bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating Founder Virus Information in Vaccine Field Trials
Authors: Follmann Dean , Huang Chiung-Yu 
Published: March 2015

SummaryVaccine clinical trials with active surveillance for infection often use the time to infection as the primary endpoint. A common method of analysis for such trials is to compare the times to infection between the vaccine and placebo groups using a Cox regression model. With new technology, we can sometimes additionally record the precise number of virions that cause infection rather than just the indicator that infection occurred. In this article, we develop a unified approach for vaccine trials that couples the time to infection with the number of infecting or founder viruses. We assume that the instantaneous risk of a potentially infectious exposure for individuals in the placebo and vaccine groups follows the same proportional intensity model. Following exposure, the number of founder viruses is assumed to be generated from some distribution on , which is allowed to be different for the two groups. Exposures that result in are unobservable. We denote the placebo and vaccine means of by and so that measures the proportion reduction in the mean number of infecting virions due to vaccination per exposure. We develop different semi-parametric methods of estimating . We allow the distribution of to be Poisson or unspecified, and discuss how to incorporate covariates that impact the time to exposure and/or . Interestingly , which is a ratio of untruncated means, can be reliably estimated using truncated data (), even if the placebo and vaccine distributions of are completely unspecified. Simulations of vaccine clinical trials show that the method can reliably recover in realistic settings. We apply our methods to an HIV vaccine trial conducted in injecting drug users.
Penalized regression for interval‐censored times of disease progression: Selection of HLA markers in psoriatic arthritis
Authors: Wu Ying , Cook Richard J. 
Published: March 2015

SummaryTimes of disease progression are interval‐censored when progression status is only known at a series of assessment times. This situation arises routinely in clinical trials and cohort studies when events of interest are only detectable upon imaging, based on blood tests, or upon careful clinical examination. We consider the problem of selecting important prognostic biomarkers from a large set of candidates when disease progression status is only known at irregularly spaced and individual‐specific assessment times. Penalized regression techniques (e.g., LASSO, adaptive LASSO, and SCAD) are adapted to handle interval‐censored time of disease progression. An expectation–maximization algorithm is described which is empirically shown to perform well. Application to the motivating study of the development of arthritis mutilans in patients with psoriatic arthritis is given and several important human leukocyte antigen (HLA) variables are identified for further investigation.
A Bayesian model for the identification of differentially expressed genes in Daphnia magna exposed to munition pollutants
Authors: Cassese Alberto , Guindani Michele , Antczak Philipp , Falciani Francesco , Vannucci Marina 
Published: March 2015

SummaryIn this article we propose a Bayesian hierarchical model for the identification of differentially expressed genes in Daphnia magna organisms exposed to chemical compounds, specifically munition pollutants in water. The model we propose constitutes one of the very first attempts at a rigorous modeling of the biological effects of water purification. We have data acquired from a purification system that comprises four consecutive purification stages, which we refer to as “ponds,” of progressively more contaminated water. We model the expected expression of a gene in a pond as the sum of the mean of the same gene in the previous pond plus a gene‐pond specific difference. We incorporate a variable selection mechanism for the identification of the differential expressions, with a prior distribution on the probability of a change that accounts for the available information on the concentration of chemical compounds present in the water. We carry out posterior inference via MCMC stochastic search techniques. In the application, we reduce the complexity of the data by grouping genes according to their functional characteristics, based on the KEGG pathway database. This also increases the biological interpretability of the results. Our model successfully identifies a number of pathways that show differential expression between consecutive purification stages. We also find that changes in the transcriptional response are more strongly associated to the presence of certain compounds, with the remaining contributing to a lesser extent. We discuss the sensitivity of these results to the model parameters that measure the influence of the prior information on the posterior inference.
Pharmacological profile of novel psychoactive benzofurans
Authors: Rickli Anna , Kopf Simone , Hoener Marius C , Liechti Matthias E 
Published: March 2015

