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  • Wiley-Blackwell  (474,673)
  • American Institute of Physics (AIP)  (154,287)
  • Munksgaard International Publishers  (13,314)
  • Sage Publications
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  • 1
    Publication Date: 2018-03-12
    Description: Background While hepatocellular carcinoma (HCC) has become a common indication for liver transplantation (LT), intrahepatic cholangiocarcinoma (ICC) and combined-Hepatocellular–cholangiocarcioma (cHCC-CC) are historically contraindicated due to their aggressive behavior. Based on recent experiences, some groups have proposed a clinical trial investigating the role of LT for patients with early CC, defined as a single lesion ≤ 2cm. The purpose of this study is to assess the clinicopathologic features and outcomes following LT for patients who were initially diagnosed with HCC and subsequently found to have either ICC or cHCC-CC on explant. Methods Patients with the diagnosis of primary liver cancer (PLC) after LT from a single center were retrospectively reviewed. Outcomes for patients with early CC were compared to patients with HCC within Milan criteria (MC). Results Out of 618 patients transplanted with PLC, 44 patients were found to have CC on explant. Based on preoperative imaging, 12 patients met criteria for early CC and were compared to 319 patients who had HCC within MC. 1- and 5- year overall survival for early CC vs. HCC was 63.6% vs. 90.0% and 63.6% vs. 70.3% (logrank, p=0.25) respectively. Overall recurrence was 33.3% for early CC vs. 11% for HCC. On explant the patients with CC were more likely understaged with higher tumor grade and vascular invasion. Conclusions Patients with CC present a diagnostic challenge which often leads to the finding of more aggressive lesions on explant after LT, higher recurrence rates and worse post-LT survival. Careful consideration of this diagnostic conundrum needs to be made before a clinical trial is undertaken. This article is protected by copyright. All rights reserved.
    Print ISSN: 1527-6465
    Electronic ISSN: 1527-6473
    Topics: Medicine
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  • 2
    Publication Date: 2018-03-12
    Print ISSN: 1527-6465
    Electronic ISSN: 1527-6473
    Topics: Medicine
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  • 3
    Publication Date: 2018-03-12
    Print ISSN: 1527-6465
    Electronic ISSN: 1527-6473
    Topics: Medicine
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  • 4
    Publication Date: 2018-03-12
    Description: Purpose 2D turbo-spin-echo (TSE) is widely used in the clinic for neuroimaging. However, the long refocusing radiofrequency pulse train leads to high specific absorption rate (SAR) and alters the contrast compared to conventional spin-echo. The purpose of this work is to develop a robust 2D spiral TSE technique for fast T 2 -weighted imaging with low SAR and improved contrast. Methods A spiral-in/out readout is incorporated into 2D TSE to fully take advantage of the acquisition efficiency of spiral sampling while avoiding potential off-resonance-related artifacts compared to a typical spiral-out readout. A double encoding strategy and a signal demodulation method are proposed to mitigate the artifacts because of the T 2 -decay-induced signal variation. An adapted prescan phase correction as well as a concomitant phase compensation technique are implemented to minimize the phase errors. Results Phantom data demonstrate the efficacy of the proposed double encoding/signal demodulation, as well as the prescan phase correction and concomitant phase compensation. Volunteer data show that the proposed 2D spiral TSE achieves fast scan speed with high SNR, low SAR, and improved contrast compared to conventional Cartesian TSE. Conclusion A robust 2D spiral TSE technique is feasible and provides a potential alternative to conventional 2D Cartesian TSE for T 2 -weighted neuroimaging.
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 5
    Publication Date: 2018-03-12
    Description: Purpose To map the cerebral metabolic rate of oxygen (CMRO 2 ) by estimating the oxygen extraction fraction (OEF) from gradient echo imaging (GRE) using phase and magnitude of the GRE data. Theory and Methods 3D multi-echo gradient echo imaging and perfusion imaging with arterial spin labeling were performed in 11 healthy subjects. CMRO 2 and OEF maps were reconstructed by joint quantitative susceptibility mapping (QSM) to process GRE phases and quantitative blood oxygen level-dependent (qBOLD) modeling to process GRE magnitudes. Comparisons with QSM and qBOLD alone were performed using ROI analysis, paired t-tests, and Bland-Altman plot. Results The average CMRO 2 value in cortical gray matter across subjects were 140.4 ± 14.9, 134.1 ± 12.5, and 184.6 ± 17.9 μmol/100 g/min, with corresponding OEFs of 30.9 ± 3.4%, 30.0 ± 1.8%, and 40.9 ± 2.4% for methods based on QSM, qBOLD, and QSM+qBOLD, respectively. QSM+qBOLD provided the highest CMRO 2 contrast between gray and white matter, more uniform OEF than QSM, and less noisy OEF than qBOLD. Conclusion Quantitative CMRO 2 mapping that fits the entire complex GRE data is feasible by combining QSM analysis of phase and qBOLD analysis of magnitude.
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
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  • 6
    Publication Date: 2018-03-12
    Description: Purpose To correct gradient timing delays in non-Cartesian MRI while simultaneously recovering corruption-free auto-calibration data for parallel imaging, without additional calibration scans. Methods The calibration matrix constructed from multi-channel k-space data should be inherently low-rank. This property is used to construct reconstruction kernels or sensitivity maps. Delays between the gradient hardware across different axes and RF receive chain, which are relatively benign in Cartesian MRI (excluding EPI), lead to trajectory deviations and hence data inconsistencies for non-Cartesian trajectories. These in turn lead to higher rank and corrupted calibration information which hampers the reconstruction. Here, a method named Simultaneous Auto-calibration and Gradient delays Estimation (SAGE) is proposed that estimates the actual k-space trajectory while simultaneously recovering the uncorrupted auto-calibration data. This is done by estimating the gradient delays that result in the lowest rank of the calibration matrix. The Gauss-Newton method is used to solve the non-linear problem. The method is validated in simulations using center-out radial, projection reconstruction and spiral trajectories. Feasibility is demonstrated on phantom and in vivo scans with center-out radial and projection reconstruction trajectories. Results SAGE is able to estimate gradient timing delays with high accuracy at a signal to noise ratio level as low as 5. The method is able to effectively remove artifacts resulting from gradient timing delays and restore image quality in center-out radial, projection reconstruction, and spiral trajectories. Conclusion The low-rank based method introduced simultaneously estimates gradient timing delays and provides accurate auto-calibration data for improved image quality, without any additional calibration scans.
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
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  • 7
    Publication Date: 2018-03-12
    Description: Purpose Avoid formation of staircase artifacts in nonlinear diffusion-based MR image reconstruction without compromising computational speed. Methods Whereas second-order diffusion encourages the evolution of pixel neighborhood with uniform intensities, fourth-order diffusion considers smooth region to be not necessarily a uniform intensity region but also a planar region. Therefore, a controlled application of fourth-order diffusivity function is used to encourage second-order diffusion to reconstruct the smooth regions of the image as a plane rather than a group of blocks, while not being strong enough to introduce the undesirable speckle effect. Results Proposed method is compared with second- and fourth-order nonlinear diffusion reconstruction, total variation (TV), total generalized variation, and higher degree TV using in vivo data sets for different undersampling levels with application to dictionary learning-based reconstruction. It is observed that the proposed technique preserves sharp boundaries in the image while preventing the formation of staircase artifacts in the regions of smoothly varying pixel intensities. It also shows reduced error measures compared with second-order nonlinear diffusion reconstruction or TV and converges faster than TV-based methods. Conclusion Because nonlinear diffusion is known to be an effective alternative to TV for edge-preserving reconstruction, the crucial aspect of staircase artifact removal is addressed. Reconstruction is found to be stable for the experimentally determined range of fourth-order regularization parameter, and therefore not does not introduce a parameter search. Hence, the computational simplicity of second-order diffusion is retained.
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
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  • 8
    Publication Date: 2018-03-13
    Description: A methodology is proposed for modeling the diffusion of fragrances released from a moving source. First, we started with a 1D model considering molecular diffusion of α-pinene in air as the only mass transport mechanism. The validation was performed in a diffusion tube, and a system was developed to move the scented source along the axial direction. Results showed that experimental data fitted well with the numerical simulation, suggesting this model as a valid tool to describe the trail of a fragrance released from a moving source for low Re of the order of 10. In the case of a person walking at the speed of 1.34 m/s in a room or corridor inside a building, 3D models are required and mass transport of the perfume to the surrounding air will be dominated by turbulent diffusion or eddy diffusion D t which is two orders of magnitude higher than molecular diffusion. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 9
    Publication Date: 2018-03-13
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
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  • 10
    Publication Date: 2018-03-13
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
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  • 11
    Publication Date: 2018-03-13
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
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  • 12
    Publication Date: 2018-03-13
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
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  • 13
    Publication Date: 2018-03-13
    Description: Uterine tumour resembling ovarian sex cord tumour (UTROSCT) is an uncommon mesenchymal neoplasm which morphologically resembles and expresses markers of ovarian sex cord-stromal tumours (1,2). It has an uncertain histogenesis and this is reflected in the 2014 World Health Organization (WHO) Classification of tumours of the female reproductive organs where it is included in the category of miscellaneous uterine neoplasms (3). This article is protected by copyright. All rights reserved.
    Print ISSN: 0309-0167
    Electronic ISSN: 1365-2559
    Topics: Medicine
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  • 14
    Publication Date: 2018-03-13
    Description: Recently, the opioid analgesic D,L-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use D,L-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of D,L-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting. Finally, the receptors mostly responsible for induction of apoptosis by D,L-methadone remain unclear as contributions of both µ-opioid receptors, Fas cell death receptors, toll-like receptors, N-Methyl-D-aspartate receptors, and opioid growth factor receptors were suggested. Such ambiguity prevents rational application of D,L-methadone or patient stratification to enhance beneficial antineoplastic effects. From a clinical point of view, D,L-methadone and other opioids might in fact prolong survival, but such effects likely originate from their analgesic and neuro-psychotropic properties and thus improvements of quality of life. Crucial obstacles to the administration of D,L-methadone are incomplete knowledge about its systemic disposition, highly variable pharmacokinetics, profound drug-drug- or drug-disease interaction, and QT-prolongation potential. This article summarizes and rates the pharmacological basis of D,L-methadone as an antineoplastic agent and puts its administration in clinical oncology into perspective. Despite enthralling experimental findings about D,L-methadone-mediated apoptosis in cancerous cells or tissues, clinicians should realize the current lack of evidence for the use of D,L-methadone as an antineoplastic agent. Its administration against cancer pain is however tenable, albeit restricted to certain clinical situations. This article is protected by copyright. All rights reserved.
