julilili42/papers huggingface dataset:
Assessment of Hepatic Perfusion Using GRASP MRI
2019-06-17

Purpose The aim of this study was to demonstrate the feasibility of hepatic perfusion imaging using dynamic contrast-enhanced (DCE) golden-angle radial sparse parallel (GRASP) magnetic resonance imaging (MRI) for characterizing liver parenchyma and hepatocellular carcinoma (HCC) before and after transarterial chemoembolization (TACE) as a potential alternative to volume perfusion computed tomography (VPCT). Methods and Materials Between November 2017 and September 2018, 10 patients (male = 8; mean age, 66.5 ± 8.6 years) with HCC were included in this prospective, institutional review board–approved study. All patients underwent DCE GRASP MRI with high spatiotemporal resolution after injection of liver-specific MR contrast agent before and after TACE. In addition, VPCT was acquired before TACE serving as standard of reference. From the dynamic imaging data of DCE MRI and VPCT, perfusion maps (arterial liver perfusion [mL/100 mL/min], portal liver perfusion [mL/100 mL/min], hepatic perfusion index [%]) were calculated using a dual-input maximum slope model and compared with assess perfusion measures, lesion characteristics, and treatment response using Wilcoxon signed-rank test. To evaluate interreader agreement for measurement repeatability, the interclass correlation coefficient (ICC) was calculated. Results Perfusion maps could be successfully generated from all DCE MRI and VPCT data. The ICC was excellent for all perfusion maps (ICC ≥ 0.88; P ≤ 0.001). Image analyses revealed perfusion parameters for DCE MRI and VPCT within the same absolute range for tumor and liver tissue. Dynamic contrast-enhanced MRI further enabled quantitative assessment of treatment response showing a significant decrease ( P ≤ 0.01) of arterial liver perfusion and hepatic perfusion index in the target lesion after TACE. Conclusions Dynamic contrast-enhanced GRASP MRI allows for a reliable and robust assessment of hepatic perfusion parameters providing quantitative results comparable to VPCT and enables characterization of HCC before and after TACE, thus posing the potential to serve as an alternative to VPCT.
Serine-Threonine Kinases Encoded by Split hipA Homologs Inhibit Tryptophanyl-tRNA Synthetase
2019-06-17

Bacterial toxin-antitoxin (TA) modules confer multidrug tolerance (persistence) that may contribute to the recalcitrance of chronic and recurrent infections. The first high-persister gene identified was hipA of Escherichia coli strain K-12, which encodes a kinase that inhibits glutamyl-tRNA synthetase. The hipA gene encodes the toxin of the hipBA TA module, while hipB encodes an antitoxin that counteracts HipA. Here, we describe a novel, widespread TA gene family, hipBST , that encodes HipT, which exhibits sequence similarity with the C terminus of HipA. HipT is a kinase that phosphorylates tryptophanyl-tRNA synthetase and thereby inhibits translation and induces the stringent response. Thus, this new TA gene family may contribute to the survival and spread of bacterial pathogens.
Evaluation of a Fluorescence-aided Identification Technique (FIT) to assist clean-up after orthodontic bracket debonding
2019-06-17

ABSTRACT Objectives: To compare a fluorescence-aided identification technique (FIT) with a conventional light source (CLS) for removing composite during debonding of brackets with respect to time needed, composite remnants, and tooth substance loss. Materials and Methods: Twelve maxillary models with 10 bovine teeth each were digitally surface-scanned and metal brackets were bonded on each tooth with Opal Seal and Opal Bond. Two operators: an experienced orthodontist (A) and an undergraduate student (B) received six models each and were asked to remove the composite remnants with a tungsten carbide bur and Sof-Lex discs by both a conventional light source (CLS group, n = 3), and fluorescent inducing light (FIT group, n = 3). The time taken was recorded, and a postoperative scan was digitally superimposed on the preoperative scan to quantify number of teeth with composite remnants and volume and thickness of enamel loss and composite remnants. Chi-square test and independent t-tests were performed to compare methods with a significance level of 5%. Results: Compared to CLS, both operators needed significantly less time when using the FIT method and degree of enamel loss, height, and volume of composite remnants and total remaining composite remnants were significantly reduced. By FIT, the volume of enamel loss was significantly reduced for operator A only. Operator B removed the same enamel volume with either method. Conclusions: Cleanup after orthodontic debonding with the FIT was superior regarding time needed and removal of composite remnants. Total enamel loss reduction was operator-dependent.
Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains
2019-06-17

Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.
Male and female preferences for nest characteristics under paternal care
2019-06-17

Abstract Nests play a critical role for offspring development across the animal kingdom. Nest quality may contribute to the builder's extended phenotype and serve as an ornament during mate choice. We examined male and female nest choice in the common goby ( Pomatoschistus microps ), a benthic fish with male‐only parental care where females deposit eggs in male‐built nests. Using prebuilt nest models, we independently manipulated two candidate nest quality traits: (a) nest entrance width with a role in oxygen ventilation, and (b) extent of sand cover with a role in camouflage. In simultaneous choice trials, male gobies exhibited no preference for any nest model type. This suggests that initial characteristics of a nesting substrate have minor importance for males, which usually remodel the nest. Females were given a choice between two males occupying either entrance‐ or cover‐manipulated nests. The same pair of males was then exposed to a second female but now with alternated nest types assigned. Most females were consistent in choosing the same, typically the heavier male of the two regardless of nest properties. However, the females that chose the same nest regardless of the male preferred low over high sand coverage and narrow over wide nest entrance. Our results indicate that females base their mating decision on a combination of male phenotype and nest traits. While we found no indication that females are attracted to highly decorated nests, our study is the first in fishes to disentangle a preference for narrow (and thus more protective) nest entrances independent of nest coverage.
The effects of anesthesia induction and positive pressure ventilation on right-ventricular function: An echocardiography-based prospective observational study
2019-06-17

<title>Abstract</title> 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.
Driver mutations in USP8 wild-type Cushing’s disease
2019-06-18

Abstract Background Medical treatment in Cushing’s disease (CD) is limited due to poor understanding of its pathogenesis. Pathogenic variants of ubiquitin specific peptidase 8 (USP8) have been confirmed as causative in around half of corticotroph tumors. We aimed to further characterize the molecular landscape of those CD tumors lacking USP8 mutations in a large cohort of patients. Methods Exome sequencing was performed on 18 paired tumor–blood samples with wild-type USP8 status. Candidate gene variants were screened by Sanger sequencing in 175 additional samples. The most frequent variant was characterized by further functional in vitro assays. Results Recurrent somatic hotspot mutations in another deubiquitinase, USP48, were found in 10.3% of analyzed samples. Several possibly damaging variants were found in TP53 in 6 of 18 samples. USP48 variants were associated with smaller tumors and trended toward higher frequency in female patients. They also changed the structural conformation of USP48 and increased its catalytic activity toward its physiological substrates histone 2A and zinc finger protein Gli1, as well as enhanced the stimulatory effect of corticotropin releasing hormone (CRH) on pro-opiomelanocortin production and adrenocorticotropic hormone secretion. Conclusions USP48 pathogenic variants are relatively frequent in USP8 wild-type tumors and enhance CRH-induced hormone production in a manner coherent with sonic hedgehog activation. In addition, TP53 pathogenic variants may be more frequent in larger CD tumors than previously reported.
Public Release of RELXILL_NK: A Relativistic Reflection Model for Testing Einstein’s Gravity
2019-06-18

