bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques
Authors: O’Connor Megan A. , Tisoncik-Go Jennifer , Lewis Thomas B. , Miller Charlene J. , Bratt Debra , Moats Cassie R. , Edlefsen Paul T. , Smedley Jeremy , Klatt Nichole R. , Gale Michael , Fuller Deborah Heydenburg 
Published: August 2018

AbstractThe immunological and virological events that contribute to the establishment of Zika virus (ZIKV) infection in humans are unclear. Here, we show that robust cellular innate immune responses arising early in the blood and tissues in response to ZIKV infection are significantly stronger in males and correlate with increased viral persistence. In particular, early peripheral blood recruitment of plasmacytoid dendritic cells and higher production of monocyte chemoattractant protein (MCP-1) correspond with greater viral persistence and tissue dissemination. We also identify non-classical monocytes as primary in vivo targets of ZIKV infection in the blood and peripheral lymph node. These results demonstrate the potential differences in ZIKV pathogenesis between males and females and a key role for early cellular innate immune responses in the blood in viral dissemination and ZIKV pathogenesis.
Hydrophobic gating in BK channels
Authors: Jia Zhiguang , Yazdani Mahdieh , Zhang Guohui , Cui Jianmin , Chen Jianhan 
Published: August 2018

AbstractThe gating mechanism of transmembrane ion channels is crucial for understanding how these proteins control ion flow across membranes in various physiological processes. Big potassium (BK) channels are particularly interesting with large single-channel conductance and dual regulation by membrane voltage and intracellular Ca2+. Recent atomistic structures of BK channels failed to identify structural features that could physically block the ion flow in the closed state. Here, we show that gating of BK channels does not seem to require a physical gate. Instead, changes in the pore shape and surface hydrophobicity in the Ca2+-free state allow the channel to readily undergo hydrophobic dewetting transitions, giving rise to a large free energy barrier for K+ permeation. Importantly, the dry pore remains physically open and is readily accessible to quaternary ammonium channel blockers. The hydrophobic gating mechanism is also consistent with scanning mutagenesis studies showing that modulation of pore hydrophobicity is correlated with activation properties.
PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma
Authors: Liu Tianrun , Ma Wenjuan , Xu Haineng , Huang Menggui , Zhang Duo , He Zhenqiang , Zhang Lin , Brem Steven , O’Rourke Donald M. , Gong Yanqing , Mou Yonggao , Zhang Zhenfeng , Fan Yi 
Published: August 2018

AbstractAngiogenesis is a hallmark of cancer. However, most malignant solid tumors exhibit robust resistance to current anti-angiogenic therapies that primarily target VEGF pathways. Here we report that endothelial-mesenchymal transformation induces glioblastoma (GBM) resistance to anti-angiogenic therapy by downregulating VEGFR-2 expression in tumor-associated endothelial cells (ECs). We show that VEGFR-2 expression is markedly reduced in human and mouse GBM ECs. Transcriptome analysis verifies reduced VEGFR-2 expression in ECs under GBM conditions and shows increased mesenchymal gene expression in these cells. Furthermore, we identify a PDGF/NF-κB/Snail axis that induces mesenchymal transformation and reduces VEGFR-2 expression in ECs. Finally, dual inhibition of VEGFR and PDGFR eliminates tumor-associated ECs and improves animal survival in GBM-bearing mice. Notably, EC-specific knockout of PDGFR-β sensitizes tumors to VEGF-neutralizing treatment. These findings reveal an endothelial plasticity-mediated mechanism that controls anti-angiogenic therapy resistance, and suggest that vascular de-transformation may offer promising opportunities for anti-vascular therapy in cancer.
Transfer printing techniques for flexible and stretchable inorganic electronics
Authors: Linghu Changhong , Zhang Shun , Wang Chengjun , Song Jizhou 
Published: August 2018

