Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Renal Impairment and Hemodialysis on the Pharmacokinetics and Safety of the Glecaprevir and Pibrentasvir Combination in Hepatitis C Virus-Negative Subjects

ABSTRACT Hepatitis C virus (HCV) infection is an independent risk factor for developing chronic renal impairment and end-stage renal disease. Limited treatment options are available for HCV genotype 2, 3, 5, and 6 infections in patients with an estimated glomerular filtration rate (eGFR) of <30 ml/min. Glecaprevir and pibrentasvir are active against all six major HCV genotypes, are primarily excreted in the bile, and have minimal renal elimination. Therefore, combined treatment with these direct-acting antivirals may be useful for patients with HCV infection and chronic kidney disease. A phase 1, multicenter, open-label study evaluated the effects of renal impairment on the pharmacokinetics and safety of glecaprevir-pibrentasvir. In substudy 1, 38 subjects with stage 2 to 5 chronic kidney disease who were not on dialysis or who had normal renal function received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir. In substudy 2, 8 subjects requiring hemodialysis received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir under dialysis and nondialysis conditions. Regression analyses demonstrated increased glecaprevir and pibrentasvir plasma exposures, as determined by the area under the curve, with decreasing renal function, up to 56% and 46%, respectively, in subjects with an eGFR of <15 ml/min/1.73 m2. In dialysis-dependent subjects, glecaprevir and pibrentasvir exposures were similar (≤18% difference) when study drugs were administered before hemodialysis or on a nondialysis day. Adverse events were mostly mild, with the most common being self-limited fatigue (3 subjects). The study findings support the clinical evaluation of glecaprevir-pibrentasvir without dose adjustment in HCV-infected subjects with renal impairment. (This study has been registered at ClinicalTrials.gov under registration number NCT02442258.)
Wear behavior of the Al (LM24)–garnet particulate composites under dry sliding conditions

Dry sliding wear behavior of LM24 cast alloy reinforced with garnet particulate composite against EN32 steel disc was investigated, using a pin-on-disc tribometer. Experiments were carried out with sliding velocity ranging from 1.0 to 3.0 m/s, different load conditions from 20 to 80 N, and with a constant sliding distance of 3000 m. Samples were prepared with different weight percentage of garnet in the alloy varying from 3% to 15% in a step of 3 wt% prepared by liquid metallurgical technique. Scanning electron microscopy was used to realize the distribution of reinforcement in the matrix material and mechanism of wear. Experiments showed that the 15% garnet composite exhibited lower wear rate at all applied loads. The wear resistance was better at low loads and mild to severe wear was exhibited when load/sliding velocity was increased.
Structure and dynamics of coupled viscous liquids

We perform Monte-Carlo simulations to analyse the structure and microscopic dynamics of a viscous Lennard-Jones liquid coupled to a quenched reference configuration of the same liquid. The coupling between the two replicas is introduced via a field ϵ conjugate to the overlap Q between the two particle configurations. This allows us to study the evolution of various static and dynamic correlation functions across the (ϵ, T) equilibrium phase diagram. As the temperature is decreased, we identify increasingly marked precursors of a first-order phase transition between a low-Q and a high-Q phase induced by the field ϵ. We show in particular that both static and dynamic susceptibilities have a maximum at a temperature-dependent value of the coupling field, which defines a ‘Widom line’. We also show that, in the high-overlap regime, diffusion and structural relaxation are strongly decoupled because single-particle motion mostly occurs via discrete hopping on the sites defined by the reference configuration. These results, obtained using conventional numerical tools, provide encouraging signs that an equilibrium phase transition exists in coupled viscous liquids, but also demonstrate that important numerical challenges must be overcome to obtain more conclusive numerical evidence.
Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine.

BACKGROUND The aim of this study was to assess the preventative effect of ketamine on the exaggerated postoperative pain observed in sufentanil-treated mice and its ability to improve the analgesic effectiveness of morphine during the postoperative period in an orthopaedic model of pain. METHODS In this study, we assessed the effects of ketamine on sufentanil enhancement of pain behaviour induced by fracture and the effects of ketamine on postoperative morphine-induced analgesia. Three tests were used to assess pain behaviour: von Frey filament application, hot-plate test, and a subjective pain scale. RESULTS When administered 1 day after surgery in mice treated with sufentanil on D0 (before surgery), morphine induced an analgesic effect as observed by the nociceptive threshold increase in saline- and ketamine-treated mice. Morphine was more effective in ketamine-treated (1 and 50 mg kg(-1)) mice. CONCLUSIONS Our results suggest that pre-emptive use of ketamine is useful in orthopaedic surgery in this mice model to diminish short- and long-term hyperalgesia, but also to improve morphine effectiveness leading to a better mobilization and more rapid rehabilitation.
Evaluating Driver Performance on Rural Two-Lane Horizontal Curved Roadways Using a Driving Simulator

