bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics and analgesic potency of oxycodone
Authors: Choi Byung‐Moon , Lee Yong‐Hun , An Sang‐Mee , Lee Soo‐Han , Lee Eun‐Kyung , Noh Gyu‐Jeong 
Published: August 2016

AimsThis prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra‐abdominal surgery.MethodsIn the pharmacokinetic study, patients were administered intravenous oxycodone (0.1 mg kg−1), and arterial blood was sampled at pre‐set intervals. In the analgesic‐potency study, patients were administered intravenous oxycodone (0.1 mg kg−1) 30 min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as ≥3 or ≥5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2 mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient.ResultsIn the population pharmacokinetic study (n = 54), oxycodone plasma concentration over time was well described by a three‐compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic‐potency study (n = 50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2–42.8) and 74.1 (29.2–128.3) ng ml−1 (first measurements) and 63.4 (15.6–120.1) and 76.1 (32.9–132.7) ng ml−1 (second measurements), respectively.ConclusionsIn major intra‐abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75 ng ml−1 and 60 ng ml−1, respectively.
Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time
Authors: Muth Christiane , Schröck Katharina , Madore Charlotte , Hartmann Kristin , Fanek Zain , Butovsky Oleg , Glatzel Markus , Krasemann Susanne 
Published: August 2016

AbstractPrion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrPC) into a misfolded isoform (PrPSc) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases; however, their impact on prion disease pathophysiology is unclear with both beneficial PrPSc‐clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology. Here, the degree of microglia activation in the brain of prion infected mice with and without an additional intraperitoneal retrovirus infection was studied. Peripheral murine retrovirus infection leads to activation of parenchymal microglia without recruitment of monocytes. This activation correlated with transient clearance or delay in accumulation of infectious prions specifically from the brain at early time points in the diseases course. Microglia expression profiling showed upregulation of genes involved in protein degradation coinciding with prion clearance. This enforces a concept where microglia act beneficial in prion disease if adequately activated. Once microglia activation has ceased, prion disease reemerges leading to disease kinetics undistinguishable from the situation in prion‐only infected mice. This might be caused by the loss of microglial homeostatic function at clinical prion disease.
Synergistic activity of Card11 mutant and Bcl6 in the development of diffuse large B‐cell lymphoma in a mouse model
Authors: Takahara Taishi , Matsuo Keitaro , Seto Masao , Nakamura Shigeo , Tsuzuki Shinobu 
Published: August 2016

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma; it derives from germinal center B cells. Although DLBCL harbors many genetic alterations, synergistic roles between such alterations in the development of lymphoma are largely undefined. We previously established a mouse model of lymphoma by transplanting gene‐transduced germinal center B cells into mice. Here, we chose one of the frequently mutated genes in DLBCL, Card11 mutant, to explore its possible synergy with other genes, using our lymphoma model. Given that BCL6 and BCL2 expression and/or function are often deregulated in human lymphoma, we examined the possible synergy between Card11, Bcl6, and Bcl2. Germinal center B cells were induced in vitro, transduced with Card11 mutant, Bcl6, and Bcl2, and transplanted. Mice rapidly developed lymphomas, with exogenously transduced Bcl2 being dispensable. Although some mice developed lymphoma in the absence of transduced Bcl6, the absence was compensated by elevated expression of endogenous Bcl6. Additionally, the synergy between Card11 mutant and Bcl6 in the development of lymphoma was confirmed by the fact that the combination of Card11 mutant and Bcl6 caused lymphoma or death significantly earlier and with higher penetrance than Card11 mutant or Bcl6 alone. Lymphoma cells expressed interferon regulatory factor 4 and PR domain 1, indicating their differentiation toward plasmablasts, which characterize activated B cell‐like DLBCL that represents a clinically aggressive subtype in humans. Thus, our mouse model provides a versatile tool for studying the synergistic roles of altered genes underlying lymphoma development.
Seroprevalence of Toxoplasma gondii in Iranian patients with idiopathic Parkinson's disease
Authors: Ramezani Mahtab , Shojaii Maziar , Asadollahi Marjan , Karimialavijeh Ehsan , Gharagozli Koorosh 
Published: August 2016