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
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  • 15
    Publication Date: 2018-03-13
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
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  • 16
    Publication Date: 2018-03-13
    Description: The evidence of gut microbiota-mediated modulation of brain function has been widely recognized from studies using germ-free rodents or animals with oral antibiotic-induced microbiota depletion. Since the number of bacteria in the large intestine greatly exceeds that found within the small intestine, large intestinal microbiota may play a crucial role in the modulation of brain function. In the present study, twelve piglets (12.08 ± 0.28 kg) fitted with a T-cannula at the distal ileum were fed a standard diet and randomly assigned to two groups (n=6) for ileal infusion of either saline (control group) or antibiotics (antibiotic group). After 25-days of infusion, ileal and fecal microbiota, serum amino acids and neurotransmitters, and hypothalamic transcriptomics were analyzed. Whilst the antibiotic infusion did not change the proximal ileal microbial composition, it markedly altered the fecal microbial composition and increased aromatic amino acid (AAAs) metabolism ( P 〈0.05), suggesting the infusion specifically targeted large intestinal microbes. Concentrations of AAAs were likewise decreased in the blood and hypothalamus ( P 〈0.05) by antibiotic infusion. Antibiotic infusion further decreased concentrations of hypothalamic 5-HT and dopamine, in line with AAAs being their precursors. Furthermore, an upregulation in gene expressions of neurotransmitter transporters and synthetases was observed ( q 〈0.001). In conclusion, the ileal-antibiotic infusion altered neurotransmitter expression in the porcine hypothalamus and this effect occurred simultaneously with changes in both the large intestinal microbiota, and AAAs in large intestine, blood and hypothalamus. These findings indirectly indicate that large intestinal microbiota affects hypothalamic neurotransmitter expressions. This article is protected by copyright. All rights reserved.
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
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  • 17
    Publication Date: 2018-03-13
    Description: Sepsis-associated encephalopathy (SAE), characterized as diffuse brain dysfunction and neurological manifestations secondary to sepsis, is a common complication in critically ill patients and can give rise to poor outcome, but understanding the molecular basis of this disorder remains a major challenge. Given the emerging role of G protein-coupled receptor 2 (GRK2), first identified as a G protein-coupled receptor (GPCR) regulator, in the regulation of non-GPCR-related molecules contributing to diverse cellular functions and pathology, including inflammation, we tested the hypothesis that GRK2 may be linked to the neuropathogenesis of SAE. When mouse MG6 microglial cells were challenged with lipopolysaccharide (LPS), GRK2 cytosolic expression was highly upregulated. The ablation of GRK2 by small interfering RNAs (siRNAs) prevented an increase in intracellular reactive oxygen species generation in LPS-stimulated MG6 cells. Furthermore, the LPS-induced upregulation of inducible nitric-oxide synthase expression and increase in nitric oxide production were negated by GRK2 inhibitor or siRNAs. However, GRK2 inhibition was without effect on overproduction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in LPS-stimulated MG cells. In mice with cecal ligation and puncture-induced sepsis, treatment with GRK2 inhibitor reduced high levels of oxidative and nitrosative stress in the mice brains, where GRK2 expression was upregulated, alleviated neurohistological damage observed in cerebral cortex sections, and conferred a significant survival advantage to CLP mice. Altogether, these results uncover the novel role for GRK2 in regulating cellular oxidative and nitrosative stress during inflammation and suggest that GRK2 may have a potential as an intriguing therapeutic target to prevent or treat SAE. This article is protected by copyright. All rights reserved.
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
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  • 18
    Publication Date: 2018-03-13
    Description: Staphylococcus aureus , a bacterial, food-borne pathogen of humans, can contaminate raw fruits and vegetables. While physical and chemical methods are available to control S. aureus , scientists are searching for inhibitory phytochemicals from plants. One promising compound from pomegranate is punicalagin, a natural antibiotic. To get a broader understanding of the inhibitory effect of punicalagin on S. aureus growth, we used high-throughput mass spectrometry and quantitative isobaric labeling to investigate the proteome of S. aureus after exposure to a sub-lethal dose of punicalagin. Nearly half of the proteins encoded by the small genome were interrogated, and nearly half of those exhibited significant changes in accumulation. Punicalagin treatment altered the accumulation of proteins and enzymes needed for iron acquisition, and it altered amounts of enzymes for glycolysis, citric acid cycling, protein biosynthesis, and purine and pyrimidine biosynthesis. Punicalagin treatment also induced an SOS cellular response to damaged DNA. Transcriptional comparison of marker genes showed that the punicalagin-induced iron-starvation, and SOS responses resembled those produced by EDTA and ciprofloxacin. These results show that punicalagin adversely alters bacterial growth by disrupting iron homeostasis and that it induces SOS, possibly through DNA biosynthesis inhibition. This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
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  • 19
    Publication Date: 2018-03-13
    Description: Brassica napus plants exposed to 200 μM arsenic (As) exhibited high-level of stress condition, which led to inhibit growth, enhanced lipid peroxidation, and disrupted cellular ultra-structures. Exogenous application of methyl jasmonate (MeJA) alleviated the As-induced oxidative stress and improves the plant growth and photosynthesis. In this study, we investigated changes in the B. napus leaf proteome in order to identify molecular mechanisms involved in MeJA -induced As tolerance. Our study identified 177 proteins were differentially expressed in cultivar ZS 758; while 200 differentially expressed proteins were accumulated in zheda 622, when exposed to As alone and MeJA+As treatments, respectively. Our main objective was to identify the MeJA-regulated protein under As stress. Consistent with this, iTRAQ detected 61 proteins which were significantly accumulated in ZS 758 leaves treated with MeJA under As stress. While in Zheda 622, iTRAQ detected 49 MeJA-induced proteins under As stress. These significantly expressed proteins were further divided into five groups on the base of their function, i.e., stress and defense, photosynthesis, carbohydrates and energy production, protein metabolism and secondary metabolites. Taken together, our study sheds light on the molecular mechanisms involved in MeJA-induced As tolerance in B. napus leaves and suggests a more active involvement of MeJA in plant physiological processes. This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
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  • 20
    Publication Date: 2018-03-14
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 21
    Publication Date: 2018-03-14
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 22
    Publication Date: 2018-03-14
    Description: The treatment landscape for mantle cell lymphoma (MCL) has changed dramatically in recent years, with findings from clinical trials reporting improvements in survival. Data on the general patient population are, however, sparse; and it is unclear whether the effects observed in clinical trials have translated into the real-world setting. To investigate this, we examined first-line and relapsed/refractory (RR) disease management in 335 MCL patients diagnosed between 2004 and 2015 in an established population-based patient cohort, along with data on demographic, diagnostic and prognostic factors. Marked treatment and survival changes were observed; first-line rituximab immunotherapy, for example, increased from 32% to 86% over the 11-year period, and median survival increased from 2·0 years among those first treated in 2004–2011 to 3·5 years among those treated in 2012–2015. Outcomes for RR disease also improved, from 8 months in 2004–2011 to 16·8 months in 2012–2015, coinciding with the introduction of agents, such as bendamustine and ibrutinib. Encouragingly, improvements were seen across all ages; 1-year overall survival among patients over 70 years treated for RR disease almost doubled. Our analyses underscore the importance of monitoring the impact of treatment changes in the real-world setting.
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 23
    Publication Date: 2018-03-14
    Description: Previously no mouse gastric cancer cell lines have been available for transplantation into C57BL/6 mice. However, a gastric cancer model in immunocompetent mice would be useful for analyzing putative therapies.MNU was given in drinking water to C57BL/6 mice and p53 heterozygous knockout mice. Only one tumor from a p53 knockout mouse could be cultured and the cells are subcutaneously transplantable into a C57BL/6 mouse. We cultured this subcutaneous tumor, and sub-cloned it. The mRNA expression in the most aggressive YTN16 subline was compared to the less aggressive YTN2 subline by microarray analysis, and FGFR4 in YTN16 cells was knocked-out with a CRISPR/Cas9 system and inhibited by an FGFR4 selective inhibitor, BLU9931. This article is protected by copyright. All rights reserved.
    Topics: Medicine
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  • 24
    Publication Date: 2018-03-14
    Description: Background : Submandibular glands (SMGs) are specialized epithelial structures which generate saliva necessary for mastication and digestion. Loss of SMGs can lead to inflammation, oral lesions, fungal infections, problems with chewing/swallowing, and tooth decay. Understanding the development of the SMG is important for developing therapeutic options for patients with impaired SMG function. Recent studies have suggested Sonic hedgehog (Shh) signaling in the epithelium plays an integral role in SMG development; however, the mechanism by which Shh influences gland development remains nebulous. Results : Using the Kif3a f/f ;Wnt1-Cre ciliopathic mouse model to prevent Shh signal transduction via the loss of primary cilia in neural crest cells, we report that mesenchymal Shh activity is necessary for gland development. Furthermore, using a variety of murine transgenic lines with aberrant mesenchymal Shh signal transduction, we determine that loss of Shh activity, via loss of the Gli activator, rather than gain of Gli repressor, is sufficient to cause the SMG aplasia. Finally, we determine that loss of the SMG correlates with reduced Neuregulin1 (Nrg1) expression and lack of innervation of the SMG epithelium. Conclusion : Together, these data suggest a novel mechanistic role for mesenchymal Shh signaling during SMG development. This article is protected by copyright. All rights reserved.