AbstractTransfer printing is an emerging deterministic assembly technique for micro-fabrication and nano-fabrication, which enables the heterogeneous integration of classes of materials into desired functional layouts. It creates engineering opportunities in the area of flexible and stretchable inorganic electronics with equal performance to conventional wafer-based devices but the ability to be deformed like a rubber, where prefabricated inorganic semiconductor materials or devices on the donor wafer are required to be transfer-printed onto unconventional flexible substrates. This paper provides a brief review of recent advances on transfer printing techniques for flexible and stretchable inorganic electronics. The basic concept for each transfer printing technique is overviewed. The performances of these transfer printing techniques are summarized and compared followed by the discussions of perspectives and challenges for future developments and applications.
A quantitative analysis linking sea turtle mortality and plastic debris ingestion
Authors: Wilcox Chris , Puckridge Melody , Schuyler Qamar A , Townsend Kathy , Hardesty Britta Denise 
Published: August 2018

AbstractPlastic in the marine environment is a growing environmental issue. Sea turtles are at significant risk of ingesting plastic debris at all stages of their lifecycle with potentially lethal consequences. We tested the relationship between the amount of plastic a turtle has ingested and the likelihood of death, treating animals that died of known causes unrelated to plastic ingestion as a statistical control group. We utilized two datasets; one based on necropsies of 246 sea turtles and a second using 706 records extracted from a national strandings database. Animals dying of known causes unrelated to plastic ingestion had less plastic in their gut than those that died of either indeterminate causes or due to plastic ingestion directly (e.g. via gut impaction and perforation). We found a 50% probability of mortality once an animal had 14 pieces of plastic in its gut. Our results provide the critical link between recent estimates of plastic ingestion and the population effects of this environmental threat.
Physicochemical properties and toxic elements in bus stop dusts from Qingyang, NW China
Authors: Wu Yongfu , Lu Xinwei 
Published: August 2018

AbstractTo appraise the content and pollution level of cadmium (Cd), arsenic (As), mercury (Hg), nickel (Ni) and lead (Pb) in bus stop dusts, representative samples (n = 53) were collected from the city of Qingyang in Gansu province, NW China. The Cd, As, Hg, Ni, and Pb contents and physicochemical properties (particle size, organic matter, pH and magnetic properties) of the bus stop dusts were investigated. Pollution levels were evaluated by the Nemero synthesis pollution index (NSPI) and geoaccumulation index (Igeo). The results indicate that the magnetic susceptibilities of the bus stop dusts were higher than those in the local soils. Cd, As, Ni, and Pb contents ranged from 0.4 to 3.1, 7.1 to 16.3, 12.7 to 151.3, and 20.1 to 96.2 mg kg−1, with average values of 1.2, 10.1, 22.2, and 44.9 mg kg−1, while Hg content ranged from 4.5 to 1357.7 µg kg−1 with an average of 214.0 µg kg−1. The mean contents of Cd, As, Hg, Ni, and Pb were 12.0, 0.8, 10.0, 0.6, and 2.4 times the local soil background value, respectively. Cd, Hg and Pb in approximately 96%, 62% and 19% of the bus stop dusts were above the “moderately polluted” level in terms of Igeo. As and Ni were defined as “practically unpolluted” in all of the bus stop dusts. The NSPI values of all of the bus stop dust samples exceeded 3, which reveals overall serious contamination of harmful elements.
Readout-segmented echo-planar diffusion-weighted MR for the evaluation of aggressive characteristics of rectal cancer
Authors: Xia Chun-chao , Pu Jin , Zhang Jin-ge , Peng Wan-lin , Li Lei , Zhao Fei , Zhang Kai , Li Yu-ming , Liu Ke-ling , Meng Wen-jian , Deng Xiang-bing , Zhou Xiao-yue , Li Zhen-lin 
Published: August 2018

