Miracle-dz/UniFAR-FTUs huggingface dataset:
The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

AIM The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. METHODS We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. RESULTS Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). CONCLUSIONS I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
Fibrinogen and mucin binding activity of EF0737, a novel protein of Enterococcus faecalis

Background and Objectives: Enterococcus faecalis is the leading cause of several human infections. This opportunist pathogen expresses surface components that have various functions in the infection process including bacterial adhesion, lytic activity, and induction of host immune responses. EF0737, a novel cell wall associated protein, may play an important role in pathogenesis of E. faecalis, based on our experiments. This study was conducted to clone and express EF0737 and demonstrate its interaction with biotinylated plasma proteins and patients’ sera. Materials and Methods: The full length of ef0737 gene was cloned in pTZ57R/T cloning vector and subcloned in pET21a expression vector. Recombinant protein expressed in Escherichia coli Origami (DE3) was confirmed by western blot technique, using anti-His tagged monoclonal antibodies, and was then purified. Interaction of the recombinant protein with plasma proteins and patients’ sera were examined by western blot. Results: The ef0737 gene was successfully cloned and expressed in E. coli Origami host. Binding activity was observed between the purified EF0737 recombinant protein and fibrinogen and mucin among other plasma proteins. Moreover, reaction was also observed between the purified product and sera obtained from patients diagnosed with E. faecalis infection. Conclusion: The observed reactions between EF0737 and fibrinogen, mucin and patients’ sera suggest that EF0737 may play important role in pathogenesis of infections caused by E. faecalis. However, more comprehensive characterization of this novel protein may provide better understanding of host pathogen interaction.
Chrysophanol inhibits proliferation and induces apoptosis through NF-κB/cyclin D1 and NF-κB/Bcl-2 signaling cascade in breast cancer cell lines

Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells. However, the effects of chrysophanol on human breast cancer remain to be elucidated. The aim of the present study was to clarify the role of chrysophanol on breast cancer cell lines MCF-7 and MDA-MB-231, and to identify the signal transduction pathways regulated by chrysophanol. MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited cell proliferation, and cell cycle progression in a dose-dependent manner. The expression of cell cycle-associated cyclin D1 and cyclin E were downregulated while p27 expression was upregulated following chrysophanol treatment at the mRNA, and protein levels. The Annexin V/propidium iodide staining assay results revealed that apoptosis levels increased following chrysophanol treatment. Chrysophanol upregulated caspase 3 and poly (ADP-ribose) polymerase cleavage in both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis regulator Bcl-2 protein, and transcription factor p65 and IκB phosphorylation. Inhbition of nuclear factor (NF)-κB by ammonium pyrrolidine dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated proteins. In conclusion, the results of the current study demonstrated that chrysophanol effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF-κB signaling pathway.
Selection against BALB/c strain cells in mouse chimaeras

ABSTRACT It has been shown previously that BALB/c strain embryos tend to contribute poorly to mouse aggregation chimaeras. In the present study we showed that BALB/c cells were not preferentially allocated to any extraembryonic lineages of mouse aggregation chimaeras, but their contribution decreased during the early postimplantation period and they were significantly depleted by E8.5. The development of BALB/c strain preimplantation embryos lagged behind embryos from some other strains and the contribution that BALB/c and other embryos made to chimaeras correlated with their developmental stage at E2.5. This relationship suggests that the poor contribution of BALB/c embryos to aggregation chimaeras is at least partly a consequence of generalised selection related to slow or delayed preimplantation development. The suitability of BALB/c embryos for maximising the ES cell contribution to mouse ES cell chimaeras is also discussed. Summary: BALB/c strain embryos contributed poorly to mouse aggregation chimaeras by E8.5. Selection appears linked to slow BALB/c development and might also explain the good ES cell contribution in BALB/c↔ES-cell chimaeras.
Posttraumatic Stress Disorder and Autobiographical Memories in Everyday Life

Evidence from self-reports and laboratory studies suggests that recall of nontrauma autobiographical memories may be disturbed in posttraumatic stress disorder (PTSD), but investigations in everyday life are sparse. This study investigated unintentional nontrauma and trauma memories in trauma survivors with and without PTSD (N = 52), who kept an autobiographical memory diary for a week. We investigated whether unintentional nontrauma memories show an overgeneral memory bias and further memory abnormalities in people with PTSD, and whether unintentional trauma memories show distinct features. Compared to the no-PTSD group, the PTSD group recorded fewer nontrauma memories, which were more overgeneral, more often from before the trauma or related to the trauma, were perceived as distant, and led to greater dwelling. Trauma memories were more vivid, recurrent, and present and led to greater suppression and dwelling. Within the PTSD group, the same features distinguished trauma and nontrauma memories. Results are discussed regarding theories of autobiographical memory and PTSD.
Evolution of galaxy stellar masses and star formation rates in the eagle simulations

