bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term maintenance of efficacy of dapagliflozin in patients with type 2 diabetes mellitus and cardiovascular disease
Authors: Leiter L. A. , Cefalu W. T. , de Bruin T. W. A. , Xu J. , Parikh S. , Johnsson E. , Gause‐Nilsson I. 
Published: March 2016

AimTo evaluate the long‐term efficacy, safety and tolerability of dapagliflozin versus placebo added to usual care in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).MethodsData were pooled from two phase III studies (NCT01031680 and NCT01042977) in high‐risk patients (N = 1887) with T2DM and CVD treated with dapagliflozin (10 mg/day) or placebo. Patients completing the double‐blind treatment studies (24 weeks) entered one or two sequential double‐blind, long‐term (LT) extensions of 28 (LT1; n = 1649) and 52 (LT2; n = 568) weeks.ResultsBaseline and CVD characteristics were similar in the two groups. Patients entering LT1 and LT2 on dapagliflozin maintained a greater mean reduction in glycated haemoglobin (HbA1c) versus placebo at 52 weeks [LT1, −0.58% (95% confidence interval −0.68, −0.49)] and 104 weeks [LT2, −0.35% (95% confidence interval −0.59, −0.12)]. Mean body weight and systolic blood pressure (SBP) reductions versus placebo were maintained in patients entering LT1 (52 weeks; −2.23 kg and −3.25 mmHg, respectively) and LT2 (104 weeks; −3.16 kg and −2.03 mmHg, respectively). Patients on dapagliflozin had a better three‐item composite endpoint of clinical benefit (glycaemia, weight and SBP) compared with placebo at week 24 (LT1, 10.1% vs. 1.1%) and week 104 (LT2, 6.7% vs. 1.4%). Genital and urinary tract infections were more frequent with dapagliflozin than with placebo. Events of hypoglycaemia, renal impairment/failure and volume depletion were similar between groups.ConclusionsThe long‐term efficacy of dapagliflozin to maintain reductions in HbA1c, SBP and body weight over 2 years, together with its tolerability profile, make dapagliflozin an appropriate option in high‐risk patients with T2DM and CVD.
Insight into the durability of plant resistance to aphids from a demo‐genetic study of Aphis gossypii in melon crops
Authors: Thomas Sophie , Vanlerberghe‐Masutti Flavie , Mistral Pascale , Loiseau Anne , Boissot Nathalie 
Published: March 2016

AbstractResistance breakdown has been observed following the deployment of plant cultivars resistant to pests. Assessing the durability of a resistance requires long‐term experiments at least at a regional scale. We collected such data for melon resistance conferred by the Vat gene cluster to melon aphids. We examined landscape‐level populations of Aphis gossypii collected in 2004–2015, from melon‐producing regions with and without the deployment of Vat resistance and with different climates. We conducted demo‐genetic analyses of the aphid populations on Vat and non‐Vat plants during the cropping seasons. The Vat resistance decreased the density of aphid populations in all areas and changed the genetic structure and composition of these populations. Two bottlenecks were identified in the dynamics of adapted clones, due to the low levels of production of dispersal morphs and winter extinction. Our results suggest that (i) Vat resistance will not be durable in the Lesser Antilles, where no bottleneck affected the dynamics of adapted clones, (ii) Vat resistance will be durable in south‐west France, where both bottlenecks affected the dynamics of adapted clones and (iii) Vat resistance will be less durable in south‐east France, where only one of the two bottlenecks was observed.
Microbial control of soil organic matter mineralization responses to labile carbon in subarctic climate change treatments
Authors: Rousk Kathrin , Michelsen Anders , Rousk Johannes 
Published: March 2016

