bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo
Authors: Yasuda S , Sho M , Yamato I , Yoshiji H , Wakatsuki K , Nishiwada S , Yagita H , Nakajima Y 
Published: January 2013

Summary
Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application.
Higher mortality in metabolically obese normal‐weight people than in metabolically healthy obese subjects in elderly Koreans
Authors: Choi Kyung Mook , Cho Hyun Joo , Choi Hae Yoon , Yang Sae Jeong , Yoo Hye Jin , Seo Ji A. , Kim Sin Gon , Baik Sei Hyun , Choi Dong Seop , Kim Nan Hee 
Published: January 2013

AbstractObjectiveThe purpose of this study was to investigate the impact of body mass index (BMI) and the presence of metabolic syndrome (MetS) on all‐cause and cardiovascular mortality in elderly Korean men and women, and especially to compare metabolically obese normal‐weight (MONW) and metabolically healthy obese (MHO) subjects.Patients and methodsA total of 2317 elderly people (over 60 years of age) were studied using follow‐up data from the South‐West Seoul (SWS) Study, a prospective cohort study. Mortality from all causes and cardiovascular disease (CVD) were evaluated according to the combination of the presence or absence of MetS and Asian‐specific body mass index (BMI) criteria (BMI <23 kg/m2; normal weight, BMI 23–24·9 kg/m2; overweight, BMI ≥25 kg/m2; obesity).ResultsDuring a median follow‐up of 10·3 years, 393 subjects died, including 126 from CVD. Among subjects with MetS, all‐cause and CVD mortality were significantly higher in normal‐weight subjects than overweight or obese individuals in Cox proportional‐hazard models adjusted for confounding factors. Furthermore, among six groups with various MetS/BMI combinations, MONW individuals had the highest risk, whereas overweight subjects without MetS had the lowest risk of death from all causes and CVD [HR = 2·2 (95% CI = 1·4–3·4), HR = 3·0 (95% CI = 1·4–6·6) respectively]. Interestingly, all‐cause mortality was significantly higher in MONW than MHO individuals.ConclusionsIn contrast to MHO subjects, elderly individuals with the MONW phenotype exhibited greater all‐cause mortality during 10 years of follow‐up.
Aberrant TGF‐β signaling underlies the pathogenesis of aortic aneurysm in Shprintzen‐Goldberg syndrome
Authors: Jan A 
Published: January 2013

Mutations in the TGF‐β repressor SKI cause Shprintzen‐Goldberg syndrome with aortic aneurysmDoyle et al. (2012)Nature Genetics 44(11):1249–54
Are early and late rate of force development differently influenced by fast‐velocity resistance training?
Authors: de Oliveira Felipe B. D. , Rizatto Guilherme F. , Denadai Benedito S. 
Published: January 2013

SummaryThis study examined the effect of fast‐velocity concentric isokinetic resistance training (FV) on the rate of force development (RFD) at early (<100 ms) and late phases (>100 ms) of rising muscle force. Nine men participated in a 6‐week resistance training intervention for the lower body, and nine matched subjects participated as controls (CON). During concentric isokinetic (180°s−1) knee extension training, subjects were instructed to do each contraction ‘as fast and forcefully as possible’. Maximal muscle strength (MVC) and RFD (0–10, 0–20, …, 0–250 ms from the onset of contraction) were measured during maximal voluntary isometric contraction of the knee extensors (KE). There were no significant changes in MVC of KE in both groups after intervention (FV = 314·2 ± 101·1 versus 338·7 ± 88·0 N∙m, P>0·05; CON = 293·3 ± 94·8 versus 280·0 ± 72·2 N∙m, P>0·05). The RFD increased 39–71% at time intervals up to 90 ms from the onset of the contraction (P<0·05), whereas no change occurred at later time intervals. Similarly, relative RFD (i.e.%MVC∙s−1) (RFDr) increased 33–56% at time intervals up to 70 ms from the onset of the contraction (P<0·05). It can be concluded that a short period of resistance training performed with concentric fast‐velocity isokinetic muscle contractions is able to enhance RFD and RFDr obtained at the early phase of rising muscle force.
International workshop: islet transplantation without borders enabling islet transplantation in Greece with international collaboration and innovative technology
Authors: Papas Klearchos K. , Karatzas Theodore , Berney Thierry , Minor Thomas , Pappas Paris , Pattou François , Shaw James , Toso Christian , Schuurman Henk‐Jan 
Published: January 2013

