julilili42/papers huggingface dataset:
Medication beliefs and use of medication lists – is there a connection? Results from a before-and-after study in Germany
2020-03-30

Abstract Background Despite increasing digitalisation the paper-based medication list remains one of the most important instruments for the documentation and exchange of medication-related information. However, even elderly patients with polypharmacy who are at high risk for medication errors and adverse drug events, frequently do not receive or use a complete and comprehensible medication list. Increasing the use of medication lists would be a great contribution to medication safety and facilitate the work of health care providers. Methods This study is related to the project MeinPlan (MyPlan) which comprised an information campaign on safe drug administration in the Rhine-Neckar region in South Germany. The campaign was evaluated in a before-and-after study based on a survey among two independent, representative samples of citizens over 65 years. In total, 5034 questionnaires were analysed. While the effects of the primary outcome (the percentage of citizens using a medication list) have been reported elsewhere, this analysis focusses on the effects of the campaign on citizens’ medication beliefs and assesses whether medication beliefs are associated with the use of medication lists, the use of over-the-counter drugs and the use of the tools offered by the campaign. Medication beliefs were assessed with the German version of the General Beliefs About Medicines Questionnaire (BMQ) which results in subscales for “General Overuse”, “General Usefulness” and “General Harm”. The use of medication lists and over-the-counter drugs was assessed with self-developed questionnaire items. Results No statistically significant change in citizens’ medication beliefs before and after the campaign could be detected. Likewise, no association between medication beliefs and the use of medication lists, the use of over-the-counter drugs or the use of the tools offered by the campaign could be shown. Conclusions A campaign focussing on the risks of drug administration did not change the medication beliefs of the targeted population. Moreover, citizens’ general medication beliefs do not seem to be crucial for their decision to use a medication list or over-the-counter drugs. Strategies to improve the use of medication lists by patients should focus on other influential factors, such as individual benefits and barriers and socio-psychological factors.
Distinct ensembles in the noradrenergic locus coeruleus evoke diverse cortical states
2020-03-30

Abstract The noradrenergic locus coeruleus (LC) is a crucial controller of brain and behavioral states. Activating LC neurons synchronously en masse by electrical or optogenetic stimulation promotes a stereotypical “activated” high-frequency cortical state. However, it has been recently reported that spontaneous LC cell-pairs have sparse yet structured time-averaged cross-correlations, which is unlike the high synchrony of en masse neuronal stimulation. This suggests the untested possibility that LC population activity may be made of distinct multi-cell ensembles each with unique temporal evolution of activity. We used non-negative matrix factorization (NMF) to analyze large populations of LC single units simultaneously recorded in the rat LC. Synthetic spike train simulations showed that NMF, unlike the traditional time-averaged pairwise correlations, detects both the precise neuronal composition and the activation time courses of each ensemble. NMF identified the existence of robust ensembles of spontaneously co-active LC neurons. Since LC neurons selectively project to specific forebrain regions, we hypothesized that individual LC ensembles produce different cortical states. To test this hypothesis, we triggered local field potentials (LFP) in cortical area 24a on the activation of distinct LC ensembles. We found four cortical states, each with different spectro-temporal LFP characteristics, that were robust across sessions and animals. While some LC ensembles triggered the activated state, others were associated with a beta oscillation-specific state or a reduced high frequency oscillation state. Thus – in contrast to the stereotypical “activated” brain state evoked by en masse LC stimulation – spontaneous activation of distinct LC ensembles can control a multitude of cortical states.
Phenotypically independent profiles relevant to mental health are genetically correlated
2020-03-30

