bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Mild to Moderate Renal Impairment on the Pharmacokinetics of the Nucleoside Analog Hepatitis C Virus Polymerase Inhibitor Mericitabine
Authors: Haznedar Joshua , Moreira Sebastian , Marbury Thomas , Robson Richard , Smith William , Kulkarni Rohit , Munson Marie L. , Thommes James A. , Lemenuel‐Diot Annabelle , Washington Carla , Smith Patrick , Chen Ya‐Chi 
Published: December 2013

Abstract

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Mericitabine is the prodrug of RO4995855, a selective inhibitor of the hepatitis C virus (HCV) NS5B polymerase. This study assessed the effect of renal impairment on RO4995855 pharmacokinetics. In this open‐label study, HCV‐negative volunteers (18–75 years) with normal renal function (NRF: creatinine clearance [CLCR] >80 mL/min, n = 10) or stable renal impairment (mild: CLCR 50–80 mL/min, n = 10; moderate: CLCR 30–49 mL/min, n = 10) received oral mericitabine 1000 mg twice daily (BID) (500 mg BID for moderate renal impairment) for 5 days. Primary outcome measures were renal clearance, maximum plasma concentration (Cmax), and area under the concentration‐time curve (0–12 h) (AUC0–12) for RO4995855. Renal clearance decreased as renal function decreased. Relative to subjects with NRF, the geometric mean ratios (GMR) for AUC0–12 and Cmax in mild renal impairment subjects were 1.45 (90% confidence interval [CI], 1.26–1.66) and 1.14 (1.02–1.28), respectively. For moderate renal impairment subjects, the dose‐normalized GMR for AUC0–12 and Cmax relative to NRF subjects were 2.51 (90% CI, 2.19–2.88) and 1.76 (1.56–1.97), respectively. Renal clearance of RO4995855 declined in subjects with mild/moderate renal impairment following mericitabine. Dose adjustment of mericitabine may be required in patients with moderate renal impairment.
Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21
Authors: Hibaoui Youssef , Grad Iwona , Letourneau Audrey , Sailani M Reza , Dahoun Sophie , Santoni Federico A , Gimelli Stefania , Guipponi Michel , Pelte Marie Françoise , Béna Frédérique , Antonarakis Stylianos E , Feki Anis 
Published: December 2013

AbstractDown syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD‐SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual‐specificity tyrosine‐(Y)‐phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contributes to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects.
Naringin Mitigates Erythrocytes Aging Induced by Paclitaxel: An In Vitro Study
Authors: Harisa Gamaleldin I. 
Published: December 2013

ABSTRACTIn this study, the protective role of naringin (NAR) against paclitaxel (PTX)‐induced erythrocytes aging has been investigated using human erythrocyte as an in vitro model. Erythrocytes were incubated with PTX in the presence and absence of NAR. Incubation of erythrocytes with PTX resulted in increased protein carbonyl content and malondialdehyde and hemolysis percentage compared with control. Furthermore, a significant increase in the ratios of glutathione peroxidase/glutathione reductase, superoxide dismutase/glutathione peroxidase, and superoxide dismutase/catalase in PTX‐treated cells was observed, compared with control cells. In contrast, reduced glutathione/oxidized glutathione ratio and glucose‐6‐phosphate dehydrogenase activity were decreased upon PTX treatment. The simultaneous incubation of erythrocytes with PTX and NAR restored these variables to values similar to those of control erythrocytes. These results suggest that NAR inhibited PTX‐induced aging by lessening the PTX‐induced oxidative stress.
Randomized, placebo‐controlled single‐ascending‐dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS‐986001, in healthy subjects
Authors: Urata Y. , Paintsil E. , Cheng Y.‐C. , Matsuda T. , Sevinsky H. , Hawthorne D. , Bertz R. , Hanna G.J. , Grasela D. , Hwang C. 
Published: December 2013

