bluuebunny/crossref_metadata_2025 huggingface dataset:
Four-Year Experience of Digital Slide Telepathology for Intraoperative Frozen Section Consultations in a Two-Site French Academic Department of Pathology
Authors: Laurent-Bellue Astrid , Poullier Eric , Pomerol Jean-François , Adnet Eric , Redon Marie-José , Posseme Katia , Trassard Olivier , Cherqui Daniel , Zarca Kevin , Guettier Catherine
Published: April 2020

Objectives

To share our experience with digital slide telepathology for intraoperative frozen section consultations (IOCs) and to describe its evolution over time by reporting performance metrics and addressing organizational and economic aspects.

Methods

Since 2013, a technician has been alone at the surgical site. At the other site, the pathologist opens the digital slide from a local server via the intranet. Three periods were compared: a 6-month period of conventional IOC (period 1), a 24-month period of telepathology at 6 months after implementation (period 2), and a 12-month period of telepathology at 3.5 years after implementation (period 3).

Results

In total, 87 conventional IOCs and 464 and 313 IOCs on digital slides were performed respectively during periods 1, 2, and 3; mean turnaround time was 27, 36, and 38 minutes, respectively, and there were a mean number of 1.1, 1.1, and 1.3 slides, respectively, per IOC. Diagnostic accuracy was achieved in 95.4%, 92.7%, and 93.9%, respectively, of IOCs (not significant). The additional cost is in the same range as the cost of urgent transport by courier.

Conclusions

Developing IOC with digital slides is a challenge but is necessary to optimize medical time in the current context of pathologist shortage and budget restrictions.
A New Practical Surgical Technique for Hymenoplasty: Primary Repair of Hymen With Vestibulo-Introital Tightening Technique
Authors: Eserdağ Suleyman , Kurban Didem , Kiseli Mine , Alan Yasemin , Alan Murat
Published: April 2020

Background

Hymenoplasty is distinct from other genital surgeries with its ethical and psychological issues. It is performed to narrow the vaginal opening to ensure vaginal bleeding with penetration. There are various kinds of techniques with different success rates.

Objectives

The authors sought to report a new hymenal reconstruction technique with vestibulo-introital tightening with the results of 145 procedures.

Methods

The new technique included a diamond-shaped incision to the vestibulum with the base in the posterior midline and superior corner 2 to 3 cm higher above the hymen. The angles were accommodated according to the degree of tightening, and the submucosal layer was closed from the apex downwards involving the vaginal mucosa.

Results

The satisfaction rate of the patients was 99.3%. No adverse events were observed.

Conclusions

Compared with previous techniques described, this hymenal reconstruction technique is an alternative with the advantage of low risk of loosening because the tension on the hymen alone is decreased. Additional tightening of the introitus increases the satisfaction rates in some patients.

Level of Evidence: 4
Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19)
Authors: Xu Kaijin , Chen Yanfei , Yuan Jing , Yi Ping , Ding Cheng , Wu Wenrui , Li Yongtao , Ni Qin , Zou Rongrong , Li Xiaohe , Xu Min , Zhang Ying , Zhao Hong , Zhang Xuan , Yu Liang , Su Junwei , Lang Guanjing , Liu Jun , Wu Xiaoxin , Guo Yongzheng , Tao Jingjing , Shi Ding , Yu Ling , Cao Qing , Ruan Bing , Liu Lei , Wang Zhaoqin , Xu Yan , Liu Yingxia , Sheng Jifang , Li Lanjuan
Published: April 2020

Background

An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding.

Methods

In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan.

Results

The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13–22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31–8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10–1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11–88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding.

Conclusions

Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.
A Phase 1, Placebo-controlled, Randomized, Single Ascending Dose Study and a Volunteer Infection Study to Characterize the Safety, Pharmacokinetics, and Antimalarial Activity of the Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048
Authors: McCarthy James S , Donini Cristina , Chalon Stephan , Woodford John , Marquart Louise , Collins Katharine A , Rozenberg Felix D , Fidock David A , Cherkaoui-Rbati Mohammed H , Gobeau Nathalie , Möhrle Jörg J
Published: April 2020

Background

MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics, and antimalarial activity of a tablet formulation of MMV390048.

Methods

A 2-part, phase 1 trial was conducted in healthy adults. Part 1 was a double-blind, randomized, placebo-controlled, single ascending dose study consisting of 3 cohorts (40, 80, 120 mg MMV390048). Part 2 was an open-label volunteer infection study using the Plasmodium falciparum induced blood-stage malaria model consisting of 2 cohorts (40 mg and 80 mg MMV390048).

