bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
Authors: Shortridge Dee , Carvalhaes Cecilia , Deshpande Lalitagauri , Castanheira Mariana 
Published: June 2021

Abstract

Objectives
Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among other indications. Vaborbactam is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC) enzymes, but not class B or D carbapenemases. We analysed the activity of meropenem/vaborbactam and comparators against 6846 Enterobacterales and 3567 Pseudomonas aeruginosa isolates from patients hospitalized with pneumonia (PHP), including VAP.

Methods
Isolates from PHP were consecutively collected during 2014–19 from 42 European hospitals located in 21 countries and susceptibility tested using the broth microdilution method. Carbapenem-resistant Enterobacterales (CRE) isolates were molecularly characterized to identify their carbapenem-resistance mechanisms. EUCAST (2020) interpretive criteria were used.

Results
The most common Gram-negative pathogens isolated from PHP were P. aeruginosa (n = 3567), K. pneumoniae (n = 1877) and Escherichia coli (n = 1646). Overall, 98.0% of Enterobacterales and 82.1% of P. aeruginosa were susceptible to meropenem/vaborbactam, with 99.8% of Enterobacterales and 89.7% of P. aeruginosa in Western Europe (WE) and 92.7% of Enterobacterales and 69.1% of P. aeruginosa in Eastern Europe (EE). CRE were more common in EE (15.1%) than WE (2.1%). KPC was the most common carbapenemase in WE, while OXA-48-like was the most common carbapenemase in EE. Meropenem/vaborbactam susceptibility was 63.0% for all CRE (92.2% in WE and 51.5% in EE). Meropenem/vaborbactam inhibited 99.1% of KPC-producing isolates and 40.5% of OXA-48-like-producing isolates.

Conclusions
These in vitro data demonstrate that meropenem/vaborbactam has potent activity against isolates from PHP, including isolates producing KPC, and may be a useful treatment option for PHP, including VAP.
Effect of plane of nutrition during the first 12 weeks of life on growth, metabolic and reproductive hormone concentrations, and testicular relative mRNA abundance in preweaned Holstein Friesian bull calves
Authors: Coen Stephen P , Keogh Kate , Byrne Colin J , Lonergan Pat , Fair Sean , Crowe Mark A , Kenny David A 
Published: June 2021

Abstract
The objective of this study was to examine the effect of nutrition during the first 12 wk of life on aspects of the physiological and transcriptional regulation of testicular and overall sexual development in the bull calf. Holstein Friesian bull calves with a mean (SD) age and bodyweight of 17.5 (2.85) d and 48.8 (5.30) kg, respectively, were assigned to either a high (HI; n = 15) or moderate (MOD; n = 15) plane of nutrition and were individually fed milk replacer and concentrate to achieve overall target growth rates of at least 1.0 and 0.5 kg/d, respectively. Throughout the trial, animal growth performance, feed intake, and systemic concentrations of metabolites, metabolic hormones, and reproductive hormones were assessed. Additionally, pulsatility of reproductive hormones (luteinizing hormone, follicle-stimulating hormone, and testosterone) was recorded at 15-min intervals during a 10-h period at 10 wk of age. At 87 ± 2.14 d of age, all calves were euthanized, testes were weighed, and testicular tissue was harvested. Differential expression of messenger ribonucleic acid (mRNA) candidate genes involved in testicular development was examined using quantitative polymerase chain reaction assays. All data were analyzed using the MIXED procedure in Statistical Analysis Software using terms for treatment as well as time for repeated measures. Blood metabolites and metabolic hormones generally reflected the improved metabolic status of the calves on the HI plane of nutrition though the concentrations of reproductive hormones were not affected by diet. Calves on the HI diet had greater mean (SED) slaughter weight (112.4 vs. 87.70 [2.98] kg; P &lt; 0.0001) and testicular tissue weight (29.2 vs. 20.1 [2.21] g; P = 0.0003) than those on the MOD diet. Relative mRNA abundance data indicated advanced testicular development through upregulation of genes involved in cellular metabolism (SIRT1; P = 0.0282), cholesterol biosynthesis (EBP; P = 0.007), testicular function (INSL3; P = 0.0077), and Sertoli cell development (CLDN11; P = 0.0054) in HI compared with MOD calves. In conclusion, results demonstrate that offering dairy-bred male calves a high plane of nutrition during the first 3 mo of life not only improves growth performance and metabolic status but also advances testicular development consistent with more precocious sexual maturation.
The Effects of Private Damage Claims on Cartel Activity: Experimental Evidence
Authors: Bodnar Olivia , Fremerey Melinda , Normann Hans-Theo , Schad Jannika 
Published: June 2021