AbstractThe objectives of this study were to evaluate the safety, tolerability and pharmacokinetics (PK) of BMS‐986001 as a single oral dose in healthy male subjects. Sixty‐four healthy male subjects were randomized to receive a single dose of BMS‐986001 or placebo in this single‐blind, placebo‐controlled, sequential ascending‐dose study. There were eight treatment groups (10, 30, 100, 300, 600, and 900 mg fed; and 100 and 300 mg fasted) of eight subjects each (BMS‐986001 n = 6/placebo n = 2). BMS‐986001 was well tolerated, with no serious adverse events (AEs), deaths, or discontinuations due to AEs reported. AEs were experienced by 14.6% of subjects receiving BMS‐986001; however, these did not appear to be dose related and were not considered to be related to study drug. BMS‐986001 was rapidly absorbed and exhibited a linear dose–exposure relationship across the dose range studied. PK appeared similar whether administered with or without food. Administration of BMS‐986001 as a single dose was generally safe and well tolerated. A linear dose–exposure relationship was seen across all doses studied, with no apparent food effect. Further clinical development is warranted.
Coccolithophore carbonate during the last 450 ka in the NW Pacific Ocean (ODP site 1209B, Shatsky Rise)
Authors: BORDIGA MANUELA , COBIANCHI MIRIAM , LUPI CLAUDIA , PELOSI NICOLA , VENTI NICHOLAS L. , ZIVERI PATRIZIA 
Published: December 2013

ABSTRACTThis study focuses on Pleistocene–Holocene sediments from the Shatsky Rise (Ocean Drilling Program Site 1209B, NW Pacific Ocean). We quantify the contribution of calcite made by coccoliths in oceanic sediments, investigating the role of calcareous nannoplankton during the last 450 ka. Coccolith carbonate constitutes 60–90% of bulk carbonate. Coccolith carbonate accumulation rates (CARs) and CaCO3 fine fraction confirm that coccolithophores are major contributors to the carbonate export and accumulation. Primary productivity shows highest values from marine isotope stage (MIS) 12 to 8. Thereafter, although coccolith calcite content remains high, other sediment components, such as as foraminifera and biogenic opal, seem to be favored, perhaps related to an increase in fertilization by eolian dust. Our results demonstrate the important role of coccolithophore production and sedimentation on the regulation of ocean carbonate chemistry on time scales >1000–100 000 years. On glacial–interglacial scales, coccolithophore productivity could have affected deep‐water saturation by buffering deep‐sea CO2 through increased carbonate dissolution episodes. Spectral and wavelet analyses are consistent with CARs primarily driven by glacial–interglacial variability and obliquity‐controlled changes. Coccolith‐based paleoceanographic reconstructions allow us to establish that during the last 450 ka the mid‐latitudes of the NW Pacific are controlled by the dynamics of the El Niño Southern Oscillation perturbations and Boreal Monsoon system.
Testing the sensitivity of the East Antarctic Ice Sheet to Southern Ocean dynamics: past changes and future implications
Authors: FOGWILL CHRISTOPHER J. , TURNEY CHRISTIAN S. M. , MEISSNER KATRIN J. , GOLLEDGE NICHOLAS R. , SPENCE PAUL , ROBERTS JASON L. , ENGLAND MATHEW H. , JONES RICHARD T. , CARTER LIONEL 
Published: December 2013

ABSTRACTThe stability of Antarctic ice sheets and their potential contribution to sea level under projected future warming remains highly uncertain. The Last Interglacial (135 000–116 000 years ago) provides a potential analogue, with global temperatures 2 °C higher and rates of sea‐level rise >5.6 m ka−1, leading to sea levels 6.6–9.4 m higher than present. The source(s) of this sea‐level rise remain fiercely debated. Here we report a series of independent model simulations exploring the effects of migrating Southern Hemisphere Westerlies (SHWs) on Southern Ocean circulation and Antarctic ice‐sheet dynamics. We suggest that southerly shifts in winds may have significantly impacted the sub‐polar gyres, inducing pervasive warming (0.2–0.8 °C in the upper 1200 m) adjacent to sectors of the East Antarctic Ice Sheet (EAIS), which due to their geometries and connectivity to the Southern Ocean are highly sensitive to ocean forcing. We conclude that the EAIS potentially made a substantial, hitherto unsuspected, contribution to interglacial sea levels, and given 21st‐century projections in the Southern Annular Mode and associated SHW migration, we highlight how pervasive circum‐Antarctic warming may threaten EAIS stability.
E‐PASS comprehensive risk score is a good predictor of postsurgical mortality from comorbid disease in elderly gastric cancer patients
Authors: Ariake Kyohei , Ueno Tatsuya , Takahashi Michinaga , Goto Shinji , Sato Shun , Akada Masanori , Naito Hiroo 
Published: December 2013

