julilili42/papers huggingface dataset:
MHCquant: Automated and Reproducible Data Analysis for Immunopeptidomics
2019-10-07

Personalized multipeptide vaccines are currently being discussed intensively for tumor immunotherapy. In order to identify epitopes-short, immunogenic peptides-suitable for eliciting a tumor-specific immune response, human leukocyte antigen-presented peptides are isolated by immunoaffinity purification from cancer tissue samples and analyzed by liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS). Here, we present MHCquant, a fully automated, portable computational pipeline able to process LC-MS/MS data automatically and generate annotated, false discovery rate-controlled lists of (neo-)epitopes with associated relative quantification information. We could show that MHCquant achieves higher sensitivity than established methods. While obtaining the highest number of unique peptides, the rate of predicted MHC binders remains still comparable to other tools. Reprocessing of the data from a previously published study resulted in the identification of several neoepitopes not detected by previously applied methods. MHCquant integrates tailor-made pipeline components with existing open-source software into a coherent processing workflow. Container-based virtualization permits execution of this workflow without complex software installation, execution on cluster/cloud infrastructures, and full reproducibility of the results. Integration with the data analysis workbench KNIME enables easy mining of large-scale immunopeptidomics data sets. MHCquant is available as open-source software along with accompanying documentation on our website at https://www.openms.de/mhcquant/ .
Clinical Situation, Therapy, and Follow-Up of Adult Craniopharyngioma
2019-10-07

Abstract Context Craniopharyngioma is a rare neoplastic entity of the central nervous system. Childhood-onset craniopharyngioma is the subject of frequent research whereas the information on adult-onset craniopharyngioma is scarce. Objective The objective of this study was to examine the level of daily impairment in adult patients suffering from craniopharyngioma. Design Noninterventional patient registry indexed as PV4842 with the local ethics committee. Setting The study is set in a hospitalized and ambulatory setting. Patients 148 patients with adult-onset craniopharyngioma were recruited from 8 centers, 22 prospectively and 126 retrospectively. Mean follow-up was 31 months. Interventions No interventions performed. Main Outcome Measures Complications, symptoms, body mass index (BMI), and quality of life (QoL; EORTC QLQ C30 and BN20) were recorded preoperatively and at follow-up. The hypotheses tested were generated after data collection. Results Complications were more frequent after transcranial than transsphenoidal approaches (31 % vs. 11%; P &amp;lt; 0.01). Preoperative obesity was present in 0% papillary and in 38% of all adamantinomatous craniopharyngiomas (P = 0.05), and diabetes insipidus was more frequent for papillary craniopharyngioma (36.8% vs. 16,7%; P &amp;lt; 0.05). Hormone deficits at follow-up were reduced in 16.9%, equal in 31.4%, and increased in 63.6% (P &amp;lt; 0.001). BMI increased from 28.7 ± 7.4 kg/m2 before surgery to 30.2 ± 7.4 kg/m2 at follow-up (P &amp;lt; 0.001). In QoL, a decrease of future uncertainty (62.5 vs. 36.8; P = 0.02) and visual disorders (38.9 vs. 12.0; P = 0.01) were observed in the prospective collective after surgery. Conclusions Adult craniopharyngioma is associated with a complex sociological and psychological burden and hypothalamic dysfunction, warranting further investigation and emphasizing the need for a wider treatment approach.
Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine
2019-10-07

