bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Oxygen During Long-term Hypothermic Machine Perfusion in a Porcine Model of Kidney Donation After Circulatory Death
Authors: Venema Leonie H. , Brat Aukje , Moers Cyril , ‘t Hart Nils A. , Ploeg Rutger J. , Hannaert Patrick , Minor Thomas , Leuvenink and Henri G.D. 
Published: April 2019

Background.
Hypothermic machine perfusion (HMP) has become standard care in many center’s to preserve kidneys donated after circulatory death (DCD). Despite a significant reduction in metabolism at low temperatures, the remaining cellular activity requires oxygen. Because of the role and safety of oxygen during HMP has not been fully clarified, its supply during HMP is not standard yet. This study investigates the effect of administering oxygen during HMP on renal function in a porcine DCD model.

Methods.
After 30 minutes of warm ischemia, porcine slaughterhouse kidneys were preserved for 24 hours by means of cold storage (CS), or HMP with Belzer Machine Perfusion Solution supplemented with no oxygen, 21% or 100% oxygen. Next, kidneys were reperfused for 4 hours in a normothermic machine perfusion setup.

Results.
HMP resulted in significantly better kidney function during normothermic machine perfusion. Thiobarbituric acid-reactive substances, markers of oxidative stress, were significantly lower in HMP preserved kidneys. HMP preserved kidneys showed significantly lower aspartate aminotransferase and lactate dehydrogenase levels compared with kidneys preserved by CS. No differences were found between the HMP groups subjected to different oxygen concentrations. Adenosine triphosphate levels significantly improved during HMP when active oxygenation was applied.

Conclusions.
This study showed that preservation of DCD kidneys with HMP is superior to CS. Although the addition of oxygen to HMP did not result in significantly improved renal function, beneficial effects were found in terms of reduced oxidative stress and energy status. Oxygen addition proofed to be safe and did not show detrimental effects.
Brain Death Enhances Activation of the Innate Immune System and Leads to Reduced Renal Metabolic Gene Expression
Authors: Zitur Laura J. , Chlebeck Peter J. , Odorico Scott K. , Danobeitia Juan S. , Zens Tiffany J. , Van Kooten Cees , Eerhart Michael , Reyes Jose A. , Springer Megan L. , Coonen Jennifer M. , Brunner Kevin G. , Capuano Saverio V. , D’Alessandro Anthony M. , Fernandez Luis A. 
Published: April 2019

Background.
Brain death (BD)–associated inflammation has been implicated in decreased kidney allograft function and survival, but the underlying mechanisms have not been well distinguished from the conditions of critical care itself. We have developed a clinically translatable model to separate and investigate strategies to improve donor management and critical care.

Methods.
Brain-dead (n = 12) and sham (n = 5) rhesus macaques were maintained for 20 hours under intensive care unit–level conditions. Samples were collected for immunophenotyping, analysis of plasma proteins, coagulation studies, and gene analysis for changes in immune and metabolic profile with comparison to naive samples (n = 10).

Results.
We observed an increase in circulating leukocytes and cytokines, activation of complement and coagulation pathways, and upregulation of genes associated with inflammation in both brain-dead and sham subjects relative to naïve controls. Sham demonstrated an intermediate phenotype of inflammation compared to BD. Analysis of gene expression in kidneys from BD kidneys revealed a similar upregulation of inflammatory profile in both BD and sham subjects, but BD presented a distinct reduction in metabolic and respiratory processes compared to sham and naïve kidneys.

