julilili42/papers huggingface dataset:
Competencies for a Healthy Physically Active Lifestyle—Validation of an Integrative Model
2020-07-07

<b>Purpose</b>: The model of physical activity-related health competence (PAHCO) provides an integrative and interdisciplinary view on competencies that are necessary when people want to lead a healthy, physically active lifestyle. Given the need to accumulate potential further evidence on the validity of this model through the development of an assessment tool, the goal of the present study was to extend first measurement models on PAHCO. <b>Method</b>: In Study 1, a measurement model with five predictors on PAHCO was tested with 341 COPD patients undergoing inpatient rehabilitation. In Study 2, data from 745 apprentices were used to create an extended eight-factor measurement model. We undertook reliability analysis, confirmatory factor analysis (CFA), and structural equation modeling (SEM) to assess the validity of the models. <b>Results</b>: The analyses showed good results for the reliability and discriminant validity of the factors. Accordingly, the CFA demonstrated satisfactory overall fits for the five-factor as well as for the extended eight-factor measurement model. The associations with physical activity and physical health parameters indicated criterion validity for seven of the eight PAHCO factors. The explained variance of the multivariate models lay between 9.8% and 10.4% in Study 1 and between 9.5% and 21.3% in Study 2. <b>Conclusion</b>: In the present study, it was possible to extract a well-fitting, eight-factor measurement model and accumulate further evidence on the validity of the PAHCO model. Future research should strive for a cross-validation of the measurement model and more deeply investigate the internal structure of the eight factors.
New Technologies in Clinical Trials in Corneal Diseases and Limbal Stem Cell Deficiency: Review from the European Vision Institute Special Interest Focus Group Meeting
2020-07-07

To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation. The unmet needs in the abovementioned disease areas are discussed, and realistically achievable new technologies for better diagnosis and use in clinical trials are outlined. To sum up, it can be said that there are several new technologies that can improve current diagnostics in the field of ophthalmology in the near future and will have impact on clinical trial end point design.
The specific PKC-α inhibitor chelerythrine blunts costunolide-induced eryptosis
2020-07-07

Abstract Costunolide, a natural sesquiterpene lactone, has multiple pharmacological activities such as neuroprotection or induction of apoptosis and eryptosis. However, the effects of costunolide on pro-survival factors and enzymes in human erythrocytes, e.g. glutathione and glucose-6-phosphate dehydrogenase (G6PDH) respectively, have not been studied yet. Our aim was to determine the mechanisms underlying costunolide-induced eryptosis and to reverse this process. Phosphatidylserine exposure was estimated from annexin-V-binding, cell volume from forward scatter in flow cytometry, and intracellular glutathione [GSH] i from high performance liquid chromatography. The oxidized status of intracellular glutathione and enzyme activities were measured by spectrophotometry. Treatment of erythrocytes with costunolide dose-dependently enhanced the percentage of annexin-V-binding cells, decreased the cell volume, depleted [GSH] i and completely inhibited G6PDH activity. The effects of costunolide on annexin-V-binding and cell volume were significantly reversed by pre-treatment of erythrocytes with the specific PKC-α inhibitor chelerythrine. The latter, however, had no effect on costunolide-induced GSH depletion. Costunolide induces eryptosis, depletes [GSH] i and inactivates G6PDH activity. Furthermore, our study reveals an inhibitory effect of chelerythrine on costunolide-induced eryptosis, indicating a relationship between costunolide and PKC-α. In addition, chelerythrine acts independently of the GSH depletion. Understanding the mechanisms of G6PDH inhibition accompanied by GSH depletion should be useful for development of anti-malarial therapeutic strategies or for synthetic lethality-based approaches to escalate oxidative stress in cancer cells for their sensitization to chemotherapy and radiotherapy.
Brain-Machine Neurofeedback: Robotics or Electrical Stimulation?
2020-07-07