Abstract Background A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria. Methods Filter-paper blood samples were collected from 725 non-febrile individuals, comprising 250 children (≤ 12 years), 250 pregnant women and 225 other adults, between October 2014 and February 2015 in Nnewi town, Southeast Nigeria. Nested PCR followed by direct sequencing was employed for the genotyping of Pfcrt and Pfmdr1 genes. Results A total of 103 parasites-positive samples were recovered, comprising of 48 (19.20%) among children, 20 (20.00%) among pregnant women and 35 (15.50%) among other adults cohort. The frequency of the mutant genotype of Pfcrt 76T, 75E and 74I was 94.50% each. Parasite isolates from children had a frequency of 100% for mutant alleles in all Pfcrt codons while isolates from pregnant women and other adults had a frequency of 91% each in all codons. Haplotype distribution of pfcrt gene were 5.45, 0.00 and 76.37% for CVMNK, SVMNT and CVIET, respectively. For Pfmdr1 gene, the frequency of 86Y, 184F and 1246Y mutant alleles were 8.54, 29.27 and 3.66%, respectively. Amongst the Pfmdr1 haplotypes analysed, NFD had the highest frequency of 24.4%, followed by YFD at 6.10%. NYF and NYY occurred the least (1.20%). Conclusion The high level of Pfcrt mutations is suggestive of a sustained CQ pressure on P. falciparum isolates in the study area, despite the change of first line treatment from CQ to artemisinin combination therapy for 11 years. A new strategy to ensure the complete withdrawal of CQ from the country is recommended.
Trends in employment and hospitalisation in patients with Sjögren's syndrome 1996-2016: results from the German National database.
2019-10-07

Overall, similar trends were observed for RA and pSS cohorts despite minor changes in pSS therapy. Work participation has improved significantly over two decades in pSS. A greater perception of pSS without systemic manifestations may have caused a shift towards less severely affected patient cohorts today.
Metascience on Peer Review: Testing the Effects of a Study’s Originality and Statistical Significance in a Field Experiment
2019-10-07

Peer review has become the gold standard in scientific publishing as a selection method and a refinement scheme for research reports. However, despite its pervasiveness and conferred importance, relatively little empirical research has been conducted to document its effectiveness. Further, there is evidence that factors other than a submission’s merits can substantially influence peer reviewers’ evaluations. We report the results of a metascientific field experiment on the effect of the originality of a study and the statistical significance of its primary outcome on reviewers’ evaluations. The general aim of this experiment, which was carried out in the peer-review process for a conference, was to demonstrate the feasibility and value of metascientific experiments on the peer-review process and thereby encourage research that will lead to understanding its mechanisms and determinants, effectively contextualizing it in psychological theories of various biases, and developing practical procedures to increase its utility.
Freezing of gait: understanding the complexity of an enigmatic phenomenon
2019-10-08

Abstract Diverse but complementary methodologies are required to uncover the complex determinants and pathophysiology of freezing of gait. To develop future therapeutic avenues, we need a deeper understanding of the disseminated functional-anatomic network and its temporally associated dynamic processes. In this targeted review, we will summarize the latest advances across multiple methodological domains including clinical phenomenology, neurogenetics, multimodal neuroimaging, neurophysiology, and neuromodulation. We found that (i) locomotor network vulnerability is established by structural damage, e.g. from neurodegeneration possibly as result from genetic variability, or to variable degree from brain lesions. This leads to an enhanced network susceptibility, where (ii) modulators can both increase or decrease the threshold to express freezing of gait. Consequent to a threshold decrease, (iii) neuronal integration failure of a multilevel brain network will occur and affect one or numerous nodes and projections of the multilevel network. Finally, (iv) an ultimate pathway might encounter failure of effective motor output and give rise to freezing of gait as clinical endpoint. In conclusion, we derive key questions from this review that challenge this pathophysiological view. We suggest that future research on these questions should lead to improved pathophysiological insight and enhanced therapeutic strategies.
Propagation of gravitational waves in Chern-Simons axion Einstein gravity
2019-10-08

In this paper we shall investigate the propagation of gravitational waves in a flat Friedman-Robertson-Walker background, in the context of a string motivated corrected Einstein gravity. Particularly, we shall consider a misalignment axion Einstein gravity in the presence of a string originating Chern-Simons coupling of the axion field to the Chern-Pontryagin density in four dimensions. We shall focus our study on the propagation of the gravitational waves, and we shall investigate whether there exists any difference in the propagation of the polarization states of the gravitational waves. As we demonstrate, the dispersion relations are different in the right-handed mode and the left-handed mode. Finally, we compare the propagation of the axion Chern-Simons Einstein theory with that of standard F(R) gravity.
Variability and Heritability of Thiamine Pharmacokinetics With Focus on OCT1 Effects on Membrane Transport and Pharmacokinetics in Humans
2019-10-08

