bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceptable Limitations on Paramedic Duty to Treat During Disaster: A Qualitative Exploration
Authors: Smith Erin , Burkle Frederick M. , Gebbie Kristine , Ford David , Bensimon Cécile 
Published: October 2018

AbstractIntroductionThe Australian prehospital profession has not yet facilitated a comprehensive discussion regarding paramedic role and responsibility during disasters. Whether paramedics have a duty to treat under extreme conditions and what acceptable limitations may be placed on such a duty require urgent consideration. The purpose of this research is to encourage discussion within the paramedic profession and broader community on this important ethical and legal issue.MethodsThe authors employed qualitative methods to gather paramedic and community member perspectives in Victoria, Australia.ResultsThese findings suggested that both paramedic and community member participants agree that acceptable limitations on paramedic duty to treat during disaster are required. These limitations should be based on consideration of the following factors: personal health circumstances (eg, pregnancy for female paramedics); pre-existing mental health conditions (eg, posttraumatic stress disorder/PTSD); competing personal obligations (eg, paramedics who are single parents); and unacceptable levels of personal risk (eg, risk of exposure and infection during a pandemic).ConclusionIt is only with the engagement of a more broadly representative segment of the prehospital profession and greater Australian community that appropriate guidance on limiting standards of care under extreme conditions can be developed and integrated within prehospital care in Australia.SmithE, BurkleFM Jr., GebbieK, FordD, BensimonC. Acceptable limitations on paramedic duty to treat during disaster: a qualitative exploration. Prehosp Disaster Med. 2018;33(5):466–470.
Origin of Earth's Water: Chondritic Inheritance Plus Nebular Ingassing and Storage of Hydrogen in the Core
Authors: Wu Jun , Desch Steven J. , Schaefer Laura , Elkins‐Tanton Linda T. , Pahlevan Kaveh , Buseck Peter R. 
Published: October 2018

AbstractRecent developments in planet formation theory and measurements of low D/H in deep mantle material support a solar nebula source for some of Earth's hydrogen. Here we present a new model for the origin of Earth's water that considers both chondritic water and nebular ingassing of hydrogen. The largest embryo that formed Earth likely had a magma ocean while the solar nebula persisted and could have ingassed nebular gases. The model considers iron hydrogenation reactions during Earth's core formation as a mechanism for both sequestering hydrogen in the core and simultaneously fractionating hydrogen isotopes. By parameterizing the isotopic fractionation factor and initial bulk D/H ratio of Earth's chondritic material, we explore the combined effects of elemental dissolution and isotopic fractionation of hydrogen in iron. By fitting to the two key constraints (three oceans' worth of water in Earth's mantle and on its surface; and D/H in the bulk silicate Earth close to 150 × 10−6), the model searches for best solutions among ~10,000 different combinations of chondritic and nebular contributions. We find that ingassing of a small amount, typically >0–0.5 oceans of nebular hydrogen, is generally demanded, supplementing seven to eight oceans from chondritic contributions. About 60% of the total hydrogen enters the core, and attendant isotopic fractionation plausibly lowers the core's D/H to ~130 × 10−6. Crystallized magma ocean material may have D/H ≈ 110 × 10−6. These modeling results readily explain the low D/H in core‐mantle boundary material and account for Earth's inventory of solar neon and helium.
Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling
Authors: Wang Shanshan , Zhu Mingyue , Wang Qiaoyun , Hou Yuli , Li Lei , Weng Honglei , Zhao Yan , Chen Dexi , Ding Huiguo , Guo Junli , Li Mengsen 
Published: October 2018