Results

Twenty four subjects were enrolled in part 1 (n = 8 per cohort, randomized 3:1 MMV390048:placebo) and 15 subjects were enrolled in part 2 (40 mg [n = 7] and 80 mg [n = 8] cohorts). One subject was withdrawn from part 2 (80 mg cohort) before dosing and was not included in analyses. No serious or severe adverse events were attributed to MMV390048. The rate of parasite clearance was greater in subjects administered 80 mg compared to those administered 40 mg (clearance half-life 5.5 hours [95% confidence interval {CI}, 5.2–6.0 hours] vs 6.4 hours [95% CI, 6.0–6.9 hours]; P = .005). Pharmacokinetic/pharmacodynamic modeling estimated a minimum inhibitory concentration of 83 ng/mL and a minimal parasiticidal concentration that would achieve 90% of the maximum effect of 238 ng/mL, and predicted that a single 120-mg dose would achieve an adequate clinical and parasitological response with 92% certainty.

Conclusions

The safety, pharmacokinetics, and pharmacodynamics of MMV390048 support its further development as a partner drug of a single-dose combination therapy for malaria.

Clinical Trials Registration

NCT02783820 (part 1); NCT02783833 (part 2).
Ryanodine receptor subtypes regulate Ca2+ sparks/spontaneous transient outward currents and myogenic tone of uterine arteries in pregnancy
Authors: Song Rui , Hu Xiang-Qun , Romero Monica , Holguin Mark A , Kagabo Whitney , Xiao Daliao , Wilson Sean M , Zhang Lubo
Published: April 2020

Aims

Our recent study demonstrated that increased Ca2+ sparks and spontaneous transient outward currents (STOCs) played an important role in uterine vascular tone and haemodynamic adaptation to pregnancy. The present study examined the role of ryanodine receptor (RyR) subtypes in regulating Ca2+ sparks/STOCs and myogenic tone in uterine arterial adaptation to pregnancy.

Methods and results

Uterine arteries isolated from non-pregnant and near-term pregnant sheep were used in the present study. Pregnancy increased the association of α and β1 subunits of large-conductance Ca2+-activated K+ (BKCa) channels and enhanced the co-localization of RyR1 and RyR2 with the β1 subunit in the uterine artery. In contrast, RyR3 was not co-localized with BKCa β1 subunit. Knockdown of RyR1 or RyR2 in uterine arteries of pregnant sheep downregulated the β1 but not α subunit of the BKCa channel and decreased the association of α and β1 subunits. Unlike RyR1 and RyR2, knockdown of RyR3 had no significant effect on either expression or association of BKCa subunits. In addition, knockdown of RyR1 or RyR2 significantly decreased Ca2+ spark frequency, suppressed STOCs frequency and amplitude, and increased pressure-dependent myogenic tone in uterine arteries of pregnant animals. RyR3 knockdown did not affect Ca2+ sparks/STOCs and myogenic tone in the uterine artery.

Conclusion

Together, the present study demonstrates a novel mechanistic paradigm of RyR subtypes in the regulation of Ca2+ sparks/STOCs and uterine vascular tone, providing new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.
Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment
Authors: Albano Clara , Silvetti Tiziana , Brasca Milena
Published: April 2020

Lactic acid bacteria (LAB) can be used to increase the folate in foods by in situ fortification. Seventy LAB were screened for their ability to produce folate during growth in de Man, Rogosa and Sharpe/M17 broth. Lactobacillus casei, Lactobacillus plantarum, Lactobacillus paracasei subsp. paracasei, Lactobacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, Lactococcus lactis subsp. lactis, Enterococcus faecium and Enterococcus lactis were able to synthetize folates in the medium, even if to a different extent. The 47 folate-producing strains were further analyzed by microbiological assay, for total, extra and intracellular folate. Enterococcus faecium VC223 and E. lactis BT161 were able to produce in cultural medium 123,625.74 ± 8.00 ng/ml and 384.22 ± 5.00 ng/ml of folate, respectively. Five strains were further examined for their ability to synthesize folate in cheese. The folate content increased with ripening up to by 54% after 30 d when L. casei VC199 was used and up to 108% and 113% after 60 d, with L. paracasei SE160 and E. lactis BT161 respectively exceeding 100 ng/100g. Results encourage the use of specific LAB to obtain natural folate bio-enriched dairy products improving folate intake.
“Christianizing” Transnistria: Romanian Orthodox Clergy as Beneficiaries, Perpetrators, and Rescuers during the Holocaust
Authors: Biliuta Ionut
Published: April 2020

The violent behavior of fascist Orthodox clerics serving in the Transnistrian Orthodox Mission during World War II contributed to the “Romanianization” of Transnistria initiated by the Antonescu government in 1941. These churchmen stand out as bystanders, beneficiaries, and even perpetrators of the Holocaust. Subscribing to the antisemitic programs of the outlawed Iron Guard and of the Antonescu government, these men took an active part in exploiting, robbing, and even murdering both local Jews and other deportees from Bessarabia, Bucovina, and elsewhere in Romania. They illustrate both the suffusion of fascist ideology into all sectors of Romanian society and the role of clergy at every level.
Nationalism, Conspiracy Theories, and Antisemitism in the Transylvanian Greek Catholic Newspaper Dumineca on the Eve of the Holocaust (1936–1940)
Authors: Popa Ion
Published: April 2020

