bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative stress promotes cellular damages in the cervix: implications for normal and pathologic cervical function in human pregnancy
Authors: Tantengco Ourlad Alzeus G , Vink Joy , Medina Paul Mark B , Menon Ramkumar 
Published: March 2021

Abstract
A physiologic increase in reactive oxygen species throughout pregnancy is required to remodel the cervix. Oxidative stress can cause cellular damage that contributes to dysfunctional tissue. This study determined the oxidative stress-induced cell fate of human cervical epithelial and cervical stromal cells. We treated the ectocervical and endocervical epithelial cells and cervical stromal cells with cigarette smoke extract, an oxidative stress inducer, for 48 h. Cell viability (crystal violet assay); cell cycle, apoptosis, and necrosis (flow cytometry); senescence (senescence-associated β-galactosidase staining); autophagy (staining for autophagosome protein, microtubule-associated protein 1 light chain 3B); stress signaler p38 mitogen-activated protein kinases pathway activation (western blot analyses); and inflammation by measuring interleukin-6 (enzyme-linked immunosorbent assay) were conducted after 48 h of cigarette smoke extract treatment. Oxidative stress induced reactive oxygen species production in cervical cells, which was inhibited by N-acetylcysteine. Oxidative stress promoted cell cycle arrest and induced necrosis in cervical cells. High senescence and low autophagy were observed in cervical stromal cells under oxidative stress. Conversely, senescence was low and autophagy was high in endocervical epithelial cells. Oxidative stress induced p38 mitogen-activated protein kinases (p38MAPK) activation in all cervical cells but only increased interleukin-6 production by the ectocervical epithelial cells. Inhibition of interleukin-6 production by a p38 mitogen-activated protein kinases inhibitor confirmed the activation of an oxidative stress-induced pathway. In conclusion, oxidative stress can promote cell death and sterile inflammation that is mediated by p38 mitogen-activated protein kinases activation in the cellular components of the cervix. These cellular damages may contribute to the normal and premature cervical ripening, which can promote preterm birth.
Why translation from basic discoveries to clinical applications is so difficult for atrial fibrillation and possible approaches to improving it
Authors: Nattel Stanley , Sager Philip T , Hüser Jörg , Heijman Jordi , Dobrev Dobromir 
Published: March 2021

Abstract
Atrial fibrillation (AF) is the most common sustained clinical arrhythmia, with a lifetime incidence of up to 37%, and is a major contributor to population morbidity and mortality. Important components of AF management include control of cardiac rhythm, rate, and thromboembolic risk. In this narrative review article, we focus on rhythm-control therapy. The available therapies for cardiac rhythm control include antiarrhythmic drugs and catheter-based ablation procedures; both of these are presently neither optimally effective nor safe. In order to develop improved treatment options, it is necessary to use preclinical models, both to identify novel mechanism-based therapeutic targets and to test the effects of putative therapies before initiating clinical trials. Extensive research over the past 30 years has provided many insights into AF mechanisms that can be used to design new rhythm-maintenance approaches. However, it has proven very difficult to translate these mechanistic discoveries into clinically applicable safe and effective new therapies. The aim of this article is to explore the challenges that underlie this phenomenon. We begin by considering the basic problem of AF, including its clinical importance, the current therapeutic landscape, the drug development pipeline, and the notion of upstream therapy. We then discuss the currently available preclinical models of AF and their limitations, and move on to regulatory hurdles and considerations and then review industry concerns and strategies. Finally, we evaluate potential paths forward, attempting to derive insights from the developmental history of currently used approaches and suggesting possible paths for the future. While the introduction of successful conceptually innovative new treatments for AF control is proving extremely difficult, one significant breakthrough is likely to revolutionize both AF management and the therapeutic development landscape.
Oviposition Response of Monarch Butterfly (Lepidoptera: Nymphalidae) to Imidacloprid-Treated Milkweed
Authors: Mullins Alexander N , Bradbury Steven P , Sappington Thomas W , Adelman James S 
Published: March 2021

