Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics, metabolite profiling, safety, and tolerability of inhalation aerosol of 101BHG-D01, a novel, long-acting and selective muscarinic receptor antagonist, in healthy Chinese subjects

101BHG-D01 is a novel, long-acting, selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD). A single-site, randomized, double-blind, placebo-controlled and dose-escalation study of 101BHG-D01 inhalation aerosol was conducted to evaluate its pharmacokinetics, metabolite profiling, safety and tolerability following the single inhaled doses ranged from 20 to 900 μg in healthy Chinese subjects. After inhalation, 101BHG-D01 was absorbed rapidly into plasma with the time to maximum concentration about 5 min, and eliminated slowly with the terminal phase half-life about 30 h. The cumulative excretion rates of 101BHG-D01 in feces and urine were about 30% and 2%, respectively, which showed the study drug was mainly excreted in feces. The maximum drug concentration and area under the plasma concentration-time curve increased with dose escalation in the range of 20–600 μg, but their values increased out of proportion to the whole studied doses. The main metabolic pathways were loss of phenyl group and hydroxylation. No metabolite that presented at greater than 10 percent of total drug-related exposure was observed. 101BHG-D01 was safe and well tolerated after administration. The study results indicate that 101BHG-D01 is a good candidate for the treatment of COPD and enable further clinical development in subsequent studies in patients. Clinical Trial Registration: http://www.chinadrugtrials. org.cn; Identifier: CTR20192058.
Effect of dietary essential oil of oregano on performance parameters, gastrointestinal traits, blood lipid profile, and antioxidant capacity of laying hens during the pullet phase

Many benefits have been found in supplementing essential oils such as oregano oil (EOO) to poultry, including increased body weight gain, antioxidant activity, and better gastrointestinal morphology. However, few studies tested the influence of EOO supplementation on laying hens and reported conflicting results regarding its efficacy in improving their health and performance. Therefore, we aimed to explore the effects of dietary EOO on performance, gastrointestinal (GIT) traits, blood lipid, and antioxidant capacity in laying hens during the rearing phase. A total of 300-day-old Hy-line-Brown chicks were used, and treatment diets consisted of corn-soybean based either without (CON) or with EOO (Ecodiar®, 0.275 g/kg diet). Birds were randomized across treatments with five pens/treatment and 30-birds/pen. Pen weights and feed rejected were recorded every two weeks (1-17 weeks of age), to calculate daily feed intake (ADFI), body weight (BW), and daily weight gain (ADWG). At 11 and 14 weeks of age, blood samples were collected from 3 birds/pen and analyzed for blood lipids and antioxidant levels, and 5-birds/treatment were euthanized, and GIT traits were tested. Differences in measured parameters across weeks and between treatments were assessed using GLMM with Tukey’s Post hoc test applied to significant results in R 3.3. 1 (α set at 0.05). Body weights at weeks 3, 11, 13, and 17 were significantly higher in the EOO group compared to the CON group (all P ≤ 0.05), ADWG was significantly higher in EOO birds compared to CON birds at 9 and 13 weeks old (all P ≤ 0.05), while no significant differences in ADFI were observed between treatments across weeks of the trials. At both 11 and 17 weeks old, triglyceride levels were significantly lower, while high-density-lipoprotein levels were higher in EOO (all P ≤ 0.05). Malondialdehyde levels were lower in the EOO group versus CON (p=0.01), while EOO birds had higher glutathione levels (p=0.01) than CON. Finally, at 12 weeks old, the weight of the entire GIT and empty gizzard were higher in the EOO group versus CON (all P ≤ 0.05), while liver and spleen weights were not significantly different between groups. In conclusion, dietary oregano supplementation exerted promoting effects on the performance of Hy-Line Brown pullets.
Lower hypothalamus subunit volumes link with impaired long-term body weight gain after preterm birth

Introduction Preterm birth is associated with an increased risk for impaired body weight gain. While it is known that in prematurity several somatic and environmental factors (e.g., endocrine factors, nutrition) modulate short- and long-term body weight gain, the contribution of potentially impaired body weight control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in body weight control is altered after preterm birth, with these alterations being associated with aberrant body weight development into adulthood. Materials and methods We assessed 101 very preterm (i.e., <32 weeks of gestational age) and/or very low birth weight (i.e., <1500g; VP/VLBW) and 110 full-term born (FT) adults of the population-based Bavarian Longitudinal Study with T1-weighted MRI, deep learning-based hypothalamus subunit segmentation, and multiple body weight assessments from birth into adulthood. Results Volumes of the whole hypothalamus and hypothalamus subunits relevant for body weight control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and body weight trajectories (i.e., trajectory slopes and cluster/types such as long-term catch-up growth). Particularly, VP/VLBW subgroups, whose individuals showed catch-up growth and/or were small for gestational age, were mostly associated with volumes of distinct hypothalamus subunits such as lateral or infundibular/ventromedial hypothalamus. Conclusion Results demonstrate lower volumes of body weight control-related hypothalamus subunits after preterm birth that link with long-term body weight gain. Data suggest postnatal development of body weight -related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body weight trajectories into adulthood.
The elevated visceral adiposity index increases the risk of hyperuricemia in Chinese hypertensive patients: A cross-sectional study

