mouse strains demonstrate at least three different haplotypes. Polymorphism at this locus is due to duplications of at least four genes, three of them encoding chemokines. At least two cutaneous T cell-attracting chemokine (CTACK), three SLC, and four ELC genes or pseudogenes are present in some haplotypes. All haplotypes share a duplication that includes two SLC genes, which demonstrate different expression patterns, a single functional ELC gene, and an ELC pseudogene. The plt mutation represents a deletion that includes the SLC gene expressed in secondary lymphoid organs and the single functional ELC gene, leaving only an SLC gene that is expressed in lymphatic endothelium and an ELC pseudogene. This lack of CCR7 ligands in the secondary lymphoid organs of plt mice provides a basis for their severe abnormalities in leukocyte migration and immune response.
Arginase-2 mediates renal ischemia-reperfusion injury.

Novel therapeutic interventions for preventing or attenuating kidney injury following ischemia-reperfusion injury (IRI) remain a focus of significant interest. Currently, there are no definitive therapeutic or preventive approaches available for ischemic acute kidney injury (AKI). Our objective is to determine 1) whether renal arginase activity or expression is increased in renal IRI, and 2) whether arginase plays a role in development of renal IRI. The impact of arginase activity and expression on renal damage was evaluated in male C57BL/6J (wild type) and arginase-2 (ARG2)-deficient (Arg2-/- ) mice subjected to bilateral renal ischemia for 28 min, followed by reperfusion for 24 h. ARG2 expression and arginase activity significantly increased following renal IRI, paralleling the increase in kidney injury. Pharmacological blockade or genetic deficiency of Arg2 conferred kidney protection in renal IRI. Arg2-/- mice had significantly attenuated kidney injury and lower plasma creatinine and blood urea nitrogen levels after renal IRI. Blocking arginases using S-(2-boronoethyl)-l-cysteine (BEC) 18 h before ischemia mimicked arginase deficiency by reducing kidney injury, histopathological changes and kidney injury marker-1 expression, renal apoptosis, kidney inflammatory cell recruitment and inflammatory cytokines, and kidney oxidative stress; increasing kidney nitric oxide (NO) production and endothelial NO synthase (eNOS) phosphorylation, kidney peroxisome proliferator-activated receptor-γ coactivator-1α expression, and mitochondrial ATP; and preserving kidney mitochondrial ultrastructure compared with vehicle-treated IRI mice. Importantly, BEC-treated eNOS-knockout mice failed to reduce blood urea nitrogen and creatinine following renal IRI. These findings indicate that ARG2 plays a major role in renal IRI, via an eNOS-dependent mechanism, and that blocking ARG2 activity or expression could be a novel therapeutic approach for prevention of AKI.
Maternal Prepregnancy Body Mass Index, Gestational Weight Gain, and Cessation of Breastfeeding: A Systematic Review and Meta-Analysis.

Background: Suboptimal breastfeeding, a major factor of maternal and child morbidity and mortality, has been reported around the world. Maternal weight status, as a significant variable influencing breastfeeding outcomes, needs to be studied sufficiently. Objective: This review is to explore the effect of different prepregnancy BMI and gestational weight gain (GWG) categories on breastfeeding initiation and cessation. Methods: Cohort studies were systematically searched in Embase, Web of Science, PubMed, and CINAHL databases from database establishment to February 2019. Summary risk ratio (RR) on breastfeeding initiation and cessation was estimated with the use of a random-effects model. Results: Thirty cohort studies were included in meta-analysis. Prepregnancy obesity was a risk factor for breastfeeding initiation (RR 1.49, 95% CI [1.33-1.67]), exclusive and any breastfeeding (ABF) duration (RR 1.26, 95% CI [1.17-1.36]; RR 1.34 95% CI [1.16-1.56]). Inadequate GWG was a risk factor for breastfeeding initiation (RR 1.27, 95% CI [1.08-1.49]). Excessive GWG was a risk factor for ABF duration when women were prepregnancy overweight and obese (RR 1.42 95% CI [1.32-1.53]; RR 1.89 95% CI [1.13-3.17]). Conclusion: If women are obese before pregnancy or gain excessive/inadequate weight during pregnancy, they are less likely to initiate and continue breastfeeding according to recommendation time. Hence, guidance about proper weight management to reproductive age women and consultation about recommended GWG to pregnant women should be fully implemented to improve breastfeeding practices. Besides, future research needs to find out the association between prepregnancy underweight status and breastfeeding outcomes.
Accounting values and inflation

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Associations between participation in organised physical activity in the school or community outside school hours and neighbourhood play with child physical activity and sedentary time: a cross-sectional analysis of primary school-aged children from the UK

Objectives To assess the extent to which participation in organised physical activity in the school or community outside school hours and neighbourhood play was associated with children’s physical activity and sedentary time. Design Cross-sectional study. Setting Children were recruited from 47 state-funded primary schools in South West England. Participants 1223 children aged 8–9 years old. Outcome measures Accelerometer-assessed moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time. Methods Children wore an accelerometer, and the mean minutes of MVPA and sedentary time per day were derived. Children reported their attendance at organised physical activity in the school or community outside school hours and neighbourhood play using a piloted questionnaire. Cross-sectional linear and logistic regression were used to examine if attendance frequency at each setting (and all settings combined) was associated with MVPA and sedentary time. Multiple imputation methods were used to account for missing data and increase sample size. Results Children who attended clubs at school 3–4 days per week obtained an average of 7.58 (95% CI 2.7 to 12.4) more minutes of MVPA per day than children who never attended. Participation in the three other non-school-based activities was similarly associated with MVPA. Evidence for associations with sedentary time was generally weaker. Associations were similar in girls and boys. When the four different contexts were combined, each additional one to two activities participated in per week increased participants’ odds (OR: 1.18, 95% CI 1.12 to 1.25) of meeting the government recommendations for 60 min of MVPA per day. Conclusion Participating in organised physical activity at school and in the community is associated with greater physical activity and reduced sedentary time among both boys and girls. All four types of activity contribute to overall physical activity, which provides parents with a range of settings in which to help their child be active.