julilili42/papers huggingface dataset:
Health-Related Quality of Life Outcomes from Botulinum Toxin Treatment in Spasticity
2020-05-04

Objective: The effects of botulinum toxin injections (BoNT) on health-related quality of life along the complex spectrum of spasticity needs further characterization to guide practitioners in a real-life therapeutic environment. Methods: In this study, we analyzed 50 consecutive and unselected patients with spasticity before and four weeks after re-injection of botulinum toxin. Health-related quality of life in terms of the EuroQol (EQ) as well as further motor and non-motor characteristics were assessed. Results: BoNT improved the EQ visual analog scale (EQ VAS). In addition, state of health and pain maxima improved. The EQ VAS improvement correlated with pre-injection characteristics of the EQ VAS and life satisfaction in the “movement disorders” domain. Conclusion: EQ VAS is sensitive for monitoring HR-QoL outcomes in an unselected real life observational cohort. This study may inform future studies intended to validate prediction variables that could inform on HR-QoL effects of BoNT treatment in spasticity.
Development of an Emotion-Sensitive mHealth Approach for Mood-State Recognition in Bipolar Disorder
2020-05-04

Internet- and mobile-based approaches have become increasingly significant to psychological research in the field of bipolar disorders. While research suggests that emotional aspects of bipolar disorders are substantially related to the social and global functioning or the suicidality of patients, these aspects have so far not sufficiently been considered within the context of mobile-based disease management approaches. As a multiprofessional research team, we have developed a new and emotion-sensitive assistance system, which we have adapted to the needs of patients with bipolar disorder. Next to the analysis of self-assessments, third-party assessments, and sensor data, the new assistance system analyzes audio and video data of these patients regarding their emotional content or the presence of emotional cues. In this viewpoint, we describe the theoretical and technological basis of our emotion-sensitive approach and do not present empirical data or a proof of concept. To our knowledge, the new assistance system incorporates the first mobile-based approach to analyze emotional expressions of patients with bipolar disorder. As a next step, the validity and feasibility of our emotion-sensitive approach must be evaluated. In the future, it might benefit diagnostic, prognostic, or even therapeutic purposes and complement existing systems with the help of new and intuitive interaction models.
Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure
2020-05-04

Significance Allergic disorders are widespread and can strongly affect quality of life. Here we show in humans that an allergic response can be triggered even in the absence of allergens by simply reencountering the environmental context in which an allergen was previously administered. This effect occurred only when participants slept during the night after allergen administration and was entirely absent when they stayed awake on that night, demonstrating that sleep is necessary for consolidating the association between environmental context and allergen. These findings have important implications for understanding the often observed “placebo” allergic responses occurring in the absence of allergens.
Quantifying the effect of ocean bed properties on ice sheet geometryover 40,000 years with a full-Stokes model
2020-05-04

Abstract. Simulations of ice sheet evolution over glacial cycles requires integration of observational constraints using ensemble studies with fast ice sheet models. These include physical parameterisations with uncertainties, for example, relating to grounding line migration. Ice dynamically more complete models are slow and have thus far only be applied for 50 % under almost equal forcing. Grounding line positions differ by up to 49 km, show significant hysteresis, and migrate non-steadily in both scenarios with long quiescent phases disrupted by leaps of rapid migration. The simulations quantify evolution of two different ice sheet geometries (namely thick and slow vs. thin and fast), triggered by the variable grounding line migration over the differing ocean beds. Our study extends the timescales of 3D full-Stokes by an order of magnitude to previous studies with the help of parallelisation. The extended time frame for full-Stokes models is a first step towards better understanding other processes such as erosion and sediment redistribution in the ice shelf cavity impacting the entire catchment geometry.
Kanamycin Uptake into Escherichia coli Is Facilitated by OmpF and OmpC Porin Channels Located in the Outer Membrane
2020-05-05

Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of <i>Escherichia coli</i>. Our analysis revealed that, despite its relatively large size, about 10-20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 μM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a defined set of <i>E. coli</i> porin mutants provide evidence that translocation of kanamycin via porins is relevant for antibiotic potency. The values are discussed with respect to other antibiotics.
Exhaustion of Skeletal Muscle Fibers Within Seconds: Incorporating Phosphate Kinetics Into a Hill-Type Model
2020-05-05