In the first half of the twentieth century churches in Eastern Europe often promoted extreme nationalism and antisemitism. Their very effectiveness discouraged many bystanders from helping Jews during the Holocaust. Here the author studies a little-known journal published by the Greek Catholic (Uniate) bishopric of Maramureş, a Transylvanian province of Romania (and Hungary from 1940 to 1944) with a significant Jewish population. This journal contributed to a climate in which the Christian population would look on with equanimity or even assist as the Nazi New Order pursued the mass murder of all Jews.
The contribution of tissue-grouped BMI-associated gene sets to cardiometabolic-disease risk: a Mendelian randomization study
Authors: Verkouter Inge , de Mutsert Renée , Smit Roelof A J , Trompet Stella , Rosendaal Frits R , van Heemst Diana , Willems van Dijk Ko , Noordam Raymond
Published: April 2020

Background

Body mass index (BMI)-associated loci are used to explore the effects of obesity using Mendelian randomization (MR), but the contribution of individual tissues to risks remains unknown. We aimed to identify tissue-grouped pathways of BMI-associated loci and relate these to cardiometabolic disease using MR analyses.

Methods

Using Genotype-Tissue Expression (GTEx) data, we performed overrepresentation tests to identify tissue-grouped gene sets based on mRNA-expression profiles from 634 previously published BMI-associated loci. We conducted two-sample MR with inverse-variance-weighted methods, to examine associations between tissue-grouped BMI-associated genetic instruments and type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), with use of summary-level data from published genome-wide association studies (T2DM: 74 124 cases, 824 006 controls; CAD: 60 801 cases, 123 504 controls). Additionally, we performed MR analyses on T2DM and CAD using randomly sampled sets of 100 or 200 BMI-associated genetic variants.

Results

We identified 17 partly overlapping tissue-grouped gene sets, of which 12 were brain areas, where BMI-associated genes were differentially expressed. In tissue-grouped MR analyses, all gene sets were similarly associated with increased risks of T2DM and CAD. MR analyses with randomly sampled genetic variants on T2DM and CAD resulted in a distribution of effect estimates similar to tissue-grouped gene sets.

Conclusions

Overrepresentation tests revealed differential expression of BMI-associated genes in 17 different tissues. However, with our biology-based approach using tissue-grouped MR analyses, we did not identify different risks of T2DM or CAD for the BMI-associated gene sets, which was reflected by similar effect estimates obtained by randomly sampled gene sets.
An Isoperimetric-Type Inequality for Spacelike Submanifold in the Minkowski Space
Authors: Tsai Chung-Jun , Wang Kai-Hsiang
Published: April 2020

We prove an isoperimetric-type inequality for maximal, spacelike submanifold in the Minkowski space. The argument is based on the recent work of Brendle.
Peptide nucleic acid restores colistin susceptibility through modulation of MCR-1 expression in Escherichia coli
Authors: Wang Xiaoming , Wang Yao , Ling Zhuoren , Zhang Chaoyang , Fu Mingming , Wang Yang , Wang Shaolin , Zhang Suxia , Shen Zhangqi
Published: April 2020

Background

Plasmid-mediated mechanisms of drug resistance accelerate the spread of polymyxin resistance, leaving clinicians with few or no antibacterial options for the treatment of infections caused by MDR bacteria, especially carbapenemase-producing strains.

Objectives

To evaluate the associations among promoter sequence variation, mcr-1 expression, host factors and levels of colistin resistance and to propose antisense agents such as peptide nucleic acids (PNAs) targeting mcr-1 as a tool to restore colistin susceptibility through modulation of MCR-1 expression in Escherichia coli.

Methods

A β-galactosidase assay was performed to study mcr-1 promoter activity. Quantitative real-time PCR and western blot assays were used to identify the expression level of MCR-1 in WT strains and transformants. Three PNAs targeting different regions of mcr-1 were designed and synthesized to determine whether they can effectively inhibit MCR-1 expression. MIC was measured to test colistin susceptibility in the presence or absence of PNA-1 in mcr-1-carrying E. coli.

Results

Variation in the mcr-1 promoter sequence and host species affect promoter activity, MCR-1 expression levels and colistin MICs. One PNA targeting the ribosome-binding site fully inhibited the expression of mcr-1 at a concentration of 4 μM, resulting in significantly increased susceptibility to colistin. The MIC90 of colistin decreased from 8 to 2 mg/L (P < 0.05) in the presence of 4 μM PNA.

Conclusions

These findings suggest that the antisense approach is a possible strategy to combat mcr-1-mediated resistance as well as other causes of emerging global resistance.
Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans
Authors: Kirchhoff Lisa , Dittmer Silke , Weisner Ann-Kathrin , Buer Jan , Rath Peter-Michael , Steinmann Joerg
Published: April 2020

Objectives

Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed.

Methods

Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm.

Results

Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans.