AbstractAlpha-fetoprotein (AFP) has been recognized as a key regulator of cell proliferation in hepatocellular carcinoma (HCC). However, whether AFP functions in cancer cell autophagy remains unknown. This study investigated the effects of AFP on autophagy in HCC cells. The role of AFP was studied in two HCC cell lines, PLC/PRF/5 and HLE. Cell autophagy, apoptosis, proliferation, migration and invasion were analysed with Western blotting, co-immunoprecipitation (CoIP), immunofluorescence, animal models, MTT assays, flow cytometry (FCM), Cell Counting Kit (CCK)-8, and scratch and transwell assays. In PLC/PRF/5 cells, AFP interacted with PTEN and activated PI3K/Akt/mTOR signalling. In HLE cells, overexpressed AFP similarly interacted with PTEN, leading to PI3K/Akt/mTOR activation and reduced cell autophagy. When AFP was silenced in PLC/PRF/5 cells, cell proliferation, tumour growth, migration and invasion were inhibited, and the numbers of S-phase and apoptotic cells were increased. In contrast, AFP overexpression in HLE cells enhanced cell proliferation, migration and invasion and reduced apoptosis. AFP-dependent autophagy, proliferation, migration and apoptosis were inhibited by rapamycin. In summary, AFP plays critical roles in the inhibition of autophagy and apoptosis in HCC cells and promotes proliferation, migration and invasion. The role of AFP in autophagy inhibition in HCC cells may involve the activation of PI3K/Akt/mTOR signalling.
High prevalence of focal and multi-focal somatic genetic variants in the human brain
Authors: Keogh Michael J. , Wei Wei , Aryaman Juvid , Walker Lauren , van den Ameele Jelle , Coxhead Jon , Wilson Ian , Bashton Matthew , Beck Jon , West John , Chen Richard , Haudenschild Christian , Bartha Gabor , Luo Shujun , Morris Chris M. , Jones Nick S. , Attems Johannes , Chinnery Patrick F. 
Published: October 2018

AbstractSomatic mutations during stem cell division are responsible for several cancers. In principle, a similar process could occur during the intense cell proliferation accompanying human brain development, leading to the accumulation of regionally distributed foci of mutations. Using dual platform >5000-fold depth sequencing of 102 genes in 173 adult human brain samples, we detect and validate somatic mutations in 27 of 54 brains. Using a mathematical model of neurodevelopment and approximate Bayesian inference, we predict that macroscopic islands of pathologically mutated neurons are likely to be common in the general population. The detected mutation spectrum also includesDNMT3AandTET2which are likely to have originated from blood cell lineages. Together, these findings establish developmental mutagenesis as a potential mechanism for neurodegenerative disorders, and provide a novel mechanism for the regional onset and focal pathology in sporadic cases.
Using Drosophila behavioral assays to characterize terebrid venom-peptide bioactivity
Authors: Eriksson Anders , Anand Prachi , Gorson Juliette , Grijuc Corina , Hadelia Elina , Stewart James C. , Holford Mandë , Claridge-Chang Adam 
Published: October 2018

AbstractThe number of newly discovered peptides from the transcriptomes and proteomes of animal venom arsenals is rapidly increasing, resulting in an abundance of uncharacterized peptides. There is a pressing need for a systematic, cost effective, and scalable approach to identify physiological effects of venom peptides. To address this discovery-to-function gap, we developed a sequence driven:activity-based hybrid approach for screening venom peptides that is amenable to large-venom peptide libraries with minimal amounts of peptide. Using this approach, we characterized the physiological and behavioral phenotypes of two peptides from the venom of predatory terebrid marine snails, teretoxins Tv1 from Terebra variegata and Tsu1.1 from Terebra subulata. Our results indicate that Tv1 and Tsu1.1 have distinct bioactivity. Tv1 (100 µM) had an antinociceptive effect in adult Drosophila using a thermal nociception assay to measure heat avoidance. Alternatively, Tsu1.1 (100 µM) increased food intake. These findings describe the first functional bioactivity of terebrid venom peptides in relation to pain and diet and indicate that Tv1 and Tsu1.1 may, respectively, act as antinociceptive and orexigenic agents. Tv1 and Tsu1.1 are distinct from previously identified venom peptides, expanding the toolkit of peptides that can potentially be used to investigate the physiological mechanisms of pain and diet.
High permittivity processed SrTiO3 for metamaterials applications at terahertz frequencies
Authors: Dupas Cyrielle , Guillemet-Fritsch Sophie , Geffroy Pierre-Marie , Chartier Thierry , Baillergeau Matthieu , Mangeney Juliette , Roux Jean-François , Ganne Jean-Pierre , Marcellin Simon , Degiron Aloyse , Akmansoy Éric 
Published: October 2018

AbstractHigh permittivity SrTiO3 for the realization of all-dielectric metamaterials operating at terahertz frequencies was fabricated. A comparison of different processing methods demonstrates that Spark Plasma Sintering is the most effective sintering process to yield high density ceramic with high permittivity. We compare this sintering process with two other processes. The fabricated samples are characterized in the low frequency and in the terahertz frequency ranges. Their relative permittivities are compared with that of a reference SrTiO3 single crystal. The permittivity of the sample fabricated by Spark Plasma Sintering is as high as that of the single crystal. The role of the signal-to-noise ratio in the measurements at terahertz frequency is detailed.
Cloning of Wing-Development-Related Genes and mRNA Expression Under Heat Stress in Chlorpyrifos-Resistant and -Susceptible Plutella xylostella
Authors: Chen Xue Zhun , Hu Qi Xing , Liu Qi Qing , Wu Gang 
Published: October 2018