Background and PurposeBenzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro.Experimental ApproachWe assessed the effects of the benzofurans 5‐APB, 5‐APDB, 6‐APB, 6‐APDB, 4‐APB, 7‐APB, 5‐EAPB and 5‐MAPDB and benzodifuran 2C‐B‐FLY on the human noradrenaline (NA), dopamine and 5‐HT uptake transporters using HEK 293 cells that express the respective transporters. We also investigated the release of NA, dopamine and 5‐HT from monoamine‐preloaded cells, monoamine receptor‐binding affinity and 5‐HT2A and 5‐HT2B receptor activation.Key ResultsAll of the benzofurans inhibited NA and 5‐HT uptake more than dopamine uptake, similar to methylenedioxymethamphetamine (MDMA) and unlike methamphetamine. All of the benzofurans also released monoamines and interacted with trace amine‐associated receptor 1 (TA1 receptor), similar to classic amphetamines. Most benzofurans were partial 5‐HT2A receptor agonists similar to MDMA, but also 5‐HT2B receptor agonists, unlike MDMA and methamphetamine. The benzodifuran 2C‐B‐FLY very potently interacted with 5‐HT2 receptors and also bound to TA1 receptors.Conclusions and ImplicationsDespite very similar structures, differences were found in the pharmacological profiles of different benzofurans and compared with their amphetamine analogues. Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA. The benzofurans also interacted with 5‐HT receptors. This pharmacological profile probably results in MDMA‐like entactogenic psychoactive properties. However, benzofurans induce 5‐HT2B receptor activation associated with heart valve fibrosis. The pharmacology of 2C‐B‐FLY indicates predominant hallucinogenic properties and a risk for vasoconstriction.
Patterns and drivers of intraspecific variation in avian life history along elevational gradients: a meta‐analysis
Authors: Alice Boyle W. , Sandercock Brett K. , Martin Kathy 
Published: March 2015

ABSTRACTElevational gradients provide powerful natural systems for testing hypotheses regarding the role of environmental variation in the evolution of life‐history strategies. Case studies have revealed shifts towards slower life histories in organisms living at high elevations yet no synthetic analyses exist of elevational variation in life‐history traits for major vertebrate clades. We examined (i) how life‐history traits change with elevation in paired populations of bird species worldwide, and (ii) which biotic and abiotic factors drive elevational shifts in life history. Using three analytical methods, we found that fecundity declined at higher elevations due to smaller clutches and fewer reproductive attempts per year. By contrast, elevational differences in traits associated with parental investment or survival varied among studies. High‐elevation populations had shorter and later breeding seasons, but longer developmental periods implying that temporal constraints contribute to reduced fecundity. Analyses of clutch size data, the trait for which we had the largest number of population comparisons, indicated no evidence that phylogenetic history constrained species‐level plasticity in trait variation associated with elevational gradients. The magnitude of elevational shifts in life‐history traits were largely unrelated to geographic (altitude, latitude), intrinsic (body mass, migratory status), or habitat covariates. Meta‐population structure, methodological issues associated with estimating survival, or processes shaping range boundaries could potentially explain the nature of elevational shifts in life‐history traits evident in this data set. We identify a new risk factor for montane populations in changing climates: low fecundity will result in lower reproductive potential to recover from perturbations, especially as fewer than half of the species experienced higher survival at higher elevations.
Belowground infections of the invasive Phytophthora plurivora pathogen enhance the suitability of red oak leaves to the generalist herbivore Lymantria dispar
Authors: MILANOVIĆ SLOBODAN , LAZAREVIĆ JELICA , KARADŽIĆ DRAGAN , MILENKOVIĆ IVAN , JANKOVSKÝ LIBOR , VULETA ANA , SOLLA ALEJANDRO 
Published: March 2015

1. Globally, vast areas of forest are currently threatened by Lymantria dispar L. and Phytophthora species, which cause widespread declines and cascading ecological impacts. One important aim of evolutionary and ecological studies is to understand their interactions.2. The present study tests whether Quercus rubra L. trees naturally infected with P. plurivora T. Jung & T.I. Burgess or free of infection are more suitable for L. dispar herbivory, and if relationships between L. dispar performance and herbivory may vary depending on whether trees are infected or free of infection.3. In choice tests, the consumed area of leaves from trees infected by P. plurivora was four times larger than that from non‐infected trees, probably because the increased values of N, soluble protein, and water content observed in the leaves of infected trees enhanced acceptability. Although larval performance was better in Phytophthora‐infected trees, relationships between larval performance and defoliation did not significantly interact with the health status of trees.4. The present results suggest that the impact of P. plurivora on natural and managed ecosystems may generate a positive feedback loop for oak decline. The link between the behavioural and physiological responses of L. dispar to infected trees and the population growth in nature deserves further investigation.
Strategy and Action: Assessing Student‐Led Culture Workshops Within the Professions
Authors: King de Ramírez Carmen 
Published: March 2015

