bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzalutamide in castration‐resistant prostate cancer patients with visceral disease in the liver and/or lung: Outcomes from the randomized controlled phase 3 AFFIRM trial
Authors: Loriot Yohann , Fizazi Karim , de Bono Johann S. , Forer David , Hirmand Mohammad , Scher Howard I. 
Published: September 2016

BACKGROUNDPatients with metastatic castration‐resistant prostate cancer (mCRPC) and visceral metastases have a worse prognosis than those with nonvisceral metastases. Treatment with the androgen receptor inhibitor enzalutamide in the phase 3 AFFIRM trial led to significant improvements in outcomes for patients with mCRPC. For the current report, the authors analyzed the efficacy of enzalutamide among patients from the AFFIRM trial who had visceral disease.METHODSPatients who had liver and/or lung metastases at baseline were selected for prespecified overall survival (OS) and exploratory post hoc analyses, including prostate‐specific antigen (PSA) response and the time to PSA and radiographic progression.RESULTSIn patients who had liver metastases (n = 92), enzalutamide was associated with a lower risk of radiographic progression (hazard ratio [HR], 0.645; 95% confidence interval [CI], 0.413‐1.008), improved 12‐month OS (37.7% vs 20.6%) and radiographic progression‐free survival (rPFS) (11.6% vs 3.0%) rates, and higher PSA response rates (35.1% vs 4.8%) compared with placebo. Enzalutamide‐treated patients who had lung metastases (n = 104) had improved median OS (HR, 0.848; 95% CI, 0.510‐1.410), a substantially reduced risk of radiographic progression (HR, 0.386; 95% CI, 0.259‐0.577), improved 12‐month OS (65.1% vs 55.3%) and rPFS (30.9% vs 8.2%) rates, increased time to PSA progression (HR, 0.358; 95% CI, 0.204‐0.627), and a better PSA response rate (52.1% vs 4.9%) compared with those who received placebo. No increase in treatment‐related adverse events was observed for the visceral metastases cohort compared with the nonvisceral metastases cohort.CONCLUSIONSAcross multiple endpoints, patients who have visceral metastases have better outcomes with enzalutamide than with placebo. Cancer 2017;123:253–262. © 2016 American Cancer Society.
Computational Study of the Interactions between Benzene and Crystalline Ice Ih: Ground and Excited States
Authors: Sharma Divya , Sameera W. M. C. , Andersson Stefan , Nyman Gunnar , Paterson Martin J. 
Published: September 2016

AbstractGround‐state geometries of benzene on crystalline ice cluster model surfaces (Ih) are investigated. It is found that the binding energies of benzene‐bound ice complexes are sensitive to the dangling features of the binding sites. We used time‐dependent DFT to study the UV spectroscopy of benzene, ice clusters, and benzene–ice complexes, by employing the M06‐2X functional. It is observed that the size of the ice cluster and the dangling features have minor effects on the UV spectral characteristics. Benzene‐mediated electronic excitations of water towards longer wavelengths (above 170 nm) are noted in benzene‐bound ice clusters, where the cross‐section of photon absorption by water is negligible, in good agreement with recent experimental results (Thrower et al., J. Vac. Sci. Technol. A, 2008, 26, 919–924). The intensities of peaks associated with water excitations in benzene–ice complexes are found to be higher than in isolated ice clusters. The π→π* electronic transition of benzene in benzene–ice complexes undergoes a small redshift compared with the isolated benzene molecule, and this holds for all benzene‐bound ice complexes.
Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis
Authors: Melenovsky Vojtech , Petrak Jiri , Mracek Tomas , Benes Jan , Borlaug Barry A. , Nuskova Hana , Pluhacek Tomas , Spatenka Jaroslav , Kovalcikova Jana , Drahota Zdenek , Kautzner Josef , Pirk Jan , Houstek Josef 
Published: September 2016

