bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate Bayesian Variable Selection Exploiting Dependence Structure Among Outcomes: Application to Air Pollution Effects on DNA Methylation
Authors: Lee Kyu Ha , Tadesse Mahlet G. , Baccarelli Andrea A. , Schwartz Joel , Coull Brent A. 
Published: July 2016

Summary
The analysis of multiple outcomes is becoming increasingly common in modern biomedical studies. It is well-known that joint statistical models for multiple outcomes are more flexible and more powerful than fitting a separate model for each outcome; they yield more powerful tests of exposure or treatment effects by taking into account the dependence among outcomes and pooling evidence across outcomes. It is, however, unlikely that all outcomes are related to the same subset of covariates. Therefore, there is interest in identifying exposures or treatments associated with particular outcomes, which we term outcome-specific variable selection. In this work, we propose a variable selection approach for multivariate normal responses that incorporates not only information on the mean model, but also information on the variance–covariance structure of the outcomes. The approach effectively leverages evidence from all correlated outcomes to estimate the effect of a particular covariate on a given outcome. To implement this strategy, we develop a Bayesian method that builds a multivariate prior for the variable selection indicators based on the variance–covariance of the outcomes. We show via simulation that the proposed variable selection strategy can boost power to detect subtle effects without increasing the probability of false discoveries. We apply the approach to the Normative Aging Study (NAS) epigenetic data and identify a subset of five genes in the asthma pathway for which gene-specific DNA methylations are associated with exposures to either black carbon, a marker of traffic pollution, or sulfate, a marker of particles generated by power plants.
15‐year follow‐up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau
Authors: Eskelund Christian W. , Kolstad Arne , Jerkeman Mats , Räty Riikka , Laurell Anna , Eloranta Sandra , Smedby Karin E. , Husby Simon , Pedersen Lone B. , Andersen Niels S. , Eriksson Mikael , Kimby Eva , Bentzen Hans , Kuittinen Outi , Lauritzsen Grete F. , Nilsson‐Ehle Herman , Ralfkiær Elisabeth , Ehinger Mats , Sundström Christer , Delabie Jan , Karjalainen‐Lindsberg Marja‐Liisa , Workman Christopher T. , Garde Christian , Elonen Erkki , Brown Peter , Grønbæk Kirsten , Geisler Christian H. 
Published: July 2016

SummaryIn recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first‐line regimens containing cytarabine, rituximab and consolidation with high‐dose‐therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15‐year updated results of the Nordic MCL2 study after a median follow‐up of 11·4 years: For all patients on an intent‐to‐treat basis, the median overall and progression‐free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI‐B) and the MIPI‐B including mIR‐18b expression (MIPI‐B‐miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease‐related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of anti-retroviral treatment
Authors: Eberhard J M , Ahmad F , Hong H S , Bhatnagar N , Keudel P , Schulze zur Wiesch J , Schmidt R E , Meyer-Olson D 
Published: July 2016

Summary
Immune senescence as well as disturbed CD8+ T cell differentiation are a hallmark of chronic HIV infection. Here, we investigated to what extent immune senescence is reversible after initiation of anti-retroviral treatment (ART). Peripheral blood mononuclear cells (PBMCs) from a cohort of HIV patients with different disease courses, including untreated viral controllers (n = 10), viral non-controllers (n = 16) and patients on ART (n = 20), were analysed and compared to uninfected controls (n = 25) by flow cytometry on bulk and HIV-specific major histocompatibility complex (MHC) class I tetramer+ CD8+ T cells for expression of the memory markers CCR7 and CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was analysed longitudinally before and after initiation of ART. Frequencies of CD57+CD8+ T cells decreased after initiation of ART in central memory (Tcm) but not in effector memory T cell populations (TemRO and TemRA). The frequency of CD127+CD8+ cells increased in Tcm and TemRO. We observed a reduction of CD127– T cells in Tcm, TemRO and partially in TemRA subsets after initiation of ART. Importantly, HIV-specific CD8+ TemRO cells predominantly displayed a CD127–CD57+ phenotype in untreated HIV-patients, whereas the CD127+CD57– phenotype was under-represented in these patients. The frequency of the CD127+CD57–CD8+ T cell subpopulation correlated strongly with absolute CD4+ counts in HIV-infected patients before and after initiation of ART. These findings can be interpreted as a phenotypical correlate of CD8+ memory T cell differentiation and the premature ‘ageing’ of the immune system, which was even observed in successfully virally suppressed HIV patients.
MicroRNA-26a–interleukin (IL)-6–IL-17 axis regulates the development of non-alcoholic fatty liver disease in a murine model
Authors: He Q , Li F , Li J , Li R , Zhan G , Li G , Du W , Tan H 
Published: July 2016

