bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Deteriorating Patients on Surgical Wards Outside the ICU by an Automated MEWS-Based Early Warning System With Paging Functionality
Authors: Heller Axel R. , Mees Sören T. , Lauterwald Benjamin , Reeps Christian , Koch Thea , Weitz Jürgen 
Published: May 2018

Background:
The establishment of early warning systems in hospitals was strongly recommended in recent guidelines to detect deteriorating patients early and direct them to adequate care. Upon reaching predefined trigger criteria, Medical Emergency Teams (MET) should be notified and directed to these patients. The present study analyses the effect of introducing an automated multiparameter early warning score (MEWS)-based early warning system with paging functionality on 2 wards hosting patients recovering from highly complex surgical interventions.

Methods:
The deployment of the system was accompanied by retrospective data acquisition during 12 months (intervention) using 4 routine databases: Hospital patient data management, anesthesia database, local data of the German Resuscitation Registry, and measurement logs of the deployed system (intervention period only). A retrospective 12-month data review using the same aforementioned databases before the deployment of the system served as control. Control and intervention phases were separated by a 6-month washout period for the installation of the system and for training.

Results:
Data from 3827 patients could be acquired from 2 surgical wards during the two 12-month periods, 1896 patients in the control and 1931 in the intervention cohorts. Patient characteristics differed between the 2 observation phases. American Society of Anesthesiologists risk classification and duration of surgery as well as German DRG case-weight were significantly higher in the intervention period. However, the rate of cardiac arrests significantly dropped from 5.3 to 2.1 per 1000 admissions in the intervention period (P < 0.001). This observation was paralleled by a reduction of unplanned ICU admissions from 3.6% to 3.0% (P < 0.001), and an increase of notifications of critical conditions to the ward surgeon. The primary triggers for MET activation were abnormal ECG alerts, specifically asystole (n = 5), and pulseless electric activity (n = 8).

Conclusion:
In concert with a well-trained and organized MET, the early deterioration detection of patients on surgical wards outside the ICU may be improved by introducing an automated MEWS-based early warning system with paging functionality.
Specifying a causal role for angular gyrus in autobiographical memory
Authors: Bonnici Heidi M. , Cheke Lucy G. , Green Deborah A.E. , FitzGerald Thomas H.B. , Simons Jon S. 
Published: May 2018

AbstractConsiderable recent evidence indicates that angular gyrus dysfunction does not result in amnesia, but does impair a number of aspects of episodic memory. Patients with parietal lobe lesions have been reported to exhibit a deficit when freely recalling autobiographical events from their pasts, but can remember details of the events when recall is cued by specific questions. In apparent contradiction, inhibitory brain stimulation targeting angular gyrus in healthy volunteers has been found to have no effect on free recall or cued recall of word pairs. The present study sought to resolve this inconsistency by testing free and cued recall of both autobiographical memories and word pair memories in the same healthy participants following continuous theta burst stimulation (cTBS) of angular gyrus and a vertex control location. Angular gyrus cTBS resulted in a selective reduction in the free recall but not cued recall of autobiographical memories, whereas free and cued recall of word pair memories were unaffected. Additionally, participants reported fewer autobiographical episodes as being experienced from a first-person perspective following angular gyrus cTBS. The findings add to a growing body of evidence that a function of angular gyrus within the network of brain regions responsible for episodic recollection is to integrate memory features within an egocentric framework into the kind of first-person perspective representation that enables the subjective experience of remembering events from our personal pasts.
Strain-level overlap between infant and hospital fungal microbiomes revealed throughde novoassembly of eukaryotic genomes from metagenomes
Authors: Olm Matthew R. , West Patrick T. , Brooks Brandon , Firek Brian A. , Baker Robyn , Morowitz Michael J. , Banfield Jillian F. 
Published: May 2018