AbstractAimsIron replacement improves clinical status in iron‐deficient patients with heart failure (HF), but the pathophysiology is poorly understood. Iron is essential not only for erythropoiesis, but also for cellular bioenergetics. The impact of myocardial iron deficiency (MID) on mitochondrial function, measured directly in the failing human heart, is unknown.Methods and resultsLeft ventricular samples were obtained from 91 consecutive HF patients undergoing transplantation and 38 HF‐free organ donors (controls). Total myocardial iron content, mitochondrial respiration, citric acid cycle and respiratory chain enzyme activities, respiratory chain components (complex I–V), and protein content of reactive oxygen species (ROS)‐protective enzymes were measured in tissue homogenates to quantify mitochondrial function. Myocardial iron content was lower in HF compared with controls (156 ± 41 vs. 200 ± 38 µg·g−1 dry weight, P < 0.001), independently of anaemia. MID (the lowest iron tercile in HF) was associated with more extensive coronary disease and less beta‐blocker usage compared with non‐MID HF patients. Compared with controls, HF patients displayed reduced myocardial oxygen2 respiration and reduced activity of all examined mitochondrial enzymes (all P < 0.001). MID in HF was associated with preserved activity of respiratory chain enzymes but reduced activity of aconitase and citrate synthase (by –26% and –15%, P < 0.05) and reduced expression of catalase, glutathione peroxidase, and superoxide dismutase 2.ConclusionMyocardial iron content is decreased and mitochondrial functions are impaired in advanced HF. MID in HF is associated with diminished citric acid cycle enzyme activities and decreased ROS‐protecting enzymes. MID may contribute to altered myocardial substrate use and to worsening of mitochondrial dysfunction that exists in HF.
Pulmonary artery pressure‐guided heart failure management: US cost‐effectiveness analyses using the results of the CHAMPION clinical trial
Authors: Martinson Melissa , Bharmi Rupinder , Dalal Nirav , Abraham William T. , Adamson Philip B. 
Published: September 2016

AbstractAimsHaemodynamic‐guided heart failure (HF) management effectively reduces decompensation events and need for hospitalizations. The economic benefit of clinical improvement requires further study.Methods and resultsAn estimate of the cost‐effectiveness of haemodynamic‐guided HF management was made based on observations published in the randomized, prospective single‐blinded CHAMPION trial. A comprehensive analysis was performed including healthcare utilization event rates, survival, and quality of life demonstrated in the randomized portion of the trial (18 months). Markov modelling with Monte Carlo simulation was used to approximate comprehensive costs and quality‐adjusted life years (QALYs) from a payer perspective. Unit costs were estimated using the Truven Health MarketScan database from April 2008 to March 2013. Over a 5‐year horizon, patients in the Treatment group had average QALYs of 2.56 with a total cost of US$56 974; patients in the Control group had QALYs of 2.16 with a total cost of US$52 149. The incremental cost‐effectiveness ratio (ICER) was US$12 262 per QALY. Using comprehensive cost modelling, including all anticipated costs of HF and non‐HF hospitalizations, physician visits, prescription drugs, long‐term care, and outpatient hospital visits over 5 years, the Treatment group had a total cost of US$212 004 and the Control group had a total cost of US$200 360. The ICER was US$29 593 per QALY.ConclusionsStandard economic modelling suggests that pulmonary artery pressure‐guided management of HF using the CardioMEMS™ HF System is cost‐effective from the US‐payer perspective. This analysis provides the background for further modelling in specific country healthcare systems and cost structures.
Using sulfur stable isotopes to assess mercury bioaccumulation and biomagnification in temperate lake food webs
Authors: Clayden Meredith G. , Lescord Gretchen L. , Kidd Karen A. , Wang Xiaowa , Muir Derek C.G. , O'Driscoll Nelson J. 
Published: September 2016

Abstract

Nitrogen and carbon stable isotopes (δ15N, δ13C) are commonly used to understand mercury (Hg) bioaccumulation and biomagnification in freshwater food webs. Though sulfur isotopes (δ34S) can distinguish between energy sources from the water column (aqueous sulfate) and from sediments to freshwater organisms, little is known about whether δ34S can help interpret variable Hg concentrations in aquatic species or food webs. Seven acidic lakes in Kejimkujik National Park (Nova Scotia, Canada) were sampled for biota, water, and sediments in 2009 and 2010. Fishes, zooplankton, and macroinvertebrates were analyzed for δ34S, δ15N, δ13C, and Hg (methyl Hg in invertebrates, total Hg in fishes); aqueous sulfate and profundal sediments were analyzed for δ34S. Within lakes, mean δ34S values in sediments and sulfate differed between 0.53‰ and 1.98‰, limiting their use as tracers of energy sources to the food webs. However, log-Hg and δ34S values were negatively related (slopes –0.14 to –0.35, R2 0.20–0.39, p &lt; 0.001–0.01) through each food web, and slopes were significantly different among lakes (analysis of covariance, lake × δ34S interaction term p = 0.04). Despite these relationships, multiple regression analyses within each taxon showed that biotic Hg concentrations were generally better predicted by δ15N and/or δ13C. The results indicate that δ34S values are predictive of Hg concentrations in these food webs, although the mechanisms underlying these relationships warrant further study. Environ Toxicol Chem 2017;36:661–670. © 2016 SETAC
Strategies for Dimensioning Two‐Wheeled Fuel Cell Hybrid Electric Vehicles Using Numerical Analysis Software
Authors: De Luca D. , Fragiacomo P. , De Lorenzo G. , Czarnetzki W. T. , Schneider W. 
Published: September 2016