Conclusions

To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.
Technology v Technocracy: Fintech as a Regulatory Challenge
Authors: Omarova Saule T
Published: April 2020

This article examines fintech as a systemic force disrupting the currently dominant technocratic paradigm of financial regulation. It offers a five-part taxonomy of (i) the key fintech-driven changes in the structure and operation of today’s financial system, and (ii) the corresponding challenges these systemic shifts pose to the continuing efficacy of the regulatory enterprise as it exists today. This exercise reveals the fundamental tension at the core of the fintech problem. In the fintech era, the financial system as a whole is growing ever bigger, moving ever faster, and getting ever more complex and difficult to manage. The emerging regulatory responses to these macro-level changes, however, continue to operate primarily on the micro-level. Surveying the presently fragmented efforts to regulate fintech, this article highlights the limiting effects of the technocratic bias built into their design. Against that background, it outlines several alternative reform options that would explicitly target the core macro-structural, as opposed to micro-transactional, aspects of the fintech challenge—and do so in a more assertive, comprehensive, and normatively unified manner.
A randomized phase III study comparing continuation and discontinuation of PD-1 pathway inhibitors for patients with advanced non-small-cell lung cancer (JCOG1701, SAVE study)
Authors: Nomura Shogo , Goto Yasushi , Mizutani Tomonori , Kataoka Tomoko , Kawai Shoko , Okuma Yusuke , Murakami Haruyasu , Tanaka Kentaro , Ohe Yuichiro
Published: April 2020

The development of PD-1 pathway inhibitors has dramatically altered the treatment of advanced/recurrent non-small-cell lung cancer patients. However, the prognostic significance of their ongoing usage is controversial, especially for patients who have not progressed for a period of time. If discontinuation has no negative impact on survival, suspension may reduce side effects from toxicity and help alleviate the economic burdens on health insurance systems and patients. This randomized controlled trial enrolls patients who have responded well to PD-1 pathway inhibitors for >12 months. The aim is to confirm the non-inferiority of discontinuation of PD-1 pathway inhibitors, relative to continuation, in terms of overall survival. A total of 216 patients will be enrolled over 3 years. This trial has been registered in the Japan Registry for Clinical Trials as jRCT1031190032 (https://jrct.niph.go.jp/). An ancillary study examining the prognostic and predictive role of circulating tumor DNA using Guardant360® is planned.
A radio burst detection method based on the Hough transform
Authors: Zuo Shifan , Chen Xuelei
Published: April 2020

We present a simple and fast method for incoherent dedispersion and fast radio burst (FRB) detection based on the Hough transform, which is widely used for feature extraction in image analysis. The Hough transform maps a point in the time–frequency data to a straight line in the parameter space and points on the same dispersed f−2 curve to a bundle of lines all crossing at the same point, thus the curve is transformed to a single point in the parameter space, enabling an easier way for the detection of radio burst. By choosing an appropriate truncation threshold, in a reasonably radio quiet environment, i.e. with radio frequency interferences present but not dominant, the computing speed of the method is very fast. Using simulation data of different noise levels, we studied how the detected peak varies with different truncation thresholds. We also tested the method with some real pulsar and FRB data.
Evidence for an accreting massive black hole in He 2–10 from adaptive optics integral field spectroscopy
Authors: Riffel Rogemar A
Published: April 2020

Henize 2–10 is a blue dwarf galaxy with intense star formation and one the most intriguing question about it is whether or not it hosts an accreting massive black hole. We use H and K-band integral field spectra of the inner 130 pc × 130 pc of He 2–10 to investigate the emission and kinematics of the gas at unprecedented spatial resolution. The observations were done using the Gemini Near-Infrared Integral Field Spectrograph (NIFS) operating with the ALTAIR adaptive optics module and the resulting spatial resolutions are 6.5 and 8.6 pc in the K and H bands, respectively. Most of the line emission is due to excitation of the gas by photoionization and shocks produced by the star forming regions. In addition, our data provide evidence of emission of gas excited by an active galactic nucleus located at the position of the radio and X-ray sources, as revealed by the analysis of the emission-line ratios. The emission lines from the ionized gas in the field present two kinematic components: one narrow with a velocity field suggesting a disc rotation and a broad component due to winds from the star forming regions. The molecular gas shows only the narrow component. The stellar velocity dispersion map presents an enhancement of about 7 km s−1 at the position of the black hole, consistent with a mass of $1.5^{+1.3}_{-1.3}\times 10^6$ M⊙.
Orthogonal pulsars as a key test for pulsar evolution
Authors: Novoselov E M , Beskin V S , Galishnikova A K , Rashkovetskyi M M , Biryukov A V
Published: April 2020

At present, there is no direct information about evolution of inclination angle χ between magnetic and rotational axes in radio pulsars. As to theoretical models of pulsar evolution, they predict both the alignment, i.e. evolution of inclination angle χ to 0°, and its counter-alignment, i.e. evolution to 90°. In this paper, we demonstrate that the statistics of interpulse pulsars can give us the key test to solve the alignment/counter-alignment problem as the number of orthogonal interpulse pulsars (χ ≈ 90°) drastically depends on the evolution trajectory.
Differential rotation in neutron stars with open and closed magnetic topologies
Authors: Anzuini F , Melatos A
Published: April 2020

