Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term health-related quality-of-life and symptom response profiles with arformoterol in COPD: results from a 52-week trial

Background Symptom severity is the largest factor in determining subjective health in COPD. Symptoms (eg, chronic cough, dyspnea) are associated with decreased health-related quality of life (HRQoL). We evaluated the impact of arformoterol on HRQoL in COPD patients, measured by St George’s Respiratory Questionnaire (SGRQ). Post hoc growth mixture model (GMM) analysis examined symptom response profiles. Methods We examined data from a randomized, double-blind, parallel-group, 12-month safety trial of twice-daily nebulized arformoterol 15 µg (n=420) versus placebo (n=421). COPD severity was assessed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status. GMM analysis identified previously unknown patient subgroups and examined the heterogeneity in response to SGRQ Symptoms scores. Results SGRQ Total score improved by 4.24 points with arformoterol and 2.02 points with placebo (P=0.006). Significantly greater improvements occurred for arformoterol versus placebo in SGRQ Symptoms (6.34 vs 4.25, P=0.031) and Impacts (3.91 vs 0.97, P=0.001) scores, but not in Activity score (3.57 vs 1.75, P=0.057). GMM identified responders and nonresponders based on the SGRQ Symptoms score. End-of-study mean difference in SGRQ Symptoms scores between these latent classes was 20.7 points (P<0.001; 95% confidence interval: 17.6–23.9). Compared with nonresponders, responders were more likely current smokers (55.52% vs 44.02%, P=0.0021) and had more severe COPD (forced expiratory volume in 1 second [FEV1]: 1.16 vs 1.23 L, P=0.0419), more exacerbations (0.96 vs 0.69, P=0.0018), and worse mean SGRQ Total (59.81 vs 40.57, P<0.0001), Clinical COPD Questionnaire (3.29 vs 2.05, P<0.0001), and Modified Medical Research Council Dyspnea Scale (3.13 vs 2.75, P<0.0001) scores. Arformoterol-receiving responders exhibited significantly greater improvements in FEV1 (0.09 vs 0.008, P=0.03) and fewer hospitalizations (0.13 vs 0.24, P=0.02) than those receiving placebo. Conclusion In this study, arformoterol treatment significantly improved HRQoL reflected by SGRQ. For the analysis performed on these data, arformoterol may be particularly effective in improving lung function and reducing hospitalizations among patients who are unable to quit smoking or present with more severe symptoms.
Effect of filler loading on physical and flexural properties of rapeseed stem/PP composites

The objective of the study is to develop a new filler for the production of natural filler thermoplastic composites using the waste rapeseed stalks. The long-term water absorption and thickness swelling behaviors and flexural properties of rapeseed filled polypropylene (PP) composites were investigated. Three different contents of filler were tested: 30, 45, and 60 wt%. Results of long-term hygroscopic tests indicated that by the increase in filler content from 30% to 60%, water diffusion absorption and thickness swelling rate parameter increased. A swelling model developed by Shi and Gardner can be used to quantify the swelling rate. The increasing of filler content reduced the flexural strength of the rapeseed/PP composites significantly. In contrast to the flexural strength, the flexural modulus improved with increasing the filler content. The flexural properties of these composites were decreased after the water uptake, due to the effect of the water molecules.
Overview of the interactive task in BioCreative V

Fully automated text mining (TM) systems promote efficient literature searching, retrieval, and review but are not sufficient to produce ready-to-consume curated documents. These systems are not meant to replace biocurators, but instead to assist them in one or more literature curation steps. To do so, the user interface is an important aspect that needs to be considered for tool adoption. The BioCreative Interactive task (IAT) is a track designed for exploring user-system interactions, promoting development of useful TM tools, and providing a communication channel between the biocuration and the TM communities. In BioCreative V, the IAT track followed a format similar to previous interactive tracks, where the utility and usability of TM tools, as well as the generation of use cases, have been the focal points. The proposed curation tasks are user-centric and formally evaluated by biocurators. In BioCreative V IAT, seven TM systems and 43 biocurators participated. Two levels of user participation were offered to broaden curator involvement and obtain more feedback on usability aspects. The full level participation involved training on the system, curation of a set of documents with and without TM assistance, tracking of time-on-task, and completion of a user survey. The partial level participation was designed to focus on usability aspects of the interface and not the performance per se. In this case, biocurators navigated the system by performing pre-designed tasks and then were asked whether they were able to achieve the task and the level of difficulty in completing the task. In this manuscript, we describe the development of the interactive task, from planning to execution and discuss major findings for the systems tested. Database URL: http://www.biocreative. org
IRSp53 accumulates at the postsynaptic density under excitatory conditions