Summary
Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. A recent paper indicated that Mir-26a regulated insulin sensitivity and metabolism of glucose and lipids. However, the role of Mir-26a in NAFLD still needs to be investigated further. In our current study, vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 × 107 transforming units of recombinant lentivirus were injected into mice through the tail vein. LV-26a-infected mice were protected from glucose dysmetabolism and showed markedly decreased total liver weight, hepatic triglyceride deposition and serum alanine transaminase (ALT) concentration when compared with LV-Con-treated mice. LV-26a-treated mice also exhibited decreased infiltration of immune cells in the liver – something attributed to reduce infiltration of T cell receptor (TCR)-γδ+, granulocyte-differentiation antigen-1 (Gr-1)+ cells and CD11b+ cells. Next, we found that Mir-26a inhibited the expression of interleukin (IL)−17 and IL-6 in vivo and in vitro. Furthermore, the decreased expression of IL-17 in the liver tissue induced by Mir-26a was abrogated completely by IL-6 overexpression. The decreased total liver weight, hepatic triglyceride deposition and serum ALT concentration induced by Mir-26a was also abrogated completely by IL-6 over-expression. In conclusion, the Mir-26a–IL-6–IL-17 axis regulates the development of NAFLD in a murine model.
Simple Incentives and Group Dependence for Successful Payments for Ecosystem Services Programs: Evidence from an Experimental Game in Rural Lao PDR
Authors: Salk Carl , Lopez Maria‐Claudia , Wong Grace 
Published: July 2016

AbstractIn this article, we use a new game‐based tool to evaluate the immediate and longer term behavioral change potential of three different payments for ecosystem services (PES) delivery mechanisms: direct payments for individual performance, direct payments for group performance, and insurance. Results from four rural shifting‐cultivation dependent communities in Lao PDR suggest that easily understood group‐oriented incentives yield the greatest immediate resource‐use reduction and experience less free‐riding. Group‐based incentives may succeed because they motivate participants to communicate about strategies and coordinate their actions and are perceived as fair. No incentive had a lasting effect after it ceased, but neither did any crowd out the participants’ baseline behavior. Temporary reductions in resource dependence may provide a buffer for development of new livelihoods and longer term change. Games like the one developed here can help policy makers appropriately target environmental incentive programs to local contexts and teach program participants how incentive schemes work.
Robust anti‐obesity and metabolic effects of a dual GLP‐1/glucagon receptor peptide agonist in rodents and non‐human primates
Authors: Henderson S. J. , Konkar A. , Hornigold D. C. , Trevaskis J. L. , Jackson R. , Fritsch Fredin M. , Jansson‐Löfmark R. , Naylor J. , Rossi A. , Bednarek M. A. , Bhagroo N. , Salari H. , Will S. , Oldham S. , Hansen G. , Feigh M. , Klein T. , Grimsby J. , Maguire S. , Jermutus L. , Rondinone C. M. , Coghlan M. P. 
Published: July 2016

AimsTo characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon‐like peptide‐1 (GLP‐1) and glucagon receptors.Materials and methods
MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP‐1 or glucagon receptors, to potentiate glucose‐stimulated insulin secretion (GSIS) in pancreatic β‐cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months.Results
MEDI0382 potently activated rodent, cynomolgus and human GLP‐1 and glucagon receptors and exhibited a fivefold bias for activation of GLP‐1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP‐1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor‐mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP‐1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys.ConclusionsRepeated administration of MEDI0382 elicits profound weight loss in DIO mice and non‐human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP‐1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients.
Enhancement of antifungal activity of Burkholderia pyrrocinia JK‐SH007 genetically modified with Bacillus subtilis Chi113 gene
Authors: He L.‐M. , Ye J.‐R. , Ren J.‐H. , Huang L. , Wu X.‐Q. 
Published: July 2016