Analytic arguments have been advanced that the degree of differential rotation in a neutron star depends on whether the topology of the internal magnetic field is open or closed. To test this assertion, the ideal-magnetohydrodynamics solver pluto is employed to investigate numerically the flow of an incompressible, viscous fluid threaded by a magnetic field with open and closed topologies in a conducting, differentially rotating, spherical shell. Rigid body corotation with the outer sphere is enforced on the Alfvén time-scale, along magnetic field lines that connect the northern and southern hemispheres of the outer sphere. Along other field lines, however, the behaviour is more complicated. For example, an initial point dipole field evolves to produce an approximately closed equatorial flux tube containing at least one predominantly toroidal and approximately closed field line surrounded by a bundle of predominantly toroidal but open field lines. Inside the equatorial flux tube, the field-line-averaged magnetic tension approaches zero, and the fluid rotates differentially, adjusting its angular velocity on the viscous time-scale to match the boundary conditions on the flux tube’s toroidal surface. Outside the equatorial flux tube, the differential rotation increases, as the magnetic tension averaged along open field lines decreases.
Quantifying torque from the Milky Way bar using Gaia DR2
Authors: Kipper Rain , Tenjes Peeter , Tuvikene Taavi , Ganeshaiah Veena Punyakoti , Tempel Elmo
Published: April 2020

We determine the mass of the Milky Way bar and the torque it causes, using Gaia DR2, by applying the orbital arc method. Based on this, we have found that the gravitational acceleration is not directed towards the centre of our Galaxy but a few degrees away from it. We propose that the tangential acceleration component is caused by the bar of the Galaxy. Calculations based on our model suggest that the torque experienced by the region around the Sun is $\approx 2400\, {\rm km^2\, s^{-2}}$ per solar mass. The mass estimate for the bar is $\sim 1.6\pm 0.3\times 10^{10}\, \mathrm{M_\odot }$. Using greatly improved data from Gaia DR2, we have computed the acceleration field to great accuracy by adapting the orbital Probability Density Function (oPDF) method (Han et al. 2016) locally and used the phase space coordinates of ∼4 × 105 stars within a distance of 0.5 kpc from the Sun. In the orbital arc method, the first step is to guess an acceleration field and then reconstruct the stellar orbits using this acceleration for all the stars within a specified region. Next, the stars are redistributed along orbits to check if the overall phase space distribution has changed. We repeat this process until we find an acceleration field that results in a new phase space distribution that is the same as the one that we started with; we have then recovered the true underlying acceleration.
Galactic outflow rates in the EAGLE simulations
Authors: Mitchell Peter D , Schaye Joop , Bower Richard G , Crain Robert A
Published: April 2020

We present measurements of galactic outflow rates from the eagle suite of cosmological simulations. We find that gas is removed from the interstellar medium (ISM) of central galaxies with a dimensionless mass loading factor that scales approximately with circular velocity as $V_{\mathrm{c}}^{-3/2}$ in the low-mass regime where stellar feedback dominates. Feedback from active galactic nuclei causes an upturn in the mass loading for halo masses ${\gt}10^{12} \, \mathrm{M_\odot }$. We find that more gas outflows through the halo virial radius than is removed from the ISM of galaxies, particularly at low redshifts, implying substantial mass loading within the circumgalactic medium. Outflow velocities span a wide range at a given halo mass/redshift, and on average increase positively with redshift and halo mass up to $M_{200} \sim 10^{12} \, \mathrm{M_\odot }$. Outflows exhibit a bimodal flow pattern on circumgalactic scales, aligned with the galactic minor axis. We present a number of like-for-like comparisons to outflow rates from other recent cosmological hydrodynamical simulations, and show that comparing the propagation of galactic winds as a function of radius reveals substantial discrepancies between different models. Relative to some other simulations, eagle favours a scenario for stellar feedback where agreement with the galaxy stellar mass function is achieved by removing smaller amounts of gas from the ISM, but with galactic winds that then propagate and entrain ambient gas out to larger radii.
Extraordinary Sequence Diversity and Promiscuity of Centromeric Satellites in the Legume Tribe Fabeae
Authors: Ávila Robledillo Laura , Neumann Pavel , Koblížková Andrea , Novák Petr , Vrbová Iva , Macas Jiří
Published: April 2020