Abstract Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Using independent component analysis, we decomposed self-report mental health questionnaires from 136,678 healthy individuals of the UK Biobank, excluding data from individuals with a diagnosed neurological or psychiatric disorder, into thirteen distinct profiles relevant to mental health, capturing different symptoms as well as social and risk factors underlying reduced mental health. Utilizing genotypes from 117,611 of those individuals with White English ancestry, we performed GWAS for each mental health profile and assessed genetic correlations between these profiles, and between the profiles and common psychiatric disorders and cognitive traits. We found that mental health profiles were genetically correlated with a wide range of psychiatric disorders and cognitive traits, with strongest effects typically observed between a given mental health profile and a disorder for which the profile is common (e.g. depression symptoms and major depressive disorder, psychosis and schizophrenia). Strikingly, although the profiles were phenotypically uncorrelated, many of them were genetically correlated with each other. This study provides evidence that statistically independent mental health profiles partly share genetic underpinnings and show genetic overlaps with psychiatric disorders, suggesting that shared genetics across psychiatric disorders cannot be exclusively attributed to the known overlapping symptomatology between the disorders.
Presentation and discussion of the high resolution atmosphere-land surface subsurface simulation dataset of the virtual Neckar catchment for the period 2007–2015
2020-03-30

Abstract. Coupled numerical models, which simulate water and energy fluxes in the subsurface-land surface-atmosphere system in a physically consistent way are a prerequisite for the analysis and a better understanding of heat and matter exchange fluxes at compartmental boundaries and interdependencies of states across these boundaries. Complete state evolutions generated by such models may be regarded as a proxy of the real world, provided they are run at sufficiently high resolution and incorporate the most important processes. Such a virtual reality can be used to test hypotheses on the functioning of the coupled terrestrial system. Coupled simulation systems, however, face severe problems caused by the vastly different scales of the processes acting in and between the compartments of the terrestrial system, which also hinders comprehensive tests of their realism. We used the Terrestrial Systems Modeling Platform TerrSysMP, which couples the meteorological model COSMO, the land-surface model CLM, and the subsurface model ParFlow, to generate a virtual catchment for a regional terrestrial system mimicking the Neckar catchment in southwest Germany. Simulations for this catchment are made for the period 2007–2015, and at a spatial resolution of 400 m for the land surface and subsurface and 1.1 km for the atmosphere. Among a discussion of modelling challenges, the model performance is evaluated based on real observations covering several variables of the water cycle. We find that the simulated (virtual) catchment behaves in many aspects quite close to observations of the real Neckar catchment, e.g. concerning atmospheric boundary-layer height, precipitation, and runoff. But also discrepancies become apparent, both in the ability of the model to correctly simulate some processes which still need improvement such as overland flow, and in the realism of some observation operators like the satellite based soil moisture sensors. The whole raw dataset is available for interested users. The dataset described here is available via the CERA database (Schalge et al., 2020): https://doi.org/10.26050/WDCC/Neckar_VCS_v1.
TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice
2020-03-31

Abstract Non-alcoholic fatty liver disease (NAFLD) shows an increasing prevalence and is associated with the development of liver fibrosis and cirrhosis as the major risk factors of liver-related mortality in this disease. The therapeutic possibilities are limited and restricted to life style intervention, since specific drugs for NAFLD are unavailable so far. TNFα has been implicated as a major pathogenic driver of NAFLD. TNFα-mediated liver injury occurs mainly via TNF-receptor-1 (TNFR1) signaling, whereas TNFR2 mediates protective pathways. In this study, we analyzed the therapeutic effects of a novel antibody, which selectively inhibits TNFR1 while retaining protective TNFR2 signaling in a high-fat diet (HFD) mouse model of NAFLD. Mice were fed with HFD for 32 weeks and treated with anti-TNFR1-antibody or control-antibody for the last 8 weeks. We then investigated the mechanisms of TNFR1 inhibition on liver steatosis, inflammatory liver injury, insulin resistance and fibrosis. Compared to control-antibody treatment, TNFR1 inhibition significantly reduced liver steatosis and triglyceride content, which was accompanied by reduced expression and activation of the transcription factor SREBP1 and downstream target genes of lipogenesis. Furthermore, inhibition of TNFR1 resulted in reduced activation of the MAP kinase MKK7 and its downstream target JNK, which was associated with significant improvement of insulin resistance. Apoptotic liver injury, NAFLD activity and alanine aminotransferase (ALT) levels, as well as liver fibrosis significantly decreased by anti-TNFR1 compared to control-antibody treatment. Thus, our results suggest selective TNFR1 inhibition as a promising approach for NAFLD treatment.
An updated patent review of p38 MAP kinase inhibitors (2014-2019)
2020-03-31