    Electronic ISSN: 1097-0177
    Topics: Medicine
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  • 25
    Publication Date: 2018-03-14
    Description: Ectotherms tend to grow faster, but reach a smaller size when reared under warmer conditions. This temperature-size rule (TSR) is a widespread phenomenon. Despite the generality of this pattern, no general explanation has been found. We therefore tested the relative importance of two proposed mechanisms for the TSR: (1) a stronger increase in development rate relative to growth rate at higher temperatures, which would cause a smaller size at maturity, and (2) resource limitation placing stronger constraints on growth in large individuals at higher temperatures, which would cause problems with attaining a large size in warm conditions. We raised Daphnia magna at eight temperatures to assess their size at maturity, asymptotic size, and size of their offspring. We used three clonal lines that differed in asymptotic size and growth rate. A resource allocation model was developed and fitted to our empirical data to explore the effect of both mechanisms for the TSR. The genetic lines of D. magna showed different temperature dependence of growth and development rates resulting in different responses for size at maturity. Also, at warm temperatures, growth was constrained in large, but not in small individuals. The resource allocation model could fit these empirical data well. Based on our empirical results and model explorations, the TSR of D. magna at maturity is best explained by a stronger increase in development rate relative to growth rate at high temperature, and the TSR at asymptotic size is best explained by a size-dependent and temperature-dependent constraint on growth, although resource limitation could also affect size at maturity. In conclusion, the TSR can take different forms for offspring size, size at maturity, and asymptotic size and each form can arise from its own mechanism, which could be an essential step toward finding a solution to this century-old puzzle. Scientists have known that ectotherms tend to reach larger sizes when they grow in colder environments. We now identified three distinct patterns in this phenomenon and discuss how these patterns could be regulated by different physiological mechanisms. We use a novel resource allocation model to describe these patterns and to test the hypothesized mechanisms underlying them.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 26
    Publication Date: 2018-03-14
    Description: Ice Binding Proteins (IBPs) contribute to the survival of many living beings at sub-zero temperature by controlling the formation and growth of ice crystals. This work investigates the structural basis of the ice binding properties of Efc IBP, obtained from Antarctic bacteria. Efc IBP is endowed with a unique combination of thermal hysteresis (TH) and ice recrystallization inhibition (IRI) activity. The three-dimensional structure, solved at 0.84 Å resolution, shows that Efc IBP belongs to the IBP-1 fold family, and is organized in a right-handed β-solenoid with a triangular cross-section that forms three protein surfaces, named A, B and C faces. However, Efc IBP diverges from other IBP-1 fold proteins in relevant structural features including the lack of a “capping” region on top of the β-solenoid, and in the sequence and organization of the regions exposed to ice that, in Efc IBP, reveal the presence of threonine-rich ice-binding motifs. Docking experiments and site-directed mutagenesis pinpoint that Efc IBP binds ice crystals not only via its B face, as common to other IBPs, but also via ice binding sites on the C face. This article is protected by copyright. All rights reserved.
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 27
    Publication Date: 2018-03-14
    Description: Global change is affecting primary productivity in forests worldwide, and this, in turn, will alter long-term carbon (C) sequestration in wooded ecosystems. On one hand, increased primary productivity, for example, in response to elevated atmospheric carbon dioxide (CO 2 ), can result in greater inputs of organic matter to the soil, which could increase C sequestration belowground. On other hand, many of the interactions between plants and microorganisms that determine soil C dynamics are poorly characterized, and additional inputs of plant material, such as leaf litter, can result in the mineralization of soil organic matter, and the release of soil C as CO 2 during so-called “priming effects”. Until now, very few studies made direct comparison of changes in soil C dynamics in response to altered plant inputs in different wooded ecosystems. We addressed this with a cross-continental study with litter removal and addition treatments in a temperate woodland (Wytham Woods) and lowland tropical forest (Gigante forest) to compare the consequences of increased litterfall on soil respiration in two distinct wooded ecosystems. Mean soil respiration was almost twice as high at Gigante (5.0 μmol CO 2  m −2  s −1 ) than at Wytham (2.7 μmol CO 2  m −2  s −1 ) but surprisingly, litter manipulation treatments had a greater and more immediate effect on soil respiration at Wytham. We measured a 30% increase in soil respiration in response to litter addition treatments at Wytham, compared to a 10% increase at Gigante. Importantly, despite higher soil respiration rates at Gigante, priming effects were stronger and more consistent at Wytham. Our results suggest that in situ priming effects in wooded ecosystems track seasonality in litterfall and soil respiration but the amount of soil C released by priming is not proportional to rates of soil respiration. Instead, priming effects may be promoted by larger inputs of organic matter combined with slower turnover rates. Taken together, results of our cross-continental study with litter removal and addition treatments in a temperate woodland (Wytham Woods) and lowland tropical forest (Gigante forest) for comparing consequences of increased litterfall on soil respiration in two distinct wooded ecosystems showed that mean soil respiration was almost twice as high at Gigante than at Wytham but surprisingly, litter manipulation treatments had a greater and more immediate effect on soil respiration at Wytham. Importantly, despite higher soil respiration rates at Gigante, priming effects were stronger and more consistent at Wytham. Our results suggest that in situ priming effects in wooded ecosystems track seasonality in litterfall and soil respiration but the amount of soil C released by priming is not proportional to rates of soil respiration.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 28
    Publication Date: 2018-03-14
    Description: Background : In the cochlea, auditory development depends on precise patterns of innervation by afferent and efferent nerve fibers, as well as a stereotyped arrangement of hair and supporting cells. NrCAM is a homophilic cell adhesion molecule that controls diverse aspects of nervous system development, but the function of NrCAM in cochlear development is not well understood. Results : Throughout cochlear innervation, NrCAM is detectable on spiral ganglion neuron (SGN) afferent and olivocochlear efferent fibers, and on the membranes of developing hair and supporting cells. Neonatal Nrcam null cochleae show errors in type II SGN fasciculation, reduced efferent innervation and defects in the stereotyped packing of hair and supporting cells. Nrcam loss also leads to dramatic changes in the profiles of presynaptic afferent and efferent synaptic markers at the time of hearing onset. Despite these numerous developmental defects, Nrcam null adults do not show defects in auditory acuity and, by postnatal day 21, the developmental deficits in ribbon synapse distribution and sensory domain structure appear to have been corrected. Conclusions : NrCAM is expressed by several neural and sensory epithelial subtypes within the developing cochlea, and the loss of Nrcam confers numerous, but non-permanent, developmental defects in innervation and sensory domain patterning. This article is protected by copyright. All rights reserved.
    Electronic ISSN: 1097-0177
    Topics: Medicine
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  • 29
    Publication Date: 2018-03-14
    Description: Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. Previously, we proposed C-terminal binding protein 1 (CTBP1), a transcripcional co-repressor, as a molecular link between these two conditions. Notably, CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed Chloride Channel Accessory 2 ( CLCA2 ) expression in prostate xenografts developed in MeS animals. CTBP1 bound to CLCA2 promoter and repressed its transcription and promoter activity in PCa cell lines. Furthermore, we found that CTBP1 formed a repressor complex with ZEB1, EP300 and HDACs that modulates the CLCA2 promoter activity. CLCA2 promoted PCa cell adhesion inhibiting Epithelial-Mesenchymal Transition (EMT) and activating CTNNB1 together with epithelial markers (CDH1) induction, and mesenchymal markers (SNAI2 and TWIST1) repression. Moreover, CLCA2 depletion in PCa cells injected s.c. in MeS mice increased the Circulating Tumor Cells (CTCs) foci compared to control. A miRNA expression microarray from PCa xenografts developed in MeS mice, showed 21 miRNAs modulated by CtBP1 involved in angiogenesis, extracellular matrix organization, focal adhesion and adherents junctions, among others. We found that miR-196b-5p directly targets CLCA2 by cloning CLCA2 3'UTR and performing reporter assays. Altogether, we identified a new molecular mechanism for PCa and MeS link based on CLCA2 repression by CTBP1 and miR-196b-5p molecules that might act as key factors in the progression onset of this disease. This article is protected by copyright. All rights reserved.
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
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  • 30
    Publication Date: 2018-03-15
    Description: The production of latexes stabilized by solid particles, so-called Pickering stabilizers, has attracted considerable attention due to its benefits, including the enhanced mechanical properties of the polymer films. Clays for instance were found to enhance particle stabilization in emulsion polymerization, in a comparable way to conventional surfactants. Their concentration thus determines the polymer particles size and number, and consequently the reaction rate. In this work, we investigate the impact of the presence of such rigid and big platelets at the polymer particle's surface on radical exchange between the aqueous phase and the polymer particles. It was found for the system underhand, that the average number of radicals per particle ( ) was independent of the stabilizer layer. Therefore, a radical capture model independent of the clay concentration could be used to simulate reactions involving different clay concentrations and predict the evolution of the monomer conversion, particle size, and . This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 31
    Publication Date: 2018-03-15
    Description: A nickel (Ni) nanoparticle catalyst, supported on 4-channel α-Al 2 O 3 hollow fibers, was synthesized by atomic layer deposition (ALD). Highly-dispersed Ni nanoparticles were successfully deposited on the outside surfaces and the inside porous structures of hollow fibers. The catalyst was employed to catalyze the dry reforming of methane (DRM) reaction and showed a methane reforming rate of 2040 Lh −1 gNi −1 at 800°C. NiAl 2 O 4 spinel was formed when Ni nanoparticles were deposited on alpha-alumina substrates by ALD, which enhanced the Ni-support interaction. Different cycles (two, five, and ten) of Al 2 O 3 ALD films were applied on the Ni/hollow fiber catalysts to further improve the interaction between the Ni nanoparticles and the hollow fiber support. Both the catalyst activity and stability were improved with the deposition of Al 2 O 3 ALD films. Among the Al 2 O 3 ALD coated catalysts, the catalyst with five cycles of Al 2 O 3 ALD showed the best performance. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 32
    Publication Date: 2018-03-15
    Description: As computers get faster, researchers — not hardware or algorithms — become the bottleneck in scientific discovery. Computational study of colloidal self-assembly is one area that is keenly affected: even after computers generate massive amounts of raw data, performing an exhaustive search to determine what (if any) ordered structures occur in a large parameter space of many simulations can be excruciating. We demonstrate how machine learning can be applied to discover interesting areas of parameter space in colloidal self-assembly. We create numerical fingerprints — inspired by bond orientational order diagrams — of structures found in self-assembly studies and use these descriptors to both find interesting regions in a phase diagram and identify characteristic local environments in simulations in an automated manner for simple and complex crystal structures. Utilizing these methods allows analysis to keep up with the data generation ability of modern high-throughput computing environments. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 33
    Publication Date: 2018-03-15
    Description: Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real-time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behaviour of the granule liquid-to-solid ratio (%w/w) at the end of the granulation unit of a commercial ConsiGma TM -25 production line. Near-infrared spectroscopy was used to monitor the granule composition in-line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25%w/w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. This article is protected by copyright. All rights reserved.
