bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of unboiled water consumption data on sensitivity analysis in quantitative microbial risk assessment
Authors: Itoh Sadahiko , Zhou Liang 
Published: August 2018

AbstractQuantitative microbial risk assessment of drinking water is generally followed by sensitivity analysis for examining the relative importance of variables of the simulation model on the outcome. This study investigated the effect of the statistical methods applied to unboiled water consumption data on sensitivity analysis. The sensitivity analysis for concentration of Escherichia coli (E. coli) in treated water showed completely different results from the analysis for E. coli dose. This was due to the application of a Poisson model to the water consumption, which suggested that 27% of the people did not drink tap water. Our study then applied a different model—an exponential distribution—to the water consumption data. In addition, incidental water intake was assigned to non-consumers in the Poisson model. The results of sensitivity analyses for these cases were very different from the ones obtained from the first analysis. This study therefore demonstrated that the statistical methods used to analyze water consumption data have great impacts on sensitivity analysis, although they do not affect the yearly risk of infection. Specifically, statistical methods may devalue sensitivity analysis. To avoid this problem, it is preferable to apply a continuous model such as the exponential model, rather than a discrete one such as the Poisson model, to describe the variability in water consumption.
Racial differences in Urinary Bladder Cancer in the United States
Authors: Wang Yu , Chang Qian , Li Yang 
Published: August 2018

AbstractUrinary bladder cancer (UBC) has a high incidence rates in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. It exhibits a wide variety of histological types that goes from less aggressive to rapid-growing ones. In order to compare the different presentations, etiologies, and prognoses among racial groups, including NHW (non-Hispanic white), HW (Hispanic white), blacks, and API (Asian and Pacific Islander), we analyzed the UBC patients diagnosed between 1973 and 2014 using SEER (Surveillance, Epidemiology, and End Results) database. Patient characteristics, age-adjusted incidence rates, and survival were compared across races. There are significant racial differences in patients’ characteristics, including gender, marital status, age at diagnosis, treatment strategies, grade, stage, survival time, and so on. Overall, non-Hispanic whites have the highest incidence rate, followed by blacks, Hispanic whites, and APIs. In the analysis of survival, significant racial differences exist when stratified by gender, age group, histological type, stage, location and treatment strategies. Racial differences exist among UBC patients in the United States in terms of characteristics, incidence, and survival. Future studies may collect and analyze more data for comprehensive description and interpretation of the racial differences.
Mutant allele quantification reveals a genetic basis for TP53 mutation-driven castration resistance in prostate cancer cells
Authors: Lei Kefeng , Sun Ran , Chen Lee H. , Diplas Bill H. , Moure Casey J. , Wang Wenzhe , Hansen Landon J. , Tao Yulei , Chen Xufeng , Chen Chin-Pu Jason , Greer Paula K. , Zhao Fangping , Yan Hai , Bigner Darell D. , Huang Jiaoti , He Yiping 
Published: August 2018

AbstractThe concept that human cancer is in essence a genetic disease driven by gene mutations has been well established, yet its utilization in functional studies of cancer genes has not been fully explored. Here, we describe a simple genetics-based approach that can quickly and sensitively reveal the effect of the alteration of a gene of interest on the fate of its host cells within a heterogeneous population, essentially monitoring the genetic selection that is associated with and powers the tumorigenesis. Using this approach, we discovered that loss-of-function of TP53 can promote the development of resistance of castration in prostate cancer cells via both transiently potentiating androgen-independent cell growth and facilitating the occurrence of genome instability. The study thus reveals a novel genetic basis underlying the development of castration resistance in prostate cancer cells and provides a facile genetic approach for studying a cancer gene of interest in versatile experimental conditions.
Longitudinal characterization of nasopharyngeal colonization with Streptococcus pneumoniae in a South African birth cohort post 13-valent pneumococcal conjugate vaccine implementation
Authors: Dube Felix S. , Ramjith Jordache , Gardner-Lubbe Sugnet , Nduru Polite , Robberts F. J. Lourens , Wolter Nicole , Zar Heather J. , Nicol Mark P. 
Published: August 2018

