bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma mortality: A retrospective cohort study consisting of 1783 patients
Authors: Zhang Shuisheng , Wang Chengfeng , Huang Huang , Jiang Qinglong , Zhao Dongbing , Tian Yantao , Ma Jie , Yuan Wei , Sun Yuemin , Che Xu , Zhang Jianwei , Chen Haibo , Zhao Yajie , Chu Yunmian , Zhang Yawei , Chen Yingtai 
Published: August 2017

AbstractThe effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma (PDAC) mortality are contradictory. Individuals who were diagnosed as PDAC and hospitalized at the China National Cancer Center between January 1999 and January 2016 were identified and included in the study. Ultimately, 1783 consecutive patients were included in the study. Patients were categorized as never, ex-drinkers/smokers or current drinkers/smokers. Hazard ratios (HRs) of all-cause mortality and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Compared with never drinkers, the HRs were 1.25 for ever drinkers, 1.24 for current drinkers, and 1.33 for ex-drinkers (trend P = 0.031). Heavy drinking and smoking period of 30 or more years were positive prognostic factors for PDAC. For different smoking and alcohol drinking status, only subjects who are both current smokers and current drinkers (HR, 1.45; 95% CI, 1.03–2.05) were associated with reduced survival after PDAC compared to those who were never smokers and never drinkers. Patients who are alcohol drinkers and long-term smokers before diagnosis have a significantly higher risk of PDAC mortality. Compared to those who neither smoker nor drink, only patients who both smokers and drinkers were associated with reduced survival from PDAC.
Detecting Photosymbiosis in Fossil Scleractinian Corals
Authors: Tornabene Chiara , Martindale Rowan C. , Wang Xingchen T. , Schaller Morgan F. 
Published: August 2017

AbstractThe evolutionary success of reef-building corals is often attributed to photosymbiosis, a mutualistic relationship scleractinian corals developed with zooxanthellae; however, because zooxanthellae are not fossilized, it is difficult (and contentious) to determine whether ancient corals harbored symbionts. In this study, we analyze the δ15N of skeletal organic matrix in a suite of modern and fossil scleractinian corals (zooxanthellate- and azooxanthellate-like) with varying levels of diagenetic alteration. Significantly, we report the first analyses that distinguish shallow-water zooxanthellate and deep-water azooxanthellate fossil corals. Early Miocene (18–20 Ma) corals exhibit the same nitrogen isotopic ratio offset identified in modern corals. These results suggest that the coral organic matrix δ15N proxy can successfully be used to detect photosymbiosis in the fossil record. This proxy will significantly improve our ability to effectively define the evolutionary relationship between photosymbiosis and reef-building through space and time. For example, Late Triassic corals have symbiotic values, which tie photosymbiosis to major coral reef expansion. Furthermore, the early Miocene corals from Indonesia have low δ15N values relative to modern corals, implying that the west Pacific was a nutrient-depleted environment and that oligotrophy may have facilitated the diversification of the reef builders in the Coral Triangle.
Methods for estimating disease transmission rates: Evaluating the precision of Poisson regression and two novel methods
Authors: Kirkeby Carsten , Halasa Tariq , Gussmann Maya , Toft Nils , Græsbøll Kaare 
Published: August 2017

AbstractPrecise estimates of disease transmission rates are critical for epidemiological simulation models. Most often these rates must be estimated from longitudinal field data, which are costly and time-consuming to conduct. Consequently, measures to reduce cost like increased sampling intervals or subsampling of the population are implemented. To assess the impact of such measures we implement two different SIS models to simulate disease transmission: A simple closed population model and a realistic dairy herd including population dynamics. We analyze the accuracy of different methods for estimating the transmission rate. We use data from the two simulation models and vary the sampling intervals and the size of the population sampled. We devise two new methods to determine transmission rate, and compare these to the frequently used Poisson regression method in both epidemic and endemic situations. For most tested scenarios these new methods perform similar or better than Poisson regression, especially in the case of long sampling intervals. We conclude that transmission rate estimates are easily biased, which is important to take into account when using these rates in simulation models.
The Value of Coastal Wetlands for Flood Damage Reduction in the Northeastern USA
Authors: Narayan Siddharth , Beck Michael W. , Wilson Paul , Thomas Christopher J. , Guerrero Alexandra , Shepard Christine C. , Reguero Borja G. , Franco Guillermo , Ingram Jane Carter , Trespalacios Dania 
Published: August 2017

