bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local climatology of fast ice in McMurdo Sound, Antarctica
Authors: Kim Stacy , Saenz Ben , Scanniello Jeff , Daly Kendra , Ainley David 
Published: February 2018

AbstractFast ice plays important physical and ecological roles: as a barrier to wind, waves and radiation, as both barrier and safe resting place for air-breathing animals, and as substrate for microbial communities. While sea ice has been monitored for decades using satellite imagery, high-resolution imagery sufficient to distinguish fast ice from mobile pack ice extends only back toc.2000. Fast ice trends may differ from previously identified changes in regional sea ice distributions. To investigate effects of climate and human activities on fast ice dynamics in McMurdo Sound, Ross Sea, the sea and fast ice seasonal events (1978–2015), ice thicknesses and temperatures (1986–2014), wind velocities (1973–2015) and dates that an icebreaker annually opens a channel to McMurdo Station (1956–2015) are reported. A significant relationship exists between sea ice concentration and fast ice extent in the Sound. While fast/sea ice retreat dates have not changed, fast/sea ice reaches a minimum later and begins to advance earlier, in partial agreement with changes in Ross Sea regional pack ice dynamics. Fast ice minimum extent within McMurdo Sound is significantly correlated with icebreaker arrival date as well as wind velocity. The potential impacts of changes in fast ice climatology on the local marine ecosystem are discussed.
Gemella bergeriinfective endocarditis: a case report and brief review of literature
Authors: Zaidi S. Javed , Husayni Tarek , Collins Mary A. 
Published: February 2018

AbstractGemellais a genus of Gram-positive bacteria found in the digestive tract of humans. They rarely cause systemic illness but have been recently implicated in several serious infections. We report infective endocarditis caused byGemella bergeriin a 23-year-old with a bicuspid aortic valve status post-intervention in infancy.
SAFETY VS. SENSITIVITY: POSSIBLE WORLDS AND THE LAW OF EVIDENCE
Authors: Pardo Michael S. 
Published: February 2018

ABSTRACTThis article defends the importance of epistemic safety for legal evidence. Drawing on discussions of sensitivity and safety in epistemology, the article explores how similar considerations apply to legal proof. In the legal context, sensitivity concerns whether a factual finding would be made if it were false, and safety concerns how easily a factual finding could be false. The article critiques recent claims about the importance of sensitivity for the law of evidence. In particular, this critique argues that sensitivity does not have much of an effect on the value of legal evidence and that it fails to explain legal doctrine. By contrast, safety affects the quality of legal evidence, and safety better explains central features of the law of evidence, including probative value, admissibility rules, and standards of proof.
The strategic use of pensions by not-for-profit organizations
Authors: CALABRESE THAD DANIEL , SEARING ELIZABETH A. M. 
Published: February 2018

AbstractDefined benefit pension plans are an important and unexplored aspect of not-for-profit compensation, covering between 15% and 21% of the estimated national not-for-profit workforce. Here we consider whether pension contributions and actuarial assumptions are mechanisms for achieving not-for-profit financial management objectives such as smoothing consumption, managing reported net earnings, and minimizing pension liabilities. The empirical results indicate a variety of these behaviors. Not-for-profit pension plan sponsors use accumulated net assets to smooth consumption. Further, not-for-profits manage reported profits downwards when they exceed expectations by increasing pension contributions, but both minimize contributions and liberalize actuarial assumptions when they underperform relative to their desired earnings targets.
A virus or more in (nearly) every cell: ubiquitous networks of virus–host interactions in extreme environments
Authors: Munson-McGee Jacob H , Peng Shengyun , Dewerff Samantha , Stepanauskas Ramunas , Whitaker Rachel J , Weitz Joshua S , Young Mark J 
Published: February 2018

