julilili42/papers huggingface dataset:
Adversarial Inpainting of Medical Image Modalities
2019-04-17

Numerous factors could lead to partial deteriorations of medical images. For\\nexample, metallic implants will lead to localized perturbations in MRI scans.\\nThis will affect further post-processing tasks such as attenuation correction\\nin PET/MRI or radiation therapy planning. In this work, we propose the\\ninpainting of medical images via Generative Adversarial Networks (GANs). The\\nproposed framework incorporates two patch-based discriminator networks with\\nadditional style and perceptual losses for the inpainting of missing\\ninformation in realistically detailed and contextually consistent manner. The\\nproposed framework outperformed other natural image inpainting techniques both\\nqualitatively and quantitatively on two different medical modalities.\\n
ST18 Enhances PV-IgG-Induced Loss of Keratinocyte Cohesion in Parallel to Increased ERK Activation
2019-04-17

Pemphigus is an autoimmune blistering disease targeting the desmosomal proteins desmoglein (Dsg) 1 and Dsg3. Recently, a genetic variant of the Suppression of tumorigenicity 18 (ST18) promoter was reported to cause ST18 up-regulation, associated with pemphigus vulgaris (PV)-IgG-mediated increase in cytokine secretion and more prominent loss of keratinocyte cohesion. Here we tested the effects of PV-IgG and the pathogenic pemphigus mouse anti-Dsg3 antibody AK23 on cytokine secretion and ERK activity in human keratinocytes dependent on ST18 expression. Without ST18 overexpression, both PV-IgG and AK23 induced loss of keratinocyte cohesion which was accompanied by prominent fragmentation of Dsg3 immunostaining along cell borders. In contrast, release of pro-inflammatory cytokines such as IL-1α, IL-6, TNFα, and IFN-γ was not altered significantly in both HaCaT and primary NHEK cells. These experiments indicate that cytokine expression is not strictly required for loss of keratinocyte cohesion. Upon ST18 overexpression, fragmentation of cell monolayers increased significantly in response to autoantibody incubation. Furthermore, production of IL-1α and IL-6 was enhanced in some experiments but not in others whereas release of TNF-α dropped significantly upon PV-IgG application in both EV- and ST18-transfected HaCaT cells. Additionally, in NHEK, application of PV-IgG but not of AK23 significantly increased ERK activity. In contrast, ST18 overexpression in HaCaT cells augmented ERK activation in response to both c-IgG and AK23 but not PV-IgG. Because inhibition of ERK by U0126 abolished PV-IgG- and AK23-induced loss of cell cohesion in ST18-expressing cells, we conclude that autoantibody-induced ERK activation was relevant in this scenario. In summary, similar to the situation in PV patients carrying ST18 polymorphism, overexpression of ST18 enhanced keratinocyte susceptibility to autoantibody-induced loss of cell adhesion, which may be caused in part by enhanced ERK signaling.
Human collectin-11 (COLEC11) and its synergic genetic interaction with MASP2 are associated with the pathophysiology of Chagas Disease
2019-04-17

Chagas Disease (CD) is an anthropozoonosis caused by Trypanosoma cruzi. With complex pathophysiology and variable clinical presentation, CD outcome can be influenced by parasite persistence and the host immune response. Complement activation is one of the primary defense mechanisms against pathogens, which can be initiated via pathogen recognition by pattern recognition molecules (PRMs). Collectin-11 is a multifunctional soluble PRM lectin, widely distributed throughout the body, with important participation in host defense, homeostasis, and embryogenesis. In complex with mannose-binding lectin-associated serine proteases (MASPs), collectin-11 may initiate the activation of complement, playing a role against pathogens, including T. cruzi. In this study, collectin-11 plasma levels and COLEC11 variants in exon 7 were assessed in a Brazilian cohort of 251 patients with chronic CD and 108 healthy controls. Gene-gene interactions between COLEC11 and MASP2 variants were analyzed. Collectin-11 levels were significantly decreased in CD patients compared to controls (p<0.0001). The allele rs7567833G, the genotypes rs7567833AG and rs7567833GG, and the COLEC11*GGC haplotype were related to T. cruzi infection and clinical progression towards symptomatic CD. COLEC11 and MASP2*CD risk genotypes were associated with cardiomyopathy (p = 0.014; OR 9.3, 95% CI 1.2-74) and with the cardiodigestive form of CD (p = 0.005; OR 15.2, 95% CI 1.7-137), suggesting that both loci act synergistically in immune modulation of the disease. The decreased levels of collectin-11 in CD patients may be associated with the disease process. The COLEC11 variant rs7567833G and also the COLEC11 and MASP2*CD risk genotype interaction were associated with the pathophysiology of CD.
Task complexity in history textbooks: A multidisciplinary case study on triangulation in history education research
2019-04-17

