Miracle-dz/UniFAR-FTUs huggingface dataset:
Pseudomonas aeruginosa rugose small-colony variants evade host clearance, are hyper-inflammatory, and persist in multiple host environments

Pseudomonas aeruginosa causes devastating infections in immunocompromised individuals. Once established, P. aeruginosa infections become incredibly difficult to treat due to the development of antibiotic tolerant, aggregated communities known as biofilms. A hyper-biofilm forming clinical variant of P. aeruginosa, known as a rugose small-colony variant (RSCV), is frequently isolated from chronic infections and is correlated with poor clinical outcome. The development of these mutants during infection suggests a selective advantage for this phenotype, but it remains unclear how this phenotype promotes persistence. While prior studies suggest RSCVs could survive by evading the host immune response, our study reveals infection with the RSCV, PAO1ΔwspF, stimulated an extensive inflammatory response that caused significant damage to the surrounding host tissue. In both a chronic wound model and acute pulmonary model of infection, we observed increased bacterial burden, host tissue damage, and a robust neutrophil response during RSCV infection. Given the essential role of neutrophils in P. aeruginosa-mediated disease, we investigated the impact of the RSCV phenotype on neutrophil function. The RSCV phenotype promoted phagocytic evasion and stimulated neutrophil reactive oxygen species (ROS) production. We also demonstrate that bacterial aggregation and TLR-mediated pro-inflammatory cytokine production contribute to the immune response to RSCVs. Additionally, RSCVs exhibited enhanced tolerance to neutrophil-produced antimicrobials including H2O2 and the antimicrobial peptide LL-37. Collectively, these data indicate RSCVs elicit a robust but ineffective neutrophil response that causes significant host tissue damage. This study provides new insight on RSCV persistence, and indicates this variant may have a critical role in the recurring tissue damage often associated with chronic infections.
Outcomes from massive paracetamol overdose: a retrospective observational study

LINKED ARTICLE This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163-5. https://doi.org/10.1111/bcp.13279 AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAPpl ) and treatment nomogram thresholds at those time points (APAPt ) provides a useful assessment tool. METHODS This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l-1 , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAPpl :APAPt ratio (based on a treatment line through 100 mg l-1 at 4 h), and time to acetylcysteine. RESULTS Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P < 0.0001) and creatinine (r = 0.138, P = 0.002) concentrations. Acute liver injury, hepatotoxicity and coagulopathy were more frequent with APAPpl :APAPt ≥ 3 with odds ratios (OR) and 95% confidence intervals (CI) of 9.19 (5.04-16.68), 35.95 (8.80-158.1) and 8.34 (4.43-15.84), respectively (P < 0.0001). Heightened risk persisted in patients receiving acetylcysteine within 8 h of overdose. CONCLUSION Patients presenting following massive paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAPpl :APAPt ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort.
Effect of poling state and morphology of piezoelectric poly(vinylidene fluoride) membranes for skeletal muscle tissue engineering

This work reports on the influence of polarization and morphology of electroactive poly(vinylidene fluoride), PVDF, on the adhesion and morphology of myoblast cells. Non-poled, “poled+” and “poled−” β-PVDF films were prepared by solvent casting followed by corona poling. Furthermore, random and aligned electrospun β-PVDF fiber mats were also prepared. It is demonstrated that negatively charged surfaces improve cell adhesion and proliferation and that the directional growth of the myoblast cells can be achieved by culturing the cell on aligned fibers. Therefore, the potential application of electroactive materials for muscle regeneration is demonstrated.
Beryllium-10 and Aluminum-26 in Individual Cosmic Spherules from Antarctica

— We present data for the cosmogenic nuclides 10Be and 26Al in a suite of 24 extraterrestrial spherules, collected from Antarctic moraines and deep sea sediments. All of the 10 large spherules collected in glacial till at Lewis Cliff are extraterrestrial. As in earlier work, the great majority of particles show prominent solar cosmic-ray (SCR) production of 26Al, indicating bombardment ages on the order of 106 years or even longer. These long ages are in direct contradiction to model ages for small particles in the inner Solar System and may require reconsideration of models of small particle lifetimes. A small fraction of the particles so far measured (6/42) possess cosmogenic radionuclide patterns consistent with predictions for meteoroid spall droplets. We believe that most of the spherules were bombarded in space primarily as bodies not much larger than their present size. The content of in situ produced 10Be and 26Al in quartz pebbles in the same moraine suggests that these spherules may have on average a significant terrestrial age.
Modelling and simulation of heat transfer by convection in aerogel treated nonwovens

