Miracle-dz/UniFAR-FTUs huggingface dataset:
Morally Injurious Experiences and Emotions of Health Care Professionals During the COVID-19 Pandemic Before Vaccine Availability

Key Points Question How did health care workers experience moral injury during the COVID-19 pandemic before the availability of vaccines? Findings In this qualitative study of 1344 health care professionals in 2020, respondents reported significant changes in their personal and professional lives during the course of the pandemic. Common themes were feeling isolated from non–health care professionals, alienated from patients, and betrayed by coworkers, administrators, and the public. Meaning Moral injury can result from chronic stressors in morally injurious environments; leadership must identify and address these stressors to effectively support health care professionals as COVID-19 continues to strain staff’s physical, mental, and emotional resources.
IFNAR1 and IFNAR2 play distinct roles in initiating type I interferon–induced JAK-STAT signaling and activating STATs

Description The earliest intracellular signaling events induced by type I interferon receptor subunit activation are clarified. Refining the mechanism of IFNAR signaling Type I interferons form a complex with the receptor subunits IFNAR1 and IFNAR2, which stimulates cross-activation of the tyrosine kinases associated with the receptor subunits, TYK2 and JAK1. This leads to tyrosine phosphorylation of the IFNARs and of the STAT proteins that mediate transcriptional responses. Shemesh et al. used forms of the IFNAR subunits with various deletions and point mutations in the intracellular domains to elucidate the molecular basis of STAT activation downstream of IFNAR in human cells. Although STAT activation depended on the association of TYK2 with IFNAR1, it required STAT binding only to IFNAR2. Tyrosine phosphorylation of IFNAR2 enhanced signaling, possibly by promoting the dissociation of activated STATs from IFNAR2. These findings show that IFNAR1-associated TYK2 initiates STAT signaling downstream of IFNAR, but IFNAR2 is the platform for STAT activation. Type I interferons bind to cell surface receptors composed of the subunits IFNAR1 and IFNAR2, the intracellular domains (ICDs) of which are associated with the kinases TYK2 and JAK1, respectively. Ligand binding results in the cross-phosphorylation of TYK2 and JAK1, which then phosphorylate tyrosine residues in the ICDs of the receptor subunits and members of the STAT family of transcription factors. The phosphorylated STATs migrate to the nucleus and drive transcription. We analyzed receptor mutants in knockout cells to study the functional importance of various regions of the receptor ICDs. For IFNAR1, only the TYK2 binding site in the ICD was required for signaling. In contrast, successive truncations of the ICD of IFNAR2 proportionally decreased constitutive STAT binding, STAT phosphorylation, and target gene activation. These findings fit a model in which nonsuccessive stretches along the ICD interact with STATs. Tyrosine residues in the IFNAR1 ICD were not required for signaling, and single tyrosine mutations in the IFNAR2 ICD did not affect signal activation. However, simultaneous mutation of all the tyrosine residues in IFNAR2-ICD reduced STAT phosphorylation, STAT-mediated transcriptional activation, and antiviral activity but not constitutive STAT2 binding. We suggest that tyrosine phosphorylation on IFNAR2-ICD drives the dissociation of phosphorylated STATs, thus maintaining high signaling flux.
Serotonin 2C Antagonism in the Lateral Orbitofrontal Cortex Ameliorates Cue-Enhanced Risk Preference and Restores Sensitivity to Reinforcer Devaluation in Male Rats

Abstract Previous research has indicated that reward-paired cues can enhance disadvantageous risky choice in both humans and rodents. Systemic administration of a serotonin 2C receptor antagonist can attenuate this cue-induced risk preference in rats. However, the neurocognitive mechanisms mediating this effect are currently unknown. We therefore assessed whether the serotonin 2C receptor antagonist RS 102221 is able to attenuate cue-enhanced risk preference via its actions in the lateral orbitofrontal cortex (lOFC) or prelimbic (PrL) area of the medial prefrontal cortex (mPFC). A total of 32 male Long–Evans rats were trained on the cued version of the rat gambling task (rGT), a rodent analog of the human Iowa gambling task, and bilateral guide cannulae were implanted into the lOFC or PrL. Intra-lOFC infusions of the 5-HT2C antagonist RS 102221 reduced risky choice in animals that showed a preference for the risky options of the rGT at baseline. This effect was not observed in optimal decision-makers, nor those that received infusions targeting the PrL. Given prior data showing that 5-HT2C antagonists also improve reversal learning through the same neural locus, we hypothesized that reward-concurrent cues may amplify risky decision-making through cognitive inflexibility. We therefore devalued the sugar pellet rewards used in the cued rGT (crGT) through satiation and observed that decision-making patterns did not shift unless animals also received intra-lOFC RS 102221. Collectively, these data suggest that the lOFC is one critical site through which reward-concurrent cues promote risky choice patterns that are insensitive to reinforcer devaluation, and that 5-HT2C antagonism may optimize choice by facilitating exploration.
Declines in alcohol consumption in Australia: some challenges to the theory of collectivity.

