bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial response to single‐cell protein production and brewery wastewater treatment
Authors: Lee Jackson Z. , Logan Andrew , Terry Seth , Spear John R. 
Published: May 2014

SummaryAs global fisheries decline, microbial single‐cell protein (SCP) produced from brewery process water has been highlighted as a potential source of protein for sustainable animal feed. However, biotechnological investigation ofSCPis difficult because of the natural variation and complexity of microbial ecology in wastewater bioreactors. In this study, we investigate microbial response across a full‐scale brewery wastewater treatment plant and a parallel pilot bioreactor modified to produce anSCPproduct. A pyrosequencing survey of the brewery treatment plant showed that each unit process selected for a unique microbial community. Notably, flow equalization basins were dominated byPrevotella, methanogenesis effluent had the highest levels of diversity, and clarifier wet‐well samples were sources of sequences for the candidate bacterial phyla ofTM7 andBD1‐5. Next, the microbial response of a pilot bioreactor producingSCPwas tracked over 1 year, showing that two different production trials produced two different communities originating from the same starting influent. However,SCPproduction resulted generally in enrichment of several clades of rhizospheric diazotrophs ofAlphaproteobacteriaandBetaproteobacteriain the bioreactor and even more so in the final product. These diazotrophs are potentially useful as the basis of aSCPproduct for commercial feed production.
WFABC: a Wright–Fisher ABC‐based approach for inferring effective population sizes and selection coefficients from time‐sampled data
Authors: Foll Matthieu , Shim Hyunjin , Jensen Jeffrey D. 
Published: May 2014

AbstractWith novel developments in sequencing technologies, time‐sampled data are becoming more available and accessible. Naturally, there have been efforts in parallel to infer population genetic parameters from these data sets. Here, we compare and analyse four recent approaches based on the Wright–Fisher model for inferring selection coefficients (s) given effective population size (Ne), with simulated temporal data sets. Furthermore, we demonstrate the advantage of a recently proposed approximate Bayesian computation (ABC)‐based method that is able to correctly infer genomewide average Ne from time‐serial data, which is then set as a prior for inferring per‐site selection coefficients accurately and precisely. We implement this ABC method in a new software and apply it to a classical time‐serial data set of the medionigra genotype in the moth Panaxia dominula. We show that a recessive lethal model is the best explanation for the observed variation in allele frequency by implementing an estimator of the dominance ratio (h).
Effects of adverse life events on heart rate variability, cortisol, and C‐reactive protein
Authors: van Ockenburg S. L. , Tak L. M. , Bakker S. J. L. , Gans R. O. B. , de Jonge P. , Rosmalen J. G. M. 
Published: May 2014

ObjectiveOur objective was to assess whether self‐reported adverse life events during childhood or over the lifespan are associated with altered activity of the autonomic nervous system (ANS), the hypothalamic‐pituitary‐adrenal axis (HPA axis), and the immune system.MethodThis study was performed in a population‐based cohort of 1094 adults aged 33–79 years, 46.3% male, average age 53 (SD 11.4). Two waves of data were collected at a 2‐year interval, enabling replication of the analyses. Cumulative exposure to adverse life events was assessed by means of the List of Threatening Experiences. ANS function was assessed by spectral analysis of heart rate variability in the high‐frequency band (HRV‐HF). HPA axis function was assessed by 24‐h urinary free cortisol (24‐h UFC) excretion. Inflammation was assessed by high‐sensitive C‐reactive protein (hsCRP).ResultsMultiple linear regression analyses did not reveal any significant associations, with the exception of one significant negative association between the lifetime score of adverse life events and HRV‐HF β = −0.028; P = 0.037 at baseline, but not at follow up 2 years later.ConclusionIn a large population‐based cohort, adverse life events were not consistently associated with HRV‐HF, 24‐h UFC or (hsCRP).
Disease‐specific health‐related quality of life instruments for IgE‐mediated food allergy
Authors: Salvilla S. A. , Dubois A. E. J. , Flokstra‐de Blok B. M. J. , Panesar S. S. , Worth A. , Patel S. , Muraro A. , Halken S. , Hoffmann‐Sommergruber K. , DunnGalvin A. , Hourihane J. O’B. , Regent L. , de Jong N. W. , Roberts G. , Sheikh A. ,   the EAACI Food Allergy and Anaphylaxis Group
Published: May 2014