Conclusion.
BD is associated with activation of specific pathways of the innate immune system and changes to metabolic gene expression in renal tissue itself; however, sham donors presented an intermediate inflammatory response attributable to the critical care environment. The early onset and penetrating impact of this inflammatory response underscores the need for early intervention to prevent perioperative tissue injury to transplantable organs.
Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder
Authors: Lobentanzer Sebastian , Hanin Geula , Klein Jochen , Soreq Hermona 
Published: April 2019

SummaryRNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male- and female-originated cell lines, and connectomics of transcription factor- and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies disease-affected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases.
Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers
Authors: Noushmehr H , Sabedot TS , Malta TM , Nelson K , Snyder J , Wells M , deCarvalho A , Mukherjee A , Chitale D , Mosella M , Asmaro K , Robin A , Rosenblum M , Mikkelsen T , Rock J , Poisson LM , Lee I , Walbert T , Kalkanis S , Castro AV 
Published: April 2019

SUMMARYGenome-wide DNA methylation profiling has shown that epigenetic abnormalities are biologically important in glioma and can be used to classify these tumors into distinct prognostic groups. Thus far, DNA profiling has required surgically resected glioma tissue; however, gliomas release tumoral material into biofluids, such as blood and cerebrospinal fluid, providing an opportunity for a minimally invasive testing. While prior studies have shown that genetic and epigenetic markers can be detected in blood or cerebrospinal fluid (e.g., liquid biopsy [LB]), there has been low sensitivity for tumor-specific markers. We hypothesize that the low sensitivity is due to the targeted assay methods. Therefore, we profiled the genome-wide CpG methylation levels in DNA of tumor tissue and cell-free DNA in serum of glioma patients, to identify non-invasive epigenetic LB (eLB) markers in the serum that reflect the characteristics of the tumor tissue. From the epigenetic profiles of serum from patients diagnosed with glioma (N=15IDHmutant and N=7IDHwildtype) and with epilepsy (N=3), we defined glioma-specific andIDH-specific eLB signatures (Glioma-eLB andIDH-eLB, respectively). The epigenetic profiles of the matched tissue demonstrate that these eLB signatures reflected the signature of the tumor. Through cross-validation we show that Glioma-eLB can accurately predict a patient’s glioma from those with other neoplasias (N=6 Colon; N=14 Pituitary; N=3 Breast; N=4 Lung), non-neoplastic immunological conditions (N=22 sepsis; N=9 pancreatic islet transplantation), and from healthy individuals (sensitivity: 98%; specificity: 99%). Finally,IDH-eLB includes promoter methylated markers associated with genes known to be involved in glioma tumorigenesis (PVT1andCXCR6). The application of the non-invasive eLB signature discovered in this study has the potential to complement the standard of care for patients harboring glioma.
Unequal interactions between alcohol and nicotine co-consumption: Suppression and enhancement of concurrent drug intake
Authors: DeBaker Margot C , Moen Janna K , Robinson Jenna M , Wickman Kevin , Lee Anna M 
Published: April 2019

AbstractRationaleAlcohol and nicotine addiction are prevalent conditions that co-occur. Despite the prevalence of co-use, factors that influence the suppression and enhancement of concurrent alcohol and nicotine intake are largely unknown.ObjectivesOur goals were to assess how nicotine abstinence and availability influenced concurrent alcohol consumption, and to determine the impact of quinine adulteration of alcohol on aversion resistant alcohol consumption and concurrent nicotine consumption.MethodsMale and female C57BL/6J mice voluntarily consumed unsweetened alcohol, nicotine and water in a chronic 3-bottle choice procedure. In Experiment 1, nicotine access was removed for 1 week and re-introduced the following week, while the alcohol and water bottles remained available at all times. In Experiment 2, quinine (100-1000 μM) was added to the 20% alcohol bottle, while the nicotine and water bottles remained unaltered.ResultsIn Experiment 1, we found that alcohol consumption and preference were unaffected by the presence or absence of nicotine access in both male and female mice. In Experiment 2a, we found that quinine temporarily suppressed alcohol intake and enhanced concurrent nicotine, but not water, preference in both male and female mice. In Experiment 2b, chronic quinine suppression of alcohol intake increased nicotine consumption and preference in female mice without affecting water preference, whereas it increased water and nicotine preference in male mice.ConclusionsQuinine suppression of alcohol consumption enhanced the preference for concurrent nicotine preference in male and female mice, suggesting that mice compensate for the quinine adulteration of alcohol by increasing their nicotine preference.
Whole genome phylogenies reflect long-tailed distributions of recombination rates in many bacterial species
Authors: Sakoparnig Thomas , Field Chris , van Nimwegen Erik 
Published: April 2019