AbstractRecently, initiatives have been undertaken to establish an islet transplantation program in Athens, Greece. A major hurdle is the high cost associated with the establishment and maintenance of a clinical‐grade islet manufacturing center. A collaboration was established with the University Hospitals of Geneva, Switzerland, to enable remote islet cell manufacturing with an established and validated fully operational team. However, remote islet manufacturing requires shipment of the pancreas from the procurement to the islet manufacturing site (in this case from anywhere in Greece to Geneva) and then shipment of the islets from the manufacturing site to the transplant site (from Geneva to Athens). To address challenges related to cold ischemia time of the pancreas and shipment time of islets, a collaboration was initiated with the University of Arizona, Tucson, USA. An international workshop was held in Athens, December 2011, to mark the start of this collaborative project. Experts in the field presented in three main sessions: (i) islet transplantation: state‐of‐the‐art and the “network approach”; (ii) technical aspects of clinical islet transplantation and outcomes; and (iii) islet manufacturing – from the donated pancreas to the islet product. This manuscript presents a summary of the workshop.
Imperilled phylogenetic endemism of Malagasy lemuriformes
Authors: Gudde Renske M. , Joy Jeffrey B. , Mooers Arne O. 
Published: January 2013

AbstractAimTo highlight where in Madagascar the phylogenetically and spatially rare lemur species at risk of extinction are concentrated.LocationMadagascar.MethodsPhylogenetic endemism (PE) is a combined measure for apportioning a phylogenetic tree across a landscape used to identify those geographical locations that contain spatially rare phylogenetic diversity (Rosauer et al., 2009). We present a simple extension (imperilled phylogenetic endemism) that scales this phylogenetic diversity by the probability of its loss to extinction. We apply these measures to a composite phylogeny of all confirmed Malagasy lemuriform species using International Union for Conservation of Nature (IUCN) extent of occurrence and threat status data.ResultsWe find that, because nonimperilled species are scattered about the lemuriform tree, interior branches of the tree are still quite secure: this also means that areas of high phylogenetic endemism for Madagascar lemuriformes are often the same areas as those of high imperilled PE (IPE), as both are heavily weighted by branches nearer the tips. However, although the North of Madagascar holds the largest amount of spatially rare evolutionary history using both PE and IPE, there are additional pockets of imperilled history in the south and west.Main ConclusionsCorrelations of endemism and threat status with phylogenetic isolation are modest across lemurs and so are not substitutable conservation values. They might best be integrated on the landscape using IPE. As illustrated here, IPE successfully highlights areas containing species which are at once threatened with extinction and that are phylogenetically and spatially rare.
Revealing a conservation challenge through partitioned long‐term beta diversity: increasing turnover and decreasing nestedness of boreal lake metacommunities
Authors: Angeler David G. 
Published: January 2013

