julilili42/papers huggingface dataset:
Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus
2019-12-01

Abstract Background Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease. Methods Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 183), liver cirrhosis (LC, n = 89) and hepatocellular carcinoma (HCC, n = 171) and 238 healthy individuals (HC) were enrolled . VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models. Results The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR = 0.5, 95%CI = 0.3–0.84, P = 0.004; dominant model, OR = 0.46, 95%CI = 0.27–0.76, P = 0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR = 2.56, 95%CI = 1.01–6.48, P = 0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR = 0.6, 95%CI = 0.4–0.98, dominant model, P = 0.04 and OR = 0.6, 95%CI = 0.38–0.90, P = 0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA ( P &lt; 0.05). No association between TaqI, FokI and BsmI polymorphisms and any clinical outcome as well as liver disease progression was found. Conclusions Among the four investigated VDR polymorphisms, ApaI is associated with clinical outcome and liver disease progression in Vietnamese HBV infected patients.
Biological treatment of pediatric sarcomas by combined virotherapy and NK cell therapy
2019-12-01

Abstract Background In pediatric sarcomas, outcomes of established therapies still remain poor, especially due to high-grade resistances to chemotherapeutic compounds. Taking novel biological approaches into account, virotherapy was found to be efficient in many pediatric sarcoma types. Also NK cell therapy was denoted to represent a promising upcoming strategy for pediatric sarcoma patients. We here investigated a combinatorial approach employing oncolytic measles vaccine virotherapeutics (MeV) together with activated human NK cells (or PBMCs). Methods The human sarcoma cell lines A673 and HT1080 were used to evaluate the efficacy of this combinatorial treatment modality. Oncolysis was determined by measuring real-time cell proliferation using the xCELLigence RTCA SP system. Furthermore, expression of receptors on NK cells and the respective ligands on A673 cells was analyzed by flow cytometry. To measure the protein release of activated NK cells a LEGENDplexTM assay was performed. Results Monotherapy with MeV led to a time- and dose-dependent oncolytic reduction of A673 and HT1080 sarcoma tumor cell masses. Concurrently, such MeV infections did not change the expression of NK cell ligands MICA/B, ULBP1, 2, and 3, CD112, and CD155. As shown by real-time proliferation assays, infections of A673 and HT1080 sarcoma cells with MeV followed by co-culture with activated NK cells or PBMCs led to enhanced sarcoma cell destruction when compared to the respective monotherapies. In parallel, this dual therapy resulted in an increased release of granzymes, perforin, and granulysin from NK cells. In contrast, expression of activation and ontogenesis receptors on NK cells was not found to be altered after co-culture with MeV-infected A673 sarcoma cells. Conclusions Taken together, the combined treatment strategy comprising oncolytic MeV and activated NK cells resulted in enhanced oncolysis of A673 and HT1080 cells when compared to the respective monotherapies. In parallel, we observed an increased release of NK cell activation markers upon co-culture with MeV-infected A673 human sarcoma cells. These results support the onset of clinical trials combining oncolytic virotherapy with NK cell based immunotherapies.
Physical activity promotion in daily exercise therapy: the perspectives of exercise therapists in German rehabilitation settings
2019-12-01

Abstract Background This study aims to explore exercise therapists’ perspectives on the topic of physical activity promotion (PAP) with a focus on identifying (i) the intervention content and methodological approaches used for promoting physical activity (PA) in daily practice and (ii) the barriers and facilitators that affect PAP. Methods This qualitative study comprised the heads of exercise therapy departments ( n = 58; 41% women; mean age = 45 years) from different rehabilitation clinics in Germany. Each participant took part in a semi-structured focus-group discussion on PAP in exercise therapy. The findings of the focus groups were processed and interpreted using a conventional qualitative content analysis. Results The exercise therapists demonstrated detailed didactic–methodological strategies and action orientations for PAP. The identified core topics of the content and methods of PAP were (1) conceptualization, (2) exercise and PA for enjoyment and pleasure, (3) education with practice–theory combinations, (4) media and materials for self-directed training, and (5) strategies to enhance personal responsibility and independence. The core topics for the associated barriers and facilitators were (1) structural conditions, (2) the role of exercise therapists, (3) the interdisciplinary rehabilitation team, (4) rehabilitant experiences and expectations, and (5) aftercare services. Conclusion The topic of PAP is addressed with a high level of variability; exercise therapists involved in this study identify various methods and content for the promotion of PA within their individual practices. However, they display a limited awareness of existing evidence- and theory-based concepts for the promotion of PA as well as underlying theories of behavioural change. This variability may be due to the lack of a defined common framework for promoting PA, insufficient emphasis being placed on PA promotion in the current curricula and training, or extensive conceptual differences within German exercise therapy departments (e.g. different weighting of PAP).
Collectively biased representations of the past: Ingroup Bias in Wikipedia articles about intergroup conflicts
2019-12-01