Thiamine is substrate of the hepatic uptake transporter organic cation transporter 1 (OCT1), and pathological lipid metabolism was associated with OCT1‐dependent thiamine transport. However, it is unknown whether clinical pharmacokinetics of thiamine is modulated by OCT1 genotype. We analyzed thiamine transport in vitro , thiamine blood concentrations after high‐dose and low‐dose (nutritional) intake, and heritability of thiamine and thiamine‐phosphate blood concentrations. The variant OCT1*2 had reduced and OCT1*3 to OCT1*6 had deficient thiamine uptake activity. However, pharmacokinetics of thiamine did not differ depending on OCT1 genotype. Further studies in primary human hepatocytes indicated that several cation transporters, including OCT1, OCT3, and THTR‐2, contribute to hepatic uptake of thiamine. As much as 54% of the variation in thiamine and 75% in variation of thiamine monophosphate plasma concentrations was determined by heritable factors. Apparently, thiamine is not useful as a probe drug for OCT1 activity, but the high heritability, particularly of thiamine monophosphate, may stimulate further genomic research.
Glycoconjugated Phthalocyanines as Photosensitizers for PDT – Overcoming Aggregation in Solution
2019-10-08

A series of new glycoconjugated zinc(II) phthalocyanines (Pcs) was synthesized and fully characterized. The major focus of the structural design for these new Pcs was upon the reduction of aggregate formation in solution. Therefore, the aglycons of the Pc‐linked sugars, the number and the position of the carbohydrate substituents on the Pc and the linker between sugar and Pc were varied. Specifically, di‐ and octasubstituted zinc(II) phthalocyanines with triazole and C–C linkages were synthesized and their aggregation behaviour was investigated by UV/Vis‐, CD‐ and NMR spectroscopy. The C‐glycosidically decorated Pcs described here are the first compound types of this kind. These C‐glycosidically substituted Pcs were shown to not form any aggregation in solution and hence, are considered to be potential photosensitizers in photodynamic therapy. All Pcs synthesized in this study exhibited excellent photophysical properties for use as photosensitizers ( λ max &gt; 675 nm with ε max &gt; 10 5 m –1 cm –1 ). Preliminary cytotoxicity studies of the Pcs presented here showed that all Pcs are photodynamically effective.
Risk aversion and the teaching profession: an analysis including different forms of risk aversion, different control groups, selection and socialization effects
2019-10-08

Risk aversion might affect current and potential teachers’ reaction to reforms, such as payment reforms. However, evidence on teachers’ risk aversion in comparison to other occupations is limited. The present study is based on twelve waves of a representative German data set (N = 18,381) and shows that teaching relates positively to risk aversion, especially to risk aversion with respect to occupational career. Teachers score higher in risk aversion even than other civil servants. Our results suggest that risk-averse individuals are attracted to teaching, while we find no evidence for a socialization effect during the career.
In‐situ photopolymerized polyhedral oligomeric silsesquioxane‐derived monolithic capillary columns with quinidine functionality for enantioseparation by nano‐liquid chromatography
2019-10-08

Abstract The successful fabrication of monolithic capillary columns for enantiomer separations was achieved within vinylized fused silica capillaries via fast “one‐pot” photo‐initiated free radical polymerization reaction. A mixture consisting of polyhedral oligomeric silsesquioxane, O ‐[2‐(methacryloyloxy)ethylcarbamoyl]‐10,11‐dihydroquinidine was copolymerized in the presence of n ‐butanol, ethylene glycol and photo‐initiator 2,2‐dimethoxy‐2‐phenylacetophenone. The morphology of the resultant polymeric hybrid inorganic‐organic material and its permeability as well as porosity can be controlled by adjusting the composition of the monomers and binary porogenic solvent. The chromatographic characteristics of the columns have been investigated. Separation factors of N ‐acetyl‐phenylalanine (Ac‐Phe) and dichlorprop dropped with decrease of chiral functional monomer. Permeability was better when the macroporogen ethyleneglycol was present at higher concentrations during the polymerization. In general, the chiral compounds were well separated (dichlorprop: α = 1.53, R s up to 4.14; Ac‐Phe: α = 1.36, R s up to 2.69) by nano‐HPLC with an optimized enantioselective monolithic capillary column which can be prepared within a few minutes.
Metascience on Peer Review: Testing the Effects of a Study’s Originality and Statistical Significance in a Field Experiment
2019-10-08