AbstractAimAssessing long‐term (1992–2009) trends of littoral invertebrate and phytoplankton metacommunities in boreal lakes with emphasis on separating the nestedness and turnover components of beta diversity. Deriving implications for regional biodiversity conservation and management, based on a data‐intensive approach with high ecological realism.LocationSweden (Northern Europe).MethodsA recently published method was used to partition beta diversity into species turnover and nestedness components. Regression analyses were used to test for monotonic temporal change of these diversity fractions through time. Associations between the temporal diversity patterns of taxonomic groups and environmental variables were studied using correlation analyses.ResultsTurnover of both metacommunities increased monotonically over the study period, while nestedness decreased. In invertebrates, these changes correlated mainly with regional changes in acidity, while phytoplankton responded more to changing water clarity. Nestedness and turnover patterns were inversely correlated in both groups, but neither turnover nor nestedness was correlated between invertebrates and phytoplankton. Nestedness of both groups explained a lower percentage of the partitioned variance compared with turnover.Main conclusionResults suggest that all lakes contribute more equally to regional diversity over time and are, as a result, all potential targets of management actions. Not only is a regional conservation strategy logistically difficult, it is also a financially expensive expectation.
The challenge of understanding the origin, pathways and extent of fungal invasions: global populations of the Neofusicoccum parvum–N. ribis species complex
Authors: Sakalidis M. L. , Slippers B. , Wingfield B. D. , Hardy G. E. St. J. , Burgess T. I. 
Published: January 2013

AbstractAimCryptic species in the Neofusicoccum parvum–N. ribis species complex have only recently been described, invalidating previous interpretations on host and geographical distribution. This study aimed to characterize the diversity and distribution of these species and to understand the patterns of host association, likely origins and their patterns of spread.LocationAustralia, Brazil, Cameroon, Chile, China, Colombia, Ethiopia, France, Greece, India, Indonesia, Iran, Italy, Japan, Kenya, Mexico, New Zealand, Panama, Portugal, Puerto Rico, South Africa, South Korea, Spain, Swaziland, Taiwan, Thailand, Uganda, United States of America, Uruguay, Zambia and Zimbabwe.MethodsUsing the unique polymorphisms that separate species within the complex, we evaluated sequence search results available in public and in our own databases. In addition, the global distribution of diversity of N. parvum was analysed using seven microsatellite markers.ResultsNeofusicoccum parvum is found in 90 hosts across six continents and 29 countries. Neofusicoccum kwambonambiense is found on four continents, six countries and on 14 hosts; N. occulatum is found on four continents, four countries and on 11 hosts; N. umdonicola is found on two continents, countries and hosts; N. cordaticola is found on three continents, countries and hosts; N. batangarum is found on two continents, three countries and three hosts; and N. ribis is found on one host in one country. Population genetic analysis of the global N. parvum population reflects admixture and repeat introductions.Main conclusionsThis study illustrates the unfettered and frequent movement of latent pathogens across international borders. Amongst the species in the N. parvum–N. ribis complex, N. parvum is the most widespread and has been reported on the majority of the hosts studied. The current dispersal of N. parvum and its sister species is probably due to repeated introductions of plant material into new growing areas, with Eucalyptus and Vitis vinifera being two prominent candidates for material transfer.
Fine‐scale regional distribution modelling of rare and threatened species: bridging GIS Tools and conservation in practice
Authors: Lyet Arnaud , Thuiller Wilfried , Cheylan Marc , Besnard Aurélien 
Published: January 2013