The purpose of history education in Austria has changed over at least the last decade. While the focus used to be to give students a master narrative of the national past based on positivist knowledge, the current objective of history education is to foster historical thinking processes that enable students to form transferable skills in the self-reflected handling and creation of history. A key factor in fostering historical thinking is the appropriation of learning tasks. This case study measures the complexity of learning tasks in Austrian history textbooks as one important aspect of their quality. It makes use of three different approaches to complexity to triangulate the notion: general task complexity (GTC), general linguistic complexity (GLC), and domain-specific task complexity (DTC). The question is which findings can be offered by the specific strengths and limitations of the different methodological approaches to give new insights into the study of task complexity in the domain of history education research. By pursuing multidisciplinary approaches in a triangulating way, the case study opens up new prospects for this field. Besides offering new insights on measuring the complexity of learning tasks, the study illustrates the need for further research in this field – not only related to the development of analytical frameworks, but also regarding the notion of complexity in the context of historical learning itself.
Microplastic–Contaminant Interactions: Influence of Nonlinearity and Coupled Mass Transfer
2019-04-18

Abstract Microplastic particles are ubiquitously detected in the environment. Despite intensive public and scientific discussions, their potential to transport contaminants in rivers and oceans under environmental conditions is still under assessment. In the present study we measured sorption isotherms and kinetics in batch experiments using phenanthrene (as a typical hydrophobic wastewater contaminant) and microplastic particles of different sizes and materials. We observed a linear sorption isotherm for polyethylene, in contrast to nonlinear sorption of polyamide and polystyrene, which could be best described by the Freundlich and the Polanyi–Dubinin–Manes isotherms, respectively. We modeled sorption kinetics as a combination of external mass transfer governed by diffusion through an aqueous boundary layer and intraparticle diffusion within the plastic. Which of these processes controls the kinetics depends on the sorption strength, particle size, diffusion coefficients, and time. We used semi-analytical and numerical methods to simulate the coupled mass transfer for both linear and nonlinear sorption. We successfully applied the semi-analytical model to polyethylene and the numerical code to polyamide and polystyrene, reproducing the measured kinetics and obtaining reasonable values for mass transfer and intraparticle diffusion coefficients. Subsequently, we used these coefficients to estimate the transport potential and relevant time scales for microplastic-bound contaminants under environmental conditions. Environ Toxicol Chem 2019;38:1635–1644. © 2019 SETAC Abstract Time scales for 50% desorption under different conditions.
Hands Ahead in Mind and Motion: Active Inference in Peripersonal Hand Space
2019-04-18

According to theories of anticipatory behavior control, actions are initiated by predicting their sensory outcomes. From the perspective of event-predictive cognition and active inference, predictive processes activate currently desired events and event boundaries, as well as the expected sensorimotor mappings necessary to realize them, dependent on the involved predicted uncertainties before actual motor control unfolds. Accordingly, we asked whether peripersonal hand space is remapped in an uncertainty anticipating manner while grasping and placing bottles in a virtual reality (VR) setup. To investigate, we combined the crossmodal congruency paradigm with virtual object interactions in two experiments. As expected, an anticipatory crossmodal congruency effect (aCCE) at the future finger position on the bottle was detected. Moreover, a manipulation of the visuo-motor mapping of the participants’ virtual hand while approaching the bottle selectively reduced the aCCE at movement onset. Our results support theories of event-predictive, anticipatory behavior control and active inference, showing that expected uncertainties in movement control indeed influence anticipatory stimulus processing.
A pilot Study: Auditory Steady-State Responses (ASSR) can be measured in human Fetuses using fetal Magnetoencephalography (fMEG)
2019-04-18

Abstract Background Auditory steady-state responses (ASSRs) are ongoing evoked brain responses to continuous auditory stimuli that play a role for auditory processing of complex sounds and speech perception. Transient auditory event-related responses (AERRs) have previously been recorded using fetal magnetoencephalography (fMEG) but involve different neurological pathways. Previous studies in children and adults demonstrated that the cortical components of the ASSR are significantly affected by state of consciousness and by maturational changes in neonates and young infants. To our knowledge, this is the first study to investigate ASSRs in human fetuses. Methods 47 fMEG sessions were conducted with 24 healthy pregnant women in three gestational age groups (30–32 weeks, 33–35 weeks and 36–39 weeks). The stimulation consisted of amplitude-modulated (AM) tones with a duration of one second, a carrier frequency (CF) of 500 Hz and a modulation frequency (MF) of 27 Hz or 42 Hz. Both tones were presented in a random order with equal probability adding up to 80–100 repetitions per tone. The ASSR across trials was quantified by assessing phase synchrony in the cortical signals at the stimulation frequency. Results and Conclusion Ten out of 47 recordings were excluded due to technical problems or maternal movements. Analysis of the included 37 fetal recordings revealed a statistically significant response for the phase coherence between trials for the MF of 27 Hz but not for 42 Hz. An exploratory subgroup analysis moreover suggested an advantage in detectability for fetal behavioral state 2F (active asleep) compared to 1F (quiet asleep) detected using fetal heart rate. In conclusion, with the present study it was possible to detect human fetal ASSRs for the first time. These findings warrant further investigations of the developing fetal brain.
Is the desire for fame related to well-being or ill-being?
2019-04-18

