bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome
Authors: Cremon C. , Stanghellini V. , Barbaro M. R. , Cogliandro R. F. , Bellacosa L. , Santos J. , Vicario M. , Pigrau M. , Alonso Cotoner C. , Lobo B. , Azpiroz F. , Bruley des Varannes S. , Neunlist M. , DeFilippis D. , Iuvone T. , Petrosino S. , Di Marzo V. , Barbara G. 
Published: February 2017

SummaryBackgroundIntestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation.AimTo assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS.MethodsWe conducted a pilot, 12‐week, randomised, double‐blind, placebo‐controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low‐grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme‐linked immunoassay, liquid chromatography and Western blot.ResultsA total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05).ConclusionsThe marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.
A population pharmacokinetic model of AT9283 in adults and children to predict the maximum tolerated dose in children with leukaemia
Authors: Duong Janna K. , Griffin Melanie J. , Hargrave Darren , Vormoor Josef , Edwards David , Boddy Alan V. 
Published: February 2017

AimsAT9283 is used to treat patients with solid tumours and patients with leukaemia. However, the maximum tolerated dose (MTD) for children with leukaemia remains unknown due to early termination of the Phase I trial. The aim of this study was to develop a population model of AT9283 to describe the pharmacokinetics in adults and children and to estimate the MTD in children with leukaemia.MethodsData from Phase I dose‐escalation studies in adults and children were used to build a population pharmacokinetic model (NONMEM v7.3). Potential covariates investigated included body weight, body surface area (BSA), glomerular filtration rate (GFR), age and sex. Model‐derived area under the concentration–time curve was used to investigate the relationship between dose and exposure in adults and children.ResultsThe plasma concentrations of AT9283 (n = 1770) from 92 patients (53 adults, 39 children) were used to build a two‐compartment model with all pharmacokinetic parameters scaled using body weight. Renal function (GFR), but not BSA, was a significant covariate for the clearance of AT9283. In children with leukaemia (median weight 16 kg), a flat dose of 500 mg 72 h–1 provided similar drug exposures at the MTD as the adult population. The estimated MTD for children with leukaemia, therefore, is 30 mg kg−1 72 h–1.ConclusionFor adults, GFR was a significant predictor of clearance, whilst body‐weight based dosing was more useful than BSA in determining the drug exposure in children. The MTD was estimated to be 30 mg kg−1 72 h–1 children with leukaemia.
Use of Moderate‐Intensity Statins for Low‐Density Lipoprotein Cholesterol Level above 190 mg/dL at Baseline in Koreans
Authors: Kim Hun‐Sung , Lee Hyeseon , Lee Sue Hyun , Jeong Yoo Jin , Kim Tong Min , Yang So Jung , Baik Sun Jung , Kim Hyunah , Lee Seung‐Hwan , Cho Jae Hyoung , Choi In‐Young , Yoon Kun‐Ho , Kim Ju Han 
Published: February 2017

AbstractThe ACC/AHA 2013 guideline recommends high‐intensity statin therapy for a decrease in low‐density lipoprotein cholesterol (LDL‐C) level by >50% among patients with baseline values of ≥190 mg/dL (approximately 4.872 mmol/L); however, this value should be modified before applying it to Korean populations. We investigated the statin‐specific LDL‐C‐lowering effects in Korean patients with baseline LDL‐C value ≥4.872 mmol/L. Data of patients prescribed a statin for the first time from January 2009 to December 2013 were assessed. In patients with baseline LDL‐C value ≥4.872 mmol/L, laboratory data for a maximum of 6 months from the date of first statin prescription were collected. Among 33,721 patients who were prescribed a statin for the first time, 655 patients had a baseline LDL‐C value ≥4.872 mmol/L (1.9%). Of these, 179 patients were analysed. Patients receiving moderate‐intensity statins were divided into two groups based on LDL‐C reduction rate (p = 0.0002), defined as moderate–high‐intensity (atorvastatin 20 mg, rosuvastatin 10 mg, simvastatin 20 mg) and moderate–low‐intensity (atorvastatin 10 mg, pitavastatin 2 mg, pravastatin 40 mg) statin groups. LDL‐C reduction rates did not significantly differ between the moderate–high‐ and high‐intensity statin groups (p = 0.4895). We found that some moderate‐intensity statins demonstrated a LDL‐C‐lowering effect of more than 50% in Korean patients with a baseline LDL‐C value ≥4.872 mmol/L. Our results reflect the need of a large‐scale, randomized, controlled trial on partial reclassification of statins for patients with baseline LDL‐C value ≥4.872 mmol/L before adopting ACC/AHC guidelines in Korea.
Biology and insights into the role of cohesin protease separase in human malignancies
Authors: Zhang Nenggang , Pati Debananda 
Published: February 2017