AbstractAimSnakes are more vulnerable to extinction than many other taxa. Additionally, their secretive behaviour makes it difficult to acquire the baseline ecological knowledge required to reliably evaluate extinction risks. Consequently, the conservation status of snakes has only been assessed for small populations; reliable methods for large‐scale evaluation remain to be tested. In this study, we explored how habitat‐suitability models (HSMs) could be used to provide relevant information to help assess extinction risks and formulate appropriate conservation strategies for the Orsini's viper (Vipera ursinii), a rare, endangered snake species.LocationProvence‐Alpes‐Côte d'Azur region in south‐eastern France (c. 30,000 km²).MethodsWe developed a high‐resolution HSM (50 × 50 m) using a large sample of species presence data and nine climatic and land cover predictors. We used this model to predict the potential distribution of the Orsini's viper as well as to investigate the main environmental drivers explaining this distribution. We also assessed the geographical barriers between local populations and tested whether forest cutting would reduce fragmentation.ResultsThe occurrence of the Orsini's viper was strongly correlated with the annual cumulative temperature and with vegetation cover type. The total extent of suitable habitat covered 2.98% of the study area and was highly fragmented into 1417 distinct areas. Among these areas of suitable habitat, 21 were confirmed to have the species. These represented 22,134 ha and a potential carrying capacity of 168,000 individuals.Main conclusionsOur HSM was consistent with the past assessment of the distribution of the Orsini's viper. Our HSM represents a sound benchmark for the distribution of the species and can provide a powerful tool to help with the search of new populations, the identification of areas for habitat restoration, the test conservation strategies and effects of climate change. We found that forest cutting may lead to reconnect close isolated areas of suitable habitat.
Hypoglycaemia‐induced changes in regional brain volume and memory function
Authors: Kirchhoff B. A. , Lugar H. M. , Smith S. E. , Meyer E. J. , Perantie D. C. , Kolody B. C. , Koller J. M. , Arbelaez A. M. , Shimony J. S. , Hershey T. 
Published: January 2013

AbstractBackgroundHypoglycaemic events can be a serious complication of insulin therapy in Type 1 diabetes mellitus. Severe hypoglycaemic exposure can lead to episodic memory impairments, including anterograde amnesia. However, relatively little is known regarding the long‐term impact of severe hypoglycaemia on brain structure in Type 1 diabetes mellitus. The goals of the present study were to gain a greater understanding of the long‐term effects of severe hypoglycaemia exposure on brain structure and the neural correlates of memory impairments in Type 1 diabetes mellitus.Case reportRegional grey and white matter volume and total white matter lesion volume were quantified in an individual with long‐standing hypoglycaemia‐induced anterograde amnesia and compared with age‐ and gender‐matched healthy controls. Our patient has significant reductions in grey matter volume in the hippocampus, thalamus and pallidum, and significant reductions in white matter volume in the splenium, isthmus of the cingulate and cerebellum. He also has a significantly larger total white matter lesion volume than controls.ConclusionThis case study highlights the potential of hypoglycaemia for permanent deleterious effects on brain structure and memory function. Our results suggest that subcortical grey matter, periventricular white matter and posterior white matter may be most susceptible to injury from hypoglycaemia exposure, and that structural damage to the hippocampus and isthmus of the cingulate may play a central role in hypoglycaemia‐induced memory impairments.
Primary‐care observational database study of the efficacy of GLP‐1 receptor agonists and insulin in the UK
Authors: Hall G. C. , McMahon A. D. , Dain M.‐P. , Wang E. , Home P. D. 
Published: January 2013

AbstractAimsWe investigated use and efficacy of glucagon‐like peptide‐1 (GLP‐1) receptor agonists in UK practice.MethodsPeople starting a GLP‐1 receptor agonist (exenatide, liraglutide) or insulin (glargine, detemir, NPH) after a regimen of two or three oral glucose‐lowering agents were identified from The Health Information Network observational primary care database (2007–2011). Mean change in HbA1c and body weight were compared at 1 year between cohorts, adjusting for baseline characteristics.ResultsBaseline characteristics of GLP‐1 receptor agonist (n = 1123) vs. insulin (n = 1842) users were HbA1c 78 vs. 84 mmol/mol (9.3 vs. 9.8%) and BMI 38.2 vs. 30.9 kg/m2. The GLP‐1 receptor agonist cohort was younger, had shorter diabetes duration and follow‐up, less microvascular disease and heart failure, higher estimated glomerular filtration rate and more use of oral glucose‐lowering agents. Lower HbA1c reduction on GLP‐1 receptor agonist [7 vs. 13 mmol/mol (0.6 vs. 1.2%) (n = 366 vs. 892)] was not statistically significant [adjusted mean difference −1.4 (95% CI −4.1, 1.2) mmol/mol], except in the highest HbA1c quintile [>96 mmol/mol (>10.9%); adjusted mean difference −17.8 (−28.6, −7.0) mmol/mol]. GLP‐1 receptor agonist users lost weight [−4.5 vs. +1.5 kg; adjusted mean difference 4.7 (3.7, 5.8) kg; n = 335 vs. 634]. A UK 6‐month target reduction for GLP‐1 receptor agonists of 11 mmol/mol (1.0%) HbA1c and 3% weight was reached by 24.9% of those continuing treatment.ConclusionsThose starting GLP‐1 receptor agonists are heavier with better glycaemic control than those starting basal insulin. Subsequently, they have improved weight change, with similar HbA1c reduction unless baseline HbA1c is very high. The UK 6‐month GLP‐1 receptor agonist target is usually not reached.
Macroevolutionary perspectives to environmental change
Authors: Condamine Fabien L. , Rolland Jonathan , Morlon Hélène 
Published: January 2013