Abstract
The application of viral and cellular metagenomics to natural environments has expanded our understanding of the structure, functioning, and diversity of microbial and viral communities. The high diversity of many communities, e.g., soils, surface ocean waters, and animal-associated microbiomes, make it difficult to establish virus-host associations at the single cell (rather than population) level, assign cellular hosts, or determine the extent of viral host range from metagenomics studies alone. Here, we combine single-cell sequencing with environmental metagenomics to characterize the structure of virus–host associations in a Yellowstone National Park (YNP) hot spring microbial community. Leveraging the relatively low diversity of the YNP environment, we are able to overlay evidence at the single-cell level with contextualized viral and cellular community structure. Combining evidence from hexanucelotide analysis, single cell read mapping, network-based analytics, and CRISPR-based inference, we conservatively estimate that &gt;60% of cells contain at least one virus type and a majority of these cells contain two or more virus types. Of the detected virus types, nearly 50% were found in more than 2 cellular clades, indicative of a broad host range. The new lens provided by the combination of metaviromics and single-cell genomics reveals a network of virus–host interactions in extreme environments, provides evidence that extensive virus–host associations are common, and further expands the unseen impact of viruses on cellular life.
TR4 nuclear receptor suppresses HCC cell invasion via downregulating the EphA2 expression
Authors: Jin Ren’an , Lin Hui , Li Gonghui , Xu Junjie , Shi Liang , Chang Chawnshang , Cai Xiujun 
Published: February 2018

Abstract
Early studies indicated that testicular nuclear receptor 4 (TR4) could function as a suppressor in the transcriptional regulation of the HBV core gene expression, which might then influence the development of hepatocellular carcinoma (HCC). The direct linkage between TR4 and HCC progression, however, remained unclear. Here, via a human clinical sample survey, we found that 13 of the 18 HCC patients studied had lower TR4 expression in metastatic lesions than in matched primary HCC lesions, suggesting that TR4 may play a negative role in HCC metastasis. Results from in vitro cell migration/invasion studied confirmed that TR4 could suppress HCC cell migration/invasion. Mechanism dissection revealed that TR4 might function through downregulating ephrin type-A receptor 2 (EphA2) expression at the transcriptional level via direct binding to the TR4REs located on the 5′ promoter of EphA2 to suppress HCC cell migration/invasion. Targeting the EphA2 via EphA2-siRNA partially reversed the enhanced HCC cell migration/invasion with confirmed TR4 knockdown. Notably, results from preclinical studies using in vivo mouse model with orthotopic xenograft of HCC LM3 cells also confirmed the in vitro findings. Taking these findings together, preclinical studies using multiple in vitro HCC cell lines and an in vivo mouse model all led to the conclusion that TR4 may function as a suppressor of HCC metastasis and that targeting this newly identified TR4-EphA2 signaling may improve our ability to suppress HCC metastasis.
Downregulation of PERK activity and eIF2α serine 51 phosphorylation by mTOR complex 1 elicits pro-oxidant and pro-death effects in tuberous sclerosis-deficient cells
Authors: Krishnamoorthy Jothilatha , Tenkerian Clara , Gupta Jyotsana , Ghaddar Nour , Wang Shuo , Darini Cedric , Staschke Kirk A. , Ghosh Abhishek , Gandin Valentina , Topisirovic Ivan , Kristof Arnold S. , Hatzoglou Maria , Simos George , Koromilas Antonis E. 
Published: February 2018

AbstractOxidative stress determines cell fate through several mechanisms, among which regulation of mRNA translation by the phosphorylation of the alpha (α) subunit of the translation initiation factor eIF2α at serine 51 (eIF2αP) plays a prominent role. Increased eIF2αP can contribute to tumor progression as well as tumor suppression. While eIF2αP is increased in most cells to promote survival and adaptation to different forms of stress, we demonstrate that eIF2αP is reduced in tuberous sclerosis complex 2 (TSC2)-deficient cells subjected to oxidative insults. Decreased eIF2αP in TSC2-deficient cells depends on reactive oxygen species (ROS) production and is associated with a reduced activity of the endoplasmic reticulum (ER)-resident kinase PERK owing to the hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1). Downregulation of PERK activity and eIF2αP is accompanied by increased ROS production and enhanced susceptibility of TSC2-deficient cells to extrinsic pro-oxidant stress. The decreased levels of eIF2αP delay tumor formation of TSC2-deficient cells in immune deficient mice, an effect that is significantly alleviated in mice subjected to an anti-oxidant diet. Our findings reveal a previously unidentified connection between mTORC1 and eIF2αP in TSC2-deficient cells with potential implications in tumor suppression in response to oxidative insults.
Inhibition of endo-lysosomal function exacerbates vascular calcification
Authors: Cai Yujun , Wang Xue-Lin , Flores Alyssa M. , Lin Tonghui , Guzman Raul J. 
Published: February 2018