Background Uncertainty still remained about the relationship between visceral adiposity index (VAI) and hyperuricemia. The aim of this study was to investigate whether VAI was an independent risk factor for hyperuricemia in hypertensive Chinese patients. Methods A cross-sectional study including 13176 hypertensive participants (6478 males) recruited from Wuyuan County, Jiangxi province, was conducted. All patients received anthropometric measurements, completed questionnaires and provided blood samples for biochemical testing. VAI was calculated by waist circumference, BMI, triglyceride and high-density lipoprotein cholesterol. Hyperuricemia was defined as serum uric acid ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Results Overall, the average level of uric acid was 7.8 ± 2.0 mg/dL in males and 6.34 ± 1.78 in females and prevalence of hyperuricemia was 61.4% and 51.30%, respectively. In multivariate logistic regression analysis, the risk of hyperuricemia increased 1.77 times and 1.88 times with the increase of ln VAI in males (OR:1.77, 95% CI: 1.62, 1.94) and females (OR:1.88, 95% CI: 1.73, 2.04). For males, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.34 (95% CI: 1.14, 1.57),1.82(95% CI: 1.54, 2.14) and 2.97 (95% CI: 2.48, 3.57). For females, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.48 (95% CI: 1.28, 1.72), 1.99 (95% CI: 1.71, 2.32) and 2.92 (95% CI: 2.50, 3.42). Conclusions This study found that VAI was an independent risk factor for hyperuricemia among hypertensive patients, which may provide some strategies for reducing the level of uric acid.
Spiders indicate delivery of an agri-environment scheme at multiple diversity levels

Agri-environment schemes (AES) are expected to counteract the negative impacts of intensive agriculture on biodiversity. These schemes were specifically designed to target farmland biodiversity and included, for instance, ecological focus areas (EFAs). In Switzerland, in order to qualify for direct payments, farmers must manage 7% or more of their land as biodiversity promotion areas (BPAs). BPAs encompass extensively managed and low intensity hay meadows, fallows (wildflower strips), traditional orchards with high-stem trees and hedgerows. Evaluation of AES delivery for biodiversity is of crucial importance but must be performed across several years and considering the various components of species diversity to avoid incomplete or wrong conclusions. From a complex study design comprising 478 fields in three regions and sampling over 7 years with four sampling times, spider assemblages of BPA habitats were compared to corresponding conventionally managed fields. A battery of investigations was performed including alpha- and beta-diversity analysis, multivariate dispersion, indicator species and species specificity to understand what BPAs deliver for spiders in the habitat scale and farming landscape. Results showed that alpha-diversity (average number of species) was usually higher in BPA habitats than in conventionally managed fields but the species composition (beta-diversity) had more power to perceive AES impact. Furthermore, the various environmental conditions of BPAs in the farming landscape led to highly diverse spider assemblages (multivariate dispersion) emphasizing that not only the agricultural management plays a role in determining species diversity but the environmental heterogeneity. Indicator (and rare) species were mostly found in woody BPAs (hedges and high-stem tree orchards) revealing the high importance of these BPA habitats for spider conservation. At regional scale, BPA hedges contributed most to the regional diversity of spiders in grassland and mixed regions while BPA meadows and wildflower strip BPAs were first delivering in the region of arable crops. Recommendations highlight the role of the woody habitats and of the environmental heterogeneity in the farming landscape as well as of regional planning to make AES effective.
Infiltration of LPAR5+ macrophages in osteosarcoma tumor microenvironment predicts better outcomes