SummaryPrevious studies showed that Burkholderia pyrrocinia JK‐SH007 is a potential biocontrol agent of poplar canker disease. In this report, B. pyrrocinia JK‐SH007 was genetically modified by introducing the Bacillus subtilis Chi113 gene to enhance its antifungal activity. The green fluorescence of B. pyrrocinia JK‐SH007E1 can be detected because of its transformation with plasmid pHKT2‐Chi113 containing a gfp reporter gene. Real‐time quantitative PCR (qPCR) showed that the B. subtilis Chi113 gene was highly expressed in B. pyrrocinia JK‐SH007E1 at mRNA level. The chitinase activity and the antifungal activity of B. pyrrocinia JK‐SH007E1 were significantly increased, and the clear halo was visible on the colloidal chitin agar plate. In addition, the constructed recombinant plasmid pHKT2‐Chi113 was stably maintained for at least 100 generations in the absence of antibiotic selection in B. pyrrocinia JK‐SH007E1. In western blot analysis, the Chi113‐GFP fusion protein was detected in B. pyrrocinia JK‐SH007E1 using the GFP polyclonal antibody. In conclusion, the B. subtilis Chi113 gene was successfully transformed into B. pyrrocinia JK‐SH007 and was expressed both at mRNA level and protein level. Moreover, the antifungal activity of B. pyrrocinia JK‐SH007 was improved through this genetic modification.
Shot hole disease on Prunus laurocerasus caused by Neofusicoccum parvum in Serbia
Authors: Zlatković M. , Keča N. , Wingfield M. J. , Jami F. , Slippers B. 
Published: July 2016

SummaryBetween 2010 and 2014, symptoms of a shot hole disease were observed on cherry laurel (Prunus laurocerasus L.) trees and shrubs in parks and other public plantings in Belgrade, Serbia. Ten symptomatic leaves were collected from each of the diseased plants and the associated fungus isolated and identified using multigene phylogenetic analyses and asexual morphological characters. The pathogen was identified as Neofusicoccum parvum. The same symptoms were produced when the pathogen was inoculated on test plants. To the best of our knowledge, this is the first report of N. parvum causing shot hole disease on P. laurocerasus.
Vitamin D deficiency and its risk factors in Malaysian children with epilepsy
Authors: Fong Choong Yi , Kong Ann Nie , Poh Bee Koon , Mohamed Ahmad Rithauddin , Khoo Teik Beng , Ng Rui Lun , Noordin Mazidah , Nadarajaw Thiyagar , Ong Lai Choo 
Published: July 2016

SummaryObjectiveLong‐term use of antiepileptic drugs (AEDs) is a significant risk factor for vitamin D deficiency in children with epilepsy. The aims of our study were to evaluate the prevalence and risk factors for vitamin D deficiency among Malaysian children with epilepsy.MethodsCross‐sectional study of ambulant children with epilepsy on long‐term AEDs for >1 year seen in three tertiary hospitals in Malaysia from April 2014 to April 2015. Detailed assessment of pubertal status, skin pigmentation, sunshine exposure behavior, physical activity, dietary vitamin D and calcium intake, anthropometric measurements and bone health blood tests (vitamin D, alkaline phosphatase, calcium, phosphate, and parathyroid hormone levels) were obtained on all patients. Vitamin D deficiency was defined as 25‐hydroxy vitamin D [25(OH)D] levels ≤35 nmol/L and insufficiency as 25(OH)D levels of 36–50 nmol/L.ResultsA total of 244 children (146 male) participated in the study. Ages ranged between 3.7 and 18.8 years (mean 12.3 years). 25(OH)D levels ranged between 7.5 and 140.9 nmol/L (mean 53.9 nmol/L). Vitamin D deficiency was identified in 55 patients (22.5%), and a further 48 (19.7%) had vitamin D insufficiency. Multivariate logistic regression analysis identified polytherapy >1 AED (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.07–4.36), age >12 years (OR 4.16, 95% CI 1.13–15.30), Indian ethnicity (OR 6.97, 95% CI 2.48–19.55), sun exposure time 30–60 min/day (OR 2.44, 95% CI 1.05–5.67), sun exposure time <30 min/day (OR 3.83, 95% CI 1.61–9.09), and female (OR 2.61, 95% CI 1.31–5.20) as statistically significant (p < 0.05) risk factors for vitamin D deficiency.SignificanceDespite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency.
Equine odontoclastic tooth resorption and hypercementosis
Authors: Hole S. L. , Staszyk C. 
Published: July 2016

SummaryEquine odontoclastic tooth resorption and hypercementosis (EOTRH) is a progressive and painful disease syndrome that affects aged horses. It affects incisor, canine and infrequently cheek teeth, and is characterised by gingival inflammation, oedema and recession, calculus deposition, feed accumulation, subgingival swellings with or without associated draining tracts, bulbous enlargement of teeth, tooth mobility, associated periodontal disease, tooth fracture and/or tooth loss. The aetiology of EOTRH is likely to be multi‐factorial. However, histopathological findings consistently suggest an aetiological contribution of initial biomechanical stresses and strains, followed by secondary involvement of micro‐organisms. Diagnosis is based on clinical presentation, age and radiographic changes including lytic changes, widening or loss of the periodontal ligament, hypercementosis, tooth fracture and alveolar bone loss. Treatment of EOTRH is not currently possible, but the condition can be managed to some degree, quite successfully for many years in some cases. However, the disease is progressive and invariably results in extraction of the tooth or teeth involved. The prognosis is most probably guarded at best and poor in most cases; however, complete removal of affected teeth carries a good prognosis for an improved quality of life in the short to medium term.
Unravelling the joint effects of flow regime, climatic variability and dispersal mode on beta diversity of riverine communities
Authors: Rolls Robert J. , Heino Jani , Chessman Bruce C. 
Published: July 2016