Peer review has become the gold standard in scientific publishing as a selection method and a refinement scheme for research reports. However, despite its pervasiveness and conferred importance, relatively little empirical research has been conducted to document its effectiveness. Further, there is evidence that factors other than a submission’s merits can substantially influence peer reviewers’ evaluations. We report the results of a metascientific field experiment on the effect of the originality of a study and the statistical significance of its primary outcome on reviewers’ evaluations. The general aim of this experiment, which was carried out in the peer-review process for a conference, was to demonstrate the feasibility and value of metascientific experiments on the peer-review process and thereby encourage research that will lead to understanding its mechanisms and determinants, effectively contextualizing it in psychological theories of various biases, and developing practical procedures to increase its utility.
Human gut mobileome during antibiotic therapy. A trajectory-based approach to analysis of the metagenomic time-series datasets
2019-10-08

Abstract Motivation Antibiotic resistance is widely recognized as a severe threat to current medical practice. Each antibiotic therapy drives the emergence and subsequent retention of antibiotics resistance genes within the human gut microbiome. However, the details on how the resistance spreads between bacteria within the human gut remain unknown, as does the role of horizontal gene transfer in this process, too. Results We present a novel approach to the analysis of time-series whole-genome metagenomic sequencing data. This involves partitioning the scaffolds from the metagenomic assembly into groups corresponding to bacterial chromosomes, plasmids and those with prophages and transposons. Using specialized sequencing of the bacteriophages we were able to track the flow of ciprofloxacin resistance genes from bacterial chromosomes, through the plasmids, to prophages and phages. Contact anna.gorska@univr.it .
The effects of anesthesia induction and positive pressure ventilation on right-ventricular function: An echocardiography-based prospective observational study
2019-10-08

Abstract Background: General anesthesia induction with the initiation of positive pressure ventilation creates a vulnerable phase for patients. The impact of positive intrathoracic pressure on cardiac performance has been studied but remains controversial. 3D echocardiography is a valid and MRI-validated bed-side tool to evaluate the right ventricle (RV). The aim of this study was to assess the impact of anesthesia induction (using midazolam, sufentanil and rocuronium, followed by sevoflurane) with positive pressure ventilation (PEEP 5, tidal volume 6 – 8 ml/kg) on 2D and 3D echocardiography derived parameters of RV function. Methods: A prospective observational study on fifty-three patients undergoing elective cardiac surgery in a tertiary care university hospital was designed. Transthoracic echocardiography exams were performed before and immediately after anesthesia induction and were recorded together with hemodynamic parameters and ventilator settings. Results: After anesthesia induction TAPSE (mean difference -1.6mm (95% CI -2.6mm to -0.7mm; p=0.0013) as well as the Tissue Doppler derived tricuspid annulus peak velocity (TDITVs’) were significantly reduced (mean difference -1.9% (95% CI: -2.6 to -1.2; p&lt;0.0001), but global right ventricular ejection fraction (RVEF; p=0.1607) and right ventricular stroke volume (RVSV; p=0.1838) did not change. Conclusions: This data shows a preserved right ventricular ejection fraction and right ventricular stroke volume after anesthesia induction and initiation of positive pressure ventilation. However, the baso-apical right ventricular function is significantly reduced. Larger studies are needed in order to determine the clinical impact of these findings especially in patients presenting with impaired right ventricular function before anesthesia induction. Trial registration: Retrospecitvely registered, 6th June 2016, ClinicalTrials.gov Identifier NCT02820727.
Tumor Vessel Normalization, Immunostimulatory Reprogramming, and Improved Survival in Glioblastoma with Combined Inhibition of PD-1, Angiopoietin-2, and VEGF
2019-10-09