IRSp53 (BAIAP2) is an abundant protein at the postsynaptic density (PSD) that binds to major PSD scaffolds, PSD-95 and Shanks, as well as to F-actin. The distribution of IRSp53 at the PSD in cultured hippocampal neurons was examined under basal and excitatory conditions by immuno-electron microscopy. Under basal conditions, label for IRSp53 is concentrated at the PSD. Upon depolarization by application of a medium containing 90 mM K+, the intensity of IRSp53 label at the PSD increased by 36±7%. Application of NMDA (50 μM) yielded 53±1% increase in the intensity of IRSp53 label at the PSD compared to controls treated with APV, an NMDA antagonist. The accumulation of IRSp53 label upon application of high K+ or NMDA was prominent at the deeper region of the PSD (the PSD pallium, lying 40–120 nm from the postsynaptic plasma membrane). IRSp53 molecules that accumulate at the distal region of the PSD pallium under excitatory conditions are too far from the plasma membrane to fulfill the generally recognized role of the protein as an effector of membrane-bound small GTPases. Instead, these IRSp53 molecules may have a structural role organizing the Shank scaffold and/or linking the PSD to the actin cytoskeleton.
Spatial Separation of Parental Genomes in Preimplantation Mouse Embryos

We have used two different experimental approaches to demonstrate topological separation of parental genomes in preimplantation mouse embryos: mouse eggs fertilized with 5-bromodeoxyuridine (BrdU)-labeled sperm followed by detection of BrdU in early diploid embryos, and differential heterochromatin staining in mouse interspecific hybrid embryos. Separation of chromatin according to parental origin was preserved up to the four-cell embryo stage and then gradually disappeared. In F1 hybrid animals, genome separation was also observed in a proportion of somatic cells. Separate nuclear compartments during preimplantation development, when extreme chromatin remodelling occurs, and possibly in some differentiated cell types, may be associated with epigenetic reprogramming.
Can cerebral microbleeds cause an acute stroke syndrome?

G RE T2* MRI sequences are sensitive to tiny areas of previous bleeding (termed cerebral microbleeds [CMBs]) due to the paramagnetic effects of blood degradation products including oxyhemoglobin and hemosiderin. CMBs are common and may be a prognostic marker of recurrent intracerebral hemorrhage, including antithrombotic related hemorrhage. Studies suggest that the chronic accumulation of CMBs may have an effect on anatomically distributed cerebral functions including cognition. As microbleeds cause focal damage to the brain tissue, acutely developing microbleeds might be expected to cause focal symptoms. We report 2 cases of acute focal neurologic symptoms and clinical signs that in each case appeared to be due to a CMB.
Deep sequential model for review rating prediction

Sentiment Analysis of review data is becoming an important task to understand the needs and expectations of customers. The challenges that lie in review sentiment analysis is capturing the long term dependencies and intricacies to model the interrelationship between the sentences of the review. In this work, we address the problem of review sentiment analysis using deep sequential model viz. Long short term memory (LSTM) and Gated Recurrent Neural Network (GRNN). LSTM, a variant of RNN is used to process the sentences to a fixed length vector. GRNN is used to capture the interdependencies that exist between the sentences of a review. The combination of LSTM and GRNN shows good performance on Amazon Electronics dataset.
α2-Adrenoceptor-ir neurons’ density changes after single dose of clonidine and yohimbine administration in the hippocampus of male rat

ABSTRACT Objective: Despite the important role of α2-adrenoceptors in pain modulation processes, the impact of administration of α2-adrenoceptor agonist and antagonist on the density of hippocampal α2-adrenoceptor-immunoreactive neurons has not been investigated. Therefore, we aimed to determine the effect of single doses of clonidine and yohimbine on the density of α2-adrenoceptor-immunoreactive neurons in rat hippocampus. Materials and Methods: Adult male Wistar rats received a single dose of clonidine (0.7 mg/kg) alone or 5 min after intraperitoneal (1 mg/kg) and/or intracerebroventricular (5 µg/kg) injection of yohimbine. After histological processing, neurons with α2-adrenoceptor immunoreactivity were identified and counted through immunohistochemical analysis of hippocampal regions. Results: Clonidine slightly increased the number of α2-adrenoceptor-immunoreactive neurons in the hippocampal subregions compared with the normal saline group. Intraperitoneal injection of yohimbine followed by injection of clonidine significantly increased the number of α2-adrenoceptor-immunoreactive neurons in subregions cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3). Intracerebroventricular injection of yohimbine after injection of clonidine significantly reduced the number of α2-adrenoceptor-immunoreactive neurons in all hippocampal subregions. Conclusion: The present study demonstrates that intraperitoneal administration of α2-adrenoceptor agonist clonidine increases the density of α2-adrenoceptor-immunoreactive neurons in rat hippocampus, while intracerebroventricular injection of yohimbine decreases the density of these neurons.
Influence of Eimeria falciformis Infection on Gut Microbiota and Metabolic Pathways in Mice