AbstractThis is one of seven interlinked systematic reviews undertaken on behalf of the European Academy of Allergy and Clinical Immunology as part of their Guidelines for Food Allergy and Anaphylaxis, which focuses on instruments developed for IgE‐mediated food allergy. Disease‐specific questionnaires are significantly more sensitive than generic ones in measuring the response to interventions or future treatments, as well as estimating the general burden of food allergy. The aim of this systematic review was therefore to identify which disease‐specific, validated instruments can be employed to enable assessment of the impact of, and investigations and interventions for, IgE‐mediated food allergy on health‐related quality of life (HRQL). Using a sensitive search strategy, we searched seven electronic bibliographic databases to identify disease‐specific quality of life (QOL) tools relating to IgE‐mediated food allergy. From the 17 eligible studies, we identified seven disease‐specific HRQL instruments, which were then subjected to detailed quality appraisal. This revealed that these instruments have undergone formal development and validation processes, and have robust psychometric properties, and therefore provide a robust means of establishing the impact of food allergy on QOL. Suitable instruments are now available for use in children, adolescents, parents/caregivers, and adults. Further work must continue to develop a clinical minimal important difference for food allergy and for making these instruments available in a wider range of European languages.
Validation of 4β‐hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects
Authors: Kasichayanula Sreeneeranj , Boulton David W. , Luo Wen‐Lin , Rodrigues A. David , Yang Zheng , Goodenough Angela , Lee Michelle , Jemal Mohammed , LaCreta Frank 
Published: May 2014

AimsThis study aimed to assess changes in the plasma concentrationss of 4β‐hydroxycholesterol (4βHC) against intravenous (i.v.) and oral midazolam (MDZ) pharmacokinetics (PK) after administration of a potent CYP3A inhibitor [ketoconazole (KETO)] and inducer [rifampicin (RIF)].MethodsThirty‐two healthy subjects (HS) were allocated into three groups of 12 each in KETO and RIF and 10 in a placebo group (PLB). All HS were randomized to receive oral and i.v. MDZ on day 1 or 2 and on day 15 or 16 after receiving RIF (600 mg once daily), KETO (400 mg once daily) or PLB for 2 weeks. Subjects were followed until day 30. The effect of treatments on 4βHC was assessed by analyzing % change from baseline using a linear spline mixed effects model.ResultsCompared with PLB, KETO decreased 4βHC mean values up to 13% (P = 0.003) and RIF increased 4βHC mean values up to 220% (P < 0.001). Within 14 days of stopping KETO and RIF, 4βHC had either returned to baseline (KETO) or was still returning to baseline (RIF). Compared with baseline, mean oral MDZ AUC increased by 11‐fold (90% CI ranging from 9‐fold to 13‐fold increase) and decreased by 92% (90% CI ranging from 90% to 95% decrease) after KETO and RIF, respectively. Similar trends were observed for 6β‐hydroxycortisol : cortisol (6βHCL : CL) urinary ratios.ConclusionsChanges in plasma 4βHC can be utilized as a surrogate for MDZ PK after multiple doses of potent CYP3A inducers. There is a more limited dynamic range for 4βHC for assessment of potential CYP3A inhibitors. 4βHC is a valuable tool for the assessment of potential CYP3A inducers in early drug development.
Vatalanib population pharmacokinetics in patients with myelodysplastic syndrome: CALGB 10105 (Alliance)
Authors: Wang Xiaofeng , Owzar Kouros , Gupta Pankaj , Larson Richard A. , Mulkey Flora , Miller Antonius A. , Lewis Lionel D. , Hurd David , Vij Ravi , Ratain Mark J. , Murry Daryl J. ,   Alliance for Clinical Trials in Oncology
Published: May 2014

