bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA‐seq of the aging brain in the short‐lived fish N. furzeri – conserved pathways and novel genes associated with neurogenesis
Authors: Baumgart Mario , Groth Marco , Priebe Steffen , Savino Aurora , Testa Giovanna , Dix Andreas , Ripa Roberto , Spallotta Francesco , Gaetano Carlo , Ori Michela , Terzibasi Tozzini Eva , Guthke Reinhard , Platzer Matthias , Cellerino Alessandro 
Published: July 2014

SummaryThe brains of teleost fish show extensive adult neurogenesis and neuronal regeneration. The patterns of gene regulation during fish brain aging are unknown. The short‐lived teleost fish Nothobranchius furzeri shows markers of brain aging including reduced learning performances, gliosis, and reduced adult neurogenesis. We used RNA‐seq to quantify genome‐wide transcript regulation and sampled five different time points to characterize whole‐genome transcript regulation during brain aging of N. furzeri. Comparison with human datasets revealed conserved up‐regulation of ribosome, lysosome, and complement activation and conserved down‐regulation of synapse, mitochondrion, proteasome, and spliceosome. Down‐regulated genes differ in their temporal profiles: neurogenesis and extracellular matrix genes showed rapid decay, synaptic and axonal genes a progressive decay. A substantial proportion of differentially expressed genes (~40%) showed inversion of their temporal profiles in the last time point: spliceosome and proteasome showed initial down‐regulation and stress‐response genes initial up‐regulation. Extensive regulation was detected for chromatin remodelers of the DNMT and CBX families as well as members of the polycomb complex and was mirrored by an up‐regulation of the H3K27me3 epigenetic mark. Network analysis showed extensive coregulation of cell cycle/DNA synthesis genes with the uncharacterized zinc‐finger protein ZNF367 as central hub. In situ hybridization showed that ZNF367 is expressed in neuronal stem cell niches of both embryonic zebrafish and adult N. furzeri. Other genes down‐regulated with age, not previously associated with adult neurogenesis and with similar patterns of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other hand, was up‐regulated with age.
Nicotine enhances modulation of food‐cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex
Authors: Kroemer Nils B. , Wuttig Franziska , Bidlingmaier Martin , Zimmermann Ulrich S. , Smolka Michael N. 
Published: July 2014

AbstractEndocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and, consequently, show associations with food and drug reward. In animal models, nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions. However, the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally. We used functional magnetic resonance imaging to investigate food‐cue reactivity after an overnight fast and following a caloric load (oral glucose tolerance test, OGTT) in 26 healthy normal‐weight never‐smokers. Moreover, we administered either nicotine (2 mg) or placebo gums using a randomized cross‐over design and assessed blood plasma levels of ghrelin and leptin. During fasting, nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased. After the OGTT, nicotine increased the modulatory effects of ghrelin and leptin on food‐cue reactivity, particularly in the ventromedial prefrontal cortex (vmPFC) and the amygdala. Critically, this led to an indirect modulation of the behavioral ‘appetizer effect’ (i.e. cue‐induced increases in subjective appetite) by homeostatic feedback signals via food‐cue reactivity in vmPFC. We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might, in turn, reduce appetite. This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal‐weight individuals might hint at a mechanism contributing to nicotine's anorexic potential.
Blood sugar levels are higher in obese young children in Sweden than in Poland
Authors: Hagman Emilia , Ighani Arani Perna , Fischer Manjula , Danielsson Pernilla , Marcinkiewicz Katarzyna , Petriczko Elzbieta , Marcus Claude 
Published: July 2014