AbstractHalf the global soil carbon (C) is held in high‐latitude systems. Climate change will expose these to warming and a shift towards plant communities with more labile C input. Labile C can also increase the rate of loss of native soil organic matter (SOM); a phenomenon termed ‘priming’. We investigated how warming (+1.1 °C over ambient using open top chambers) and litter addition (90 g m−2 yr−1) treatments in the subarctic influenced the susceptibility of SOM mineralization to priming, and its microbial underpinnings. Labile C appeared to inhibit the mineralization of C from SOM by up to 60% within hours. In contrast, the mineralization of N from SOM was stimulated by up to 300%. These responses occurred rapidly and were unrelated to microbial successional dynamics, suggesting catabolic responses. Considered separately, the labile C inhibited C mineralization is compatible with previously reported findings termed ‘preferential substrate utilization’ or ‘negative apparent priming’, while the stimulated N mineralization responses echo recent reports of ‘real priming’ of SOM mineralization. However, C and N mineralization responses derived from the same SOM source must be interpreted together: This suggested that the microbial SOM‐use decreased in magnitude and shifted to components richer in N. This finding highlights that only considering SOM in terms of C may be simplistic, and will not capture all changes in SOM decomposition. The selective mining for N increased in climate change treatments with higher fungal dominance. In conclusion, labile C appeared to trigger catabolic responses of the resident microbial community that shifted the SOM mining to N‐rich components; an effect that increased with higher fungal dominance. Extrapolating from these findings, the predicted shrub expansion in the subarctic could result in an altered microbial use of SOM, selectively mining it for N‐rich components, and leading to a reduced total SOM‐use.
Progress in upscaling Miscanthus biomass production for the European bio‐economy with seed‐based hybrids
Authors: Clifton‐Brown John , Hastings Astley , Mos Michal , McCalmont Jon P. , Ashman Chris , Awty‐Carroll Danny , Cerazy Joanna , Chiang Yu‐Chung , Cosentino Salvatore , Cracroft‐Eley William , Scurlock Jonathan , Donnison Iain S. , Glover Chris , Gołąb Izabela , Greef Jörg M. , Gwyn Jeff , Harding Graham , Hayes Charlotte , Helios Waldemar , Hsu Tsai‐Wen , Huang Lin S. , Jeżowski Stanisław , Kim Do‐Soon , Kiesel Andreas , Kotecki Andrzej , Krzyzak Jacek , Lewandowski Iris , Lim Soo Hyun , Liu Jianxiu , Loosely Marc , Meyer Heike , Murphy‐Bokern Donal , Nelson Walter , Pogrzeba Marta , Robinson George , Robson Paul , Rogers Charlie , Scalici Giovanni , Schuele Heinrich , Shafiei Reza , Shevchuk Oksana , Schwarz Kai‐Uwe , Squance Michael , Swaller Tim , Thornton Judith , Truckses Thomas , Botnari Vasile , Vizir Igor , Wagner Moritz , Warren Robin , Webster Richard , Yamada Toshihiko , Youell Sue , Xi Qingguo , Zong Junqin , Flavell Richard 
Published: March 2016

AbstractField trials in Europe with Miscanthus over the past 25 years have demonstrated that interspecies hybrids such as M. × giganteus (M × g) combine both high yield potentials and low inputs in a wide range of soils and climates. Miscanthus hybrids are expected to play a major role in the provision of perennial lignocellulosic biomass across much of Europe as part of a lower carbon economy. However, even with favourable policies in some European countries, uptake has been slow. M × g, as a sterile clone, can only be propagated vegetatively, which leads to high establishment costs and low multiplication rates. Consequently, a decade ago, a strategic decision to develop rapidly multiplied seeded hybrids was taken. To make progress on this goal, we have (1) harnessed the genetic diversity in Miscanthus by crossing and progeny testing thousands of parental combinations to select several candidate seed‐based hybrids adapted to European environments, (2) established field scale seed production methods with annual multiplication factors >1500×, (3) developed the agronomy for establishing large stands from seed sown plug plants to reduce establishment times by a year compared to M × g, (4) trialled a range of harvest techniques to improve compositional quality and logistics on a large scale, (5) performed spatial analyses of yield potential and land availability to identify regional opportunities across Europe and doubled the area within the bio‐climatic envelope, (6) considered on‐farm economic, practical and environmental benefits that can be attractive to growers. The technical barriers to adoption have now been overcome sufficiently such that Miscanthus is ready to use as a low‐carbon feedstock in the European bio‐economy.
Ablation Characteristic of Ilmenite using UV Nanosecond and Femtosecond Lasers: Implications for Non‐Matrix‐Matched Quantification
Authors: Li Zhen , Hu Zhaochu , Günther Detlef , Zong Keqing , Liu Yongsheng , Luo Tao , Zhang Wen , Gao Shan , Hu Shenghong 
Published: March 2016