Abstract
Monarch butterfly (Danaus plexippus) populations have declined over the last two decades, attributable in part to declines in its larval host plant, milkweed (Asclepias spp.), across its breeding range. Conservation efforts in the United States call for restoration of 1.3 billion milkweed stems into the Midwestern landscape. Reaching this goal will require habitat establishment in marginal croplands, where there is a high potential for exposure to agrochemicals. Corn and soybean crops may be treated with neonicotinoid insecticides systemically or through foliar applications to provide protection against insect pests. Here, we investigate whether ovipositing monarchs discriminate against milkweed plants exposed to the neonicotinoid insecticide imidacloprid, either systemically or through foliar application. In our first experiment, we placed gravid females in enclosures containing a choice of two cut stems for oviposition: one in 15 ml of a 0.5 mg/ml aqueous solution of imidacloprid and one in 15 ml water. In a second experiment, females were given a choice of milkweed plants whose leaves were treated with 30 µl of a 0.825 mg/ml imidacloprid-surfactant solution or plants treated with surfactant alone. To evaluate oviposition preference, we counted and removed eggs from all plants daily for 3 d. We also collected video data on a subset of butterflies to evaluate landing behavior. Results indicate that neither systemic nor foliar treatment with imidacloprid influenced oviposition behavior in female monarchs. The implications of these findings for monarch conservation practices will be informed by the results of ongoing egg and larval toxicity studies.
Long-term outcomes of patients with primary graft dysfunction after cardiac transplantation
Authors: Squiers John J , DiMaio J Michael , Van Zyl Johanna , Lima Brian , Gonzalez-Stawisnksi Gonzalo , Rafael Aldo E , Meyer Dan M , Hall Shelley A 
Published: March 2021

Abstract

OBJECTIVES
The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year.

METHODS
A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan–Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days.

RESULTS
A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P &lt; 0.001). Landmark analyses demonstrated that patients with moderate or severe PGD were at increased risk of mortality during the first 90-days after transplantation as compared to those with none or mild PGD [hazard ratio (95% confidence interval) 18.9 (7.1–50.5); P &lt; 0.001], but this hazard did not persist beyond 90-days in survivors (P = 0.64).

CONCLUSIONS
A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.
Joint multizonal transdimensional Bayesian inversion of surface wave dispersion and ellipticity curves for local near-surface imaging
Authors: Hallo Miroslav , Imperatori Walter , Panzera Francesco , Fäh Donat 
Published: March 2021

SummaryPhysical properties of near-surface soil and rock layers play a fundamental role in the seismic site effects analysis, being an essential element of seismic hazard assessment. Site-specific mechanical properties (i.e. shear- and compressional-wave velocities and mass density) can be inferred from surface wave dispersion and horizontal-to-vertical or ellipticity data by non-linear inversion techniques. Nevertheless, results typically exhibit significant inherent non-uniqueness as different models may fit the data equally well. Standard optimization inversion techniques minimize data misfit, resulting in a single representative model, rejecting other models providing similar misfit values. An alternative inversion technique can be formulated in the Bayesian framework, where the posterior probability density on the model space is inferred. This paper introduces an inversion approach of surface wave dispersion and ellipticity data based on a novel multizonal transdimensional Bayesian formulation. In particular, we parametrize 1-D layered velocity models by the varying number of Voronoi nuclei, allowing us to treat the number of layers as an unknown parameter of the inverse problem. The chosen parametrization leads to the transdimensional formulation of the model space, sampled by a reversible jump Markov chain Monte Carlo algorithm to provide an ensemble of random samples following the posterior probability density of model parameters. The used type of the sampling algorithm controls a model complexity (i.e. the number of layers) self-adaptively based on the measured data's information content. The method novelty lies in the parsimonious selection of sampling models and in the multizonal formulation of prior assumptions on model parameters, the latter allows including additional site-specific constraints in the inversion. These assumptions may be based on, e.g. stratigraphic logs, standard penetration tests, known water table, and bedrock depth. The multizonal formulation fully preserves the validity of the transdimensional one, as demonstrated analytically. The resultant ensemble of model samples is a discrete approximation of the posterior probability density function of model parameters and associated properties (e.g. VS30, quarter-wavelength average velocity profile and theoretical SH-wave amplification function). Although the ultimate result is the posterior probability density function, some representative models are selected according to data fit and maximum of the posterior probability density function. We first validate our inversion approach based on synthetic tests and then apply it to field data acquired from the active seismic survey and single-station measurements of ambient vibrations at the SENGL seismic station site in central Switzerland.
Evaluating an organizational innovation: evidence from the conglomerate merger wave
Authors: Klein Peter , Wuebker Robert , Chen Mo , Zoeller Kathrin 
Published: March 2021

AbstractHow do we assess new forms of economic organization? As with other innovations, the value of a new organizational form is initially unknown. When assets are traded in financial markets, the information embodied in prices represent one mechanism through which organizational innovations are evaluated. We apply an experimental-learning framework to explore the influence of the capital markets on economic organization, using the conglomerate merger wave of the 1960s and 1970s as an empirical context. In our setting, the initial market popularity of conglomerates, followed by their rapid decline, is indicative of investors attempting to determine the value of a new organizational form. We provide event-study evidence that investors systematically updated their beliefs about the value of the conglomerate form based on new information (positive or negative) about the largest and most newsworthy conglomerates. Our results suggest that financial market participants make judgments not only about specific companies, but about organizational structure itself.
Stress at Work: Individuals or Structures?
Authors: Davies A C L 
Published: March 2021