Abstract Simulation and numerical modeling are becoming increasingly popular due to the ability to seek solutions for a problem without undertaking real-life experiments. For the problems of heat transfer, these techniques to generate relevant data by incorporating different changes to the input parameters. Heat transfer property of textile materials is a major concern since it influences comfort properties of clothing. In this paper, numerical simulation was applied to evaluate the heat flux, temperature distributions, and convective heat transfer coefficients of the fibrous insulating materials treated with aerogel. The computational model simulated the insulation behavior of nonwoven fabrics without and with aerogel. Ansys and Comsol were used to model and simulate heat transfer. The simulation was performed assuming laminar flow and since the Mach number was < 0.3, the compressible flow model with Mach number < 0.3 was used. The results of simulation were correlated to experimental measurements for validation. Furthermore, aerogel-treated fabric samples showed better thermal performance. Using this model, the heat transfer properties of the nonwoven fabrics treated with aerogel can be optimized further.
Evolutionary radiation of earless frogs in the Andes: molecular phylogenetics and habitat shifts in high-elevation terrestrial breeding frogs

The loss of hearing structures and loss of advertisement calls in many terrestrial breeding frogs (Strabomantidae) living at high elevations in South America are common and intriguing phenomena. The Andean frog genus Phrynopus Peters, 1873 has undergone an evolutionary radiation in which most species lack the tympanic membrane and tympanic annulus, yet the phylogenetic relationships among species in this group remain largely unknown. Here, we present an expanded molecular phylogeny of Phrynopus that includes 24 nominal species. Our phylogeny includes Phrynopus peruanus, the type species of the genus, and 10 other species for which genetic data were previously unavailable. We found strong support for monophyly of Phrynopus, and that two nominal species—Phrynopus curator and Phrynopus nicoleae—are junior synonyms of Phrynopus tribulosus. Using X-ray computed tomography (CT) imaging, we demonstrate that the absence of external hearing structures is associated with complete loss of the auditory skeletal elements (columella) in at least one member of the genus. We mapped the tympanum condition on to a species tree to infer whether the loss of hearing structures took place once or multiple times. We also assessed whether tympanum condition, body size, and body shape are associated with the elevational distribution and habitat use. We identified a single evolutionary transition that involved the loss of both the tympanic membrane and tympanic annulus, which in turn is correlated with the absence of advertisement calls. We also identified several species pairs where one species inhabits the Andean grassland and the other montane forest. When accounting for phylogenetic relatedness among species, we detected a significant pattern of increasing body size with increasing elevation. Additionally, species at higher elevations tend to develop shorter limbs, shorter head, and shorter snout than species living at lower elevations. Our findings strongly suggest a link between ecological divergence and morphological diversity of terrestrial breeding frogs living in montane gradients.
Seeking Value Through Deviation? Economic Impacts of IT Overinvestment and Underinvestment

This study addresses the economic impacts of information technology IT overinvestment and underinvestment decisions. Based on the view of Red Queen competition in conjunction with institutional theory, we hypothesize that overinvestment and underinvestment in IT have nonlinear performance impacts. Drawing on the idea of management control mechanisms, we further hypothesize that the performance impacts are conditional on ownership concentration. Using a sample of S&P 500 firms, we find that, on average, there is a positive relationship between a firm's overinvestment in IT and Tobin's q, although that relationship attenuates at higher levels of overinvestment. However, there is, on average, no relationship between a firm's underinvestment in IT and its Tobin's q. Importantly, the payoff for underinvestment becomes positive for companies with founding-family ownership. Implications for research and practice are discussed. The online appendix is available at https://doi.org/10.1287/isre.2017. 0710 .
Human FOXP3+ T regulatory cell heterogeneity

FOXP3‐expressing CD4+ T regulatory (Treg) cells are instrumental for the maintenance of self‐tolerance. They are also involved in the prevention of allergy, allograft rejection, foetal rejection during pregnancy and of exaggerated immune response towards commensal pathogens in mucosal tissues. They can also prevent immune responses against tumors and promote tumor progression. FOXP3‐expressing Treg cells are not a homogenous population. The different subsets of Treg cells can have different functions or roles in the maintenance of immune homeostasis and can therefore be differentially targeted in the management of autoimmune diseases or in cancer. We discuss here how Treg cell subsets can be differentiated phenotypically, functionally and developmentally in humans.
A Pilot Test of Transformational Leadership Training for Sports Coaches: Impact on the Developmental Experiences of Adolescent Athletes