We investigate the evolution of galaxy masses and star formation rates in the Evolution and Assembly of Galaxies and their Environment (EAGLE) simulations. These comprise a suite of hydrodynamical simulations in a $\Lambda$CDM cosmogony with subgrid models for radiative cooling, star formation, stellar mass loss, and feedback from stars and accreting black holes. The subgrid feedback was calibrated to reproduce the observed present-day galaxy stellar mass function and galaxy sizes. Here we demonstrate that the simulations reproduce the observed growth of the stellar mass density to within 20 per cent. The simulation also tracks the observed evolution of the galaxy stellar mass function out to redshift z = 7, with differences comparable to the plausible uncertainties in the interpretation of the data. Just as with observed galaxies, the specific star formation rates of simulated galaxies are bimodal, with distinct star forming and passive sequences. The specific star formation rates of star forming galaxies are typically 0.2 to 0.4 dex lower than observed, but the evolution of the rates track the observations closely. The unprecedented level of agreement between simulation and data makes EAGLE a powerful resource to understand the physical processes that govern galaxy formation.
Optical and pharmacological strategies of myopia control

Recent increases in global myopia prevalence rates have raised significant concerns as myopia increases the lifelong risk of various sight‐threatening ocular conditions. This growing public health burden has generated significant research interests into understanding both its aetiology and developing effective methods to slow down or stop its development, methods collectively termed ‘myopia control’. The growing body of research has demonstrated benefits of various optical and pharmacological treatments resulting in myopia control management increasingly becoming a part of main stream clinical practice. This review will discuss the peer‐reviewed literature on the efficacy of various myopia control interventions including multifocal spectacles and contact lenses, orthokeratology and pharmaceutical eye drops, as well as potential future research directions.
Serum Fibroblast Growth Factor 21 and New-Onset Metabolic Syndrome: KoGES-ARIRANG Study

Purpose Fibroblast growth factor 21 (FGF21) is a crucial metabolic regulator, with multiple favorable effects on glucose homeostasis and lipid metabolism. Since serum FGF21 level has been implicated as a potential marker for the early identification of metabolic syndrome (MetS), we investigated the association between serum FGF21 level and the development of MetS in a population-based prospective study. Materials and Methods We conducted a prospective study of 221 randomly sampled adults without MetS from a general population-based cohort study who were examined from 2005–2008 (baseline) and from 2008–2011 (follow-up). Baseline serum FGF21 levels were analyzed using enzyme-linked immunosorbent assay. Results During the average 2.8-year follow-up period, 82 participants (36.6%) developed new-onset MetS. Serum FGF21 levels were significantly higher in patients with new-onset MetS than in those without MetS (209.56±226.80 vs. 110.09±81.10, p<0.01). In multivariate adjusted models, the odds for MetS development were greater in patients with serum FGF21 levels in the highest quartile, compared to those in the lowest quartile (3.84, 95% confidence interval: 1.59–9.28). Conclusion Serum FGF21 level was an independent predictor for new-onset MetS in a population-based prospective study.
Lineage Diversity and Size Disparity in Musteloidea: Testing Patterns of Adaptive Radiation Using Molecular and Fossil‐Based Methods

Abstract. Adaptive radiation is hypothesized to be a primary mechanism that drives the remarkable species diversity and morphological disparity across the Tree of Life. Tests for adaptive radiation in extant taxa are traditionally estimated from calibrated molecular phylogenies with little input from extinct taxa. With 85 putative species in 33 genera and over 400 described extinct species, the carnivoran superfamily Musteloidea is a prime candidate to investigate patterns of adaptive radiation using both extant‐ and fossil‐based macroevolutionary methods. The species diversity and equally impressive ecological and phenotypic diversity found across Musteloidea is often attributed to two adaptive radiations coinciding with two major climate events, the Eocene‐Oligocene transition and the Mid‐Miocene Climate Transition. Here, we compiled a novel time‐scaled phylogeny for 88% of extant musteloids and used it as a framework for testing the predictions of adaptive radiation hypotheses with respect to rates of lineage diversification and phenotypic evolution. Contrary to expectations, we found no evidence for rapid bursts of lineage diversification at the origin of Musteloidea, and further analyses of lineage diversification rates using molecular and fossil‐based methods did not find associations between rates of lineage diversification and the Eocene‐Oligocene transition or Mid‐Miocene Climate Transition as previously hypothesized. Rather, we found support for decoupled diversification dynamics driven by increased clade carrying capacity in the branches leading to a subclade of elongate mustelids. Supporting decoupled diversification dynamics between the subclade of elongate mustelids and the ancestral musteloid regime is our finding of increased rates of body length evolution, but not body mass evolution, within the decoupled mustelid subclade. The lack of correspondence in rates of body mass and length evolution suggest that phenotypic evolutionary rates under a single morphological metric, even one as influential as mass, may not capture the evolution of diversity in clades that exhibit elongate body shapes. The discordance in evolutionary rates between body length and body mass along with evidence of decoupled diversification dynamics suggests that body elongation might be an innovation for the exploitation of novel Mid‐Miocene resources, resulting in the radiation of some musteloids.
Albumin microvascular leakage in brains with diabetes mellitus

