bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid function and ischemic heart disease: a Mendelian randomization study
Authors: Zhao Jie V. , Schooling C. Mary 
Published: August 2017

AbstractTo clarify the role of thyroid function in ischemic heart disease (IHD) we assessed IHD risk and risk factors according to genetically predicted thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) positivity. Separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used in an extensively genotyped case (n = 64,374)-control (n = 130,681) study, CARDIoGRAMplusC4D. Associations with lipids, diabetes and adiposity were assessed using the Global Lipids Genetics Consortium Results (n = 196,475), the DIAbetes Genetics Replication And Meta-analysis case (n = 34,380)-control (n = 114,981) study, and the Genetic Investigation of ANthropometric Traits (body mass index in 152,893 men and 171,977 women, waist-hip ratio in 93,480 men and 116,741 women). Genetically predicted thyroid function was not associated with IHD (odds ratio (OR) per standard deviation for TSH 1.05, 95% confidence interval (CI) 0.97 to 1.12; for FT4 1.01, 95% CI 0.91 to 1.12; for TPOAb positivity 1.10, 95% CI 0.83 to 1.46) or after Bonferroni correction with risk factors, except for an inverse association of FT4 with low-density lipoprotein-cholesterol. The associations were generally robust to sensitivity analyses using a weighted median method and MR Egger. This novel study provides little indication that TSH, FT4 or TPOAb positivity affects IHD, despite potential effects on its risk factors.
Cytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner
Authors: Wijesundara Danushka K. , Yu Wenbo , Quah Ben J. C. , Eldi Preethi , Hayball John D. , Diener Kerrilyn R. , Voskoboinik Ilia , Gowans Eric J. , Grubor-Bauk Branka 
Published: August 2017

AbstractThe use of cost-effective vaccines capable of inducing robust CD8+T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8+T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8+T cell immunity.In vitrodata showed that transfection of HEK293T cells with the cytolytic DNA resulted in the release of lactate dehydrogenase, indicative of necrotic/lytic cell death.In vitroexposure of this lytic cell debris to purified DCs from naïve C57BL/6 mice resulted in maturation of DCs as determined by up-regulation of CD80/CD86. Using activation/proliferation of adoptively transferred OT-I CD8+T cells to measure antigen presentation by DCsin vivo, it was determined that cytolytic DNA immunisation resulted in a time-dependent increase in the proliferation of OT-I CD8+T cells compared to canonical DNA immunisation. Overall, the data suggest that the cytolytic DNA vaccine increases the activity of DCs which has important implications for the design of DNA vaccines to improve their translational prospects.
Remote sensing of seasonal light use efficiency in temperate bog ecosystems
Authors: Tortini R. , Coops N. C. , Nesic Z. , Christen A. , Lee S. C. , Hilker T. 
Published: August 2017

AbstractDespite storing approximately half of the atmosphere’s carbon, estimates of fluxes between wetlands and atmosphere under current and future climates are associated with large uncertainties, and it remains a challenge to determine human impacts on the net greenhouse gas balance of wetlands at the global scale. In this study we demonstrate that the relationship between photochemical reflectance index, derived from high spectral and temporal multi-angular observations, and vegetation light use efficiency was strong (r2 = 0.64 and 0.58 at the hotspot and darkspot, respectively), and can be utilized to estimate carbon fluxes from remote at temperate bog ecosystems. These results improve our understanding of the interactions between vegetation physiology and spectral characteristics to understand seasonal magnitudes and variations in light use efficiency, opening new perspectives on the potential of this technique over extensive areas with different landcover.
Hypotension in ICU Patients Receiving Vasopressor Therapy
Authors: Yapps Bryce , Shin Sungtae , Bighamian Ramin , Thorsen Jill , Arsenault Colleen , Quraishi Sadeq A. , Hahn Jin-Oh , Reisner Andrew T. 
Published: August 2017