AbstractAimAn elevated fasting glucose level is an early sign of metabolic dysfunction in obese children. This study compared fasting glucose levels in obese young children in Poland and Sweden.MethodsWe identified 109 obese children aged between two and 10 years from a Polish obesity register, with a mean BMI SDS (SD) of 3.72 (0.86). Each Polish child was matched by gender, age and degree of obesity, with ten children (n = 1090) from BORIS, the Swedish national childhood obesity treatment register. A group of 86 Swedish nonobese children served as controls.ResultsThe mean fasting glucose values of the Polish, Swedish and nonobese cohorts were 4.73 (0.51) mmol/L, 4.92 (0.50) mmol/L and 4.56 (0.39) mmol/L, respectively. After adjusting for variables affecting fasting glucose, the mean glucose value of the Swedish obese children was 0.20 mmol/L higher than that of Polish obese children (p < 0.0001) and 0.41 mmol/L higher than in nonobese controls (p < 0.0001).ConclusionSwedish obese young children had higher glucose levels than Polish obese young children. This suggests that Swedish obese children face a higher risk of the prediabetic stage impaired fasting glycaemia.
The severity of circulating neutrophil dysfunction in patients with cirrhosis is associated with 90‐day and 1‐year mortality
Authors: Taylor N. J. , Manakkat Vijay G. K. , Abeles R. D. , Auzinger G. , Bernal W. , Ma Y. , Wendon J. A. , Shawcross D. L. 
Published: July 2014

SummaryBackgroundPatients with cirrhosis are susceptible to sepsis, pre‐disposing to the development of encephalopathy, bleeding and organ dysfunction with associated high mortality.AimTo characterise circulating neutrophil function in a cirrhotic cohort as a determinant of 90‐day and 1‐year mortality.MethodsSixty‐two patients with cirrhosis [49 stable (Child–Pugh A/B/C = 24%/39%/37%); 13 acute‐on‐chronic liver failure] were prospectively studied and compared with 11 healthy controls. Neutrophil function was evaluated at baseline and repeated at critical points during the course of the patient's illness until death/transplantation. Neutrophil phenotype was determined using fluorochrome‐labelled antibodies to CD16/CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) and capacity (NPC) were determined using FITC‐labelled opsonised Escherichia coli. Oxidative burst (OB) was quantified by the percentage of neutrophils producing reactive oxygen species (ROS) and mean fluorescence intensity at rest, and after stimulation with E. coli. Physiological variables, biochemistry, microbiology and outcomes were collected. Plasma pro‐ and anti‐inflammatory cytokine profiles were performed by ELISA.ResultsNPA/NPC was impaired in cirrhosis with the most significant dysfunction being observed in those with advanced disease and in those treated with propranolol. NPC predicted survival in stable cirrhosis [AUROC 0.83 (95% CI 0.68–0.97); P = 0.021] and differentiated survivors from nonsurvivors (90‐day P = 0.01; 1 year P < 0.001). Resting OB ≥12% predicted 90‐day mortality with 80% sensitivity and 71% specificity [AUROC 0.81 (95% CI 0.64–0.97); P = 0.026 and differentiated survivors from nonsurvivors; P = 0.015].ConclusionCirculating neutrophils in patients with cirrhosis are dysfunctional and predict the development of infection, organ dysfunction and survival at 90 days and 1 year.
Systematic review with meta‐analysis: the I148M variant of patatin‐like phospholipase domain‐containing 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis
Authors: Chamorro A.‐J. , Torres J.‐L. , Mirón‐Canelo J.‐A. , González‐Sarmiento R. , Laso F.‐J. , Marcos M. 
Published: July 2014

SummaryBackgroundSeveral studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409 (C>G) in adiponutrin/patatin‐like phospholipase domain‐containing 3 gene (PNPLA3).AimTo evaluate the influence of this variant on ALC and other forms of ALD.MethodsWe performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta‐analysis was conducted in a random‐effects model. Calculations of the odds ratios (ORs) and their confidence intervals (CIs), tests for heterogeneity and sensitivity analyses were performed.ResultsDatabase search identified 11 previous studies available for inclusion with a total of 3495 patients with ALD (2087 with ALC) and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD). Patients with ALC compared to controls had a significantly higher prevalence of the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25–5.69; P < 0.00001) or GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67–2.17) or under a recessive or dominant model. Similar results were found when comparing separately patients with ALC vs. alcoholics without ALD or healthy subjects. An association of the G allele with ALD emerged when comparing ALD patients vs. alcoholics without ALD and/or healthy subjects although moderate to large heterogeneity was observed. Our data suggested an additive genetic model for this variant in ALD.ConclusionOur meta‐analysis shows that the rs738409 variant of PNPLA3 is clearly associated with alcoholic liver cirrhosis.
Disease‐specific death and metastasis do not occur in patients with Gleason score ≤6 at radical prostatectomy
Authors: Kweldam Charlotte F. , Wildhagen Mark F. , Bangma Chris H. , van Leenders Geert J.L.H. 
Published: July 2014