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    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 34
    Publication Date: 2018-03-15
    Description: The turbulent flow of surfactant solution in the wide-rib rectangular grooved channels was studied by direct numerical simulation. Moreover, the variations of near-wall streamwise vortices with time were discussed and the distributions of streamwise vortex radius, swirling strength and density were quantitatively investigated. It was found that the influence of microgrooves on the fluid mainly occurred within the buffer layer and microgrooves could induce numerous streamwise vortices with small size and swirling strength within the grooved valleys. The drag-reducing enhancement mechanism of microgroove in the surfactant solution could be mainly considered as the competing results between the “restriction effect” and “tip effect” of microgroove, and the essential factor should be the numerous secondary streamwise vortices with small size and swirling strength within the grooved valleys. Furthermore, a predicted method for the optimal drag-reducing size of microgroove was proposed, and the prediction values agreed well with the numerical results. This article is protected by copyright. All rights reserved.
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    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 35
    Publication Date: 2018-03-15
    Description: Nanosheet HZSM-5 film vertically grown on the substrate with the tailorable macro- and meso-pores between the layers of nanosheets is hydrothermally synthesized by seed-assisted secondary growth method. The as-prepared nanosheet HZSM-5 film exhibits reaction rate enhancement up to 312% in catalytic cracking of n -dodecane as well as twice light olefins selectivity, ascribed to the better mass transfer of reactants in the hierarchical porous structure and the ultra-thin b -axis pores of nanosheets. This article is protected by copyright. All rights reserved.
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    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 36
    Publication Date: 2018-03-15
    Description: Vitamin K antagonists (VKAs) used for the prevention and treatment of thromboembolic disease, increase the risk of bleeding complications. We developed and validated a model to predict the risk of an international normalised ratio (INR) ≥ 4·5 during a hospital stay. Adult patients admitted to a tertiary hospital and treated with VKAs between 2006 and 2010 were analysed. Bleeding risk was operationalised as an INR value ≥4·5. Multivariable logistic regression analysis was used to assess the association between potential predictors and an INR ≥ 4·5 and validated in an independent cohort of patients from the same hospital between 2011 and 2014. We identified 8996 admissions of patients treated with VKAs, of which 1507 (17%) involved an INR ≥ 4·5. The final model included the following predictors: gender, age, concomitant medication and several biochemical parameters. Temporal validation showed a c statistic of 0·71. We developed and validated a clinical prediction model for an INR ≥ 4·5 in VKA-treated patients admitted to our hospital. The model includes factors that are collected during routine care and are extractable from electronic patient records, enabling easy use of this model to predict an increased bleeding risk in clinical practice.
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 37
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    Wiley-Blackwell
    Publication Date: 2018-03-15
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 38
    Publication Date: 2018-03-15
    Description: Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a novel biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, HBV-infected, HCV-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively). A PCR array was used to detect the changes in transcription factor expression in hepatic stellate cells (HSCs) with SYK knockdown. The effects of SYK antagonism on liver fibrogenesis were studied in LX-2 cells, TWNT-4 cells, primary human HSCs, and three progressive fibrosis/cirrhosis animal models, including a carbon tetrachloride mouse model, and diethylnitrosamine and bile duct ligation rat models. We found that SYK protein in HSCs and hepatocytes correlated positively with liver fibrosis stage in human liver tissue. HBV or HCV infection significantly increased SYK and cytokine expression in hepatocytes. Increasing cytokine production further induced SYK expression and fibrosis-related gene transcription in HSCs. Up-regulated SYK in HSCs promoted HSC activation by increasing the expression of specific transcription factors related to activation of HSCs. SYK antagonism effectively suppressed liver fibrosis via inhibition of HSC activation, and decreased obstructive jaundice and reduced HCC development in animal models. Conclusions : SYK promotes liver fibrosis via activation of HSCs and is an attractive potential therapeutic target for liver fibrosis and prevention of HCC development. This article is protected by copyright. All rights reserved.
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
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  • 39
    Publication Date: 2018-03-15
    Description: Low-grade adenosquamous carcinoma of the breast (LGASC) is a rare variant of metaplastic carcinoma characterized by a favorable outcome and histologically composed of glandular and squamous elements in a spindle cell background typically associated with a lymphocytic stromal reaction. Due to its rarity, the immunophenoptypical and genetic profile LGASC has not been sufficiently characterized. The aim of this study was to gain insight into the molecular and phenotypic characteristics of LGASC. We reviewed the clinical, morphological features and detailed the immunohistochemical characteristics of a retrospective series of 13 LGASCs. Targeted sequencing of 50 genes was performed in 10/13 cases. Identified mutations were further assessed by Sanger sequencing in a validation series of 11 additional cases. This article is protected by copyright. All rights reserved.
    Print ISSN: 0309-0167
    Electronic ISSN: 1365-2559
    Topics: Medicine
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  • 40
    Publication Date: 2018-03-15
    Description: Background Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear. Objectives We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density(BMD). Methods We investigated the association between milk intake, LCT-13910 C/T (rs4988235) which is associated with lactase persistence ( TT/TC ) in Northern Europeans, and hip fractures in three Danish prospective studies(N=97,811,age ≥20 years). We added meta-analyses of LCT-13910 and fractures and BMD from 5 published Northern European population studies. Results In the Danish studies, the adjusted hazard ratio(HR) for hip fracture per 1 glass/week higher milk intake was 1.00(95%CI:0.99-1.01). The per T -allele milk intake was 0.58(0.49-0.68) glasses/week but HR was 1.01(0.94-1.09) for hip fracture. In meta-analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture were 0.86(0.61-1.21;I 2 =73%) for TT vs . CC and 0.90(0.68-1.21;I 2 =63%) for TC vs . CC . The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18;I 2 =0%) g/cm 2 for TT vs . CC and 0.06 (-0.04-0.17;I 2 =17%)g/cm 2 for TC vs . CC . There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC . Conclusion Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population-based cohorts. A meta-analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD. This article is protected by copyright. All rights reserved.
    Print ISSN: 0954-6820
    Electronic ISSN: 1365-2796
    Topics: Medicine
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  • 41
    Publication Date: 2018-03-15
    Description: Colorectal cancer (CRC) is the third most common cancer worldwide, with more than 1.3 million new cases and 690,000 deaths each year. In China, the incidence of CRC has increased dramatically due to dietary and lifestyle changes, to become the fifth leading cause of cancer-related death. Here, we performed whole-exome sequencing in 50rectal cancer cases among the Chinese population as part of the International Cancer Genome Consortium research project. Frequently-mutated genes and enriched pathways were identified. Moreover, a previously unreported gene, PCDHB3 , was found frequently mutated in 5.19% cases. Additionally, PCDHB3 expression was found decreased in 81.6% of CRC tissues and all eight CRC cell lines tested. Low expression and cytoplasmic localization of PCDHB3 predict poor prognosis in advanced CRC. Copy number decrease and/or CpG island hypermethylation contribute to the pervasive decreased expression of PCDHB3. PCDHB3 inhibits CRC cell proliferation, migration, and epithelial-mesenchymal transition. The tumor suppressive effects of PCDHB3 are partially due to inhibition of NF-κB transcriptional activity through K63-deubiquitination of p50 at lysine 244/252, which increases the binding affinity of inactive p50 homodimer to κB DNA, resulting in competitive inhibition of the transcription of NF-κB target genes byp65 dimers. Our study identified PCDHB3 as a novel tumor suppressor in CRC via inhibition of the NF-κB pathway, and its expression and localization may serve as prognostic markers for advanced CRC.