AbstractTo evaluate whether aggressive characteristics of rectal cancer can be predicted by the apparent diffusion coefficient (ADC) obtained using readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted magnetic resonance. We enrolled one hundred and fifteen patients. The image quality of ADC maps by rs-EPI was compared with that by traditional single-shot echo-planar imaging (ss-EPI), and ADC measurement was performed on the rs-EPI based ADC maps. Differences in ADC values of tumors grouped according to differentiation grade, clinical T stage and plasmatic carcinoembryonic antigen (CEA) level were tested. The correlation between each aggressive characteristic and the corresponding ADC values was evaluated. The image quality of ADC maps obtained by rs-EPI was superior toss-EPI (P < 0.05). The ADC values of tumor were categorized based on the following differentiation grades: poor (0.89 ± 0.12 × 10−3 mm2/s), moderate (1.13 ± 0.25 × 10−3 mm2/s), and good (1.31 ± 0.19 × 10−3 mm2/s); P < 0.001. Tumors with lower differentiation grades corresponded to lower ADC values (r = 0.59, P < 0.001). However, ADC differences were not observed in different clinical T stage (P = 0.22) and plasmatic CEA level (P = 0.38). Rs-EPI sequence-based ADC values represent a potential imaging marker for the aggressive rectal cancer characteristics.
Predicting changes to INa from missense mutations in human SCN5A
Authors: Clerx Michael , Heijman Jordi , Collins Pieter , Volders Paul G. A. 
Published: August 2018

AbstractMutations in SCN5A can alter the cardiac sodium current INa and increase the risk of potentially lethal conditions such as Brugada and long-QT syndromes. The relation between mutations and their clinical phenotypes is complex, and systems to predict clinical severity of unclassified SCN5A variants perform poorly. We investigated if instead we could predict changes to INa, leaving the link from INa to clinical phenotype for mechanistic simulation studies. An exhaustive list of nonsynonymous missense mutations and resulting changes to INa was compiled. We then applied machine-learning methods to this dataset, and found that changes to INa could be predicted with higher sensitivity and specificity than most existing predictors of clinical significance. The substituted residues’ location on the protein correlated with channel function and strongly contributed to predictions, while conservedness and physico-chemical properties did not. However, predictions were not sufficiently accurate to form a basis for mechanistic studies. These results show that changes to INa, the mechanism through which SCN5A mutations create cardiac risk, are already difficult to predict using purely in-silico methods. This partly explains the limited success of systems to predict clinical significance of SCN5A variants, and underscores the need for functional studies of INa in risk assessment.
From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
Authors: Plou J. , Juste-Lanas Y. , Olivares V. , del Amo C. , Borau C. , García-Aznar J. M. 
Published: August 2018

AbstractCancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-β regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-β in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-β induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-β activity.
An Adult Zebrafish Model Reveals that Mucormycosis Induces Apoptosis of Infected Macrophages
Authors: López-Muñoz Azucena , Nicolás Francisco E. , García-Moreno Diana , Pérez-Oliva Ana B. , Navarro-Mendoza María I. , Hernández-Oñate Miguel A. , Herrera-Estrella Alfredo , Torres-Martínez Santiago , Ruiz-Vázquez Rosa M. , Garre Victoriano , Mulero Victoriano 
Published: August 2018

AbstractMucormycosis is a life-threatening fungal infection caused by various ubiquitous filamentous fungi of the Mucorales order, althoughRhizopusspp. andMucorspp. are the most prevalent causal agents. The limited therapeutic options available together with a rapid progression of the infection and a difficult early diagnosis produce high mortality. Here, we developed an adult zebrafish model ofMucor circinelloidesinfection which allowed us to confirm the link between sporangiospore size and virulence. Transcriptomic studies revealed a local, strong inflammatory response of the host elicited after sporangiospore germination and mycelial tissue invasion, while avirulent and UV-killed sporangiospores failed to induce inflammation and were rapidly cleared. Of the 857 genes modulated by the infection, those encoding cytokines, complement factors, peptidoglycan recognition proteins, and iron acquisition are particularly interesting. Furthermore, neutrophils and macrophages were similarly recruited independently of sporangiospore virulence and viability, which results in a robust depletion of both cell types in the hematopoietic compartment. Strikingly, our model also reveals for the first time the ability of mucormycosis to induce the apoptosis of recruited macrophages but not neutrophils. The induction of macrophage apoptosis, therefore, might represent a key virulence mechanism of these fungal pathogens, providing novel targets for therapeutic intervention in this lethal infection.
Nucleation of superfluid-light domains in a quenched dynamics
Authors: Figueroa Joaquín , Rogan José , Valdivia Juan Alejandro , Kiwi Miguel , Romero Guillermo , Torres Felipe 
Published: August 2018

