bluuebunny/crossref_metadata_2025_split 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

AbstractObjectivesTo 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.MethodsSince 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).ResultsIn 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.ConclusionsDeveloping 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

Abstract

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

AbstractBackgroundAn 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.MethodsIn 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.ResultsThe 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 (&lt;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 &lt; .001) and focal absorption on radiograph images (P &lt; .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.ConclusionsMale 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

Abstract

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

Abstract

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

ABSTRACTLactic 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

Abstract
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

Abstract
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

Abstract

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.
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

Abstract

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 &lt; 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

Abstract

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

Abstract
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

Abstract
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 &gt;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

ABSTRACT
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

ABSTRACT
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⊙.