Neurotechnology such as brain-machine interfaces (BMI) are currently being investigated as training devices for neurorehabilitation, when active movements are no longer possible. When the hand is paralyzed following a stroke for example, a robotic orthosis, functional electrical stimulation (FES) or their combination may provide movement assistance; i.e., the corresponding sensory and proprioceptive neurofeedback is given contingent to the movement intention or imagination, thereby closing the sensorimotor loop. Controlling these devices may be challenging or even frustrating. Direct comparisons between these two feedback modalities (robotics vs. FES) with regard to the workload they pose for the user are, however, missing. Twenty healthy subjects controlled a BMI by kinesthetic motor imagery of finger extension. Motor imagery-related sensorimotor desynchronization in the EEG beta frequency-band (17-21 Hz) was turned into passive opening of the contralateral hand by a robotic orthosis or FES in a randomized, cross-over block design. Mental demand, physical demand, temporal demand, performance, effort, and frustration level were captured with the NASA Task Load Index (NASA-TLX) questionnaire by comparing these workload components to each other (weights), evaluating them individually (ratings), and estimating the respective combinations (adjusted workload ratings). The findings were compared to the task-related aspects of active hand movement with EMG feedback. Furthermore, both feedback modalities were compared with regard to their BMI performance. Robotic and FES feedback had similar workloads when weighting and rating the different components. For both robotics and FES, mental demand was the most relevant component, and higher than during active movement with EMG feedback. The FES task led to significantly more physical (<i>p</i> = 0.0368) and less temporal demand (<i>p</i> = 0.0403) than the robotic task in the adjusted workload ratings. Notably, the FES task showed a physical demand 2.67 times closer to the EMG task, but a mental demand 6.79 times closer to the robotic task. On average, significantly more onsets were reached during the robotic as compared to the FES task (17.22 onsets, SD = 3.02 vs. 16.46, SD = 2.94 out of 20 opportunities; <i>p</i> = 0.016), even though there were no significant differences between the BMI classification accuracies of the conditions (<i>p</i> = 0.806; CI = -0.027 to -0.034). These findings may inform the design of neurorehabilitation interfaces toward human-centered hardware for a more natural bidirectional interaction and acceptance by the user.
Trivalent Rare‐Earth Metal Amide Complexes as Catalysts for the Hydrosilylation of Benzophenone Derivatives with HN(SiHMe2)2 by Amine‐Exchange Reaction
2020-07-07

Abstract The rare‐earth metal complexes Ln( L 1 )[N(SiHMe 2 ) 2 ](thf) (Ln=La, Ce, Y; L 1 = N , N′′ ‐bis(pentafluorophenyl)diethylenetriamine dianion) were synthesized by treating Ln[N(SiHMe 2 ) 2 ] 3 (thf) 2 with L 1 H 2 . The lanthanum and cerium derivatives are active catalysts for the hydrosilylation of benzophenone derivatives with HN(SiHMe 2 ) 2 . An amine‐exchange reaction was revealed as a key step of the catalytic cycle, in which Ln−Si−H β‐agostic interactions are proposed to promote insertion of the carbonyl moiety into the Si−H bond.
Computed Histological Quantification of Atherosclerotic Plaque Microcalcifications
2020-07-07

Inflammation has a central role in atherosclerotic plaque formation and rupture. Intense macrophage inflammatory activity results in microcalcifications which are strongly associated with plaque vulnerability. Microcalcifications with specific critical size between 5 and 65 μ, located in the fibrous cap producing local mechanical stress on the plaque surface and may directly contribute to plaque rupture. Hence, accurate assessment of microcalcifications size and dimension has significant clinical importance. Current invasive and noninvasive plaque imaging has limited spatial resolution which limits accurate definition of microcalcifications in the atherosclerotic plaques. We describe a new imaging technique with high spatial resolution, based on confocal microscopic analysis, using a dedicated software which allows automatic characterization of microcalcifications and quantitative assessment of their extent and localization.
VLT/SPHERE survey for exoplanets around young early-type stars, including systems with multi-belt architectures
2020-07-07