AbstractIn order to prepare students to successfully engage with native speakers and members of heritage language communities both at home and abroad, educators must develop course curricula that emphasize cultural practices, products, perspectives, and comparisons as well as provide students with opportunities to directly apply the skills that they have acquired in the classroom across a range of other settings. This article describes a Culture for the Professions course whose curriculum was based on the four steps of the cultural intelligence model (Earley & Ang, 2003): drive, knowledge, strategy, and action. The study focuses in particular on how students implemented the last two components of the model (strategy and action) by collaborating with local organizations to design and present culture workshops that were specifically tailored to each organization's needs and mission. In addition to benefiting the organizations themselves, data obtained from evaluation rubrics and postworkshop reflections suggest that community culture workshops allow students to become more aware of how culture influences the work of an organization and to develop strategies to bridge cultural differences in the workplace.
Fluid inclusion and isotopic constraints on the origin of ore‐forming fluid of the Jinman–Liancheng vein Cu deposit in the Lanping Basin, western Yunnan, China
Authors: Song Y. , Hou Z. , Cheng Y. , Yang T. , Xue C. 
Published: March 2015

AbstractExtensive quartz–carbonate–Cu sulfide veins occur in clastic rocks and are spatially related to Paleocene granites in the western border of the Lanping Basin, western Yunnan, China. Abundant aqueous‐carbonic fluid inclusions occur in these veins but their origin is debated. In the Jinman–Liancheng deposit, individual primary inclusion groups contain either exclusively liquid‐rich inclusions (Gl), or coexisting liquid‐rich and vapor‐rich inclusions (Glv). Microthermometry and estimate of CO2 content indicate that type Gl inclusions either have homogenization temperatures (Th) 238–263°C and contain c. 3.9–5.5 mole % CO2, or have Th 178–222°C and contain c. 1.6–3.2 mole % CO2. Type Glv inclusions are thought to represent samples of fluid unmixing that occurred at 183–218°C. At that time, the liquid phase in the unmixing fluid may contain c. 2.0–3.3 mole % CO2. As such, the correlation of CO2 content with Th for type Gl inclusions is thought to be caused by fluid unmixing with decreasing temperature and subsequent CO2 escape. δ18O and δD values of the parent water mainly fall in the field below that of primary magmatic water, indicative of fluid derivation from degassed (in open system) magmatic water, with no contributions from basinal or meteoric water. Initial Sr isotopic compositions of hydrothermal carbonates suggest that the fluid was magmatic, probably derived from the Paleogene granites. δ13CPDB values (−4‰ to −7‰) of the hydrothermal carbonates and δ34SV‐CDT values of sulfides (mainly −11‰ to +5‰) indicate that the carbon and sulfur can be derived from (degassed) magma and/or nonmagmatic sources. The CO2‐rich and magmatic‐water‐derived fluid at Jinman–Liancheng differs from the CO2‐poor and basinally derived fluid in sediment‐hosted stratiform Cu (SSC) deposits, which suggests that there are no genetic linkages between the vein Cu and SSC deposits in the Lanping Basin.
Can size 20, .04 taper rotary files reproducibly create a glide path for the self‐adjusting file? An ex vivo study in MB canals of mandibular molars
Authors: Kfir A. , Goldberger T. , Koren T. , Pawar A. M. , Abramovitz I. 
Published: March 2015