<b>Introduction</b>: During the first half of the last decade the p38 MAP kinase family was a very popular target in academic as well as industrial research programs. Many attempts to achieve marketing authorization for a p38 MAPK inhibitor for the treatment of pro-inflammatory diseases, like rheumatoid arthritis (RA), failed at the state of clinical trials, mostly due to selectivity and/or toxicity issues.<b>Areas covered</b>: Herein, the patents and corresponding publications of international companies, universities and other research institutions, which focus on the development, identification and optimization of new selective p38 inhibitors and their fields of use are summarized.<b>Expert opinion</b>: p38 MAP kinase inhibitors are a mature field with many pre-clinically validated structural classes, more than 20 candidates in clinical trials but still (except the weak and unselective p38 inhibitor pirfenidone) no approved drug. Big Pharma hasn't contributed much to the patents of the last five years but remarkable contribution have come from academic environment or small biotech companies. Three general punchlines of innovation have shown up. Tailor-made molecules with properties for local application, mainly type-II (Urea-type) inhibitors for lung- or skin diseases, isoform p38γ,δ-selective inhibitors for the treatment of cutaneous t-cell lymphoma (CTCL) and substrate-specific inhibitors (e.g. p38/MK2).
It Takes Two: Expectancy-Value Constructs and Vocational Interests Jointly Predict STEM Major Choices
2020-03-31

The supply of STEM graduates is an issue in many countries—raising the question of why more students do not choose STEM careers. We aimed to address this question by drawing on two of the most prominent theories on career choices: Eccles et al.'s (1983) expectancy-value theory (EVT) and Holland's (1997) theory of vocational interests. In a large longitudinal data set, we used EVT constructs and vocational interests assessed at the end of high school (T1) to explain differences in math achievement (a critical filter for later STEM choices) at the end of high school (school sample: N = 4,984) and to predict actual STEM major choices in college 2 years later (T2; college sample: N = 2,145). To investigate their distinct and relative contributions, we conducted a set of hierarchical regression analyses (linear and logistic) in which we considered EVT constructs and vocational interests separately and simultaneously. Whereas both groups of constructs were significant predictors of both outcomes, vocational interests were better predictors of STEM major choice (Pseudo-R2 = .26) than EVT constructs (Pseudo-R2 = .19), and EVT constructs were better predictors of math achievement (R2 = .47) than vocational interests (R2 = .30) when investigated separately. In addition, the combined analyses revealed that the best predictions of math achievement (R2 = .48) and STEM major choice (Pseudo-R2 = .28) were achieved when EVT constructs and vocational interests were used jointly. Results suggest that EVT constructs and vocational interests contribute differently to STEM major choices, a finding that may have important implications for research and practice, including the choice of which constructs to target in interventions.
Topological neutron stars in tensor-multi-scalar theories of gravity
2020-03-31

In the present paper we demonstrate that there exists a new type of neutron stars in the tensor-multi-scalar theories of gravity. We call this new type of neutron stars topological neutron stars. In addition to the standard characteristics of the usual neutron stars the topological neutron stars are also characterized by a topological charge. We numerical construct explicit examples of topological neutron stars in tensor-multi-scalar theories whose target space is . Besides the topological charge the topological neutron stars also exhibit other attractive features which can place them among the realistic compact objects that could exist in Nature. For example they possess zero scalar charge and thus evades the strong binary pulsar constraints on the dipole scalar radiation.
Cellular Metabolism in High-Throughput In Vitro Reporter Gene Assays and Implications for the Quantitative In Vitro–In Vivo Extrapolation
2020-03-31