ABSTRACTSeparase, an enzyme that resolves sister chromatid cohesion during the metaphase‐to‐anaphase transition, plays a pivotal role in chromosomal segregation and cell division. Separase protein, encoded by the extra spindle pole bodies like 1 (ESPL1) gene, is overexpressed in numerous human cancers including breast, bone, brain, and prostate. Separase is oncogenic, and its overexpression is sufficient to induce mammary tumours in mice. Either acute or chronic overexpression of separase in mouse mammary glands leads to aneuploidy and tumorigenesis, and inhibition of separase enzymatic activity decreases the growth of human breast tumour xenografts in mice. This review focuses on the biology of and insights into the molecular mechanisms of separase as an oncogene, and its significance and implications for human cancers.
Using individual‐condition measures to predict the long‐term importance of habitat extent for population persistence
Authors: Cosgrove Anita J. , McWhorter Todd J. , Maron Martine 
Published: February 2017

AbstractHabitat loss and fragmentation are causing widespread population declines, but identifying how and when to intervene remains challenging. Predicting where extirpations are likely to occur and implementing management actions before losses result may be more cost‐effective than trying to reestablish lost populations. Early indicators of pressure on populations could be used to make such predictions. Previous work conducted in 2009 and 2010 identified that the presence of Eastern Yellow Robins (Eopsaltria australis) in 42 sites in a fragmented region of eastern Australia was unrelated to woodland extent within 500 m of a site, but the robins’ heterophil:lymphocyte (H:L) ratios (an indicator of chronic stress) were elevated at sites with low levels of surrounding woodland. We resurveyed these 42 sites in 2013 and 2014 for robin presence to determine whether the H:L ratios obtained in 2009 and 2010 predicted the locations of extirpations and whether the previous pattern in H:L ratios was an early sign that woodland extent would become an important predictor of occupancy. We also surveyed for robins at 43 additional sites to determine whether current occupancy could be better predicted by landscape context at a larger scale, relevant to dispersal movements. At the original 42 sites, H:L ratios and extirpations were not related, although only 4 extirpations were observed. Woodland extent within 500 m had become a strong predictor of occupancy. Taken together, these results provide mixed evidence as to whether patterns of individual condition can reveal habitat relationships that become evident as local shifts in occupancy occur but that are not revealed by a single snapshot of species distribution. Across all 85 sites, woodland extent at scales relevant to dispersal (5 km) was not related to occurrence. We recommend that conservation actions focus on regenerating areas of habitat large enough to support robin territories rather than increasing connectivity within the landscape.
Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta‐regression analysis
Authors: Mainou Maria , Madenidou Anastasia‐Vasiliki , Liakos Aris , Paschos Paschalis , Karagiannis Thomas , Bekiari Eleni , Vlachaki Efthymia , Wang Zhen , Murad Mohammad Hassan , Kumar Shaji , Tsapas Apostolos 
Published: February 2017

AbstractObjectivesWe performed a systematic review and meta‐regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM).MethodsResponse outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression‐free survival (PFS). We used random‐effect meta‐regression models and conducted sensitivity analyses based on definition of CR and study quality.ResultsSeventy‐two trials were included in the systematic review, 63 of which contributed data in meta‐regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] −0.06, 0.10), in patients undergoing ASCT (−.11, 95% CI −0.44, 0.22) and in trials comparing ASCT with non‐ASCT patients (.04, 95% CI −0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results.ConclusionsThis meta‐regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.
Midbrain dopaminergic neuron activity across alternating brain states of urethane anaesthetized rat
Authors: Walczak Magdalena , Błasiak Tomasz 
Published: February 2017

AbstractMidbrain dopaminergic neurons are implicated in the control of motor functions and reward‐driven behaviours. The function of this neuronal population is strongly connected with distinct patterns of firing – irregular or bursting, which either maintains basal levels of dopamine (DA) or leads to phasic release, respectively. Heterogeneity of dopaminergic neurons, observed on both structural and functional levels, is also reflected in different responses of DA neurons to changes in global brain states. Preparation of urethane anaesthetized animal is a broadly used model to study brain state dependent activity of neurons. Unfortunately activity of midbrain DA neurons across urethane induced cyclic, spontaneous brain state alternations is poorly described. To fulfil this gap in our knowledge we have performed simultaneous, extracellular recordings of the firing of single putative DA neurons combined with continuous brain state monitoring. We found that during slow wave activity, the firing rate of recorded putative DA neurons was significantly higher compared to firing rates during activated state, both in ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). In the presence of cortical slow waves, putative dopaminergic neurons also intensified bursting activity, but the magnitude of this phenomena differed in respect to the examined region (VTA or SNc). Our results show that activity of DA neurons under urethane anaesthesia is brain‐state dependent and emphasize the importance of brain state monitoring during electrophysiological experiments.
Aged biochar affects gross nitrogen mineralization and recovery: a 15N study in two contrasting soils
Authors: Mia Shamim , Singh Balwant , Dijkstra Feike A. 
Published: February 2017