Introduction Tumor microenvironment (TME) has been shown to be extensively involved in tumor development. However, the dynamic change of TME components and their effects are still unclear. Here, we attempted to identify TME-related genes that could help predict survival and may be potential therapeutic targets. Methods Data was collected from UCSC Xena and GEO database. ESTIMATE and CIBERSORT algorithms were applied to estimate the components and the proportions of TIICs in TME. We analyzed the gene expression differences of immune components and stromal components, respectively, and finally got the overlapped DEGs. Through protein-protein interaction (PPI) network and univariate Cox regression analysis based on shared DEGs, we screened out and validated the TME-related genes. Focusing on this gene, we analyzed the expression and prognostic value of this gene, and investigated its relationship with immune cells by correlation analysis, single cell analysis, immunohistochemistry and immunofluorescence analysis. Results Through a series analysis, we found that the proportion of immune and stromal components was an important prognostic factor, and screened out a key gene, LPAR5, which was highly correlated with prognosis and metastasis. And the expression of LPAR5 was positively correlated with immune cells, especially macrophages, indicating LPAR5+ macrophages played an important role in tumor microenvironment of osteosarcoma. Meanwhile, the genes in LPAR5 high expression group were enriched in immune-related activities and pathways, and differentially expressed genes between LPAR5+ macrophages and LPAR5- macrophages were enriched in the biological processes associated with phagocytosis and antigen presentation. What’ more, we found that LPAR5 was mainly expressed in TME, and high LPAR5 expression predicting a better prognosis. Conclusion We identified a TME-related gene, LPAR5, which is a promising indicator for TME remodeling in osteosarcoma. Particularly, LPAR5+ macrophages might have great potential to be a prognostic factor and therapeutic target for osteosarcoma.
Baseline emotional state influences on the response to animated short films: A randomized online experiment

Introduction Considering the relevance of the emotional state, it is necessary to understand how daily stimuli can modulate the emotions. Animated short films are common stimuli, but it is unknown how they can modulate the emotional state. The study aimed to evaluate: how participants’ emotional state changed after watching animated short films with positive or negative emotional valence in an online experiment; the relationship between participants’ baseline score on an Emotional Intensity Scale and their potential change in the main emotion after watching the films; and the association between the initial main emotion valence and the potential change in this emotion with participants’ sociodemographic information. Methods A sample of 2,269 participants recruited during COVID-19 pandemic were randomly assigned to either watch a negative or positive animated short film. Results The results showed that, after watching a film with negative valence, participants were in a more negative emotional state than at baseline and compared with those who watched the film with positive valence. Also, individuals who had a negative baseline emotion and maintained the same emotion after the film had presented higher baseline emotional state scores (more negative emotion) than those who changed their emotions. In addition, the individuals who kept the baseline emotion had an association with age, marital status, level of education and psychiatric disorders, use of medication, and emotional awareness, while the individuals who changed the baseline emotion had an association with age, gender, and following or not social distancing recommendations. Conclusion Baseline emotional state may influence the response to animated short films and sociodemographic characteristics are associated with the initial main emotion valence and its potential change in this emotion.
Transcriptome analysis of fat accumulation in 3T3-L1 adipocytes induced by chlorantraniliprole

Introduction Chlorantraniliprole is a diamide insecticide widely used in agriculture. Chlorantraniliprole has been previously found to increase the accumulation of triglycerides (fats) in adipocytes, however, the underlying molecular mechanism is unknown. The present study aimed to explore the molecular mechanisms of chlorantraniliprole-induced fat accumulation in 3T3-L1 adipocytes. Methods We measured the triglyceride content in chlorantraniliprole-treated 3T3-L1 adipocytes, and collected cell samples treated with chlorantraniliprole for 24 h and without any treatment for RNA sequencing. Results Compared with the control group, the content of triglyceride in the treatment group of chlorantraniliprole was significantly increased. The results of RNA sequencing (RNA-seq) showed that 284 differentially expressed genes (DEGs) were identified after treatment with chlorantraniliprole, involving 39 functional groups of gene ontology (GO) and 213 KEGG pathways. Moreover, these DEGs were significantly enriched in several key genes that regulate adipocyte differentiation and lipogenesis including Igf1, Rarres2, Nr1h3, and Psmb8. Discussion In general, these results suggest that chlorantraniliprole-induced lipogenesis is attributed to a whole-gene transcriptome response, which promotes further understanding of the potential mechanism of chlorantraniliprole-induced adipogenesis.
Iodine-125 brachytherapy treatment for newly diagnosed brain metastasis in non-small cell lung cancer: A biocentric analysis

Purpose The aim of the present study is to evaluate the safety and efficacy of iodine-125 brachytherapy for newly diagnosed brain metastasis in patients with non-small cell lung cancer (NSCLC). Materials and methods The study included 158 NSCLC patients diagnosed with brain metastasis from December 2003 to August 2017. Ninety-nine patients underwent external beam radiotherapy (EBRT group), and 59 patients received iodine-125 brachytherapy (125I group). In addition, the 6- and 12-month progression-free survival (PFS) rates and the 12- and 24-month overall survival (OS) rates were compared between the EBRT group and the 125I group. Median OS and PFS were analyzed using the Kaplan−Meier method with a log-rank test. Results The 6-month PFS rate was significantly higher in the 125I group (p = 0.002) than in the EBRT group, while no differences were found in the 12-month PFS rate (p = 0.184). Additionally, the 12- (p = 0.839) and 24-month (p = 0.284) OS rates were not significantly different between the two groups. No significant differences in median OS (p = 0.525) or PFS (p = 0.425) were found between the two groups. Conclusions Iodine-125 brachytherapy is an alternative therapy for patients unable to undergo surgical resection.
An acoustic study of vocal expression in two genres of Yoruba oral poetry