High-throughput <i>in vitro</i> reporter gene assays are increasingly applied to assess the potency of chemicals to alter specific cellular signaling pathways. Genetically modified reporter gene cell lines provide stable readouts of the activation of cellular receptors or transcription factors of interest, but such reporter gene assays have been criticized for not capturing cellular metabolism. We characterized the metabolic activity of the widely applied AREc32 (human breast cancer MCF-7), ARE-bla (human liver cancer HepG2), and GR-bla (human embryonic kidney HEK293) reporter gene cells in the absence and in the presence of benzo[<i>a</i>]pyrene (BaP), an AhR ligand known to upregulate cytochrome P450 <i>in vitro</i> and <i>in vivo</i>. We combined fluorescence microscopy with chemical analysis, real-time PCR, and ethoxyresorufin-<i>O</i>-deethylase activity measurements to track temporal changes in BaP and its metabolites in the cells and surrounding medium over time in relation to the expression and activity of metabolic enzymes. Decreasing BaP concentrations and formation of metabolites agreed with the high basal CYP1 activity of ARE-bla and the strong <i>CYP1A1</i> mRNA induction in AREc32, whereas BaP concentrations were constant in GR-bla, in which neither metabolites nor CYP1 induction was detected. The study emphasizes that differences in sensitivity between reporter gene assays may be caused not only by different reporter constructs but also by a varying biotransformation rate of the evaluated parent chemical. The basal metabolic capacity of reporter gene cells in the absence of chemicals is not a clear indication because we demonstrated that the metabolic activity can be upregulated by AhR ligands during the assay. The combination of methods presented here is suitable to characterize the metabolic activity of cells <i>in vitro</i> and can improve the interpretation of <i>in vitro</i> reporter gene effect data and extrapolation to <i>in vivo</i> human exposure.
Next-Generation Sequencing of Advanced GI Tumors Reveals Individual Treatment Options
2020-03-31

PURPOSE Precision oncology connects highly complex diagnostic procedures with patient histories to identify individualized treatment options in interdisciplinary molecular tumor boards (MTBs). Detailed data on MTB-guided treatments and outcome with a focus on advanced GI cancers have not been reported yet. PATIENTS AND METHODS Next-generation sequencing of tumor and normal tissue pairs was performed between April 2016 and February 2018. After identification of relevant molecular alterations, available clinical studies or in-label, off-label, or matched experimental treatment options were recommended. Follow-up data and a response assessment that was based on radiologic imaging were recorded. RESULTS Ninety-six patients were presented to the MTB of Tuebingen University Hospital. Sixteen (17%) showed “pathogenic” or “likely pathogenic” germline variants. Recommendations on the basis of molecular alterations or tumor mutational burden were given for 41 patients (43%). Twenty-five received the suggested drug, and 20 were evaluable for best response assessment. Three patients (15%) reached a partial response (PR), and 6 (30%), stable disease (SD), whereas 11 (55%) had tumor progression (progressive disease). Median progression-free survival (PFS) for all treated and evaluable patients was 2.8 months (range, 1.0-9.0 months), and median overall survival (OS) of all treated patients was 5.2 months (range, 0.1 months to not reached). Patients with SD for ≥ 3 months or PR compared with progressive disease showed both a statistically significant longer median PFS (7.8 months [95% CI, 4.2 to 11.4 months] v 2.2 months [95% CI, 1.5 to 2.8 months], P &lt; .0001) and median OS (18.0 months [95% CI, 10.4 to 25.6 months] v 3.8 months [95% CI, 2.3 to 5.4 months], P &lt; .0001). CONCLUSION Next-generation sequencing diagnostics of advanced GI cancers identified a substantial number of pathogenic or likely pathogenic germline variants and unique individual treatment options. Patients with PR or SD in the course of MTB-recommended treatments seemed to benefit with respect to PFS and OS.
Electric heating and angular momentum transport in laminar models of protoplanetary discs
2020-03-31