AbstractMonitoring changes in pneumococcal carriage is key to understanding vaccination-induced shifts in the ecology of carriage and impact on health. We longitudinally investigated pneumococcal carriage dynamics in infants. Pneumococcal isolates were obtained from nasopharyngeal (NP) swabs collected 2-weekly from 137 infants enrolled from birth through their first year of life. Pneumococci were serotyped by sequetyping, confirmed by Quellung. Pneumococci were isolated from 54% (1809/3331) of infants. Median time to first acquisition was 63 days. Serotype-specific acquisition rates ranged from 0.01 to 0.88 events/child-year and did not differ between PCV13 and non-PCV13 serotypes (0.11 events/child-year [95% CI 0.07–0.18] vs. 0.11 events/child-year [95% CI 0.06–0.18]). There was no difference in carriage duration between individual PCV13 and non-PCV13 serotypes (40.6 days [95% CI 31.9–49.4] vs. 38.6 days [95% CI 35.1–42.1]), however cumulatively the duration of carriage of non-PCV13 serotypes was greater than PCV13 serotypes (141.2 days (95% CI 126.6–155.8) vs. 30.7 days (95% CI 22.3–39.0). Frequently carried PCV13 serotypes included 19F, 9V, 19A and 6A, while non-PCV13 serotypes included 15B/15C, 21, 10A, 16F, 35B, 9N and 15A. Despite high immunization coverage in our setting, PCV13 serotypes remain in circulation in this cohort, comprising 22% of isolates. Individual PCV13 serotypes were acquired, on average, at equivalent rate to non-PCV13 serotypes, and carried for a similar duration, although the most common non-PCV13 serotypes were more frequently acquired than PCV13 serotypes.
Unique resistance traits against downy mildew from the center of origin of grapevine (Vitis vinifera)
Authors: Toffolatti Silvia Laura , De Lorenzis Gabriella , Costa Alex , Maddalena Giuliana , Passera Alessandro , Bonza Maria Cristina , Pindo Massimo , Stefani Erika , Cestaro Alessandro , Casati Paola , Failla Osvaldo , Bianco Piero Attilio , Maghradze David , Quaglino Fabio 
Published: August 2018

AbstractThe Eurasian grapevine (Vitis vinifera), an Old World species now cultivated worldwide for high-quality wine production, is extremely susceptible to the agent of downy mildew, Plasmopara viticola. The cultivation of resistant V. vinifera varieties would be a sustainable way to reduce the damage caused by the pathogen and the impact of disease management, which involves the economic, health and environmental costs of frequent fungicide application. We report the finding of unique downy mildew resistance traits in a winemaking cultivar from the domestication center of V. vinifera, and characterize the expression of a range of genes associated with the resistance mechanism. Based on comparative experimental inoculations, confocal microscopy and transcriptomics analyses, our study shows that V. vinifera cv. Mgaloblishvili, native to Georgia (South Caucasus), exhibits unique resistance traits against P. viticola. Its defense response, leading to a limitation of P. viticola growth and sporulation, is determined by the overexpression of genes related to pathogen recognition, the ethylene signaling pathway, synthesis of antimicrobial compounds and enzymes, and the development of structural barriers. The unique resistant traits found in Mgaloblishvili highlight the presence of a rare defense system in V. vinifera against P. viticola which promises fresh opportunities for grapevine genetic improvement.
Gut microbiota composition and butyrate production in children affected by non-IgE-mediated cow’s milk allergy
Authors: Berni Canani Roberto , De Filippis Francesca , Nocerino Rita , Paparo Lorella , Di Scala Carmen , Cosenza Linda , Della Gatta Giusy , Calignano Antonio , De Caro Carmen , Laiola Manolo , Gilbert Jack A. , Ercolini Danilo 
Published: August 2018