AbstractPrivate damage claims against cartels may have negative effects on leniency: whereas whistleblowers obtain full immunity regarding the public cartel fines, they have no or only restricted protection against private third-party damage claims. This may stabilize cartels. We run an experiment to study this issue. Firms choose whether to join a cartel, may apply for leniency afterward, and then potentially face private damages. We find that the implementation of private damage claims reduces cartel formation but makes cartels indeed more stable. The negative effect of damages is avoided in a novel setting where the whistleblower is also protected from damages (JEL C90, L41, L44).
Nächstenliebe in the Age of Nationalism: Reclaiming a Jewish Emotion between the Fin-de-Siècle and the First World War
Authors: Bailey Christian 
Published: June 2021

Abstract
This article asks why the concept of ‘Nächstenliebe’ or ‘love of neighbour’ became a source of contestation between Jewish and Christian intellectuals between the fin-de-siècle and the First World War. For some Christian intellectuals, highlighting differences between an apparently more expansive Christian love of neighbour and an allegedly narrower Jewish conception could provide a novel means of questioning how fully Jews could belong as members of German society. As the article shows, Jewish intellectuals did not simply seek to counter those definitions that claimed a moral superiority for Christian Nächstenliebe, however. Some went further and argued that Jewish ideas of neighbourly love were actually the more cosmopolitan, in contrast to Christian conceptions that had become increasingly self-serving and sectarian. In some instances, these Jewish intellectuals used such arguments about love of neighbour to make the case for Zionism. The article then investigates how the First World War affected these ideas about Nächstenliebe. It suggests that the war furthered the ‘negative integration’ of German society in ways that left little room for love between diverse kinds of German.
Strain Counterstrain Pain Treatment: A Solution for Military Members to Succeed
Authors: Biery John C , Savoia-McHugh Kimberly S , Savoia-McHugh Lee A 
Published: June 2021

ABSTRACT
Military members are required to perform in austere environments in which standard medical care routinely provided in the civilian setting is not available. Medical problems requiring hospital-based treatment which is not available in the field, shipboard, or deployed setting can be a cause for military members to be permanently discharged from active duty for medical reasons. We present a case of chronic low back pain treated with epidural steroid injections not routinely available aboard ship. The member was found unfit for shipboard duties, potentially ending her career in the military. The patient’s low back pain resolved with Strain Counterstrain (SCS) techniques. Additionally, SCS treatments also resolved undisclosed chronic pelvic pain, leading to improved overall quality of life. Strain Counterstrain is a non-interventional treatment which does not require special equipment, is available in austere environments and aboard ship, and allowed the member to remain on active duty. Strain Counterstrain is a manual muscle-retraining procedure easily learned, which can be performed in the field, on ship, in the deployed setting, in primary care, as well as in specialty pain medicine clinics.
On accretion discs formed in MHD simulations of black hole–neutron star mergers with accurate microphysics
Authors: Most Elias R , Papenfort L Jens , Tootle Samuel D , Rezzolla Luciano 
Published: June 2021