Background and ObjectivesThe long‐term prognosis of elderly gastric cancer patients is poor because of the cancer and unrelated comorbidities. We investigated the risk factors for mortality after gastrectomy to aid surgeons in deciding the correct operative procedure for elderly gastric cancer patients.MethodsA total of 414 gastric cancer patients surgically treated between 2002 and 2012 were divided into two groups A (≥75 years) and B (<75 years). Data were collected retrospectively and analyzed using the Estimation of Physiological Ability and Surgical Stress (E‐PASS) scoring system as a predictor of postoperative complications.ResultsOverall survival (P < 0.001), disease‐specific survival (P = 0.029), and survival rate related to comorbid disease (P < 0.001) were significantly reduced in elderly patients compared with younger patients. Surgical treatment for Group A involved lesser extent of nodal resection (P < 0.001). Multivariate analysis revealed that a comprehensive risk score (CRS) ≥0.5 based on the E‐PASS score (P = 0.022) and severe postoperative complication (P = 0.002) were independent risk factors for mortality from comorbid disease.ConclusionsThus, E‐PASS‐based CRS was a good predictor of comorbidity‐related mortality. CRS may help surgeons select elderly patients with gastric cancer for surgical or other therapies. J. Surg. Oncol. 2014 109:586–592. © 2013 Wiley Periodicals, Inc.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: A case‐control study from a Chinese center
Authors: Huang Chao‐Qun , Feng Jue‐Ping , Yang Xiao‐Jun , Li Yan 
Published: December 2013

AbstractBackgroundAdvanced colorectal cancer (CRC) is prone to developing peritoneal carcinomatosis (PC). This case‐control study was to compare the efficacy and safety of cytoreductive surgery (CRS) versus CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Chinese patients with CRC PC.MethodsThe 62 consecutive PC patients were treated with CRS (Control group, n = 29) or CRS + HIPEC (Study group, n = 33). The primary end point was overall survival (OS), the secondary end points were perioperative safety profiles.ResultsFor the comparison of Control versus Study groups, the peritoneal cancer index (PCI) ≤20 was 13 (44.8%) versus 16 (48.5%) patients (P = 0.78), complete cytoreduction (CC0‐1) was achieved in 9 (31.0%) versus 14 (42.4%) cases (P = 0.36). At the median OS was 8.5 (95% confidence interval [CI] 4.7–12.4) versus 13.7 (95% CI 10.0–16.5) months (P = 0.02), the 1‐, 2‐, and 3‐year survival rates were 27.5% versus 63.6%, 12.0% versus 20.0%, and 0.0% versus 16.0%, respectively. Serious adverse events in postoperative 30 days were 9.4% versus 28.6% (P = 0.11). Multivariate analysis revealed that CRS + HIPEC, CC0‐1, adjuvant chemotherapy ≥6 cycles were independent factors for OS benefit.ConclusionCRS + HIPEC could improve OS for CRC PC patients, with acceptable perioperative safety. J. Surg. Oncol 2014; 109:730–739. © 2013 The Authors. Journal of Surgical Oncology. Published by Wiley Periodicals, Inc.
APPRAISING AND SELECTING STRATEGIES TO COMBAT AND MITIGATE DESERTIFICATION BASED ON STAKEHOLDER KNOWLEDGE AND GLOBAL BEST PRACTICES IN CAPE VERDE ARCHIPELAGO
Authors: De Pina Tavares Jacques , Ferreira António J. D. , Reis Eduardo A. , Baptista Isaurinda , Amoros Regla , Costa Lenira , Furtado Adriano M. , Coelho Celeste 
Published: December 2013