AbstractCow’s milk allergy (CMA) is one of the earliest and most common food allergy and can be elicited by both IgE- or non-IgE-mediated mechanism. We previously described dysbiosis in children with IgE-mediated CMA and the effect of dietary treatment with extensively hydrolyzed casein formula (EHCF) alone or in combination with the probioticLactobacillus rhamnosusGG (LGG). On the contrary, the gut microbiota in non-IgE-mediated CMA remains uncharacterized. In this study we evaluated gut microbiota composition and fecal butyrate levels in children affected by non-IgE-mediated CMA. We found a gut microbiota dysbiosis in non-IgE-mediated CMA, driven by an enrichment ofBacteroidesandAlistipes. Comparing these results with those previously obtained in children with IgE-mediated CMA, we demonstrated overlapping signatures in the gut microbiota dysbiosis of non-IgE-mediated and IgE-mediated CMA children, characterized by a progressive increase inBacteroidesfrom healthy to IgE-mediated CMA patients. EHCF containg LGG was more strongly associated with an effect on dysbiosis and on butyrate production if compared to what observed in children treated with EHCF alone. If longitudinal cohort studies in children with CMA will confirm these results, gut microbiota dysbiosis could be a relevant target for innovative therapeutic strategies in children with non-IgE-mediated CMA.
Secreted products of oral bacteria and biofilms impede mineralization of apical papilla stem cells in TLR-, species-, and culture-dependent fashion
Authors: Petridis Xenos , van der Sluis Luc W. M. , Dijkstra René J. B. , Brinker Marja G. L. , van der Mei Henny C. , Harmsen Martin C. 
Published: August 2018

AbstractRegenerative endodontics exploits the mineralization potential of stem cells from the apical papilla (SCAPs) in order to promote root maturation of permanent immature teeth. SCAPs may encounter post-disinfection residual bacteria either in planktonic or in biofilm growth mode. Bacterial components bind to Toll-like receptors (TLRs) and trigger pro-inflammatory responses. We hypothesized that biofilm-triggered TLR activation affects the mineralization potential of human SCAPs. SCAPs were challenged with conditioned media derived from standardized dual-species biofilms and planktonic bacterial cultures and their inflammatory status and mineralization capacity were studied. Bacterial products from both growth modes (planktonic vs. biofilm) compromised cell viability, proliferation and mineralization capacity of SCAPs, but in a species- and growth mode-dependent fashion. While TLR4 expression remained unaffected, TLR2 expression was upregulated coinciding with a pro-inflammatory activation of SCAPs. Moreover, TLR and its downstream TGF-β-associated kinase (TAK1) appeared to be blocking mineralization, as inhibition of these factors restored it. In conclusion, bacterial products promoted the pro-inflammatory status and inhibited mineralization of human SCAPs in a TLR-, species-, and culture-dependent fashion. TLR2 emerged as the pivotal mediator of these responses and further research is warranted towards the judicious manipulation of SCAPs in order to modify the untoward events of TLR-priming and signaling.
The small heat shock protein HSPB1 protects mice from sepsis
Authors: Breed Elise R. , Hilliard Carolyn A. , Yoseph Benyam , Mittal Rohit , Liang Zhe , Chen Ching-Wen , Burd Eileen M. , Brewster Luke P. , Hansen Laura M. , Gleason Rudolph L. , Pandita Tej K. , Ford Mandy L. , Hunt Clayton R. , Coopersmith Craig M. 
Published: August 2018

AbstractIn vitro studies have implicated the small heat shock protein HSPB1 in a range of physiological functions. However, its in vivo relevance is unclear as the phenotype of unstressed HSPB1−/− mice is unremarkable. To determine the impact of HSPB1 in injury, HSPB1−/− and wild type (WT) mice were subjected to cecal ligation and puncture, a model of polymicrobial sepsis. Ten-day mortality was significantly higher in HSPB1−/− mice following the onset of sepsis (65% vs. 35%). Ex vivo mechanical testing revealed that common carotid arteries from HSPB1−/− mice were more compliant than those in WT mice over pressures of 50–120 mm Hg. Septic HSPB1−/− mice also had increased peritoneal levels of IFN-γ and decreased systemic levels of IL-6 and KC. There were no differences in frequency of either splenic CD4+ or CD8+ T cells, nor were there differences in apoptosis in either cell type. However, splenic CD4+ T cells and CD8+ T cells from HSPB1−/− mice produced significantly less TNF and IL-2 following ex vivo stimulation. Systemic and local bacterial burden was similar in HSPB1−/− and WT mice. Thus while HSPB1−/− mice are uncompromised under basal conditions, HSPB1 has a critical function in vivo in sepsis, potentially mediated through alterations in arterial compliance and the immune response.
Binding kinetics of cariprazine and aripiprazole at the dopamine D3 receptor
Authors: Frank Annika , Kiss Dóra J. , Keserű György M. , Stark Holger 
Published: August 2018

