julilili42/papers huggingface dataset:
Usability Tests in Medicine: A Cost-Benefit Analysis for Hospitals Before Acquiring Medical Devices for Theatre
2017-04-11

Purpose: The use of active medical devices in clinical routine should be as safe and efficient as possible. Usability tests (UTs) help improve these aspects of medical devices during their development, but UTs can be of use for hospitals even after a product has been launched. The present pilot study examines the costs and possible benefits of UT for hospitals before buying new medical devices for theatre. Methods: Two active medical devices with different complexity were tested in a standardized UT and a cost-benefit analysis was carried out assuming a different device bought at the same price with a higher usability could increase the efficiency of task solving and due to that save valuable theatre time. Results: The cost of the UT amounted up to €19.400. Hospitals could benefit from UTs before buying new devices for theatre by reducing time-consuming operator errors and thereby increase productivity and patient safety. The possible benefits amounted from €23.300 to €1.570.000 (median = €797.000). Conclusion: Not only hospitals could benefit economically from investing in a UT before deciding to buy a medical device, but especially patients would profit from a higher usability by reducing possible operator errors and increase safety and performance of use.
Iron Isotope Fractionation during Fe(II) Oxidation Mediated by the Oxygen-Producing Marine Cyanobacterium Synechococcus PCC 7002
2017-04-12

In this study, we couple iron isotope analysis to microscopic and mineralogical investigation of iron speciation during circumneutral Fe(II) oxidation and Fe(III) precipitation with photosynthetically produced oxygen. In the presence of the cyanobacterium Synechococcus PCC 7002, aqueous Fe(II) (Fe(II)<sub>aq</sub>) is oxidized and precipitated as amorphous Fe(III) oxyhydroxide minerals (iron precipitates, Fe<sub>ppt</sub>), with distinct isotopic fractionation (ε<sup>56</sup>Fe) values determined from fitting the δ<sup>56</sup>Fe(II)<sub>aq</sub> (1.79‰ and 2.15‰) and the δ<sup>56</sup>Fe<sub>ppt</sub> (2.44‰ and 2.98‰) data trends from two replicate experiments. Additional Fe(II) and Fe(III) phases were detected using microscopy and chemical extractions and likely represent Fe(II) and Fe(III) sorbed to minerals and cells. The iron desorbed with sodium acetate (Fe<sub>NaAc</sub>) yielded heavier δ<sup>56</sup>Fe compositions than Fe(II)<sub>aq</sub>. Modeling of the fractionation during Fe(III) sorption to cells and Fe(II) sorption to Fe<sub>ppt</sub>, combined with equilibration of sorbed iron and with Fe(II)<sub>aq</sub> using published fractionation factors, is consistent with our resulting δ<sup>56</sup>Fe<sub>NaAc</sub>. The δ<sup>56</sup>Fe<sub>ppt</sub> data trend is inconsistent with complete equilibrium exchange with Fe(II)<sub>aq</sub>. Because of this and our detection of microbially excreted organics (e.g., exopolysaccharides) coating Fe<sub>ppt</sub> in our microscopic analysis, we suggest that electron and atom exchange is partially suppressed in this system by biologically produced organics. These results indicate that cyanobacteria influence the fate and composition of iron in sunlit environments via their role in Fe(II) oxidation through O<sub>2</sub> production, the capacity of their cell surfaces to sorb iron, and the interaction of secreted organics with Fe(III) minerals.
Downstream element determines RNase Y cleavage of the saePQRS operon in Staphylococcus aureus
2017-04-12