AbstractBiochar is a pyrolysed biomass and largely consists of pyrogenic carbon (C), which takes much longer to decompose compared to the biomass it is made from. When applied to soil, it could increase agricultural productivity through nutrient retention and changing soil properties. The biochar‐mediated nutrient retention capacity depends on the biochar properties, which change with time, and on soil properties. Here, we examined the effects of a wood biochar (20 t ha−1), that has aged (21 months) in a grassland field, on gross nitrogen (N) mineralization (GNM) and 15N recovery using a 15N tracer. A field experiment was conducted in two soil types, that is a Tenosol and a Dermosol, and also included a phosphorus (P) addition treatment (1 kg ha−1). Compared to the control, biochar with P addition significantly increased GNM in the Tenosol. Possibly, biochar and P addition enhanced nutrient availability in this nutrient‐limited soil, thereby stimulating microbial activity. In contrast, biochar addition reduced GNM in the Dermosol, possibly by protecting soil organic matter (SOM) from decomposition through sorption onto biochar surfaces and enhanced formation of organo‐mineral complexes in this soil that had a higher clay content (29% vs. 8% in the Tenosol). Compared to the control, biochar significantly increased total 15N recovery in the Tenosol (on average by 12%) and reduced leaching to subsurface soil layers (on average by 52%). Overall, 15N recovery was greater in the Dermosol (83%) than the Tenosol (63%), but was not affected by biochar or P. The increased N recovery with biochar addition in the sandy Tenosol may be due to retention at exchange sites on aged biochar, while such beneficial effects may not be visible in soils with higher clay content. Our results suggest that aged biochar may increase N use efficiency through reduced leaching or gaseous losses in sandy soils.
Sovereign Reputation and Yield Spreads: A Case Study on Retroactive Legislation
Authors: Randl Otto , Zechner Josef 
Published: February 2017

AbstractThis paper uses recent legislation in Austria to establish a link between sovereign reputation and yield spreads. In 2009, Hypo Alpe Adria International, a bank previously co-owned by the regional government of Carinthia, had been nationalized by Austria’s central government in order to avoid a default triggering multi-billion Euro local government guarantees. In 2015, special legislation retroactively introduced collective action clauses allowing a haircut on both the bonds and the guarantees while avoiding formal default. We document that legislative and administrative action designed to partly abrogate the guarantees resulted in a loss of reputation, leading to higher yield spreads for sovereign debt. Our analysis of covered bonds uncovers an increase in yield spreads on the secondary market and a deterioration of primary market conditions.
Banks’ Interest Rate Risk and Search for Yield: A Theoretical Rationale and Some Empirical Evidence
Authors: Memmel Christoph , Seymen Atılım , Teichert Max 
Published: February 2017

Abstract
We investigate German banks’ exposure to interest rate risk. In finance, higher demand for a risky asset is typically associated with higher expected return. However, employing a utility function which implies both risk-averse and risk-seeking behavior depending on the level of profits, we show that this relationship may get weaker and even change its sign at low profit levels. For the period 2005-14, we find not only the common positive relationship of higher expected returns and rising interest rate exposure but also that this relationship does become weaker with falling operative income, its sign eventually changing.
U‐Pb Geochronological and Thermochronological Time–Temperature Constraints of 40Ar/39Ar Hornblende Reference Material HB3gr
Authors: Blackburn Terrence , McLean Noah , Bowring Samuel A. 
Published: February 2017