Between 2005 and 2009, single-vehicle run-off-road (ROR) crashes on two-lane rural-roadway horizontal curves have resulted in an average of 4,748 fatalities per year. Driving while familiar with the roadway, inattentive, and in a hurry have been identified as factors that increase the likelihood of these crashes. The goal of the present study was to evaluate methods that elicit familiarity with the roadway, inattention, and driving in a hurry. Fourteen participants drove a simulated two-lane rural roadway. Familiarity was elicited by having participants drive the test route seven times. Two methods to elicit inattention were used: mental mathematics problems and noun classification. Two methods to elicit being in a hurry were used: with visual travel time feedback and without. The method to elicit familiarity with the roadway resulted in significant changes in behavior when compared to driving while unfamiliar. Results suggested that solving mental mathematics problems was more effective in producing driving behaviors associated with inattention than noun classification. Both methods to elicit being in a hurry were effective in producing noticeable changes in behavior when compared to driving while not under time pressure. The promise of using these elicitation methods in driving simulators to evaluate engineering countermeasures to ROR crashes on two-lane rural-roadway horizontal curves is discussed.
Association of perceived medical errors with resident distress and empathy: a prospective longitudinal study.

CONTEXT Medical errors are associated with feelings of distress in physicians, but little is known about the magnitude and direction of these associations. OBJECTIVE To assess the frequency of self-perceived medical errors among resident physicians and to determine the association of self-perceived medical errors with resident quality of life, burnout, depression, and empathy using validated metrics. DESIGN, SETTING, AND PARTICIPANTS Prospective longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic Rochester. Data were provided by 184 (84%) of 219 eligible residents. Participants began training in the 2003-2004, 2004-2005, and 2005-2006 academic years and completed surveys quarterly through May 2006. Surveys included self-assessment of medical errors and linear analog scale assessment of quality of life every 3 months, and the Maslach Burnout Inventory (depersonalization, emotional exhaustion, and personal accomplishment), Interpersonal Reactivity Index, and a validated depression screening tool every 6 months. MAIN OUTCOME MEASURES Frequency of self-perceived medical errors was recorded. Associations of an error with quality of life, burnout, empathy, and symptoms of depression were determined using generalized estimating equations for repeated measures. RESULTS Thirty-four percent of participants reported making at least 1 major medical error during the study period. Making a medical error in the previous 3 months was reported by a mean of 14.7% of participants at each quarter. Self-perceived medical errors were associated with a subsequent decrease in quality of life (P = .02) and worsened measures in all domains of burnout (P = .002 for each). Self-perceived errors were associated with an odds ratio of screening positive for depression at the subsequent time point of 3.29 (95% confidence interval, 1.90-5.64). In addition, increased burnout in all domains and reduced empathy were associated with increased odds of self-perceived error in the following 3 months (P=.001, P<.001, and P=.02 for depersonalization, emotional exhaustion, and lower personal accomplishment, respectively; P=.02 and P=.01 for emotive and cognitive empathy, respectively). CONCLUSIONS Self-perceived medical errors are common among internal medicine residents and are associated with substantial subsequent personal distress. Personal distress and decreased empathy are also associated with increased odds of future self-perceived errors, suggesting that perceived errors and distress may be related in a reciprocal cycle.
Hydrophobic Collapse of Trigger Factor Monomer in Solution

Trigger factor (TF) is a chaperone, found in bacterial cells and chloroplasts, that interacts with nascent polypeptide chains to suppress aggregation. While its crystal structure has been resolved, the solution structure and dynamics are largely unknown. We performed multiple molecular dynamics simulations on Trigger factor in solution, and show that its tertiary domains display collective motions hinged about inter-domain linkers with minimal or no loss in secondary structure. Moreover, we find that isolated TF typically adopts a collapsed state, with the formation of domain pairs. This collapse of TF in solution is induced by hydrophobic interactions and stabilised by hydrophilic contacts. To determine the nature of the domain interactions, we analysed the hydrophobicity of the domain surfaces by using the hydrophobic probe method of Acharya et al. [1], [2], as the standard hydrophobicity scales predictions are limited due to the complex environment. We find that the formation of domain pairs changes the hydrophobic map of TF, making the N-terminal and arm2 domain pair more hydrophilic and the head and arm1 domain pair more hydrophobic. These insights into the dynamics and interactions of the TF domains are important to eventually understand chaperone-substrate interactions and chaperone function.
TOWARDS OPTIMIZING ENTERTAINMENT IN COMPUTER GAMES