ABSTRACT
Remnant accretion discs formed in compact object mergers are an important ingredient in the understanding of electromagnetic afterglows of multimessenger gravitational-wave events. Due to magnetically and neutrino-driven winds, a significant fraction of the disc mass will eventually become unbound and undergo r-process nucleosynthesis. While this process has been studied in some detail, previous studies have typically used approximate initial conditions for the accretion discs, or started from purely hydrodynamical simulations. In this work, we analyse the properties of accretion discs formed from near equal-mass black hole–neutron star mergers simulated in general-relativistic magnetohydrodynamics in dynamical spacetimes with an accurate microphysical description. The post-merger systems were evolved until $120\, {\rm ms}$ for different finite-temperature equations of state and black hole spins. We present a detailed analysis of the fluid properties and of the magnetic-field topology. In particular, we provide analytic fits of the magnetic-field strength and specific entropy as a function of the rest-mass density, which can be used for the construction of equilibrium disc models. Finally, we evolve one of the systems for a total of $350\, \rm ms$ after merger and study the prospect for eventual jet launching. While our simulations do not reach this stage, we find clear evidence of continued funnel magnetization and clearing, a prerequisite for any jet-launching mechanism.
A new photometric and dynamical study of the eclipsing binary star HW Virginis
Authors: Brown-Sevilla S B , Nascimbeni V , Borsato L , Tartaglia L , Nardiello D , Granata V , Libralato M , Damasso M , Piotto G , Pollacco D , West R G , Colombo L S , Cunial A , Piazza G , Scaggiante F 
Published: June 2021

ABSTRACT
A growing number of eclipsing binary systems of the ‘HW Virginis’ (HW Vir) kind (i.e. composed by a subdwarf-B/O primary star and an M dwarf secondary) show variations in their orbital period, also called eclipse time variations (ETVs). Their physical origin is not yet known with certainty: While some ETVs have been claimed to arise from dynamical perturbations due to the presence of circumbinary planetary companions, other authors suggest that the Applegate effect or other unknown stellar mechanisms could be responsible for them. In this work, we present 28 unpublished high-precision light curves of one of the most controversial of these systems, the prototype HW Vir. We homogeneously analysed the new eclipse timings together with historical data obtained between 1983 and 2012, demonstrating that the planetary models previously claimed do not fit the new photometric data, besides being dynamically unstable. In an effort to find a new model able to fit all the available data, we developed a new approach based on a global-search genetic algorithm and eventually found two new distinct families of solutions that fit the observed timings very well, yet dynamically unstable at the 105-yr time-scale. This serves as a cautionary tale on the existence of formal solutions that apparently explain ETVs but are not physically meaningful, and on the need of carefully testing their stability. On the other hand, our data confirm the presence of an ETV on HW Vir that known stellar mechanisms are unable to explain, pushing towards further observing and modeling efforts.
Self-sustaining vortices in protoplanetary discs: Setting the stage for planetary system formation
Authors: Regály Zsolt , Kadam Kundan , Dullemond Cornelis P 
Published: June 2021

ABSTRACT
The core accretion scenario of planet formation assumes that planetesimals and planetary embryos are formed during the primordial, gaseous phases of the protoplanetary disc. However, how the dust particles overcome the traditional growth barriers is not well understood. The recently proposed viscous ring-instability may explain the concentric rings observed in protoplanetary discs by assuming that the dust grains can reduce the gas conductivity, which can weaken the magnetorotational instability. We present an analysis of this model with the help of GPU-based numerical hydrodynamic simulations of coupled gas and dust in the thin-disc limit. During the evolution of the disc the dusty rings become Rossby unstable and breakup into a cascade of small-scale vortices. The vortices form secularly stable dusty structures, which could be sites of planetesimal formation by the streaming instability as well as direct gravitational collapse. The phenomenon of self-sustaining vortices is consistent with observational constraints of exoplanets and sets a favourable environment for planetary system formation.
Physical conditions of iron-peak low-ionization lines in the FeLoBAL quasar Q0059-2735
Authors: Xu Xinfeng , Arav Nahum , Miller Timothy , Korista Kirk T , Benn Chris 
Published: June 2021