    Print ISSN: 0022-3417
    Electronic ISSN: 1096-9896
    Topics: Medicine
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  • 42
    Publication Date: 2018-03-16
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 43
    Publication Date: 2018-03-16
    Description: Nasopharyngeal colonization with Streptococcus pneumoniae (the pneumococcus) is known to mount protective adaptive immune responses in rodents and humans. However, the cellular response of the nasopharyngeal compartment to pneumococcal colonization and its importance for the ensuing adaptive immune response is only partially defined. Here we show that nasopharyngeal colonization with S. pneumoniae triggered substantial expansion of both integrin αE (CD103) positive dendritic cells (DC) and T lymphocytes in nasopharynx, nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) of WT mice. However, nasopharyngeal de-colonization and pneumococcus-specific antibody responses were similar between WT and CD103 KO mice or Batf3 KO mice. Also, naïve WT mice passively immunized with antiserum from previously colonized WT and CD103 KO mice were similarly protected against invasive pneumococcal disease (IPD). In summary, the data show that CD103 is dispensable for pneumococcal colonization-induced adaptive immune responses in mice. This article is protected by copyright. All rights reserved
    Print ISSN: 0014-2980
    Electronic ISSN: 1521-4141
    Topics: Medicine
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  • 44
    Publication Date: 2018-03-16
    Description: Background Early detection and classification of chronic pancreatitis (CP) are both important and challenging. Purpose To investigate the diagnostic performance of MR elastography (MRE) and T 1 mapping of the pancreas for different stages of CP. Study Type Retrospective. Subjects Clinical and imaging records of 81 patients (from 5/2015 to 7/2017) with suspected CP were analyzed. Patients were categorized into the normal control ( n  = 35), mild CP ( n  = 30), and moderate/severe CP groups ( n  = 16) according to the Cambridge Classification based on concordant endoscopic retrograde cholangiopancreatography or ultrasound endoscopy findings. Field Strength/Sequence 3T pancreatic MRI, which included MRE and T 1 mapping. Assessment T 1 relaxation times, pancreatic stiffness values, the main pancreatic duct (MPD) diameter, and pancreatic thickness were measured in all patients. Statistical Tests: Cutoff values of T 1 relaxation times and pancreatic stiffness values for diagnosis of CP were calculated using receiver operating characteristic analysis. Associations of imaging parameters with different stages of CP were assessed using logistic regression analysis. Results Both T 1 relaxation times (865 ± 220 msec vs. 1075 ± 221 msec vs. 1350 ± 139 msec) and pancreatic stiffness (1.21 ± 0.13 kPa vs. 1.50 ± 0.15 kPa vs. 1.90 ± 0.16 kPa) differed significantly ( P  〈 0.001) among the control, mild CP, and moderate/severe CP groups. Pancreatic stiffness (〉1.34 kPa) achieved significantly higher area under the curve (AUC) than T 1 relaxation time (〉908.4 msec) for detection of mild CP (AUC: 0.928 vs. 0.751, P  = 0.011). Pancreatic stiffness values (〉1.61 kPa) also achieved significantly higher AUC than T 1 relaxation time (〉1131.6 msec) (AUC: 0.981 vs. 0.910, P  = 0.033) for diagnosing moderate/severe CP from the other two groups. Multiple regression analysis showed that T 1 relaxation time and stiffness were the independent factors associated with mild CP ( P  = 0.025 and 〈0.001, respectively). Data Conclusion Both MRE and T 1 mapping are promising quantitative imaging methods for evaluation of CP; MRE slightly outperformed T 1 mapping. Level of Evidence : 1 Technical Efficacy : Stage 1 J. Magn. Reson. Imaging 2018.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
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  • 45
    Publication Date: 2018-03-16
    Description: Background Systemic lupus erythematosus (SLE) is associated with cognitive deficit but the exact neural mechanisms remain unclear. Purpose To explore sequential brain activities using functional magnetic resonance imaging (fMRI) during the performance of a decision-making task, and to determine whether serum or clinical markers can reflect the involvement of the brain in SLE. Subjects Sixteen female SLE patients without overt clinical neuropsychiatric symptoms and 16 healthy controls were included. Field Strength/Sequence 1.5T, T 1 -weighted anatomic images, gradient-echo echo-planar imaging sequence, and 3D images. Assessment The computer-based Iowa Gambling Task (IGT) for assessing decision-making was performed by SLE patients and 16 matched controls; brain activity was recorded via blood oxygen level-dependent (BOLD) fMRI. The amplitudes of the average BOLD responses were calculated for each individual subject, and activation data from fMRI experiments were compared between the two groups. Statistical Tests Two-sample t -test; repeated-measures analysis of variance (ANOVA); linear regression analyses. Results Imaging revealed activity in a distributed network of brain regions in both groups, including the ventromedial prefrontal cortex (vmPFC), the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC), the posterior cingulate cortex (PCC), and the striatum, as well as the insular, parietal, and occipital cortices. Compared to controls, SLE patients showed lower activation in a convergence zone and the limbic system, namely, the OFC, vmPFC, ACC, and PCC, but greater activation in memory, emotion, and behavior systems involving the dlPFC, the insular cortex and the striatum. Furthermore, brain activation in the vmPFC was positively correlated with IGT scores ( r  = 0.63, P  〈 0.001), but inversely related to disease activity ( r  = −0.57, P  〈 0.01). Data Conclusion The dynamics among the aforementioned neural systems (some hyperfunctioning, others hypofunctioning) may shed some light on the pathologic mechanisms underlying SLE without overt clinical neuropsychiatric symptoms. In addition, disease activity may potentially be used as an effective biomarker reflecting cerebral involvement in SLE. Level of Evidence 1 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2018.
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  • 46
    Publication Date: 2018-03-16
    Description: Background Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. Purpose We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. Study Type Longitudinal (baseline and 2-year follow-up) retrospective study. Subjects Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects. Field Strength/Sequence 4.7T 10-echo gradient-echo acquisition. Assessment Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. Statistical Tests We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P  = 0.1) to regress bulk and DARE measures with the follow-up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. Results Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease ( r  = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS ( r  = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS ( r  = 0.68; Q = 0.0005). Data Conclusion DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age-matched controls, respectively. Specific DARE measures of MS DGM correlated with follow-up MSSS, and may reflect complex disease pathology. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.
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    Topics: Medicine
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  • 47
    Publication Date: 2018-03-16
    Description: Background Our study was aimed at detecting the expression levels of miR-206 in prostate cancer (PCa) tissues and PCa cell lines, and exploring the potential functions of miR-206 by targeting chemokine ligand 11 ( CXCL11 ). Methods RT-qPCR was applied to detect the expressions of miR-206 and CXCL11 in PCa tissues and in PCa cell lines. Expression of the CXCL11 protein was detected using Western blot. After manipulating the expression of miR-206 and CXCL11 in PC-3 and DU-145 cells, the changes of cell proliferation and cell cycle were observed through cell counting kit-8 (CCK-8) and flow cytometry. Wound healing and transwell assay were conducted for cell migration and invasion examination in vitro. The luciferase reporter assay was applied to validate the association between miR-206 and CXCL11 . Results MiR-206 was significantly under-expressed in PCa tissues and in PCa cell lines. Up-regulation of miR-206 could inhibit proliferation, migration, invasion and induced G1/G0 arrest of PCa cells, and vice versa. MiR-206 bound to the 3′-UTR of CXCL11 and significantly repressed the luciferase activity. Overexpression of miR-206 decreased the expression level of CXCL11 significantly. CXCL11 mRNA and protein levels were significantly decreased in PCa cells. Downregulation of CXCL11 presented tumor-suppressing effects on PCa cells as miR-206 mimics did. And co-transfection miR-206 attenuated the tumor-promoting effects induced by CXCL11 overexpression. Conclusion Our current finding demonstrated that miR-206 negatively regulated PCa cell proliferation and migration, and arrested cell cycle by targeting CXCL11 as a tumor suppressor in prostate cancer.
    Print ISSN: 0270-4137
    Electronic ISSN: 1097-0045
    Topics: Medicine
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  • 48
    Publication Date: 2018-03-16
    Description: Background A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long-term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy. Methods From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for 〉2 years follow-up. One-fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery. Results For the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy ( P  = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47-0.97; P  = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point. Conclusions Repeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid-term to long-term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low- to intermediate-risk prostate cancer.
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    Electronic ISSN: 1097-0045
    Topics: Medicine
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  • 49
    Publication Date: 2018-03-16
    Description: Purpose Recent years have brought many changes in the management of localized prostate cancer as national screening guidelines have been updated and diagnostic practice patterns evolved. We sought to better understand how the changing landscape influenced treatment utilization in the United States. Methods We used the SEER database in this retrospective analysis of patients with clinically localized prostate cancer between 2004 and 2013. We evaluated utilization of primary treatment modalities over time with descriptive and trend analyses, and examined treatment utilization by cancer risk group and age at diagnosis. Results Of 398 074 patients in the analytic data set, 38% elected radiation therapy, 38% underwent radical prostatectomy, and 24% opted for expectant management. While in 2004 radiation treatment was almost twice as common as expectant management (42% vs 23%), by 2013 approximately equal percentages of patients were treated with each of the three modalities. Expectant management use increased over time, while the proportion of patients opting for surgery decreased remarkably with increasing age at diagnosis in intermediate- and higher-risk disease. Among radiotherapy options, brachytherapy was most common among lower-risk patients in 2004 but substantially decreased over time ( P  〈 0.001). Conclusions Management of localized prostate cancer changed substantially over time in the United States. Utilization of expectant management has increased for men with low- and intermediate risk cancer. Among those who pursue curative therapy, younger men remain more likely to elect surgery whereas older men tend to choose radiotherapy. Further studies are needed to better characterize factors contributing to treatment selection.
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    Electronic ISSN: 1097-0045
    Topics: Medicine
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  • 50
    Publication Date: 2018-03-16
    Description: In a commentary on our 1996 publication[1], Al-Yassin suggests that we mischaracterized the results of the classical neonatal tolerance experiments of Billingham, Brent, and Medawar (BBM)[2] when we stated that “[BBM} found that rodents injected at birth with hemopoietic cells from a genetically different donor were later able to accept transplants from the same donor”. Al-Yassin points out that “BBM could only reliably induce tolerance by giving fetal mice allogeneic cells” and “BBM concluded that neonatal mice were in a ‘null’ period, during which inoculation with MHC-incompatible cells had no effect, i.e. the recipient mice became neither tolerant nor primed against the ‘test’ graft”. As to the charge of mischaracterization, we plead “guilty”. We referenced the wrong paper. This article is protected by copyright. All rights reserved.
    Print ISSN: 0300-9475
    Electronic ISSN: 1365-3083
    Topics: Medicine
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  • 51
    Publication Date: 2018-03-16
    Description: The use of outcome-dependent sampling with longitudinal data analysis has previously been shown to improve efficiency in the estimation of regression parameters. The motivating scenario is when outcome data exist for all cohort members but key exposure variables will be gathered only on a subset. Inference with outcome-dependent sampling designs that also incorporates incomplete information from those individuals who did not have their exposure ascertained has been investigated for univariate but not longitudinal outcomes. Therefore, with a continuous longitudinal outcome, we explore the relative contributions of various sources of information toward the estimation of key regression parameters using a likelihood framework. We evaluate the efficiency gains that alternative estimators might offer over random sampling, and we offer insight into their relative merits in select practical scenarios. Finally, we illustrate the potential impact of design and analysis choices using data from the Cystic Fibrosis Foundation Patient Registry.
