bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevation of O-GlcNAc and GFAT expression by nicotine exposure promotes epithelial‐mesenchymal transition and invasion in breast cancer cells
Authors: Zhang Nana , Zhu Tong , Yu Kairan , Shi Meiyun , Wang Xue , Wang Lingyan , Huang Tianmiao , Li Wenli , Liu Yubo , Zhang Jianing 
Published: April 2019

AbstractCigarette smoking has been shown to be a carcinogenic factor in breast cancer. Nicotine (Nic), an active component of tobacco, has been found to induce epithelial-mesenchymal transition (EMT) in breast cancer cells. However, the alterations in protein O-GlcNAcylation in Nic-mediated tumorigenesis and malignization mechanisms are less well studied. Herein, we found that cellular O-GlcNAcylation dramatically increased in human breast cancer cells with EMT activation induced by Nic. Elevated O-GlcNAcylation subsequently promoted Nic-induced EMT activation and increased cell migratory abbility. In addition, we demonstrated that a differentiation factor for the mammary epithelium, CCAAT/enhancer-binding protein B (CEBPB), was involved in Nic-induced hyper-O-GlcNAcylation via transcriptional regulation of the expression of the key enzyme glutamine: fructose-6-phosphate amidotransferase (GFAT) and thus increased the flux through the hexosamine biosynthetic pathway (HBP). Finally, elevated O-GlcNAcylation of the transcriptional repressor C/EBP homologous protein (CHOP) suppressed its heterodimerization with CEBPB and facilitated the DNA-binding activity of CEBPB, further generating positive feedback that enhanced EMT upon Nic stimulation. In conclusion, our results have revealed a new regulatory mechanism involving CEBPB/GFAT-induced hyper-O-GlcNAcylation that plays a key role in EMT and smoking-mediated breast cancer progression.
In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers
Authors: Watanabe Sumiyo , Hayashi Kotaro , Toh Kazuko , Kim Hyun Jin , Liu Xueying , Chaya Hiroyuki , Fukushima Shigeto , Katsushima Keisuke , Kondo Yutaka , Uchida Satoshi , Ogura Satomi , Nomoto Takahiro , Takemoto Hiroyasu , Cabral Horacio , Kinoh Hiroaki , Tanaka Hiroyoshi Y. , Kano Mitsunobu R. , Matsumoto Yu , Fukuhara Hiroshi , Uchida Shunya , Nangaku Masaomi , Osada Kensuke , Nishiyama Nobuhiro , Miyata Kanjiro , Kataoka Kazunori 
Published: April 2019

AbstractStabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into ~100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (~18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity.
A comparative analysis of methods for de novo assembly of hymenopteran genomes using either haploid or diploid samples
Authors: Yahav Tal , Privman Eyal 
Published: April 2019

AbstractDiverse invertebrate taxa including all 200,000 species of Hymenoptera (ants, bees, wasps and sawflies) have a haplodiploid sex determination system, where females are diploid and males are haploid. Thus, hymenopteran genome projects can make use of DNA from a single haploid male sample, which is assumed advantageous for genome assembly. For the purpose of gene annotation, transcriptome sequencing is usually conducted using RNA from a pool of individuals. We conducted a comparative analysis of genome and transcriptome assembly and annotation methods, using genetic sources of different ploidy: (1) DNA from a haploid male or a diploid female (2) RNA from the same haploid male or a pool of individuals. We predicted that the use of a haploid male as opposed to a diploid female will simplify the genome assembly and gene annotation thanks to the lack of heterozygosity. Using DNA and RNA from the same haploid individual is expected to provide better confidence in transcript-to-genome alignment, and improve the annotation of gene structure in terms of the exon/intron boundaries. The haploid genome assemblies proved to be more contiguous, with both contig and scaffold N50 size at least threefold greater than their diploid counterparts. Completeness evaluation showed mixed results. The SOAPdenovo2 diploid assembly was missing more genes than the haploid assembly. The SPAdes diploid assembly had more complete genes, but a higher level of duplicates, and a greatly overestimated genome size. When aligning the two transcriptomes against the male genome, the male transcriptome gave 2–3% more complete transcripts than the pool transcriptome for genes with comparable expression levels in both transcriptomes. However, this advantage disappears in the final results of the gene annotation pipeline that incorporates evidence from homologous proteins. The RNA pool is still required to obtain the full transcriptome with genes that are expressed in other life stages and castes. In conclusion, the use of a haploid source material for a de novo genome project provides a substantial advantage to the quality of the genome draft and the use of RNA from the same haploid individual for transcriptome to genome alignment provides a minor advantage for genes that are expressed in the adult male.
Compatibility of ciprofloxacin with commercial peritoneal dialysis solutions
Authors: Kussmann Manuel , Ferth Alexander , Obermüller Markus , Pichler Petra , Zeitlinger Markus , Wiesholzer Martin , Burgmann Heinz , Poeppl Wolfgang , Reznicek Gottfried 
Published: April 2019