ABSTRACT
Quasar Q0059–2735, one of the first known iron low-ionization broad-absorption-line quasars (FeLoBAL), has a plethora of outflow absorption features at different velocities. Given multiple outflow systems, their troughs from high-ionization transitions form very wide BAL features, e.g. C iv troughs extend from ∼−1000 to −25 000 km s−1. The troughs from low-ionization transitions show more than 1000 narrow absorption lines (NALs) with velocities from −1000 to −3000 km s−1. These include troughs from iron-peak elements, e.g. Fe ii, Fe iii, Cr ii, Mn ii, Ni ii, and Co ii, which are rarely detected in quasar outflows. Most of these troughs are non-black saturated. We constrain the physical conditions of the NALs by fitting the observed Fe ii and Fe iii absorption troughs. We find that the Fe ii absorption arises from a region with an electron temperature (Te) of ∼8000 K and an electron number density (ne) of ∼108 cm−3. The same model also fits well the troughs from other iron-peak elements. In contrast to the Fe ii lines, Fe iii lines are formed in a hotter region, i.e. Te ∼20 000 K. To fit the Fe ii and Fe iii lines simultaneously in a single photoionized cloud, they require a supersolar iron abundance and/or other heating mechanisms for the Fe iii region. The distance (R) of the outflows to the central quasar is determined to be ∼40 pc. The high-resolution data afforded by the Very Large Telescope (VLT)/UVES observations from 2006 and 2018, along with the narrow lines, allow us to constrain the smallest outflow deceleration in any known quasars.
Variation of the nebular dust attenuation curve with the properties of local star-forming galaxies
Authors: Rezaee Saeed , Reddy Naveen , Shivaei Irene , Fetherolf Tara , Emami Najmeh , Khostovan A A 
Published: June 2021

ABSTRACT
We use a sample of 78 340 star-forming galaxies at z ≃ 0.04–0.1 from the Sloan Digital Sky Survey (SDSS) data release (DR8) survey to calculate the average nebular dust attenuation curve and its variation with the physical properties of galaxies. Using the first four low-order Balmer emission lines (H α, H β, H γ, and H δ) detected in the composite spectrum of all galaxies in the sample, we derive a nebular attenuation curve in the range of 0.41 to $0.66\, \mu$m that has a similar shape and normalization to that of the Galactic extinction curve (Milky Way curve), the SMC curve and the nebular attenuation curve derived recently for typical star-forming galaxies at z ∼ 2. We divide the galaxies into bins of stellar mass, gas-phase metallicity, and specific star formation rate, and derive the nebular attenuation curve in each of these bins. This analysis indicates that there is very little variation in the shape of the nebular dust attenuation curve with the properties used to bin the galaxies, and suggests a near universal shape of the nebular dust attenuation curve at least among the galaxies and the range of properties considered in our sample.
Cognate restriction of transposition by piggyBac-like proteins
Authors: Beckermann Thomas M , Luo Wentian , Wilson Catherine M , Veach Ruth Ann , Wilson Matthew H 
Published: June 2021

Abstract
Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein production, creation of transgenic animals, and engineering cell and gene therapy products. The piggyBac transposon family includes transposase or transposase-like proteins from a variety of species including insect, bat and human. Recently, human piggyBac transposable element derived 5 (PGBD5) protein was reported to be able to transpose piggyBac transposons in human cells raising possible safety concerns for piggyBac-mediated gene transfer applications. We evaluated three piggyBac-like proteins across species including piggyBac (insect), piggyBat (bat) and PGBD5 (human) for their ability to mobilize piggyBac transposons in human cells. We observed a lack of cross-species transposition activity. piggyBac and piggyBat activity was restricted to their cognate transposons. PGBD5 was unable to mobilize piggyBac transposons based on excision, colony count and plasmid rescue analysis, and it was unable to bind piggyBac terminal repeats. Within the piggyBac family, we observed a lack of cross-species activity and found that PGBD5 was unable to bind, excise or integrate piggyBac transposons in human cells. Transposition activity appears restricted within species within the piggyBac family of mobile genetic elements.
A comparative integrated multi-omics analysis identifies CA2 as a novel target for chordoma
Authors: Meng Tong , Huang Runzhi , Jin Jiali , Gao Jianxuan , Liu Fuyan , Wei Ziheng , Xu Xiaowen , Chang Zhengyan , Lin Jun , Ta Na , Huang Zongqiang , Yin Huabin , Zhou Wang , Song Dianwen 
Published: June 2021

Abstract

Background
Chordoma is a rare mesenchymal malignancy, with a high recurrence rate and unclear tumorigenic mechanism. Genetic alterations, epigenetic regulators, and chromatin spatial organization play crucial roles in the initiation and progression of chordoma. In the current study, we aim to uncover the novel therapeutical targets for chordoma via using integrated multi-omics analysis.