ABSTRACT Coccidiosis, caused by different species of Eimeria parasites, is an economically important disease of poultry and livestock worldwide. Here we report previously unknown alterations in the gut microbes and metabolism of BALB/c mice infected with Eimeria falciformis. Specifically, we observed a significant shift in the abundance of cecal bacteria and disrupted metabolism in parasitized animals. The relative abundances of Lachnospiraceae bacterium NK4A136, Ruminiclostridium, Alistipes, and Lactobacillus declined in response to E. falciformis infection, whereas Escherichia, Shigella, Helicobacter, Klebsiella, and Bacteroides were increased. Carbohydrate and amino acid metabolites in the serum samples of infected mice were significantly altered compared to naïve controls. Levels of amino acids, including asparagine, histidine, l-cysteine, tryptophan, lysine, glycine, serine, alanine, proline, ornithine, methionine, and valine, decreased on day 7 postinfection before returning to baseline on day 14. In addition, increased levels of indolelactate and mannitol and a reduced amount of oxalic acid indicated impaired carbon metabolism upon parasitic infection. These data demonstrate that intestinal coccidial infection perturbs the microbiota and disrupts carbon and nitrogen metabolism.
Influence of nocturnal oxygen desaturation on circadian rhythm of testosterone secretion.

To investigate the influence of nocturnal oxygen desaturation on the circadian rhythm of testosterone secretion, polysomnography was performed on 2 consecutive nights in 24 male subjects who complained of loud snoring and/or obesity. During the first night, we collected blood samples every 4 h via a catheter and measured serum testosterone. We arbitrarily defined severe oxygen desaturation as that exceeding the baseline SaO2 by 4% during 80 min of total sleep time. The subjects were divided into 2 groups from the data of the second night; one was the severe desaturation group as mentioned above, and those who suffered less desaturation were classified as the free to mild oxygen desaturation group. We found that in the latter group peak testosterone levels appeared at 6 a.m. On the other hand, the severe desaturation group exhibited delayed peak testosterone levels, i.e. at 10 a.m. We calculated the ratio of the testosterone level at 10 a.m. to that at 6 a.m., and found a significant correlation between this ratio and total desaturation time (r = 0.446, p less than 0.05). These data suggest that severe oxygen desaturation may alter the circadian rhythm of testosterone secretion.
The nature and inheritance of an elongated secondary constriction on chromosome 9 of man.

An unusually long secondary constriction on chromosome 9 was shown by C-staining to involve duplication of heterochromatin in this region. The constriction stained darkly following the C-staining procedure but was unstained following the G-staining procedure. The heterochromatic constriction generally completed DNA replication earlier than the remainder of chromosome 9. The abnormal chromosome was detected in 17 individuals belonging to three generations of a family. There were twice as many carriers as noncarriers. Similar excesses of carriers were noted in two other pedigrees reported in the literature. Disturbed segregation of this abnormal chromosome 9 is suggested and is consistent with the increased centromeric heterochromatin present. No linkage to chromosome 9 was demonstrated, but Rh-linkage was discounted.
The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific

ABSTRACT The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17.5) and neonatal (D3) mouse offspring. By further comparing female versus male, lung versus liver, or fetal versus neonatal time point, our results demonstrate that CpG site-specific aberrant methylation patterns sex-dependently vary per organ and time point. Moreover, PSE reduces gene expression of Igf1r and Igf1, dependent on organ, sex, and offspring's age. Our results indicate that PSE may be a source of organ-specific rather than general systemic fetal programming. This is exemplified here by gene promoter methylation and mRNA levels of Igf1r and Igf1, together with a sex- and organ-specific naturally established correlation of both parameters that is affected by prenatal smoke exposure. Moreover, the comparison of fetuses with neonates suggests a CpG site-dependent reversibility/persistence of PSE-induced differential methylation patterns.
Effect of laser irradiation on few-layer graphene in air probed by Raman spectroscopy