AbstractPredicting how biodiversity will be affected and will respond to human‐induced environmental changes is one of the most critical challenges facing ecologists today. Here, we put current environmental changes and their effects on biodiversity in a macroevolutionary perspective. We build on research in palaeontology and recent developments in phylogenetic approaches to ask how macroevolution can help us understand how environmental changes have affected biodiversity in the past, and how they will affect biodiversity in the future. More and more paleontological and phylogenetic data are accumulated, and we argue that much of the potential these data have for understanding environmental changes remains to be explored.
Evolution of suicide as a defence strategy against pathogens in a spatially structured environment
Authors: Berngruber Thomas W. , Lion Sébastien , Gandon Sylvain 
Published: January 2013

AbstractSuicide upon infection by lytic phages is known in several bacteria species and represents an effective defence strategy to limit phage spread. However, the ecological conditions favouring the evolution of such a radically altruistic behaviour are unclear. Here, we model the feedback of epidemiology on host evolution in a spatially structured environment and we generate several specific predictions on altruistic suicide evolution. We test these predictions experimentally by competing E. coli cells carrying the suicide gene Lit against non‐carrier cells in the presence or in the absence of the lytic phage T6. We show that in accord with our theoretical analysis altruistic suicide is only favoured in the presence of the phage in spatially structured environments at intermediate levels of mixing. Our work provides a general explanation for the evolution of altruistic defence strategies against pathogens. We discuss the implications of these results for oncolytic virus therapy.
Somatosensory profiling of intra‐oral capsaicin and menthol in healthy subjects
Authors: Lu Shengyi , Baad‐Hansen Lene , List Thomas , Zhang Zhenting , Svensson Peter 
Published: January 2013

This study was designed to investigate the effect of surrogate orofacial pain models on the quantitative sensory testing (QST) profile in healthy participants. Capsaicin, menthol, or saline (control) were applied topically onto the gingiva of 15 healthy subjects for 15 min. During application, the subjects rated pain intensity on a score of 0–10, on an electronic visual analog scale (VAS). A standardized intra‐oral QST protocol was performed before and immediately after application. Data obtained before and after application were compared using rank‐sum tests, and QST profiles were made after Z‐transformation. Application of capsaicin caused moderate levels of pain (VASpeak = 6.0 ± 0.7), and application of menthol produced mild levels of pain (VASpeak = 1.8 ± 0.6). Capsaicin induced hypersensitivity to warmth, heat pain and cold pain and hyposensitivity to mechanical stimuli. Menthol induced hypersensitivity to cold and warmth. Saline caused hypersensitivity to heat pain and hyposensitivity to mechanical stimuli. However, somatosensory profiles from Z‐scores demonstrated sensory gains regarding warmth detection and heat pain only after application of capsaicin. In conclusion, a standardized battery of QST showed somatosensory changes after application of capsaicin, menthol and saline to the gingiva. However, the Z‐score‐based profiles may only reflect the most prominent somatosensory changes and thus represent a conservative approach for evaluation of data.