bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid palm oil (Elaeis oleifera × Elaeis guineensis) supplementation improves plasma antioxidant capacity in humans
Authors: Ojeda Myriam , Borrero Martha , Sequeda Gonzalo , Diez Ofelia , Castro Vivian , García Ángela , Ruiz Álvaro , Pacetti Deborah , Frega Natale , Gagliardi Riccardo , Lucci Paolo 
Published: May 2016

Hybrid palm oil obtained from interspecific hybrid Elaeis oleifera × Elaeis guineensis palm (HPO) has been recently proved to have a favorable impact on human plasma lipids related to cardiovascular disease risk factors. In the present work, we describe for the first time, the functional effect of crude HPO supplementation on human antioxidant plasma/serum status as assessed by the total phenolic content (Folin–Ciocalteu), ORAC and TEAC assays. One hundred sixty eligible participants (>50 years) were randomized and assigned to one of the two treatments: 25 mL hybrid palm oil (HPO group) or 25 mL extra virgin olive oil (EVOO group) daily for 3 months. This study showed that supplementation of 25 mL of HPO for a period of 3 months significantly increased (p < 0.01) the total phenolic content (19.2%) as well as the antioxidant capacity of human plasma measured by both ORAC (92.1%) and TEAC (42.9%) methods. Furthermore, no significant differences were found between HPO and EVOO groups in a repeated measures analysis of variance for TPC (p = 0.344), TEAC (p = 0.217), and ORAC (p = 0.318) values. These results confirm that HPO can be considered a promising tropical edible oil with potential beneficial health effects.Practical applications: The understanding of the antioxidant properties of an edible oil in vivo is of primary importance when evaluating its nutritional/functional characteristics and/or its potentiality to serve as an active ingredient for functional food preparations. The results of this study confirm that HPO can be considered a promising tropical edible oil with beneficial health properties since it is able to improve the antioxidant status of plasma in humans.This 3‐month randomized trial reported examines and compares the effects of 25 mL/day supplementation of crude hybrid palm oil (Elaeis oleifera × Elaeis guineensis), thought to be a possible tropical equivalent of the Mediterranean extra‐virgin olive oil, to the ones of extra‐virgin olive oil, which is considered as a gold standard in the functional dietary oils skyline. Interestingly, at the end of the third month of study, the effects obtained by the supplementation with hybrid palm oil are similar to those provided by the extra‐virgin olive oil supplementation. In fact, hybrid palm oil consumption has been shown to significantly increase the total phenolic content (19.2%, p < 0.01) as well as the antioxidant capacity of human plasma measured by both TEAC (42.9%, p < 0.01) and ORAC (92.1% p < 0.01) assays.
Discrepancies between cortical and behavioural long‐term readouts of hyperalgesia in awake freely moving rats
Authors: Ljungquist B. , Jensen T. , Etemadi L. , Thelin J. , Lind G. , Garwicz M. , Petersson P. , Tsanakalis F. , Schouenborg J. 
Published: May 2016

AbstractBackgroundIt is still unclear to what extent the most common animal models of pain and analgesia, based on indirect measures such as nocifensive behaviours, provide valid measures of pain perception.MethodsTo address this issue, we developed a novel animal model comprising a more direct readout via chronically (>1 month) implanted multichannel electrodes (MCE) in rat primary somatosensory cortex (S1; known to be involved in pain perception in humans) and compared this readout to commonly used behavioural pain‐related measures during development of hyperalgesia. A translational method to induce hyperalgesia, UVB irradiation of the skin, was used. Localized CO2 laser stimulation was made of twenty skin sites (20 stimulations/site/observation day) on the plantar hind paw, before and during the time period when enhanced pain perception is reported in humans after UVB irradiation.ResultsWe demonstrate a 2–10 fold significant enhancement of cortical activity evoked from both irradiated and adjacent skin and a time course that corresponds to previously reported enhancement of pain magnitude during development of primary and secondary hyperalgesia in humans. In contrast, withdrawal reflexes were only significantly potentiated from the irradiated skin area and this potentiation was significantly delayed as compared to activity in S1.ConclusionsThe present findings provide direct evidence that chronic recordings in S1 in awake animals can offer a powerful, and much sought for, translational model of the perception of pain magnitude during hyperalgesia.What does this study add?
In a novel animal model, chronic recordings of nociceptive activity in primary somatosensory cortex (S1) in awake freely moving rats are compared to behavioural readouts during UVB‐induced hyperalgesia. Evoked activity in rat S1 replicates altered pain perception in humans during development of hyperalgesia, but withdrawal reflexes do not.
Censored and shifted gamma distribution based EMOS model for probabilistic quantitative precipitation forecasting
Authors: Baran Sándor , Nemoda Dóra 
Published: May 2016