AbstractAlthough homologous recombination is accepted to be common in bacteria, so far it has been challenging to accurately quantify its impact on genome evolution within bacterial species. We here introduce methods that use the statistics of single-nucleotide polymorphism (SNP) splits in the core genome alignment of a set of strains to show that, for many bacterial species, recombination dominates genome evolution. Each genomic locus has been overwritten so many times by recombination that it is impossible to reconstruct the clonal phylogeny and, instead of a consensus phylogeny, the phylogeny typically changes many thousands of times along the core genome alignment.We also show how SNP splits can be used to quantify the relative rates with which different subsets of strains have recombined in the past. We find that virtually every strain has a unique pattern of frequencies with which its lineages have recombined with those of other strains, and that the relative rates with which different subsets of strains share SNPs follow long-tailed distributions. Our findings show that bacterial populations are neither clonal nor freely recombining, but structured such that recombination rates between different lineages vary along a continuum spanning several orders of magnitude, with a unique pattern of rates for each lineage. Thus, rather than reflecting clonal ancestry, whole genome phylogenies reflect these long-tailed distributions of recombination rates.
YAP controls cell migration and invasion through a Rho-GTPase switch
Authors: Shah Sagar R. , Ren Chunxiao , Tippens Nathaniel D. , Park JinSeok , Mohyeldin Ahmed , Wang Shuyan , Vela Guillermo , Martinez-Gutierrez Juan C. , Margolis Seth S. , Schmidt Susanne , Xia Shuli , Quiñones-Hinojosa Alfredo , Levchenko Andre 
Published: April 2019

AbstractDelineating the mechanisms controlling the invasive spread of non-diseased and transformed cells is central to understanding diverse processes including cancer progression. Here, we found that Yes-associated protein (YAP), a central transcriptional regulator implicated in controlling organ and body size, modulated a Rho-GTPase switch that drives cellular migration by transactivating the Rac1-GEF protein TRIO through direct modulation of its intronic enhancer. Additionally, YAP and TRIO may promote invasive behavior through putative crosstalk with STAT3 signaling, a potential downstream target. Although we found this YAP-dependent infiltrative program in many cell types, it was particularly enhanced in a patient-specific manner in the most common malignant brain tumor, glioblastoma (GBM), where hyperactivation of the YAP, TRIO, and STAT3 signatures also conferred poor clinical outcome. Our analysis suggests that the YAP-TRIO-Rho-GTPase signaling network identified in this study is a ubiquitous regulator of invasive cell spread in both physiological and pathological contexts.
Dynamic chromosome rearrangements of the white-spotted bamboo shark shed light on cartilaginous fish diversification mechanisms
Authors: Zhang Yaolei , Gao Haoyang , Li Hanbo , Guo Jiao , Wang Meiniang , Xu Qiwu , Wang Jiahao , Lv Meiqi , Guo Xinyu , Liu Qun , Wei Likun , Ren Han , Xi Yang , Guo Yang , Zhao Qian , Pan Shanshan , Liu Chuxin , Sang Liping , Ding Xiaoyan , Wang Chen , Xiang Haitao , Song Yue , Liu Yujie , Liu Shanshan , Jiang Yuan , Shao Changwei , Shi Jiahai , Liu Shiping , Sabir Jamal S. M. , Sabir Mumdooh J. , Khan Muhummadh , Hajrah Nahid H. , Lee Simon Ming-Yuen , Xu Xun , Yang Huanming , Wang Jian , Fan Guangyi , Yang Naibo , Liu Xin 
Published: April 2019