Mainly motivated by the current lack of a qualitative and quantitative entertainment formulation of computer games and the procedures to generate it, this article covers the following issues: It presents the features—extracted primarily from the opponent behavior—that make a predator/prey game appealing; provides the qualitative and quantitative means for measuring player entertainment in real time, and introduces a successful methodology for obtaining games of high satisfaction. This methodology is based on online (during play) learning opponents who demonstrate cooperative action. By testing the game against humans, we confirm our hypothesis that the proposed entertainment measure is consistent with the judgment of human players. As far as learning in real time against human players is concerned, results suggest that longer games are required for humans to notice some sort of change in their entertainment.
Investigating the impact of deploying commercial Bombus terrestris for crop pollination on pathogen dynamics in wild bumble bees

Summary The use of commercial bumble bees for crop pollination has been implicated in the decline of wild bumble bees through the spread of pathogens. This study investigates whether diseases from commercial bumble bees threaten native species in the UK. We sampled bumble bees from ten soft fruit farms: five that deploy commercial Bombus terrestris and five that do not. Each farm was visited monthly throughout the summer and workers of B. terrestris, B. pratorum, B. pascuorumand B. lapidarius were captured. The faeces of these bees were inspected for the gut microparasites Crithidia spp. , Nosema bombi and Apicystis bombi. Prevalence was defined as the proportion of individuals infected and abundance was defined as the number of pathogen cells per volume of bumble bee faeces. The prevalence of A. bombi and N. bombi was too low to analyse. The prevalence and abundance of Crithidia spp. was significantly different among bumble bee species. Overall, the prevalence of Crithidia spp. was initially lower on farms deploying commercial bumble bees, possibly due to a dilution effect caused by the high density of imported bees. Crithidia spp. prevalence in Bombus terrestris, however, rose sharply on commercial farms at the end of the season. One potential explanation is that commercial bumble bees contract the local pathogen, which is then rapidly transmitted among them due to the high bee density. Whilst our data provide no evidence of pathogen spillover to wild species, it would be premature to conclude with certainty that commercial colonies do not represent a disease risk to native bees in the UK and we urge further studies into this phenomenon.
Recent trends in Hard Gelatin capsule delivery System

INTRODUCTION The word ‘Capsule’ is derived from the Latin word ‘Capsula’ which mean small box or container. The gelatin capsule was invented early in the 19th century as a result of the need to mask the obnoxious taste of many medicinal substances such as oleoresin of copaiba, which is extremely nauseating when taken by mouth. The first patent was granted on 25th March 1834 for soft gelatin capsule to Mr. François Achille Barnabe Mothes, a French pharmacy student. Further development was done in soft gelatin capsule fill formulation and soft shell manufacturing. Hard gelatin capsule was invented by Jules Cesar Lehuby, a Parisian pharmacist who was granted patent on 20th October 1846. Earlier, the soft gelatin capsule was known as one piece capsule and hard gelatin as hard two piece capsule. [1] A capsule is a shell or container prepared from gelatin containing one or more medicinal and/or inert substances. Capsules are intended to be swallowed whole by the patient. In instances where patients (especially children) are unable to swallow capsules, the contents of the capsule can be removed and added (e.g., sprinkled) on soft food immediately before ingestion. In this case, capsules are used as a vehicle to deliver premeasured medicinal powder. Capsule dosage forms occupy more than 10% of the total dosage forms on the market. [2] Capsules account for about 20% of all prescriptions dispensed. [3] Advantages of capsule over tablets [4]  Fewer developmental problems in capsules, hence allow quicker submission of a new drug for clinical trials.  It is easier to vary the dose.  Less adjuncts are necessary than for tablets  Capsule manufacturing requires fewer steps than tablet manufacturing.  Easy to swallow hence improves patient compliance  Simple separation of two incompatible products (combination)  More possibilities for product identification (printing)  Drug with high dose and low compressibility can be incorporated in capsules Types of capsule 1. Soft gelatin capsule (SGC) 2. Hard gelatin capsule (HGC)
A Design of Broadband Circularly Polarized C-Shaped Slot Antenna With Sword-Shaped Radiator and Its Array for L/S-Band Applications