In gram-positive bacteria, RNase J1, RNase J2 and RNase Y are thought to be major contributors to mRNA degradation and maturation. In Staphylococcus aureus, RNase Y activity is restricted to regulating the mRNA decay of only certain transcripts. Here the saePQRS operon was used as a model to analyze RNase Y specificity in living cells. A RNase Y cleavage site is located in an intergenic region between saeP and saeQ. This cleavage resulted in rapid degradation of the upstream fragment and stabilization of the downstream fragment. Thereby, the expression ratio of the different components of the operon was shifted towards saeRS, emphasizing the regulatory role of RNase Y activity. To assess cleavage specificity different regions surrounding the sae CS were cloned upstream of truncated gfp, and processing was analyzed in vivo using probes up- and downstream of CS. RNase Y cleavage was not determined by the cleavage site sequence. Instead a 24-bp double-stranded recognition structure was identified that was required to initiate cleavage 6 nt upstream. The results indicate that RNase Y activity is determined by secondary structure recognition determinants, which guide cleavage from a distance.
Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam
2017-04-12

Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%). Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings indicate that HDV infection is highly prevalent and HDV-2 is predominant in Central Vietnam. The data will add new information to the management of HBsAg-positive patients in a highly HBV endemic region to in- or exclude HDV infection in terms of diagnostic and treatment options.
Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata Extracts
2017-04-12

Abstract Boswellic acids constitute a group of unique pentacyclic triterpene acids from Boswellia serrata with multiple pharmacological activities that confer them anti-inflammatory and anti-tumoral properties. A subgroup of boswellic acids, characterized by an 11-keto group, elevates intracellular Ca2+ concentrations [Ca2+]i and causes moderate aggregation of human platelets. How different BAs and their mixtures in pharmacological preparations affect these parameters in activated platelets has not been addressed, so far. Here, we show that boswellic acids either antagonize or induce Ca2+ mobilization and platelet aggregation depending on defined structural determinants with inductive effects predominating for a B. serrata gum resin extract. 3-O-Acetyl-11-keto-β-boswellic acid potently suppressed Ca2+ mobilization (IC50 = 6 μM) and aggregation (IC50 = 1 μM) when platelets were activated by collagen or the thromboxane A2 receptor agonist U-46619, but not upon thrombin. In contrast, β-boswellic acid and 3-O-acetyl-β-boswellic acid, which lack the 11-keto moiety, were weak inhibitors of agonist-induced platelet responses, but instead they elicited elevation of [Ca2+]i and aggregation of platelets (≥ 3 μM). 11-Keto-β-boswellic acid, the structural intermediate between 3-O-acetyl-11-keto-β-boswellic acid and β-boswellic acid, was essentially inactive independent of the experimental conditions. Together, our study unravels the complex agonizing and antagonizing properties of boswellic acids on human platelets in pharmacologically relevant preparations of B. serrata gum extracts and prompts for careful evaluation of the safety of such extracts as herbal medicine in cardiovascular risk patients.
Mitotic figure in the peripheral blood smear
2017-04-12

A previously healthy 19-year-old man presented with fever, sore throat, and strong feeling of illness. Physical examination showed strong swelling of throat tonsils and moderate hepatosplenomegaly. The laboratory values were as follows: a total white blood count of 10.9 × 109/L, hemoglobin 14.1 g/dL, and a platelet count of 109 × 109/L. Total bilirubin was 1.4 mg/dL and CRP was 1.32 mg/dL. The serological analyses revealed IgG and IgM antibodies against EBV-VCA consistent with an acute Epstein–Barr virus infection. The peripheral blood smear revealed 80.0% lymphocytes, 12.4% neutrophils, 6.9% monocytes, 0.4% eosinophils, and 0.3% basophils. In it a mitotic figure was found (see Image 1). Mitotic figures are an extremely uncommon finding as they are usually seen in patients with acute leukemia or rarer in EBV infections. Symptomatic therapy led to complete resolution of the symptoms. Nothing to report.
The Verticillium‐specific protein VdSCP7 localizes to the plant nucleus and modulates immunity to fungal infections
2017-04-13