Recently, all major weather prediction centers provide forecast ensembles of different weather quantities, which are obtained from multiple runs of numerical weather prediction models with various initial conditions and model parametrizations. However, ensemble forecasts often show an underdispersive character and may also be biased, so that some post‐processing is needed to account for these deficiencies. Probably the most popular modern post‐processing techniques are the ensemble model output statistics (EMOS) and the Bayesian model averaging (BMA), which provide estimates of the density of the predictable weather quantity.In the present work, an EMOS method for calibrating ensemble forecasts of precipitation accumulation is proposed, where the predictive distribution follows a censored and shifted gamma (CSG) law with parameters depending on the ensemble members. The CSG EMOS model is tested on ensemble forecasts of 24‐h precipitation accumulation of the eight‐member University of Washington mesoscale ensemble and on the 11‐member ensemble produced by the operational Limited Area Model Ensemble Prediction System of the Hungarian Meteorological Service. The predictive performance of the new EMOS approach is compared with the fit of the raw ensemble, the generalized extreme value (GEV) distribution‐based EMOS model, and the gamma BMA method. According to the results, the proposed CSG EMOS model slightly outperforms the GEV EMOS approach in terms of calibration of probabilistic and accuracy of point forecasts and shows significantly better predictive skill than the raw ensemble and the BMA model. Copyright © 2016 John Wiley & Sons, Ltd.
Combining exposure and effect modeling into an integrated probabilistic environmental risk assessment for nanoparticles
Authors: Jacobs Rianne , Meesters Johannes A.J. , ter Braak Cajo J.F. , van de Meent Dik , van der Voet Hilko 
Published: May 2016

Abstract

There is a growing need for good environmental risk assessment of engineered nanoparticles (ENPs). Environmental risk assessment of ENPs has been hampered by lack of data and knowledge about ENPs, their environmental fate, and their toxicity. This leads to uncertainty in the risk assessment. To deal with uncertainty in the risk assessment effectively, probabilistic methods are advantageous. In the present study, the authors developed a method to model both the variability and the uncertainty in environmental risk assessment of ENPs. This method is based on the concentration ratio and the ratio of the exposure concentration to the critical effect concentration, both considered to be random. In this method, variability and uncertainty are modeled separately so as to allow the user to see which part of the total variation in the concentration ratio is attributable to uncertainty and which part is attributable to variability. The authors illustrate the use of the method with a simplified aquatic risk assessment of nano–titanium dioxide. The authors’ method allows a more transparent risk assessment and can also direct further environmental and toxicological research to the areas in which it is most needed. Environ Toxicol Chem 2016;35:2958–2967. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Still room for improvement: Preclinical and bench testing of a thin‐strut cobalt–chromium bare‐metal stent with passive coating
Authors: Wittchow Eric , Hartwig Sonja 
Published: May 2016

AbstractThere is a renewed interest in bare‐metal stent (BMS) design as degradable polymer coatings are increasingly used as drug‐delivery vehicles in drug‐eluting stents (DESs), leaving it to the BMS platform to determine the long‐term outcome of DES treatment. In this study comprising preclinical and bench tests, we compare two modern thin‐strut BMSs of different design. Angiography, morphometry, and histopathology data were acquired in a porcine coronary artery model in a 28‐day single‐stent study (13 hybrid farm pigs) and in a 90‐day overlapping‐stent study (8 Yucatan mini‐pigs). Standardized bench tests including ion release test were performed to compare mechanical performance of the two stent systems. We found that the optimized stent group induced significantly less neointimal formation and less inflammation than Multi‐Link Vision in both (single stent and overlapping stent) porcine studies. The higher efficacy was also associated with a markedly reduced release of cobalt, nickel, chromium, and tungsten ions in physiological solution and better performance in mechanical delivery tests. In conclusion, a further increase in efficacy and better safety profile than the well‐known Multi‐Link Vision BMS can be achieved by careful optimization of the BMS backbone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1612–1621, 2017.
Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer
Authors: Chamberlin Mary D. , Bernhardt Erica B. , Miller Todd W. 
Published: May 2016

ABSTRACTThe majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next‐generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin‐dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial‐and‐error approach with each patient. Next‐generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3‐kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD‐1), and programmed T cell death ligand 1 (PD‐L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first‐line setting. However, the bulk of medical decision‐making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD‐1, and PD‐L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454–2463, 2016. © 2016 Wiley Periodicals, Inc.
Sex Differences in mRNA Expression of Reduced Folate Carrier‐1, Folypolyformyl Glutamate Synthase, and γ‐Glutamyl Hydrolase in a Healthy Japanese Population
Authors: Hashiguchi Masayuki , Tanaka Takanori , Shimizu Mikiko , Tsuru Tomomi , Chiyoda Takeshi , Miyawaki Kumika , Irie Shin , Takeuchi Osamu , Hakamata Jun , Mochizuki Mayumi 
Published: May 2016