This study investigated the impact of a transformational leadership training program for youth sport coaches on adolescent athletes' perceptions of transformational leadership and positive developmental experiences. The transformational leadership training program was associated with higher rates of perceived transformational leadership behaviour at follow-up when compared to baseline measures. Importantly, these increases were associated with significantly higher rates of self-reported developmental experiences. Coach training was associated with a predictability and reliability to athlete outcomes that was not evident in athletes of a comparison group. Transformational leadership may provide a theoretically sound foundation for coaching practice and education in the service of facilitating positive developmental outcomes for athletes.
Basic Characterization of Natural Transformation in a Highly Transformable Haemophilus parasuis Strain SC1401

Haemophilus parasuis causes Glässer's disease and pneumonia, incurring serious economic losses in the porcine industry. In this study, natural competence was investigated in H. parasuis. We found competence genes in H. parasuis homologous to ones in Haemophilus influenzae and a high consensus battery of Sxy-dependent cyclic AMP (cAMP) receptor protein (CRP-S) regulons using bioinformatics. High rates of natural competence were found from the onset of stationary-phase growth condition to mid-stationary phase (OD600 from 0.29 to 1.735); this rapidly dropped off as cells reached mid-stationary phase (OD600 from 1.735 to 1.625). As a whole, bacteria cultured in liquid media were observed to have lower competence levels than those grown on solid media plates. We also revealed that natural transformation in this species is stable after 200 passages and is largely dependent on DNA concentration. Transformation competition experiments showed that heterogeneous DNA cannot outcompete intraspecific natural transformation, suggesting an endogenous uptake sequence or other molecular markers may be important in differentiating heterogeneous DNA. We performed qRT-PCR targeting multiple putative competence genes in an effort to compare bacteria pre-cultured in TSB++ vs. TSA++ and SC1401 vs. SH0165 to determine expression profiles of the homologs of competence-genes in H. influenzae. Taken together, this study is the first to investigate natural transformation in H. parasuis based on a highly naturally transformable strain SC1401.
Quality of Life Among Primary Family Caregivers of Patients with Heart Failure in Southwest China

Purpose: The aim of this study was to investigate the quality of life (QOL) and to identify the factors (characteristics of patients and caregivers, caregiver burden, self-efficacy, and social support) related to QOL among family caregivers of patients with heart failure (HF) in Southwest China. Design: The study had a cross-sectional descriptive design. Methods: Patients and their family caregiver dyads (N = 251) in three hospitals in Chengdu were recruited from April 2013 to September 2014. Data were collected by in-person interviews. Multivariate analyses were used to identify the factors associated with physical and mental QOL of caregivers. Findings: The median scores of physical and mental QOL were 70 and 60, respectively. Multivariate analysis demonstrated that higher New York Heart Association (NYHA) classification, more caregiving hours per day, more readmissions in the last 6 months, higher caregiver burden, and lower social support were associated with poorer physical and mental QOL. Lower self-efficacy was also associated with poorer physical QOL. The variances of physical (73%) and mental (70%) QOL of caregivers were explained by these identified significant factors. Conclusions: The caregivers of patients with HF in Southwest China had perceived reduced QOL and experienced more seriously impaired mental health than physical health. Clinical Relevance: Early assessments, strategies, and policy supports developed particularly for caregivers in undeveloped areas are necessary to identify caregivers who are at a high risk of reduced QOL and to improve their well-being.
CRYPTOCOCCAL MENINGITIS IN HIV-INFECTED PATIENTS AT

Cryptococcal meningitis (CM) is a common central nervous system infection in HIV-infected patients. This study aimed to determine treatment outcomes among HIV-infected patients who had cryptococcal meningitis and to determine predictors of death. We conducted a retrospective cohort study among HIV-infected patients receiving care at Chiang Mai University Hospital from January 1, 2005 to December 31, 2010. We studied 79 patients; 45 (57.0%) were male and the mean age was 35.1±7.2 years. Eleven patients (13.9%) had previous opportunistic infection. The most common presenting symptoms were headache (63 patients, 79.8%), fever (49 patients, 62.0%), and altered consciousness (21 patients, 26.6%). The median CD4+ cell count was 20 cells/mm3 [Interquartile range (IQR) 10, 53]. The in-hospital, 90-day, and 1-year mortality rates were 24.1%, 32.4%, and 52.2%, respectively. The CM attributable in-hospital, 90-day and 1-year mortality rates were 13.9%, 20.3%, and 23.2%, respectively. Predictors associated with a 1-year mortality were a high cerebrospinal (CSF) cryptococcal antigen titer (>1:10,000) [Odds Ratio (OR) =7.08, 95% confidence interval (CI): 1.62-31.00, p=0.009], and altered consciousness at presentation (OR=5.27; 95% CI: 1.16-24.05; p=0.032). Cryptococcal meningitis is an important cause of death in HIV-infected patients. HIV-infected patients with a low CD4+ cell count, a headache, fever and altered consciousness should be investigated for CM and those with a high CSF cryptococcal antigen titer are at high risk for mortality.
Niclosamide inhibits vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in injured rat carotid arteries

