Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacovigilance and assessment of drug safety reports during COVID 19

The speed and volume of clinical research to discover effective drug against novel corona virus has been remarkable. To address the unmet medical need, the regulations are made flexible and convenient without any relaxation in drug safety reporting. The pharmacovigilance activities, especially adverse event reporting regardless of clinical trials or clinical practice should continue as usual because patient safety is the priority. The exposure to experimental drugs with limited evidence of risk - benefit makes it more crucial to adapt robust safety monitoring, accuracy in adverse event reporting, and timely assessment. With the current restriction on physical contact, travel and free movements, isolation, quarantine, and huge clinical workload during pandemic, causality assessment will be more challenging. It may not be possible to capture details of all adverse events, thereby affecting completeness and quality of safety reports. A substantial number of COVID 19 patients will receive investigational drugs along with multiple other medications for clinical manifestations and drug therapy for lifestyle diseases. Causality assessment will be a challenge due to overlapping toxicities, multiple confounding, contributory factors, and insufficient data on safety and risk profile of combining drugs. Assessment will be unable to precisely determine the causality as certain or unlikely, although, it will be valuable in categorizing the causal association as “possible” adverse drug reactions and their scientific basis. Several of these detailed reports, when collated, can identify risk factors for possibilities of prevention or avoid harm. In the current situation of pandemic and uncertainty of experimental new and old repurposed drugs, causation needs to be viewed for the study drug with a public health perspective. After all, this is the best time tested approach to generate evidence and drug evaluation to prevent damage to prospective patients.
Effects of Elevated pCO2 on the Survival and Growth of Portunus trituberculatus

Identifying the response of Portunus trituberculatus to ocean acidification (OA) is critical to understanding the future development of this commercially important Chinese crab species. Recent studies have reported negative effects of OA on crustaceans. Here, we subjected swimming crabs to projected oceanic CO2 levels (current: 380 μatm; 2100: 750 μatm; 2200: 1500 μatm) for 4 weeks and analyzed the effects on survival, growth, digestion, antioxidant capacity, immune function, tissue metabolites, and gut bacteria of the crabs and on seawater bacteria. We integrated these findings to construct a structural equation model to evaluate the contribution of these variables to the survival and growth of swimming crabs. Reduced crab growth shown under OA is significantly correlated with changes in gut, muscle, and hepatopancreas metabolites whereas enhanced crab survival is significantly associated with changes in the carbonate system, seawater and gut bacteria, and activities of antioxidative and digestive enzymes. In addition, seawater bacteria appear to play a central role in the digestion, stress response, immune response, and metabolism of swimming crabs and their gut bacteria. We predict that if anthropogenic CO2 emissions continue to rise, future OA could lead to severe alterations in antioxidative, immune, and metabolic functions and gut bacterial community composition in the swimming crabs through direct oxidative stress and/or indirect seawater bacterial roles. These effects appear to mediate improved survival, but at the cost of growth of the swimming crabs.
An evaluation of allowing for mismatches as a way to manage genotyping errors in parentage assignment by exclusion

In parentage assignment by exclusion, using multiple and very polymorphic loci, genotyping errors are a major cause of non-assignment. Using stochastic simulations, we tested the possibility to allow for mismatches at one or more allele as a way to recover assignment power. This was very efficient provided the set of loci used had a high assignment power (> 99%) and the error rate was not too high (below 3–4%). In these cases, most of the theoretical assignment power could be recovered. We also showed the efficiency of the method in a practical experiment with rainbow trout.
Whole-Cell Photobleaching Reveals Time-Dependent Compartmentalization of Soluble Proteins by the Axon Initial Segment

By limiting protein exchange between the soma and the axon, the axon initial segment (AIS) enables the segregation of specific proteins and hence the differentiation of the somatodendritic compartment and the axonal compartment. Electron microscopy and super-resolution fluorescence imaging have provided important insights in the ultrastructure of the AIS. Yet, the full extent of its filtering properties is not fully delineated. In particular, it is unclear whether and how the AIS opposes the free exchange of soluble proteins. Here we describe a robust framework to combine whole-cell photobleaching and retrospective high-resolution imaging in developing neurons. With this assay, we found that cytoplasmic soluble proteins that are not excluded from the axon upon expression over tens of hours exhibit a strong mobility reduction at the AIS – i.e., are indeed compartmentalized – when monitored over tens of minutes. This form of compartmentalization is developmentally regulated, requires intact F-actin and may be correlated with the composition and ultrastructure of the submembranous spectrin cytoskeleton. Using computational modeling, we provide evidence that both neuronal morphology and the AIS regulate this compartmentalization but act on distinct time scales, with the AIS having a more pronounced effect on fast exchanges. Our results thus suggest that the rate of protein accumulation in the soma may impact to what extent and over which timescales freely moving molecules can be segregated from the axon. This in turn has important implications for our understanding of compartment-specific signaling in neurons.
Perceptual Advantage of Animal Facial Attractiveness: Evidence From b-CFS and Binocular Rivalry