AbstractOwing to the limitation of fossil fuels and high consumption and pollution for transportation, the vehicle industry is looking for other sources of energy. A fuel cell hybrid electric vehicle (FCHEV) could be a suitable solution considering the state of the art of main components. This paper presents the simulation of powertrains for FCHEVs in order to dimension the fuel cell (FC) as primary source of energy and to investigate the power flows during both motoring and recuperative braking. For this purpose a Matlab/Simulink® model has been built up which can be used for a wide range of applications. The results of simulation show which is the best powertrain configuration for two‐wheeled vehicles in three different cases: a bike in which the traction force is provided by both electric motor and the pedaling of the cyclist, a bike in which the traction force is provided only by an electric motor without pedaling and a motorcycle for 2 passengers. Specifically, the consumption, the state of charge (SOC) of battery and the amount of energy generated by each source of energy have been monitored. The model validation was done by comparison between the obtained results and scientific articles in the literature.
Meta‐analysis of randomized, double‐blind, placebo‐controlled trials of melatonin in Alzheimer's disease
Authors: Wang Yuan‐Yuan , Zheng Wei , Ng Chee H. , Ungvari Gabor S. , Wei Wei , Xiang Yu‐Tao 
Published: September 2016

ObjectiveThis is a meta‐analysis of randomized controlled trials (RCTs) of the efficacy of melatonin in Alzheimer's disease (AD).MethodsBoth English (PubMed, PsycINFO, Embase, Cochrane Library databases, and the Cochrane Controlled Trials Register) and Chinese (WanFang Database, Chinese Biomedical Database, and China Journal Net) databases were systematically and independently searched by two authors from their inception until 1 March 2016. Weighted and standard mean differences (SMDs), risk ratio (RR) ±95% confidence intervals (CIs) were calculated. In all cases, the random effects model was used.ResultsSeven studies (n = 462) with the duration ranging from 10 days to 24 weeks were identified and analyzed. AD patients receiving melatonin treatment showed prolonged total sleep time at night (n = 305; SMD: 0.26, 95% CI: 0.01 to 0.51, I2 = 9%, p = 0.04). Melatonin did not improve cognitive abilities assessed by the mini‐mental state examination and the Alzheimer's Disease Assessment Cognitive Subscale. The discontinuation rate was similar between the melatonin and placebo groups (n = 453, RR = 0.77, 95% CI: 0.51 to 1.16, I2 = 0%, p = 0.21).ConclusionMelatonin appears to be effective and safe in improving sleep quality in patients with AD. Copyright © 2016 John Wiley & Sons, Ltd.
The Effects of Multilevel Signals on Sex Discrimination Experiences Among Female Employees
Authors: Yong Kim Kyoung , Elkins Longacre Teri , Werner Steve 
Published: September 2016

AbstractIn this study, we examine the effect of organizational‐level and individual‐level signals on sex discrimination experiences, job satisfaction, and turnover intentions in a sample of South Korean female employees and organizations. Results indicate that the percentage of women employed in organizations was negatively associated with sex discrimination experienced by women. The number of family‐friendly policies was also negatively associated with sex discrimination in a panel design but not in a cross‐sectional design. We also found that the relationship between individual participation in development activities (e.g., leadership development course, academic degree) and sex discrimination experiences was moderated by organizational‐level participation in development activities. Specifically, the negative impact of participation in development activities on sex discrimination is stronger for individuals in organizations with lower compared to higher levels of overall participation. The same was true for the individual educational level. The negative impact of individual educational level on sex discrimination is stronger for individuals in organizations with high educational level than for those in low organizational educational level. Further, experienced sex discrimination influences individual turnover intention via job satisfaction. © 2016 Wiley Periodicals, Inc.
Mass transport triggered by heavy rainfall: the role of endorheic basins and epikarst in a regional karst aquifer
Authors: Fidelibus Maria Dolores , Balacco Gabriella , Gioia Andrea , Iacobellis Vito , Spilotro Giuseppe 
Published: September 2016