    Print ISSN: 0277-6715
    Electronic ISSN: 1097-0258
    Topics: Mathematics , Medicine
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  • 52
    Publication Date: 2018-03-16
    Description: Randomized experiments are often complicated because of treatment noncompliance. This challenge prevents researchers from identifying the mediated portion of the intention-to-treated (ITT) effect, which is the effect of the assigned treatment that is attributed to a mediator. One solution suggests identifying the mediated ITT effect on the basis of the average causal mediation effect among compliers when there is a single mediator. However, considering the complex nature of the mediating mechanisms, it is natural to assume that there are multiple variables that mediate through the causal path. Motivated by an empirical analysis of a data set collected in a randomized interventional study, we develop a method to estimate the mediated portion of the ITT effect when both multiple dependent mediators and treatment noncompliance exist. This enables researchers to make an informed decision on how to strengthen the intervention effect by identifying relevant mediators despite treatment noncompliance. We propose a nonparametric estimation procedure and provide a sensitivity analysis for key assumptions. We conduct a Monte Carlo simulation study to assess the finite sample performance of the proposed approach. The proposed method is illustrated by an empirical analysis of JOBS II data, in which a job training intervention was used to prevent mental health deterioration among unemployed individuals.
    Print ISSN: 0277-6715
    Electronic ISSN: 1097-0258
    Topics: Mathematics , Medicine
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  • 53
    Publication Date: 2018-01-02
    Description: Myt1 and Myt1l (Myelin transcription factor 1, and Myt1-like) are members of a small family of closely related zinc finger transcription factors, characterized by two clusters of C2HC zinc fingers. Both are widely expressed during early embryogenesis, but are largely restricted to expression within the brain in the adult. Myt1l, as part of a three transcription factor mix, can reprogram fibroblasts to neurons and plays a role in maintaining neuronal identity. Previous analyses have indicated roles in both transcriptional activation and repression and suggested that Myt1 and Myt1l may have opposing functions in gene expression. We show that when targeted to DNA via multiple copies of the consensus Myt1/Myt1l binding site Myt1 represses transcription, whereas Myt1l activates. By targeting via a heterologous DNA binding domain we mapped an activation function in Myt1l to an amino-terminal region that is poorly conserved in Myt1. However, genome wide analyses of the effects of Myt1 and Myt1l expression in a glioblastoma cell line suggest that the two proteins have largely similar effects on endogenous gene expression. Transcriptional repression is likely mediated by binding to DNA via the known consensus site, whereas this site is not associated with the transcriptional start sites of genes with higher expression in the presence of Myt1 or Myt1l. This work suggests that these two proteins function similarly, despite differences observed in analyses based on synthetic reporter constructs. This article is protected by copyright. All rights reserved
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 54
    Publication Date: 2018-01-03
    Description: Vibrational circular dichroism (VCD) has become a standard method for determination of absolute stereochemistry, particularly now that reliable commercial instrumentation has become available. These instruments use a now well-documented Fourier transform infrared-based approach to measure VCD that has virtually displaced initial dispersive infrared-based designs. Nonetheless, many papers have appeared reporting dispersive VCD data, especially for biopolymers. Instrumentation designed with these original methods, particularly after more recent updates optimizing performance in selected spectral regions, has been shown still to have advantages for specific applications. This article presents a mini-review of dispersive VCD instrument designs and includes sample spectra obtained for various biopolymer (particularly peptide) samples. Complementary reviews of Fourier transform-VCD designs are broadly available.
    Print ISSN: 0899-0042
    Electronic ISSN: 1520-636X
    Topics: Chemistry and Pharmacology
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  • 55
    Publication Date: 2018-01-03
    Description: Precise quantification of extracellular glutamate concentrations upon neuronal activation is crucial for the understanding of brain function and neurological disorders. While optogenetics is an outstanding method for the correlation between distinct neurons and their role in circuitry and behavior, the electrochemically inactive nature of glutamate has proven challenging for recording upon optogenetic stimulations. This difficulty is due to the necessity for using enzyme-coated microelectrodes and the risk for light-induced artifacts. In this study, we establish a method for the combination of in vivo optogenetic stimulation with selective measurement of glutamate concentrations using enzyme-coated multielectrode arrays and amperometry. The glutamatergic subthalamic nucleus (STN), which is the main electrode target site in deep brain stimulation treatment of advanced Parkinson′s disease, has recently proven opotogenetically targetable in Pitx2-Cre-transgenic mice and was here used as model system. Upon stereotactic injection of viral Channelrhodopsin2-eYFP constructs into the STN, amperometric recordings were performed at a range of optogenetic stimulation frequencies in the globus pallidus, the main STN target area, in anaesthetized mice. Accurate quantification was enabled through a multi-step analysis approach based on self-referencing microelectrodes and repetition of the experimental protocol at two holding potentials, which allowed for the identification, isolation and removal of photoelectric and photoelectrochemical artifacts. This study advances the field of in vivo glutamate detection with combined optogenetics and amperometric recordings by providing a validated analysis framework for application in a wide variety of glutamate-based approaches in neuroscience. This article is protected by copyright. All rights reserved.
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
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  • 56
    Publication Date: 2018-01-04
    Description: The kinetic characteristics of microwave-assisted pyrolysis of biomass components were investigated in a self-designed microwave TGA using the KAS model and the master plot method. Compared with conventional pyrolysis, the initial decomposition temperatures of biomass components were reduced by 50-100°C and the fastest weight loss regions were shifted to lower temperatures. The average apparent activation energies of cellulose, hemicellulose and lignin were 47.82, 44.81 and 51.54 kJ/mol, respectively. Analysis with master plot method suggested the MAP of cellulose followed the 2-D diffusion reaction model, while hemicellulose and lignin could be interpreted by 3rd order-based and 3-D diffusion model. The change of dielectric properties was consistent with the weight loss behaviors of biomass components during the pyrolysis process. The increase of dielectric properties with temperature can lead to a thermal gradient and “hot spots” within biomass, which accelerated the pyrolysis process at low temperatures and reduced the apparent activation energy. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 57
    Publication Date: 2018-01-04
    Description: The challenging of this work is to present a thorough study of implementing heat transfer intensification in heat exchanger network (HEN) retrofitting, including all details of exchanger geometry, stream bypassing and splitting, temperature-variation of properties, LMTD and its correction, and pressure drops. This leads to very complex mixed integer nonlinear programming (MINLP) problems rarely reported before. By adopting the MILP-based iterative approach proposed in the earlier work (Pan et al. in 2013), temperature-variation of properties, LMTD and its correction are initialised to parameters at first, and the rest nonlinear terms are then linearized and expressed as first order Taylor series expansions. Finally, two iteration loops are executed to find optimal solutions. A small-scale motivating problem and an industrial scale problem are presented to demonstrate the validity and efficiency of the proposed methods. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 58
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    Wiley-Blackwell
    Publication Date: 2018-01-04
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 59
    Publication Date: 2018-01-04
    Description: The normal surface impacts of wet and dry agglomerates are simulated in a DEM framework. While the impact behavior of dry agglomerates has been addressed previously, similar studies on wet agglomerate impact are missing. We show that by adding a small amount of liquid the impact behavior changes significantly. The impact behavior of the agglomerates at different moisture contents and impact energies are analyzed through post-impact parameters and coupled to their microscopic and macroscopic properties. While increasing the impact energy breaks more inter-particle bonds and intensifies damage and fragmentation, increasing the moisture content is found to provide the agglomerates with higher deformability and resistance against breakage. It is shown that the interplay of the two latter parameters together with the agglomerate structural strength creates various impact scenarios, which are classified into different regimes and addressed with a regime map. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 60
    Publication Date: 2018-01-04
    Description: The transport phase of the animal-mediated plant dispersal process is critical to dispersal effectiveness as it determines the spatial distribution of the diaspores released and their chance for further recruitment. Assessing this specific phase of the dispersal process generally requires combining diaspore retention times with the associated distances covered. Here, we specifically tested the effect of grooming behavior, interindividual contacts and ungulate fur on diaspore retention times and associated dispersal distances for the hooked diaspores of Xanthium strumarium L. experimentally attached to tamed individuals of three ungulate species. We used a comparative approach based on differing fur quality on different body zones of these three ungulates. During 6-hr sessions, we monitored for grooming and social interactions that may induce intended or inadvertent diaspore detachment. Additionally, we proposed innovative approaches to directly assessing diaspore dispersal distances by red deer in situ. Fat-tailed functions fitted diaspore retention time, highlighting the potential for long-distance dispersal events. The longer the hair, the higher the retention capacity of diaspores in the animal's fur. As predicted, donkey retained diaspores longer than red deer and dwarf goat; and we also confirmed that diaspores attached to the short hair of the head fell off more quickly than did those on the other body zones. Dwarf goat groomed more often than both red deer and donkey, but also when it carried diaspores. Up to 14% of the diaspores detached from animal fur after specific grooming behavior. We observed, in controlled conditions, for the first time and for each ungulate species, interindividual transfers of diaspores, representing 5% of the diaspores attached to animals’ fur. Our results militate for incorporating animal behavior into plant dispersal modeling approaches. We present important methodological updates stressing the potential for long-distance animal-mediated diaspore dispersal events using short monitoring sessions and a trait-based cross-comparative approach. We highlight the interest of coupling diaspore fate monitoring with behavioral census. This helped us describing for the first time unsuspected diaspore transfers among conspecifics.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 61
    Publication Date: 2018-01-04
    Description: The interaction between HLA class II peptide complexes on antigen-presenting cells and CD4 + T cells is of fundamental importance for anti-cancer and anti-pathogen immunity as well as for the maintenance of immunological tolerance. To study CD4 + T cell reactivities, detailed knowledge of the presented peptides is necessary. In recent years, dramatic advances in the characterization of membranal and soluble HLA class I peptidomes could be observed. However, the same is not true for HLA class II peptidomes, where only few studies identify more than hundred peptides. Here we describe a mass spectrometry-based workflow for the characterization of membranal and soluble HLA class II DR and DQ peptidomes. Using this workflow, we identified a total of 8595 and 3727 HLA class II peptides from Maver-1 and DOHH2 cells, respectively. Based on this data, a motif-based binding predictor was developed and compared to NetMHCIIpan 3.1. We then applied the workflow to human plasma, resulting in the identification of between 34 and 152 HLA-DR and between 100 and 180 HLA-DQ peptides, respectively. Finally, we implemented a data-independent acquisition workflow to increase reproducibility and sensitivity of HLA class II peptidome characterizations. This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
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  • 62
    Publication Date: 2018-01-04
    Description: A challenge in developing personalized cancer immunotherapies is the prediction of putative cancer-specific antigens. Currently, predictive algorithms are used to infer binding of peptides to human leukocyte antigen (HLA) heterodimers to aid in the selection of putative epitope targets. One drawback of current epitope prediction algorithms is that they are trained on datasets containing biochemical HLA-peptide binding data that may not completely capture the rules associated with endogenous processing and presentation. The field of mass spectrometry has made great improvements in instrumentation speed and sensitivity, chromatographic resolution, and proteogenomic database search strategies to facilitate the identification of HLA-ligands from a variety of cell types and tumor tissues. As such, these advances have enabled mass spectrometry profiling of HLA-binding peptides to be a tractable, orthogonal approach to lower throughput biochemical assays for generating comprehensive datasets to train epitope prediction algorithms. In this review, we will highlight the progress made in the field of HLA-ligand profiling enabled by mass spectrometry and its impact on current and future epitope prediction strategies. This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
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  • 63
    Publication Date: 2018-01-04
    Description: Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance. Here, we report that Nestin loss triggers mitochondrial network remodeling and enhances oxidative phosphorylation (OXPHOS) in NSPCs treated with Nestin RNA interference (RNAi). Mitochondrial morphology is dynamically controlled by the balance between fission and fusion mediators; one of these mediators, the pro-fission factor, dynamin-related protein 1 (Drp1), shows decreased activation in Nestin-knockdown cells. Upstream, Drp1 phosphorylation is under control of the cytosolic cyclin-dependent kinase 5 (Cdk5). Inhibition of Cdk5 using RNAi or a chemical inhibitor (roscovitine) induces mitochondrial elongation and promotes mitochondrial respiration, indicating that Cdk5-dependent Drp1 phosphorylation participates in mitochondrial metabolism and NSPC stemness regulation. Strikingly, Nestin knockdown results in Cdk5 redistribution, with less remaining in the cytosol, leading to mitochondrial remodeling. We identify Nestin1-640 sequester Cdk5 in the cytosol and phosphorylate Drp1 subsequently. Together, our results show that a Nestin-Cdk5-Drp1 axis negatively regulates mitochondrial OXPHOS, which is indispensable for the maintenance of NSPC stemness. This article is protected by copyright. All rights reserved.