AbstractCartilaginous fishes have a very high phenotypical diversity, a phenomenon for which the mechanisms have been largely unexplored. Here, we report the genome of the white-spotted bamboo shark as the first chromosome-level genome assembly of cartilaginous fish. Using this genome, we illustrated a dynamic chromosome rearrangement process in the bamboo shark, which resulted in the formation of 13 chromosomes, all of which were sparsely distributed with conserved genes and fast-evolving. We found the fast-evolving chromosomes to be enriched in immune-related genes with two chromosomes harboring the major genes for developing the single-chain antibody. We also found chromosome rearrangements to have resulted in the loss of two genes (p2rx3andp2rx5) which we also showed were involved in cartilage development using a CRISPR/Cas9 approach in zebrafish. Our study highlighted the significance of chromosome rearrangements in the phenotypical evolution of cartilaginous fishes, providing clues to inform further studies on mechanisms for fish diversification.
Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine
Authors: Yesylevskyy Semen , Rivel Timothée , Ramseyer Christophe 
Published: April 2019

ABSTRACTIn this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown that permeability of the membranes increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results show that the membrane curvature is an important factor which should be considered during evaluation of drug translocation.TOC GRAPHICS
tRNA dissociation from EF-Tu after GTP hydrolysis and Pirelease: primary steps and antibiotic inhibition
Authors: Warias Malte , Grubmüller Helmut , Bock Lars V. 
Published: April 2019

AbstractIn each round of ribosomal translation, the translational GTPase EF-Tu delivers a tRNA to the ribosome. After successful decoding, EF-Tu hydrolyses GTP, which triggers a conformational change that ultimately results in the release of the tRNA from EF-Tu. To identify the primary steps of these conformational changes and how they are prevented by the antibiotic kirromycin, we employed all-atom explicit-solvent Molecular Dynamics simulations of the full ribosome-EF-Tu complex. Our results suggest that after GTP hydrolysis and Pi release, the loss of interactions between the nucleotide and the switch 1 loop of EF-Tu allows domain D1 of EF-Tu to rotate relative to domains D2 and D3 and leads to an increased flexibility of the switch 1 loop. This rotation induces a closing of the D1-D3 interface and an opening of the D1-D2 interface. We propose that the opening of the D1-D2 interface, which binds the CCA-tail of the tRNA, weakens the crucial EF-Tu-tRNA interactions which lowers tRNA binding affinity, representing the first step of tRNA release. Kirromycin binds within the D1-D3 interface, sterically blocking its closure, but does not prevent hydrolysis. The resulting increased flexibility of switch 1 explains why it is not resolved in kirromycin-bound structures.
Ventriculo-arterial uncoupling is associated with VO2dependency in cardiac surgical patients
Authors: Guinot Pierre-Grégoire , Nguyen Maxime , Huette Pierre , Abou-Arab Osama , Bouhemad Belaid , Longrois Dan 
Published: April 2019

AbstractBackgroundThe clinical relevance of V-A (un)coupling in critically ill patients is under investigation. In this study we measured the association between V-A coupling and oxygen consumption (VO2) response in patients with acute circulatory instability following cardiac surgery.Methods and resultsSixty-one cardio-thoracic ICU patients who received fluid challenge or norepinephrine infusion were included. Arterial pressure, cardiac output (CO), heart rate (HR), arterial (EA), and ventricular elastances (EV), total indexed peripheral resistance (TPRi) were assessed before and after hemodynamic interventions. VO2responders were defined as VO2increase > 15 %. V-A coupling was evaluated by the ratio EA/EV.Left ventricle stroke work (SW) to pressure volume area (PVA) ratio was calculated. In the overall population, 24 patients (39%) were VO2responders and 48 patients were uncoupled (i.e., EA/EVratio > 1.3): 1.9 (1.6-2.4). Most of the uncoupled patients were classified as VO2responders (28 of 31 patients, p=0.031). Changes in VO2were correlated with those of TPRi, EA, EA/EVand CO. EA/EVratio predicted VO2increase with an AUC of 0.76 [95 % CI: 0.62-0.87]; p=0.001. In multivariate and principal component analyses, EA/EVand SW/PVA ratios were independently associated (P < 0.05) with VO2response following interventions.ConclusionsVO2responders were characterized by baseline V-A uncoupling due to high EAand low EV. Baseline EA/EVand SW/PVA ratios were associated with VO2changes independently of the hemodynamic intervention used. These results further underline the pathophysiological significance of V-A uncoupling in patients with hemodynamic instability.
Large-scale Lassa fever outbreaks in Nigeria: quantifying the association between disease reproduction number and local rainfall
Authors: Zhao Shi , Musa Salihu S. , Fu Hao , He Daihai , Qin Jing 
Published: April 2019