SUMMARYEukaryotes are a leading cause of nosocomial infections in neonates, but their diversity and population heterogeneity are rarely investigated. This has led to an incomplete understanding of eukaryotic strains that colonize infants and of the neonatal intensive care unit (NICU) as a possible source of these strains. Analysis of 1,174 time-series metagenomes from 161 premature infants revealed fungal colonization of 13 infants, primarily in the first two weeks of life. Nearly all 24 NICU samples contained eukaryotes, and the most diverse communities were in NICU sinks. Five of fourteen newly-assembled eukaryotic genomes derived from genomically undescribed species.Purpureocillium lilacinumgenomes from infant and NICU samples shared 99.999% average nucleotide identity, highlighting the potential of hospital-associated fungi to colonize hospitalized infants. We quantified zygosity and within-population variation associated with the diploid eukaryotes, and thus defined the genetic reservoirs of eukaryotes in room environments and infants.
Integrated RNA-seq and sRNA-seq revealed differences in transcriptome between susceptible and resistant tomato responding toFusarium oxysporum
Authors: Zhao Min , Ji Hui-Min , Gao Ying , Cao Xin-Xin , Mao Hui-Ying , Liu Peng , Ouyang Shou-Qiang 
Published: May 2018

ABSTRACTTomato wilt disease caused byFusarium oxysporumf. sp.lycopersici(FOL) is a worldwide destructive disease of tomato. As exploring gene expression and function approaches constitute an initial point for investigating pathogen-host interaction, we performed RNA-seq and sRNA-seq analysis to unravel regulated genes and miRNAs in tomato infected by FOL. Differentially expressed (DE) protein coding gene and miRNA gene profiles upon inoculation with FOL were presented at twenty-four hours post-inoculation including four treatments. Total of more than 182.6 million and 132.2 million high quality clean reads were obtained by RNA-seq and sRNA-seq, respectively. A large overlap was found in DE mRNAs between susceptible cultivar Moneymaker and resistant cultivar Motelle. All Gene Ontology terms were mainly classified into catalytic activity, metabolic process and binding. Combining with qRT-PCR, five disease resistance genes, Solyc01g095630, Solyc03g059080, Solyc00g174340, Solyc11g071750 and Solyc05g050350, were verified to involved in the disease resistance in the resistant cultivar Motelle treated with FOL. Northern blot analysis further confirmed the results from sRNA-Seq and demonstrated that several miRNAs including Sly-miR477-5p, sly-miR167a, novel_mir_675, novel_mir_504 and novel_mir_762 conferred FOL infection. Our data resulted that pathogen resistant genes/miRNAs may play a critical role with the benefit of a coordinated machinery in prompting the response in prompting FOL response in tomato, which offered us with a future direction and surely help in generating models of mediated resistance responses with assessment of genomic gene expression patterns.
Transient effect of mossy fiber stimulation on spatial firing of CA3 neurons
Authors: Lee Joonyeup , Yun Miru , Cho Eunjae , Lee Jong Won , Lee Doyun , Jung Min Whan 
Published: May 2018

AbstractStrong hippocampal mossy fiber synapses are thought to function as detonators, imposing ‘teaching’ signals onto CA3 neurons during new memory formation. For an empirical test of this long-standing view, we examined effects of stimulating mossy fibers on spatial firing of CA3 neurons in freely-moving mice. We found that optogenetic stimulation of mossy fibers can alter CA3 spatial firing, but their effects are only transient. Spatially restricted mossy fiber stimulation, either congruent or incongruent with CA3 place fields, was more likely to suppress than enhance CA3 neuronal activity. Also, changes in spatial firing induced by optogenetic stimulation reverted immediately upon stimulation termination, leaving CA3 place fields unaltered. Our results do not support the traditional view that mossy fibers impose teaching signals onto CA3 network, and show robustness of established CA3 spatial representations.
Japanese Encephalitis Virus Infected Microglial Cells Secrete Exosomes Containing let-7a/b that Facilitate Neuronal Damage via Caspase Activation
Authors: Mukherjee Sriparna , Akbar Irshad , Kumari Bharti , Vrati Sudhanshu , Basu Anirban , Banerjee Arup 
Published: May 2018