Individuals tend to present their own group (the ingroup) in a systematically more favourable way (ingroup bias). By examining socially negotiated and publicly accessible Wikipedia articles about intergroup conflicts, we investigated ingroup bias at a collective level. Specifically, we compared articles about the same intergroup conflicts (e.g., the Falklands War) in the corresponding language versions of Wikipedia (e.g., the Spanish and English Wikipedia articles about the Falklands War). Study 1 featured a content coding of translated Wikipedia articles by trained raters, which showed that articles systematically presented the ingroup in a more favourable way (e.g., Argentina in the Spanish article and the United Kingdom in the English article) and, in reverse, the outgroup as more immoral and more responsible for the conflict. These findings were replicated and extended in Study 2, which was limited to the lead sections of articles but included considerably more conflicts and many participants instead of a few trained coders. This procedure allowed for separate analyses for each conflict, which showed considerable variance in the results pattern with a stronger ingroup bias for (1) more recent conflicts and (2) conflicts in which the proportion of ingroup members among the top editors was larger. Finally, a third study ruled out that these effects were driven by translations or the raters’ own nationality. Therefore, this paper is the first to demonstrate ingroup bias in Wikipedia – a finding that is of practical as well as theoretical relevance as we outline in the discussion.
Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human
2019-12-01

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well.
Translational Highlights in Breast and Ovarian Cancer 2019 – Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy
2019-12-01

Abstract In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the pBRCA1/2 germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.
Disc kinematics and stability in high-mass star formation - Linking simulations and observations
2019-12-01

Context. In the disc-mediated accretion scenario for the formation of the most massive stars, high densities and high accretion rates could induce gravitational instabilities in the disc, forcing it to fragment and produce companion objects.Aims. We investigate the effects of inclination and spatial resolution on the observable kinematics and stability of discs in high-mass star formation.Methods. We studied a high-resolution 3D radiation-hydrodynamic simulation that leads to the fragmentation of a massive disc. Using RADMC-3D we produced 1.3 mm continuum and CH3 CN line cubes at different inclinations. The model was set to different distances, and synthetic observations were created for ALMA at ~80 mas resolution and NOEMA at ~0.4′′.Results. The synthetic ALMA observations resolve all fragments and their kinematics well. The synthetic NOEMA observations at 800 pc with linear resolution of ~300 au are able to resolve the fragments, while at 2000 pc with linear resolution of ~800 au only a single structure slightly elongated towards the brightest fragment is observed. The position–velocity (PV) plots show the differential rotation of material best in the edge-on views. A discontinuity is seen at a radius of ~250 au, corresponding to the position of the centrifugal barrier. As the observations become less resolved, the inner high-velocity components of the disc become blended with the envelope and the PV plots resemble rigid-body-like rotation. Protostellar mass estimates from PV plots of poorly resolved observations are therefore overestimated. We fit the emission of CH3 CN (12K −11K ) lines and produce maps of gas temperature with values in the range of 100–300 K. Studying the Toomre stability of the discs, we find low Q values below the critical value for stability against gravitational collapse at the positions of the fragments and in the arms connecting the fragments for the resolved observations. For the poorly resolved observations we find low Q values in the outskirts of the disc. Therefore, although we could not resolve any of the fragments, we are able to predict that the disc is unstable and fragmenting. This conclusion is valid regardless of our knowledge about the inclination of the disc.Conclusions. These synthetic observations reveal the potential and limitations of studying discs in high-mass star formation with current (millimetre) interferometers. While the extremely high spatial resolution of ALMA reveals objects in extraordinary detail, rotational structures and instabilities within accretion discs can also be identified in poorly resolved observations.
Prune and Replace NAS
2019-12-01