Abstract We present the public release version of relxill _ nk , an X-ray reflection model for testing the Kerr hypothesis and general relativity. This model extends the relxill model that assumes the black hole (BH) spacetime is described by the Kerr metric. We also present relxilllp _ nk , the first non-Kerr X-ray reflection model with a lamppost corona configuration, as well as all other models available in the full relxill _ nk package. In all models the relevant relativistic effects are calculated through a general relativistic ray-tracing code that can be applied to any well-behaved, stationary, axisymmetric, and asymptotically flat BH spacetime. We show that the numerical error introduced by using a ray-tracing code is not significant compared with the observational error present in current X-ray reflection spectrum observations. In addition, we present the reflection spectrum for the Johannsen metric as calculated by relxill _ nk .
Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints
2019-06-18

Mitochondria are dynamic organelles with diverse functions in tissues such as liver and skeletal muscle. To unravel the mitochondrial contribution to tissue-specific physiology, we performed a systematic comparison of the mitochondrial proteome and lipidome of mice and assessed the consequences hereof for respiration. Liver and skeletal muscle mitochondrial protein composition was studied by data-independent ultra-high-performance (UHP)LC-MS/MS-proteomics, and lipid profiles were compared by UHPLC-MS/MS lipidomics. Mitochondrial function was investigated by high-resolution respirometry in samples from mice and humans. Enzymes of pyruvate oxidation as well as several subunits of complex I, III, and ATP synthase were more abundant in muscle mitochondria. Muscle mitochondria were enriched in cardiolipins associated with higher oxidative phosphorylation capacity and flexibility, in particular CL(18:2) 4 and 22:6-containing cardiolipins. In contrast, protein equipment of liver mitochondria indicated a shuttling of complex I substrates toward gluconeogenesis and ketogenesis and a higher preference for electron transfer via the flavoprotein quinone oxidoreductase pathway. Concordantly, muscle and liver mitochondria showed distinct respiratory substrate preferences. Muscle respired significantly more on the complex I substrates pyruvate and glutamate, whereas in liver maximal respiration was supported by complex II substrate succinate. This was a consistent finding in mouse liver and skeletal muscle mitochondria and human samples. Muscle mitochondria are tailored to produce ATP with a high capacity for complex I-linked substrates. Liver mitochondria are more connected to biosynthetic pathways, preferring fatty acids and succinate for oxidation. The physiologic diversity of mitochondria may help to understand tissue-specific disease pathologies and to develop therapies targeting mitochondrial function.
Dust Storm Outbreak in Central Asia After ~3.5 kyr BP
2019-06-18

Abstract The evolution and driving factors underlying dust activity in central Asia remain controversial, particularly in its effects on downwind regions. We present a Holocene dust storm activity record retrieved from the Tarim Basin (TB) and perform linear and nonlinear analyses on dust records from the TB and the Greenland areas. The results indicate a similar response of dust activities to total solar irradiance in both areas, and an outbreak of dust storms in the TB at ~3.5 kyr BP. We suggest that decreasing temperature in high northern latitudes, aided by solar activity change, reached a critical threshold near ~3.5 kyr BP. The resulting steepening of the meridional temperature gradient would have facilitated strengthening and southward shift of the Northern Hemisphere westerly jet, leading to the outbreak of dust storms through intensification of low level wind intensity and prolonged spring conditions in the Asian interior.
Prediction of Survival With Long‐Term Disease Progression in Most Common Spinocerebellar Ataxia
2019-06-18

Abstract Background Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. Objective To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. Methods Four hundred sixty‐two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. Results Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18–1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12–1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19–1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11–1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: “severe” (n = 13; 12%), “intermediate” (n = 31; 29%), and “moderate” (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. Conclusion Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxia. © 2019 International Parkinson and Movement Disorder Society
Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants
2019-06-18

Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18 and 30 years (early adulthood) after ketamine or placebo infusion. Dissociative symptoms were generally increased only in the ketamine group post-infusion. Specifically, within the ketamine group, men reported significantly more depersonalization and amnestic symptoms than women. Furthermore, with rising age only men were less affected overall with respect to dissociative symptoms. This suggests a sex-specific protective effect of higher age which may be due to delayed brain maturation in men compared to women. We conclude that it is crucial to include sex and age in studies of drug effects in general and of ketamine-action in specific to tailor more efficient psychiatric treatments. <b>Clinical Trial Registration:</b> EU Clinical Trials Register (EudraCT), trial number: 2010-023414-31.
Fatty Acid-Binding Protein 4 and Risk of Type 2 Diabetes, Myocardial Infarction and Stroke: A Prospective Cohort Study
2019-06-18