AbstractVasopressor infusion (VPI) is used to treat hypotension in an ICU. We studied compliance with blood pressure (BP) goals during VPI and whether a statistical model might be efficacious for advance warning of impending hypotension, compared with a basic hypotension threshold alert. Retrospective data were obtained from a public database. Studying adult ICU patients receiving VPI at submaximal dosages, we analyzed characteristics of sustained hypotension episodes (>15 min) and then developed a logistic regression model to predict hypotension episodes using input features related to BP trends. The model was then validated with prospective data. In the retrospective dataset, 102-of-215 ICU stays experienced >1 hypotension episode (median of 2.5 episodes per day in this subgroup). When trained with 75% of retrospective dataset, testing with the remaining 25% of the dataset showed that the model and the threshold alert detected 99.6% and 100% of the episodes, respectively, with median advance forecast times (AFT) of 12 and 0 min. In a second, prospective dataset, the model detected 100% of 26 episodes with a median AFT of 22 min. In conclusion, episodes of hypotension were common during VPI in the ICU. A logistic regression model using BP temporal trend features predicted the episodes before their onset.
Context conditioning in humans using commercially available immersive Virtual Reality
Authors: Kroes Marijn C. W. , Dunsmoor Joseph E. , Mackey Wayne E. , McClay Mason , Phelps Elizabeth A. 
Published: August 2017

AbstractDespite a wealth of knowledge on how humans and nonhuman animals learn to associate meaningful events with cues in the environment, far less is known about how humans learn to associate these events with the environment itself. Progress on understanding spatiotemporal contextual processes in humans has been slow in large measure by the methodological constraint of generating and manipulating immersive spatial environments in well-controlled laboratory settings. Fortunately, immersive Virtual Reality (iVR) technology has improved appreciably and affords a relatively straightforward methodology to investigate the role of context on learning, memory, and emotion while maintaining experimental control. Here, we review context conditioning literature in humans and describe challenges to study contextual learning in humans. We then provide details for a novel context threat (fear) conditioning paradigm in humans using a commercially available VR headset and a cross-platform game engine. This paradigm resulted in the acquisition of subjective threat, threat-conditioned defensive responses, and explicit threat memory. We make the paradigm publicly available and describe obstacles and solutions to optimize future studies of context conditioning using iVR. As computer technology advances to replicate the sensation of realistic environments, there are increasing opportunities to bridge the translational gap between rodent and human research on how context modulates cognition, which may ultimately lead to more optimal treatment strategies for anxiety- and stress-related disorders.
Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo
Authors: Altenburg Arwen F. , van de Sandt Carolien E. , Li Bobby W. S. , MacLoughlin Ronan J. , Fouchier Ron A. M. , van Amerongen Geert , Volz Asisa , Hendriks Rudi W. , de Swart Rik L. , Sutter Gerd , Rimmelzwaan Guus F. , de Vries Rory D. 
Published: August 2017

AbstractModified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performedin vitro,ex vivoandin vivoexperiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequentin vivoexperiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.
Long-term (2001–2013) observations of water-soluble dicarboxylic acids and related compounds over the western North Pacific: trends, seasonality and source apportionment
Authors: Boreddy Suresh K. R. , Kawamura Kimitaka , Tachibana Eri 
Published: August 2017

