Miracle-dz/UniFAR-FTUs huggingface dataset:
Rutin and Its Combination With Inulin Attenuate Gut Dysbiosis, the Inflammatory Status and Endoplasmic Reticulum Stress in Paneth Cells of Obese Mice Induced by High-Fat Diet

Gut dysbiosis induced by high fat diet (HF) or obesity is a predisposing factor to develop diverse inflammatory diseases. Polyphenols and fibers, often eaten together, have been reported to have prebiotic actions, but their health promoting benefits still need to be further characterized and defined. This study attempted to understand how polyphenol rutin and polysaccharide inulin influence intestinal health in mouse model fed a HF (60 kcal%) diet. A total of 48 C57BL/6J mice were divided into four groups fed with a low fat (10% kcal%) control diet (LC), a high fat control diet (HC), a high-fat diet supplemented with rutin (HR), or a high-fat diet supplemented rutin and inulin (HRI) for 20 weeks. Rutin supplementation reduced the HF diet-induced increase of Firmicutes/Bacteroidetes (F/B) ratio, Deferribacteraceae population and plasma lipopolysaccharide (LPS) (p < 0.05); ameliorated inflammation as indicated by the decreased circulating inflammatory cytokines (p < 0.05) and the reduced expressions of intestinal inflammatory mediators (p < 0.05); and attenuated the endoplasmic reticulum (ER) stress in Paneth cells as indicated by the decreased expressions of the ER markers (p < 0.05). Compared to the rutin supplementation alone, the co-administration of rutin with inulin improved the utilization of rutin as indicated by its decreased excretion, suppressed a number of harmful bacteria including Deferribacteraceae and Desulfovibrionaceae (p < 0.05), and further reduced the expression of the key inflammatory cytokine TNF-α and increased the production of butyrate, despite the supplementation of inulin reversed the decrease of body weight induced by rutin supplementation due to an increased food intake. Taken together, our data demonstrated that rutin supplementation ameliorated the inflammatory status and ER stress in Paneth cells under a HF-induced obese state, and its co-administration with inulin further mitigated the inflammatory status, indicating the potential to combine polyphenol rutin and the polysaccharide inulin as a dietary strategy to ameliorate gut dysbiosis, to improve inflammatory status and thereby to reduce medical disorders associated with HF-induced obesity.
Overtime work a review of literature and initial empirical analysis

Overtime is normally defined as working hours that are done in addition to normal (legislated) working hours during a day or a week. In many countries it may be compensated by overtime premium pay, which can play a role in worker remuneration. Overtime working hours can have important benefits for worker compensation if a premium is paid for each overtime hour worked, but can pose health and well-being concerns for workers if they work too many hours. Working conditions in general, and overtime in particular, are crucially dependent of the prevailing institutional set-up at the national and supranational level. Furthermore, the behaviour of governments, employers and trade-union organisations is important for understanding a country’s working time regime, and in turn how they address overtime. This paper reviews some of the evidence, mainly from labour economics, industrial relations and sociology, to provide an inter-disciplinary overview on how overtime issues are addressed by different academic disciplines. It also examines the incidence of overtime work within the context of several distinct national employment regimes and industrial relations systems, which provides a useful framework to enhance our understanding of overtime in theory and in practice.
Genome-Wide Analysis of the NAC Transcription Factor Gene Family Reveals Differential Expression Patterns and Cold-Stress Responses in the Woody Plant Prunus mume