AbstractVascular calcification is a pathologic response to mineral imbalances and is prevalent in atherosclerosis, diabetes mellitus, and chronic kidney disease. When located in the media, it is highly associated with increased cardiovascular morbidity and mortality, particularly in patients on dialysis. Vascular calcification is tightly regulated and controlled by a series of endogenous factors. In the present study, we assess the effects of lysosomal and endosomal inhibition on calcification in vascular smooth muscle cells (VSMCs) and aortic rings. We observed that lysosomal function was increased in VSMCs cultured in calcification medium containing 3.5 mM inorganic phosphate (Pi) and 3 mM calcium (Ca2+) for 7 days. We also found that the lysosomal marker lysosome-associated membrane protein 2 was markedly increased and colocalized with osteogenic markers in calcified aortas from vitamin D3-treated rats. Interestingly, both the lysosomal inhibitor chloroquine and the endosomal inhibitor dynasore dose-dependently enhanced Pi + Ca2+-mediated VSMC calcification. Inhibition of lysosomal and endosomal function also promoted osteogenic transformation of VSMCs. Additionally, lysosome inhibition increased Pi-induced medial calcification of aortic rings ex vivo. These data suggest that the endosome-lysosome system may play a protective role in VSMC and medial artery calcification.
Luminescent and paramagnetic properties of nanoparticles shed light on their interactions with proteins
Authors: Dal Cortivo Giuditta , Wagner Gabriel E. , Cortelletti Paolo , Padmanabha Das Krishna Mohan , Zangger Klaus , Speghini Adolfo , Dell’Orco Daniele , Meyer N. Helge 
Published: February 2018

AbstractNanoparticles have been recognized as promising tools for targeted drug-delivery and protein therapeutics. However, the mechanisms of protein-nanoparticle interaction and the dynamics underlying the binding process are poorly understood. Here, we present a general methodology for the characterization of protein-nanoparticle interaction on a molecular level. To this end we combined biophysical techniques including nuclear magnetic resonance (NMR), circular dichroism (CD), resonance energy transfer (RET) and surface plasmon resonance (SPR). Particularly, we analyzed molecular mechanisms and dynamics of the interaction of CaF2 nanoparticles with the prototypical calcium sensor calmodulin (CaM). We observed the transient formation of an intermediate encounter complex involving the structural region linking the two domains. Specific interaction of CaM with CaF2 NPs is driven by the N-terminal EF-hands, which seem to recognize Ca2+ on the surface of the nanoparticle. We conclude that CaF2 NP-CaM interaction is fully compatible with potential applications in nanomedicine. Overall, the methods presented in this work can be extended to other systems and may be useful to quantitatively characterize structural and dynamic features of protein-NP interactions with important implications for nanomedicine and nano-biotechnology.
The mechanistic causes of peripheral intravenous catheter failure based on a parametric computational study
Authors: Piper Russell , Carr Peter J. , Kelsey Lachlan J. , Bulmer Andrew C. , Keogh Samantha , Doyle Barry J. 
Published: February 2018

AbstractPeripheral intravenous catheters (PIVCs) are the most commonly used invasive medical device, yet up to 50% fail. Many pathways to failure are mechanistic and related to fluid mechanics, thus can be investigated using computational fluid dynamics (CFD). Here we used CFD to investigate typical PIVC parameters (infusion rate, catheter size, insertion angle and tip position) and report the hemodynamic environment (wall shear stress (WSS), blood damage, particle residence time and venous stasis volumes) within the vein and catheter, and show the effect of each PIVC parameter on each hemodynamic measure. Catheter infusion rate has the greatest impact on our measures, with catheter orientation also playing a significant role. In some PIVC configurations WSS was 3254 times higher than the patent vein, and blood damage was 512 times greater, when compared to control conditions. Residence time is geometry-dependent and decreases exponentially with increasing insertion angle. Stasis volume decreased with increasing infusion rate and, to a lesser degree, insertion angle. Even without infusion, the presence of the catheter changes the flow field, causing low velocity recirculation at the catheter tip. This research demonstrates how several controllable factors impact important mechanisms of PIVC failure. These data, the first of their kind, suggest limiting excessive infusion rates in PIVC.
Metabolic profile associated with distinct behavioral coping strategies of 129Sv and Bl6 mice in repeated motility test
Authors: Narvik Jane , Vanaveski Taavi , Innos Jürgen , Philips Mari-Anne , Ottas Aigar , Haring Liina , Zilmer Mihkel , Vasar Eero 
Published: February 2018