ObjectivesTo assess the metastasis‐free survival (MFS) and disease‐specific survival (DSS) in men with Gleason score ≤6 prostate cancer at radical prostatectomy (RP).Patients and MethodsWe included 1101 consecutive RP patients operated between March 1985 to July 2013 at a single institution. The outcome variables were MFS and DSS. The postoperative survival was estimated by the Kaplan–Meier method.ResultsThe Gleason score distribution of the study population (1101 patients) was Gleason score ≤6 (449, 41%), Gleason score 3 + 4 = 7 (436, 40%), Gleason score 4 + 3 = 7 (99, 9%) and Gleason score 8–10 (117, 11%). The median (interquartile range) postoperative follow‐up was 100 (48–150) months. During follow‐up 197 men (18%) died, of whom 42 (3.8%) died from prostate cancer‐related causes. In all, 19/1101 patients (1.7%) had documented lymph node metastasis at the time of RP: none with Gleason score ≤6, seven with Gleason score 3 + 4 = 7 (1.6%), six with Gleason score 4 + 3 = 7 (6.1%) and six with Gleason score 8–10 (5.1%). Distant metastasis occurred in 56/1101 patients (5.1%): none with Gleason score ≤6, 23 with Gleason score 3 + 4 = 7 (5.3%), 17 with Gleason score 4 + 3 = 7 (17%) and 16 with Gleason score 8–10 (14%). Disease‐specific death, stratified per Gleason‐score group was: none in ≤6, 16 (3.7%) in 3 + 4 = 7, 16 (16%) in 4 + 3 = 7 and 10 (8.5%) in 8–10 group.ConclusionNo metastasis or disease‐specific death were seen in men with Gleason score ≤6 prostate cancer at RP, showing the negligible potential to metastasise in this large subgroup of patients with prostate cancer.
Intracystic interferon therapy in childhood craniopharyngioma: who, when and how?
Authors: Bailey Simon , Parkes Jeannette 
Published: July 2014

SummaryA 13‐year‐old male presents with fluctuating visual disturbance and headaches. Imaging reveals a significant predominantly cystic suprasellar tumour, typical of a craniopharyngioma. The patient has growth hormone deficiency but the rest of the hypothalamic/pituitary axis is intact. What are the options for therapy in 2014? Specifically, is there a role for local treatment with interferon injected into the cyst cavity? The aim of management in children with craniopharyngiomas is to reduce the impact of the tumour as much as possible, while minimising the morbidity associated with treatment. There are a number of therapeutic options available: surgery, radiotherapy and the insertion of therapeutic agents directly into the tumour cyst. The role of intracystic therapy in the form of interferon is discussed; including when to use this therapeutic option and practical details of its use.
Evaluating multispecies landscape connectivity in a threatened tropical mammal community
Authors: Brodie Jedediah F. , Giordano Anthony J. , Dickson Brett , Hebblewhite Mark , Bernard Henry , Mohd‐Azlan Jayasilan , Anderson Jesse , Ambu Laurentius 
Published: July 2014

AbstractHabitat corridors are important tools for maintaining connectivity in increasingly fragmented landscapes, but generally they have been considered in single‐species approaches. Corridors intended to facilitate the movement of multiple species could increase persistence of entire communities, but at the likely cost of being less efficient for any given species than a corridor intended specifically for that species. There have been few tests of the trade‐offs between single‐ and multispecies corridor approaches. We assessed single‐species and multispecies habitat corridors for 5 threatened mammal species in tropical forests of Borneo. We generated maps of the cost of movement across the landscape for each species based on the species’ local abundance as estimated through hierarchical modeling of camera‐trap data with biophysical and anthropogenic covariates. Elevation influenced local abundance of banded civets (Hemigalus derbyanus) and sun bears (Helarctos malayanus). Increased road density was associated with lower local abundance of Sunda clouded leopards (Neofelis diardi) and higher local abundance of sambar deer (Rusa unicolor). Pig‐tailed macaque (Macaca nemestrina) local abundance was lower in recently logged areas. An all‐species‐combined connectivity scenario with least‐cost paths and 1 km buffers generated total movement costs that were 27% and 23% higher for banded civets and clouded leopards, respectively, than the connectivity scenarios for those species individually. A carnivore multispecies connectivity scenario, however, increased movement cost by 2% for banded civets and clouded leopards. Likewise, an herbivore multispecies scenario provided more effective connectivity than the all‐species‐combined scenario for sambar and macaques. We suggest that multispecies habitat connectivity plans be tailored to groups of ecologically similar, disturbance‐sensitive species to maximize their effectiveness.Evaluación de la Conectividad de Terrenos Multiespecie en una Comunidad Tropical de Mamíferos
Substance use and risk of death in young offenders: A prospective data linkage study
Authors: Kinner Stuart A. , Degenhardt Louisa , Coffey Carolyn , Hearps Stephen , Spittal Matthew , Sawyer Susan M. , Patton George C. 
Published: July 2014