AbstractTo better understand the impact of East Asian pollutants on the molecular composition of marine organic aerosols, we conducted long-term (2001–2013) observations of water-soluble dicarboxylic acids and related compounds in total suspended particulate samples collected at Chichijima Island in the western North Pacific (WNP). Seasonal variations of all the diacids and related compounds showed maxima in winter and spring and minima in summer, except for azelaic acid (C9), which maximized in summer to autumn. The overall annual concentrations of the total diacids, ω-oxoacids and α-dicarbonyls showed an increase during 2001–2013. We found a significant (p < 0.05) decadal increase in the inter-annual trends of pyruvic and glyoxylic (p > 0.05) acids, and methylglyoxal (MeGly). In contrast, phthalic acid (p < 0.05) and glyoxal (Gly) showed a decrease in their trends. We also found a significant decrease in the trend of the Gly/MeGly mass ratios. These results demonstrate that the enhanced concentrations of diacids over the WNP are majorly attributed to the aqueous-phase photooxidation of biogenic volatile organic compounds from East Asia followed by long-range atmospheric transport. Further, positive matrix factorization analysis showed a biogenic photochemical contribution (42%) was the dominant source of oxalic acid in the WNP.
The Gαi-GIV binding interface is a druggable protein-protein interaction
Authors: DiGiacomo Vincent , de Opakua Alain Ibáñez , Papakonstantinou Maria P. , Nguyen Lien T. , Merino Nekane , Blanco-Canosa Juan B. , Blanco Francisco J. , Garcia-Marcos Mikel 
Published: August 2017

AbstractHeterotrimeric G proteins are usually activated by the guanine-nucleotide exchange factor (GEF) activity of GPCRs. However, some non-receptor proteins are also GEFs. GIV (a.k.a Girdin) was the first non-receptor protein for which the GEF activity was ascribed to a well-defined protein sequence that directly binds Gαi. GIV expression promotes metastasis and disruption of its binding to Gαi blunts the pro-metastatic behavior of cancer cells. Although this suggests that inhibition of the Gαi-GIV interaction is a promising therapeutic strategy, protein-protein interactions (PPIs) are considered poorly “druggable” targets requiring case-by-case validation. Here, we set out to investigate whether Gαi-GIV is a druggable PPI. We tested a collection of >1,000 compounds on the Gαi-GIV PPI by in silico ligand screening and separately by a chemical high-throughput screening (HTS) assay. Two hits, ATA and NF023, obtained in both screens were confirmed in secondary HTS and low-throughput assays. The binding site of NF023, identified by NMR spectroscopy and biochemical assays, overlaps with the Gαi-GIV interface. Importantly, NF023 did not disrupt Gαi-Gβγ binding, indicating its specificity toward Gαi-GIV. This work establishes the Gαi-GIV PPI as a druggable target and sets the conceptual and technical framework for the discovery of novel inhibitors of this PPI.
Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
Authors: Ren Jun , Ding Xiuqing , Trudel Marie , Greer John J. , MacLean Joanna E. 
Published: August 2017

AbstractThe nature and development of cardiorespiratory impairments associated with sickle cell disease are poorly understood. Given that the mechanisms of these impairments cannot be addressed adequately in clinical studies, we characterized cardiorespiratory pathophysiology from birth to maturity in the sickle cell disease SAD mouse model. We identified two critical phases of respiratory dysfunction in SAD mice; the first prior to weaning and the second in adulthood. At postnatal day 3, 43% of SAD mice showed marked apneas, anemia, and pulmonary vascular congestion typical of acute chest syndrome; none of these mice survived to maturity. The remaining SAD mice had mild lung histological changes in room air with an altered respiratory pattern, seizures, and a high rate of death in response to hypoxia. Approximately half the SAD mice that survived to adulthood had an identifiable respiratory phenotype including baseline tachypnea at 7–8 months of age, restrictive lung disease, pulmonary hypertension, cardiac enlargement, lower total lung capacity, and pulmonary vascular congestion. All adult SAD mice demonstrated impairments in exercise capacity and response to hypoxia, with a more severe phenotype in the tachypneic mice. The model revealed distinguishable subgroups of SAD mice with cardiorespiratory pathophysiology mimicking the complications of human sickle cell disease.
Prognostic factors and outcomes of unplanned extubation
Authors: Chao Chien-Ming , Sung Mei-I. , Cheng Kuo-Chen , Lai Chih-Cheng , Chan Khee-Siang , Cheng Ai-Chin , Hsing Shu-Chen , Chen Chin-Ming 
Published: August 2017