\\nContext. Dusty debris disks around pre- and main-sequence stars are potential signposts for the existence of planetesimals and exoplanets. Giant planet formation is therefore expected to play a key role in the evolution of the disk. This is indirectly confirmed by extant submillimeter near-infrared images of young protoplanetary and cool dusty debris disks around main-sequence stars that usually show substantial spatial structures. With two decades of direct imaging of exoplanets already studied, it is striking to note that a majority of recent discoveries of imaged giant planets have been obtained around young early-type stars hosting a circumstellar disk.\\nAims. Our aim was to create a direct imaging program designed to maximize our chances of giant planet discovery and target 22 young early-type stars. About half of them show indications of multi-belt architectures.\\nMethods. Using the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE to acquire high-constrast coronagraphic differential near-infrared images, we conducted a systematic search in the close environment of these young, dusty, and early-type stars. We used a combination of angular and spectral differential imaging to reach the best detection performances down to the planetary mass regime.\\nResults. We confirm that companions detected around HIP 34276, HIP 101800, and HIP 117452 are stationary background sources and binary companions. The companion candidates around HIP 8832, HIP 16095, and HIP 95619 are determined as background contaminations. Regarding the stars for which we infer the presence of debris belts, a theoretical minimum mass for planets required to clear the debris gaps can be calculated. The dynamical mass limit is at least 0.1 MJ and can exceed 1 MJ. Direct imaging data is typically sensitive to planets down to ~3.6 MJ at 1′′, and 1.7 MJ in the best case. These two limits tightly constrain the possible planetary systems present around each target. These systems will be probably detectable with the next generation of planet imagers. \\n
Ion Transport in Eryptosis, the Suicidal Death of Erythrocytes
2020-07-08

Erythrocytes are among the most abundant cells in mammals and are perfectly adapted to their main functions, i.e., the transport of O<sub>2</sub> to peripheral tissues and the contribution to CO<sub>2</sub> transport to the lungs. In contrast to other cells, they are fully devoid of organelles. Similar to apoptosis of nucleated cells erythrocytes may enter suicidal death, eryptosis, which is characterized by the presentation of membrane phosphatidylserine on the cell surface and cell shrinkage, hallmarks that are also typical of apoptosis. Eryptosis may be triggered by an increase in the cytosolic Ca<sup>2+</sup> concentration, which may be due to Ca<sup>2+</sup> influx via non-selective cation channels of the TRPC family. Eryptosis is further induced by ceramide, which sensitizes erythrocytes to the eryptotic effect of Ca<sup>2+</sup>. Signaling regulating eryptosis further involves a variety of kinases including AMPK, PAK2, cGKI, JAK3, CK1α, CDK4, MSK1/2 and casein kinase. Eryptosis-dependent shrinkage is induced by K<sup>+</sup> efflux through Ca<sup>2+</sup>-activated K<sup>+</sup> channel K<sub>Ca</sub>3.1, the Gardos channel. Eryptotic cells are phagocytosed and may adhere to endothelial cells. Eryptosis may help prevent hemolysis since defective erythrocytes usually undergo eryptosis followed by rapid clearance from circulating blood. Excessive eryptosis stimulated by various diseases and xenobiotics may result in anemia and/or impaired microcirculation. This review focuses on the significance and mechanisms of eryptosis as well as on the ion fluxes involved. Moreover, a short summary of further ion transport mechanisms of the erythrocyte membrane is provided.
Charge Transfer from Organic Molecules to Molybdenum Disulfide: Influence of the Fluorination of Iron Phthalocyanine
2020-07-08

Layered transition metal dichalcogenides (TMDCs), such as molybdenum disulfide (MoS2), are currently in the focus of interest due to their novel electronic properties. The adsorption of molecules is a promising way to tune the electronic structure of TMDCs. We study interface properties between MoS2 and differently fluorinated iron phthalocyanines (FePcFx, x = 0, 4, 16) using X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), angle-resolved photoelectron spectroscopy (ARPES), and X-ray absorption spectroscopy (XAS). A key parameter for the charge transfer is the ionization potential of FePcFx. A distinct electron transfer from a molecule to a substrate is observed for FePc and FePcF4. From energy-momentum ARPES maps, we suppose that the substrate and FePc-related states hybridize at the interface. This study demonstrates that a controlled tuning of the electronic structure of MoS2 by electron donors is possible, driven by the ionization potential difference between the substrate and the adsorbate.
HLA Evolutionary Divergence as a Prognostic Marker for AML Patients Undergoing Allogeneic Stem Cell Transplantation
2020-07-08