BACKGROUND AND AIMS There is significant debate about whether or not changes in per-capita alcohol consumption occur collectively across the entire distribution of drinking. This study used data from a decade of declining drinking in Australia to test the collectivity of drinking trends. DESIGN Repeated cross-sectional surveys (2010, 2013, 2016, 2019), analysed with quantile regression techniques assessing trends in drinking for 20 quantile groups. SETTING Australia PARTICIPANTS: A general population sample (total n= 85,891; males =39,182, females = 46,709) aged 14 and over. MEASUREMENTS Past year volume of alcohol consumed was measured using standard graduated frequency survey questions. Models were stratified by sex and age group. FINDINGS Across the whole population, alcohol consumption had declined in all percentile groups, with the largest proportional declines evident for light and moderate drinkers (e.g. drinkers at in 25th percentile declined by 33%; 95% confidence interval (CI) 22%-42% per wave). Broadly collective declines were also found for younger men and women with significant declines in every percentile group, but older groups showed some evidence of polarisation. For example, women aged 45-64 significantly increased their consumption (3% per wave, 95%CI: 0.3%-6%), while consumption for those for the 25th percentile fell significantly (17%, 95%CI: 4%-28%). CONCLUSIONS The declines in Australian drinking since 2010 have included important deviations from the collectivity predicted by Skog's influential theory of collectivity of drinking, with markedly different patterns evident across different demographic groups.
Sport supplements and the athlete’s gut: a review.

Vigorous or prolonged exercise poses a challenge to gastrointestinal system functioning and is associated with digestive symptoms. This narrative review addresses 1) the potential of dietary supplements to enhance gut function and reduce exercise-associated gastrointestinal symptoms and 2) strategies for reducing gastrointestinal-related side effects resulting from popular sports supplements. Several supplements, including probiotics, glutamine, and bovine colostrum, have been shown to reduce markers of gastrointestinal damage and permeability with exercise. Yet, the clinical ramifications of these findings are uncertain, as improvements in symptoms have not been consistently observed. Among these supplements, probiotics modestly reduced exercise-associated gastrointestinal symptoms in a few studies, suggesting they are the most evidenced-based choice for athletes looking to manage such symptoms through supplementation. Carbohydrate, caffeine, and sodium bicarbonate are evidence-based supplements that can trigger gastrointestinal symptoms. Using glucose-fructose mixtures is beneficial when carbohydrate ingestion is high (>50 g/h) during exercise, and undertaking multiple gut training sessions prior to competition may also be helpful. Approaches for preventing caffeine-induced gastrointestinal disturbances include using low-to-moderate doses (<500 mg) and avoiding/minimizing exacerbating factors (stress, anxiety, other stimulants, fasting). Adverse gastrointestinal effects of sodium bicarbonate can be avoided by using enteric-coated formulations, low doses (0.2 g/kg), or multi-day loading protocols.
Minor hallucinations in isolated rapid eye movement sleep behavior disorder indicative of early phenoconversion: A preliminary study

Minor hallucinations (MH) are psychotic symptoms that can occur anywhere between prodromal to early Parkinson's disease and after onset of motor problems. MH include visual illusions, presence hallucinations, and passage hallucinations. Isolated rapid eye movement sleep behavior disorder (RBD) is a harbinger of neurodegenerative diseases. We conducted a retrospective cohort study to investigate the clinical characteristics of isolated RBD with MH and the risk of phenoconversion.
Fault-tolerant drive-by-wire systems

The article begins with a review of electronic driver assisting systems such as ABS, traction control, electronic stability control, and brake assistant. We then review drive-by-wire systems with and without mechanical backup. Drive-by-wire systems consist of an operating unit with an electrical output, haptic feedback to the driver, bus systems, microcomputers, power electronics, and electrical actuators. For their design safety, integrity methods such as reliability, fault tree and hazard analysis, and risk classification are required. Different fault-tolerance principles with various forms of redundancy are considered, resulting in fail-operational, fail-silent, and fail-safe systems. Fault-detection methods are discussed for use in low-cost components, followed by a review of principles for fault-tolerant design of sensors, actuators, and communication. We evaluate these methods and principles and show how they can be applied to low-cost automotive components and drive-by-wire systems. A brake-by-wire system with electronic pedal and electric brakes is then considered in more detail, showing the design of the components and the overall architecture. Finally, we present conclusions and an outlook for further development of drive-by-wire systems.
Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children