AbstractChlorpyrifos-resistant (Rc) Plutella xylostella (DBM) shows higher wing-vein injury than chlorpyrifos-susceptible (Sm) DBM under heat stress in our previous study. To investigate the toxicological mechanisms of the differences in injury of wing vein between Rc- and Sm-DBM collected from Fuzhou, China, total ten cDNA sequences of wing-development-related genes were isolated and characterized in DBM, including seven open reading frame (ORF) (ash1, ah2, ash3, ase, dpp, srf and dll encoded 187 amino acids, 231 aa, 223aa, 397aa, 423aa, 229aa and 299aa, respectively), and three partly sequences (salm, ser and wnt-1 encoded 614aa, 369aa and 388aa, respectively). The mRNA expression of the genes was inhibited in Rc- and Sm-DBM under heat stress, as compared with that an average temperature (25 °C). And, in general, significantly higher down-regulated expressions of the mRNA expression of the wing development-related genes were found in Rc-DBM as compared to those in Sm-DBM under heat stress. The results indicated that Sm-DBM displayed higher adaptability at high temperature because of significantly lower inhibition the mRNA expressions of wing-development-related genes. We suggest that significantly higher injury of wing vein showed in Rc-DBM under heat stress might be associated with the strong down-regulation of wing-development-related genes.
Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease)
Authors: Sindelar Miriam , Dyke Jonathan P. , Deeb Ruba S. , Sondhi Dolan , Kaminsky Stephen M. , Kosofsky Barry E. , Ballon Douglas J. , Crystal Ronald G. , Gross Steven S. 
Published: October 2018

AbstractLate infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a rare lysosomal storage disorder caused by a monogenetic deficiency of tripeptidyl peptidase-1 (TPP1). Despite knowledge that lipofuscin is the hallmark disease product, the relevant TPP1 substrate and its role in neuronal physiology/pathology is unknown. We hypothesized that untargeted metabolite profiling of cerebrospinal fluid (CSF) could be used as an effective tool to identify disease-associated metabolic disruptions in CLN2 disease, offering the potential to identify biomarkers that inform on disease severity and progression. Accordingly, a mass spectrometry-based untargeted metabolite profiling approach was employed to differentiate CSF from normal vs. CLN2 deficient individuals. Of 1,433 metabolite features surveyed, 29 linearly correlated with currently employed disease severity scores. With tandem mass spectrometry 8 distinct metabolite identities were structurally confirmed based on retention time and fragmentation pattern matches, vs. standards. These putative CLN2 biomarkers include 7 acetylated species – all attenuated in CLN2 compared to controls. Because acetate is the major bioenergetic fuel for support of mitochondrial respiration, deficient acetylated species in CSF suggests a brain energy defect that may drive neurodegeneration. Targeted analysis of these metabolites in CSF of CLN2 patients offers a powerful new approach for monitoring CLN2 disease progression and response to therapy.
Whole Exome Sequencing of HIV-1 long-term non-progressors identifies rare variants in genes encoding innate immune sensors and signaling molecules
Authors: Nissen Sara Konstantin , Christiansen Mette , Helleberg Marie , Kjær Kathrine , Jørgensen Sofie Eg , Gerstoft Jan , Katzenstein Terese L , Benfield Thomas , Kronborg Gitte , Larsen Carsten S , Laursen Alex , Pedersen Gitte , Jakobsen Martin R , Tolstrup Martin , Mogensen Trine H 
Published: October 2018