    Print ISSN: 1066-5099
    Electronic ISSN: 1549-4918
    Topics: Medicine
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  • 64
    Publication Date: 2018-01-05
    Description: Aims Cystic lesions derived from the synovial and ligamentous structures of the spine have varied histologic appearances. Not uncommonly, there is discrepancy between the clinico-radiologic diagnosis and histology. Therefore, we sought to characterize the histologic features of tissue submitted as “synovial cysts” of the spine. Methods Resected specimens of the spine labeled “synovial cysts” and “lumbar cysts” were histologically evaluated and classified based on histopathologic features. Results 75 histologic samples of spinal cysts were identified. 31 were classified as synovial cysts (definite synovial lining), 28 showed pseudocystic degeneration of the ligamentum flavum, 7 showed pseudocyst formation without evidence of synovial lining or degeneration of the ligamentum flavum, 8 showed cyst contents only or no histologic evidence of cyst wall for evaluation. Twenty-five cases (33%), especially those showing pseudocystic degeneration of the ligamentum flavum were associated with very characteristic tumor calcinosis-like calcium deposition with surrounding foreign-body giant cell reaction. Conclusion Histology of “synovial cysts” of the spine shows varied types of cysts; a large proportion are not synovial lined cysts but rather show pseudocystic degenerative changes of the ligamentum flavum often associated with very characteristic finely granular calcifications and foreign body giant cell reaction. This may have implications, not only in understanding the pathogenesis of these lesions, but also in their varied response to non-surgical interventions. This article is protected by copyright. All rights reserved.
    Print ISSN: 0309-0167
    Electronic ISSN: 1365-2559
    Topics: Medicine
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  • 65
    Publication Date: 2018-01-05
    Description: Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8 + T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for seven days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8 + T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8 + T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8 + T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L, and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8 + T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo . This article is protected by copyright. All rights reserved.
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
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  • 66
    Publication Date: 2018-01-05
    Description: Human DEAD-box RNA helicase gene DDX6 was cloned from B-cell lymphoma cell line RC-K8. Previously, we reported that DDX6 acts as oncogene in several cancers such as colorectal cancer and hepatocellular carcinoma. However, the detailed mechanism of DDX6 action in carcinogenesis is largely unknown. In this study, we examined the functions of DDX6 in clinical gastric cancer (GC) samples and GC cells. DDX6 protein expression levels of cancer samples were higher than those of the adjacent normal tissues in 25 clinical GC samples (median value: 1.4 times higher). Also, the results of an RNA immunoprecipitation-assay (RIP-assay) showed that DDX6 associated with c-Myc mRNA. Moreover, enforced overexpression of DDX6 promoted both mRNA and protein expression of c-Myc in GC cells. On the other hand, the gene silencing of DDX6 induced growth suppression through down-regulation of c-Myc in GC cells grown in either 2 or 3 dimensions. Furthermore, c-Myc mRNA expression levels of cancer samples were higher than those of the adjacent normal tissues in DDX6 up-regulated-GC clinical samples. Our findings in this study suggested that DDX6 acted as oncogene in GC cells through promotion of c-Myc expression by association with the mRNA of c-Myc. This article is protected by copyright. All rights reserved
    Print ISSN: 0899-1987
    Electronic ISSN: 1098-2744
    Topics: Medicine
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  • 67
    Publication Date: 2018-01-06
    Description: In the southwestern USA, recent large-scale die-offs of conifers raise the question of their resilience and mortality under droughts. To date, little is known about the interannual structural response to droughts. We hypothesized that piñon pines ( Pinus edulis ) respond to drought by reducing the drop of leaf water potential in branches from year to year through needle morphological adjustments. We tested our hypothesis using a 7-year experiment in central New Mexico with three watering treatments (irrigated, normal, and rain exclusion). We analyzed how variation in “evaporative structure” (needle length, stomatal diameter, stomatal density, stomatal conductance) responded to watering treatment and interannual climate variability. We further analyzed annual functional adjustments by comparing yearly addition of needle area (LA) with yearly addition of sapwood area (SA) and distance to tip ( d ), defining the yearly ratios SA:LA and SA:LA/ d . Needle length ( l ) increased with increasing winter and monsoon water supply, and showed more interannual variability when the soil was drier. Stomatal density increased with dryness, while stomatal diameter was reduced. As a result, anatomical maximal stomatal conductance was relatively invariant across treatments. SA:LA and SA:LA/ d showed significant differences across treatments and contrary to our expectation were lower with reduced water input. Within average precipitation ranges, the response of these ratios to soil moisture was similar across treatments. However, when extreme soil drought was combined with high VPD, needle length, SA:LA and SA:LA/ d became highly nonlinear, emphasizing the existence of a response threshold of combined high VPD and dry soil conditions. In new branch tissues, the response of annual functional ratios to water stress was immediate (same year) and does not attempt to reduce the drop of water potential. We suggest that unfavorable evaporative structural response to drought is compensated by dynamic stomatal control to maximize photosynthesis rates. The leaf and sapwood structures determine the design of the hydraulic system of a tree and affect the water exchanges between the plant and the atmosphere. We investigated the effect of drought on the yearly addition of sapwood area, leaf area, and elongation in branches, as well as their interannual variability. Using two functional ratios, we showed that during drought, new tissues added in branches do not support a reduction in the leaf water potential.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 68
    Publication Date: 2018-01-06
    Description: There are a number of ecogeographical “rules” that describe patterns of geographical variation among organisms. The island rule predicts that populations of larger mammals on islands evolve smaller mean body size than their mainland counterparts, whereas smaller-bodied mammals evolve larger size. Bergmann's rule predicts that populations of a species in colder climates (generally at higher latitudes) have larger mean body sizes than conspecifics in warmer climates (at lower latitudes). These two rules are rarely tested together and neither has been rigorously tested in treeshrews, a clade of small-bodied mammals in their own order (Scandentia) broadly distributed in mainland Southeast Asia and on islands throughout much of the Sunda Shelf. The common treeshrew, Tupaia glis , is an excellent candidate for study and was used to test these two rules simultaneously for the first time in treeshrews. This species is distributed on the Malay Peninsula and several offshore islands east, west, and south of the mainland. Using craniodental dimensions as a proxy for body size, we investigated how island size, distance from the mainland, and maximum sea depth between the mainland and the islands relate to body size of 13 insular T. glis populations while also controlling for latitude and correlation among variables. We found a strong negative effect of latitude on body size in the common treeshrew, indicating the inverse of Bergmann's rule. We did not detect any overall difference in body size between the island and mainland populations. However, there was an effect of island area and maximum sea depth on body size among island populations. Although there is a strong latitudinal effect on body size, neither Bergmann's rule nor the island rule applies to the common treeshrew. The results of our analyses demonstrate the necessity of assessing multiple variables simultaneously in studies of ecogeographical rules. Although there are latitudinal and island effects on body size, neither Bergmann's rule nor the island rule applies to the common treeshrew. The results of our analyses demonstrate the necessity of assessing multiple variables simultaneously in studies of ecogeographical rules.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 69
    Publication Date: 2018-01-06
    Print ISSN: 1527-6465
    Electronic ISSN: 1527-6473
    Topics: Medicine
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  • 70
    Publication Date: 2018-01-06
    Description: Abnormally high levels of the ‘oncometabolite’ 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field ( ≥ 7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér–Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) ( p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG ( p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma. Long-echo time (long-TE) magnetic resonance spectroscopy (MRS) has been proposed to be useful for the measurement of the biomarker 2-hydroxyglutarate (2-HG) in patients with glioma. In this study, a comparison using semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) at 3 T and 7 T reveals significantly improved 2-HG Cramér–Rao lower bounds (CRLBs) in patients with glioma, together with improvement in the pairwise fitting correlation with γ-aminobutyric acid (GABA) at 7 T. The superior spectral profile at 7 T allowed for the detection (CRLB 〈 20%) of 2-HG after two acquired transients compared with ~64 at 3 T.