Initiated by neural impulses and subsequent calcium release, skeletal muscle fibers contract (actively generate force) as a result of repetitive power strokes of acto-myosin cross-bridges. The energy required for performing these cross-bridge cycles is provided by the hydrolysis of adenosine triphosphate (ATP). The reaction products, adenosine diphosphate (ADP) and inorganic phosphate (P <sub><i>i</i></sub> ), are then used-among other reactants, such as creatine phosphate-to refuel the ATP energy storage. However, similar to yeasts that perish at the hands of their own waste, the hydrolysis reaction products diminish the chemical potential of ATP and thus inhibit the muscle's force generation as their concentration rises. We suggest to use the term "exhaustion" for force reduction (fatigue) that is caused by combined P <sub><i>i</i></sub> and ADP accumulation along with a possible reduction in ATP concentration. On the basis of bio-chemical kinetics, we present a model of muscle fiber exhaustion based on hydrolytic ATP-ADP-P <sub><i>i</i></sub> dynamics, which are assumed to be length- and calcium activity-dependent. Written in terms of differential-algebraic equations, the new sub-model allows to enhance existing Hill-type excitation-contraction models in a straightforward way. Measured time courses of force decay during isometric contractions of rabbit <i>M. gastrocnemius</i> and <i>M. plantaris</i> were employed for model verification, with the finding that our suggested model enhancement proved eminently promising. We discuss implications of our model approach for enhancing muscle models in general, as well as a few aspects regarding the significance of phosphate kinetics as one contributor to muscle fatigue.
Nontopological spontaneously scalarized neutron stars in tensor-multiscalar theories of gravity
2020-05-05

In the present paper, we numerically construct new non-topological,\\nspontaneously scalarized neutron stars in the tensor-multi-scalar theories of\\ngravity whose target space is a three-dimensional maximally symmetric space,\\nnamely either , or , and in the case\\nof a nontrivial map . The theories of gravity admitting scalarization are characterized by\\nthe fact that the field equations always admit the general relativistic\\nsolution but for certain ranges of the parameters space it loses stability and\\nnonlinear development of a scalar field is observed. Thus, in order to\\ndetermine the values of the parameters where such scalarization is possible we\\nstudied the stability of the general relativistic solution within the framework\\nof the considered tensor-multi-scalar theories. Based on these results we could\\nobtain a family of scalarized branches characterized by the number of the\\nscalar field nodes. These branches bifurcate from the general relativistic\\nsolution at the points where new unstable modes appear and they are\\nenergetically more favorable over the pure Einstein solutions. Interestingly,\\nin certain parameter ranges, we could obtain non-uniqueness within a single\\nbranch of scalarized solutions.\\n
Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays
2020-05-05

Exposure assessment in <i>in vitro</i> cell-based bioassays is challenging for ionizable organic chemicals (IOCs), because they are present as more than one chemical species in the bioassay medium. Furthermore, compared to neutral organic chemicals, their binding to medium proteins and lipids is driven by more complex molecular interactions. Total medium concentrations (<i>C</i><sub>total,medium</sub>) and/or freely dissolved medium concentrations (<i>C</i><sub>free,medium</sub>) were determined for one neutral chemical and 14 IOCs (acids, bases, multifunctional) at concentrations relevant for determination of cytotoxicity and effect. <i>C</i><sub>free,medium</sub> was measured in two <i>in vitro</i> bioassays at the time of dosing and after 24 h of incubation using solid-phase microextraction. <i>C</i><sub>free,medium</sub> was maximally 1.7 times lower than the nominal concentrations (<i>C</i><sub>nom</sub>) for the hydrophilic chemicals (caffeine and lamotrigine). For the organic acids (naproxen, ibuprofen, warfarin, and diclofenac), <i>C</i><sub>free,medium</sub> was by a factor of 4 lower than <i>C</i><sub>nom</sub> at high concentrations, but the ratio was much higher at low concentrations, indicating a nonlinear binding behavior. The experimental <i>C</i><sub>free,medium</sub> was also compared with <i>C</i><sub>free,medium</sub> predicted with a mass balance model accounting for binding to medium proteins and lipids. The mass balance model performed well for five of the test chemicals (within a factor of 10), but it underestimated <i>C</i><sub>free,medium</sub> by up to a factor of 1200 for chemicals that showed nonlinear binding to medium components. These findings emphasize that experimental exposure assessment is required for improved understanding of <i>in vitro</i> toxicity data.
Development of Reading Abilities in Children with ADHD Following fNIRS-Neurofeedback or EMG-Biofeedback
2020-05-05