AimsVatalanib is an oral anti‐angiogenesis agent that inhibits vascular endothelial growth factor receptor tyrosine kinases, which in patients showed auto induction of metabolism and variability in pharmacokinetic (PK) disposition. The objective was to characterize the population PK and time‐dependent change in vatalanib clearance and assess exposure–toxicity relationship in patients with myelodysplastic syndrome (MDS).MethodsThis was an open‐label phase II study of vatalanib in MDS patients receiving 750–1250 mg once daily in 28‐day cycles. Serial blood samples were obtained and plasma vatalanib concentrations measured by HPLC. Population PK analysis was performed using nonmem 7.2 with FO estimation since FOCE failed. The final model was evaluated using goodness‐of‐fit plots, bootstrap analysis, and visual predictive check.ResultsPharmacokinetic data were complete for 137 patients (86 M, 51 F), of median age 70 years (range 20–91). A one‐compartment model with lagged first‐order absorption and time‐dependent change in oral clearance was fitted to the vatalanib plasma concentration versus time data. The population means for pre‐induction and post‐induction oral clearance were 24.1 l h–1 (range: 9.6–45.5) and 54.9 l h–1 (range: 39.8–75.6), respectively. The apparent oral clearance increased 2.3‐fold, (range: 1.7–4.1‐fold) from first dose to steady state. Our data did not identify a significant relationship of the predefined covariates with vatalanib pharmacokinetics, although power to detect such a relationship was limited.ConclusionsVatalanib pharmacokinetics were highly variable and the extent of auto induction was not determined to correlate with any of the pre‐defined covariates.
Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
Authors: Johnson Mark , Borland Julie , Chen Shuguang , Savina Paul , Wynne Brian , Piscitelli Stephen 
Published: May 2014

AimsThe aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone.MethodsThis was a single‐centre, randomized, open‐label, two‐cohort, two‐period, one‐way study in healthy adult subjects. Dolutegravir 50 mg once daily was administered for 5 days in Period 1, and dolutegravir 50 mg once daily was coadministered with either boceprevir 800 mg every 8 h (Cohort 1) or telaprevir 750 mg every 8 h (Cohort 2) for 10 days in Period 2.ResultsNo deaths or serious adverse events were reported during the study. Four subjects were withdrawn from the study because of adverse events (elevated alanine aminotransferase, cellulitis, increased serum creatinine and dizziness). One subject became pregnant during the study. Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration–time curve (AUC) and maximal plasma concentration (Cmax) and caused a small increase in concentration at the end of the dosing interval (Cτ; 8%). Coadministration of dolutegravir with telaprevir resulted in increased dolutegravir plasma exposures compared with those after administration of dolutegravir alone; AUC0–τ, Cmax and Cτ increased by 25, 19 and 37%, respectively. Coadministration of boceprevir or telaprevir with dolutegravir had no clinically significant effect on dolutegravir PK. Plasma boceprevir and telaprevir PK data for either combined treatment were similar to historical data, indicating no effect of dolutegravir on boceprevir or telaprevir exposure.ConclusionsDolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.
The Behavioural Outcomes of Anxiety scale (BOA): A preliminary validation in stroke survivors
Authors: Linley‐Adams Beth , Morris Reg , Kneebone Ian 
Published: May 2014

ObjectivesTo determine the psychometric properties of an observational scale of anxiety.DesignA cross‐sectional and longitudinal survey with stroke survivor–carer dyads.MethodsEighty‐nine dyads recruited in community stroke groups completed: a demographic questionnaire; the Behavioural Outcomes of Anxiety scale (BOA), survivor‐rated (survivor BOA) and carer‐rated (carer BOA) versions; the anxiety scale of the Hospital Anxiety and Depression Scales (HADS‐A), also in carer and survivor versions. Twenty‐seven survivors and carers repeated the BOA after 1 week.ResultsCorrelations between the carer BOA and the survivor HADS‐A (r = .55, p < .001) and the survivor BOA (r = .73, p < .001) demonstrated construct validity. Cronbach's alpha for the carer BOA was .81; item statistics did not identify any items for exclusion. The test–retest coefficient at 1 week was 0.83. Receiver operating characteristic analysis against the survivor HADS‐A and BOA produced areas under the curve of 0.75 and 0.88, respectively. At a cut‐off score of 13/14 sensitivity and specificity against the HADS‐A were 0.77 and 0.58, respectively, and 0.86 and 0.68 against the survivor BOA. The impact of stroke on memory was associated with elevated anxiety. Scores for both BOA versions were independent of demographic variables.ConclusionsThe carer BOA has acceptable psychometric properties and is independent of survivor demographic variables such as age. It identifies self‐reported cases with acceptable sensitivity and specificity. It has potential for use with persons unable to self‐report anxiety. Further validation is recommended, but its continuing use is supported.
Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co‐express gamma and beta globins
Authors: Yang Cheng‐Tao , French Anna , Goh Pollyanna Agnes , Pagnamenta Alistair , Mettananda Sachith , Taylor Jenny , Knight Sam , Nathwani Amit , Roberts David J. , Watt Suzanne M. , Carpenter Lee 
Published: May 2014