AbstractWe investigated the metabolic outcome of different coping strategies in 129S6/SvEvTac (129Sv) and C57BL/6Ntac (Bl6) strains. Two different batches of male 129Sv and Bl6 mice were used. One batch was not subjected to any behavioral manipulations (home cage control; HCC), whereas the other batch was treated with saline for 11 days and exposed after every treatment to the motor activity measurement (repeated motility tested; RMT). Bl6 RMT mice displayed a robust increase in number of rearings during repeated testing. 129Sv RMT mice experienced significant loss of body weight, but showed enhanced weight gain in HCC batch compared to Bl6. Serum metabolites (acylcarnitines, amino acids, biogenic amines, hexoses, glycerophospholipids and sphingolipids) were determined with AbsoluteIDQ p180 kit. Results of the metabolomic study revealed prominent peculiarities between strains in two different conditions. Comparison of both batches of mice demonstrated that in Bl6 biogenic amines (acetyl-ornithine, alpha-amionadipic acid, carnosine) and lysophosphatidylcholine PC(16:1/0:0) dominated. However in 129Sv acylcarnitine C5 clearly dominated, indicating shift towards short-chain acylcarnitines. Stable strain-specific ratios also emerged for both lines, ratio of glycine/PC ae C38:2 for Bl6 and ratios of C5/C0 as well as PC(16:0/0:0)/PC(16:1/0:0) for 129Sv. The described metabolic changes probably reflect different behavioral coping strategies of 129Sv and Bl6 mice.
InForm software: a semi-automated research tool to identify presumptive human hepatic progenitor cells, and other histological features of pathological significance
Authors: Kramer Anne S. , Latham Bruce , Diepeveen Luke A. , Mou Lingjun , Laurent Geoffrey J. , Elsegood Caryn , Ochoa-Callejero Laura , Yeoh George C. 
Published: February 2018

AbstractHepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists’ reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies. In this study we utilise PerkinElmer’s “InForm” software package to semi-automate the scoring of patient liver biopsies, and compare outputs to a pathologist’s assessment. We examined a cohort of eleven acute hepatitis samples and three non-alcoholic fatty liver disease (NAFLD) samples, stained with HPC markers (GCTM-5 and Pan Cytokeratin), an inflammatory marker (CD45), Sirius Red to detect collagen and haematoxylin/eosin for general histology. InForm was configured to identify presumptive HPCs, CD45+ve inflammatory cells, areas of necrosis, fat and collagen deposition (p < 0.0001). Hepatitis samples were then evaluated both by a pathologist using the Ishak-Knodell scoring system, and by InForm through customised algorithms. Necroinflammation as evaluated by a pathologist, correlated with InForm outputs (r2 = 0.8192, p < 0.05). This study demonstrates that the InForm software package provides a useful tool for liver disease research, allowing rapid, and objective quantification of the presumptive HPCs and identifies histological features that assist with assessing liver disease severity, and potentially can facilitate diagnosis.
Deep learning based tissue analysis predicts outcome in colorectal cancer
Authors: Bychkov Dmitrii , Linder Nina , Turkki Riku , Nordling Stig , Kovanen Panu E. , Verrill Clare , Walliander Margarita , Lundin Mikael , Haglund Caj , Lundin Johan 
Published: February 2018

AbstractImage-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79–3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28–2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30–2.15; AUC 0.57) in the stratification into low- and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.
Trend and risk factors of low birth weight and macrosomia in south China, 2005–2017: a retrospective observational study
Authors: Rao Jiaming , Fan Dazhi , Wu Shuzhen , Lin Dongxin , Zhang Huishan , Ye Shaoxin , Luo Xin , Wang Lijuan , Yang Jianwei , Pang Minhui , Zhang Jiayi , Xia Qing , Yang Xiaoke , Wang Wen , Fu Yao , Liu Yan , Guo Xiaoling , Liu Zhengping 
Published: February 2018