AbstractStrong correlation effects emerge from light-matter interactions in coupled resonator arrays, such as the Mott-insulator to superfluid phase transition of atom-photon excitations. We demonstrate that the quenched dynamics of a finite-sized complex array of coupled resonators induces a first-order like phase transition. The latter is accompanied by domain nucleation that can be used to manipulate the photonic transport properties of the simulated superfluid phase; this in turn leads to an empirical scaling law. This universal behavior emerges from the light-matter interaction and the topology of the array. The validity of our results over a wide range of complex architectures might lead to a promising device for use in scaled quantum simulations.
A healthy lifestyle attenuates the effect of polypharmacy on total and cardiovascular mortality: a national prospective cohort study
Authors: Martinez-Gomez David , Guallar-Castillon Pilar , Higueras-Fresnillo Sara , Banegas Jose R. , Sadarangani Kabir P. , Rodriguez-Artalejo Fernando 
Published: August 2018

AbstractThis work examines whether the increased all-cause and cardiovascular disease (CVD) mortality associated with polypharmacy could be offset by a healthy lifestyle. We included a prospective cohort of 3,925 individuals representative of the Spanish population aged ≥60 years, who were recruited in 2000–2001 and followed up through 2014. Polypharmacy was defined as treatment with ≥5 medications. The following lifestyle behaviors were considered healthy: not smoking, eating a healthy diet, being physically active, moderate alcohol consumption, low sitting time, and adequate sleep duration. Individuals were classified into three lifestyle categories s: unfavorable (0–2), intermediate (3–4) favorable (5–6). Over a median 13.8-y follow-up, 1,822 all-cause and 675 CVD deaths occurred. Among individuals with polypharmacy, intermediate and favorable lifestyles were associated with an all-cause mortality reduction (95% confidence interval [CI]) of 47% (34–58%) and 54% (37–66%), respectively; 37% (9–56%) and 60% (33–76%) for CVD death, respectively. The theoretical adjusted hazard ratio (95%CI) associated with replacing 1 medication with 1 healthy lifestyle behavior was 0.73 (0.66–0.81) for all-cause death and 0.69 (0.59–0.82) for CVD death. The theoretical adjusted hazard ratio (95%CI) for all-cause and CVD mortality associated with simply reducing 1 medication was 0.88 (0.83–0.94) and 0.83 (0.76–0.91), respectively. Hence, adherence to a healthy lifestyle behavior can reduce mortality risk associated with polypharmacy in older adults.
Unfavourable gender effect of high body mass index on brain metabolism and connectivity
Authors: Malpetti Maura , Sala Arianna , Vanoli Emilia Giovanna , Gianolli Luigi , Luzi Livio , Perani Daniela 
Published: August 2018

AbstractThe influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer’s Dementia (AD) (n = 206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (R = 0.269, p = 0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (p < 0.05 FDR-corrected, k = 100 voxels). This suggests a major vulnerability of neural systems known to be selectively involved in brain compensatory mechanisms in AD females. These findings indicate a strong gender effect of high BMI and obesity in AD, namely reducing the available reserve mechanisms in female patients. This brings to considerations for medical practice and health policy.
Tidal Records as Liquid Climate Archives for Large-Scale Interior Mediterranean Variability
Authors: Rubino Angelo , Zanchettin Davide , Androsov Alexey , Voltzinger Naum E. 
Published: August 2018