SummaryHuman induced pluripotent stem cells (hiPSCs), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hiPSCs from a variety of sources and show that, irrespective of origin or method of reprogramming, hiPSCs can be differentiated on OP9 stroma towards a multi‐lineage haemo‐endothelial progenitor that can contribute to CD144+ endothelium, CD235a+ erythrocytes (myeloid lineage) and CD19+ B lymphocytes (lymphoid lineage). Within the erythroblast lineage, we were able to demonstrate by single cell analysis (flow cytometry), that hiPSC‐derived erythroblasts express alpha globin as previously described, and that a sub‐population of these erythroblasts also express haemoglobin F (HbF), indicative of fetal definitive erythropoiesis. More notably however, we were able to demonstrate that a small sub‐fraction of HbF positive erythroblasts co‐expressed HbA in a highly heterogeneous manner, but analogous to cord blood‐derived erythroblasts when cultured using similar methods. Moreover, the HbA expressing erythroblast population could be greatly enhanced (44·0 ± 6·04%) when a defined serum‐free approach was employed to isolate a CD31+ CD45+ erythro‐myeloid progenitor. These findings demonstrate that hiPSCs may represent a useful alternative to standard sources of erythrocytes (RBCs) for future applications in transfusion medicine.
Effect of von Willebrand factor on inhibitor eradication in patients with severe haemophilia A: a systematic review
Authors: van Velzen Alice S. , Peters Marjolein , van der Bom Johanna G. , Fijnvandraat Karin 
Published: May 2014

SummaryThis systematic review was designed to summarize the reported valid quantitative evidence on the association between use of von Willebrand factor (VWF)‐containing Factor VIII (FVIII) concentrates and successful immune tolerance induction (ITI) in patients with severe haemophilia A. The primary outcome was successful ITI; secondary outcomes were time to success, complications of the inhibitor or ITI and relapse of the inhibitor. A systematic literature search identified 26 randomized controlled trials, registries and cohort studies, evaluating a total of 1284 patients. For a pooled meta‐analysis, 13 studies evaluating 382 patients were included. Due to incomplete data we were not able to assign pre‐ITI risk categories to all patients for risk factor analysis. The meta‐analysis did not demonstrate a difference in the proportion of patients with successful inhibitor eradication between those treated with VWF‐containing products and those treated with FVIII concentrates devoid of VWF (relative risk [RR] 0·70 (95% confidence interval [CI] 0·52–0·89) and 0·84 (95% CI 0·75–0·93) respectively). Bleeding rate during ITI ranged from 0·00 to 0·85 bleeding episodes per year. The proportion of patients with a relapse of the inhibitor (range 0–20%) was mentioned in four studies that were included in the meta‐analysis. The results of this systematic review do not support the idea of a positive effect of VWF‐containing products in ITI.
Effects of large herbivores on grassland arthropod diversity
Authors: van Klink R. , van der Plas F. , van Noordwijk C. G. E. (Toos) , WallisDeVries M. F. , Olff H. 
Published: May 2014