AbstractExtracellular microRNAs (miRNAs) are essential for the cell to cell communication in the healthy and diseased brain. MicroRNAs released from the activated microglia upon neurotropic virus infection may exacerbate CNS damage. Here, we identified let-7a and let-7b (let-7a/b) as the overexpressed miRNAs in Japanese Encephalitis virus (JEV) infected microglia and assessed their role in JEV pathogenesis. We measured the let-7a/b expressions in JEV infected post-mortem human brains, mice brains and in mouse microglial N9 cells by the qRT-PCR and in situ hybridization assay. The interaction between let-7a/b and NOTCH signaling pathway further examined in Toll-like receptor 7 knockdown (TLR7 KD) mice to assess the functions. Exosomes released from JEV infected or let-7a/b mimic transfected N9, and HEK-293 cells were isolated and evaluated their function. We observed an upregulation of let-7a/b in the infected brains as well as in microglia. Knockdown of TLR7 or Inhibition of let-7a/b suppressed the JEV induced NOTCH activation possibly via NF-κB dependent manner and subsequently, attenuated JEV induced TNFα production in microglial cells. Further, exosomes secreted from JEV-infected microglial cells specifically contained let-7a/b. Exosomes overexpressed with let-7a/b were injected into BALB/c mice as well as co-incubated with mouse neuronal (Neuro2a) cells, or primary cortical neuron resulted in caspase activation leading to neuronal damage in the brain. Thus, our results provide evidence for the multifaceted role of let-7a/b miRNAs and unravel the exosomes mediated mechanism for JEV induced pathogenesis.
Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1
Authors: Ye Siying , Cowled Chris , Yap Cheng-Hon , Stambas John 
Published: May 2018

ABSTRACTCurrent prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly up-regulated, including the cell adhesion moleculeCEACAM1. The up-regulation ofCEACAM1was blocked in the presence of the reactive oxygen species inhibitor, apocynin. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to low pathogenic PR8 H1N1 virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenousCEACAM1resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.
Characterization of apo-form selective inhibition of indoleamine 2,3-dioxygenase
Authors: Ortiz-Meoz Rodrigo , Wang Liping , Matico Rosalie , Rutkowska Anna , De la Rosa Martha , Bedard Sabrina , Midgett Robert , Strohmer Katrin , Thomson Douglas , Zhang Cunyu , Mebrahtu Makda , Guss Jeffrey , Totoritis Rachel , Consler Thomas , Campobasso Nino , Taylor David , Lewis Tia , Weaver Kurt , Mülbaier Marcel , Seal John , Dunham Richard , Kazmierski Wieslaw , Favre David , Bergamini Giovanna , Shewchuk Lisa , Rendina Alan , Zhang Guofeng 
Published: May 2018

ABSTRACTIndoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of established and novel IDO1 inhibitors remains of great interest. Comparison of a newly-developed IDO1 inhibitor (GSK5628) to the existing best-in-class compound, epacadostat (Incyte), allows us to report on a unique inhibition mechanism for IDO1. Here, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1) while epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition may help design superior inhibitors or may confer a unique competitive advantage over other IDO1 inhibitorsvis-à-visspecificity and pharmacokinetic parameters.
Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4
Authors: Kattnig D. R. , Nielsen C. , Solov’yov I. A. 
Published: May 2018