AbstractIntraperitoneal administration of antibiotics together with peritoneal dialysis fluids (PDFs) remains the preferable route for treatment of peritoneal dialysis-related peritonitis. For home based therapy, antibiotic-containing PDFs are stored for up to two weeks and warmed up to body-temperature before administration. The present study investigated the compatibility of ciprofloxacin with five commercial PDFs at refrigeration-temperature, room-temperature and body-temperature. Ciprofloxacin concentrations were determined using high-performance liquid chromatography. Drug-diluent stability was evaluated by measurement of pH-values and visual inspection at each sampling point. The antimicrobial activity of ciprofloxacin was assessed by an E. coli disk diffusion method. Ciprofloxacin was stable at refrigeration-temperature and body-temperature in all PDFs evaluated over the whole study period of 14 days and 24 hours, respectively. At room-temperature, in contrast, ciprofloxacin demonstrated only limited stability in particular when tested in mixed Physioneal. Except for Physioneal 1.36%, no relevant drug adsorption was observed and the antimicrobial activity of ciprofloxacin was found to be preserved in each PDF at each storage condition investigated. Intraperitoneal ciprofloxacin might be used for inpatient and home based therapy of peritoneal dialysis-related peritonitis and no compensatory dose adjustment is needed when stored for up to two weeks at refrigeration-temperature before use.
Propidium iodide staining underestimates viability of adherent bacterial cells
Authors: Rosenberg Merilin , Azevedo Nuno F. , Ivask Angela 
Published: April 2019

AbstractCombining membrane impermeable DNA-binding stain propidium iodide (PI) with membrane-permeable DNA-binding counterstains is a widely used approach for bacterial viability staining. In this paper we show that PI staining of adherent cells in biofilms may significantly underestimate bacterial viability due to the presence of extracellular nucleic acids (eNA). We demonstrate that gram-positive Staphylococcus epidermidis and gram-negative Escherichia coli 24-hour initial biofilms on glass consist of 76 and 96% PI-positive red cells in situ, respectively, even though 68% the cells of either species in these aggregates are metabolically active. Furthermore, 82% of E. coli and 89% S. epidermidis are cultivable after harvesting. Confocal laser scanning microscopy (CLSM) revealed that this false dead layer of red cells is due to a subpopulation of double-stained cells that have green interiors under red coating layer which hints at eNA being stained outside intact membranes. Therefore, viability staining results of adherent cells should always be validated by an alternative method for estimating viability, preferably by cultivation.
SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons
Authors: Qu Ruobing , Yao Fuping , Zhang Xiaomin , Gao Yuan , Liu Tong , Hua Yimin 
Published: April 2019