Background: The World Health Organization (WHO) 2019 antiretroviral treatment guidelines recommend use of optimal treatment regimens in all populations. Dolutegravir-based regimens are the preferred first-line and second-line treatment in infants and children with HIV 4 weeks of age and above. There is an urgent need for optimal pediatric formulations of dolutegravir as single-entity (SE) and fixed-dose combination (FDC) to ensure correct dosing and adherence for swallowing and palatability. This article outlines the chronology of dolutegravir pediatric formulation development as granules and conventional and dispersible tablets in a total of 5 pharmacokinetic studies evaluating the relative bioavailability of dolutegravir SE and FDC formulations in healthy adults. Methods: The relative bioavailability studies were 2-part, Phase I, open-label, randomized studies in healthy adults. Dolutegravir SE study compared conventional dolutegravir 50 and 25 mg with equivalent conventional 10-mg and dispersible 5-mg tablets, respectively. Subsequently, dolutegravir FDC study compared adult FDC of abacavir/dolutegravir/lamivudine and adult FDC of dolutegravir/lamivudine with their respective pediatric FDC formulations, taken as dispersion immediately or swallowed whole. Results: As observed in previous studies, dolutegravir administered as dispersion (granules/dispersible tablets) showed relatively higher bioavailability compared with conventional tablets. The bioavailability of dolutegravir dispersible tablets (both SE and FDC) was approximately 1.6-fold higher when compared with conventional tablets. In addition, the bioavailability of abacavir/lamivudine was not impacted by dispersible formulation. Conclusions: These studies demonstrate the successful development of pediatric dolutegravir-containing formulations as SE and FDC that permit pediatric dosing in line with WHO recommendations.
Comparison of EMI performance of PWM and resonant power converters

When utilized in a power supply, hard switching and soft switching converters have different noise performances. Depending on their power, frequency range, and application, zero-current switching (ZCS) and zero-voltage switching (ZVS) techniques can significantly lower the noise. This work characterizes and compares the conducted and radiated electromagnetic interference (EMI) performance of hard and soft switching, including both ZVS and ZCS converters. An experimentally tested topology selection procedure for EMI minimization in power supplies is presented. The effects of increasing the switching and resonant frequencies and of utilization of snubbers and integrated control circuits for the purpose of EMI reduction are studied and demonstrated. <<ETX>>
Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab

Background and Objectives To determine the frequency of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) receiving rituximab (RTX). Methods This prospective observational study included all consecutive PwMS receiving RTX at the university hospital of Marseille, France, between 2015 and 2020. Patient visits occurred at least every 6 months. Results We included 188 patients (151 with relapsing-remitting MS; the mean age was 43.4 years [SD 12.9], median disease duration 10 years [range 0–36], median Expanded Disability Status Scale 5 [range 0–8], median follow-up 3.5 years [range 1–5.8], and median number of RTX infusions 5 [range 1–9]). Overall, 317 symptomatic infections and 13 severe infections occurred in 133 of 188 (70.7%) and 11 of 188 (5.9%) patients, respectively. After 4 years, 24.4% of patients (95% CI 18.0–33.1) were free of any infection and 92.0% (95% CI 87.1–97.1) had not experienced a severe infection. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 32 of 188 (17%) patients. After RTX, IgG level was <7, <6, <4 and <2 g/L for 83 (44%), 44 (23.4%), 8 (4.2%) and 1 (0.53%) patients, respectively. The risk of infection was associated with reduced IgG levels (multivariate Cox proportional hazards hazard ratio [HR] = 0.86, 95% CI 0.75–0.98, p = 0.03). The risk of reduced IgG level <6 g/L increased with age (HR = 1.36, 95% CI 1.05–1.75, p = 0.01). Discussion In PwMS receiving RTX, reduced IgG level was frequent and interacted with the risk of infection.
Efficient Electrically Small Antenna Facilitated by a

An electrically small electric-based metamaterial-in- spired antenna system that is designed for narrow bandwidth op- eration near 300 MHz is presented. It consists of a lumped ele- ment-based resonant parasitic element that is introduced into the very near field of a coax-fed monopole. It is demonstrated that sev- eral idealized lossless versions are capable of achieving a near per- fect impedance match to the source and, thus, have overall effi- ciencies near 100% without an external matching circuit. It is es- tablished that the entire system makes effective use of the radian- sphere volume it occupies. The overall efficiencies are shown to re- main high even when conductor losses are introduced. Potential frequency agility is also demonstrated.
Congenital transmission of Mexican strains of Trypanosoma cruzi TcIa: interaction between parasite and human placental explants