AbstractIntroduction and AimsYoung offenders are at increased risk of preventable death after release from custody, but risk factors for death in this population are poorly understood. Despite their poor health profiles, no studies have examined mortality outcomes in young people who have served community‐based orders. The aims of this study were to describe the causes and identify risk factors for death in a cohort of young offenders in Victoria, Australia.Design and MethodsWe interviewed young people serving a custodial (n = 273) or community‐based order (n = 242) in Victoria, Australia in 2002–2003. Measures included demographics and family history, offence history, experience of victimisation, mental illness, self‐harm and substance use. Deaths up to 31 December 2011 were identified through a probabilistic linkage with the National Death Index.ResultsThe all‐cause crude mortality rate was 4.2 (95% confidence interval 2.7–6.8) per 1000 person years and was not significantly different for those who had served custodial and community‐based orders. Most deaths were due to drug overdose, traffic accidents or suicide. Adjusting for age, sex and order type, risk factors for death from the baseline interview included weekly use of opioids, sleeping pills or painkillers, polydrug use and injecting drug use.Discussion and ConclusionsYoung people who have served community‐based and custodial orders are at an increased risk of preventable death. Those engaging in risky substance use, particularly injecting drug use and use of multiple central nervous system depressants, are at greatest risk. There is an urgent need to develop and rigorously evaluate preventive interventions. [Kinner SA, Degenhardt L, Coffey C, Hearps S, Spittal M, Sawyer SM, Patton GC. Substance use and risk of death in young offenders: A prospective data linkage study. Drug Alcohol Rev 2015;34:46–50]
Generalized “avatar” niche shifts improve distribution models for invasive species
Authors: Larson Eric R. , Gallagher Rachael V. , Beaumont Linda J. , Olden Julian D. 
Published: July 2014

AbstractAimSpecies distribution models are an invaluable tool for anticipating the potential range of invasive species. These models often improve when both native and non‐native occurrences are available for model development and validation. Therefore, how might ecologists anticipate the potential distributions for emerging invasive species that lack any or abundant non‐native range occurrences? Here, we evaluate the recent suggestion of transferring niche shifts from well‐established ‘avatar’ invaders to emerging invaders by testing if ensemble niche shifts from a group of globally invasive plants improve model predictions when each of these species is iteratively treated as an ‘emerging’ invader.LocationGlobal.MethodsWe built species distribution models using Mahalanobis distance and four climatic predictors (maximum and minimum temperature and precipitation) for 26 invasive terrestrial plants from an Australian priority list of weeds. Models using only native range occurrences for each species were modified with avatar niche shifts from the remaining ensemble of 25 species based on both a typical (median) niche shift and a large (extreme) niche shift (or niche expansion). Native range and both median and extreme avatar models were then compared with total range models (developed with both native and non‐native occurrences) for performance by measures of discrimination and an approximation of calibration.ResultsAvatar niche shifts reduced errors of omission for known non‐native occurrences relative to native range models, with a trade‐off of increased errors of commission of lesser magnitude. Further, our approximation of model calibration measured relative to total range models improved with avatar niche shifts. Differences between native range and avatar models were most pronounced for the larger ‘extreme’ avatar niche shifts (or expansion) based on increased niche size and decreased (towards 0) covariance among climatic axes.Main conclusionsWe suggest that researchers and managers evaluating risk of invasion of their jurisdiction by emerging data‐poor invaders modify native range models with observed avatar niche shifts from ensembles of well‐studied invaders. Alternative implementations of the avatar invader concept are discussed and research needs for methodological improvements proposed. Despite these opportunities for improved implementation of avatar niche shifts, ample evidence now supports that researchers should expect models based on only native ranges to underestimate or misrepresent the total range for data‐poor emerging invaders. Avatar niche shifts (and specifically expansion) from well‐studied species offer a precautionary means to anticipate the extent to which native range models may underestimate total ranges.
Clinical course of gastrointestinal stromal tumor diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration
Authors: Sekine Masanari , Imaoka Hiroshi , Mizuno Nobumasa , Hara Kazuo , Hijioka Susumu , Niwa Yasumasa , Tajika Masahiro , Tanaka Tsutomu , Ishihara Makoto , Ito Seiji , Misawa Kazunari , Ito Yuichi , Shimizu Yasuhiro , Yatabe Yasushi , Ohnishi Hirohide , Yamao Kenji 
Published: July 2014