AbstractSex differences in the prevalence of autoimmune diseases such as rheumatoid arthritis (RA) are well known, but little is known about those differences in relation to therapeutic response. Reduced folate carrier‐1 (RFC‐1), folypolyformyl glutamate synthase (FPGS), and γ‐glutamyl hydrolase (GGH) are important transporters and enzymes that convert methotrexate (MTX) in the body. This study investigated the sex differences in mRNA expression of RFC‐1, FPGS, and GGH in 190 unrelated healthy Japanese people. The genotypes and mRNA expression were determined using the real‐time PCR method. Significant differences between men and women were observed in RFC‐1, FPGS, and GGH mRNA expression. The mRNA expression of FPGS and GGH was greater in women than that in men, but the expression of RFC‐1 was less in the former than the latter. In stratified analysis by genotype, significant differences in sex‐specific mRNA expression were observed in G/G of FPGS, C/C of GGH 452, and C/C of GGH –401. All showed greater mRNA expression in women than in men. In the 5 single‐nucleotide polymorphisms RFC‐1 80G>A, RFC‐1 –43T>C, FPGS 1994G>A, GGH 452C>T, and GGH –401C>T examined, the FPGS 1994 G/G (1.46‐fold), GGH 452 C/C (2.16‐fold), and GGH –401 C/C (2.68‐fold) genotypes showed significantly higher mRNA expression in women than in men. Healthy Japanese adults in this study showed sex‐specific differences in mRNA expression that differed among RFC‐1, FPGS, and GGH. Therefore, the relationship between genetic polymorphisms and mRNA expression including sex differences might contribute to the variation in the efficacy/toxicity of MTX in patients with RA.
Brivaracetam Population Pharmacokinetics and Exposure‐Response Modeling in Adult Subjects With Partial‐Onset Seizures
Authors: Schoemaker Rik , Wade Janet R. , Stockis Armel 
Published: May 2016

AbstractBrivaracetam is a selective high‐affinity ligand for synaptic vesicle protein 2A, recently approved as adjunctive therapy in the treatment of partial‐onset (focal) seizures in patients 16 years of age and older with epilepsy. A population pharmacokinetic (PK) model and a population pharmacokinetic/pharmacodynamic (PKPD) model were developed describing brivaracetam plasma concentration and the relationship with daily seizure counts in adequate well‐controlled efficacy trials. The effect of body weight on clearance and volume was implemented using allometric scaling, and a range of covariates were investigated for their influence on brivaracetam clearance. The PKPD model described daily seizure counts using a negative binomial distribution, taking previous day seizures into account, and using a mixture model to separate “placebo‐like” and “response” subpopulations. The PK and PKPD models provided a good description of the data, documented using visual predictive checks. Coadministration with carbamazepine, phenytoin, and phenobarbital decreased brivaracetam exposure by 26%, 21%, and 19%, respectively, without significant effects on PD response. Covariate analysis indicated that levetiracetam coadministration reduced the fraction of subjects in the mixture model response population to 4% and identified baseline seizure frequency as a strong predictor for being assigned to the mixture model response population. Simulation allowed characterization of the dose‐response curve, suggesting maximum response is obtained at brivaracetam 150–200 mg/day.
Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis
Authors: Netzer Cordula , Urech Karin , Hügle Thomas , Benz Robyn Melanie , Geurts Jeroen , Schären Stefan 
Published: May 2016

ABSTRACTFacet joint osteoarthritis may be a cause of low back pain in degenerative spine diseases including lumbar spinal stenosis. Subchondral bone is regarded as a potential therapeutic target for osteoarthritis treatment. The goal of this study was to characterize subchondral bone histopathology in osteoarthritic facet joints from lumbar spinal stenosis patients. Fifteen patients with degenerative spinal stenosis scheduled for transforaminal lumbar interbody fusion surgery were recruited for this study. Osteoarthritis severity was graded on T1‐ and T2‐weighted MRI images using Weishaupt scoring system. Dissected osteoarthritic facet joints were subjected to histological and immunohistochemistry analyses to study relative abundance of osteoblast, osteoclasts, and macrophages using van Gieson‘s, tartrate‐resistant acid phosphatase and CD68‐antibody staining, respectively. Presence of nerve fibers was evaluated by PGP9.5‐antibody staining. Differential bone histopathology, independent from radiological osteoarthritis grade, was observed in facet joints. Extensive de novo bone formation was found in subchondral bone tissues of eight of fifteen specimens. Regions of bone formation showed high abundance of blood vessels and CD68‐positive macrophages, but were devoid of multinucleated osteoclasts. Additional pathological changes in subchondral marrow spaces, including inflammatory infiltration and enhanced osteoclast activity, were characterized by macrophage‐rich tissues. PGP9.5‐positive nerve fibers were detected near arterioles, but not in regions displaying bone pathology. Individual histopathological parameters did not associate with clinical features or radiological osteoarthritis severity. Subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis is characterized by marrow infiltration by macrophage‐rich tissues and enhanced de novo bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1475–1480, 2016.
Lumbar disc degeneration is an equally important risk factor as lumbar fusion for causing adjacent segment disc disease
Authors: Natarajan Raghu N. , Andersson Gunnar B.J. 
Published: May 2016