Methods
The RNA-sequencing (RNA-seq), assay for transposable accessible chromatin by high-throughput sequencing (ATAC-seq), and Hi-C were performed between chordoma and human nucleus pulposus (HNP), along with imageological examination and clinical information. The expressions of identified targets were validated by clinical samples and their functions were further evaluated by cell and animal experiments via gene knockdown and inhibitors.

Results
The integrated multi-omics analysis revealed the important roles of bone microenvironment in chordoma tumorigenesis. By comparing the hierarchical structures, CA2 (carbonic anhydrase II) and THNSL2 (threonine synthase-like 2) were identified in the switched compartments, cell-specific boundaries, and loops. Additionally, CA2 was highly expressed in chordoma but barely found in HNP. The cell growth and migration of chordoma cells were dramatically suppressed via inhibition of CA2 either with genetic deletion or pharmaceutical treatment with Dorzolamide HCl. Furthermore, Dorzolamide HCl also regulated the bone microenvironment by blocking the osteoclast differentiation of bone marrow monocytes.

Conclusion
This study uncovers the roles of bone microenvironment in the chordoma tumorigenesis and identifies CA2 as a novel therapeutic target for chordoma. Besides, our findings suggest Dorzolamide HCl as a promising therapeutic option for chordoma.
A novel patient stratification strategy to enhance the therapeutic efficacy of dasatinib in glioblastoma
Authors: Alhalabi Obada T , Fletcher Michael N C , Hielscher Thomas , Kessler Tobias , Lokumcu Tolga , Baumgartner Ulrich , Wittmann Elena , Schlue Silja , Göttmann Mona , Rahman Shaman , Hai Ling , Hansen-Palmus Lea , Puccio Laura , Nakano Ichiro , Herold-Mende Christel , Day Bryan W , Wick Wolfgang , Sahm Felix , Phillips Emma , Goidts Violaine 
Published: June 2021

Abstract

Background
Glioblastoma is the most common primary malignancy of the central nervous system with a dismal prognosis. Genomic signatures classify isocitrate dehydrogenase 1 (IDH)-wildtype glioblastoma into three subtypes: proneural, mesenchymal, and classical. Dasatinib, an inhibitor of proto-oncogene kinase Src (SRC), is one of many therapeutics which, despite promising preclinical results, have failed to improve overall survival in glioblastoma patients in clinical trials. We examined whether glioblastoma subtypes differ in their response to dasatinib and could hence be evaluated for patient enrichment strategies in clinical trials.

Methods
We carried out in silico analyses on glioblastoma gene expression (TCGA) and single-cell RNA-Seq data. In addition, in vitro experiments using glioblastoma stem-like cells (GSCs) derived from primary patient tumors were performed, with complementary gene expression profiling and immunohistochemistry analysis of tumor samples.

Results
Patients with the mesenchymal subtype of glioblastoma showed higher SRC pathway activation based on gene expression profiling. Accordingly, mesenchymal GSCs were more sensitive to SRC inhibition by dasatinib compared to proneural and classical GSCs. Notably, SRC phosphorylation status did not predict response to dasatinib treatment. Furthermore, serpin peptidase inhibitor clade H member 1 (SERPINH1), a collagen-related heat-shock protein associated with cancer progression, was shown to correlate with dasatinib response and with the mesenchymal subtype.

Conclusion
This work highlights further molecular-based patient selection strategies in clinical trials and suggests the mesenchymal subtype as well as SERPINH1 to be associated with response to dasatinib. Our findings indicate that stratification based on gene expression subtyping should be considered in future dasatinib trials.