Abstract. Children with attention deficit/hyperactivity disorder (ADHD) show deficient reading skills, which, like ADHD symptoms, are associated with limitations in neurocognitive abilities. Neurofeedback (NF) aims to improve the latter, to alleviate ADHD symptoms, and to promote school and reading performances. Whether frontal lobe-NF based on functional near-infrared spectroscopy (fNIRS) and electromyogram (EMG)-biofeedback (BF), however, improve reading abilities of children with ADHD and whether these changes are associated with changes in neurocognitive abilities, has not yet been clarified. It was also unclear whether embedding trainings in virtual reality (VR) could increase their effectiveness. These questions were examined using data of 35 children with ADHD (6–11 years) who participated in 15 sessions of fNIRS-NF in VR, fNIRS-NF in 2D, or EMG-BF in VR. On average, children's reading performance improved in all training groups. Stronger improvements were found after VR trainings. Improvements in reading natural words were, on a trend level, accompanied by decreasing attention, while improvements in reading pseudowords were accompanied by improved sustained attention and response inhibition. The results suggest that fNIRS-NF and EMG-BF effectively improve reading abilities of children with ADHD, especially when training in VR.
Cytotoxic drugs in combination with the CXCR4 antagonist AMD3100 as a potential treatment option for pediatric rhabdomyosarcoma
2020-05-05

Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The prognosis of advanced stage RMS remains poor, and metastatic invasion is a major cause of treatment failure. Therefore, there is an urgent need for treatment alternatives focusing on metastatic invasion and drug resistance. The stromal cell‐derived factor‐1 (SDF‐1)/chemokine receptor 4 (CXCR4) axis is a crucial factor for metastatic invasion in RMS. Clinical data has revealed that high CXCR4 expression is associated with a poor outcome and a high metastatic rate in several malignancies, including RMS. Thus, targeting CXCR4 in addition to classical chemotherapy may improve the effectiveness of RMS treatment. In the present study, flow cytometry and reverse transcription‐quantitative PCR were used to assess the effects of the combined treatment with a CXCR4 antagonist and chemotherapy on CXCR4 expression in the embryonal RMS (RME) cell line RD and in the alveolar RMS (RMA) cell line RH30. The functional effect of CXCR4 expression on the migratory behavior of RMS cells was analyzed using Transwell assays. Treatment with cytotoxic agents modulated CXCR4 expression in RMS cells in a dose‐, drug‐ and cell line dependent manner; however, this was not observed in RD cells with vincristine. The expression levels of CXCR4 significantly increased the migratory behavior of RMA and did not affect RME cell migration towards stromal cell‐derived factor‐1α (SDF‐1α). AMD3100 markedly reduced the migration of RH30 cells in the Transwell assays compared with SDF‐1α alone, and the cytotoxic agents doxorubicin and vincristine increased this effect. The results of the combined treatment in RMS cells using the CXCR4 antagonist AMD3100 together with cytotoxic drugs demonstrated that this approach may be a promising alternative for the treatment of advanced stage pediatric RMS. The observed effects of circumventing metastatic invasion and drug resistance should be further investigated in vivo.
Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study
2020-05-05

SUMMARY Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies.
How much total ovarian tissue can be removed without compromising ovarian function? An animal study
2020-05-05

For the first time, we demonstrated that even up to 75% of total ovarian tissue can be removed without impact on E2 and P production in rats, which, if confirmed in women, would mean that hazardous (or possibly contraindicated in cancer patients) hormone therapy is not required to avoid the negative consequences of hormone depletion.
Deep XMM-Newton observations of the northern disc of M31 - II. Tracing the hot interstellar medium
2020-05-05

Aims. We use new deep XMM-Newton observations of the northern disc of M31 to trace the hot interstellar medium (ISM) in unprecedented detail and to characterise the physical properties of the X-ray emitting plasmas. Methods. We used all XMM-Newton data up to and including our new observations to produce the most detailed image yet of the hot ISM plasma in a grand design spiral galaxy such as our own. We compared the X-ray morphology to multi-wavelength studies in the literature to set it in the context of the multi-phase ISM. We performed spectral analyses on the extended emission using our new observations as they offer sufficient depth and count statistics to constrain the plasma properties. Data from the Panchromatic Hubble Andromeda Treasury were used to estimate the energy injected by massive stars and their supernovae. We compared these results to the hot gas properties. Results. The brightest emission regions were found to be correlated with populations of massive stars, notably in the 10 kpc star-forming ring. The plasma temperatures in the ring regions are ~0.2 up to ~0.6 keV. We suggest this emission is hot ISM heated in massive stellar clusters and superbubbles. We derived X-ray luminosities, densities, and pressures for the gas in each region. We also found large extended emission filling low density gaps in the dust morphology of the northern disc, notably between the 5 and 10 kpc star-forming rings. We propose that the hot gas was heated and expelled into the gaps by the populations of massive stars in the rings. Conclusions. It is clear that the massive stellar populations are responsible for heating the ISM to X-ray emitting temperatures, filling their surroundings, and possibly driving the hot gas into the low density regions. Overall, the morphology and spectra of the hot gas in the northern disc of M31 is similar to other galaxy discs.
Positive feedback induces switch between distributive and processive phosphorylation of Hog1
2020-05-05