While recent NAS algorithms are thousands of times faster than the pioneering\\nworks, it is often overlooked that they use fewer candidate operations,\\nresulting in a significantly smaller search space. We present PR-DARTS, a NAS\\nalgorithm that discovers strong network configurations in a much larger search\\nspace and a single day. A small candidate operation pool is used, from which\\ncandidates are progressively pruned and replaced with better performing ones.\\nExperiments on CIFAR-10 and CIFAR-100 achieve 2.51% and 15.53% test error,\\nrespectively, despite searching in a space where each cell has 150 times as\\nmany possible configurations than in the DARTS baseline. Code is available at\\nhttps://github.com/cogsys-tuebingen/prdarts\\n
Self-supervised Multi-stage Estimation of Remaining Useful Life for Electric Drive Units
2019-12-01

The use of pedelecs as a mobility solution has increased considerably in recent years. One of their main components, the drive unit, consists of several mechanical elements such as bearings and gears, which deteriorate over time and, thus, increasing the probability of a major failure. This work introduces a data-based approach for monitoring the drive unit's condition and forecasting failures, in order to ensure the reliability of the system. A trustworthy prediction of anomalies requires a vast dataset to train and test the selected algorithms. To this end, we make use of a database consisting of data collected for the past couple of years during endurance tests of almost one hundred drive units. The collected database allow us to test machine learning approaches under more realistic prognosis applications in comparison to existing published works, which brings diverse challenges such as unlabeled and unbalaced data. The focus of the present approach is the data preprocessing through different stages, such as data labeling and undersampling, to reduce the negative impact of the problematics that involve this database. Afterwards, a Gaussian process for regression is trained with these preprocessed data to predict the remaining useful life of the drive unit. The experimental study shows that by performing these preprocessing stages, an accurate estimation of the time to failure of the drive unit can be achieved.
Sonographic features of carotid artery dissection due to extension of aortic dissection: a case report
2019-12-01

Abstract Background Carotid artery dissection due to extension of aortic dissection (CAEAD) is a severe complication of acute aortic dissection. The risk of ischemic stroke is increased. Early sonographic detection and repeat evaluation are necessary to guide clinical management. Case presentation A 58-year-old male patient presents with sudden, tearing retrosternal pain. Point-of-care carotid ultrasound is used to establish the diagnosis of CAEAD. We describe a number of sonographic features and compare ultrasound to other imaging modalities. Conclusions Bedside carotid ultrasound enables rapid, sensitive and safe hemodynamic assessment, especially in critically ill patients.
Diabetes and Fatty Liver
2019-12-01

Nonalcoholic fatty liver disease (NAFLD) affects more than 25% of the adult population worldwide. According to analyses for 2016, Germany ranks third behind Greece (41%) and Italy (25.4%) in the prevalence of NAFLD (22.9% of the total population). An increase in the prevalence of NAFLD to 26.4% has been calculated for Germany (2.3) for the year 2030. At around 70%, the frequency of NAFLD is particularly high in people with obesity and/or type 2 diabetes [2]. However, NAFLD also occurs in about 7% of lean people and is then primarily of genetic origin [2]. In Europe and the USA, NAFLD is now regarded as the most frequent cause of chronic liver diseases although most people with NAFLD die from secondary diseases resulting from diabetes or cardiovascular diseases. Therefore, it is particularly important to test patients with type 2 diabetes for the presence, and especially the degree of severity, of NAFLD, and to plan therapy accordingly [3] [4].
Assessing Aesthetics of Generated Abstract Images Using Correlation Structure
2019-12-01

Can we generate abstract aesthetic images without bias from natural or human\\nselected image corpi? Are aesthetic images singled out in their correlation\\nfunctions? In this paper we give answers to these and more questions. We\\ngenerate images using compositional pattern-producing networks with random\\nweights and varying architecture. We demonstrate that even with the randomly\\nselected weights the correlation functions remain largely determined by the\\nnetwork architecture. In a controlled experiment, human subjects picked\\naesthetic images out of a large dataset of all generated images. Statistical\\nanalysis reveals that the correlation function is indeed different for\\naesthetic images.\\n
Position Paper on Lipid Therapy in Patients with DiabetesMellitus
2019-12-01