AbstractThe dissociation behaviours of aripiprazole and cariprazine at the human D2 and D3 receptor are evaluated. A potential correlation between kinetics and in vivo profiles, especially cariprazine’s action on negative symptoms in schizophrenia, is investigated. The binding kinetics of four ligands were indirectly evaluated. After the receptor preparations were pre-incubated with the unlabelled ligands, the dissociation was initiated with an excess of [3H]spiperone. Slow dissociation kinetics characterizes aripiprazole and cariprazine at the D2 receptor. At the D3 receptor, aripiprazole exhibits a slow monophasic dissociation, while cariprazine displays a rapid biphasic behaviour. Functional ß-arrestin assays and molecular dynamics simulations at the D3 receptor confirm a biphasic binding behaviour of cariprazine. This may influence its in vivo action, as the partial agonist could react rapidly to variations in the dopamine levels of schizophrenic patients and the ligand will not quantitatively dissociate from the receptor in one single step. With these findings novel agents may be developed that display rapid, biphasic dissociation from the D3R to further investigate this effect on in vivo profiles.
The intertwined metabolism during symbiotic nitrogen fixation elucidated by metabolic modelling
Authors: Pfau Thomas , Christian Nils , Masakapalli Shyam K. , Sweetlove Lee J. , Poolman Mark G. , Ebenhöh Oliver 
Published: August 2018

AbstractGenome-scale metabolic network models can be used for various analyses including the prediction of metabolic responses to changes in the environment. Legumes are well known for their rhizobial symbiosis that introduces nitrogen into the global nutrient cycle. Here, we describe a fully compartmentalised, mass and charge-balanced, genome-scale model of the clover Medicago truncatula, which has been adopted as a model organism for legumes. We employed flux balance analysis to demonstrate that the network is capable of producing biomass components in experimentally observed proportions, during day and night. By connecting the plant model to a model of its rhizobial symbiont, Sinorhizobium meliloti, we were able to investigate the effects of the symbiosis on metabolic fluxes and plant growth and could demonstrate how oxygen availability influences metabolic exchanges between plant and symbiont, thus elucidating potential benefits of inter organism amino acid cycling. We thus provide a modelling framework, in which the interlinked metabolism of plants and nodules can be studied from a theoretical perspective.
Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams
Authors: Labriet H. , Nemoz C. , Renier M. , Berkvens P. , Brochard T. , Cassagne R. , Elleaume H. , Estève F. , Verry C. , Balosso J. , Adam J. F. , Brun E. 
Published: August 2018

AbstractSince the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.
Characterization and treatment of landfill leachate membrane concentrate by Fe2+/NaClO combined with advanced oxidation processes
Authors: Qiao Meng , Zhao Xu , Wei Xiaoyun 
Published: August 2018

AbstractLandfill leachate membrane concentrate (LLMC) is a type of non-biodegradable wastewater intercepted by the membrane filtration of the landfill leachate membrane bioreactor (MBR) effluent. The concentrations of chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N) in the LLMC collected from a landfill in Beijing were determined to be 4700 mg/L and 487 mg/L, 2–5 times higher than those in the MBR effluent. The photoelectro oxidation (PEO) followed with the NaClO enhanced Fe2+ coagulation were more effective for the removal of COD than the Fenton oxidation followed with the enhanced coagulation. The final removal efficiencies of COD, UV254, NH4+-N and color degree were 86%, 95%, 93% and 95% with Fe2+ (90 mmol/L) and NaClO (60 mmol/L, Fe2+:NaClO = 1.5:1), and PEO for 3 hours with a current density of 400 A/m2. Due to the existence of Cl−, the chlorinated intermediates, which would be more toxic, were detected in the PEO treatment. However, the intermediates could be eliminated finally. As a result, the NaClO enhanced Fe2+ coagulation treatment combined with PEO treatment was efficient for the treatment of LLMC.
MicroRNA (miR) 125b regulates cell growth and invasion in pediatric low grade glioma
Authors: Yuan Ming , Da Silva Ana Cristina A. L. , Arnold Antje , Okeke Laurence , Ames Heather , Correa-Cerro Lina S. , Vizcaino M. Adelita , Ho Cheng-Ying , Eberhart Charles G. , Rodriguez Fausto J. 
Published: August 2018