AbstractThis study aims at recognizing the mechanisms of mass transport between the karst surface and the saturated zone in a morphostructural relief of the Mesozoic karst carbonate platform of Murgia (Puglia, Southern Italy). The large dimension of the karst aquifer, the regional scale of the flow system, the boundary condition constituted by the sea, and the lack of freshwater springs constrain to the use of wells as monitoring points and limit the study area to the recharge area comprising 986 endorheic basins. The concentrations of non‐reactive tracers (nitrates) in the waters of autogenic recharge (from endorheic basins) have been modeled through the evaluation of effective infiltration, land use, and nitrogen surplus, with reference to a time window, which includes a low precipitation period followed by significant rainfall events. The comparison between the modeled nitrate concentrations and the nitrate concentrations measured in ground waters, coupled with the analysis of groundwater chemograms and records of hydraulic heads (all referred to the same time window), allows inferring the mechanism of mass transport between the karst surface and the groundwater table. The mass transport conceptual model requires the presence of the epikarst. The infiltration of significant rainfall in the endorheic basins after a low precipitation period displaces waters stored in the epikarst toward the saturated zone. Ground waters in the post‐event period show higher concentrations of nitrates, lower concentrations of total organic carbon, and higher Mg/Ca ratios than both those of the pre‐event period and the autumn‐winter recharge period. The post‐event recharge from epikarst storage determines a transient hazard of groundwater pollution with a time lag from the occurrence of the heavy rainfall.
Low‐level laser therapy stimulates bone metabolism and inhibits root resorption during tooth movement in a rodent model
Authors: Suzuki Selly Sayuri , Garcez Aguinaldo Silva , Suzuki Hideo , Ervolino Edilson , Moon Won , Ribeiro Martha Simões 
Published: September 2016

This study evaluated the biological effects of low‐level laser therapy (LLLT) on bone remodeling, tooth displacement and root resorption, occurred during the orthodontic tooth movement. Upper first molars of a total of sixty‐eight male rats were subjected to orthodontic tooth movement and euthanized on days 3, 6, 9, 14 and 21 days and divided as negative control, control and LLLT group. Tooth displacement and histomorphometric analysis were performed in all animals; scanning electron microscopy analysis was done on days 3, 6 and 9, as well as the immunohistochemistry analysis of RANKL/OPG and TRAP markers. Volumetric changes in alveolar bone were analyzed using MicroCT images on days 14 and 21. LLLT influenced bone resorption by increasing the number of TRAP‐positive osteoclasts and the RANKL expression at the compression side. This resulted in less alveolar bone and hyalinization areas on days 6, 9 and 14. LLLT also induced less bone volume and density, facilitating significant acceleration of tooth movement and potential reduction in root resorption besides stimulating bone formation at the tension side by enhancing OPG expression, increasing trabecular thickness and bone volume on day 21. Taken together, our results indicate that LLLT can stimulate bone remodeling reducing root resorption in a rat model.
LLLT improves tooth movement via bone formation and bone resorption in a rat model.magnified imageLLLT improves tooth movement via bone formation and bone resorption in a rat model.
The chemokines secretion and the oxidative stress are targets of low‐level laser therapy in allergic lung inflammation
Authors: Costa Carvalho Jorge Luis , de Brito Auriléia Aparecida , de Oliveira Ana Paula Ligeiro , de Castro Faria Neto Hugo Caire , Pereira Thiago Martini , de Carvalho Regiane Albertini , Anatriello Elen , Aimbire Flávio 
Published: September 2016