Ilmenite (FeTiO3) is a common accessory mineral and has been used as a powerful petrogenetic indicator in many geological settings. Elemental fractionation and matrix effects in ilmenite (CRN63E‐K) and silicate glass (NIST SRM 610) were investigated using 193 nm ArF excimer nanosecond (ns) laser and 257 nm femtosecond (fs) laser ablation systems coupled to an inductively coupled plasma‐mass spectrometer. The concentration‐normalised 57Fe and 49Ti responses in ilmenite were higher than those in NIST SRM 610 by a factor of 1.8 using fs‐LA. Compared with the 193 nm excimer laser, smaller elemental fractionation was observed using the 257 nm fs laser. When using 193 nm excimer laser ablation, the selected range of the laser energy density had a significant effect on the elemental fractionation in ilmenite. Scanning electron microscopy images of ablation craters and the morphologies of the deposited aerosol materials showed more melting effects and an enlarged particle deposition area around the ablation site of the ns‐LA‐generated crater when compared with those using fs‐LA. The ejected material around the ns crater predominantly consisted of large droplets of resolidified molten material; however, the ejected material around the fs crater consisted of agglomerates of fine particles with ‘rough' shapes. These observations are a result of the different ablation mechanisms for ns‐ and fs‐LAs. Non‐matrix‐matched calibration was applied for the analysis of ilmenite samples using NIST SRM 610 as a reference material for both 193 nm excimer LA‐ICP‐MS and fs‐LA‐ICP‐MS. Similar analytical results for most elements in ilmenite samples were obtained using both 193 nm excimer LA‐ICP‐MS at a high laser energy density of 12.7 J cm−2 and fs‐LA‐ICP‐MS.
Effect of Different Sampling Methodologies on Measured Methane Concentrations in Groundwater Samples
Authors: Molofsky Lisa J. , Richardson Stephen D. , Gorody Anthony W. , Baldassare Fred , Black June A. , McHugh Thomas E. , Connor John A. 
Published: March 2016

AbstractAnalysis of dissolved light hydrocarbon gas concentrations (primarily methane and ethane) in water supply wells is commonly used to establish conditions before and after drilling in areas of shale gas and oil extraction. Several methods are currently used to collect samples for dissolved gas analysis from water supply wells; however, the reliability of results obtained from these methods has not been quantified. This study compares dissolved methane and ethane concentrations measured in groundwater samples collected using three sampling methods employed in pre‐ and post‐drill sampling programs in the Appalachian Basin. These include an open‐system collection method where 40 mL volatile organic analysis (VOA) vials are filled directly while in contact with the atmosphere (Direct‐Fill VOA) and two alternative methods: (1) a semi‐closed system method whereby 40 mL VOA vials are filled while inverted under a head of water (Inverted VOA) and (2) a relatively new (2013) closed system method in which the sample is collected without direct contact with purge water or the atmosphere (IsoFlask®). This study reveals that, in the absence of effervescence, the difference in methane concentrations between the three sampling methods was relatively small. However, when methane concentrations equaled or exceeded 20 mg/L (the approximate concentration at which effervescence occurs in the study area), IsoFlask® (closed system) samples yielded significantly higher methane concentrations than Direct‐Fill VOA (open system) samples, and Inverted VOA (semi‐closed system) samples yielded lower concentrations. These results suggest that open and semi‐closed system sample collection methods are adequate for non‐effervescing samples. However, the use of a closed system collection method provides the most accurate means for the measurement of dissolved hydrocarbon gases under all conditions.
Crude Oil Metabolites in Groundwater at Two Spill Sites
Authors: Bekins Barbara A. , Cozzarelli Isabelle M. , Erickson Melinda L. , Steenson Ross A. , Thorn Kevin A. 
Published: March 2016