Summary

Differences in the composition of ecological communities among rivers with contrasting flow regimes have been detected in many regions worldwide. However, we know little of how climatic variation alters these spatial patterns for constituent species with varying dispersal modes and strengths.

We predicted that beta diversity (spatial variation in composition) of macroinvertebrate and fish assemblages among streams with near‐perennial, mildly intermittent and highly intermittent flow regimes would be greater during prolonged drought than under wetter climate conditions. We hypothesised that changes in beta diversity between these climate phases would be greater for taxa with stronger dispersal ability. We tested these predictions with biomonitoring data from Australian subtropical rivers.

Differences in average community composition among flow regimes were statistically significant for six groups of macroinvertebrates with differing dispersal (non‐swimmers, weak swimmers, strong swimmers, non‐fliers, weak fliers and strong fliers) and two groups of fish (potamodromous and diadromous), but not for locally dispersing fish. For each of these biotic groups, shifts in assemblage composition between supra‐seasonal drought and a subsequent non‐drought period were either statistically non‐significant or of similar magnitude among flow regimes. Therefore, beta diversity among flow regimes did not change significantly with climate phase.

Beta diversity within flow‐regime classes was greater during the drought than afterwards or not significantly different between climate phases, depending on the flow regime and biotic group. Stronger powers of flight were associated with greater change in beta diversity between climate phases in near‐perennial streams, but stronger powers of swimming were not. Within‐regime beta diversity was driven more by replacement of taxa among samples than by nestedness, except for diadromous fish in near‐perennial streams.

Our findings are consistent with the hypothesis that decreasing hydrological connectivity and greater environmental heterogeneity during prolonged drought increase beta diversity of stream communities. However, changes in beta diversity between climate phases were not as pronounced as we expected. The communities may have been somewhat drought resistant because the magnitude and duration of the drought were within the range of historical variability and because surface water persisted at study sites during drought‐imposed flow cessations. Our findings suggest that maintenance of refuge pools will be critical to lessening drought impacts on river biodiversity at landscape scales, particularly if drought duration and intensity increase in the future.
Effect of non‐alcoholic fatty liver disease on left ventricular diastolic function and geometry in the Korean general population
Authors: Jung Ju Young , Park Sung Keun , Ryoo Jae‐Hong , Oh Chang‐Mo , Kang Jeong Gyu , Lee Jae‐Hon , Choi Joong‐Myung 
Published: July 2016

AbstractAimPrevious studies showed that non‐alcoholic fatty liver disease (NALFD) could be related to subclinical left ventricular (LV) diastolic dysfunction and remodeling. However, this association is still equivocal in the general population. Thus, this study was carried out to examine whether NAFLD is associated with the risk for LV diastolic dysfunction and remodeling.MethodsA cross‐sectional study was carried out for 20 821 Korean men and women who received a health checkup including echocardiography from 2011 to 2012. The study population was divided into three groups of normal, mild and moderate‐to‐severe NAFLD detected by ultrasonography. Using multivariable logistic regression analysis, the odd ratios of abnormal LV relaxation and remodeling were analyzed according to the degree of NAFLD. Additionally, adjusted mean values of LV diastolic functional and structural parameters were evaluated in the three groups.ResultsCompared with the normal group, the mild and moderate‐to‐severe NAFLD groups had higher odd ratios for abnormal LV relaxation (mild group 1.29, 95% confidence interval 1.15–1.46; moderate‐to‐severe group 1.95, 95% confidence interval 1.61–2.35) and increased relative wall thickness (>0.42; mild group 1.26, 95% confidence interval 1.05–1.52; moderate‐to‐severe group 1.46, 95% confidence interval 1.08–1.95). Analyzing adjusted mean values of LV parameters also showed the significant association between the degree of NAFLD and impaired LV diastolic function and concentric LV remodeling.ConclusionsThe risk for LV diastolic dysfunction and remodeling proportionally increased according to the degree of NAFLD. NAFLD is significantly associated with LV functional and structural alteration.