AbstractAimTo test and compare the effectiveness and safety of two size 20, .04 taper rotary files that were used to create a glide path for the self‐adjusting file (SAF) in curved canals of mandibular molars.MethodologyForty mandibular molars with curved mesial roots and narrow MB root canals were selected based on a passage of size 15 K‐files to WL; size 20 K‐files could not reach WL. Only roots with no visible microcracks were included. Two types of size 20 rotary files were used for glide path preparation, the new Pre‐SAF size 20, .04 taper file and the ProFile size 20, .04 taper, which served as the reference and control. Both files were used with 3–4 pecking strokes, which brought them to WL. Two parameters were tested whether the glide path allowed manual insertion of a 1.5‐mm SAF file to WL and whether the procedure caused microcracks in the root dentine. Paired t‐tests were used to compare the groups.ResultsGlide path preparation with both files allowed the manual insertion of the SAF file to WL in all 20 root canals, with no difference between the two groups. No cracks were detected after the procedure in any of the roots in either group.ConclusionsBoth types of size 20, .04 taper rotary files were effective for glide path preparation for the SAF file in curved canals. Neither file type caused microcracks in root dentine.
Changing an unfavorable employer reputation: the roles of recruitment message‐type and familiarity with employer
Authors: Kanar Adam M. , Collins Christopher J. , Bell Bradford S. 
Published: March 2015

AbstractAn unfavorable employer reputation can impair an organization's ability to recruit job seekers. The present research used a 4 week longitudinal experimental design to investigate whether recruitment messages can positively change an existing unfavorable employer reputation. Two hundred and twenty‐two job seekers rated their perceptions of an organization before and after being randomly assigned to receive a series of high‐ or low‐information recruitment messages. As expected, job seekers receiving high‐information messages changed their perceptions more than job seekers who were exposed to low‐information messages. In addition, job seekers' initial familiarity with the employer was negatively related to change in their perceptions of employer reputation. Finally, there was some evidence that job seekers' familiarity with the employer influenced the impact of different recruitment messages. Implications for research and practice are discussed.
Effects of Different Classes of Antihypertensive Agents on the Outcome of Acute Ischemic Stroke
Authors: Tziomalos Konstantinos , Giampatzis Vasilios , Bouziana Stella D. , Spanou Marianna , Papadopoulou Maria , Kazantzidou Pavlina , Kostaki Stavroula , Kouparanis Antonios , Savopoulos Christos , Hatzitolios Apostolos I. 
Published: March 2015

It is unclear whether antihypertensive treatment before stroke affects acute ischemic stroke severity and outcome. To evaluate this association, the authors studied 482 consecutive patients (age 78.8±6.7 years) admitted with acute ischemic stroke. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). The outcome was assessed with rates of adverse outcome (modified Rankin scale at discharge ≥2). Independent predictors of severe stroke (NIHSS ≥16) were female sex and atrial fibrillation. Treatment with diuretics before stroke was associated with nonsevere stroke. At discharge, patients with adverse outcome were less likely to be treated before stroke with β‐blockers or with diuretics. Independent predictors of adverse outcome were older age, higher NIHSS at admission, and history of ischemic stroke. Treatment with diuretics before stroke appears to be associated with less severe neurologic deficit in patients with acute ischemic stroke.
Fluorescence Intensity of Composite Layering Combined with Surface Sealant Submitted to Staining Solutions
Authors: Catelan Anderson , Guedes Ana Paula Albuquerque , Suzuki Thaís Yumi Umeda , Takahashi Marcos Kenzo , de Souza Evelise Machado , Briso André Luiz Fraga , dos Santos Paulo Henrique 
Published: March 2015

AbstractPurposeThe aim of this study was to evaluate the fluorescence intensity of a composite in different layering techniques combined to a surface sealant submitted to staining solutions.Methods and MaterialsOne surface sealant and one composite resin (shades A2‐0, A2, and YE) were tested. Specimens were carried out using layering with different shades of composite, and dental blocks (dentin/enamel) were obtained of human molars. Fluorescence intensity measurement performed using a spectrofluorophotometer, before and after storage in cola, orange juice, red wine, and distilled water. Data were subjected to analysis of variance and Fisher's test (α = 0.05).ResultsInitially, only A2‐O + A2 layering showed fluorescence intensity statistically similar to the natural tooth. Overall, groups sealed showed the highest fluorescence intensity compared with unsealed groups. The aging decreased the fluorescence intensity compared with initial values. Red wine showed the highest decrease on the fluorescence intensity.ConclusionThe fluorescence of composite restorations is dependent of the layering technique and is affected by the diet.Clinical SignificanceThe staining solutions decreased the fluorescence intensity, even when the composite resins were sealed. Different shades of the same composite showed distinct fluorescence values, so there should be greater standardization of this property for tooth reconstruction success by the layering technique with large tissue loss.
Macrophage activation marker soluble CD163 and non‐alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery
Authors: Kazankov Konstantin , Tordjman Joan , Møller Holger Jon , Vilstrup Hendrik , Poitou Christine , Bedossa Pierre , Bouillot Jean‐Luc , Clement Karine , Grønbæk Henning 
Published: March 2015