Satellite repeats are major sequence constituents of centromeres in many plant and animal species. Within a species, a single family of satellite sequences typically occupies centromeres of all chromosomes and is absent from other parts of the genome. Due to their common origin, sequence similarities exist among the centromere-specific satellites in related species. Here, we report a remarkably different pattern of centromere evolution in the plant tribe Fabeae, which includes genera Pisum, Lathyrus, Vicia, and Lens. By immunoprecipitation of centromeric chromatin with CENH3 antibodies, we identified and characterized a large and diverse set of 64 families of centromeric satellites in 14 species. These families differed in their nucleotide sequence, monomer length (33–2,979 bp), and abundance in individual species. Most families were species-specific, and most species possessed multiple (2–12) satellites in their centromeres. Some of the repeats that were shared by several species exhibited promiscuous patterns of centromere association, being located within CENH3 chromatin in some species, but apart from the centromeres in others. Moreover, FISH experiments revealed that the same family could assume centromeric and noncentromeric positions even within a single species. Taken together, these findings suggest that Fabeae centromeres are not shaped by the coevolution of a single centromeric satellite with its interacting CENH3 proteins, as proposed by the centromere drive model. This conclusion is also supported by the absence of pervasive adaptive evolution of CENH3 sequences retrieved from Fabeae species.
rMAPS2: an update of the RNA map analysis and plotting server for alternative splicing regulation
Authors: Hwang Jae Y , Jung Sungbo , Kook Tae L , Rouchka Eric C , Bok Jinwoong , Park Juw W
Published: April 2020

The rMAPS2 (RNA Map Analysis and Plotting Server 2) web server, freely available at http://rmaps.cecsresearch.org/, has provided the high-throughput sequencing data research community with curated tools for the identification of RNA binding protein sites. rMAPS2 analyzes differential alternative splicing or CLIP peak data obtained from high-throughput sequencing data analysis tools like MISO, rMATS, Piranha, PIPE-CLIP and PARalyzer, and then, graphically displays enriched RNA-binding protein target sites. The initial release of rMAPS focused only on the most common alternative splicing event, skipped exon or exon skipping. However, there was a high demand for the analysis of other major types of alternative splicing events, especially for retained intron events since this is the most common type of alternative splicing in plants, such as Arabidopsis thaliana. Here, we expanded the implementation of rMAPS2 to facilitate analyses for all five major types of alternative splicing events: skipped exon, mutually exclusive exons, alternative 5′ splice site, alternative 3′ splice site and retained intron. In addition, by employing multi-threading, rMAPS2 has vastly improved the user experience with significant reductions in running time, ∼3.5 min for the analysis of all five major alternative splicing types at once.
EXOSC10 sculpts the transcriptome during the growth-to-maturation transition in mouse oocytes
Authors: Wu Di , Dean Jurrien
Published: April 2020

Growing mammalian oocytes accumulate substantial amounts of RNA, most of which is degraded during subsequent meiotic maturation. The growth-to-maturation transition begins with germinal vesicle or nuclear envelope breakdown (GVBD) and is critical for oocyte quality and early development. The molecular machinery responsible for the oocyte transcriptome transition remains unclear. Here, we report that an exosome-associated RNase, EXOSC10, sculpts the transcriptome to facilitate the growth-to-maturation transition of mouse oocytes. We establish an oocyte-specific conditional knockout of Exosc10 in mice using CRISPR/Cas9 which results in female subfertility due to delayed GVBD. By performing multiple single oocyte RNA-seq, we document dysregulation of several types of RNA, and the mRNAs that encode proteins important for endomembrane trafficking and meiotic cell cycle. As expected, EXOSC10-depleted oocytes have impaired endomembrane components including endosomes, lysosomes, endoplasmic reticulum and Golgi. In addition, CDK1 fails to activate, possibly due to persistent WEE1 activity, which blocks lamina phosphorylation and disassembly. Moreover, we identified rRNA processing defects that cause higher percentage of developmentally incompetent oocytes after EXOSC10 depletion. Collectively, we propose that EXOSC10 promotes normal growth-to-maturation transition in mouse oocytes by sculpting the transcriptome to degrade RNAs encoding growth-phase factors and, thus, support the maturation phase of oogenesis.
Design and Physical Properties of 3-Dimensional Printed Models Used for Neurointervention: A Systematic Review of the Literature
Authors: Waqas Muhammad , Mokin Maxim , Lim Jaims , Vakharia Kunal , Springer Michael E , Meess Karen M , Ducharme Richard W , Ionita Ciprian N , Nagesh Swetadri Vasan Setlur , Gutierrez Liza C , Snyder Kenneth V , Davies Jason M , Levy Elad I , Siddiqui Adnan H
Published: April 2020

Background

Three-dimensional (3D) printing has revolutionized training, education, and device testing. Understanding the design and physical properties of 3D-printed models is important.

Objective

To systematically review the design, physical properties, accuracy, and experimental outcomes of 3D-printed vascular models used in neurointervention.

Methods

We conducted a systematic review of the literature between January 1, 2000 and September 30, 2018. Public/Publisher MEDLINE (PubMed), Web of Science, Compendex, Cochrane, and Inspec databases were searched using Medical Subject Heading terms for design and physical attributes of 3D-printed models for neurointervention. Information on design and physical properties like compliance, lubricity, flow system, accuracy, and outcome measures were collected.

Results

A total of 23 articles were included. Nine studies described 3D-printed models for stroke intervention. Tango Plus (Stratasys) was the most common material used to develop these models. Four studies described a population-representative geometry model. All other studies reported patient-specific vascular geometry. Eight studies reported complete reconstruction of the circle of Willis, anterior, and posterior circulation. Four studies reported a model with extracranial vasculature. One prototype study reported compliance and lubricity. Reported circulation systems included manual flushing, programmable pistons, peristaltic, and pulsatile pumps. Outcomes included thrombolysis in cerebral infarction, post-thrombectomy flow restoration, surgical performance, and qualitative feedback.