AbstractAs exposure to coastal hazards increases there is growing interest in nature-based solutions for risk reduction. This study uses high-resolution flood and loss models to quantify the impacts of coastal wetlands in the northeastern USA on (i) regional flood damages by Hurricane Sandy and (ii) local annual flood losses in Barnegat Bay in Ocean County, New Jersey. Using an extensive database of property exposure, the regional study shows that wetlands avoided $625 Million in direct flood damages during Hurricane Sandy. The local study combines these models with a database of synthetic storms in Ocean County and estimates a 16% average reduction in annual flood losses by salt marshes with higher reductions at lower elevations. Together, the studies quantify the risk reduction ecosystem services of marsh wetlands. Measuring these benefits in collaboration with the risk modelling industry is crucial for assessing risk accurately and, where appropriate, aligning conservation and risk reduction goals.
Responses of renal hemodynamics and tubular functions to acute sodium–glucose cotransporter 2 inhibitor administration in non-diabetic anesthetized rats
Authors: Ansary Tuba M. , Fujisawa Yoshihide , Rahman Asadur , Nakano Daisuke , Hitomi Hirofumi , Kobara Hideki , Masaki Tsutomu , Titze Jens M. , Kitada Kento , Nishiyama Akira 
Published: August 2017

AbstractThe aim of this study is to examine the effects of acute administration of luseogliflozin, the sodium–glucose cotransporter 2 (SGLT2) inhibitor, on renal hemodynamics and tubular functions in anesthetized non-diabetic Sprague Dawley (SD) rats and 5/6 nephrectomized (Nx) SD rats. Renal blood flow (RBF), mean arterial pressure (MAP), and heart rate (HR) were continuously measured and urine was collected directly from the left ureter. Intraperitoneal injection of luseogliflozin (0.9 mg kg−1) did not change MAP, HR, RBF, or creatinine clearance (CrCl) in SD rats (n = 7). Luseogliflozin significantly increased urine volume, which was associated with significantly increased urinary glucose excretion rates (P < 0.001). Similarly, luseogliflozin significantly increased urinary sodium excretion (from 0.07 ± 0.01 µmol min−1 at baseline to 0.76 ± 0.08 µmol min−1 at 120 min; P < 0.001). Furthermore, luseogliflozin resulted in significantly increased urinary pH (P < 0.001) and decreased urinary osmolality and urea concentration (P < 0.001) in SD rats. Similarly, in Nx SD rats (n = 5–6), luseogliflozin significantly increased urine volume and urinary glucose excretion (P < 0.001) without altering MAP, HR, RBF, or CrCl. Luseogliflozin did not elicit any significant effects on the other urinary parameters in Nx SD rats. These data indicate that SGLT2 inhibitor elicits direct tubular effects in non-diabetic rats with normal renal functions.
Probing charge transfer between molecular semiconductors and graphene
Authors: Matković Aleksandar , Kratzer Markus , Kaufmann Benjamin , Vujin Jasna , Gajić Radoš , Teichert Christian 
Published: August 2017

AbstractThe unique density of states and exceptionally low electrical noise allow graphene-based field effect devices to be utilized as extremely sensitive potentiometers for probing charge transfer with adsorbed species. On the other hand, molecular level alignment at the interface with electrodes can strongly influence the performance of organic-based devices. For this reason, interfacial band engineering is crucial for potential applications of graphene/organic semiconductor heterostructures. Here, we demonstrate charge transfer between graphene and two molecular semiconductors, parahexaphenyl and buckminsterfullerene C60. Through in-situ measurements, we directly probe the charge transfer as the interfacial dipoles are formed. It is found that the adsorbed molecules do not affect electron scattering rates in graphene, indicating that charge transfer is the main mechanism governing the level alignment. From the amount of transferred charge and the molecular coverage of the grown films, the amount of charge transferred per adsorbed molecule is estimated, indicating very weak interaction.
Generation of a new infectious recombinant prion: a model to understand Gerstmann–Sträussler–Scheinker syndrome
Authors: Elezgarai Saioa R. , Fernández-Borges Natalia , Eraña Hasier , Sevillano Alejandro M. , Charco Jorge M. , Harrathi Chafik , Saá Paula , Gil David , Kong Qingzhong , Requena Jesús R. , Andréoletti Olivier , Castilla Joaquín 
Published: August 2017