Their aim was to examine whether microvascular leakage of endogenous albumin, a representative marker for blood–brain barrier (BBB) damage, was induced in the periventricular area of diabetic db/db mice because periventricular white matter hyperintensity formation in magnetic resonance images was accelerating in elderly patients with diabetes mellitus. Using light and electron microscopes, and semi‐quantitative analysis techniques, immunoreactivity of endogenous albumin, indicating vascular permeability, was examined in the periventricular area and spinal cord of db/db mice and db/+m control mice. Greater immunoreactivity of albumin was observed in the vessel wall of the periventricular area of db/db mice than in controls. Additionally, weak immunoreactivity was observed in the spinal cord of both db/db mice and controls. The number of gold particles, indicating immunoreactivity of albumin, in the perivascular area of db/db mice was significantly higher than that of control mice, but there was no significant difference in the number of particles in the spinal cord between db/db mice and controls. These findings suggest that albumin microvascular leakage, or BBB breakdown, is induced in the periventricular area of diabetic mice. Microsc. Res. Tech. 79:833–837, 2016. © 2016 Wiley Periodicals, Inc.
Seasonal size spectra of transparent exopolymeric particles (TEP) in a coastal sea and comparison with those predicted using coagulation theory

: The abundance and size distribution of transparent exopolymeric particles (TEP) were monitored in the Kattegat (Denmark) during 1 yr. TEP number concentration ranged from 0.5 X 105 to 3.8 X 105 ml-' and the volume concentration between 3 and 310 ppm. TEP volume concentration peaked during the spring bloon~ and again during the summer period. The observed accun~ulation of TEP during summer is consistent with the recent observation that dissolved organic matter (DOM) concen- tration has a similar seasonal distribution and suggests that TEP are formed from DOM. The supposed mode of formation of TEP (coagulation of colloidal organic particles) was tested by companng the observed TEP size spectra with those predicted by means of a coagulation model. The model used was a steady-state version of a particle coagulation model extended to include interactions between TEP and non-TEP particles. The spectra generated by the model were fitted to the observed TEP size spectra. The spectra predicted from the model fitted the observations relatively well, suggesting that the model provides a good description of the hnetics of TEP coagulation and that coagulation of colloids is an important mode of TEP formation. The best fits of the simulated steady-state TEP spectra to the observed ones were used to estimate TEP turnover rates. Seasonal estimates of TEP turnover rates, calculated assuming a sticlung coefficient of 0.6 for TEP-TEP interactions and 0.3 for interactions between TEP and non-TEP particles, ranged between 0.1 and 0.9 d-l. TEP turnover rate appeared to be most sensitive to interactions between TEP and non-TEP particles. Relative TEP carbon fluxes were compared with histoncal primary production estimates and showed almost identical seasonal patterns. According to TEP concentration, turnover times and estlrnates of carbon content, TEP carbon accumu- lation may represent an important fraction of the primary production and, thus, TEP and their colloidal precursors may represent a significant pathway for dissolved organic carbon in the ocean.
Trajectory of MS disease course for men and women over three eras

Background: Heterogeneity in disease course exists within multiple sclerosis (MS) subtypes. Objective: The objective was to estimate disease course heterogeneity over three distinct onset periods (pre-1995, 1995–2004, and 2005–present) for men and women. Methods: Group-based trajectory model (GBTM) was used to estimate clusters of patients following stable or unstable disease progression trajectories based on the Expanded Disability Status Scale (EDSS). Inception cohorts were generated from the Montreal Neurological Institute MS Clinic registry. Stable trajectories were defined as an EDSS ⩽3.0 and change ⩽1 point over the study period. Annualized relapse rate (ARR) based on the first 5 years of disease was an explanatory variable. Results: Proportion of women classified as stable was 0% for pre-1995, 69.0% for 1995–2004, and 83.9% post-2005; for men, these proportions were 18.4%, 41.4%, and 53.8%, respectively. Men had lower percentage of stable disease than women in both post-1995 cohorts (chi-square p < 0.0001). ARR was associated with higher disability trajectories in both post-1995 cohort (odds ratios >1.0) but not in the pre-1995 cohort. Conclusion: Large proportions of patients remain stable at their initial disability level for at least 15 years. Higher ARR increases the odds of patients being in a higher disability trajectory in the latter cohorts.
Relationship Between Sensory Processing and Sleep in Typically Developing Children