The anti‐helminthic drug niclosamide regulates multiple cellular signals including STAT3, AMP‐activated protein kinase (AMPK), Akt, Wnt/β‐catenin and mitochondrial uncoupling which are involved in neointimal hyperplasia. Here we have examined the effects of niclosamide on vascular smooth muscle cell proliferation, migration and neointimal hyperplasia and assessed the potential mechanisms.
Characterization of Moist Processes Associated With Changes in the Propagation of the MJO With Increasing CO2

The processes that lead to changes in the propagation and maintenance of the Madden‐Julian Oscillation (MJO) as a response to increasing CO2 are examined by analyzing moist static energy budget of the MJO in a series of NASA GISS model simulations. It is found changes in MJO propagation is dominated by several key processes. Horizontal moisture advection, a key process for MJO propagation, is found to enhance predominantly due to an increase in the mean horizontal moisture gradients. The terms that determine the strength of the advecting wind anomalies, the MJO horizontal scale and the dry static stability, are found to exhibit opposing trends that largely cancel out. Furthermore, reduced sensitivity of precipitation to changes in column moisture, i.e., a lengthening in the convective moisture adjustment time scale, also opposes enhanced propagation. The dispersion relationship of Adames and Kim, which accounts for all these processes, predicts an acceleration of the MJO at a rate of ∼3.5% K−1, which is consistent with the actual phase speed changes in the simulation. For the processes that contribute to MJO maintenance, it is found that damping by vertical MSE advection is reduced due to the increasing vertical moisture gradient. This weaker damping is nearly canceled by weaker maintenance by cloud‐radiative feedbacks, yielding the growth rate from the linear moisture mode theory nearly unchanged with the warming. Furthermore, the estimated growth rates are found to be a small, negative values, suggesting that the MJO in the simulation is a weakly damped mode.
Coherent Ising machine based on degenerate optical parametric oscillators

A degenerate optical parametric oscillator network is proposed to solve the NP-hard problem of finding a ground state of the Ising model. The underlying operating mechanism originates from the bistable output phase of each oscillator and the inherent preference of the network in selecting oscillation modes with the minimum photon decay rate. Computational experiments are performed on all instances reducible to the NP-hard MAX-CUT problems on cubic graphs of order up to 20. The numerical results reasonably suggest the effectiveness of the proposed network.
Infection of XC Cells by MLVs and Ebola Virus Is Endosome-Dependent but Acidification-Independent

Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.
A controlled trial of trauma-focused therapy versus problem-solving in Islamic children affected by civil conflict and disaster in Aceh, Indonesia

Objective: To evaluate the relative efficacies of trauma-focused cognitive behavior therapy and problem-solving therapy in treating post-traumatic stress disorder in children affected by civil conflict in Aceh, Indonesia. Method: A controlled trial of children with post-traumatic stress disorder (N = 64) randomized children to either five individual weekly sessions of trauma-focused cognitive behavior therapy or problem-solving therapy provided by lay-counselors who were provided with brief training. Children were assessed by blind independent assessors at pretreatment, posttreatment and 3-month follow-up on post-traumatic stress disorder, depression and anger, as well as caregiver ratings of the child’s post-traumatic stress disorder levels. Results: Intent-to-treat analyses indicated no significant linear time × treatment condition interaction effects for post-traumatic stress disorder at follow-up (t(129.05) = −0.55, p = 0.58), indicating the two conditions did not differ. Across both conditions, there were significant reductions in post-traumatic stress disorder on self-reported (t(131.26) = −9.26, p < 0.001) and caregiver-reported (t(170.65) = 3.53, p = 0.001) measures and anger (t(127.66) = −7.14, p < 0.001). Across both conditions, there was a large effect size for self-reported post-traumatic stress disorder (cognitive behavior therapy: 3.73, 95% confidence interval = [2.75, 3.97]; problem-solving: 2.68, 95% confidence interval = [2.07, 3.29]). Conclusions: These findings suggest that trauma-focused cognitive behavior therapy and problem-solving approaches are comparably successful in reducing post-traumatic stress disorder and anger in treating mental health in children in a post-conflict setting. This pattern may reflect the benefits of non-specific therapy effects or gains associated with trauma-focused or problem-solving approaches.