NAC transcription factors (TFs) participate in multiple biological processes, including biotic and abiotic stress responses, signal transduction and development. Cold stress can adversely impact plant growth and development, thereby limiting agricultural productivity. Prunus mume, an excellent horticultural crop, is widely cultivated in Asian countries. Its flower can tolerate freezing-stress in the early spring. To investigate the putative NAC genes responsible for cold-stress, we identified and analyzed 113 high-confidence PmNAC genes and characterized them by bioinformatics tools and expression profiles. These PmNACs were clustered into 14 sub-families and distributed on eight chromosomes and scaffolds, with the highest number located on chromosome 3. Duplicated events resulted in a large gene family; 15 and 8 pairs of PmNACs were the result of tandem and segmental duplicates, respectively. Moreover, three membrane-bound proteins (PmNAC59/66/73) and three miRNA-targeted genes (PmNAC40/41/83) were identified. Most PmNAC genes presented tissue-specific and time-specific expression patterns. Sixteen PmNACs (PmNAC11/19/20/23/41/48/58/74/75/76/78/79/85/86/103/111) exhibited down-regulation during flower bud opening and are, therefore, putative candidates for dormancy and cold-tolerance. Seventeen genes (PmNAC11/12/17/21/29/42/30/48/59/66/73/75/85/86/93/99/111) were highly expressed in stem during winter and are putative candidates for freezing resistance. The cold-stress response pattern of 15 putative PmNACs was observed under 4 °C at different treatment times. The expression of 10 genes (PmNAC11/20/23/40/42/48/57/60/66/86) was upregulated, while 5 genes (PmNAC59/61/82/85/107) were significantly inhibited. The putative candidates, thus identified, have the potential for breeding the cold-tolerant horticultural plants. This study increases our understanding of functions of the NAC gene family in cold tolerance, thereby potentially intensifying the molecular breeding programs of woody plants.
The age of secrecy and unfairness in recidivism prediction

In our current society, secret algorithms make important decisions about individuals. There has been substantial discussion about whether these algorithms are unfair to groups of individuals. While noble, this pursuit is complex and ultimately stagnating because there is no clear definition of fairness and competing definitions are largely incompatible. We argue that the focus on the question of fairness is misplaced, as these algorithms fail to meet a more important and yet readily obtainable goal: transparency. As a result, creators of secret algorithms can provide incomplete or misleading descriptions about how their models work, and various other kinds of errors can easily go unnoticed. By partially reverse engineering the COMPAS algorithm -- a recidivism-risk scoring algorithm used throughout the criminal justice system -- we show that it does not seem to depend linearly on the defendant's age, despite statements to the contrary by the algorithm's creator. Furthermore, by subtracting from COMPAS its (hypothesized) nonlinear age component, we show that COMPAS does not necessarily depend on race, contradicting ProPublica's analysis, which assumed linearity in age. In other words, faulty assumptions about a proprietary algorithm lead to faulty conclusions that go unchecked without careful reverse engineering. Were the algorithm transparent in the first place, this would likely not have occurred. The most important result in this work is that we find that there are many defendants with low risk score but long criminal histories, suggesting that data inconsistencies occur frequently in criminal justice databases. We argue that transparency satisfies a different notion of procedural fairness by providing both the defendants and the public with the opportunity to scrutinize the methodology and calculations behind risk scores for recidivism.
Grip Strength Moderates the Association between Anthropometric and Body Composition Indicators and Liver Fat in Youth with an Excess of Adiposity

Paediatric non-alcoholic fatty liver disease (NAFLD) is considered the most common early driver of chronic liver disease. The aim of this study was to examine whether grip strength moderates the association between anthropometric and body composition parameters and controlled attenuation parameter (CAP), an indicator of fat deposits in the liver, in children and adolescents with excess of adiposity. A total of 127 adolescents (67% girls) aged between 11 and 17, attending two public schools in Bogotá (Colombia), who had an axiological evaluation of obesity were included in this study. A grip strength test was assessed as an indicator of muscular strength, and cardiorespiratory fitness by maximal oxygen uptake was assessed using the 20 m shuttle-run test. Waist circumference (WC), waist-to-height ratio (WHtR), fat mass, and visceral adipose tissue (VAT) (cm3) were included as anthropometric and body composition measures. CAP was determined with a FibroScan® 502 Touch device (Echosens, Paris, France). The anthropometric and body composition parameters including WC, WHtR, fat mass, and VAT were positively associated with the CAP (range β = 0.423 to 0.580), slightly reduced after being adjusted for handgrip strength/weight. The Johnson-Neyman technique revealed a significant inverse relationship between WC, WHtR, VAT, and CAP when grip strength normalized by body mass was above but not equal to or below 0.475 (8.1% of the sample), 0.469 (8.9% of the sample), and 0.470 (8.5% of the sample), respectively. In conclusion, grip strength adjusted by body mass, has a moderating effect on the association between anthropometric and body composition parameters (including WC, WHtR, and VAT) and CAP in in children and adolescents with excess of adiposity, suggesting the importance of promoting muscular strength during paediatric population in order to prevent NAFLD.
A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions

Eosinophilic esophagitis (EoE), a Th2-type allergic immune disorder characterized by an eosinophil-rich esophageal immune infiltrate, is often associated with food impaction (FI) in pediatric patients but the molecular mechanisms underlying the development of this complication are not well understood. We aim to identify molecular pathways involved in the development of FI. Due to large variations in disease presentation, our analysis was further geared to find markers capable of distinguishing EoE patients that are prone to develop food impactions and thus expand an established medical algorithm for EoE by developing a secondary analysis that allows for the identification of patients with food impactions as a distinct patient population. To this end, mRNA patterns from esophageal biopsies of pediatric EoE patients presenting with and without food impactions were compared and machine learning techniques were employed to establish a diagnostic probability score to identify patients with food impactions (EoE+FI). Our analysis showed that EoE patients with food impaction were indistinguishable from other EoE patients based on their tissue eosinophil count, serum IgE levels, or the mRNA transcriptome-based p(EoE). Irrespectively, an additional analysis loop of the medical algorithm was able to separate EoE+FI patients and a composite FI-score was established that identified such patients with a sensitivity of 93% and a specificity of 100%. The esophageal mRNA pattern of EoE+FI patients was typified by lower expression levels of mast cell markers and Th2 associated transcripts, such as FCERIB, CPA3, CCL2, IL4, and IL5. Furthermore, lower expression levels of regulators of esophageal motility (NOS2 and HIF1A) were detected in EoE+FI. The EoE+FI -specific mRNA pattern indicates that impaired motility may be one underlying factor for the development of food impactions in pediatric patients. The availability of improved diagnostic tools such as a medical algorithm for EoE subpopulations will have a direct impact on clinical practice because such strategies can identify molecular inflammatory characteristics of individual EoE patients, which, in turn, will facilitate the development of individualized therapeutic approaches that target the relevant pathways affected in each patient.
Bias in heritability estimates from genomic restricted maximum likelihood methods under different genotyping strategies

We investigated the effects of different strategies for genotyping populations on variance components and heritabilities estimated with an animal model under restricted maximum likelihood (REML), genomic REML (GREML), and single-step GREML (ssGREML). A population with 10 generations was simulated. Animals from the last one, two or three generations were genotyped with 45,116 SNP evenly distributed on 27 chromosomes. Animals to be genotyped were chosen randomly or based on EBV. Each scenario was replicated five times. A single trait was simulated with three heritability levels (low, moderate, high). Phenotypes were simulated for only females to mimic dairy sheep and also for both sexes to mimic meat sheep. Variance component estimates from genomic data and phenotypes for one or two generations were more biased than from three generations. Estimates in the scenario without selection were the most accurate across heritability levels and methods. When selection was present in the simulations, the best option was to use genotypes of randomly selected animals. For selective genotyping, heritabilities from GREML were more biased compared to those estimated by ssGREML, because ssGREML was less affected by selective or limited genotyping.
Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors

Purpose: This first-in-human, open-label phase I study evaluated AMG 337, an oral, highly selective small-molecule inhibitor of MET in advanced solid tumors. Patients and Methods: Patients enrolled into dose-escalation cohorts received AMG 337 up to 400 mg once daily or up to 250 mg twice daily, following a modified 3+3+3 design. Dose expansion was conducted in MET-amplified patients at the maximum tolerated dose (MTD). Primary endpoints included assessment of adverse events (AEs), establishment of the MTD, and pharmacokinetics; clinical response was a secondary endpoint. Results: The safety analysis set included 111 patients who received ≥1 dose of AMG 337. Thirteen patients had ≥1 AE qualifying as dose-limiting toxicity. The MTD was determined to be 300 mg once daily; the MTD for twice-daily dosing was not reached. Most frequent treatment-related AEs were headache (63%) and nausea (31%). Grade ≥3 treatment-related AEs occurred in 23 patients (21%), most commonly headache (n = 6) and fatigue (n = 5). Maximum plasma concentration occurred at 3.0 hours following 300-mg once-daily dosing, indicating AMG 337 absorption soon after treatment. Objective response rate was 9.9% (11/111; 95% CI, 5.1%–17.0%) in all patients and 29.6% (8/27; 95% CI, 13.8%–50.2%) in MET-amplified patients; median (range) duration of response was 202 (51–1,430+) days in all patients and 197 (64–1,430+) days in MET-amplified patients. Conclusions: Oral AMG 337 was tolerated with manageable toxicities, with an MTD and recommended phase II dose of 300 mg once daily. The promising response rate observed in patients with heavily pretreated MET-amplified tumors warrants further investigation. See related commentary by Ma, p. 2375
Contribution of the Economic Crisis to the Risk Increase of Poor Mental Health in a Region of Spain

Previous research suggests that the economic crisis can affect mental health. The purpose of this study was to analyse the association of risk of poor mental health with various socioeconomic, demographic, health, quality of life, and social support variables; and to evaluate the contribution of socioeconomic variables most affected by the beginning of the economic crisis (employment situation and income) on the changes in the prevalence of the risk of poor mental health between 2005 and 2010. A study of prevalence evolution in adult population residents of the Valencian Community in the Spanish Mediterranean was conducted. We studied 5781 subjects in 2005 and 3479 in 2010. Logistic regression models have been adjusted to analyse the association between variables. A standardisation procedure was carried out to evaluate which part of the changes in overall prevalence could be attributed to variations in the population structure by age, sex, employment status, and income between the years under study. The prevalence of GHQ+ increased from 2005 to 2010, in both men and women. Several variables were closely associated with the risk of poor mental health (sex, age, country of birth, number of nonmental chronic diseases, social support, disability, cohabitation in couple, employment status, and income). The changes produced as a result of the onset of the economic crisis in income and unemployment (increase in low income and in unemployment rates) contributed to the increase of poor mental health risk. This could confirm the sensitivity of mental health to the economic deterioration caused by the crisis.
A modular software framework for compression of structured climate data

Through the introduction of next-generation models the climate sciences have experienced a breakthrough in high-resolution simulations. In the past, the bottleneck was the numerical complexity of the models, nowadays it is the required storage space for the model output. One way to tackle the data storage challenge is through data compression. In this article we introduce a modular framework for the compression of structured climate data. Our modular framework supports the creation of individual predictors, which can be customised and adjusted to the data at hand. We provide a framework for creating interfaces and customising components, which are building blocks of individualised compression modules that are optimised for particular applications. Furthermore, the framework provides additional features such as the execution of benchmarks and validity tests for sequential as well as parallel execution of compression algorithms.
Human-Initiative Variable Autonomy: An Experimental Analysis of the Interactions Between a Human Operator and a Remotely Operated Mobile Robot which also Possesses Autonomous Capabilities

This paper presents an experimental analysis of the Human-Robot Interaction (HRI) between human operators and a Human-Initiative (HI) variable-autonomy mobile robot during navigation tasks. In our HI system the human operator is able to switch the Level of Autonomy (LOA) on-the-ﬂy be-tween teleoperation (joystick control) and autonomous con-trol (robot navigates autonomously towards waypoints selected by the human). We present statistically-validated re-sults on: the preferred LOA of human operators; the amount of time spent in each LOA; the frequency of human-initiated LOA switches; and human perceptions of task difﬁculty. We also investigate the correlation between these variables; their correlation with performance in the primary task (navigation of the robot); and their correlation with performance in a secondary task, in which humans are required to perform mental rotations of 3D objects, while simultaneously trying to continue with the primary task of driving the robot.
Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma

Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), in combination with a pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Cediranib (CED), encapsulated in NPs will provide the medical field with new research on the possible ways to treat glioblastoma. Concomitant administration of BPD and CED NPs have the potential to induce dual photocytotoxic and cytostatic effects in U87 MG cells by (1) remotely triggering BPD through photodynamic therapy by irradiating laser at 690 nm and subsequent production of reactive oxygen species and (2) inhibiting cell proliferation by VEGFR interference and growth factor signaling mechanisms which may allow for longer progression free survival in patients and fewer systemic side effects. The specific aims of this research were to synthesize, characterize and assess cell viability and drug interactions for polyethylene-glycolated (PEGylated) polymeric based CED and BPD NPs which were less than 100 nm in size for enhanced permeation and retention effects. Synergistic effects were found using the co-administered therapies compared to the individual drugs. The major goal of this research was to investigate a new combination of photodynamic-chemotherapy drugs in nano-formulation for increased efficacy in glioblastoma treatment at reduced concentrations of therapeutics for enhanced drug delivery in vitro.
Structural Studies of the 3′,3′-cGAMP Riboswitch Induced by Cognate and Noncognate Ligands Using Molecular Dynamics Simulation

Riboswtich RNAs can control gene expression through the structural change induced by the corresponding small-molecule ligands. Molecular dynamics simulations and free energy calculations on the aptamer domain of the 3′,3′-cGAMP riboswitch in the ligand-free, cognate-bound and noncognate-bound states were performed to investigate the structural features of the 3′,3′-cGAMP riboswitch induced by the 3′,3′-cGAMP ligand and the specificity of ligand recognition. The results revealed that the aptamer of the 3′,3′-cGAMP riboswitch in the ligand-free state has a smaller binding pocket and a relatively compact structure versus that in the 3′,3′-cGAMP-bound state. The binding of the 3′,3′-cGAMP molecule to the 3′,3′-cGAMP riboswitch induces the rotation of P1 helix through the allosteric communication from the binding sites pocket containing the J1/2, J1/3 and J2/3 junction to the P1 helix. Simultaneously, these simulations also revealed that the preferential binding of the 3′,3′-cGAMP riboswitch to its cognate ligand, 3′,3′-cGAMP, over its noncognate ligand, c-di-GMP and c-di-AMP. The J1/2 junction in the 3′,3′-cGAMP riboswitch contributing to the specificity of ligand recognition have also been found.
Prognostic value of using neutrophil-lymphocyte ratio in patients with burn injury for the diagnosis of sepsis and bacteraemia.

OBJECTIVE At present time, despite the progress made in the treatment of burn injuries, mortality rate among seriously ill patients remains high. The main causes of fatal cases with the extensive deep burns are generalized infectious complications, the major of which is sepsis. According to the authors, from 25 to 85% of deceased in later periods of burn injuries die from sepsis. The frequency and severity of infectious complications in patients with burn injuries requires an accurate diagnosis of infection that will determine the tactics of therapeutic and surgical treatment of such patients (Di Lonardo A. et al., 1993). However, the clinical diagnosis of wound infection in patients with burn injuries is quite difficult. MATERIALS AND METHODS Clinical material makes 188 patients with burn injuries. The average age of patients ranged from 20 to 59 years. Men  98 (52.1%), women  90 (47.9%). The survey has been conducted from April 2014 to July 2016. RESULTS In our opinion, the strength of the NLR (neutrophil-lymphocyte ratio) is the possibility of implementing this parameter simply by using already available biomarkers (neutrophil count and lymphocyte count). Therefore, this ratio is easy to integrate in clinical practice and cost effective. CONCLUSION The application of NLR for the diagnosis of sepsis in patients with burn injuries is the option of choice, since its determination requires only the overall blood test.