Summary Fungal pathogens secrete effector proteins to suppress plant basal defense for successful colonization. Resistant plants, however, can recognize effectors by cognate R proteins to induce effector‐triggered immunity (ETI). By analyzing secretomes of the vascular fungal pathogen Verticillium dahliae , we identified a novel secreted protein VdSCP7 that targets the plant nucleus. The green fluorescent protein (GFP)‐tagged VdSCP7 gene with either a mutated nuclear localization signal motif or with additional nuclear export signal was transiently expressed in Nicotiana benthamiana , and investigated for induction of plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized by gene knockout and complementation, and GFP labeling. Expression of the VdSCP7 gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and altered the plant's susceptibility to the pathogens Botrytis cinerea and Phytophthora capsici . The immune response activated by Vd SCP 7 was highly dependent on its initial extracellular secretion and subsequent nuclear localization in plants. Knockout of the Vd SCP 7 gene significantly enhanced V. dahliae aggressiveness on cotton. GFP ‐labeled Vd SCP 7 is secreted by V. dahliae and accumulates in the plant nucleus. We conclude that VdSCP7 is a novel effector protein that targets the host nucleus to modulate plant immunity, and suggest that plants can recognize Vd SCP 7 to activate ETI during fungal infection.
HLA ligandome analysis of primary chronic lymphocytic leukemia (CLL) cells under lenalidomide treatment confirms the suitability of lenalidomide for combination with T-cell-based immunotherapy
2017-04-13

Recent studies suggest that CLL is an immunogenic disease, which might be effectively targeted by antigen-specific T-cell-based immunotherapy. However, CLL is associated with a profound immune defect, which might represent a critical limitation for mounting clinically effective antitumor immune responses. As several studies have demonstrated that lenalidomide can reinforce effector T-cell responses in CLL, the combination of T-cell-based immunotherapy with the immunomodulatory drug lenalidomide represents a promising approach to overcome the immunosuppressive state in CLL. Antigen-specific immunotherapy also requires the robust presentation of tumor-associated HLA-presented antigens on target cells. We thus performed a longitudinal study of the effect of lenalidomide on the HLA ligandome of primary CLL cells <i>in vitro</i>. We showed that lenalidomide exposure does not affect absolute HLA class I and II surface expression levels on primary CLL cells. Importantly, semi-quantitative mass spectrometric analyses of the HLA peptidome of three CLL patient samples found only minor qualitative and quantitative effects of lenalidomide on HLA class I- and II-restricted peptide presentation. Furthermore, we confirmed stable presentation of previously described CLL-associated antigens under lenalidomide treatment. Strikingly, among the few HLA ligands showing significant modulation under lenalidomide treatment, we identified upregulated IKZF-derived peptides, which may represent a direct reflection of the cereblon-mediated effect of lenalidomide on CLL cells. Since we could not observe any relevant influence of lenalidomide on the established CLL-associated antigen targets of anticancer T-cell responses, this study validates the suitability of lenalidomide for the combination with antigen-specific T-cell-based immunotherapies.
A high resolution ion microscope for cold atoms
2017-04-13

We report on an ion-optical system that serves as a microscope for ultracold\\nground state and Rydberg atoms. The system is designed to achieve a\\nmagnification of up to 1000 and a spatial resolution in the 100 nm range,\\nthereby surpassing many standard imaging techniques for cold atoms. The\\nmicroscope consists of four electrostatic lenses and a microchannel plate in\\nconjunction with a delay line detector in order to achieve single particle\\nsensitivity with high temporal and spatial resolution. We describe the design\\nprocess of the microscope including ion-optical simulations of the imaging\\nsystem and characterize aberrations and the resolution limit. Furthermore, we\\npresent the experimental realization of the microscope in a cold atom setup and\\ninvestigate its performance by patterned ionization with a structure size down\\nto 2.7 {\\\\mu}m. The microscope meets the requirements for studying various\\nmany-body effects, ranging from correlations in cold quantum gases up to\\nRydberg molecule formation.\\n
Evaluation of reduced-dose CT for acute non-traumatic abdominal pain: evaluation of diagnostic accuracy in comparison to standard-dose CT
2017-04-13