AbstractThe percentages of low birth weight (LBW) increased from 7.7% in 2005 to 11.3% in 2011 and declined to 8.1% in 2017. For very low birth weight (VLBW) individuals, the proportion declined −1.0% annually, from 2.5% in 2005 to 1.4% in 2017. Among moderately low birth weight (MLBW) individuals, the proportion first increased 12.8% annually, from 5.0% in 2005 to 9.3% in 2011, and then declined −3.8% annually, from 9.4% in 2011 to 7.0% in 2017. The percentages of macrosomia monotone decreased from 4.0% in 2005 to 2.5% in 2017, an annual decline of −4.0%. Multiple regression analyses showed that boys, maternal age, hypertensive disorders complicating pregnancy (HDCP), and diabetes were significant risk factors for LBW. Boys, maternal age, gestational age, HDCP, diabetes, and maternal BMI were significant risk factors for macrosomia. Although the relevant figures declined slightly in our study, it is likely that LBW and macrosomia will remain a major public health issue over the next few years in China. More research aimed at control and prevention of these risk factors for LBW and macrosomia and their detrimental outcome in the mother and perinatal child should be performed in China.
Maternal obesity-induced decreases in plasma, hepatic and uterine polyunsaturated fatty acids during labour is reversed through improved nutrition at conception
Authors: Muir Ronan , Liu Ge , Khan Raheela , Shmygol Anatoly , Quenby Siobhan , Gibson Robert Alan , Muhlhausler Beverly , Elmes Matthew 
Published: February 2018

AbstractMaternal obesity is associated with prolonged and dysfunctional labour, potentially through decreased synthesis of prostaglandins that stimulate myometrial contractions. We assessed the impact of maternal obesity on concentrations of precursor fatty acids (FA) for prostaglandin synthesis and whether any changes could be reversed by improved nutrition post-conception. Wistar rats were fed control (CON) or High-Fat, High-cholesterol (HFHC) diets 6 weeks before mating. At conception half the dams switched diets providing 4 dietary groups: (1) CON, (2) HFHC, (3) CON-HFHC or (4) HFHC-CON. During parturition rats were euthanized and FA composition of plasma, liver and uterus determined. Visceral fat was doubled in rats exposed to the HFHC diet prior to and/or during pregnancy compared to CON. HFHC diet increased MUFAs but decreased omega-3 and omega-6 PUFAs in plasma and liver. Uterine omega-3 FA concentrations were halved in HFHC versus CON rats, but all other FAs were similar. Switching from HFHC to CON diet at conception restored all FA profiles to those seen in CON rats. The increased MUFA and decreased PUFA concentrations in obese HFHC dams may contribute to aberrant prostaglandin synthesis and dysfunctional myometrial activity and it may be possible to reverse these changes, and potentially improve labour outcomes, by improving nutrition at conception.
AP-2ε Expression in Developing Retina: Contributing to the Molecular Diversity of Amacrine Cells
Authors: Jain Saket , Glubrecht Darryl D. , Germain Devon R. , Moser Markus , Godbout Roseline 
Published: February 2018

AbstractAP-2 transcription factors play important roles in the regulation of gene expression during development. Four of the five members of the AP-2 family (AP-2α, AP-2β, AP-2γ and AP-2δ) have previously been shown to be expressed in developing retina. Mouse knockouts have revealed roles for AP-2α, AP-2β and AP-2δ in retinal cell specification and function. Here, we show that the fifth member of the AP-2 family, AP-2ε, is also expressed in amacrine cells in developing mammalian and chicken retina. Our data indicate that there are considerably fewer AP-2ε-positive cells in the developing mouse retina compared to AP-2α, AP-2β and AP-2γ-positive cells, suggesting a specialized role for AP-2ε in a subset of amacrine cells. AP-2ε, which is restricted to the GABAergic amacrine lineage, is most commonly co-expressed with AP-2α and AP-2β, especially at early stages of retinal development. Co-expression of AP-2ε and AP-2γ increases with differentiation. Analysis of previously published Drop-seq data from single retinal cells supports co-expression of multiple AP-2s in the same cell. Since AP-2s bind to their target sequences as either homodimers or heterodimers, our work suggests spatially- and temporally-coordinated roles for combinations of AP-2 transcription factors in amacrine cells during retinal development.