Research has shown that attractive human faces enjoy an advantage in both conscious and preconscious processing. Here we examined whether this preference for attractiveness is exclusive to human faces by measuring participants’ sensitivity to the attractiveness of cat and tiger faces. Experiment 1 measured the time taken to break continuous flash suppression (b-CFS), whereas Experiment 2 measured the dominant time in binocular rivalry (BR). The results showed that attractive cat faces were detected more quickly (Experiment 1) and dominated for longer time in visual awareness (Experiment 2). However, no effect of attractiveness was found for tiger faces in Experiment 1, while attractive tiger faces also dominated for longer time in visual awareness in Experiment 2. The results provide first evidence that the preference for attractive animal faces can be shown involuntarily or without apparent conscious control. The findings suggest that human preference for facial attractiveness may contain an aesthetic element rather than being a purely adaptive means for mate choice.
Flucytosine-Fluconazole Cross-Resistance in Purine-Cytosine Permease-Deficient Candida lusitaniae Clinical Isolates: Indirect Evidence of a Fluconazole Uptake Transporter

ABSTRACT An unusual interaction between flucytosine and fluconazole was observed when a collection of 60 Candida lusitaniae clinical isolates was screened for cross-resistance. Among eight isolates resistant to flucytosine (MIC ≥ 128 μg/ml) and susceptible to fluconazole (0.5 < MIC < 2 μg/ml), four became flucytosine-fluconazole cross resistant when both antifungals were used simultaneously. Fluconazole resistance occurred only in the presence of high flucytosine concentrations, and the higher the fluconazole concentration used, the greater the flucytosine concentration necessary to trigger the cross-resistance. When the flucytosine- and fluconazole-resistant cells were grown in the presence of fluconazole alone, the cells reversed to fluconazole susceptibility. Genetic analyses of the progeny from crosses between resistant and sensitive isolates showed that resistance to flucytosine was derived from a recessive mutation in a single gene, whereas cross-resistance to fluconazole seemed to vary like a quantitative trait. We further demonstrated that the four clinical isolates were susceptible to 5-fluorouracil and that cytosine deaminase activity was unaffected. Kinetic transport studies with [14C]flucytosine showed that flucytosine resistance was due to a defect in the purine-cytosine permease. Our hypothesis was that extracellular flucytosine would subsequently behave as a competitive inhibitor of fluconazole uptake transport. Finally, in vitro selection of spontaneous and induced mutants indicated that such a cross-resistance mechanism could also affect other Candida species, including C. albicans, C. tropicalis, and C. glabrata. This is the first report of a putative fluconazole uptake transporter in Candida species and of a possible resistance mechanism associated with a deficiency in the uptake of this drug.
Regulation of C2C12 myogenic terminal differentiation by MKK3/p38α pathway

The signal transduction pathways connecting cell surface receptors to the activation of muscle-specific promoters and leading to myogenesis are still largely unknown. Recently, a contribution of the p38 mitogen-activated protein kinase (MAPK) pathway to this process was evoked through the use of pharmacological inhibitors. We used several mutants of the kinases composing this pathway to modulate the activity of the muscle-specific myosin light chain and myogenin promoters in C2C12 cells by transient transfections. In addition, we show for the first time, using a stable C2C12 cell line expressing a dominant-negative form of the p38 activator MAPK kinase (MKK)3, that a functional p38 MAPK pathway is indeed required for terminal muscle cell differentiation. The most obvious phenotype of this cell line, besides the inhibition of the activation of p38, is its inability to undergo terminal differentiation. This phenotype is accompanied by a drastic inhibition of cell cycle and myogenesis markers such as p21, p27, MyoD, and troponin T, as well as a profound disorganization of the cytoskeleton.
Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function