AbstractHuman transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders that include Kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia. GSS is a genetically determined TSE caused by a range of mutations within the prion protein (PrP) gene. Several animal models, based on the expression of PrPs carrying mutations analogous to human heritable prion diseases, support that mutations might predispose PrP to spontaneously misfold. An adapted Protein Misfolding Cyclic Amplification methodology based on the use of human recombinant PrP (recPMCA) generated different self-propagating misfolded proteins spontaneously. These were characterized biochemically and structurally, and the one partially sharing some of the GSS PrPSc molecular features was inoculated into different animal models showing high infectivity. This constitutes an infectious recombinant prion which could be an invaluable model for understanding GSS. Moreover, this study proves the possibility to generate recombinant versions of other human prion diseases that could provide a further understanding on the molecular features of these devastating disorders.
Homogeneity evaluation of mesenchymal stem cells based on electrotaxis analysis
Authors: Kim Min Sung , Lee Mi Hee , Kwon Byeong-Ju , Kim Dohyun , Koo Min-Ah , Seon Gyeung Mi , Park Jong-Chul 
Published: August 2017

AbstractStem cell therapy that can restore function to damaged tissue, avoid host rejection and reduce inflammation throughout body without use of immunosuppressive drugs. The established methods were used to identify and to isolate specific stem cell markers by FACS or by immunomagnetic cell separation. The procedures for distinguishing population of stem cells took a time and needed many preparations. Here we suggest an electrotaxis analysis as a new method to evaluate the homogeneity of mesenchymal stem cells which can observe the stem cell population in culture condition and wide use to various types of stem cells. Human mesenchymal stem cell, adipose derived stem cell, tonsil derived stem cell and osteogenic differentiated cells migrated toward anode but the migration speed of differentiated cells was significantly decreased versus that of stem cells. In mixture of stem cells and differentiated cells condition, we identified that the ratio of stem cell versus differentiated cell was matched with the homogeneity evaluation data of stem cells based on electrotaxis analysis. As a result, our evaluation tool has the possibility of the wide use to stem cell homogeneity evaluation and might be used as the stem cell quality control during stem cell culture without any additional antibodies.
Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin β3 Signaling
Authors: Cai Zhihui , Dong Liangbo , Song Chengwei , Zhang Yanqing , Zhu Chenghui , Zhang Yibo , Ling Qinjie , Hoffmann Peter R. , Li Jun , Huang Zhi , Li Wei 
Published: August 2017

AbstractTargeting angiogenesis has emerged as a promising strategy for cancer treatment. Methylseleninic acid (MSA) is a metabolite of selenium (Se) in animal cells that exhibits anti-oxidative and anti-cancer activities at levels exceeding Se nutritional requirements. However, it remains unclear whether MSA exerts its effects on cancer prevention by influencing angiogenesis within Se nutritional levels. Herein, we demonstrate that MSA inhibited angiogenesis at 2 µM, which falls in the range of moderate Se nutritional status. We found that MSA treatments at 2 µM increased cell adherence, while inhibiting cell migration and tube formation of HUVECs in vitro. Moreover, MSA effectively inhibited the sprouts of mouse aortic rings and neoangiogenesis in chick embryo chorioallantoic membrane. We also found that MSA down-regulated integrin β3 at the levels of mRNA and protein, and disrupted clustering of integrin β3 on the cell surface. Additionally, results showed that MSA inhibited the phosphorylation of AKT, IκBα, and NFκB. Overall, our results suggest that exogenous MSA inhibited angiogenesis at nutritional Se levels not only by down-regulating the expression of integrin β3 but also by disorganizing the clustering of integrin β3, which further inhibited the phosphorylation involving AKT, IκBα, NFκB. These findings provide novel mechanistic insight into the function of MSA for regulating angiogenesis and suggest that MSA could be a potential candidate or adjuvant for anti-tumor therapy in clinical settings.
Regulation of HGF-induced hepatocyte proliferation by the small GTPase Arf6 through the PIP2-producing enzyme PIP5K1A
Authors: Tsai Meng-Tsz , Katagiri Naohiro , Ohbayashi Norihiko , Iwasaki Kenichi , Ohkohchi Nobuhiro , Ding Shih-Torng , Kanaho Yasunori , Funakoshi Yuji 
Published: August 2017