Conclusion

Variations exist in the material, design, and extent of reconstruction of vasculature of 3D-printed models. There is a need for objective characterization of 3D-printed vascular models. We propose the development of population representative 3D-printed models for skill improvement or device testing.
Analysis of niche characteristics of phytoplankton functional groups in fluvial ecosystems
Authors: Nagy-László Zsolt , Padisák Judit , Borics Gábor , Abonyi András , B-Béres Viktória , Várbíró Gábor
Published: April 2020

Assigning species to functional response groups in phytoplankton ecology reduces the number of functional units, which helps understand the processes that shape diversity and functioning of planktonic assemblages. Although the concept has become widespread in recent years, numerical characterization of the groups’ positions in the niche space remained a challenging task. Using a large river phytoplankton dataset, we characterized the functional groups (FGs) of phytoplankton by their niche position and niche breadth in the niche space defined by the relevant environmental variables using the Outlying Main Index approach. The niche space has been defined primarily by trophic-related (nutrients) and river size-related variables (water residence time, discharge). Although we hypothesized that FGs with central niche position would have wide, while those with marginal niche position have narrow niche breadth, these have not been corroborated by the results. Rather, FGs occurred both with central niche position and intermediate breadth, as well as with marginal niche position and wide breadth. Niche position of several FGs was different from that suggested by their known habitat templates in lakes. Furthermore, we found no significant relationship between niche position and niche breadth, suggesting that the occurrence of FGs in rivers is simultaneously influenced by both niche characteristics.
Diuretic lounge and the impact on hospital admissions for treatment of decompensated heart failure
Authors: Ioannou A , Browne T , Jordan S , Metaxa S , Mandal A K J , Missouris C G
Published: April 2020

Background

Heart failure is a prevalent condition associated with frequent and costly hospital admissions. Hospitalizations are primarily related to worsening fluid retention and often require admission for decongestion with intravenous diuretics.

Objective

To assess the safety of an outpatient intravenous diuresis service for heart failure patients, and its impact on emergency admissions and the cost of treatment.

Methods

We conducted a prospective observational cohort registry study on patients referred to the diuretic lounge at our acute hospital between May 2017 and April 2018.

Results

We analysed 245 patients treated in the diuretic lounge, of which 190 (77.6%) avoided hospitalization or any adverse events during the 60 days of follow up (77.6% vs. 22.4%; P < 0.001). The diuretic lounge service resulted in a significant decrease in emergency heart failure admissions compared to the previous 12 months (823 vs. 715 per annum; 68.6 ± 10.1 vs. 59.6 ± 14 per month; P = 0.04), and a numerical reduction in readmission rates (17.3% vs. 16.2%). The 13.1% decrease in admissions lead to financial savings of £315 497 per annum and £2921 per admission avoided. During the same time period, at the other acute hospital site in our trust, where no diuretic lounge service is available, the number of admissions did not significantly change (457 vs. 450 per annum; 37.5 ± 7.0 vs. 38.1 ± 7.6 per month; P = 0.81).

Conclusion

Ambulatory administration of intravenous diuretics reduces emergency admissions and is a safe and cost-effective alternative to treat acute decomposition in heart failure patients.
How Do Executives Exercise Their Stock Options?*
Authors: Klein Daniel , Maug Ernst
Published: April 2020

We analyze how 14,000 top U.S. executives exercise their stock options. Factors suggested by existing theories have low or moderate explanatory power. Variables that model executives’ motive to diversify fare particularly poorly, whereas variables that capture reference-dependent preference, such as past highs and lows of stock prices, perform better. By contrast, characteristics of option portfolios are of first-order importance and suggest that managers have target ownership levels. Institutional features like vesting restrictions or blackout periods also have a first-order impact. We conclude that executives’ main motivations for exercising stock options early seem to be outside the scope of extant models. (JEL G30, M52)

Received August 20, 2018; editorial decision December 28, 2019 by Editor Andrew Ellul.
Pattern similarity and connectivity of hippocampal-neocortical regions support empathy for pain
Authors: Wagner Isabella C , Rütgen Markus , Lamm Claus
Published: April 2020