ABSTRACTDesertification is the most disturbing and detrimental cause of rural vulnerability in Cape Verde, affecting families' material and environmental resources. Combating desertification in Cape Verde is complex because it involves addressing a mixture of endogenous (manual agriculture, fuel wood and fodder extraction, land tenure and steep slopes) and exogenous drivers (high rainfall variability, climate change, prolonged drought or heavy rainfall). To address and mitigate the adverse effects of desertification, it is necessary to develop an approach that identifies and brings together all the key stakeholders affected by and acting on the desertification issue, including land users, policy makers, managers, researchers and rural development technicians. This paper presents a hybrid methodology based on global best practices, applied in Cape Verde. It combines experiences and skills of local stakeholders (farmers, local association of land users and local non‐governmental organizations) with scientific knowledge of external stakeholders such as technicians of the Ministry of Rural Development, environmental advisors of Municipalities and researchers. Integration takes place following a participatory process of appraising and selecting desertification control strategies. The paper presents the first results obtained from application of the hybrid methodology to Ribeira Seca, the largest watershed of Santiago Island. The approach was evaluated with local and external stakeholders. Both groups appreciated that they could voice their views and discuss ways to overcome barriers and also to take full advantage of the opportunities offered by jointly selected promising desertification mitigation options. Copyright © 2013 John Wiley & Sons, Ltd.
FORMAL INSTITUTIONS AND THEIR ROLE IN PROMOTING SUSTAINABLE LAND MANAGEMENT IN BOTETI, BOTSWANA
Authors: Mulale K. , Chanda R. , Perkins J. S. , Magole L. , Sebego R. J. , Atlhopheng J. R. , Mphinyane W. , Reed M. S. 
Published: December 2013

ABSTRACTThe aim of this paper is to discuss the role of existing policies, programmes and legislation in promoting sustainable land management and livelihoods in mid‐central Botswana. The paper is based on data from the survey of relevant literature, analysis of policy and legal documents, field observations and a series of stakeholder workshops held in the villages of Mopipi, Mokobaxane and Rakops in Boteti Sub‐District between 2008 and 2009. The study's findings indicate that formal land use and rangeland management institutions have influenced the process of environmental change in the study area, mostly in a negative way. Institutional failure and support to the expansion of the livestock sector have promoted overstocking; arable production support has encouraged land clearance in a drought‐prone and windy area; whereas protectionist wildlife management has been in conflict with, rather than complementary to, traditional uses of the communal rangelands. The environmental outcomes of all this have been the shrinkage of the Boteti commons, overgrazing, deforestation and wind erosion. The study recommends adoption of a community‐based natural resource management strategy, which could simultaneously secure livelihoods and conserve the commons. Copyright © 2013 John Wiley & Sons, Ltd.
Deposit formation from lubricant degradation: a uniform layer deposition model
Authors: Kouame Sylvain‐Didier B. , Vander Wal Randall L. , Perez Joseph 
Published: December 2013

ABSTRACTReported is a new model describing deposit formation and ageing along the so‐called universal mass deposition curve. The penn state micro‐oxidation (PSMO) apparatus produced model deposits at varied test durations in order to study the ageing mechanism of thin film deposits from mineral base oil. Along the ‘universal’ mass deposition curve, mass deposition rates were correlated to film chemistry. Formed by concerted oxidation‐polymerisation reactions, chemical group and elemental content analyses were performed by Fourier transformed infrared spectroscopy‐attenuated total reflectance and energy dispersive spectroscopy, respectively. The results showed that deposit formation initiates as a film — uniform in composition. After an induction period, the film growth accelerates then slows and eventually falls off, with a decrease in mass often observed. These stages reflect underlying physical and chemical changes as the deposit progresses from an initial polymeric, lacquer‐type deposit, towards a final dark, carbonaceous deposit, along the universal mass deposition curve. Carbonyl, hydroxyl and sp3 hybridised carbon were identified as the main functional groups found across all deposit types albeit at different levels. Correlative behaviour was observed between changes in functional group infrared intensities and O‐atom and C‐atom content. These trends are interpreted as reflecting concerted deoxygenation and dehydrogenation processes, throughout the deposit, over the course of ageing, thus providing a foundation for the uniform layer model. Copyright © 2013 John Wiley & Sons, Ltd.
Findings from a fleet test on the performance of two engine oil formulations in automotive CNG engines
Authors: Macián V. , Tormos B. , Olmeda P. , Gómez Y. A. 
Published: December 2013