The construct of fame in self-determination theory is very similar to the construct of social status in Anderson, Hildreth, and Howland’s (2015) status-as-fundamental-motive perspective. Both fame and social status are characterized by admiration and (admiring) respect by other people. Yet, while desiring fame is believed to distract or interfere with the fulfillment of basic needs (e.g., Ryan et al., 1999), desiring social status is believed to be very much equivalent to a basic need (Anderson et al., 2015). Inspired by these two theoretical standpoints, we tested opposing hypotheses in a pre-registered secondary data analysis of prospective longitudinal data spanning 10 years (N = 4,625; Mage at T1 = 19.60). Specifically, we tested whether or not desire for fame among early adults is related to their (a) concurrent subjective well-being, self-esteem, and health, (b) subsequent subjective well-being, self-esteem, and health, and (c) subsequent changes in subjective well-being, self-esteem, and health. Furthermore, we investigated (d) whether changes in desire for fame are related to contemporaneous changes in subjective well-being, self-esteem, and health. In line with self-determination theory, we found several positive correlations between desire for fame and the negative affect subscale of the PANAS, low self-esteem, and self-reported health complaints. In line with the status-as-fundamental-motive perspective, we found almost no substantial negative correlations between desire for fame and life satisfaction, the positive affect subscale of the PANAS, and self-rated health status. Thus, our results did not support either of the two positions unequivocally, indicating the need for further theoretical refinement.
The genetic architecture of Parkinson disease in Spain: characterizing population-specific risk, differential haplotype structures, and providing etiologic insight
2019-04-18

ABSTRACT Background The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives To perform the largest Parkinson disease (PD) genome-wide association study (GWAS) restricted to a single country. Methods We performed a GWAS for both risk of PD and age-at-onset (AAO) in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations and burden analyses. Results We identified a novel population-specific GWAS signal at PARK2 associated with AAO. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT and HLA-DQB1 . A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence via two-sample Mendelian randomization in expression and methylation datasets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Conclusions Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain.
Culturomics of the plant prokaryotic microbiome and the dawn of plant-based culture media – A review
2019-04-19

Improving cultivability of a wider range of bacterial and archaeal community members, living natively in natural environments and within plants, is a prerequisite to better understanding plant-microbiota interactions and their functions in such very complex systems. Sequencing, assembling, and annotation of pure microbial strain genomes provide higher quality data compared to environmental metagenome analyses, and can substantially improve gene and protein database information. Despite the comprehensive knowledge which already was gained using metagenomic and metatranscriptomic methods, there still exists a big gap in understanding <i>in vivo</i> microbial gene functioning <i>in planta</i>, since many differentially expressed genes or gene families are not yet annotated. Here, the progress in culturing procedures for plant microbiota depending on plant-based culture media, and their proficiency in obtaining single prokaryotic isolates of novel and rapidly increasing candidate phyla are reviewed. As well, the great success of culturomics of the human microbiota is considered with the main objective of encouraging microbiologists to continue minimizing the gap between the microbial richness in nature and the number of species in culture, for the benefit of both basic and applied microbiology. The clear message to fellow plant microbiologists is to apply plant-tailored culturomic techniques that might open up novel procedures to obtain not-yet-cultured organisms and extend the known plant microbiota repertoire to unprecedented levels.
Prospective Clinical and Molecular Evaluation of Potential Plasmodium ovale curtisi and wallikeri Relapses in a High-transmission Setting
2019-04-19

Abstract Background Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites. Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce. The aim of this prospective study was to characterize the reappearance patterns of ovale parasites. Methods P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia. Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria. Results At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri. The median duration of follow-up was 35 weeks. Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32. Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi. Conclusion These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated. Interestingly, no relapse of P. ovale wallikeri was observed.
Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells
2019-04-19