In this paper, a novel wideband circularly polarized (CP) slot antenna and its array are presented. The antenna element consists of a C-shaped slot and a 50-<inline-formula> <tex-math notation="LaTeX">$\Omega $ </tex-math></inline-formula> microstrip-fed port to achieve left-hand circular polarization. Both the impedance bandwidth (IBW) and the 3-dB axial ratio bandwidth (ARBW) are greatly broadened by off-center microstrip-fed sword-shaped structure. A <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> array prototype based on the proposed CP element is also designed. Sequential rotation microstrip-feeding structure is used to excite four antennas and to realize good symmetric unidirectional radiation. To verify this design, both the CP antenna element and <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> array are fabricated and measured. The measured results of the antenna element exhibit an IBW of 132% (0.85–<inline-formula> <tex-math notation="LaTeX">$4.15~GHz$ </tex-math></inline-formula>) and an ARBW of <inline-formula> <tex-math notation="LaTeX">$95.7{\%} (1.20-3.40$ </tex-math></inline-formula> GHz). The measured ARBW and IBW of the <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> antenna array are about 108.3% (1.10–<inline-formula> <tex-math notation="LaTeX">$3.70~GHz$ </tex-math></inline-formula>) and <inline-formula> <tex-math notation="LaTeX">$100{\%} (1.15-3.45$ </tex-math></inline-formula> GHz), respectively. And the measured peak gain of the antenna array reaches 13.4 dBic. The proposed antenna is very suitable for CP applications in L/S bands.
Normal gut microbiota modulates brain development and behavior

Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
Impact of urbanization on coastal wetland structure and function

Urbanization is a major cause of loss of coastal wetlands. Urbanization also exerts significant influences on the structure and function of coastal wetlands, mainly through modifying the hydrological and sedimentation regimes, and the dynamics of nutrients and chemical pollutants. Natural coastal wetlands are characterized by a hydrological regime comprising concentrated flow to estuarine and coastal areas during flood events, and diffused discharge into groundwater and waterways during the non-flood periods. Urbanization, through increasing the amount of impervious areas in the catchment, results in a replacement of this regime by concentrating rain run-off. Quality of run-off is also modified in urban areas, as loadings of sediment, nutrients and pollutants are increased in urban areas. While the effects of such modifications on the biota and the physical environment have been relatively well studied, there is to date little information on their impact at the ecosystem level. Methodological issues, such as a lack of sufficient replication at the whole-habitat level, the lack of suitable indices of urbanization and tools for assessing hydrological connectivity, have to be overcome to allow the effects of urbanization to be assessed at the ecosystem level. A functional model is presented to demonstrate the impact of urbanization on coastal wetland structure and function.
Automated Fault Diagnosis at Philips Medical Systems

While our machines get faster, better and cheaper every day the increase in complexity of these systems is huge. This is not different for the medical systems developed and serviced by Philips Medical Systems (PMS). Fault diagnosis is an essential key to keep these systems dependable. Currently, most fault diagnosis practices in industry are based on manual effort. An area that is not readily explored and exploited by industry, but could offer improvement, is automated fault diagnosis. Although, many useful mechanisms inside the PMS systems exist, so far, no research has been done on how to set up a diagnostic system. This work is a first exploration of the benefits that such a technique could have for the fault diagnosis of the Philips Cardio-Vascular X-Ray System. In particular, it defines the goals and qualities of a diagnostic approach in industry. Model-Based fault Diagnosis (MBD) is a reasoning technique for finding root causes of failures based upon a model. MBD suits the goals and desired attributes for a fault diagnosis approach at PMS best. A case study of a subsystem is used to examine what issues play a role when implementing a model-based approach to fault diagnosis. It is found that, at PMS, it is not possible to quantify the diagnostic accuracy of the current practice to fault diagnosis and MBD implementations. Consequently, it cannot be concluded that MBD improves fault diagnosis with respect to higher dependability of Philips Cardio-Vascular X-Ray Systems. However, by means of entropy it is shown that the accuracy of the model-based approach is expected to be higher than an approach in which experts define a mapping between symptoms and diagnoses. Further, it is shown that entropy is a valuable feedback mechanism to improve MBD implementations. keywords: Model-Based Diagnosis, Fault Diagnosis, Service
Hamiltonian approach to geodesic image matching

This paper presents a generalization to image matching of the Hamiltonian approach for planar curve matching developed in the context of group of diffeomorphisms. We propose an efficient framework to deal with discontinuous images in any dimension, for example 2D or 3D. In this context, we give the structure of the initial momentum (which happens to be decomposed in a smooth part and a singular part) thanks to a derivation lemma interesting in itself. The second part develops a Hamiltonian interpretation of the variational problem, derived from the optimal control theory point of view.