The pathogenic bacterium Helicobacter pylori is genetically highly diverse and a major risk factor for the development of peptic ulcer disease and gastric adenocarcinoma in humans. During evolution, H. pylori has acquired multiple type IV secretion systems (T4SSs), and then adapted for various purposes. These T4SSs represent remarkable molecular transporter machines, often associated with an extracellular pilus structure present in many bacteria, which are commonly composed of multiple structural proteins spanning the inner and outer membranes. By definition, these T4SSs exhibit central functions mediated through the contact-dependent conjugative transfer of mobile DNA elements, the contact-independent release and uptake of DNA into and from the extracellular environment as well as the secretion of effector proteins in mammalian host target cells. In recent years, numerous features on the molecular functionality of these T4SSs were disclosed. H. pylori encodes up to four T4SSs on its chromosome, namely the Cag T4SS present in the cag pathogenicity island (cagPAI), the ComB system, as well as the Tfs3 and Tfs4 T4SSs, some of which exhibit unique T4SS functions. The Cag T4SS facilitates the delivery of the CagA effector protein and pro-inflammatory signal transduction through translocated ADP-heptose and chromosomal DNA, while various structural pilus proteins can target host cell receptors such as integrins or TLR5. The ComB apparatus mediates the import of free DNA from the extracellular milieu, whereas Tfs3 may accomplish the secretion or translocation of effector protein CtkA. Both Tfs3 and Tfs4 are furthermore presumed to act as conjugative DNA transfer machineries due to the presence of tyrosine recombinases with cognate recognition sequences, conjugational relaxases, and potential origins of transfer (oriT) found within the tfs3 and tfs4 genome islands. In addition, some extrachromosomal plasmids, transposons and phages have been discovered in multiple H. pylori isolates. The genetic exchange mediated by DNA mobilization events of chromosomal genes and plasmids combined with recombination events could account for much of the genetic diversity found in H. pylori. In this review, we highlight our current knowledge on the four T4SSs and the involved mechanisms with consequences for H. pylori adaptation to the hostile environment in the human stomach.
Race, Gender, and the Development of Cross-Race Egalitarianism

Over the course of development, children acquire adult-like thinking about social categories such as race, which in turn informs their perceptions, attitudes, and behavior. However, children’s developing perceptions of race have been understudied particularly with respect to their potential influence on cross-race egalitarianism. Specifically, the acquisition of racial constancy, defined as the perception that race is a concrete and stable category, has been associated with increased awareness of racial stereotypes and group status differences. Yet, little work has investigated behavioral outcomes stemming from the acquisition of racial constancy beliefs. Here, we investigate whether the presence or absence of racial constancy beliefs differentially predicts inequality aversion with racial ingroup versus outgroup members for young children. White children (N = 202; ages 3–8) completed three sticker resource-allocation games with either a White or a Black partner shown in a photograph, after which racial constancy was measured. Results revealed that the acquisition of racial constancy interacted with partner race to predict inequality aversion outcomes in one game; however, age and gender also exerted strong effects.
The Association Between Personality Traits and eSports Performance

This study focuses on the relationship between personality traits, derived from the Big Five model, and performance in the competitive electronic sports (eSports) video game League of Legends (LoL). Data were gathered from 206 LoL players of various in-game success levels, as measured by their position within the competitive hierarchy (division) of the video game. The NEO-Five Factor Inventory (NEO-FFI) questionnaire was used to measure personality traits within the gathered sample, which was divided into two groups of higher and lower ranked players. The results indicate that players who reach higher divisions in LoL tend to be less extraverted, less agreeable, but more open to experience. This is one of the few reported links between eSports performance and personality traits, in what is still a nascent yet rapidly developing research topic. The results are discussed within the context of available knowledge on personality and traditional competitive sports performance.
A Trait Conceptualization of Reward-Reactivity Psychometric Properties of the Appetitive Motivation Scale (AMS)

The Appetitive Motivation Scale (AMS; Jackson & Smillie, 2004) represents a recent attempt to conceptualize individual differences in the functioning of Gray’s (1981) Behavioral Activation/Approach System (BAS). In this paper we subject the AMS to psychometric scrutiny via factor analysis, item response theory (IRT) analysis, and concurrent construct validation. In Study 1 (N = 1,366 university students, 53% male), results from factor analysis (FA) and IRT led to the removal of several problematic items from the scale. The revised AMS was shown to have improved unidimensional structure and item properties. In Study 2 (N = 122 university students, 20% male), correlational data and factor analysis indicated that the revised AMS was: (1) highly related to the original scale along with various BAS-related measures, and (2) more strongly related to a reward-reactivity factor than an impulsivity factor, relative to other putative BAS measures. We conclude that the improved AMS is a promising tool for future research.
Efficiency of Sensory Substitution Devices Alone and in Combination With Self-Motion for Spatial Navigation in Sighted and Visually Impaired