AbstractSpinal muscular atrophy (SMA) is a devastating motor neuron degeneration disease caused by a deficiency of the SMN protein. Majority of patients also suffer from chronic pain. However, the pathogenesis of pain in the context of SMA has never been explored. In this study, using various pain tests, we found that a mild SMA mouse model presents with multiple forms of pain hypersensitivity. Patch-clamp recording showed that nociceptive neurons in SMA mouse dorsal root ganglia (DRGs) are hyperexcitable and their sodium current densities are markedly increased. Using quantitative RT-PCR, western blotting and immunofluorescence, we observed enhanced expression of two main voltage-gated sodium channels Nav1.7 and Nav1.8 in SMA mouse DRGs, which is at least in part due to increase in both expression and phosphorylation of NF-κB p50/p65 heterodimer. Moreover, we revealed that plasma norepinephrine levels are elevated in SMA mice, which contributes to mechanical hypersensitivity via the β2-adrenergic receptor. Finally, we uncovered that β2-adrenergic signaling positively modulates expression as well as phosphorylation of p50 and p65 in SMA mouse DRGs. Therefore, our data demonstrate that SMA mice, similar to humans, also develop pain hypersensitivity, and highlight a peripheral signaling cascade that elicits the mechanical sensitization in the mouse model, suggesting potential targets for therapeutic intervention.
The impact of oxidative stress, inflammation, and senescence on the maintenance of immunological memory in the bone marrow in old age
Authors: Naismith Erin , Pangrazzi Luca 
Published: April 2019

AbstractThe bone marrow (BM) provides a preferential survival environment for the long-term maintenance of antigen-experienced adaptive immune cells. After the contact with antigens, effector/memory T cells and plasma cell precursors migrate to the BM, in which they can survive within survival niches in an antigen-independent manner. Despite this, the phenotype of adaptive immune cells changes with aging, and BM niches themselves are affected, leading to impaired long-term maintenance of immunological memory in the elderly as a result. Oxidative stress, age-related inflammation (inflammaging), and cellular senescence appear to play a major role in this process. This review will summarize the age-related changes in T and B cell phenotype, and in the BM niches, discussing the possibility that the accumulation of highly differentiated, senescent-like T cells in the BM during aging may cause inflammation in the BM and promote oxidative stress and senescence. In addition, senescent-like T cells may compete for space with other immune cells within the marrow, partially excluding effector/memory T cells and long-lived plasma cells from the niches.
Climate and land-use change homogenise terrestrial biodiversity, with consequences for ecosystem functioning and human well-being
Authors: Newbold Tim , Adams Georgina L. , Albaladejo Robles Gonzalo , Boakes Elizabeth H. , Braga Ferreira Guilherme , Chapman Abbie S. A. , Etard Adrienne , Gibb Rory , Millard Joseph , Outhwaite Charlotte L. , Williams Jessica J. 
Published: April 2019

Abstract
Biodiversity continues to decline under the effect of multiple human pressures. We give a brief overview of the main pressures on biodiversity, before focusing on the two that have a predominant effect: land-use and climate change. We discuss how interactions between land-use and climate change in terrestrial systems are likely to have greater impacts than expected when only considering these pressures in isolation. Understanding biodiversity changes is complicated by the fact that such changes are likely to be uneven among different geographic regions and species. We review the evidence for variation in terrestrial biodiversity changes, relating differences among species to key ecological characteristics, and explaining how disproportionate impacts on certain species are leading to a spatial homogenisation of ecological communities. Finally, we explain how the overall losses and homogenisation of biodiversity, and the larger impacts upon certain types of species, are likely to lead to strong negative consequences for the functioning of ecosystems, and consequently for human well-being.
The young stellar population in NGC 247
Authors: Rodríguez M. J. , Baume G. , Feinstein C. 
Published: April 2019