AbstractBirds appear to be equipped with a light-dependent, radical-pair-based magnetic compass that relies on truly quantum processes. While the identity of the sensory protein has remained speculative, cryptochrome 4 has recently been identified as the most auspicious candidate. Here, we report on allatom molecular dynamics (MD) simulations addressing the structural reorganisations that accompany the photoreduction of the flavin cofactor in a model of the European robin cryptochrome 4 (ErCry4). Extensive MD simulations reveal that the photo-activation of ErCry4 induces large-scale conformational changes on short (hundreds of nanoseconds) timescales. Specifically, the photo-reduction is accompanied with the release of the C-terminal tail, structural rearrangements in the vicinity of the FAD-binding site, and the noteworthy formation of an α-helical segment at the N-terminal part. Some of these rearrangements appear to expose potential phosphorylation sites. We describe the conformational dynamics of the protein using a graph-based approach that is informed by the adjacency of residues and the correlation of their local motions. This approach reveals densely coupled reorganisation communities, which facilitate an efficient signal transduction due to a high density of hubs. These communities are interconnected by a small number of highly important residues characterized by high betweenness centrality. The network approach clearly identifies the sites restructuring upon photoactivation, which appear as protrusions or delicate bridges in the reorganisation network. We also find that, unlike in the homologous cryptochrome fromD. melanogaster, the release of the C-terminal domain does not appear to be correlated with the transposition of a histidine residue close to the FAD cofactor.
Evolution of sex determination and heterogamety changes in sectionOtitesof the genusSilene
Authors: Balounova, Veronika , Gogela Roman , Cegan Radim , Cangren Patrik , Zluvova Jitka , Safar Jan , Kovacova Viera , Bergero Roberta , Hobza Roman , Vyskot Boris , Oxelman Bengt , Charlesworth Deborah , Janousek Bohuslav 
Published: May 2018

AbstractSwitches in heterogamety occasionally occur both in animals and plants, although plant sex determination systems are mostly more recently evolved than those of animals, and have had less time for switches to occur. However, our previous research revealed a switch in heterogamety in sectionOtitesof the plant genusSilene.Here we analyse in detail the evolution of genetic sex determination in sectionOtites, which is estimated to have evolved about 0.55 MYA. Our study confirms female heterogamety inS. otitesand newly reveals female heterogamety inS. borysthenica. Sequence analyses and genetic mapping show that the sex-linked regions of these two species are the same, but the region inS. colpophylla, a close relative with male heterogamety, is different. The sex chromosome pairs ofS. colpophyllaandS. otiteseach correspond to an autosome of the other species, and both differ from the XY pair inS. latifolia, in a different section of the genus. Our phylogenetic analysis suggests a possible change from female to male heterogamety withinSilenesectionOtites,making these species suitable for detailed studies of the events involved.
The effectiveness of clove oil and cautery disbudding methods on preventing horn growth in dairy goat kids
Authors: Hempstead Melissa N , Waas Joseph R. , Stewart Mairi , Cave Vanessa M. , Turner Amanda R. , Sutherland Mhairi A. 
Published: May 2018

AbstractThe effectiveness of clove oil and cautery disbudding on horn growth was evaluated in goat kids. The study used 243 Saanen doe kids (4±1.0 days old; mean ± SD) on two commercial dairy goat farms, and were disbudded with either (i) clove oil injection (CLOVE), (ii) a cautery iron and bud removed (BUDOFF), or (iii) a cautery iron with bud left intact (BUDON). Each kid received a different treatment per bud, which were balanced between buds (left and right) and randomly allocated. A trained observer monitored bud growth following treatment for 3 months recording either: N: no growth, H: normal horn, S: abnormal horn (scur), or SC: soft, fibrous lump (scorn). After the final observation, buds were assessed for the probability of detecting (i) success (no growth), (ii) scurs, (iii) horns or (iv) scorns [with 95% CI]. The probability of success for BUDOFF (0.77 [0.63, 0.87]) was higher than for BUDON (0.20 [0.11, 0.34]) and CLOVE (0.09 [0.04, 0.18]; P ≤ 0.05). Furthermore, the probability of success for BUDON was higher than for CLOVE (P ≤ 0.05). The probability of scurs was higher for CLOVE (0.72 [0.63, 0.80]) than BUDOFF (0.25 [0.17, 0.34]) and BUDON (0.30 [0.21, 0.39]; P ≤ 0.05). There was no difference in the probability of scurs for BUDOFF and BUDON (P > 0.05). The probability of horns was higher for CLOVE (0.21 [0.15, 0.29]) than BUDON (0.02 [0.01, 0.06]; P ≤ 0.05); horns were not observed for BUDOFF. The probability of scorns for BUDON, the only treatment that led to scorns, was 0.41 (0.25, 0.60). These results suggest that BUDOFF was more effective at preventing growth than CLOVE and BUDON and appears the most effective method, of the methods tested, for disbudding kids. Future research should explore different clove oil administration methods or other alternatives to cautery disbudding that may be both efficacious and cause less pain.
Molecular analysis of long non-coding RNA GAS5 and microRNA-34a expression signature in common solid tumors: A pilot study
Authors: Toraih Eman A. , Alghamdi Saleh Ali , El-Wazir Aya , Hosny Marwa M , Hussein Mohammad H. , Khashana Motaz S. , Fawzy Manal S. 
Published: May 2018

AbstractAccumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and glioblastoma (GB) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. GAS5 was significantly under-expressed in the three types of cancer. However, levels of miR-34a greatly varied according to the tumor type; it displayed an increased expression in RCC [4.05 (1.003-22.69),p<0.001] and a decreased expression in GB [0.35 (0.04-0.95),p<0.001]. A weak negative correlation was observed between levels of GAS5 and miR-34a in GB [r = −0.39,p=0.006]. Univariate analyses revealed a correlation ofGAS5downregulation with poor disease-free survival (r = 0.31,p=0.018) and overall survival (r = 0.28,p=0.029) in RCC but not in GB, and a marginal significance correlation with a higher number of lesions in HCC. Hierarchical clustering analysis showed RCC patients among others, could be clustered by GAS5 and miR-34a co-expression profile. Our results confirm the tumor suppressor role of GAS5 in cancer and suggest its potential applicability to be a predictor of bad outcomes with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.
Discovery of microRNA-like RNAs during early fruiting body development in the model mushroom Coprinopsis cinerea
Authors: Lau Amy Yuet Ting , Cheng Xuanjin , Cheng Chi Keung , Nong Wenyan , Cheung Man Kit , Chan Raymond Hon-Fu , Hui Jerome Ho Lam , Kwan Hoi Shan 
Published: May 2018

AbstractCoprinopsis cinerea is a model mushroom particularly suited to study fungal fruiting body development and the evolution of multicellularity in fungi. While microRNAs (miRNAs) are extensively studied in animals and plants for their essential roles in post-transcriptional regulation of gene expression, miRNAs in fungi are less well characterized and their potential roles in controlling mushroom development remain unknown. To identify miRNA-like RNAs (milRNAs) in C. cinerea and explore their expression patterns during the early developmental transition of mushroom development, small RNA libraries of vegetative mycelium and primordium were generated and putative milRNA candidates were identified following the standards of miRNA prediction in animals and plants. Two out of 22 novel predicted milRNAs, cci-milR-12c and cci-milR-13e-5p, were validated by northern blot and stem-loop reverse transcription real-time PCR. Cci-milR-12c was differentially expressed whereas the expression levels of cci-milR-13e-5p were similar in the two developmental stages. Target prediction of the validated milRNAs resulted in genes associated with fruiting body development, including pheromone, hydrophobin, cytochrome P450, and protein kinase. Besides, essential genes for miRNA biogenesis, including three coding for Dicer-like (DCL), two for Argonaute-like (AGO-like) and one for quelling deficient-2 (QDE-2) proteins, were identified in the C. cinerea genome. Phylogenetic analysis showed that the DCL and AGO-like proteins of C. cinerea were more closely related to those in other basidiomycetes and ascomycetes than to animals and plants. Taken together, our findings provided the first evidence of milRNAs in the model mushroom and their potential roles in regulating fruiting body development. Information on the evolutionary relationship of milRNA biogenesis proteins across kingdoms has also provided new insights into further functional and evolutionary studies of miRNAs.