Abstract
Stress is a significant practical problem in modern workplaces. According to the Health and Safety Executive (HSE), more than half of all working days lost to ill health each year are attributed to stress, depression or anxiety. This article offers an overview of the occupational psychology literature on workplace stress, focussing on the job demands–resources or JD-R model, developed by Demerouti et al., and highlighting two important points: first, that stress at work is not just about excessive job ‘demands’ but also about inadequate ‘resources’ to cope with those demands; second, that stress-related ill-health is not just a matter of vulnerability on the part of the individual worker, but is also about the way in which the workplace is organised. The article then draws on these insights to offer a critique of the way in which health and safety law and tort law approach workplace stress, arguing that both bodies of law are overly focussed on treating stress as a matter of individual vulnerability. It concludes by drawing out some broader implications of the occupational psychology literature for areas of employment law less obviously related to workplace stress, and for casual or platform working.
Robotic Antimicrobial Susceptibility Platform (RASP): a next-generation approach to One Health surveillance of antimicrobial resistance
Authors: Truswell Alec , Abraham Rebecca , O’Dea Mark , Lee Zheng Zhou , Lee Terence , Laird Tanya , Blinco John , Kaplan Shai , Turnidge John , Trott Darren J , Jordan David , Abraham Sam 
Published: March 2021

Abstract

Background
Surveillance of antimicrobial resistance (AMR) is critical to reducing its wide-reaching impact. Its reliance on sample size invites solutions to longstanding constraints regarding scalability. A robotic platform (RASP) was developed for high-throughput AMR surveillance in accordance with internationally recognized standards (CLSI and ISO 20776-1:2019) and validated through a series of experiments.

Methods
Experiment A compared RASP’s ability to achieve consistent MICs with that of a human technician across eight replicates for four Escherichia coli isolates. Experiment B assessed RASP’s agreement with human-performed MICs across 91 E. coli isolates with a diverse range of AMR profiles. Additionally, to demonstrate its real-world applicability, the RASP workflow was then applied to five faecal samples where a minimum of 47 E. coli per animal (239 total) were evaluated using an AMR indexing framework.

Results
For each drug–rater–isolate combination in Experiment A, there was a clear consensus of the MIC and deviation from the consensus remained within one doubling dilution (the exception being gentamicin at two dilutions). Experiment B revealed a concordance correlation coefficient of 0.9670 (95% CI: 0.9670–0.9670) between the robot- and human-performed MICs. RASP’s application to the five faecal samples highlighted the intra-animal diversity of gut commensal E. coli, identifying between five and nine unique isolate AMR phenotypes per sample.

Conclusions
While adhering to internationally accepted guidelines, RASP was superior in throughput, cost and data resolution when compared with an experienced human technician. Integration of robotics platforms in the microbiology laboratory is a necessary advancement for future One Health AMR endeavours.
Ethidium bromide exposure unmasks an antibiotic efflux system in Rhodococcus equi
Authors: Rampacci Elisa , Marenzoni Maria Luisa , Cannalire Rolando , Pietrella Donatella , Sabatini Stefano , Giovagnoli Stefano , Felicetti Tommaso , Pepe Marco , Passamonti Fabrizio 
Published: March 2021

Abstract

Background
This study introduces a newly created strain (Rhodococcus equiEtBr25) by exposing R. equi ATCC 33701 to ethidium bromide (EtBr), a substrate for MDR transporters. Such an approach allowed us to investigate the resulting phenotype and genetic mechanisms underlying the efflux-mediated resistance in R. equi.

Methods
R. equi ATCC 33701 was stimulated with increasing concentrations of EtBr. The antimicrobial susceptibility of the parental strain and R. equiEtBr25 was investigated in the presence/absence of efflux pump inhibitors (EPIs). EtBr efflux was evaluated by EtBr-agar method and flow cytometry. The presence of efflux pump genes was determined by conventional PCR before to quantify the expression of 30 genes coding for membrane transporters by qPCR. The presence of erm(46) and mutations in 23S rRNA, and gyrA/gyrB was assessed by PCR and DNA sequencing to exclude the occurrence of resistance mechanisms other than efflux.