AbstractCharacterization of interior ocean variability is necessary for understanding climate. Water mass evolution shapes ocean-atmosphere interactions and contributes to determine timescales for global and regional climate variability. However, a robust assessment of past state and variability of the ocean interior is prevented by sparseness/shortness of historical subsurface observations and uncertainties affecting proxy-based reconstructions. Here, we propose a novel approach to infer past large-scale interior ocean variability with unprecedented accuracy and temporal resolution. It exploits links between stratification determined by “large-scale” water mass distributions and local dynamics. We characterize interannual interior ocean variability in the Mediterranean Sea in the early 20th century contained in tidal measurements in the Strait of Messina, and demonstrate the general applicability of our method, paving the way to a new approach to analyze historical oceanographic records: Regions where different water masses are known to collide can thus act as magnifying glasses for basin-scale interior ocean variability, hence providing “liquid archives” for climatology.
Identification of beagle food taking patterns and protocol for food effects evaluation on bioavailability
Authors: Zhang Guoqing , Wang Caifen , Wu Li , Xu Jian , Hu Xiaoxiao , Shakya Shailendra , He Yuanzhi , Ren Xiaohong , Chen Weidong , Zhang Jiwen 
Published: August 2018

AbstractFood is a known primary role to the exposure of the drugs orally administered. Since each animal may have unique food taking pattern and it is difficult to manipulate the food taking to animals, there lacks rationalized protocol for the food effects in pre-clinic study. The objective of this study was to identify the beagle food taking patterns and demonstrate their effects on bioavailability in valsartan. Herein, four types of food taking patterns of beagle were identified via inter-day and intra-day analysis, and named as Persisting, Pulsing, Postponing, Pushing (“4P Modes”), respectively, which were also validated by principal component analysis (PCA). Interestingly, food intake resulted in a reduced area under the concentration-time curve (AUC0–12h), maximum concentration (Cmax) and absorption rate, whilst the reduction varied in “4P Modes” of food taking. General considerations in the design of experiment for food effect to the bioavailability in beagles have been established as: to recognize the food taking patterns in each animal, to confirm the inter-day stability of the food taking behaviors, to trace the food taking patterns in parallel with plasma sampling. In conclusion, the right animals with proper food taking patterns should be assessed and selected for pre-clinic bioavailability evaluations.
Numerical and Experimental Investigation of the Hemodynamic Performance of Bifurcated Stent Grafts with Various Torsion Angles
Authors: Liu Ming , Sun Anqiang , Deng Xiaoyan 
Published: August 2018

AbstractThe “crossed limbs” strategy for bifurcated stent grafts (BSGs) is widely employed when abdominal aortic aneurysm (AAA) patients have unfavorable neck or highly splayed iliac arteries. Helical flow is regarded as a typical flow pattern within the human arterial system and is believed to have the positive physiological effects of inhibiting thrombosis formation and atherosclerosis. The “crossed limbs” strategy may induce helical flow and improve the stent graft outcome. To verify the performance of this strategy by considering hemodynamics, we constructed a series of idealized BSGs with various torsion angles and evaluated the hemodynamic performance, including the helical strength, time-averaged wall shear stress (TAWSS), oscillatory shear index, relative resident time (RRT), and displacement force. Our numerical results indicate that an increased torsion angle enhances the helicity strength at the iliac outlets. However, with increasing torsion angle, the TAWSS in the iliac graft decreases and the RRT increases. In addition, our numerical simulations and in vitro experiments reveal that the displacement force increases gradually with increasing torsion angle. In summary, the “crossed limbs” strategy may have benefits for AAA treatment in terms of helical flow, but because of the unfavorable hemodynamic performance verified by analyzing the hemodynamic indicators, the risk of stent graft migration increases with increasing torsion angle. Therefore, the “crossed limbs” strategy should be carefully employed in surgical AAA treatment.