This pilot study proposes an acoustic study of the vocal expressions in Ìjálá and Ẹ̀sà, two genres of Yorùbá oral poetry. For this study, we conducted an experiment, involving the vocalization of an original poem in speech mode, Ìjálá and Èsá. The vocalizations were recorded and analyzed acoustically. The results of the study show that cepstral peak prominence (CPP), Hammarberg index and Energy of voiced sound below 500 Hz distinguish comparisons of Ẹ̀sà, Ìjálá and speech but are not as reliable as F0 height and vibrato. By comparing the pitch trajectories of the speech tones and poetic tunes, we show that poetry determines tone-to-tune mapping but can accommodate language when it is feasible. The results of our investigation are not only in line with the previous impressionistic observations about vocal expression in Yorùbá oral poetry but contribute with new findings. Notably, our investigation supports vocal tremor as the historical origin of vibrato in Ìjálá. As a result of this, we strongly recommend the instruments of phonetic science for the study of vocal expression in African oral poetry.
Development and application of an indirect ELISA to detect antibodies to Neospora caninum in cattle based on a chimeric protein rSRS2-SAG1-GRA7

Neospora caninum is an important apicomplexan parasite causing neosporosis in cattle. The disease is recognized as one of the most important cause of reproductive problems and abortion in cattle worldwide. In this context, we developed an indirect enzyme-linked immunosorbent assays (ELISA) with chimeric protein rSRS2-SAG1-GRA7 to diagnose antibodies to Neospora-infection. This indirect ELISA was compared to indirect fluorescent antibody test (IFAT) and western blotting (WB), and the sensitivity and specificity results of ELISA were calculated to be 86.7 and 96.1%, respectively. The overall coincidence rate was 92.6% using IFAT and WB. Additionally, 329 aborting dairy cattle serum samples were tested using this ELISA to evaluate the prevalence of N. caninum in Ningxia, China. The positive rate of N. caninum in these farms was from 19.05 to 57.89%, and the mean rate was 41.64% (±11.01%), indicating that infection with N. caninum may be one of the important causes of cattle abortion in this region. This established rSRS2-SAG1-GRA7 indirect ELISA is capable for detecting the antibodies against N. caninum, and it could be a useful screening tool for monitoring the epidemiology of neosporosis in cattle.
Fermentation quality and bacterial ecology of red clover dominated silage modulated by different management factors

Identification of bacterial communities in both the raw material and the subsequent silages provides new insights into understanding the silage fermentation process. The objective was to evaluate how different silage management factors affect silage preservation characteristics, the microbiome, and their correlations. A red clover dominated sward was used as the raw material and ensiled in pilot scale using a 3 × 4 design, with three management conditions including the level of compaction (loose and tight), and further, for the tightly compacted silages contamination with soil and faeces was conducted; and four different additive treatments with different modes of action: Control without additive (CONT), formic and propionic acid-based additive (FPA), homofermentative lactic acid bacteria inoculant (LAB) and salt-based additive (SALT). Samples of the raw material and subsequent silages were taken and routinely analysed, including DNA extraction and PCR amplification using universal primers. Tight compaction reduced slightly the extent of silage fermentation, but contamination with soil and faeces stimulated a non-desired type of fermentation with higher concentrations of ethanol, acetic acid and propionic acid and a higher pH. Use of LAB and SALT had only minimal effects on silage fermentation, but FPA clearly restricted fermentation and resulted in a better fermentation quality (lower pH, ammonia N and acetic acid concentration) of the silages compared to CONT. The FPA silages presented greater diversity of bacterial communities compared to the other silages. Proteobacteria were the most abundant in raw material, followed by Firmicutes, and major shifts happened in these communities during the silage fermentation process. Weissella was found in small amounts in the raw material but it dominated in the silages. The most abundant communities in the silages, such as Weissella, Lactobacillus and Pseudomonas, were correlated with several silage fermentation characteristics. Use of FPA improved fermentation quality of silages, but SALT and LAB differed from CONT to a smaller extent. All additives modified the bacterial profiles of grasses ensiled under different management conditions. The combination of parameters related to silage quality and bacterial communities provided a deeper understanding of the silage fermentation process and how they can be manipulated to obtain better feed quality.