AbstractThis study investigated the prognostic factors and outcomes of unplanned extubation (UE) in patients in a medical center’s 6 intensive care units (ICUs) and calculated their mortality risk. We retrospectively reviewed the medical records of all adult patients in Chi Mei Medical Center who underwent UE between 2009 and 2015. During the study period, there were 305 episodes of UE in 295 ICU patients (men: 199 [67.5%]; mean age: 65.7 years; age range: 18–94 years). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16.4, mean therapeutic intervention scoring system (TISS) score was 26.5, and mean Glasgow coma scale score was 10.4. One hundred thirty-six patients (46.1%) were re-intubated within 48 h. Forty-five died (mortality rate: 15.3%). Multivariate analyses showed 5 risk factors—respiratory rate, APACHE II score, uremia, liver cirrhosis, and weaning status—were independently associated with mortality. In conclusion, five risk factors including a high respiratory rate before UE, high APACHE II score, uremia, liver cirrhosis, and not in the process of being weaned—were associated with high mortality in patients who underwent UE.
Development and assessment of a lysophospholipid-based deep learning model to discriminate geographical origins of white rice
Authors: Long Nguyen Phuoc , Lim Dong Kyu , Mo Changyeun , Kim Giyoung , Kwon Sung Won 
Published: August 2017

AbstractGeographical origin determination of white rice has become the major issue of food industry. However, there is still lack of a high-throughput method for rapidly and reproducibly differentiating the geographical origins of commercial white rice. In this study, we developed a method that employed lipidomics and deep learning to discriminate white rice from Korea to China. A total of 126 white rice of 30 cultivars from different regions were utilized for the method development and validation. By using direct infusion-mass spectrometry-based targeted lipidomics, 17 lysoglycerophospholipids were simultaneously characterized within minutes per sample. Unsupervised data exploration showed a noticeable overlap of white rice between two countries. In addition, lysophosphatidylcholines (lysoPCs) were prominent in white rice from Korea while lysophosphatidylethanolamines (lysoPEs) were enriched in white rice from China. A deep learning prediction model was built using 2014 white rice and validated using two different batches of 2015 white rice. The model accurately discriminated white rice from two countries. Among 10 selected predictors, lysoPC(18:2), lysoPC(14:0), and lysoPE(16:0) were the three most important features. Random forest and gradient boosting machine models also worked well in this circumstance. In conclusion, this study provides an architecture for high-throughput classification of white rice from different geographical origins.
Highly Stabilized Core-Satellite Gold Nanoassemblies in Vivo: DNA-Directed Self-Assembly, PEG Modification and Cell Imaging
Authors: Tang Liangfeng , Yu Guiping , Tan Lishan , Li Min , Deng Xiulong , Liu Jianyu , Li Aiqing , Lai Xuandi , Hu Jianqiang 
Published: August 2017

AbstractAu nanoparticles (NPs) have important applications in bioimaging, clinical diagnosis and even therapy due to its water-solubility, easy modification and drug-loaded capability, however, easy aggregation of Au NPs in normal saline and serum greatly limits its applications. In this work, highly stabilized core-satellite Au nanoassemblies (CSAuNAs) were constructed by a hierarchical DNA-directed self-assembly strategy, in which satellite Au NPs number could be effectively tuned through varying the ratios of core-AuNPs-ssDNA and satellite-AuNPs-ssDNAc. It was especially interesting that PEG-functionalized CSAuNAs (PEG-CSAuNAs) could not only bear saline solution but also resist the enzymatic degradation in fetal calf serum. Moreover, cell targeting and imaging indicated that the PEG-CSAuNAs had promising biotargeting and bioimaging capability. Finally, fluorescence imaging in vivo revealed that PEG-CSAuNAs modified with N-acetylation chitosan (CSNA) could be selectively accumulate in the kidneys with satisfactory renal retention capability. Therefore, the highly stabilized PEG-CSAuNAs open a new avenue for its applications in vivo.
Community outbreaks of group A Streptococcus revealed by genome sequencing
Authors: Turner Claire E. , Bedford Luke , Brown Nicholas M. , Judge Kim , Török M. Estée , Parkhill Julian , Peacock Sharon J. 
Published: August 2017