AbstractBackground and AimsMacrophages play an important role in non‐alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS).MethodsDemographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme‐linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real‐time quantitative polymerase chain reaction for CD163 mRNA were performed.ResultssCD163 was higher in patients with NAS ≥ 5 compared with those with NAS < 5 (2.4(2.0–3.1) vs 1.9(1.5–2.3) mg/L, P < 0.001) and in patients with bridging fibrosis (F ≥ 3) compared with lower fibrosis stages (2.6(2.0–4.9) vs 2.0(1.5–2.4) mg/L, P = 0.001). Preoperative sCD163 was independently associated with both the NAS (P = 0.002) and the fibrosis score (P = 0.024). sCD163 decreased after BS and was greatly reduced after 12 months, more rapidly so in patients with NAS ≥ 5 (P < 0.001) and non‐alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P = 0.03). Immunohistochemistry showed CD163‐positive macrophages aligning fat‐laden hepatocytes and forming microgranulomas in patients with NASH. CD163 mRNA expression did not vary with NAS.ConclusionsCD163 increased in parallel with the severity of NAFLD in morbid obesity, indicating macrophage activation. BS reduced sCD163 even in patients with severe liver injury and fibrosis, suggesting full reversibility of macrophage activation associated with improved insulin sensitivity.
Impact of epidermal growth factor receptor protein and gene alteration on Taiwanese hepatocellular carcinomas
Authors: Su Yu‐Hung , Ng Kwai‐Fong , Yu Ming‐Chin , Wu Ting‐Jung , Yeh Ta‐Sen , Lee Wei‐Chen , Lin Yong‐Shiang , Hsieh Tsung‐Han , Lin Chun‐Yen , Yeh Chau‐Ting , Chen Tse‐Ching 
Published: March 2015

AbstractBackground and AimEpidermal growth factor receptor (EGFR) overexpression is associated with disease progression and poor survival in a variety of solid tumors. The role of EGFR in hepatocellular carcinoma (HCC) remains controversial.MethodsOne hundred thirty‐eight HCCs were analyzed for total EGFR (t‐EGFR) and phospho‐EGFR (p‐EGFR) expression and gene amplification using immunohistochemistry and fluorescence in situ hybridization. The role of EGFR was analyzed in relation to the clinicopathological features.ResultsWeak to strong p‐EGFR immunostaining was noted in 42 of the 138 HCCs. p‐EGFR expression correlated with alcoholism (P = 0.03) and chronic hepatitis B infection (P = 0.041). There was no correlation between t‐EGFR expression and any of the clinicopathological features. Amplification of the EGFR gene was not identified in the 138 HCCs, but 39.1% of the HCCs showed balanced polysomy of both the EGFR gene and centromere 7. Moreover, 65 tumors showed > 2.2 copies per tumor cell. EGFR copy number gain (CNG) was significantly correlated with gender (P = 0.0491), tumor grade (P = 0.006), and vascular invasion (P = 0.005). HCCs with EGFR CNG also had a poor recurrence‐free survival (RFS), as compared with HCCs without EGFR CNG (P = 0.031). When exploring the impact of gender, a significant association of EGFR CNG was found with tumor grade (P = 0.044) and cirrhosis (P = 0.015) exclusively in the male group only; however, the OS and RFS analysis show no significant difference between male and female groups.ConclusionsEGFR CNG was related to crucial clinicopathological features and early recurrence, indicating that EGFR CNG might be a poor prognosis factor for Taiwanese HCC.