The diversity of human leukocyte antigens (HLAs) enables the presentation of immense repertoires of peptides, including tumor-associated antigens (TAAs). As a surrogate for immunopeptidome diversity, the HLA evolutionary divergence (HED) between individual HLA alleles might directly define the ability to present TAAs, a prerequisite for graft-versus-leukemia effects. We therefore analyzed the impact of HED on survival within a cohort of 171 acute myeloid leukemia (AML) patients after matched donor allogeneic hematopoietic stem cell transplantation (HSCT). Low HED (&lt;25th percentile) of HLA class I (HEDclass I) or HLA-DR antigens (HEDDR) was a strong determinant for adverse overall survival after allogeneic HSCT (OS), with a hazard ratio for death of 1.9 (95% CI 1.2–3.2) and 2.1 (95% CI 1.3–3.4), respectively. Defining a cutoff value for the combined HEDtotal (HEDclass I and HEDDR), the respective 5 year OS was 29.7% and 64.9% in patients with low and high HEDtotal (p &lt; 0.001), respectively. Furthermore, the risk of relapse was significantly higher in patients with low HEDtotal (hazard ratio (HR) 2.2, 95% CI 1.3–3.6) and event-free survival (EFS) was significantly reduced (5 year EFS 25.7% versus 54.4%, p &lt; 0.001). We here introduce HED, a fundamental metric of immunopeptidome diversity, as a novel prognostic factor for AML patients undergoing allogeneic HSCT.
Apolipophorin-II/I Contributes to Cuticular Hydrocarbon Transport and Cuticle Barrier Construction in Locusta migratoria
2020-07-08

Apolipophorins are carrier proteins that bind lipids and mediate their transport from tissue to tissue in animals. Apolipophorin I and II (apoLp-II/I) are the major apolipophorins in insects. The implication of apoLp-II/I in cuticle lipid-barrier formation in insects has not been addressed to date. In the present study, we investigated the function of apoLp-II/I in the migratory locust <i>Locusta migratoria</i> (<i>LmapoLp-II/I</i>). During the development of fifth instar nymphs, <i>LmapoLp-II/I</i> transcript levels increased until mid-instar, and then decreased gradually until molting to the adult stage. We found that <i>LmapoLp-II/I</i> was predominately expressed in the fat body and the integument including oenocytes and epidermal cells. Immunodetection experiments revealed that LmapoLp-I mainly localized in the cytoplasm of oenocytes and epidermal cells. Silencing of <i>LmapoLp-II/I</i> caused molting defects in nymphs. Importantly, RNA interference against <i>LmapoLp-II/I</i> resulted in a significant decrease in the content of cuticle surface lipids including alkanes and methyl alkanes. Cuticular permeability was significantly enhanced in these nymphs in Eosin Y penetration assays. By consequence, desiccation resistance and insecticide tolerance of ds<i>LmapoLp-II/I</i>-treated locusts were reduced. Taken together, our results indicate that <i>LmapoLp-II/I</i> is involved in the transport and deposition of surface-cuticular lipids that are crucial for maintaining normal cuticle barrier function in <i>L. migratoria</i>.
Biopolymer Systems in Soft Tissue Engineering: Cell Compatibility and Effect Studies Including Material, Catalyst, and Surface Properties
2020-07-08

Cell compatibility of biomaterials is one of the most important issues in tissue engineering. It is affected by the catalyst, the chemical composition, and the surface topography of the material. Our aim was to study the influence of these factors for three standard FDA-approved biopolymers on the proliferation of preadipocytes. The analyzed materials were polyesters, which were synthesized by ring-opening polymerization. Tin(II) octanoate is the standard catalysts for the ring-opening polymerization; however, it is considered to be cytotoxic. Therefore, we compare its compatibility with iron catalysts. Our study suggests that neither polymers nor catalysts or mechanical properties have a significant impact on cell compatibility in short-term 2D cell cultures in vitro. In contrast, nanoroughness can influence how cells attach and spread in a material, showing an influence on preadipocyte proliferation. Higher nanoroughness leads to higher cell compatibility, which becomes more pronounced with time.
Treatment outcomes in hepatitis C virus genotype 1a infected patients with and without baseline NS5A resistance‐associated substitutions
2020-07-08