Background Patients with acute non-traumatic abdominal pain often undergo abdominal computed tomography (CT). However, abdominal CT is associated with high radiation exposure. Purpose To evaluate diagnostic performance of a reduced-dose 100 kVp CT protocol with advanced modeled iterative reconstruction as compared to a linearly blended 120 kVp protocol for assessment of acute, non-traumatic abdominal pain. Material and Methods Two radiologists assessed 100 kVp and linearly blended 120 kVp series of 112 consecutive patients with acute non-traumatic pain (onset &lt; 48 h) regarding image quality, noise, and artifacts on a five-point Likert scale. Both radiologists assessed both series for abdominal pathologies and for diagnostic confidence. Both 100 kVp and linearly blended 120 kVp series were quantitatively evaluated regarding radiation dose and image noise. Comparative statistics and diagnostic accuracy was calculated using receiver operating curve (ROC) statistics, with final clinical diagnosis/clinical follow-up as reference standard. Results Image quality was high for both series without detectable significant differences ( P = 0.157). Image noise and artifacts were rated low for both series but significantly higher for 100 kVp ( P ≤ 0.021). Diagnostic accuracy was high for both series (120 kVp: area under the curve [AUC] = 0.950, sensitivity = 0.958, specificity = 0.941; 100 kVp: AUC ≥ 0.910, sensitivity ≥ 0.937, specificity = 0.882; P ≥ 0.516) with almost perfect inter-rater agreement (Kappa = 0.939). Diagnostic confidence was high for both dose levels without significant differences (100 kVp 5, range 4–5; 120 kVp 5, range 3–5; P = 0.134). The 100 kVp series yielded 26.1% lower radiation dose compared with the 120 kVp series (5.72 ± 2.23 mSv versus 7.75 ± 3.02 mSv, P &lt; 0.001). Image noise was significantly higher in reduced-dose CT (13.3 ± 2.4 HU versus 10.6 ± 2.1 HU; P &lt; 0.001). Conclusion Reduced-dose abdominal CT using 100 kVp yields excellent image quality and high diagnostic accuracy for the assessment of acute non-traumatic abdominal pain.
Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial
2017-04-13

Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the "Eplerenone in Primary Hyperparathyroidism" (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e', diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e' (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 0.198, P = 0.030) were each independently related with e'. CTX showed no correlations with LVEF or e'. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies.
Doxepin inhibits GPVI-dependent platelet Ca2+signaling and collagen-dependent thrombus formation
2017-04-13

Platelet adhesion, activation, and aggregation are essential for primary hemostasis, but are also critically involved in the development of acute arterial thrombotic occlusion. Stimulation of the collagen receptor glycoprotein VI (GPVI) leads to phospholipase Cγ2-dependent inositol triphosphate (IP 3 ) production with subsequent platelet activation, due to increased intracellular Ca 2+ concentration ([Ca 2+ ] i ). Although tricyclic antidepressants have been shown to potentially impair platelet activation, nothing is hitherto known about potential effects of the tricyclic antidepressant doxepin on platelet Ca 2+ signaling and thrombus formation. As shown in the present study, doxepin significantly diminished the stimulatory effect of GPVI agonist collagen-related peptide (CRP) on intracellular Ca 2+ release as well as subsequent extracellular Ca 2+ influx. Doxepin was partially effective by impairment of CRP-dependent IP 3 production. Moreover, doxepin abrogated CRP-induced platelet degranulation and integrin α IIb β 3 activation and aggregation. Finally, doxepin markedly blunted in vitro platelet adhesion to collagen and thrombus formation under high arterial shear rates (1,700 −s ). In conclusion, doxepin is a powerful inhibitor of GPVI-dependent platelet Ca 2+ signaling, platelet activation, and thrombus formation.
Validation of enhanced kinect sensor based motion capturing for gait assessment
2017-04-14