ABSTRACTTreatment of degenerative spinal disorders by fusion produces abnormal mechanical conditions at mobile segments above or below the site of spinal disorders and is clinically referred to as adjacent segments disc disease (ASDD) or transition syndrome in the case of a previous surgical treatment. The aim of the current study is to understand with the help of poro‐elastic finite element models how single or two level degeneration of lower lumbar levels influences motions at adjacent levels and compare the findings to motions produced by single or two level fusions when the adjacent disk has varying degree of degeneration. Validated grade‐specific finite element models including varying grades of disc degeneration at lower lumbar levels with and without fusion were developed and used to determine motions at all levels of the lumbar spine due to applied moment loads. Results showed that adjacent disc motions do depend on severity of disc degeneration, number of disc degenerated or fused, and level at which degeneration or fusion occurred. Furthermore, single level degeneration and single level fusion produced similar amount of adjacent disc motions. The pattern of increase in adjacent segment motions due to disc degeneration and increase in motions at segment adjacent to fusion was similar. Based on the current study, it can be concluded that disc degeneration should also be considered as a risk factor in addition to fusion for generating adjacent disc degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:123–130, 2017.
Mouse JMJD4 is dispensable for embryogenesis
Authors: Yoo Hyunjin , Son Dabin , Lee Young Jae , Hong Kwonho 
Published: May 2016

SUMMARYJumonji C domain‐containing demethylase 4 (JMJD4) is thought to help regulate mRNA translation, yet its precise in vivo role during mouse development has not been addressed. In the present study, we examined the contribution of this demethylase to embryonic stem cell (ESC) differentiation, and established a Jmjd4‐knockout mouse to explore its role during embryonic development. Jmjd4 expression is diminished upon ESC differentiation, and becomes restricted to certain developing organs, such as the eyes and gut, in embryonic Day‐11.5 embryos. Unexpectedly, Jmjd4‐null ESCs exhibited normal colony morphology and maintained normal expression of pluripotent genes. Furthermore, Jmjd4‐knockout embryos are born at a normal Mendelian ratio. Thus, JMJD4 is dispensable in murine development. Mol. Reprod. Dev. 83: 588–593, 2016. © 2016 Wiley Periodicals, Inc.
A minimum of 1‐year follow‐up for MiniArc single incision slings compared to Monarc transobturator slings: An analysis to evaluate durability of continence and medium‐term outcomes
Authors: Tutolo Manuela , De Ridder Dirk J.M.K. , Montorsi Francesco , Castagna Giulia , Deprest Jan , Schellart Renè P. , Ammirati Enrico , Van Der Aa Frank 
Published: May 2016

AimsTo compare efficacy and safety of two commercially available single incision slings (SIS) and trans‐obturator vaginal tapes (TOT), namely MiniArc™ and Monarc™ slings, and report the results at 5‐year follow‐up.MethodsA retrospective‐observational study of prospectively collected data was conducted on 381 women with primary stress urinary incontinence (SUI) in a single tertiary referral center. Patients treated with MiniArc™ and Monarc™ were compared. Data regarding intraoperative and post‐operative outcomes were collected and compared. Kaplan–Meier analyses assessed continence rate (CR), objective cure (OC) rate, de novo overactive bladder symptoms (OAB), surgical failure (SF), and erosion free rates at 1‐, 3‐, and 5‐year follow‐up. The log‐rank test was used to compare efficacy and complication between patients stratified according to the type of surgery.ResultsMedian follow‐up was 60 months. Of 381 patients, 215 (56%) were treated with Monarc™ slings and 166 (44%) with MiniArc™. The two groups were homogeneous in terms of pre‐operative characteristics. At 5‐year follow‐up, no difference was found in CR between Monarc™ and Miniarc™ patients (87% vs. 89%; P = 0.41). Monarc™ showed better OAB free rates (97% vs. 92%; P = 0.012). No significant differences have been found in terms of SF, erosion, and OC rates. These results are limited by their retrospective nature.ConclusionsWe demonstrated that the short‐term results of MiniArc™, are maintained over time, defining the comparability of the two slings at 5 years in terms of subjective and objective outcomes and complications. Neurourol. Urodynam. 36:803–807, 2017. © 2016 Wiley Periodicals, Inc.