AbstractThe frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute outbreaks in hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution to this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic surveillance of 93 clinical GAS isolates from individuals in a defined geographic region. Detailed clinical information was obtained for closely related clusters of isolates. Genomic sequence data was contextualised through comparison with international data. We identified 18 different emm genotypes within our bacterial population, and revealed both highly diverse and closely related isolates. This high level of diversity was maintained even in the context of international sequence data. We also identified two emm1 clusters, and one emm3 cluster, of closely-related isolates that differed only by 1 to 4 single nucleotide polymorphisms. Analysis of clinical information identified no healthcare associated contact between patients, indicating cryptic community transmission. Our findings suggest that genomic surveillance of GAS would increase detection of transmission and highlight opportunities for intervention.
Curcumin liposomes interfere with quorum sensing system of Aeromonas sobria and in silico analysis
Authors: Ding Ting , Li Tingting , Wang Zhi , Li Jianrong 
Published: August 2017

AbstractAeromonas sobria is opportunistic pathogen frequently found in environment and food. Interfering with its quorum sensing (QS) system could be a promising way to alleviate its virulence. In this study, curcumin liposomes were prepared and their characteristics like particle size, zeta potential, PDI (Polymey Disperse Index), encapsulation efficiency and loading capacity were measured. The quorum sensing inhibitory effect of curcumin liposomes under sub-MIC (Minimum Inhibitory Concentration) on siderophore production, swimming and swarming motility, extracellular proteases, biofilm formation and AHLs (N-acylhomoserine lactones) production of A. sobria were also determined. The results showed that, the curcumin liposomes with high encapsulation capacity (84.51 ± 0.58%) were stable and homogeneous. QS-regulated phenotypes of the pathogen were significantly inhibited by curcumin liposomes. The in silico analysis revealed that the QS system of A. sobria may be inhibited by released curcumin from curcumin liposomes through interacting with the built LuxI type protein and blocking the production of AHLs.
The protein and mRNA expression levels of glial cell line-derived neurotrophic factor in post stroke depression and major depressive disorder
Authors: Zhang Yanran , Jiang Haitang , Yue Yingying , Yin Yingying , Zhang Yuqun , Liang Jinfeng , Li Shenghua , Wang Jun , Lu Jianxin , Geng Deqin , Wu Aiqin , Yuan Yonggui 
Published: August 2017

AbstractPrevious studies have indicated that the level of glial cell line-derived neurotrophic factor (GDNF) may be correlated with stroke and depression. Here, we investigated whether GDNF can be a discriminant indicator for post stroke depression (PSD). 159 participants were divided into four groups: PSD, stroke without depression (Non-PSD), major depressive disorder (MDD) and normal control (NC) group, and the protein and mRNA expression levels of GDNF in serum were measured. The results showed that only MDD group had statistical difference in protein and mRNA levels compared with the other three groups (Bonferroni test, P < 0.05). The results of receiver operating curve (ROC) analysis supported GDNF as general distinguishing models in PSD and MDD groups with the area under the curve (AUC) at 0.797 (P < 0.001) and 0.831 (P < 0.001) respectively. In addition, the Spearman analysis demonstrated that the GDNF protein level negatively correlated with the value of Hamilton depression rating scale (HAMD) in PSD patients (correlation coefficient = −0.328,P = 0.047). Together, these findings suggest the protein and mRNA expression levels of GDNF decreased in patients with depression. GDNF may serve as a potential biomarker for differential diagnosis of PSD from MDD patients.