Optical motion capturing systems are expensive and require substantial dedicated space to be set up. On the other hand, they provide unsurpassed accuracy and reliability. In many situations however flexibility is required and the motion capturing system can only temporarily be placed. The Microsoft Kinect v2 sensor is comparatively cheap and with respect to gait analysis promising results have been published. We here present a motion capturing system that is easy to set up, flexible with respect to the sensor locations and delivers high accuracy in gait parameters comparable to a gold standard motion capturing system (VICON). Further, we demonstrate that sensor setups which track the person only from one-side are less accurate and should be replaced by two-sided setups. With respect to commonly analyzed gait parameters, especially step width, our system shows higher agreement with the VICON system than previous reports.
Neutrino mass, electron capture, and the shake-off contributions
2017-04-14

Electron capture can determine the electron neutrino mass, while the beta\\ndecay of Tritium measures the electron antineutrino mass and the neutrinoless\\ndouble beta decay observes the Majorana neutrino mass. Electron capture e. g.\\non 163Ho plus bound electron to 163Dy* plus neutrino can determine the electron\\nneutrino mass from the upper end of the decay spectrum of the excited Dy*,\\nwhich is given by the Q-Value minus the neutrino mass. The Dy* states decay by\\nX-ray and Auger electron emissions. The total decay energy is measured in a\\nbolometer. These excitations have been studied by Robertson and by Faessler et\\nal.. In addition the daughter atom Dy can also be excited by moving in the\\ncapture process one electron into the continuum. The escape of these continuum\\nelectrons is automatically included in the experimental bolometer spectrum.\\nRecently a method developed by Intemann and Pollock was used by DeRujula and\\nLusignoli for a rough estimate of this shake-off process for "s" wave electrons\\nin capture on 163Ho. The purpose of the present work is to give a more reliable\\ndescription of "s" wave shake-off in electron capture on Holmium. For that one\\nneeds very accurate atomic wave functions of Ho in its ground state and excited\\natomic wave functions of Dy* including a description of the continuum\\nelectrons. In the present approach the wave functions of Ho and Dy* are\\ndetermined selfconsistently with the antisymmetrized relativistic\\nDirac-Hartree-Fock approach. The relativistic continuum electron wave functions\\nfor the ionized Dy* are obtained in the corresponding selfconsistent\\nDirac-Hartree-Fock-Potential. In this improved approach shake-off can hardly be\\nseen after electron capture in 163Ho and thus can probably not affect the\\ndetermination of the electron neutrino mass.\\n
Catheter-based tricuspid valve replacement: first experimental data of a newly designed bileaflet stent graft prosthesis†
2017-04-14

This study demonstrated that this new valved stent graft could be delivered safely with correct positioning and valve function in this ovine model. Further long-term studies in animals implanted with the device after creation of tricuspid regurgitation are necessary to prove the haemodynamic benefit of this procedure.
Polar and charged extracellular residues conserved among barrier‐forming claudins contribute to tight junction strand formation
2017-04-17

Claudins (Cldn) form the backbone of tight junction (TJ) strands and thereby regulate paracellular permeability for solutes and water. Polymeric strands are formed by homo‐ and heterophilic cis ‐ and trans ‐interactions between claudin protomers. Crystal structures of some claudins have been resolved; however, the mechanism by which claudins assemble into TJ strands remains unclear. To elucidate strand architecture, TJ‐like strands were reconstituted in HEK293 cells by claudin transfection. Determinants of prototypic, classic barrier‐forming claudins (Cldn1, ‐3, and ‐5) involved in strand formation were analyzed by mutagenesis. The capability of claudin constructs to interact in trans and to form strands was investigated by cell contact–enrichment assays and freeze‐fracture electron microscopy. Residues in extracellular loops 1 and 2 of the claudins affecting strand formation were identified. Using homology modeling and molecular docking, we tested working concepts for the arrangement of claudin protomers within TJ strands. We show that the charge of Lys65 in Cldn1 and Glu158 in Cldn3, but not of Arg30 or Asp145 in Cldn3, and the polarity of Gln56 and Gln62 in Cldn3 and of Gln57 in Cldn5 are necessary for TJ strand formation. These residues are all conserved among barrier‐forming classic claudins. The results contribute to mechanistic understanding of claudin‐based regulation of paracellular permeability.