AbstractCommonCCR5-∆32 and HLA alleles only explain a minority of the HIV long-term non-progressor (LTNP) and elite controller (EC) phenotypes. To identify rare genetic variants contributing to the slow disease progression phenotypes, we performed whole exome sequencing (WES) on seven LTNPs and four ECs. HLA andCCR5allele status, total HIV DNA reservoir size, as well as variant-related functional differences between the ECs, LTNPs, and eleven age- and gender-matched HIV-infected non-controllers on antiretroviral therapy (NCARTs) were investigated. Several rare variants were identified in genes involved in innate immune sensing, CD4-dependent infectivity, HIV trafficking, and HIV transcription mainly within the LTNP group. ECs and LTNPs had a significantly lower HIV reservoir compared to NCARTs. Furthermore, three LTNPs with variants affecting HIV nuclear import showed integrated HIV DNA levels below detection limit afterin vitroinfection. HIV slow progressors with variants in the TLR and NOD2 pathways showed reduced pro-inflammatory responses compared to matched controls. Low-range plasma levels of fibronectin was observed in a LTNP harboring twoFN1variants. Taken together, this study identified rare variants in LTNPs as well as in one EC, which may contribute to understanding of HIV pathogenesis and these slow progressor phenotypes, especially in individuals without protectingCCR5-∆32 and HLA alleles.
Synthetic cADPR analogues may form only one of two possible conformational diastereoisomers
Authors: Watt Joanna M. , Thomas Mark P. , Potter Barry V. L. 
Published: October 2018

AbstractCyclic adenosine 5′-diphosphate ribose (cADPR) is an emerging Ca2+-mobilising second messenger. cADPR analogues have been generated as chemical biology tools via both chemo-enzymatic and total synthetic routes. Both routes rely on the cyclisation of a linear precursor to close an 18-membered macrocyclic ring. We show here that, after cyclisation, there are two possible macrocyclic product conformers that may be formed, depending on whether cyclisation occurs to the “right” or the “left” of the adenine base (as viewed along the H-8 → C-8 base axis). Molecular modelling demonstrates that these two conformers are distinct and cannot interconvert. The two conformers would present a different spatial layout of binding partners to the cADPR receptor/binding site. For chemo-enzymatically generated analogues Aplysia californica ADP-ribosyl cyclase acts as a template to generate solely the “right-handed” conformer and this corresponds to that of the natural messenger, as originally explored using crystallography. However, for a total synthetic analogue it is theoretically possible to generate either product, or a mixture, from a given linear precursor. Cyclisation on either face of the adenine base is broadly illustrated by the first chemical synthesis of the two enantiomers of a “southern” ribose-simplified cIDPR analogue 8-Br-N9-butyl-cIDPR, a cADPR analogue containing only one chiral sugar in the “northern” ribose, i.e. 8-Br-D- and its mirror image 8-Br-L-N9-butyl-cIDPR. By replacing the D-ribose with the unnatural L-ribose sugar, cyclisation of the linear precursor with pyrophosphate closure generates a cyclised product spectroscopically identical, but displaying equal and opposite specific rotation. These findings have implications for cADPR analogue design, synthesis and activity.
Multi-scale digital soil mapping with deep learning
Authors: Behrens Thorsten , Schmidt Karsten , MacMillan Robert A. , Viscarra Rossel Raphael A. 
Published: October 2018

AbstractWe compared different methods of multi-scale terrain feature construction and their relative effectiveness for digital soil mapping with a Deep Learning algorithm. The most common approach for multi-scale feature construction in DSM is to filter terrain attributes based on different neighborhood sizes, however results can be difficult to interpret because the approach is affected by outliers. Alternatively, one can derive the terrain attributes on decomposed elevation data, but the resulting maps can have artefacts rendering the approach undesirable. Here, we introduce ‘mixed scaling’ a new method that overcomes these issues and preserves the landscape features that are identifiable at different scales. The new method also extends the Gaussian pyramid by introducing additional intermediate scales. This minimizes the risk that the scales that are important for soil formation are not available in the model. In our extended implementation of the Gaussian pyramid, we tested four intermediate scales between any two consecutive octaves of the Gaussian pyramid and modelled the data with Deep Learning and Random Forests. We performed the experiments using three different datasets and show that mixed scaling with the extended Gaussian pyramid produced the best performing set of covariates and that modelling with Deep Learning produced the most accurate predictions, which on average were 4–7% more accurate compared to modelling with Random Forests.
Probiotics and carriage of Streptococcus pneumoniae serotypes in Danish children, a double-blind randomized controlled trial
Authors: Fjeldhøj Sine , Laursen Rikke Pilmann , Larnkjær Anni , Mølgaard Christian , Fuursted Kurt , Krogfelt Karen Angeliki , Slotved Hans-Christian 
Published: October 2018