ABSTRACTThis work presents a comparative assessment of engine oil performance on field test using urban transport vehicles powered by compressed natural gas engines using two different mineral oil formulations approved by engine manufacturer. The first one is considered as a baseline reference, and the second one is a higher quality formulation in terms of base stock refining and additive content. Higher quality oil has shown a significant enhanced lubricant performance, leading to reach the oil drain interval defined by engine manufacturer on these engines without penalties in maintenance costs.In order to assess oil performance, an oil analysis programme has been established for oil samples collected from vehicles operated under real service conditions in an urban transport fleet. Monitored parameters include oxidation, nitration, aminic anti‐oxidant additives depletion, anti‐wear additives depletion, total acid number, total basic number and remaining useful life number (as an estimation of anti‐oxidant additive depletion including aminic and zinc dialkyldithiophosphate).Results obtained in more than 90 samples from 15 different vehicles have shown higher degradation rates for low quality lubricant oil formulation. This deviation can be explained taking into account factors related with lower anti‐oxidant additives content and lower thermal stability that can be mainly related with the base stock quality. This lower oil performance can be finally converted into higher vehicle maintenance cost and lower engine reliability. Copyright © 2013 John Wiley & Sons, Ltd.
The effect of topical anesthetic hydration on the depth of thermal injury from the plasma skin regeneration device
Authors: Sanderson Alicia R. , Wu Edward C. , Liaw Lih‐Huei L. , Garg Rohit , Gangnes Richard A. 
Published: December 2013

ABSTRACTBackground and ObjectivesThe plasma skin regeneration (PSR) device delivers thermal energy to the skin by converting nitrogen gas to plasma. Prior to treatment, hydration of the skin is recommended as it is thought to limit the zone of thermal damage. However, there is limited data on optimal hydration time. This pilot study aims to determine the effect of topical anesthetic application time on the depth of thermal injury from a PSR device using histology.Study Design/Materials and MethodsPSR (1.8 and 3.5 J) was performed after 0, 30, or 60 minutes of topical anesthetic application. Rhytidectomy was then performed and skin was fixed for histologic analysis. Four patients (two control and four treatment sites per patient) undergoing rhytidectomy were recruited for the study. Each patient served as his/her own control (no hydration). A scoring system for tissue injury was developed. Epidermal injury, the presence of vacuolization, blistering, damage to adnexal structures, and depth of dermal collagen changes were evaluated in over 1,400 high‐power microscopy fields.ResultsThere was a significant difference in the average thermal injury score, depth of thermal damage, and epidermal injury when comparing controls to 30 minutes of hydration (P = 0.012, 0.012, 0.017, respectively). There was no statistical difference between controls and 60 minutes of hydration or between 30 and 60 minutes of hydration. Epidermal vacuolization at low energy and patchy distribution of thermal injury was also observed.ConclusionTopical hydration influences the amount of thermal damage when applied to skin for 30 minutes prior to treatment with the PSR device. There was a trend toward decreasing thermal damage at 60 minutes, and there was no difference between treatment for 30 or 60 minutes. The data suggest that application of topical anesthetic for a short period of time prior to treatment with the PSR device is cost‐effective, safe, and may be clinically beneficial. Lasers Surg. Med. 46:127–131, 2014. © 2013 Wiley Periodicals, Inc.
Graphene–Epoxy Flexible Transparent Capacitor Obtained By Graphene–Polymer Transfer and UV‐Induced Bonding
Authors: Sangermano Marco , Chiolerio Alessandro , Veronese Giulio Paolo , Ortolani Luca , Rizzoli Rita , Mancarella Fulvio , Morandi Vittorio 
Published: December 2013

A new approach is reported for the preparation of a graphene–epoxy flexible transparent capacitor obtained by graphene–polymer transfer and UV‐induced bonding. SU8 resin is employed for realizing a well‐adherent, transparent, and flexible supporting layer. The achieved transparent graphene/SU8 membrane presents two distinct surfaces: one homogeneous conductive surface containing a graphene layer and one dielectric surface typical of the epoxy polymer. Two graphene/SU8 layers are bonded together by using an epoxy photocurable formulation based on epoxy resin. The obtained material showed a stable and clear capacitive behavior.
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