AbstractBackgroundLassa fever (LF) is increasingly recognized as an important rodent-borne viral hemorrhagic fever presenting a severe public health threat to sub-Saharan West Africa. In 2018, LF caused an unprecedented outbreak in Nigeria, and the situation was worse in 2019. This work aims to study the epidemiological features of outbreaks in different Nigerian regions and quantify the association between reproduction number (R) and local rainfall by using modeling analysis.MethodsWe quantify the infectivity of LF by the reproduction numbers estimated from four different growth models: the Richards, three-parameter logistic, Gompertz, and Weibull growth models. LF surveillance data are used to fit the growth models and estimate theRs and epidemic turning points (τ) in different regions at different time periods. Cochran’s Q test is further applied to test the spatial heterogeneity of the LF epidemics. A linear random-effect regression model is adopted to quantify the association betweenRand local rainfall with various lag terms.FindingsOur estimatedRs for 2017-18 (1.33 with 95% CI: [1.29, 1.37]) and 2018-19 (1.29 with 95% CI: [1.27, 1.32]) are significantly higher than those for 2016-17 (1.23 with 95% CI: [1.22, 1.24]). We report spatial heterogeneity in theRs for outbreaks in different Nigerian regions. For the association between rainfall andR, we find that a one unit (mm) increase in average rainfall over the past 7 months could cause a 0.62% (95% CI: [0.20%, 1.05%]) rise inR.ConclusionThere is significant spatial heterogeneity in the LF epidemics in different Nigerian regions. We report clear evidence of rainfall impacts on LF outbreaks in Nigeria and quantify the impact.
Internationalization of Bosnian black coffee brand: bringing the traditional coffee experience to the world
Authors: Kadić-Maglajlić Selma , Arslanagic-Kalajdzic Maja 
Published: April 2019

Learning outcomes
The teaching objectives of the case study are to provide students with an understanding of how strategic marketing tools are applied in an international marketing context and how brands, especially brands that come from emerging markets, are introduced and managed within modern versus traditional trade (e.g. ethnic shops).

Case overview/synopsis
This case illustrates the challenges and opportunities related to the introduction of a brand to a new market wherein the product (traditional coffee), although part of a very well-developed product category (coffee), may have been new to consumers in the new market. The brand itself, Zlatna džezva, is a flagship brand in its home country (Bosnia and Herzegovina) within a developing market. However, both the brand and the traditional coffee experience are relatively unknown to other markets. The case study focuses on Vispak’s CEO and CMO who are contemplating their next business move in the new market. Finally, the Dutch market and consumers are presented to facilitate the process of segmentation, targeting and positioning for students. The case study concludes with a task and dilemma for managers of the company.

Complexity academic level
This case could be used in a variety of undergraduate level classes, depending on what the instructor wishes to emphasize. The authors use the case for following courses: principles of marketing, marketing management and international marketing. In all courses, the case is allowing students to obtain the greater overview of the scope of the strategic marketing decision-making. Before starting with case analysis, students should have some familiarity with central marketing issues and concepts, specifically related to analysis of environment, segmentation-targeting-positioning, product and brand management.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 8: Marketing.