AbstractMembers of the miR-125 family are strongly expressed in several tissues, particularly brain, but may be dysregulated in cancer including adult and pediatric glioma. In this study, miR-125 members were downregulated in pilocytic astrocytoma (PA) as a group compared to non-neoplastic brain in the Agilent platform. In the Nanostring platform, miR-125 members were downregulated primarily in pleomorphic xanthoastrocytomas and gangliogliomas. Using CISH for miR-125b, highest levels of expression were present in grade II tumors (11/33, 33% grade II tumors with 3+ expression compared to 3/70, 4% grade I tumors) (p < 0.001). When focusing on the two histologic subgroups with the largest number of samples, PA and diffuse astrocytoma (DA), the highest expression levels were present in DA, in comparison with the PA group (p = 0.01). Overexpression of miR-125b in pediatric low grade glioma (PLGG) derived cell lines (Res186, Res259, and BT66) resulted in decreased growth and invasion, as well as apoptosis. Additionally, miR-125b overexpression in BT66 resulted in senescence. These findings suggest that miR-125 is frequently underexpressed in PLGG, and overexpression results in a decrease in cell growth and induction of apoptosis, findings that deserve further investigation given its potential as a novel therapeutic strategy for PLGG.
Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts
Authors: Frimodt-Møller Jakob , Rossi Elio , Haagensen Janus Anders Juul , Falcone Marilena , Molin Søren , Johansen Helle Krogh 
Published: August 2018

AbstractIn 474 genome sequenced Pseudomonas aeruginosa isolates from 34 cystic fibrosis (CF) patients, 40% of these harbor mutations in the mexZ gene encoding a negative regulator of the MexXY-OprM efflux pump associated with aminoglycoside and fluoroquinolone resistance. Surprisingly, resistance to aminoglycosides and fluoroquinolones of mexZ mutants was far below the breakpoint of clinical resistance. However, the fitness increase of the mutant bacteria in presence of the relevant antibiotics, as demonstrated in competition experiments between mutant and ancestor bacteria, showed that 1) very small phenotypic changes cause significant fitness increase with severe adaptive consequences, and 2) standardized phenotypic tests fail to detect such low-level variations. The frequent appearance of P. aeruginosa mexZ mutants in CF patients is directly connected to the intense use of the target antibiotics, and low-level antibiotic resistance, if left unnoticed, can result in accumulation of additional genetic changes leading to high-level resistance.
A FTIR microspectroscopy study of the structural and biochemical perturbations induced by natively folded and aggregated transthyretin in HL-1 cardiomyocytes
Authors: Ami Diletta , Mereghetti Paolo , Leri Manuela , Giorgetti Sofia , Natalello Antonino , Doglia Silvia Maria , Stefani Massimo , Bucciantini Monica 
Published: August 2018

AbstractProtein misfolding and aggregation are associated with a number of human degenerative diseases. In spite of the enormous research efforts to develop effective strategies aimed at interfering with the pathogenic cascades induced by misfolded/aggregated peptides/proteins, the necessary detailed understanding of the molecular bases of amyloid formation and toxicity is still lacking. To this aim, approaches able to provide a global insight in amyloid-mediated physiological alterations are of importance. In this study, we exploited Fourier transform infrared microspectroscopy, supported by multivariate analysis, to investigatein situthe spectral changes occurring in cultured intact HL-1 cardiomyocytes exposed to wild type (WT) or mutant (L55P) transthyretin (TTR) in native, or amyloid conformation. The presence of extracellular deposits of amyloid aggregates of WT or L55P TTR, respectively, is a key hallmark of two pathological conditions, known as senile systemic amyloidosis and familial amyloid polyneuropathy. We found that the major effects, associated with modifications in lipid properties and in the cell metabolic/phosphorylation status, were observed when natively folded WT or L55P TTR was administered to the cells. The effects induced by aggregates of TTR were milder and in some cases displayed a different timing compared to those elicited by the natively folded protein.