AbstractObjectiveThe aim of this research was to investigate the hypothesized association between Toxoplasma gondii infection and idiopathic Parkinson's disease (IPD).MethodsIn the present cross‐sectional study, we investigated T. gondii seropositivity in IPD patients in comparison with patients suffering from other neurological diseases (excluding movement disorders) and healthy people. Initially, all participants underwent a thorough clinical and paraclinical investigation. After this, 5 mL of blood was taken from all participants, and sera were tested for immunoglobulin M and immunoglobulin G (IgG) anti‐toxoplasma antibodies.ResultsA total of 41 IPD patients, 69 patients with other neurological diseases (excluding movement disorders) comprising 40 stroke patients, 10 epilepsy patients, 10 Alzheimer's disease patients and nine with chronic headaches, and 40 healthy people were investigated. All participants were matched in regard to sex, age and socioeconomic status. The frequency of anti‐toxoplasmosis seropositivity and the levels of IgG antibodies were significantly higher in the IPD patients (82.5%), in comparison with healthy participants (65%) and patients with neurological disease (65.2%; P = 0.01).ConclusionThe present findings support the hypothesis of a probable association between T. gondii infection and IPD.
Relationship between damage‐associated molecular patterns and cytokines in myasthenia gravis
Authors: Uzawa Akiyuki , Kanai Tetsuya , Kawaguchi Naoki , Oda Fumiko , Ozawa Yukiko , Himuro Keiichi , Kuwabara Satoshi 
Published: August 2016

AbstractObjectiveDamage‐associated molecular patterns (DAMP) and cytokines can play a crucial role in inflammation at neuromuscular junctions in myasthenia gravis (MG). However, the relationship between DAMP and cytokine levels in MG pathogenesis remains unknown. To clarify this, we examined the relationship between serum levels of DAMP and cytokines in MG patients.MethodsUsing serum data from 26 patients with anti‐acetylcholine receptor antibody‐positive MG, we investigated the relationship between the levels of DAMP (high‐mobility group box 1 [HMGB1] and peroxiredoxin 5) and cytokines (interleukin [IL]‐4, IL‐15, IL‐19, IL‐20, IL‐28A, IL‐35, a proliferation‐inducing ligand [APRIL] and vascular endothelial growth factor), which were reported to be significantly elevated in MG.ResultsSerum levels of APRIL (r = 0.4789, P = 0.0133), IL‐19 (r = 0.5496, P = 0.0036) and IL‐35 (r = 0.5396, P = 0.0044) were correlated with those of HMGB1, but no cytokine levels were correlated with peroxiredoxin 5 levels. When we carried out multivariate analyses, only APRIL (P = 0.0244) and IL‐19 (P = 0.0009) levels were correlated with HMGB1 levels.ConclusionsHMGB1 might be related with upregulation of IL‐19 and APRIL levels in MG immunopathogenesis. These molecules could play a key role in controlling autoimmune inflammatory response, and represent a potent therapeutic target in MG.
Frequency of peri‐implant diseases and associated factors
Authors: Gurgel Bruno César de Vasconcelos , Montenegro Sheyla Christine Lira , Dantas Poliana Medeiros Cunha , Pascoal Ana Luísa de Barros , Lima Kenio Costa , Calderon Patrícia dos Santos 
Published: August 2016

AbstractObjectiveTo evaluate the frequency of peri‐implant diseases and factors associated with its occurrence.Material and methodsOne hundred and fifty‐five patients with dental implants were evaluated in this cross‐sectional study. Dental implants were clinically and radiographically evaluated to diagnose their peri‐implant condition, according to Mombelli (Proceedings of the 3rd European Workshop on Periodontology, 1999, Quintessence, London). Associations between peri‐implant diseases and independent variables (socioeconomic, demographic and periodontal characteristics) were evaluated through bivariate analysis with chi‐squared and Fisher's exact tests, as well as by multiple logistic regression. The significance level was set at 5%.ResultsThe frequencies of the peri‐implant diseases, mucositis and peri‐implantitis, in individuals were 54% and 28% (CI, 95%), respectively. The sample was almost exclusively of patients with untreated periodontal disease (93%). Bivariate analysis showed that these peri‐implant diseases were associated with male patients (prevalence ratio [PR], 3.38), medication use (PR, 2.94), systemic diseases (PR, 2.25), number of implants (PR, 2.53), visible plaque index (PR, 2.49) and gingival index (PR, 2.70). Multiple logistic regression analysis showed that medication use (prevalence ratio adjusted [PRadj], 1.23; 95% CI: 1.04–1.46; P = 0.017), having two or more implants (PRadj, 1.22; 95% CI: 1.02–1.46; P = 0.029) and gingival bleeding index > 10% (PRadj, 1.22; 95% CI: 1.03–1.44; P = 0.022) were associated with the presence of peri‐implant disease.ConclusionPeri‐implant diseases were diagnosed in 54% of patients; gingival index of greater than 10%, having more than two implants and use of medication were associated with the frequency of peri‐implant disease.
Persistent Disparities between Recent Rates of Habitat Conversion and Protection and Implications for Future Global Conservation Targets
Authors: Watson James E.M. , Jones Kendall R. , Fuller Richard A. , Marco Moreno Di , Segan Daniel B. , Butchart Stuart H.M. , Allan James R. , McDonald‐Madden Eve , Venter Oscar 
Published: August 2016