Summary Cellular decision making often builds on ultrasensitive MAPK pathways. The phosphorylation mechanism of MAP kinase has so far been described as either distributive or processive, with distributive mechanisms generating ultrasensitivity in theoretical analyses. However, the in vivo mechanism of MAP kinase phosphorylation and its regulation by feedback loops remain unclear. We thus characterized the regulation of the MAP kinase Hog1 in Saccharomyces cerevisiae , which is transiently activated in response to hyperosmolarity. Specifically, we combined Hog1 activation data from different modalities and multiple conditions. We constructed ODE models with different pathway topologies, which were then assessed via parameter estimation and model selection. Interestingly, our best fitting model switches between distributive and processive phosphorylation behavior via a positive feedback loop targeting the MAP kinase-kinase Pbs2. Simulations further suggest that this mixed mechanism is required not only for full sensitivity to stimuli, but also to ensure robustness to different perturbations.
The processing of pseudoword form and meaning in production and comprehension: A computational modeling approach using linear discriminative learning
2020-05-06

Abstract Pseudowords have long served as key tools in psycholinguistic investigations of the lexicon. A common assumption underlying the use of pseudowords is that they are devoid of meaning: Comparing words and pseudowords may then shed light on how meaningful linguistic elements are processed differently from meaningless sound strings. However, pseudowords may in fact carry meaning. On the basis of a computational model of lexical processing, linear discriminative learning (LDL Baayen et al., Complexity, 2019 , 1–39, 2019), we compute numeric vectors representing the semantics of pseudowords. We demonstrate that quantitative measures gauging the semantic neighborhoods of pseudowords predict reaction times in the Massive Auditory Lexical Decision (MALD) database (Tucker et al., 2018). We also show that the model successfully predicts the acoustic durations of pseudowords. Importantly, model predictions hinge on the hypothesis that the mechanisms underlying speech production and comprehension interact. Thus, pseudowords emerge as an outstanding tool for gauging the resonance between production and comprehension. Many pseudowords in the MALD database contain inflectional suffixes. Unlike many contemporary models, LDL captures the semantic commonalities of forms sharing inflectional exponents without using the linguistic construct of morphemes. We discuss methodological and theoretical implications for models of lexical processing and morphological theory. The results of this study, complementing those on real words reported in Baayen et al., ( Complexity, 2019 , 1–39, 2019), thus provide further evidence for the usefulness of LDL both as a cognitive model of the mental lexicon, and as a tool for generating new quantitative measures that are predictive for human lexical processing.
Nitrate Feed Improves Growth and Ethanol Production of Clostridium ljungdahlii With CO2 and H2, but Results in Stochastic Inhibition Events
2020-05-06

The pH-value in fermentation broth is a critical factor for the metabolic flux and growth behavior of acetogens. A decreasing pH level throughout time due to undissociated acetic acid accumulation is anticipated under uncontrolled pH conditions such as in bottle experiments. As a result, the impact of changes in the metabolism (e.g., due to a genetic modification) might remain unclear or even unrevealed. In contrast, pH-controlled conditions can be achieved in bioreactors. Here, we present a self-built, comparatively cheap, and user-friendly multiple-bioreactor system (MBS) consisting of six pH-controlled bioreactors at a 1-L scale. We tested the functionality of the MBS by cultivating the acetogen <i>Clostridium ljungdahlii</i> with CO<sub>2</sub> and H<sub>2</sub> at steady-state conditions (=chemostat). The experiments (total of 10 bioreactors) were addressing the two questions: (1) does the MBS provide replicable data for gas-fermentation experiments?; and (2) does feeding nitrate influence the product spectrum under controlled pH conditions with CO<sub>2</sub> and H<sub>2</sub>? We applied four different periods in each experiment ranging from pH 6.0 to pH 4.5. On the one hand, our data showed high reproducibility for gas-fermentation experiments with <i>C. ljungdahlii</i> under standard cultivation conditions using the MBS. On the other hand, feeding nitrate as sole N-source improved growth by up to 62% and ethanol production by 2-3-fold. However, we observed differences in growth, and acetate and ethanol production rates between all nitrate bioreactors. We explained the different performances with a pH-buffering effect that resulted from the interplay between undissociated acetic acid production and ammonium production and because of stochastic inhibition events, which led to complete crashes at different operating times.