AbstractTwo groundwater plumes in north central Minnesota with residual crude oil sources have 20 to 50 mg/L of nonvolatile dissolved organic carbon (NVDOC). These values are over 10 times higher than benzene and two to three times higher than Diesel Range Organics in the same wells. On the basis of previous work, most of the NVDOC consists of partial transformation products from the crude oil. Monitoring data from 1988 to 2015 at one of the sites located near Bemidji, MN show that the plume of metabolites is expanding toward a lakeshore located 335 m from the source zone. Other mass balance studies of the site have demonstrated that the plume expansion is driven by the combined effect of continued presence of the residual crude oil source and depletion of the electron accepting capacity of solid phase iron oxide and hydroxides on the aquifer sediments. These plumes of metabolites are not covered by regulatory monitoring and reporting requirements in Minnesota and other states. Yet, a review of toxicology studies indicates that polar metabolites of crude oil may pose a risk to aquatic and mammalian species. Together the results suggest that at sites where residual sources are present, monitoring of NVDOC may be warranted to evaluate the fates of plumes of hydrocarbon transformation products.
Flares during long‐term entecavir therapy in chronic hepatitis B
Authors: Chi Heng , Arends Pauline , Reijnders Jurriën G P , Carey Ivana , Brown Ashley , Fasano Massimo , Mutimer David , Deterding Katja , Oo Ye H , Petersen Jörg , van Bommel Florian , de Knegt Robert J , Santantonio Teresa A , Berg Thomas , Welzel Tania M , Wedemeyer Heiner , Buti Maria , Pradat Pierre , Zoulim Fabien , Hansen Bettina E , Janssen Harry L A ,   for the VIRGIL Surveillance Study Group (European surveillance network for vigilance against viral resistance)
Published: March 2016

AbstractBackground and AimThe incidence and consequences of flares during first‐line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of alanine aminotransferase (ALT) flares during long‐term entecavir (ETV) in chronic hepatitis B (CHB).MethodsCHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as > 3× increase in ALT compared with baseline or lowest on‐treatment level and an absolute ALT > 3× ULN. Flares were designated as host‐induced (preceded by hepatitis B virus (HBV)‐DNA decline), virus‐induced (HBV‐DNA increase), or indeterminate (stable HBV‐DNA).ResultsSeven hundred and twenty‐nine patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline hepatitis B e antigen (HBeAg)‐positivity (HR 2.84; P = 0.005) and high HBV‐DNA (Hazard ratio (HR) 1.30; P = 0.003) predicted flares. There were 12 (40%) host‐induced, 7 (23%) virus‐induced, and 11 (37%) indeterminate flares. Host‐induced flares occurred earlier than virus‐induced (median: 15 vs 83 weeks; P = 0.027) or indeterminate flares (15 vs 109 weeks; P = 0.011). Host‐induced flares were associated with biochemical remission, and HBeAg (n = 3) and hepatitis B surface antigen (n = 2) seroconversions were exclusively observed among patients with these flares. Virus‐induced flares were associated with ETV resistance (n = 2) and non‐compliance (n = 1).ConclusionThe incidence of ALT flares during ETV was low in this real‐life cohort. ETV can be safely continued in patients with host‐induced flares. Treatment adherence and drug resistance must be assessed in patients with virus‐induced flares.
Asian consensus on the relationship between obesity and gastrointestinal and liver diseases
Authors: Koh Jianyi Calvin , Loo Wai Mun , Goh Khean Lee , Sugano Kentaro , Chan Wah Kheong , Chiu Wai Yan Philip , Choi Myung‐Gyu , Gonlachanvit Sutep , Lee Wei‐Jei , Lee Wei Jie Jonathan , Lee Yeong Yeh , Lesmana Laurentius A , Li You‐Ming , Liu Chun Jen , Matsuura Bunzo , Nakajima Atsushi , Ng Enders Kwok Wai , Sollano Jose D , Wong Simon Kin Hung , Wong Vincent W S , Yang Yunsheng , Ho Khek Yu , Dan Yock Young 
Published: March 2016