AbstractAnthropogenic conversion of natural habitats is the greatest threat to biodiversity and one of the primary reasons for establishing protected areas (PAs). Here, we show that PA establishment outpaced habitat conversion between 1993 and 2009 across all biomes and the majority (n= 567, 71.4%) of ecoregions globally. However, high historic rates of conversion meant that 447 (56.2%) ecoregions still exhibit a high ratio of conversion to protection, and of these, 127 (15.9%) experienced further increases in this ratio between 1993 and 2009. We identify 41 “crisis ecoregions” in 45 countries where recent habitat conversion is severe and PA coverage remains extremely low. While the recent growth in PAs is a notable conservation achievement, international conventions and associated finance mechanisms should prioritize areas where habitat is being lost rapidly relative to protection, such as the crisis ecoregions identified here.
Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach
Authors: Wadia Subeer Kanwar , Shah Trushil G. , Hedstrom Grady , Kovach Julie A. , Tandon Rajive 
Published: August 2016

PurposeRight ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS.MethodsWe retrospectively measured changes in the following RV parameters from a pre‐ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift.ResultsOver 24 months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4 mm pre‐ARDS to 16.3 mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67 m/s pre‐ARDS to 3.31 m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre‐ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO2/FiO2 ratios), P=.004, and was lower among 30‐day nonsurvivors compared with survivors, P=.002.ConclusionsMild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality.
NicheMapR – an R package for biophysical modelling: the microclimate model
Authors: Kearney Michael R. , Porter Warren P. 
Published: August 2016

Microclimatic variables are necessary for a wide range of pure and applied problems in environmental science. In ecology, microclimatic conditions are prerequisites for modelling the heat and water budgets of organisms, from which climatic constraints on behaviour, life histories, distribution and abundance can be inferred. Despite the critical importance of microclimates, there is no general‐purpose, accessible microclimate model available for use in ecological studies.Here we introduce and document the microclimate model of the biophysical modelling package NicheMapR, an R package that includes a suite of programs for mechanistic modelling of heat and mass exchange between organisms and their environments. The NicheMapR microclimate model is based on a Fortran program originally developed by Porter, Mitchell, Beckman and McCullough for predicting hourly above‐ and below‐ground conditions from meteorological, terrain, vegetation and soil data. The model includes routines for computing solar radiation, including effects of shading, slope, aspect and horizon angles (hillshade), and can include variable substrate properties with depth.Here we configure the program to be called from R as part of the NicheMapR package, and describe the model in detail including new functionality for modelling soil water balance and snow, optional input of hourly or daily weather input data, and an R implementation of the Global Aerosol Data Set for obtaining local estimates of aerosol profiles as input to the model. We include scripts for core operation of the model, for building a global, monthly long‐term average dataset with all necessary environmental inputs, for computing physical properties of air, and for running the model with the global climate database. Example applications are provided in the paper and in the associated vignettes, including customisation the model to run with user‐supplied weather inputs.
A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice
Authors: Steurer Michael , Quittet Philippe , Papadaki Helen A. , Selleslag Dominik , Viallard Jean‐François , Kaiafa Georgia , Janssens Ann , Kozak Tomas , Wadenvik Hans , Schoonen Marieke , Belton Laura , Kreuzbauer Georg 
Published: August 2016

AbstractObjectiveRomiplostim has maintained long‐term platelet counts in patients with immune thrombocytopenia (ITP) for up to 5 yr in clinical studies. This prospective observational study aimed to describe romiplostim utilisation and outcomes in European clinical practice.MethodsAdults with primary ITP who received romiplostim in routine care were eligible.ResultsThree‐hundred and forty patients were eligible for analysis, of whom 299 (88%) completed the 2‐yr observation period. The median age was 62 yr, with 43% of patients aged ≥65 yr, and two‐thirds of patients initiated romiplostim before splenectomy. The median average weekly dose of romiplostim was 2.8 μg/kg. The median baseline platelet count was 20 × 109/L, which increased after 2 wk of romiplostim treatment and remained >50 × 109/L thereafter. After romiplostim initiation, there was a decrease in rates of grade ≥3 bleeding events (from 12 to 2 per 100 patient‐years) and ITP‐related hospitalisations (from 87 to 33 per 100 patient‐years). The rate of thrombotic events was 2 per 100 patient‐years, and bone marrow fibrosis occurred in two patients.ConclusionsRomiplostim dosing, effectiveness and safety in an unselected real‐world ITP population seemed comparable with that observed in clinical studies.
Extractability of Pb in urban gardens and orchards linked to soil properties
Authors: McBride M. B. 
Published: August 2016