Empathy is thought to engage mental simulation, which in turn is known to rely on hippocampal-neocortical processing. Here, we tested how hippocampal-neocortical pattern similarity and connectivity contributed to pain empathy. Using this approach, we analyzed a data set of 102 human participants who underwent functional MRI while painful and non-painful electrical stimulation was delivered to themselves or to a confederate. As hypothesized, results revealed increased pattern similarity between first-hand pain and pain empathy (compared to non-painful control conditions) within the hippocampus, retrosplenial cortex, the temporo-parietal junction and anterior insula. While representations in these regions were unaffected by confederate similarity, pattern similarity in the dorsal medial prefrontal cortex was increased the more dissimilar the other individual was perceived. Hippocampal-neocortical connectivity during first-hand pain and pain empathy engaged largely distinct but neighboring primary motor regions, and empathy-related hippocampal coupling with the fusiform gyrus positively scaled with trait measures of perspective taking. These findings suggest that shared representations and mental simulation might contribute to pain empathy via hippocampal-neocortical pattern similarity and connectivity, partially affected by personality traits and the similarity of the observed individual.
Local Sympathectomy Promotes Anti-inflammatory Responses and Relief of Paclitaxel-induced Mechanical and Cold Allodynia in Mice
Authors: Tonello Raquel , Xie Wenrui , Lee Sang Hoon , Wang Min , Liu Xiaojuan , Strong Judith A. , Zhang Jun-Ming , Berta Temugin
Published: April 2020

Background

Patients undergoing cancer treatment often experience chemotherapy-induced neuropathic pain at their extremities, for which there is no U.S. Food and Drug Administration–approved drug. The authors hypothesized that local sympathetic blockade, which is used in the clinic to treat various pain conditions, can also be effective to treat chemotherapy-induced neuropathic pain.

Methods

A local sympathectomy (i.e., cutting the ipsilateral gray rami entering the spinal nerves near the L3 and L4 dorsal root ganglia) was performed in mice receiving intraperitoneal injections every other day of the chemotherapeutic drug paclitaxel. Sympathectomy effects were then assessed in chemotherapy-induced pain-like behaviors (i.e., mechanical and cold allodynia) and neuroimmune and electrophysiologic responses.

Results

Local microsympathectomy produced a fast recovery from mechanical allodynia (mean ± SD: sympathectomy vs. sham at day 5, 1.07 ± 0.34 g vs. 0.51 ± 0.17g, n = 5, P = 0.030 in male mice, and 1.08 ± 0.28 g vs. 0.62 ± 0.16 g, n = 5, P = 0.036 in female mice) and prevented the development of cold allodynia in both male and female mice after paclitaxel. Mechanistically, microsympathectomy induced transcriptional increases in dorsal root ganglia of macrophage markers and anti-inflammatory cytokines, such as the transforming growth factor-β. Accordingly, depletion of monocytes/macrophages and blockade of transforming growth factor-β signaling reversed the relief of mechanical allodynia by microsympathectomy. In particular, exogenous transforming growth factor-β was sufficient to relieve mechanical allodynia after paclitaxel (transforming growth factor-β 100 ng/site vs. vehicle at 3 h, 1.21 ± 0.34g vs. 0.53 ± 0.14 g, n = 5, P = 0.001 in male mice), and transforming growth factor-β signaling regulated neuronal activity in dorsal root ganglia.

Conclusions

Local sympathetic nerves control the progression of immune responses in dorsal root ganglia and pain-like behaviors in mice after paclitaxel, raising the possibility that clinical strategies already in use for local sympathetic blockade may also offer an effective treatment for patients experiencing chemotherapy-induced neuropathic pain.

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Accuracy and Feasibility of Clinically Applied Frailty Instruments before Surgery
Authors: Aucoin Sylvie D. , Hao Mike , Sohi Raman , Shaw Julia , Bentov Itay , Walker David , McIsaac Daniel I.
Published: April 2020

Background

A barrier to routine preoperative frailty assessment is the large number of frailty instruments described. Previous systematic reviews estimate the association of frailty with outcomes, but none have evaluated outcomes at the individual instrument level or specific to clinical assessment of frailty, which must combine accuracy with feasibility to support clinical practice.

Methods

The authors conducted a preregistered systematic review (CRD42019107551) of studies prospectively applying a frailty instrument in a clinical setting before surgery. Medline, Excerpta Medica Database, Cochrane Library and the Comprehensive Index to Nursing and Allied Health Literature, and Cochrane databases were searched using a peer-reviewed strategy. All stages of the review were completed in duplicate. The primary outcome was mortality and secondary outcomes reflected routinely collected and patient-centered measures; feasibility measures were also collected. Effect estimates were pooled using random-effects models or narratively synthesized. Risk of bias was assessed.

Results

Seventy studies were included; 45 contributed to meta-analyses. Frailty was defined using 35 different instruments; five were meta-analyzed, with the Fried Phenotype having the largest number of studies. Most strongly associated with: mortality and nonfavorable discharge was the Clinical Frailty Scale (odds ratio, 4.89; 95% CI, 1.83 to 13.05 and odds ratio, 6.31; 95% CI, 4.00 to 9.94, respectively); complications was associated with the Edmonton Frail Scale (odds ratio, 2.93; 95% CI, 1.52 to 5.65); and delirium was associated with the Frailty Phenotype (odds ratio, 3.79; 95% CI, 1.75 to 8.22). The Clinical Frailty Scale had the highest reported measures of feasibility.

Conclusions

Clinicians should consider accuracy and feasibility when choosing a frailty instrument. Strong evidence in both domains support the Clinical Frailty Scale, while the Fried Phenotype may require a trade-off of accuracy with lower feasibility.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New