Abstract Glioblastoma (GBM) is a non-T-cell–inflamed cancer characterized by an immunosuppressive microenvironment that impedes dendritic cell maturation and T-cell cytotoxicity. Proangiogenic cytokines such as VEGF and angiopoietin-2 (Ang-2) have high expression in glioblastoma in a cell-specific manner and not only drive tumor angiogenesis and vascular permeability but also negatively regulate T-lymphocyte and innate immune cell responses. Consequently, the alleviation of immunosuppression might be a prerequisite for successful immune checkpoint therapy in GBM. We here combined antiangiogenic and immune checkpoint therapy and demonstrated improved therapeutic efficacy in syngeneic, orthotopic GBM models. We observed that blockade of VEGF, Ang-2, and programmed cell death protein-1 (PD-1) significantly extended survival compared with vascular targeting alone. In the GBM microenvironment, triple therapy increased the numbers of CTLs, which inversely correlated with myeloid-derived suppressor cells and regulatory T cells. Transcriptome analysis of GBM microvessels indicated a global vascular normalization that was highest after triple therapy. Our results propose a rationale to overcome tumor immunosuppression and the current limitations of VEGF monotherapy by integrating the synergistic effects of VEGF/Ang-2 and PD-1 blockade to reinforce antitumor immunity through a normalized vasculature.
Physiological and neuromotor changes induced by two different stand-walk-sit work rotations
2019-10-09

The potential of rotating postures to alleviate the effects of prolonged standing and sitting postures has been advocated to attenuate the accumulation of muscle fatigue, considered a precursor to musculoskeletal disorders. We aimed to evaluate the effects of two posture rotations, both including standing, walking, sitting, on physiological and neuromotor measures. Twenty-two participants followed two posture rotations, with different rest-break distributions, for 5.25 h. Lower-leg muscle twitch force, volume, force control and discomfort perception were evaluated during and after work exposure on two non-consecutive days. Significant changes in all measures indicate a detrimental effect in lower-leg long-lasting muscle fatigue, oedema, performance and discomfort after 5 h for both exposures. However, for both exposures recovery was significant 1 h and 15 h post-workday. Differences between the two rotation schedules were not significant. Hence, stand-walk-sit posture rotation promotes recovery of the tested measures and is likely to better prevent muscle fatigue accumulation. <b>Practitioner summary:</b> Lower-leg muscle twitch force, volume, force control, and discomfort were quantified during and after 5 h of stand-walk-sit work rotations with two different rest-break distributions. Measures revealed similar significant effects of work exposures regardless of rotation; which did not persist post-work. This beneficial recovery contrasts with the standing only situations. <b>Abbreviations:</b> MSDs: musculoskeletal disorders; MTF: muscle twitch force; RMSE: root mean square error; MVC: maximum voluntary contraction; <i>M</i>: mean; SE: standard error.
Editorial: Active ageing, social inclusion and wellbeing: Benefits of learning in later life
2019-10-09

The education of older adults has been considered the fastest growing branch of adult education in post-industrial countries and one of the most crucial challenges facing current adult European education (Formosa, 2000). Early research on the learning preferences, motivations and trends of older persons – as well as the impact of learning on the quality of life of older learners – can be traced to the 1950s (Havighurst, 1953), even before the field of educational gerontology was formally established in the 1975 by David Peterson (1976). In recent years, an unprecedented level of influence of the concept of lifelong learning on policies on active ageing have led to a ‘renaissance’ moment in the practice and research of older adult learning (Glendenning 1992; Findsen & Formosa, 2016). Whilst at the turn of the millennium, one found only a handful of book publications in the field of older adult learning, and the few published articles were often in specialised and off the radar journals, in a space of less than two decades the situation is markedly different. Nowadays, as societies are experiencing, or anticipating, unprecedented number of older persons, the field of late-life learning is firmly established in both adult education and gerontology graduate programmes, as well as mainstream adult education and gerontology journals. Indeed, the field of older adult learning boasts an exciting and innovative field of practice, led by experts who group themselves under the mantles of adult educators, educational gerontologists, geragogists or gerontagogists (Kern, 2014). Learning in later life has entrenched itself as an integral part of adult education research, focusing on the diverse provision of late-life learning, the motivations and interests of older learners; wide-participation and emancipatory policies for older adult learning; and the benefits of learning for learners, providers, and society in general.