Abstract Abstract Congenital transmission of Chagas disease plays an important role in endemic countries because it is not a diagnosis that is encountered frequently in prenatal care. Due to limited information regarding congenital transmission of Trypanosoma cruzi in Mexico, the present study aimed to investigate protozoan infectivity and modulation of immune responses in human placental explants infected with T. cruzi Ia Mexican strains. The Inc-5 strain showed increased infectivity and modulated IL-1β, IL-10 and TLR-4, decreasing their expression after 24 h of infection. Both strains (Inc-5 and Ninoa) stimulated the production of TNF-α and decreased IL-6 levels 96 h after infection. An important detachment of the syncytiotrophoblast caused by infection with T. cruzi was observed after 24 h of infection. In this study, ex vivo infection of human placental villi was performed to better understand interactions involving parasitic T. cruzi and human placental tissue. It was concluded that the strains of TcIa present parasitism in placental tissue, modulation of the innate immune system of the placenta, and cause intense detachment of the syncytiotrophoblast, a fact that may be more associated with abortion and premature birth events than the congenital transmission itself, justifying the low rate of this transmission mechanism by this genotype.
A Novel Trehalose Synthase for the Production of Trehalose and Trehalulose

Trehalose is a rare sugar of high importance in biological research, with its property to stabilize cell membrane and proteins and protect the organism from drought. It is instrumental in the cryopreservation of human cells, e.g., sperm and blood stem cells. ABSTRACT A novel putative trehalose synthase gene (treM) was identified from an extreme temperature thermal spring. The gene was expressed in Escherichia coli followed by purification of the protein (TreM). TreM exhibited the pH optima of 7.0 for trehalose and trehalulose production, although it was functional and stable in the pH range of 5.0 to 8.0. Temperature activity profiling revealed that TreM can catalyze trehalose biosynthesis in a wide range of temperatures, from 5°C to 80°C. The optimum activity for trehalose and trehalulose biosynthesis was observed at 45°C and 50°C, respectively. A catalytic reaction performed at the low temperature of 5°C yielded trehalose with significantly reduced by-product (glucose) production in the reaction. TreM displayed remarkable thermal stability at optimum temperatures, with only about 20% loss in the activity after heat (50°C) exposure for 24 h. The maximum bioconversion yield of 74% trehalose (at 5°C) and 90% trehalulose (at 50°C) was obtained from 100 mM maltose and 70 mM sucrose, respectively. TreM was demonstrated to catalyze trehalulose biosynthesis utilizing the low-cost feedstock jaggery, cane molasses, muscovado, and table sugar. IMPORTANCE Trehalose is a rare sugar of high importance in biological research, with its property to stabilize cell membrane and proteins and protect the organism from drought. It is instrumental in the cryopreservation of human cells, e.g., sperm and blood stem cells. It is also very useful in the food industry, especially in the preparation of frozen food products. Trehalose synthase is a glycosyl hydrolase 13 (GH13) family enzyme that has been reported from about 22 bacterial species so far. Of these enzymes, to date, only two have been demonstrated to catalyze the biosynthesis of both trehalose and trehalulose. We have investigated the metagenomic data of an extreme temperature thermal spring to discover a novel gene that encodes a trehalose synthase (TreM) with higher stability and dual transglycosylation activities of trehalose and trehalulose biosynthesis. This enzyme is capable of catalyzing the transformation of maltose to trehalose and sucrose to trehalulose in a wide pH and temperature range. The present investigation endorses the thermal aquatic habitat as a promising genetic resource for the biocatalysts with high potential in producing high-value rare sugars.
Closed-loop control of a prosthetic finger via evoked proprioceptive information

Objective. Proprioceptive information plays an important role for recognizing and coordinating our limb’s static and dynamic states relative to our body or the environment. In this study, we determined how artificially evoked proprioceptive feedback affected the continuous control of a prosthetic finger. Approach. We elicited proprioceptive information regarding the joint static position and dynamic movement of a prosthetic finger via a vibrotactor array placed around the subject’s upper arm. Myoelectric signals of the finger flexor and extensor muscles were used to control the prosthesis, with or without the evoked proprioceptive feedback. Two control modes were evaluated: the myoelectric signal amplitudes were continuously mapped to either the position or the velocity of the prosthetic joint. Main results. Our results showed that the evoked proprioceptive information improved the control accuracy of the joint angle, with comparable performance in the position- and velocity-control conditions. However, greater angle variability was prominent during position-control than velocity-control. Without the proprioceptive feedback, the position-control tended to show a smaller angle error than the velocity-control condition. Significance. Our findings suggest that closed-loop control of a prosthetic device can potentially be achieved using non-invasive evoked proprioceptive feedback delivered to intact participants. Moreover, the evoked sensory information was integrated during myoelectric control effectively for both control strategies. The outcomes can facilitate our understanding of the sensorimotor integration process during human-machine interactions, which can potentially promote fine control of prosthetic hands.