AbstractThis study examined the carriage of Streptococcus pneumoniae in healthy Danish children aged 8–19 months and assessed the effect of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis on the pneumococcal carriage during daycare enrolment. Potential risk factors of pneumococcal carriage were analysed and the carriage study was compared with registered invasive pneumococcal disease (IPD) data. This study is a part of the ProbiComp study, which was a double-blind, randomized controlled trial, including 290 children allocated to probiotics or placebo for 6 months and recruited during two autumn seasons (2014/2015). Pneumococci were identified by optochin sensitivity, bile solubility, α-hemolysis and/or capsular reaction. Serotyping was performed by latex agglutination kit and Quellung reaction. The carriage rate of S. pneumoniae was 26.0% at baseline and 67.4% at the end of intervention. No significant difference was observed between the placebo group and the probiotics group (p = 0.508). Children aged 8–19 months were carriers of non-pneumococcal vaccine serotypes causing IPD in children aged 0–4 years. However, serotypes causing most IPD cases in Danish elderly were either not found or found with low prevalence suggesting that children are not the main reservoir of those serotypes and other age groups need to be considered as carriers.
Inspiratory Lung Expansion in Patients with Interstitial Lung Disease: CT Histogram Analyses
Authors: Park Junghoan , Jung Julip , Yoon Soon Ho , Goo Jin Mo , Hong Helen , Yoon Jeong-Hwa 
Published: October 2018

AbstractThis study aimed to evaluate inspiratory lung expansion in patients with interstitial lung disease (ILD) using histogram analyses based on advanced image registration between inspiratory and expiratory CT scans. We included 16 female ILD patients and eight age- and sex-matched normal controls who underwent full-inspiratory and expiratory CT scans. The CT scans were sequentially aligned based on the surface, landmarks, and attenuation of the lung parenchyma. Histogram analyses were performed on the degree of lung expansion (DLE) of each pixel between the aligned images in x-, y-, z-axes, and 3-dimensionally (3D). The overall mean registration error was 1.9 mm between the CT scans. The DLE3D in ILD patients was smaller than in the controls (mean, 17.6 mm vs. 26.9 mm; p = 0.023), and less heterogeneous in terms of standard deviation, entropy, and uniformity (p < 0.05). These results were mainly due to similar results in the DLEZ of the lower lungs. A forced vital capacity tended to be weakly correlated with mean (r2 = 0.210; p = 0.074), and histogram parameters (r2 = 0.194–0.251; p = 0.048–0.100) of the DLE3D in the lower lung in ILD patients. Our findings indicate that reduced and less heterogeneous inspiratory lung expansion in ILD patients can be identified by using advanced accurate image registration.
Deep-RBPPred: Predicting RNA binding proteins in the proteome scale based on deep learning
Authors: Zheng Jinfang , Zhang Xiaoli , Zhao Xunyi , Tong Xiaoxue , Hong Xu , Xie Juan , Liu Shiyong 
Published: October 2018

AbstractRNA binding protein (RBP) plays an important role in cellular processes. Identifying RBPs by computation and experiment are both essential. Recently, an RBP predictor, RBPPred, is proposed in our group to predict RBPs. However, RBPPred is too slow for that it needs to generate PSSM matrix as its feature. Herein, based on the protein feature of RBPPred and Convolutional Neural Network (CNN), we develop a deep learning model called Deep-RBPPred. With the balance and imbalance training set, we obtain Deep-RBPPred-balance and Deep-RBPPred-imbalance models. Deep-RBPPred has three advantages comparing to previous methods. (1) Deep-RBPPred only needs few physicochemical properties based on protein sequences. (2) Deep-RBPPred runs much faster. (3) Deep-RBPPred has a good generalization ability. In the meantime, Deep-RBPPred is still as good as the state-of-the-art method. Testing in A. thaliana, S. cerevisiae and H. sapiens proteomes, MCC values are 0.82 (0.82), 0.65 (0.69) and 0.85 (0.80) for balance model (imbalance model) when the score cutoff is set to 0.5, respectively. In the same testing dataset, different machine learning algorithms (CNN and SVM) are also compared. The results show that CNN-based model can identify more RBPs than SVM-based. In comparing the balance and imbalance model, both CNN-base and SVM-based tend to favor the majority class in the imbalance set. Deep-RBPPred forecasts 280 (balance model) and 265 (imbalance model) of 299 new RBP. The sensitivity of balance model is about 7% higher than the state-of-the-art method. We also apply deep-RBPPred to 30 eukaryotes and 109 bacteria proteomes downloaded from Uniprot to estimate all possible RBPs. The estimating result shows that rates of RBPs in eukaryote proteomes are much higher than bacteria proteomes.