AbstractHGF and its receptor c-Met are critical molecules in various biological processes. Others and we have previously shown that the small GTPase Arf6 plays a pivotal role in HGF signaling in hepatocytes. However, the molecular mechanism of how Arf6 regulates HGF signaling is unclear. Here, we show that Arf6 plays an important role in HGF-stimulated hepatocyte proliferation and liver regeneration through the phosphatidylinositol 4,5-bisphosphate (PIP2)-producing enzyme PIP5K1A. We find that knockdown of Arf6 and PIP5K1A in HepG2 cells inhibits HGF-stimulated proliferation, Akt activation, and generation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and its precursor PIP2. Interestingly, PIP5K1A is recruited to c-Met upon HGF stimulation in an Arf6 activity-dependent manner. Finally, we show that hepatocyte proliferation and liver regeneration after partial hepatectomy are suppressed in Pip5k1a knockout mice. These results provide insight into the molecular mechanism for HGF-stimulated hepatocyte proliferation and liver regeneration: Arf6 recruits PIP5K1A to c-Met and activates it upon HGF stimulation to produce PIP2 and subsequently PIP3, which in turn activates Akt to promote hepatocyte proliferation, thereby accelerating liver regeneration after liver injury.
Inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface
Authors: Abrahams Katherine A. , Cox Jonathan A. G. , Fütterer Klaus , Rullas Joaquín , Ortega-Muro Fátima , Loman Nicholas J. , Moynihan Patrick J. , Pérez-Herrán Esther , Jiménez Elena , Esquivias Jorge , Barros David , Ballell Lluís , Alemparte Carlos , Besra Gurdyal S. 
Published: August 2017

AbstractDrug discovery efforts against the pathogen Mycobacterium tuberculosis (Mtb) have been advanced through phenotypic screens of extensive compound libraries. Such a screen revealed sulfolane 1 and indoline-5-sulfonamides 2 and 3 as potent inhibitors of mycobacterial growth. Optimization in the sulfolane series led to compound 4, which has proven activity in an in vivo murine model of Mtb infection. Here we identify the target and mode of inhibition of these compounds based on whole genome sequencing of spontaneous resistant mutants, which identified mutations locating to the essential α- and β-subunits of tryptophan synthase. Over-expression studies confirmed tryptophan synthase as the biological target. Biochemical techniques probed the mechanism of inhibition, revealing the mutant enzyme complex incurs a fitness cost but does not prevent inhibitor binding. Mapping of the resistance conferring mutations onto a low-resolution crystal structure of Mtb tryptophan synthase showed they locate to the interface between the α- and β-subunits. The discovery of anti-tubercular agents inhibiting tryptophan synthase highlights the therapeutic potential of this enzyme and draws attention to the prospect of other amino acid biosynthetic pathways as future Mtb drug targets.
Sost deficiency led to a greater cortical bone formation response to mechanical loading and altered gene expression
Authors: Pflanz David , Birkhold Annette I. , Albiol Laia , Thiele Tobias , Julien Catherine , Seliger Anne , Thomson Erin , Kramer Ina , Kneissel Michaela , Duda Georg N. , Kornak Uwe , Checa Sara , Willie Bettina M. 
Published: August 2017

AbstractBone adaptation optimizes mass and structure, but the mechano-response is already reduced at maturation. Downregulation of sclerostin was believed to be a mandatory step in mechano-adaptation, but in young mice it was shown that load-induced formation can occur independent of sclerostin, a product of the Sost gene. We hypothesized that the bone formation and resorption response to loading is not affected by Sost deficiency, but is age-specific. Our findings indicate that the anabolic response to in vivo tibial loading was reduced at maturation in Sost Knockout (KO) and littermate control (LC) mice. Age affected all anabolic and catabolic parameters and altered Sost and Wnt target gene expression. While load-induced cortical resorption was similar between genotypes, loading-induced gains in mineralizing surface was enhanced in Sost KO compared to LC mice. Loading led to a downregulation in expression of the Wnt inhibitor Dkk1. Expression of Dkk1 was greater in both control and loaded limbs of Sost KO compared to LC mice suggesting a compensatory role in the absence of Sost. These data suggest physical activity could enhance bone mass concurrently with sclerostin-neutralizing antibodies, but treatment strategies should consider the influence of age on ultimate load-induced bone mass gains.
Small RNA profiles from Panax notoginseng roots differing in sizes reveal correlation between miR156 abundances and root biomass levels
Authors: Zheng Yun , Chen Kun , Xu Zhenning , Liao Peiran , Zhang Xiaotuo , Liu Li , Wei Kangning , Liu Diqiu , Li Yong-Fang , Sunkar Ramanjulu , Cui Xiuming 
Published: August 2017