Patients with diabetes mellitus generally have a significantly increased cardiovascular risk. For this reason, lipid therapy and a reduction in LDL cholesterol based on risk stratification are an integral part of diabetes therapy; the following position paper should therefore also be viewed as a topic-related supplement to the annually updated recommendation for the treatment of type 2 diabetes and should also be updated annually in future together with the DDG's practical recommendations.
Synthesis and application of magnetic nanoparticles (MNPs) in siRNA delivery to the retina
2019-12-01

Abstract Introduction Small interfering RNA (siRNA) is an important RNA interference tool that has found significant application in ocular therapy. For this reason, there is a considerable demand of siRNA delivery platforms able to effectively transfect cells within the retina. Up to now several strategies have been investigated for this application such as lipids, nanoparticles and polymers but in all the cases invasive injections are the only administration routes explored. Moreover, a major limitation shared by all these delivery systems is the lack of active targeting toward the posterior segment of the eye that hampers high transfection efficiencies. Purpose We aim to synthesize and formulate a new magnetic nanoparticles‐mediated delivery technology that shall allow safe and efficient siRNA delivery to the retina assisted by magnetic targeting. Methods (1) Cationic MNPs have been synthesized, characterized, and their ability to form complexes with siRNA has been demonstrated by Zeta Potential. (2) The in vitro MNPs mediated gene silencing have been tested on green fluorescent protein (GFP)‐stably transfected cells (661W &amp; RPE). Also, gene silencing of the endogenous glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) gene has been monitored. (3) Finally, the in vitro toxicity of the formulations has been determined in term of apoptosis, cell proliferation and protein production. Results MNPs were able to efficiently complex siRNA while maintain their size and charge. MNPs complexed with siRNA achieved high transfection efficiency and gene silencing of GFP as shown by fluorescence microscopy and flow cytometry. The knock‐down efficiency has been confirmed by targeting GAPDH by immunohistochemistry. Finally, proliferation, apoptosis and total protein content assays demonstrate the full biocompatibility of these gene delivery platforms. Conclusions Magnetic nanoparticles are a promising platform for gene therapy in the context of ocular therapy and allow to achieve high transfection efficiencies in retinal cell lines. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.
Preservation of the bladder, but at what cost?
2019-12-01

Radical cystectomy (rCx) with pelvic lymphadenectomy is the gold standard for muscle invasive bladder cancer. Nevertheless advantages of trimodal treatment (TMT) over rCx is an ongoing discussion in urology. According to the guidelines of the European Association of Urology and the SIU, TMT should only be offered to “selected, well-informed, compliant” patients (1,2). Due to a lack of randomized studies comparing the two, we can only rely on retrospective analysis. Most of these focus on the functional and oncological outcome. With aging populations in most industrialized countries and therefore rising healthcare expenses, cost effectiveness is of growing importance. This is reflected in a trend in current publications to investigate the differences in cost of different treatments available. However, as stated in the article this does not mean cost-effectiveness, i.e., oncological outcome and quality of life.
Kazuo Ishiguro’s Authoritarian Narrators:An Artist of the Floating World,The Remains of the Day,Never Let Me Go, and the Authoritarian Personality
2019-12-01

Abstract This essay examines how Kazuo Ishiguro’s narrators – namely, those of his novels An Artist of the Floating World , The Remains of the Day , and Never Let Me Go – are all variations of one central theme: the authoritarian personality. By drawing on the findings of the eponymous study by Theodor W. Adorno et al., it analyses the role of the narrators’ respective upbringings in the formation of their authoritarian predisposition as well as how their authoritarian tendencies later manifest themselves in their conduct. The way these tendencies – or the limitations imposed by them on the narrators’ imagination – also manifest themselves aesthetically in the narrative discourse further allows a comparison to Hannah Arendt’s analysis of Adolf Eichmann in Eichmann in Jerusalem: A Report on the Banality of Evil .