Recent studies show that low‐level laser therapy (LLLT) has an important anti‐inflammatory action in acute lung inflammation. The present work explored if laser therapy is able to antagonize eosinophils and allergic inflammation induced by oxidative stress in Balb/c mice. Forty‐eight hours after challenge, the leukocyte counting, ROS and nitrite/nitrate level, RANTES, CCL3, CCL8 as well as eotaxins were measured in the bronchoalveolar lavage fluid (BALF) of laser‐treated mice or not. Into the lung, some chemokines receptors, the iNOS activity and mRNA expression, and the activities of superoxide dismutase (SOD), catalase, gluthatione, NADPH oxidase activities and thiobarbituric acid reactive species (T‐Bars) were measured. Laser‐treated allergic mice presented reduction of both the ICAM‐1 and eosinophil in the lungs. RANTES, CCL8, CCL3 and eotaxins were reduced in BALF of laser‐treated allergic mice. In allergic mice lung LLLT decreased the CCR1 and CCR3 and restored the oxidative stress balance as well. Laser decreased the lipidic peroxidation in allergic mice lung as much as increased SOD, GPx and GR. It shows that LLLT on allergic lung inflammation involves leukocyte‐attractant chemokines and endogenous antioxidant. Based on results, LLLT may ultimately become a non‐ invasive option in allergic lung disease treatment.
The top figure illustrates the laser decreasing the eosinophils migration into BALF and the bottom figure shows the laser upregulating the expression of heme‐oxygenase (anti‐oxidant enzyme) in lung tissue anti‐oxidant.magnified imageThe top figure illustrates the laser decreasing the eosinophils migration into BALF and the bottom figure shows the laser upregulating the expression of heme‐oxygenase (anti‐oxidant enzyme) in lung tissue anti‐oxidant.
Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling
Authors: Ho-Le Thao P , Center Jacqueline R , Eisman John A , Nguyen Hung T , Nguyen Tuan V 
Published: September 2016

ABSTRACT

Although the susceptibility to fracture is partly determined by genetic factors, the contribution of newly discovered genetic variants to fracture prediction is still unclear. This study sought to define the predictive value of a genetic profiling for fracture prediction. Sixty-two bone mineral density (BMD)-associated single-nucleotide polymorphisms (SNPs) were genotyped in 557 men and 902 women who had participated in the Dubbo Osteoporosis Epidemiology Study. The incidence of fragility fracture was ascertained from X-ray reports between 1990 and 2015. Femoral neck BMD was measured by dual-energy X-ray absorptiometry. A weighted polygenic risk score (genetic risk score [GRS]) was created as a function of the number of risk alleles and their BMD-associated regression coefficients for each SNP. The association between GRS and fracture risk was assessed by the Cox proportional hazards model. Individuals with greater GRS had lower femoral neck BMD (p &lt; 0.01), but the variation in GRS accounted for less than 2% of total variance in BMD. Each unit increase in GRS was associated with a hazard ratio of 1.20 (95% CI, 1.04 to 1.38) for fracture, and this association was independent of age, prior fracture, fall, and in a subset of 33 SNPs, independent of femoral neck BMD. The significant association between GRS and fracture was observed for the vertebral and wrist fractures, but not for hip fracture. The area under the receiver-operating characteristic (ROC) curve (AUC) for the model with GRS and clinical risk factors was 0.71 (95% CI, 0.68 to 0.74). With GRS, the correct reclassification of fracture versus nonfracture ranged from 12% for hip fracture to 23% for wrist fracture. A genetic profiling of BMD- associated genetic variants could improve the accuracy of fracture prediction over and above that of clinical risk factors alone, and help stratify individuals by fracture status. © 2016 American Society for Bone and Mineral Research.
The tipping point: The critical role of therapeutic apheresis in a case of refractory acquired hemophilia
Authors: Losos Michael , Scrape Scott , Joshi Sarita , Shmookler Aaron , Chen Jian 
Published: September 2016

AbstractAcquired hemophilia A (AHA) is a rare autoimmune disorder that leads to factor VIII (FVIII) deficiency via autoantibody formation. Standard treatment options include FVIII bypassing factors and immunosuppression. However, the role of therapeutic plasma exchange (TPE) is not clear in the treatment of AHA. We present a case of idiopathic AHA in a 66 year old female with severe bleeding and a FVIII inhibitor of 17.6 Bethesda units (BU). She failed to respond to standard treatment including maximum dose of recombinant FVIIa (rFVIIa), rituximab, and other immunosuppressive agents. Her FVIII inhibitor rapidly increased to 140 BU and FVIII was below 5%. TPE was initiated 3 weeks after admission and her bleeding stabilized after the first treatment and completely stopped after three treatments. Repeat testing revealed increased FVIII to 15% and FVIII inhibitor decreased to 2.0 BU. After an additional TPE treatment, her FVIII increased to 27% and FVIII inhibitor decreased to 0.6 BU and she was discharged without bleeding 40 days after admission. In this case, TPE played a critical role in reducing FVIII inhibitor, which resulted in a recovery of FVIII activity and hemostasis. Therefore, TPE should be initiated early in AHA patients with bleeding and high titer of FVIII inhibitor.