Background and AimGastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract. However, little is known about the clinical presentation of GIST, especially small lesions. The purpose of the present study was to clarify the efficacy of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for the diagnosis of GIST and to determine its clinical course.MethodsPathological and clinical records of GIST extracted from our institutional database between 1996 and 2012 were reviewed. All GIST cases were diagnosed pathologically by surgical specimen or EUS‐FNA. To examine the efficacy of EUS‐FNA for the diagnosis of GIST, the pathological findings of EUS‐FNA were compared with the surgical findings from resected cases. Next, to clarify the clinical presentation of GIST, imaging findings and changes in tumor size over time were evaluated in follow up.ResultsOf 84 cases of GIST, 67 were resected surgically after EUS‐FNA; tumor size was <20 mm in 19 patients, and ≥20 mm in 48 patients. For the diagnosis of small GIST<20 mm, sensitivity and positive predictive value of EUS‐FNA were 81.3% and 100%, respectively. A total of 27 patients with GIST was follow up for more than 1 year. Tumor size increased significantly during follow up. However, generalized linear analysis showed that there was no significant relationship between tumor size and follow up period.ConclusionsThe present results showed that even small GIST can be correctly identified by EUS‐FNA. Moreover, size of small GIST increased significantly during follow up.
Effect of sitagliptin therapy on triglyceride‐rich lipoprotein kinetics in patients with type 2 diabetes
Authors: Tremblay A. J. , Lamarche B. , Kelly I. , Charest A. , Lépine M.‐C. , Droit A. , Couture P. 
Published: July 2014

AimTo investigate the effects of sitagliptin therapy on the kinetics of triglyceride‐rich lipoprotein (TRL) apolipoprotein (apo)B‐48, VLDL apoB‐100, apoE and apoC‐III in patients with type 2 diabetes.MethodsTwenty‐two subjects with type 2 diabetes were recruited in this double‐blind crossover study, during which the subjects received sitagliptin (100 mg/day) or placebo for a 6‐week period each. At the end of each phase of treatment, the in vivo kinetics of the different apolipoproteins were assessed using a primed‐constant infusion of l‐[5,5,5‐D3]leucine for 12 h, with the participants in a constantly fed state.ResultsSitagliptin therapy significantly reduced fasting plasma triglyceride (−15.4%, p = 0.03), apoB‐48 (−16.3%, p = 0.03) and free fatty acid concentrations (−9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% ± 0.8 vs. sitagliptin: 6.6% ± 0.7, p < 0.0001) and plasma glucose levels (−13.5%, p = 0.001), without any significant effect on insulin levels. Kinetic results showed that treatment with sitagliptin significantly reduced the pool size of TRL apoB‐48 by −20.8% (p = 0.03), paralleled by a reduction in the production rate of these particles (−16.0%, p = 0.03). The VLDL apoB‐100 pool size was also significantly decreased by sitagliptin therapy (−9.3%, p = 0.03), mainly because of a reduction in the hepatic secretion of these lipoproteins, although this difference did not reach statistical significance (−9.2%, p = 0.06).ConclusionsTreatment with sitagliptin for 6 weeks reduced triglyceride‐rich apoB‐containing lipoprotein levels by reducing the synthesis of these particles.