SummaryThe hypothesis that lability and bioavailability of lead (Pb) in strongly contaminated soil is limited by interaction with phosphate and organic matter was tested on soil from urban gardens and orchards by extracting available Pb and P with the modified Morgan's extractant (ammonium acetate, pH 4.8) and measuring organic matter by loss‐on‐ignition. The extractable fraction of total Pb was larger in general in the urban garden than orchard soil, which indicates greater lability in urban garden soil than was expected if insoluble Pb phosphates such as pyromorphite were limiting Pb extractability. The extractable Pb fraction was generally larger in soil with greater total Pb, an indication that soil with large Pb concentrations contained Pb in more labile forms than soil with small concentrations. Larger organic matter contents in garden soil reduced the extractable fraction of Pb, but large available phosphate concentrations did not have this effect. The results indicate that soil organic matter has an important role in limiting Pb extractability in strongly contaminated soil, whereas a large soil phosphate concentration does not, despite the expectation that formation of insoluble Pb phosphates would reduce Pb lability. Nevertheless, a spatial association of P with Pb in Pb‐rich particles identified in urban garden soil with the electron microprobe suggests that Pb phosphates have formed in such soil from more reactive forms of Pb. The hypothesis is that a small fraction only of the total Pb in the urban soil occurs in a phosphate phase, and more acid‐labile forms of Pb co‐exist with insoluble phosphates for long time periods.HighlightsLead bioavailability in soil can potentially be reduced with phosphate.
Hypothesis is that soil Pb availability is limited by available phosphate or total organic matter.
Large soil organic matter content correlated with reduced Pb extractability, but not large available phosphorus content.
Lead‐phosphate phases did not appear to limit soil Pb extractability.
Modeled ecohydrological responses to climate change at seven small watersheds in the northeastern United States
Authors: Pourmokhtarian Afshin , Driscoll Charles T. , Campbell John L. , Hayhoe Katharine , Stoner Anne M. K. , Adams Mary Beth , Burns Douglas , Fernandez Ivan , Mitchell Myron J. , Shanley James B. 
Published: August 2016

AbstractA cross‐site analysis was conducted on seven diverse, forested watersheds in the northeastern United States to evaluate hydrological responses (evapotranspiration, soil moisture, seasonal and annual streamflow, and water stress) to projections of future climate. We used output from four atmosphere–ocean general circulation models (AOGCMs; CCSM4, HadGEM2‐CC, MIROC5, and MRI‐CGCM3) included in Phase 5 of the Coupled Model Intercomparison Project, coupled with two Representative Concentration Pathways (RCP 8.5 and 4.5). The coarse resolution AOGCMs outputs were statistically downscaled using an asynchronous regional regression model to provide finer resolution future climate projections as inputs to the deterministic dynamic ecosystem model PnET‐BGC. Simulation results indicated that projected warmer temperatures and longer growing seasons in the northeastern United States are anticipated to increase evapotranspiration across all sites, although invoking CO2 effects on vegetation (growth enhancement and increases in water use efficiency (WUE)) diminish this response. The model showed enhanced evapotranspiration resulted in drier growing season conditions across all sites and all scenarios in the future. Spruce‐fir conifer forests have a lower optimum temperature for photosynthesis, making them more susceptible to temperature stress than more tolerant hardwood species, potentially giving hardwoods a competitive advantage in the future. However, some hardwood forests are projected to experience seasonal water stress, despite anticipated increases in precipitation, due to the higher temperatures, earlier loss of snow packs, longer growing seasons, and associated water deficits. Considering future CO2 effects on WUE in the model alleviated water stress across all sites. Modeled streamflow responses were highly variable, with some sites showing significant increases in annual water yield, while others showed decreases. This variability in streamflow responses poses a challenge to water resource management in the northeastern United States. Our analyses suggest that dominant vegetation type and soil type are important attributes in determining future hydrological responses to climate change.