    Print ISSN: 0952-3480
    Electronic ISSN: 1099-1492
    Topics: Medicine
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  • 71
    Publication Date: 2018-01-06
    Description: Background Selenium status is inversely associated with the incidence of prostate cancer. However, supplementation trials have not indicated a benefit of selenium supplementation in reducing cancer risk. Polymorphisms in the gene encoding selenoprotein 15 (SELENOF) are associated with cancer incidence/mortality and present disproportionately in African Americans. Relationships among the genotype of selenoproteins implicated in increased cancer risk, selenium status, and race with prostate cancer were investigated. Methods Tissue microarrays were used to assess SELENOF levels and cellular location in prostatic tissue. Sera and DNA from participants of the Chicago-based Adiposity Study Cohort were used to quantify selenium levels and genotype frequencies of the genes for SELENOF and the selenium-carrier protein selenoprotein P (SELENOP). Logistic regression models for dichotomous patient outcomes and regression models for continuous outcome were employed to identify both clinical, genetic, and biochemical characteristics that are associated with these outcomes. Results SELENOF is dramatically reduced in prostate cancer and lower in tumors derived from African American men as compared to tumors obtained from Caucasians. Differing frequency of SELENOF polymorphisms and lower selenium levels were observed in African Americans as compared to Caucasians. SELENOF genotypes were associated with higher histological tumor grade. A polymorphism in SELENOP was associated with recurrence and higher serum PSA. Conclusions These results indicate an interaction between selenium status and selenoprotein genotypes that may contribute to the disparity in prostate cancer incidence and outcome experienced by African Americans.
    Print ISSN: 0270-4137
    Electronic ISSN: 1097-0045
    Topics: Medicine
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  • 72
    Publication Date: 2018-01-07
    Description: The rheological behavior of micellar solutions is analyzed under non-homogeneous velocity and stress flow conditions. The framework is based on the extended irreversible thermodynamics and the transient network formulation coupled to the underlying kinetics embodying two relevant processes: formation of wormlike chains from a free micellar solution through a thermally activated process and their flow induced degradation. The second kinetic process consists in the formation of entanglements from the free wormlike chains and their flow-induced breakage. These processes are modeled in a coupled kinetic scheme constituted by a set of reversible kinetic equations describing the evolution in average of the three microstates (free short rod-like micelles, free wormlike chains and entangled wormlike chains) that reflect the complexity of macromolecular interactions. The predictions of the shear stress and first normal stress difference as a function of shear-rate under banded flow are in good agreement with experimental data. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 73
    Publication Date: 2018-01-07
    Description: Aim Blauvelt et al. (The Lancet 2017; 389: 2287-303) aimed to compare the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids (TCS) versus placebo with TCS in adults with moderate-to-severe atopic dermatitis (AD). Setting and design This multicentre randomised, double-blinded, placebo-controlled trial was conducted in hospitals, clinics and academic institutions across 161 sites in 14 countries. Study exposure Adults with moderate-to-severe AD were randomly assigned (3:1:3) to receive subcutaneous dupilumab 300mg once weekly (qw) plus TCS, dupilumab 300mg every 2 weeks (q2w) plus TCS, or placebo plus TCS until week-52. Primary outcome measures Co-primary efficacy endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-points or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week-16. Results 740 patients were included in the trial: 319 were randomly assigned to dupilumab qw, 106 to dupilumab q2w and 315 to the placebo arm. At week-16, more patients in the dupilumab groups achieved the co-primary endpoints: IGA 0/1 (39% [125 patients] qw dosing, 39% [41 patients] q2w dosing vs 12% [39 patients] receiving placebo; p〈0.0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p〈0.0001). Whilst no new safety signals were identified, adverse effects (AEs) were noted in 261 (83%) in those receiving dupilumab qw plus TCS, 97 (88%) dupilumab q2w plus TCS and 266 (84%) for placebo plus TCS. Rates of conjunctivitis, injection site reactions and local herpes simplex infections were higher in the dupilumab groups compared with placebo. Conclusions Blauvelt et al . concluded that dupilumab treatment added to TCS improved AD up to week-52 compared with TCS alone, and also demonstrated acceptable safety. This article is protected by copyright. All rights reserved.
    Print ISSN: 0007-0963
    Electronic ISSN: 1365-2133
    Topics: Medicine
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  • 74
    Publication Date: 2018-01-07
    Description: ABSTRACT Background : The CLLflow score was recently suggested as an improvement over the Moreau score for the diagnosis and classification of B-cell lymphoproliferative disorders (B-LPD). Methods : We determined the CLLflow score in peripheral blood or bone marrow of a series of cases with an inconclusive immunophenotype, including samples with a Moreau score of 3 (n=52) and CD5-positive with a score of 2 (n=38). As controls, B-LPD with a Moreau score of 0-1 (n=95), CD5-negative score 2 (n=24) and score 4-5 (i.e., chronic lymphocytic leukemia [CLL], n=166) were included. Results : The CLLflow score was positive (suggestive of CLL) in all CLL cases and negative in all Moreau score 〈2, regardless of CD200-positivity, which occurred in 31% (29/95) of cases. The CLLflow score was positive in 71%, 29% and 8% of samples with a Moreau score 3, CD5-positive score 2 and CD5-negative score 2, respectively. Discussion : Our results suggest that the CLLflow is useful in the differential diagnosis of cases with inconclusive immunophenotype. This article is protected by copyright. All rights reserved.
    Topics: Biology , Medicine
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  • 75
    Publication Date: 2018-01-07
    Description: ABSTRACT Background : Multiparametric flow cytometry (MFC) is a useful tool for diagnosis of plasma cell dyscrasias and assessment of minimal residual disease (MRD) in plasma cell myeloma (PCM). However, the immunophenotypic differences between the clonal plasma cells (PCs) of plasma cell myeloma (PCM) and those of monoclonal gammopathy of undetermined significance (MGUS) as well as the correlation of these flow cytometric markers with pertinent laboratory parameters have not been evaluated. Methods : We retrospectively identified all newly diagnosed treatment-naive PCM and MGUS patients between 09/2014 and 06/2015 who underwent 10-color flow-cytometric evaluation: CD45, CD38, CD138, cKappa, cLambda, CD19, CD27, CD28, CD56, CD117. FACSDiva analysis was utilized to identify antigenic aberrancies and associations with pertinent laboratory parameters were evaluated. Results : All cases demonstrated at least 2 aberrancies. There was a trend toward a greater number of aberrancies in PCM, with 68% showing 〉/= 4 aberrancies compared to 44% in MGUS (p=0.11). The only marker more frequently aberrant in one disease class was CD19, aberrant in 68% of PCM and 25% of MGUS (p〈0.01). In PCM, significant associations were found for CD56 non-aberrancy (p=0.05) and the presence of amyloid and CD27 aberrancy and normal serum albumin (p=0.05). In MGUS, CD117 expression was associated with normal hemoglobin (p=0.03). Conclusions : The plasma cells of PCM show a trend toward more antigenic aberrancy than those of MGUS. There is significant association between the antigenic profiles of PCM/MGUS and clinical parameters including amyloidosis, albumin level, and hemoglobin. This article is protected by copyright. All rights reserved.
    Topics: Biology , Medicine
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  • 76
    Publication Date: 2018-01-07
    Description: ABSTRACT Background: Quantification of regulatory T cells is crucial in immunomonitoring in clinical trials as this cell population has been shown to be involved in a wide range of diseases, including cancers, autoimmune diseases, infections and allergies. Human regulatory T cells are defined as CD4 + CD25 + CD127 low FoxP3 + cells, and the standardization of their staining by flow cytometry is a challenge, especially in multicenter clinical trials, notably because of the intracellular location of FoxP3. Method: A flow cytometry staining procedure was settled and standardized to measure human regulatory T cells in peripheral whole blood using pre-coated dried antibodies in ready-to-use tubes. It was compared to reference methods and implemented and validated to be suitable with different cytometer platforms. Results: The standardized protocol developed with dried antibodies and reduced volumes of whole blood allows an optimal identification of regulatory T cells. Compared to classical staining procedure, it reduces the number of steps required, in a very fast and simple technique. The accuracy of the method was confirmed by a multicenter comparison with different cytometer brands. Conclusion: Our results highlight the reliability of this high-standard protocol that could become a reference method for the monitoring of regulatory T cells in clinical trials. This article is protected by copyright. All rights reserved.
    Topics: Biology , Medicine
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  • 77
    Publication Date: 2018-01-07
    Description: Lung cancer is the leading cause of cancer-related death throughout the world and cisplatin chemoresistance is one of the major hindrances of efficiency in this malignancy therapy. It has been reported that miR-451, a tumor suppressor, is involved in sensitivity of cancer cells to cisplatin. However, the role of miR-451 in chemosensitivity of lung cancer cells and the underlying mechanism still remains to be not fully illuminated. We first assessed the expression of ERCC1 and miR-451 in six NSCLS cell lines and NHBE cells by qRT-PCR. Then ERCC1-low and ERCC1-high NSCLC cells were transfected with miR-451 mimic and mimic control. And cell viability, apoptotic cell rates, and migration activity was respectively measured by CCK-8 assay, flow cytometry, and wound healing assay. The expression of ERCC1, Wnt/β-catenin and PI3K/AKT pathway related factors were measured by western blot. The expression of miR-451 was higher in ERCC1-low NSCLC cells, while lower in ERCC1-high NSCLC cells. miR-451 overexpression inhibited the expression of ERCC1 in ERCC1-high NSCLC cells. Furthermore, miR-451 overexpression selectively enhanced cisplatin sensitivity in ERCC1-high NSCLC cells, as evidenced by reduction of cell viability with a dose manner. We further found that miR-451 overexpression significantly inhibited cell migration in ERCC1-high NSCLC cells. Interesting, Wnt/β-catenin and PI3K/AKT pathways were inhibited by miR-451 overexpression. This study demonstrates that miR-451 selectively promotes sensitivity to cisplatin in ERCC1-high NSCLC cells. This article is protected by copyright. All rights reserved
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Published by Wiley-Blackwell
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