These data support the hypothesis that elevated FABP4 levels may contribute to T2D risk. In contrast, our data did not support the hypothesis that circulating FABP4 may be relevant for MI, whereas the observed association with stroke in men may need further evaluation.
DEUS: an R package for accurate small RNA profiling based on differential expression of unique sequences
2019-06-18

Abstract Summary Despite their fundamental role in various biological processes, the analysis of small RNA sequencing data remains a challenging task. Major obstacles arise when short RNA sequences map to multiple locations in the genome, align to regions that are not annotated or underwent post-transcriptional changes which hamper accurate mapping. In order to tackle these issues, we present a novel profiling strategy that circumvents the need for read mapping to a reference genome by utilizing the actual read sequences to determine expression intensities. After differential expression analysis of individual sequence counts, significant sequences are annotated against user defined feature databases and clustered by sequence similarity. This strategy enables a more comprehensive and concise representation of small RNA populations without any data loss or data distortion. Availability and implementation Code and documentation of our R package at http://ibis.helmholtz-muenchen.de/deus/. Supplementary information Supplementary data are available at Bioinformatics online.
Testing General Relativity with Supermassive Black Holes Using X-Ray Reflection Spectroscopy
2019-06-18

In this paper, we review our current efforts to test General Relativity in the strong field regime by studying the reflection spectrum of supermassive black holes. So far we have analyzed 11 sources with observations of NuSTAR, Suzaku, Swift, and XMM-Newton. Our results are consistent with General Relativity, according to which the spacetime metric around astrophysical black holes should be well approximated by the Kerr solution. We discuss the systematic uncertainties in our model and we present a preliminary study on the impact of some of them on the measurement of the spacetime metric.
PgCuckoo
2019-06-18

We demonstrate how to use PostgreSQL's planner hook to open a side entrance through which we can pass plan trees for immediate execution. Since this reaches deep into PostgreSQL, we implement plan detail inference and decoration to ensure that externally crafted trees perfectly mimic regular plans. Plan trees may then (1) be generated by external code generators that want to use PostgreSQL as a reliable and efficient back-end for new (maybe even non-relational) languages, or (2) stem from experimental rewrites of SQL plans that PostgreSQL itself does not implement (yet). The demonstration provides a live account of what becomes possible once we let PostgreSQL hatch foreign plan eggs.
New insights into Early Celtic consumption practices: Organic residue analyses of local and imported pottery from Vix-Mont Lassois
2019-06-19

The rich Mediterranean imports found in Early Celtic princely sites (7th-5th cent. BC) in Southwestern Germany, Switzerland and Eastern France have long been the focus of archaeological and public interest. Consumption practices, particularly in the context of feasting, played a major role in Early Celtic life and imported ceramic vessels have consequently been interpreted as an attempt by the elite to imitate Mediterranean wine feasting. Here we present the first scientific study carried out to elucidate the use of Mediterranean imports in Early Celtic Central Europe and their local ceramic counterparts through organic residue analyses of 99 vessels from Vix-Mont Lassois, a key Early Celtic site. In the Mediterranean imports we identified imported plant oils and grape wine, and evidence points towards appropriation of these foreign vessels. Both Greek and local wares served for drinking grape wine and other plant-based fermented beverage(s). A wide variety of animal and plant by-products (e.g. fats, oils, waxes, resin) were also identified. Using an integrative approach, we show the importance of beehive products, millet and bacteriohopanoid beverage(s) in Early Celtic drinking practices. We highlight activities related to biomaterial transformation and show intra-site and status-related differences in consumption practices and/or beverage processing.