OBJECTIVE. The relationship between sensory processing factors and the sleep habits and patterns of typically developing children ages 8–12 yr was investigated. METHOD. Forty‐five typically developing children and their parents or caregivers took part. Parents completed the Sensory Processing Measure‐Home Form, Children's Sleep Hygiene Scale, and Children's Sleep Habits Questionnaire, and the children completed the Children's Report of Sleep Patterns. Spearman &rgr; correlation and linear regression analyses were completed with the children's sleep habits and patterns as the dependent variables and the sensory processing factors as the independent variables. RESULTS. Sensory processing factors were significantly associated with the children's sleep habits and patterns, as reported by parents and children. Predictive relationships were established between the children's sensory processing factors and sleep habits and patterns. CONCLUSION. Occupational therapy practitioners should consider sensory processing factors when working with children who present with suspected sleep problems.
First‐in‐human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL‐17A and IL‐17F, in mild psoriasis

Aims To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)‐17A and IL‐17F, in subjects with mild plaque psoriasis. Methods Randomized, double‐blind, first‐in‐human study of bimekizumab in 39 subjects who received single‐dose intravenous bimekizumab (8–640 mg) or placebo (NCT02529956). Results Bimekizumab demonstrated dose‐proportional linear PK and was tolerated across the dose range assessed. No subject discontinued due to treatment‐emergent adverse events and no severe adverse events were reported. Bimekizumab demonstrated fast onset of clinically‐meaningful effects on skin of patients with mild psoriasis as early as Week 2. Maximal improvements (100% or near 100% reductions from baseline) in all measures of disease activity were observed between Weeks 8–12 in subjects receiving 160–640 mg bimekizumab. The duration of effect at doses ≥160 mg was evident up to Weeks 12–20 after a single intravenous dose, dependent on endpoint. Conclusions This is the first study to demonstrate the safety, tolerability and clinical efficacy of a dual IL‐17A and IL‐17F inhibitor, in subjects with mild psoriasis. Bimekizumab showed fast onset of clinically‐meaningful efficacy by Week 2, with a maximal or near‐maximal magnitude of response that was maintained up to study Weeks 12–20. These findings support the continued clinical development of bimekizumab for diseases mediated by both IL‐17A and IL‐17F, including psoriasis.
Phase II Conjugates of Urolithins Isolated from Human Urine and Potential Role of β-Glucuronidases in Their Disposition

In recent years, many xenobiotics derived from natural products have been shown to undergo extensive metabolism by gut microbiota. Ellagitannins, which are high molecular polyphenols, are metabolized to dibenzo[b,d]pyran-6-one derivatives—urolithins. These compounds, in contrast with their parental compounds, have good bioavailability and are found in plasma and urine at micromolar concentrations. In vivo studies conducted for ellagitannin-containing natural products indicate their beneficial health effects toward inflammation and cancer, which are associated with the formation of urolithins. However, the great majority of in vitro experiments that have revealed the molecular mechanisms responsible for the observed effects were conducted for urolithin aglycones. These studies are thus incongruent with the results of pharmacokinetic studies that clearly indicate that glucuronide conjugates are the dominant metabolites present in plasma, tissue, and urine. The aim of this study was to isolate and structurally characterize urolithin conjugates from the urine of a volunteer who ingested ellagitannin-rich natural products, and to evaluate the potential role of β-glucuronidase–triggered cleavage in urolithin disposition. Glucuronides of urolithin A, iso-urolithin A, and urolithin B were isolated and shown to be cleaved by the β-glucuronidases released by neutrophils from azurophilic granules upon N-formylmethionine-leucyl-phenylalanine stimulation as well as by Escherichia coli standard strains and clinical isolates from patients with urinary tract infections. These results justify the hypothesis that the selective activation of urolithin glucuronides by β-glucuronidase, which are present at high concentrations at inflammation and infection sites and in the microenvironments of solid tumors, could locally increase the concentration of bioactive urolithin aglycones.