ABSTRACT The vertical temperature structure of a protoplanetary disc bears on several processes relevant to planet formation, such as gas and dust grain chemistry, ice lines, and convection. The temperature profile is controlled by irradiation from the central star and by any internal source of heat such as might arise from gas accretion. We investigate the heat and angular momentum transport generated by the resistive dissipation of magnetic fields in laminar discs. We use local 1D simulations to obtain vertical temperature profiles for typical conditions in the inner disc (0.5–4 au). Using simple assumptions for the gas ionization and opacity, the heating and cooling rates are computed self-consistently in the framework of radiative non-ideal magnetohydrodynamics. We characterize steady solutions that are symmetric about the mid-plane and which may be associated with saturated Hall-shear unstable modes. We also examine the dissipation of electric currents driven by global accretion-ejection structures. In both cases we obtain significant heating for a sufficiently high opacity. Strong magnetic fields can induce an order-unity temperature increase in the disc mid-plane, a convectively unstable entropy profile, and a surface emissivity equivalent to a viscous heating of α ∼ 10−2. These results show how magnetic fields may drive efficient accretion and heating in weakly ionized discs where turbulence might be inefficient, at least for a range of radii and ages of the disc.
Discovery of a retrogradely rotating neutron star in the X-ray pulsar GX 301–2
2020-03-31

ABSTRACT We report on the analysis of the spin evolution of a slow X-ray pulsar GX 301–2 along the orbit using long-term monitoring by Fermi/Gamma-ray Burst Monitor. Based on the observationally confirmed accretion scenario and an analytical model for the accretion of angular momentum, we demonstrate that in this system, the neutron star spins retrogradely, that is, in a direction opposite to the orbital motion. This first-of-a-kind discovery of such a system proves the principal possibility of retrograde rotation in accreting systems with suitable accretion torque, and might have profound consequences for our understanding of the spin evolution of X-ray pulsars, estimates of their initial spin periods, and the ultimate result of their evolution.
<p>Management of double-head pterygium with conjunctival autograft and primary closure</p>
2020-03-31

A surgical excision combined with conjunctival autograft transplantation and primary closure in a one-time intervention seems to be effective and economical for the treatment of double-head pterygium.
Faculty Opinions recommendation of Serial tests of T-cell function predict long-term survival in an elderly cohort from a Scottish general practice.
2020-03-31

INTRODUCTION The care of the elderly presents serious challenges to general practice. In 1979, the first author took over the care of a general practice in Scotland where 21% of registered patients were elderly. This resulted in a high workload and prompted research into how this might be mitigated. AIM To measure serial tests of T-cell function in these individuals in order to identify those whose immune response was impaired and assess the effect of this in a long term follow up. METHODS This research comprised two phases. In the assessment phase (1979-82), patients were invited to have a 3-monthly visit from a research nurse where clinical measurements were made and blood taken for immunological tests of lymphocyte proliferation after culture with phytohaemagglutinin (PHA). For each patient, all records were surveyed and problems identified. In the follow-up phase (post 1982), all deaths were assessed with complete life-long follow up. RESULTS Of 405 people originally invited to participate in this research, 314 (78%) agreed and 246 (153 female, 93 male) entered the follow-up phase and were followed for 36.5 years. Factors significantly associated with lower survival were age, male sex, diastolic blood pressure, current smoking and poor immune function, as demonstrated by the percentage of negative responses in at least six PHA tests. Considered in four groups by percentage of failing tests, the lowest group had a life span 4 years shorter than the highest (P< 0.01). The four groups did not differ significantly in general practitioner workload, diagnosed problems or causes of death. DISCUSSION Poor cellular immune function was associated with poor survival over lifetime follow up of >30 years. A sensitive, specific and longitudinally consistent measure of T-cell function is required to predict who may be at risk of poorer survival within our practices. PMID: 32223846