Hornblende from the Lone Grove Pluton, Llano Uplift, Texas, has served as an irradiation reference material in 40Ar/39Ar studies for decades. In order to evaluate the apparent age bias that currently exists between the U‐Pb and 40Ar/39Ar systems, zircon and titanite were dated by isotope dilution‐thermal ionisation mass spectrometry (ID‐TIMS) from the same rock from which the hornblende 40Ar/39Ar reference material HB3gr is derived. Zircon U‐Pb data indicate initial crystallisation at 1090.10 ± 0.16 Ma (2s), a date that is 1.7% older than the accepted K‐Ar date (1072 ± 14 Ma, 2s) for HB3gr; an offset that exceeds the typical 0.5–1% bias between the two systems, though remaining within uncertainty due to the large uncertainties in the 40K decay constant. Zircon data are presented using both EARTHTIME tracers ET535 and ET2535 and are statistically indistinguishable. Single grain titanite analyses range between 1082 ± 0.75 and 1086 ± 0.81 Ma (2s) and are interpreted to record the subsequent cooling following crystallisation at rates between 30 and 50 °C Ma−1. This is supported by the observation that hornblende 40Ar/39Ar dates corrected for decay constant bias are resolvably younger than the zircon U‐Pb date and in good agreement with titanite U‐Pb dates, permitting the conclusion that both titanite U‐Pb and hornblende 40Ar/39Ar systems provide a record of cooling.
Composite reinforcement: Recent development of continuous glass fibers
Authors: Li Hong , Charpentier Thibault , Du Jincheng , Vennam Sandeep 
Published: February 2017

AbstractLight weight, glass fiber‐reinforced composites have gained a broad, global acceptance in commercial markets with a total of more than 7 billion of US dollars in revenue since its first commercial production in US in mid 1930s. This article briefly reviews recent development of continuous glass fibers with a focus on high‐performance glass fibers. With accelerated commercial demands on high‐performance glasses and/or glass fibers, there is a growing realization of fundamental needs in decoding nature of glass structures or “genes” of glass structure building blocks and establishing their relationships to properties of glasses or glass fibers. The related database development can enable researchers shortening the number of product development cycles to bring new fiber products to the market. A special section is, therefore, provided illustrating recent progress in characterizations of glass structures by using techniques of nuclear magnetic resonance spectroscopy, Raman spectroscopy, and molecular dynamics simulations.
Phenotypic analysis of circulating T‐cell subset and its association with burden of skin disease in patients with chronic actinic dermatitis: a hematologic and clinicopathologic study of 20 subjects
Authors: Hamada Toshihisa , Aoyama Yumi , Shirafuji Yoshinori , Iwatsuki Keiji 
Published: February 2017

AbstractBackgroundChronic actinic dermatitis (CAD) is a recurrent photosensitive dermatitis that occurs predominantly on sun‐exposed areas with unknown etiology. In severe cases, it may present with erythroderma, which is clinicopathologically analogous to cutaneous T‐cell lymphoma. Typically, inflammatory infiltrates in the skin lesions are mainly CD8+ reactive T cells. However, hematologic characteristics of CAD have not been fully elucidated.MethodsTwenty patients with CAD ranging in age from 45 to 86 years (median, 64), including 17 males and three females (M/F ratio, 5.7), were examined. All patients were phototested for UV light. In addition, seven of the 20 patients with extensive eruption were also tested for visible light. All biopsy specimens were obtained from the CAD eruptions (n = 25 lesions). Histopathologic and immunohistochemical studies were performed. Furthermore, flow cytometric analysis was performed to determine the CD4/8 ratio using peripheral blood mononuclear cells of 13 of the 20 patients.ResultsIn 11 of the 20 patients (55%), the eruption was localized to sun‐exposed areas. Skin‐infiltrating T cells were CD8‐dominant in the CAD eruption. Three patients (15%) showed erythroderma with a reduced CD4/8 ratio (median, 0.7) of peripheral mononuclear cells. As for treatment, eight of the 20 patients (40%) required oral cyclosporine in addition to topical therapies. Subsequently, the reduced CD4/8 ratio was normalized after treatment in two of the three patients with erythroderma.ConclusionsWe considered that there appeared to be a relationship between the reduced CD4/8 ratio of circulating T cells (hematologic burden) and the affected area (skin burden).
The IL15 +96522 A>T functional polymorphism is related to the differentiation of Th17 cells and the severity of Hashimoto's disease
Authors: Arakawa Y. , Watanabe M. , Takemura K. , Inoue N. , Hidaka Y. , Iwatani Y. 
Published: February 2017

SummaryTo clarify the association between the genetic producibility of IL‐15, a pro‐inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves’ disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD. The serum levels of IL‐15 were higher in individuals with the IL15 +96522 AA genotype than in those with the T allele, and they were also higher in patients with severe HD than in those with mild HD. On the other hand, the mRNA levels of IL‐15 were not significantly different among individuals with each genotype of both SNPs. After incubation with recombinant human IL‐15, the proportions of Th17 cells in CD4+ cells were increased, and those of Treg cells in CD4+ cells were maintained. Our study indicates that the IL15 +96522A/C polymorphism correlates with the severity of HD, most likely by increasing Th17 cells.