AbstractPlant genomes encode several classes of small regulatory RNAs (sRNAs) that play critical roles in both development and stress responses. Panax notoginseng (Burk.) F.H. Chen (P. notoginseng) is an important traditional Chinese herbal medicinal plant species for its haemostatic effects. Therefore, the root yield of P. notoginseng is a major economically important trait since the roots of P. notoginseng are the parts used to produce medicine. To identify sRNAs that are critical for the root biomass of P. notoginseng, we performed a comprehensive study of miRNA transcriptomes from P. notoginseng roots of different biomasses. We identified 675 conserved miRNAs, of which 180 pre-miRNAs are also identified, and three TAS3 loci in P. notoginseng. By using degradome sequencing, we identified 79 conserved miRNA:target or tasiRNA:target interactions, of which eight were further confirmed with the RLM 5′-RACE experiments. More importantly, our results revealed that a member of miR156 family and one of its SPL target genes have inverse expression levels, which is tightly correlated with greater root biomass contents. These results not only contributes to overall understanding of post-transcriptional gene regulation in roots of P. notoginseng but also could serve as markers for breeding P. notoginseng with greater root yield.
Perfused Three-dimensional Organotypic Culture of Human Cancer Cells for Therapeutic Evaluation
Authors: Wan Xiao , Ball Steven , Willenbrock Frances , Yeh Shaoyang , Vlahov Nikola , Koennig Delia , Green Marcus , Brown Graham , Jeyaretna Sanjeeva , Li Zhaohui , Cui Zhanfeng , Ye Hua , O’Neill Eric 
Published: August 2017

AbstractPharmaceutical research requires pre-clinical testing of new therapeutics using both in-vitro and in-vivo models. However, the species specificity of non-human in-vivo models and the inadequate recapitulation of physiological conditions in-vitro are intrinsic weaknesses. Here we show that perfusion is a vital factor for engineered human tissues to recapitulate key aspects of the tumour microenvironment. Organotypic culture and human tumour explants were allowed to grow long-term (14–35 days) and phenotypic features of perfused microtumours compared with those in the static culture. Differentiation status and therapeutic responses were significantly different under perfusion, indicating a distinct biological response of cultures grown under static conditions. Furthermore, heterogeneous co-culture of tumour and endothelial cells demonstrated selective cell-killing under therapeutic perfusion versus episodic delivery. We present a perfused 3D microtumour culture platform that sustains a more physiological tissue state and increased viability for long-term analyses. This system has the potential to tackle the disadvantages inherit of conventional pharmaceutical models and is suitable for precision medicine screening of tumour explants, particularly in hard-to-treat cancer types such as brain cancer which suffer from a lack of clinical samples.
Serum fibronectin distinguishes the early stages of hepatocellular carcinoma
Authors: Kim Hyunsoo , Park JiYoung , Kim Yongkang , Sohn Areum , Yeo Injun , Jong Yu Su , Yoon Jung-Hwan , Park Taesung , Kim Youngsoo 
Published: August 2017

AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, necessitating the discovery of serum markers for its early detection. In this study, a total of 180 serum samples from liver cirrhosis (LC), hepatocellular carcinoma (HCC) patients and paired samples of HCC patients who recovered (Recovery) were analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) to verify biomarkers. The three-fold crossvalidation was repeated 100 times in the training and test sets to evaluate statistical significance of 124 candidate proteins. This step resulted in 2 proteins that had an area under the receiver operating curve (AUROC) values ≥0.800 in the training (n = 90) and test sets (n = 90). Specifically, fibronectin (FN1, WCGTTQNYDADQK), distinguished HCC from LC patients, with an AUROC value of 0.926 by logistic regression. A FN1 protein was selected for validation in an independent sample (n = 60) using enzyme-linked immunosorbent assay (ELISA). The combination of alpha-fetoprotein (AFP) and FN1 improved the diagnostic performance and differentiated HCC patients with normal AFP levels. Our study has examined candidate markers for the benign disease state and malignancy and has followed up on the consequent recovery. Thus, improvement in the early detection of HCC by a 2-marker panel (AFP + FN1) might benefit HCC patients.