The effect of laser irradiation on few-layer graphene in air was investigated by Raman spectroscopy. The irradiation results in an increase of D band intensity and a concomitant drop in 2D band intensity. Furthermore, both frequencies of G and 2D bands increase. For bilayer and trilayer graphenes, the shape of the 2D band is also changed after the irradiation. Namely, the high-frequency components decrease. From these results, it is suggested that the laser irradiation in air leads to the thermal oxidation with the hole doping and the change in the stacking sequence in the decomposed few-layer graphene with smaller size.
Perinatal expression of the Lewis and secretor blood group systems

Studies on expression at birth and on maturation of the secretor and Lewis blood group systems, as manifest on red cells and in saliva, have been carried out on a series of infants using three Lewis reagents: anti-Lea,-Leb and -Lex.Among adults, 20% are Lewis red cell type Le(a+b+−x+) and 70% are Le(a−b+x+); both types are essentially absent at birth. A third type Le(a−b−x−) is found in both 10% of adults and in 10% of infants: 90% of newborn infants, however, have the unique type Le(a−b−x−+). Infants of the latter type undergo a rapid maturation during the first week of life of the adult Le(a+b−x+) type. Then, if they are salivary non secretors of ABH, they remain that type throughout life. Whereas those who are secretors evolve during the ensuing four months to Le(a+b+x+) which is also a type practically unique to infancy; finally, by two years of age, they evolve to the most common adult type, Le(a−b+x+). Salivary phenotypic expression of the genes involved in the above red cell types is found in soluble form but the state of development at birth is more advanced than on the red cell and the subsequent maturation is more rapid. Prematures show a relatively delayed maturation in the expression of these genes. Thus, unlike other blood group systems, the Lewis system is unique in infancy; it shows differential tissue expressivity and, with growth and development, undergoes a systematic pattern of distinct qualitative changes.The biological significance of the phenotypic expression of this blood group system during fetal life and of its well organized maturation process during early infancy remains obscure.
Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR‐defective cells

Nucleolytic processing by nucleases can be a relevant mechanism to allow repair/restart of stalled replication forks. However, nuclease action needs to be controlled to prevent overprocessing of damaged replication forks that can be detrimental to genome stability. The checkpoint protein Rad9/53BP1 is known to limit nucleolytic degradation (resection) of DNA double‐strand breaks (DSBs) in both yeast and mammals. Here, we show that loss of the inhibition that Rad9 exerts on resection exacerbates the sensitivity to replication stress of Mec1/ATR‐defective yeast cells by exposing stalled replication forks to Dna2‐dependent degradation. This Rad9 protective function is independent of checkpoint activation and relies mainly on Rad9‐Dpb11 interaction. We propose that Rad9/53BP1 supports cell viability by protecting stalled replication forks from extensive resection when the intra‐S checkpoint is not fully functional.
Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma

Purpose: Neuroblastoma displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. Experimental Design: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 neuroblastoma patients. Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of single-nucleotide variants (SNV) and copy number alterations, with 41% and 93% of all detected alterations common to the primary neuroblastoma and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate time points during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2. Conclusions: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating toward tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies. Clin Cancer Res; 24(4); 939–49. ©2017 AACR.
Solubility and Ingrowth Behaviour of Degradable and Figuline Calcium Alkaline Phosphate Cements

The thrust of the investigations presented here is to point out the degradation behaviour in vitro and the ingrowth behaviour in vivo of four different calcium alkaline phosphate cements. Two of the figuline and mouldable composites consist of the crystalline phase Ca2KNa(PO4)2 and two of the crystalline phase Ca10[K/Na](PO4)2 each containing 2wt% medium gel strength porcine gelatin. Furthermore Α-TCP was added to both Ca10[K/Na](PO4)2 cements as a hardening supporting reactant. The testing material groups differ in small amorphous portions containing either silica phosphate (GB9), magnesium potassium phosphate (GB14) or diphosphates (401545 and 401545(70)). The respective composites show a monomodal particle size distribution (d50~7µm; span~4) and an average total porosity around 28vol%. For the solubility studies cylindrical samples (d=6mm; h=12mm) were stored in a 0.1mol TRIS buffer solution and incubated at 37°C for maximum 50 weeks. The storage solution was analysed and renewed every week. The results are plotted cumulative. For the in vivo studies critical size defects were dissected to mandibles in a sheep model in which a 1cm3 area of the bottom of the mandibles was surgically resected and replaced with the figuline cements whereas the mouldability allows the reconstruction of the original outer contour without draining off even when replacing upside down.