ABSTRACTBoth arthropods and large grazing herbivores are important components and drivers of biodiversity in grassland ecosystems, but a synthesis of how arthropod diversity is affected by large herbivores has been largely missing. To fill this gap, we conducted a literature search, which yielded 141 studies on this topic of which 24 simultaneously investigated plant and arthropod diversity. Using the data from these 24 studies, we compared the responses of plant and arthropod diversity to an increase in grazing intensity. This quantitative assessment showed no overall significant effect of increasing grazing intensity on plant diversity, while arthropod diversity was generally negatively affected. To understand these negative effects, we explored the mechanisms by which large herbivores affect arthropod communities: direct effects, changes in vegetation structure, changes in plant community composition, changes in soil conditions, and cascading effects within the arthropod interaction web. We identify three main factors determining the effects of large herbivores on arthropod diversity: (i) unintentional predation and increased disturbance, (ii) decreases in total resource abundance for arthropods (biomass) and (iii) changes in plant diversity, vegetation structure and abiotic conditions. In general, heterogeneity in vegetation structure and abiotic conditions increases at intermediate grazing intensity, but declines at both low and high grazing intensity. We conclude that large herbivores can only increase arthropod diversity if they cause an increase in (a)biotic heterogeneity, and then only if this increase is large enough to compensate for the loss of total resource abundance and the increased mortality rate. This is expected to occur only at low herbivore densities or with spatio‐temporal variation in herbivore densities. As we demonstrate that arthropod diversity is often more negatively affected by grazing than plant diversity, we strongly recommend considering the specific requirements of arthropods when applying grazing management and to include arthropods in monitoring schemes. Conservation strategies aiming at maximizing heterogeneity, including regulation of herbivore densities (through human interventions or top‐down control), maintenance of different types of management in close proximity and rotational grazing regimes, are the most promising options to conserve arthropod diversity.
Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non‐alcoholic fatty liver disease
Authors: Wu Chen‐Lu , Zhao Shui‐Ping , Yu Bi‐Lian 
Published: May 2014

ABSTRACTExchangeable apolipoproteins play an important role in systemic lipid metabolism, especially for lipoproteins with which they are associated. Recently, emerging evidence has suggested that exchangeable apolipoproteins, such as apolipoprotein A4 (apoA4), apolipoprotein A5 (apoA5), apolipoprotein C3 (apoC3) and apolipoprotein E (apoE), also exert important effects on intracellular lipid homeostasis. There is a close link between lipid metabolism in adipose tissue and liver because the latter behaves as the metabolic sensor of dysfunctional adipose tissue and is a main target of lipotoxicity. Given that the energy balance between these two major lipogenic organs is intimately involved in the pathogenesis of obesity and non‐alcoholic fatty liver disease (NAFLD), we here review recent findings concerning the intracellular function of exchangeable apolipoproteins in triglyceride metabolism in adipocytes and hepatocytes. These apolipoproteins may act as mediators of crosstalk between adipose tissue and liver, thus influencing development of obesity and hepatosteatosis. This review provides new insights into the physiological role of exchangeable apolipoproteins and identifies latent targets for therapeutic intervention of obesity and its related disorders.
Incidental findings on array comparative genomic hybridization: detection of carrier females of dystrophinopathy without any family history
Authors: Nguyen K. , Putoux A. , Busa T. , Cordier M.P. , Sigaudy S. , Till M. , Chabrol B. , Michel‐Calemard L. , Bernard R. , Julia S. , Malzac P. , Labalme A. , Missirian C. , Edery P. , Popovici C. , Philip N. , Sanlaville D. 
Published: May 2014

AbstractArray comparative genomic hybridization (aCGH) has progressively replaced conventional karyotype in the diagnostic strategy of intellectual disability (ID) and congenital malformations. This technique increases not only the diagnostic rate but also the possibility of finding unexpected variants unrelated to the indication of referral, namely incidental findings. The incidental finding of copy number variants (CNVs) located in X‐linked genes in girls addresses the crucial question of genetic counseling in the family. We report here five cases of CNVs involving the dystrophin gene detected by aCGH in girls referred for developmental delay, without any family history of dystrophinopathy. The rearrangements included three in‐frame deletions; one maternally and two paternally inherited, and two frameshift duplications: one de novo and one from undetermined inheritance. In two cases, the deletion identified in a girl was transmitted by the asymptomatic father. In the case of the maternally inherited deletion, prenatal diagnosis of dystrophinopathy was proposed for an ongoing pregnancy, whereas the cause of developmental delay in the index case remained unknown. Through these cases, we discussed the challenges of genetic counseling in the family, regarding the predictive issues for male individuals at risk for a muscular dystrophy without precise knowledge of the clinical consequences of some CNVs in the DMD gene.