AbstractThe incidence of obesity is increasing in Asia, with implications on gastrointestinal (GI) and liver diseases. The Gut and Obesity in Asia Workgroup comprises regional experts with the aim of studying relationship between obesity and the GI and liver diseases in Asia. Through literature review and the modified Delphi process, consensus statements examining the impact of obesity on esophageal, gastric, pancreatic, colorectal, and liver diseases, exploring relationship between gut microbiome and obesity, and assessing obesity therapies have been produced by the Gut and Obesity in Asia Workgroup. Sixteen experts participated with 9/15 statements having strong consensus (>80% agreement). The prevalence of obesity in Asia is increasing (100% percentage agreement in brackets), and this increased prevalence of obesity will result in a greater burden of obesity‐related GI and liver diseases (93.8%). There was consensus that obesity increases the risk of gastric cancer (75%) and colorectal neoplasia (87.5%). Obesity was also associated with Barrett's esophagus and esophageal adenocarcinoma (66.7%) and pancreatic cancer (66.7%) in Asia. The prevalence of non‐alcoholic fatty liver disease (NAFLD) in Asia is on the rise (100%), and the risk of NAFLD in Asia (100%) is increased by obesity. Obesity is a risk factor for the development of hepatocellular carcinoma (93.8%). Regarding therapy, it was agreed that bariatric surgery was an effective treatment modality for obesity (93.8%) but there was less agreement on its benefit for NAFLD (62.5%). These experts' consensus on obesity and GI diseases in Asia forms the basis for further research, and its translation into addressing this emerging issue.
All‐oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub‐analysis in Asian patients from the HALLMARK DUAL study
Authors: Kao Jia‐Horng , Lee Youn‐Jae , Heo Jeong , Ahn Sang‐Hoon , Lim Young‐Suk , Peng Cheng‐Yuan , Chang Ting‐Tsung , Torbeyns Anne , Hughes Eric , Bhore Rafia , Noviello Stephanie 
Published: March 2016

AbstractBackground & AimsDaclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT‐1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients.MethodsTreatment‐naive patients were randomly assigned (2:1; double‐blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non‐responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post‐treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated.ResultsThis post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3% were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0% of treatment‐naive, ineligible/intolerant and non‐responder patients, respectively, and was comparable with non‐Asian patients. SVR12 by baseline factors including age, viral load, interleukin‐28B genotype and cirrhosis status was similar between the Asian sub‐cohorts. Among 18 Asian patients with NS5A‐Y93H or NS5A‐L31M/V resistance‐associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non‐Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2%). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12.ConclusionsAll‐oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT‐1b infection.
Infection of non‐host model plant species with the narrow‐host‐range Cacao swollen shoot virus
Authors: Friscina Arianna , Chiappetta Laura , Jacquemond Mireille , Tepfer Mark 
Published: March 2016

SummaryCacao swollen shoot virus (CSSV) is a major pathogen of cacao (Theobroma cacao) in Africa, and long‐standing efforts to limit its spread by the culling of infected trees have had very limited success. CSSV is a particularly difficult virus to study, as it has a very narrow host range, limited to several tropical tree species. Furthermore, the virus is not mechanically transmissible, and its insect vector can only be used with difficulty. Thus, the only efficient means to infect cacao plants that have been experimentally described so far are by particle bombardment or the agroinoculation of cacao plants with an infectious clone. We have genetically transformed three non‐host species with an infectious form of the CSSV genome: two experimental hosts widely used in plant virology (Nicotiana tabacum and N. benthamiana) and the model species Arabidopsis thaliana. In transformed plants of all three species, the CSSV genome was able to replicate, and, in tobacco, CSSV particles could be observed by immunosorbent electron microscopy, demonstrating that the complete virus cycle could be completed in a non‐host plant. These results will greatly facilitate the preliminary testing of CSSV control strategies using plants that are easy to raise and to transform genetically.
Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure
Authors: Inomata Kei , Taniguchi Shinji , Yonemoto Hiroki , Inoue Takeshi , Kawase Akihiko , Kondo Yuichi 
Published: March 2016

AbstractBackgroundEarly postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO2) target range (85–92%) from April 2011. Lower SpO2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO2 target range, during the early postnatal stage, increases the risk of DA closure failure.MethodsInfants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84–100% in study period 1 and 85–92% in period 2.ResultsEighty‐two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure.ConclusionLower early postnatal oxygen saturation target range increases the risk of DA closure failure.