Aims. We seek to investigate the characteristics of the young stellar population in the spiral galaxy NGC 247. In particular, we focused our attention in its hierarchical clustering distributions and the properties of the smallest groups.
Methods. We used multiband Hubble Space Telescope (HST) data from three fields covering more than half of NGC 247 to select the young population. Then, through the path linkage criterion (PLC), we found compact young star groups and estimated their fundamental parameters, such as their stellar densities, sizes, number of members, and luminosity function (LF) slopes. We also performed a fractal analysis to determinate the clustering properties of this population. We built a stellar density map and dendrograms corresponding to the galactic young population to detect large structures and depict their main characteristics.
Results. We detect 339 young star groups, for which we compute a mean radius of ∼60 pc and a maximum size distribution between 30 and 70 pc. We also obtain LF slopes with a bimodal distribution showing peaks at ∼0.1 and ∼0.2. We identify several candidates for HII regions that follow an excellent spatial correlation with the young groups found by the PLC. We observe that the young populations are hierarchically organized, wherein the smaller and denser structures are within larger and less dense structures. We notice that all these groups present a fractal subclustering, following the hierarchical distribution observed in the corresponding stellar density map. For the large young structures observed in this map, we obtain a fractal dimension of ∼1.6–1.8 using the perimeter-area relation and cumulative size distribution. These values are consistent with a scenario of hierarchical star formation.
Reducing Surgeon's Physical Stress in Minimally Invasive Neurosurgery
Authors: Nakayashiki Atsushi , Kawaguchi Tomohiro , Nakagawa Atsuhiro , Mochizuki Fusako , Furukawa Hiroaki , Nagai Arata , Suematsu Takuya , Tominaga Teiji 
Published: April 2019

Background and Study Aims Various minimally invasive approaches are used in neurosurgery. Surgeons must perform nondynamic fine movements in a narrow corridor, so specially designed surgical devices are essential. Unsophisticated instruments may pose potential hazards. The purpose of this study was to assess the factors associated with muscle fatigue during minimally invasive neurosurgery and to investigate whether physical stress can be reduced by refining the devices used.
Material and Methods Four physical aspects of a handpiece were investigated: torque of conduits (0.20, 0.28, and 0.37 kgf*cm), shape of hand grip (five types), angle of the nozzle (0, 20, and 40 degrees), and weight balance (neutral, proximal, and distal). To evaluate muscle fatigue, surface electromyography was recorded from the extensor carpi radialis muscle and flexor carpi radialis muscle during a geometric tracing task. The maximum voluntary contraction (MVC) of each muscle and %MVC (muscle contraction during a task/MVC × 100) were used as the indexes of muscle fatigue.
Results The shape of the hand grip significantly reduced %MVC, which is associated with muscle fatigue. The torque of conduits and angle of the nozzle tended to reduce muscle fatigue but not significantly. Weight balance did not affect muscle fatigue. Based on these results, we made two refined models: model α (torque of conduits 0.2 kgf*cm, angle of nozzle 20 degrees, neutral balance, hand grip with a 2.9 × 2.0-cm oval section with angled finger rest), and model β (torque of conduits 0.2 kgf*cm, angle of nozzle 20 degrees, neutral balance, hand grip with a 2.9-cm round section with a curved finger rest). The %MVC was significantly decreased with both types (p < 0.05 and p < 0.01, respectively), indicating reduction of muscle fatigue.
Conclusions The geometrically refined surgical device can improve muscle load during surgery and reduce the surgeon's physical stress, thus minimizing the risk of complications.
Composer—Visual Cohort Analysis of Patient Outcomes
Authors: Rogers Jen , Spina Nicholas , Neese Ashley , Hess Rachel , Brodke Darrel , Lex Alexander 
Published: April 2019