KRAS-mutated colorectal cancers (CRCs) are resistant to cetuximab treatment. The multifunctional Y-box binding protein 1 (YB-1) is overexpressed in CRC and is associated with chemoresistance. In this study, the effects of oncogenic mutated KRAS(G12V) and KRAS(G13D) on YB-1 phosphorylation were investigated in CRC cells. The effects of the inhibition of p90 ribosomal S6 kinase (RSK) on YB-1 phosphorylation, cell proliferation and survival were tested with and without treatment with 5-fluorouracil using pharmacological inhibitors and siRNA. YB-1 phosphorylation status and subcellular distribution in CRC patient tissues were determined by immunofluorescence staining and confocal microscopy. Endogenous expression of mutated KRAS(G13D) and conditional expression of KRAS(G12V) significantly stimulated YB-1 phosphorylation via RSK and were associated with cetuximab resistance. Inhibition of YB-1 by targeting RSK stimulated the Akt signaling pathway, and this stimulation occurred independently of KRAS mutational status. Akt activation interfered with the antiproliferative effect of the RSK inhibitor. Consequently, dual targeting of RSK and Akt efficiently inhibited cell proliferation in KRAS(G13D)-mutated HCT116 and KRAS wild-type SW48 cells. Treatment with 5-fluorouracil (5-FU) significantly enhanced YB-1 phosphorylation in KRAS(G13D)-mutated HCT116 cells but not in KRAS wild-type SW48 cells. Dual targeting of Akt and RSK sensitized HCT116 cells to 5-FU by stimulating 5-FU-induced apoptosis and inhibiting repair of 5-FU-induced DNA damage. YB-1 was highly phosphorylated in CRC patient tumor tissues and was mainly localized in the nucleus. Together, dual targeting of RSK and Akt may be an alternative molecular targeting approach to cetuximab for treating CRC in which YB-1 is highly phosphorylated.
Extracellular Pax6 Regulates Tangential Cajal–Retzius Cell Migration in the Developing Mouse Neocortex
2019-04-19

The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal-Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.
ClinOmicsTrailbc: a visual analytics tool for breast cancer treatment stratification
2019-04-19

Abstract Motivation Breast cancer is the second leading cause of cancer death among women. Tumors, even of the same histopathological subtype, exhibit a high genotypic diversity that impedes therapy stratification and that hence must be accounted for in the treatment decision-making process. Results Here, we present ClinOmicsTrailbc, a comprehensive visual analytics tool for breast cancer decision support that provides a holistic assessment of standard-of-care targeted drugs, candidates for drug repositioning and immunotherapeutic approaches. To this end, our tool analyzes and visualizes clinical markers and (epi-)genomics and transcriptomics datasets to identify and evaluate the tumor’s main driver mutations, the tumor mutational burden, activity patterns of core cancer-relevant pathways, drug-specific biomarkers, the status of molecular drug targets and pharmacogenomic influences. In order to demonstrate ClinOmicsTrailbc’s rich functionality, we present three case studies highlighting various ways in which ClinOmicsTrailbc can support breast cancer precision medicine. ClinOmicsTrailbc is a powerful integrated visual analytics tool for breast cancer research in general and for therapy stratification in particular, assisting oncologists to find the best possible treatment options for their breast cancer patients based on actionable, evidence-based results. Availability and implementation ClinOmicsTrailbc can be freely accessed at https://clinomicstrail.bioinf.uni-sb.de. Supplementary information Supplementary data are available at Bioinformatics online.
Upper limits on very-high-energy gamma-ray emission from core-collapse supernovae observed with H.E.S.S.
2019-04-19

Young core-collapse supernovae with dense-wind progenitors may be able to accelerate cosmic-ray hadrons beyond the knee of the cosmic-ray spectrum, and this may result in measurable gamma-ray emission. We searched for gamma-ray emission from ten supernovae observed with the High Energy Stereoscopic System (H.E.S.S.) within a year of the supernova event. Nine supernovae were observed serendipitously in the H.E.S.S. data collected between December 2003 and December 2014, with exposure times ranging from 1.4 to 53 h. In addition we observed SN 2016adj as a target of opportunity in February 2016 for 13 h. No significant gamma-ray emission has been detected for any of the objects, and upper limits on the &gt;1 TeV gamma-ray flux of the order of ~10 −13 cm −2 s −1 are established, corresponding to upper limits on the luminosities in the range ~2 × 10 39 to ~1 × 10 42 erg s −1 . These values are used to place model-dependent constraints on the mass-loss rates of the progenitor stars, implying upper limits between ~2 × 10 −5 and ~2 × 10 −3 M ⊙ yr −1 under reasonable assumptions on the particle acceleration parameters.