Human adults can optimally combine vision with self-motion to facilitate navigation. In the absence of visual input (e.g., dark environments and visual impairments), sensory substitution devices (SSDs), such as The vOICe or BrainPort, which translate visual information into auditory or tactile information, could be used to increase navigation precision when integrated together or with self-motion. In Experiment 1, we compared and assessed together The vOICe and BrainPort in aerial maps task performed by a group of sighted participants. In Experiment 2, we examined whether sighted individuals and a group of visually impaired (VI) individuals could benefit from using The vOICe, with and without self-motion, to accurately navigate a three-dimensional (3D) environment. In both studies, 3D motion tracking data were used to determine the level of precision with which participants performed two different tasks (an egocentric and an allocentric task) and three different conditions (two unisensory conditions and one multisensory condition). In Experiment 1, we found no benefit of using the devices together. In Experiment 2, the sighted performance during The vOICe was almost as good as that for self-motion despite a short training period, although we found no benefit (reduction in variability) of using The vOICe and self-motion in combination compared to the two in isolation. In contrast, the group of VI participants did benefit from combining The vOICe and self-motion despite the low number of trials. Finally, while both groups became more accurate in their use of The vOICe with increased trials, only the VI group showed an increased level of accuracy in the combined condition. Our findings highlight how exploiting non-visual multisensory integration to develop new assistive technologies could be key to help blind and VI persons, especially due to their difficulty in attaining allocentric information.
Distribution, hatch-date, growth, and mortality of larval Benthosema pterotum (Pisces: Myctophidae) in the shelf region of the East China Sea

We examined the distribution, hatch-date, growth, and mortality of larval Benthosema pterotum, a dominant pseudoceanic myctophid in the shelf region of the East China Sea, during early autumn when the main spawning has been predicted. This species is a key species in the food web of this area. Larvae were abundant in the area south of Cheju Island (60–80 m depth), corresponding with the adult habitat. Occurrence of the larvae was restricted to the onshore side of the shelf-break salinity front, indicating that this front acted as a barrier restricting the offshore dispersion of the larvae. In the area where the larvae occurred, a cyclonic eddy is formed, which is considered to limit the dispersal of the larvae, enabling them to recruit into the area of adult habitat. Modes of hatch-date appeared from late August to early September and from mid to late September, suggesting that large-scale spawning events occurred at least twice during the spawning season. Since the modes coincided with the new moon period, B. pterotum is suggested to spawn periodically once a month around the new moon, resulting in efficient mating and fertilization. Mean absolute growth rate (0.26 mm d−1) and weight-specific growth rate (18.8% of dry body weight d−1) were higher than previously reported values of other subtropical–tropical myctophids, which would be related to the high food availability in the study area. Daily instantaneous mortality coefficient during the first two weeks after hatching was estimated to be 0.28 d−1 (equivalent to 24.7% mortality d−1).
Genetic Relatedness of SalmonellaIsolates from Nondomestic Birds in Southeastern United States

ABSTRACT Salmonella infections have been implicated in large-scale die-offs of wild birds in the United States. Although we know quite a bit about the epidemiology of Salmonellainfection among domestic fowl, we know little about the incidence, epidemiology, and genetic relatedness of salmonellae in nondomestic birds. To gain further insight into salmonellae in these hosts, 22Salmonella isolates from diseased nondomestic birds were screened for the presence of virulence and antibiotic resistance-associated genes and compared genetically using pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA analysis. Of the 22 Salmonella isolates examined, 15 were positive for the invasion gene invA and the virulence plasmid-associated genes spvC and pef. Most (15 of 22) were generally sensitive to antibiotics. However, twoSalmonella isolates from pet birds were identified asSalmonella enterica serovar Typhimurium DT104. Despite the general susceptibility of these Salmonella isolates to most antimicrobial agents, antibiotic resistance-associated genesintI1, merA, and aadA1 were identified in a number of these isolates. Five distinctXbaI and nine distinct BlnI DNA patterns were observed for the 22 Salmonella isolates typed by PFGE. PFGE analysis determined that Salmonella isolates from passerines in Georgia and Wyoming were genetically related.
METHODS FOR DISTINGUISHING GENETIC AND ENVIRONMENTAL VARIANCE IN STRESS TOLERANCE

Variations in stress response among separate populations of the same species have often been interpreted as local adaptations to different degrees of past exposure to specific stresses. However, it is possible that such interpopulation divergence may also be caused by developmental differences that are attributable to proximate environmental heterogeneity. In order to elucidate the origin and dynamics of stress tolerance, and to predict how individual populations may be affected by environmental changes or stress, it would be instructive to distinguish between genetic divergence and phenotypic variations. This paper, using examples of freshwater snails, examines two experimental procedures, namely, quantitative genetical and mass-culture techniques, available to separate genetic and environmental causes of interpopulation differences in stress responses, and discusses the potential complications in differentiating the above two hypotheses. Overall, a combination of controlled-breeding and mass-culture exp.