Objective Visual cohort analysis utilizing electronic health record data has become an important tool in clinical assessment of patient outcomes. In this article, we introduce Composer, a visual analysis tool for orthopedic surgeons to compare changes in physical functions of a patient cohort following various spinal procedures. The goal of our project is to help researchers analyze outcomes of procedures and facilitate informed decision-making about treatment options between patient and clinician.
Methods In collaboration with orthopedic surgeons and researchers, we defined domain-specific user requirements to inform the design. We developed the tool in an iterative process with our collaborators to develop and refine functionality. With Composer, analysts can dynamically define a patient cohort using demographic information, clinical parameters, and events in patient medical histories and then analyze patient-reported outcome scores for the cohort over time, as well as compare it to other cohorts. Using Composer's current iteration, we provide a usage scenario for use of the tool in a clinical setting.
Conclusion We have developed a prototype cohort analysis tool to help clinicians assess patient treatment options by analyzing prior cases with similar characteristics. Although Composer was designed using patient data specific to orthopedic research, we believe the tool is generalizable to other healthcare domains. A long-term goal for Composer is to develop the application into a shared decision-making tool that allows translation of comparison and analysis from a clinician-facing interface into visual representations to communicate treatment options to patients.
Irregular perspective shifts and perspective persistence, discourse-oriented and theoretical approaches
Authors: Gentens Caroline , Sansiñena María Sol , Spronck Stef , Van linden An 
Published: April 2019

AbstractIn this introduction, we set out the central themes of the special issue. It concentrates on imperfect function-form mappings, and discusses several cases in which specific perspectival meanings are not fully predictable on the basis of a perspectivizing grammatical construction alone. We distinguish two kinds of form-function mismatches: (1) perspective-persistent phenomena, i.e. grammatically signaled deictic and/or cognitive perspective shifts which are not realized in interpretation, and (2) irregular perspective shifts, which involve either grammatically un(der)specified shifts or grammatically signaled shifts that are interpreted as mixing multiple sources of deictic and/or cognitive perspective (‘multiple-perspective constructions’). We briefly discuss and contextualize each of the contributions, and highlight their central findings.
Translation for communicative purposes
Authors: Lo Siowai 
Published: April 2019

Abstract
An underexplored aspect of the use of translation in the L2 classroom is its potential to foster in-class communication. This article explores the efficacy of translation tasks as compared to monolingual writing tasks in engendering language-related discussions in class. The study is longitudinal and includes two experiments carried out in an EFL college setting. Data were collected over two semesters and a comparatively stronger presence of language-related episodes (LREs) was found among those who worked on translation tasks. This higher level of engagement in L2 class discussions suggests that translation tasks are advantageous in engendering student-initiated LREs, drawing learners’ attention to lexis and grammar, and fostering communication in the classroom.
A remark on the Tate Conjecture
Authors: Moonen Ben 
Published: April 2019

The strong version of the Tate conjecture has two parts: an assertion (S) about semisimplicity of Galois representations and an assertion (T) which says that every Tate class is algebraic. We show that in characteristic

0
0

, (T) implies (S). In characteristic

p
p

an analogous result is true under stronger assumptions.
Multicenter study to evaluate the benefits of technology-assisted workflow on i.v. room efficiency, costs, and safety in small community hospitals
Authors: Higgins Jordyn P , Hardt Sarah , Cowan Debby , Beasley Eula , Eckel Stephen F 
Published: April 2019

Abstract

Purpose
To evaluate the benefits of technology-assisted workflow (TAWF) compared to manual workflow (non-TAWF) on i.v. room efficiency, costs, and safety at community hospitals with less than 200 beds.

Methods
Four hospitals in the United States (2 with and 2 without TAWF) were evaluated, and characteristics of medication errors and frequency of each error type were measured across the institutions. The average turnaround time per workflow step and cost to prepare each compounded sterile product (CSP) were also calculated. The results were evaluated using descriptive and inferential statistics.

Results
The TAWF hospital sites detected errors at a significantly higher rate (3.78%) compared to the non-TAWF hospital sites (0.13%) (p < 0.05). The top error-reporting category for the TAWF sites was incorrect medication (71.66%), whereas the top error-reporting category for the non-TAWF sites could not be determined because of the small number of errors detected. Use of TAWF may be associated with a decrease in turnaround time and a decrease in overall cost to prepare a CSP.

Conclusion
Significantly more errors were detected in small community hospitals that use TAWF in the i.v. room compared to those not using it. There were differences in error types observed between technology and nontechnology groups. The use of TAWF was associated with faster preparation times and lower costs of preparation per CSP.