Abstract Background &amp; Aims The presence of baseline resistance‐associated substitutions (RASs) reduced sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) genotype 1a infected patients treated with Elbasvir/Grazoprevir (EBR/GZR). This study aimed to evaluate the frequency of NS5A RASs and treatment outcomes in patients for whom EBR/GZR was intended. Methods We sequenced NS5A in 832 samples from German genotype1a‐infected DAA‐naïve patients population‐based, which were collected in the European Resistance Database. Treatment outcomes and clinical parameters were evaluated in 519 of such patients retrospectively. Results Overall, 6.5% of patients harboured EBR‐specific NS5A RASs at baseline, including Q30H/R (3.3%), L31M (1.8%), Y93H (1.6%) and other individual variants. Antiviral treatment, including EBR/GZR, was initiated in 88% of the patients. In the absence of RASs, the majority of patients received EBR/GZR for 12 weeks (57%) and the SVR rate was 97% compared to 99% SVR achieved using other DAA regimens (LDV/SOF ± RBV, G/P, PrOD + RBV, VEL/SOF). Various regimens were used in the presence of RASs and SVR rates were high following treatment with LDV/SOF (100%), G/P (83%), PrOD/RBV (100%), VEL/SOF (100%), SMV/SOF (100%) and EBR/GZR + RBV for 16 weeks (100%). However, two patients received EBR/GZR for 16 weeks without RBV and one relapsed. Conclusions EBR/GZR treatment with or without RBV for 12 or 16 weeks according to a baseline RAS analysis was highly effective with ≥97% SVR in patients with genotype 1a. EBR/GZR without RBV should be avoided in patients with RASs. High SVR rates were also achieved using other 8‐ or 12‐week DAA regimens.
Enhanced COVID-19 data for improved prediction of survival
2020-07-08

Abstract The current COVID-19 pandemic, caused by the rapid world-wide spread of the SARS-CoV-2 virus, is having severe consequences for human health and the world economy. The virus effects individuals quite differently, with many infected patients showing only mild symptoms, and others showing critical illness. To lessen the impact of the pandemic, one important question is which factors predict the death of a patient? Here, we construct an enhanced COVID-19 dataset by processing two existing databases (from Kaggle and WHO) and using natural language processing methods to enhance the data by adding local weather conditions and research sentiment. Author summary In this study, we contribute an enhanced COVID-19 dataset, which contains 183 samples and 43 features. Application of Extreme Gradient Boosting (XGBoost) on the enhanced dataset achieves 95% accuracy in predicting patients survival, with country-wise research sentiment, and then age and local weather, showing the most importance. All data and source code are available at http://ab.inf.uni-tuebingen.de/publications/papers/COVID-19 .
Behavioral tests assessing neuropsychiatric phenotypes in adolescent mice reveal strain- and sex-specific effects
2020-07-09

Abstract In humans, infancy and adolescence are associated with major changes in synaptic functions and ongoing maturation of neural networks, which underlie the major behavioral changes during these periods. Among adult cases with neuropsychiatric disorders including autism spectrum disorder, schizophrenia, attention deficit hyperactivity, and bipolar disorders, 50% have developed behavioral symptoms and received a diagnosis before 15 years of age. However, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we explored which behavioral experiments assessing neuropsychiatric phenotypes can be performed during a specific window of development in adolescent male and female C57BL/6N, DBA/2, and FVB/N mice that are typically used as background strains for generating genetically-modified mouse models. The three wild-type strains were evaluated across anxiety, social behaviors, and cognitive functions in order to cover the main behavioral impairments that occur in neuropsychiatric disorders. During adolescence, the three strains displayed significant differences under certain behavioral paradigms. In addition, C57BL/6N and FVB/N, but not DBA/2 mice revealed some sex-related differences. Our results provide new insights into discrete behaviors during development and emphasize the crucial importance of the genetic background, sex, and experimental settings in the age-dependent regulation of different behaviors.