Results
R. equi EtBr25 showed an increased EtBr efflux. Against this strain, the activity of EtBr, azithromycin and ciprofloxacin was more affected than that of rifampicin and azithromycin/rifampicin combinations. Resistances were reversed by combining the antimicrobials with EPIs. Gene expression analysis detected a marked up-regulation of REQ_RS13460 encoding for a Major Facilitator Superfamily (MFS) transporter. G→A transition occurred in the transcriptional repressor tetR/acrR adjacent to REQ_RS13460.

Conclusions
Exposure of R. equi to EtBr unmasked an efflux-mediated defence against azithromycin and ciprofloxacin, which seemingly correlates with the overexpression of a specific MFS transporter. This genotype may mirror an insidious low-level resistance of clinically important isolates that could be countered by EPI-based therapies.
PaleoCodage—Enhancing machine-readable cuneiform descriptions using a machine-readable paleographic encoding
Authors: Homburg Timo 
Published: March 2021

Abstract
This publication introduces PaleoCodage, a new machine-readable way to capture cuneiform paleographic shapes. Many different systems of listing and describing cuneiform signs exist, but none of the systems can be used to describe the shape, i.e. paleographic features of cuneiform signs. PaleoCodage aims to fill this missing link of description which can benefit the Semantic Web community of linked open data dictionaries, the assyrologist community in documenting signs and their variants and the cuneiform image recognition community in providing a gold standard encoding to match against. The publication evaluates the encoding on more than 200 Unicode cuneiform signs, describes already available application cases, a linked data vocabulary for paleography and concludes by describing future work on further validating PaleoCodage and applying the paleographic vocabulary to more languages.
A Talmudic norms approach to many-valued logic
Authors: Lethen Tim 
Published: March 2021

AbstractIn three-valued logic, the third truth-value is often interpreted as undefined. However, the value of a logical term may be well defined if its ‘history’ is taken into account. Following this approach, the analogy to the Sorites paradox meets the eye, which in turn has recently been addressed by means of a ‘Talmudic Norms’ approach. This paper thus lays bare a religious contribution to the field of many-valued logic and implements a simplified dynamic model for the theory of Talmudic mixtures—and, thus, for the outlined Sorites logic—using standard AI search and planning techniques.
Z-Sequence: photometric redshift predictions for galaxy clusters with sequential random k-nearest neighbours
Authors: Chan Matthew C , Stott John P 
Published: March 2021

ABSTRACTWe introduce Z-Sequence, a novel empirical model that utilizes photometric measurements of observed galaxies within a specified search radius to estimate the photometric redshift of galaxy clusters. Z-Sequence itself is composed of a machine learning ensemble based on the k-nearest neighbours algorithm. We implement an automated feature selection strategy that iteratively determines appropriate combinations of filters and colours to minimize photometric redshift prediction error. We intend for Z-Sequence to be a standalone technique but it can be combined with cluster finders that do not intrinsically predict redshift, such as our own DEEP-CEE. In this proof-of-concept study, we train, fine-tune, and test Z-Sequence on publicly available cluster catalogues derived from the Sloan Digital Sky Survey. We determine the photometric redshift prediction error of Z-Sequence via the median value of |Δ$z$|/(1 + $z$) (across a photometric redshift range of 0.05 ≤ $z$ ≤ 0.6) to be ∼0.01 when applying a small search radius. The photometric redshift prediction error for test samples increases by 30–50 per cent when the search radius is enlarged, likely due to line-of-sight interloping galaxies. Eventually, we aim to apply Z-Sequence to upcoming imaging surveys such as the Legacy Survey of Space and Time to provide photometric redshift estimates for large samples of as yet undiscovered and distant clusters.
Genomic editing of intronic enhancers unveils their role in fine-tuning tissue-specific gene expression in Arabidopsis thaliana
Authors: Meng Fanli , Zhao Hainan , Zhu Bo , Zhang Tao , Yang Mingyu , Li Yang , Han Yingpeng , Jiang Jiming 
Published: March 2021

Abstract
Enhancers located in introns are abundant and play a major role in the regulation of gene expression in mammalian species. By contrast, the functions of intronic enhancers in plants have largely been unexplored and only a handful of plant intronic enhancers have been reported. We performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing. We identified 941 candidate intronic enhancers associated with 806 genes in seedling tissue and 1,271 intronic enhancers associated with 1,069 genes in floral tissue. We validated the function of 15 of 21 (71%) of the predicted intronic enhancers in transgenic assays using a reporter gene. We also created deletion lines of three intronic enhancers associated with two different genes using CRISPR/Cas. Deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes. Remarkably, the transcriptional repression of the deletion lines occurred at specific developmental stages and resulted in distinct phenotypic effects on plant morphology and development. Clearly, these three intronic enhancers are important in fine-tuning tissue- and development-specific expression of their cognate genes.