bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the Perceived Food Environment Questionnaire in a French-Canadian population
Authors: Carbonneau Elise , Robitaille Julie , Lamarche Benoît , Corneau Louise , Lemieux Simone 
Published: April 2017

AbstractObjectiveThe present study aimed to develop and validate a questionnaire assessing perceived food environment in a French-Canadian population.DesignA questionnaire, the Perceived Food Environment Questionnaire, was developed assessing perceived accessibility to healthy (nine items) and unhealthy foods (three items). A pre-test sample was recruited for a pilot testing of the questionnaire. For the validation study, another sample was recruited and completed the questionnaire twice. Exploratory factor analysis was performed on the items to assess the number of factors (subscales). Cronbach’s α was used to measure internal consistency reliability. Test–retest reliability was assessed with Pearson correlations.SettingOnline survey.SubjectsMen and women from the Québec City area (n 31 in the pre-test sample; n 150 in the validation study sample).ResultsThe pilot testing did not lead to any change in the questionnaire. The exploratory factor analysis revealed a two-subscale structure. The first subscale is composed of six items assessing accessibility to healthy foods and the second includes three items related to accessibility to unhealthy foods. Three items were removed from the questionnaire due to low loading on the two subscales. The subscales demonstrated adequate internal consistency (Cronbach’s α=0·77 for healthy foods and 0·62 for unhealthy foods) and test–retest reliability (r=0·59 and 0·60, respectively; both P<0·0001).ConclusionsThe Perceived Food Environment Questionnaire was developed for a French-Canadian population and demonstrated good psychometric properties. Further validation is recommended if the questionnaire is to be used in other populations.
Inorganic nitrogen losses to groundwater are minimal from two management-intensive grazing dairy farms in Maryland
Authors: Gilker Rachel E. , Weil Ray R. 
Published: April 2017

AbstractWith the advent of confined feeding systems and associated herd size increases, dairy farms have had to import more feed from off the farm, leading to on farm nutrient surpluses. Management-intensive grazing (MIG) is an alternative to confined feeding. Under MIG, the herd is rotated among small paddocks every 12–24 h for efficient conversion of forage into milk using grass pasture to provide most of the herd's nutritional needs. Previous research on MIG reported high concentrations of nitrate under grassed monolith lysimeters and grazed pastures. However, because of the high levels of nitrogen (N) fertilization and ponding of cow urine in lysimeters, these previous studies may have overestimated nitrate leaching losses from MIG systems as practiced in the mid-Atlantic region. To determine the extent of nitrate losses to groundwater under MIG in the mid-Atlantic, we sampled shallow groundwater biweekly for 3 yrs on six watersheds in three Maryland dairy farms, one confined and two MIG-based farms. Transects of nested piezometers and ceramic tipped suction lysimeters were installed in each watershed. Seasonal mean nitrate-N concentrations under the four grazed watersheds were generally lower than under the confined feeding farm watersheds and were generally below the widely used drinking water standard of 10 mg L−1. Average nitrate-N concentrations for all four grazed watersheds were between 4 and 7 mg L−1, while the two confined feeding farm watersheds averaged 7 and 11 mg L−1, indicating that the MIG system did not cause excessive nitrate leaching.
Demographic risk in deep-deferred annuity valuation
Authors: Ji Min , Zhou Rui 
Published: April 2017

AbstractA deep-deferred annuity is a deferred annuity where payments start very late in life, i.e. well after the normal retirement age. This annuity has received much attention lately as it was made accessible to 401(k) plans in the United States in 2014. By transferring the risk of outliving retirement savings at high ages to annuity providers, deep-deferred annuities provide annuitants with enhanced later-life financial security. However, the valuation of this annuity suffers from high uncertainty because the mortality data at high ages are sparse and possibly unreliable. In this paper, we use risk ratio to measure demographic risk in the valuation. Demographic risk is decomposed into the following four components: (1) mortality tail curve risk, (2) mortality improvement model risk, (3) parameter risk in mortality tail curves, and (4) parameter risk in mortality improvement rate models. Our quantitative analysis aims to provide insights into the development and risk management of deep-deferred annuities.
Does living in remote Australia lessen the impact of hardship on psychological distress?
Authors: Butterworth P. , Kelly B. J. , Handley T. E. , Inder K. J. , Lewin T. J. 
Published: April 2017

Aims.Rural and remote regions tend to be characterised by poorer socioeconomic conditions than urban areas, yet findings regarding differences in mental health between rural and urban areas have been inconsistent. This suggests that other features of these areas may reduce the impact of hardship on mental health. Little research has explored the relationship of financial hardship or deprivation with mental health across geographical areas.Methods.Data were analysed from a large longitudinal Australian study of the mental health of individuals living in regional and remote communities. Financial hardship was measured using items from previous Australian national population research, along with measures of psychological distress (Kessler-10), social networks/support and community characteristics/locality, including rurality/remoteness (inner regional; outer regional; remote/very remote). Multilevel logistic regression modelling was used to examine the relationship between hardship, locality and distress. Supplementary analysis was undertaken using Australian Household, Income and Labour Dynamics in Australia (HILDA) Survey data.Results.2161 respondents from the Australian Rural Mental Health Study (1879 households) completed a baseline survey with 26% from remote or very remote regions. A significant association was detected between the number of hardship items and psychological distress in regional areas. Living in a remote location was associated with a lower number of hardships, lower risk of any hardship and lower risk of reporting three of the seven individual hardship items. Increasing hardship was associated with no change in distress for those living in remote areas. Respondents from remote areas were more likely to report seeking help from welfare organisations than regional residents. Findings were confirmed with sensitivity tests, including replication with HILDA data, the use of alternative measures of socioeconomic circumstances and the application of different analytic methods.Conclusions.Using a conventional and nationally used measure of financial hardship, people residing in the most remote regions reported fewer hardships than other rural residents. In contrast to other rural residents, and national population data, there was no association between such hardship and mental health among residents in remote areas. The findings suggest the need to reconsider the experience of financial hardship across localities and possible protective factors within remote regions that may mitigate the psychological impact of such hardship.
A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages
Authors: Pereira Mafalda M. A. , Mahú Inês , Seixas Elsa , Martinéz-Sánchez Noelia , Kubasova Nadiya , Pirzgalska Roksana M , Cohen Paul , Dietrich Marcelo O , López Miguel , Bernardes Gonçalo J. L. , Domingos Ana I. 
Published: April 2017

AbstractConditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood–brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood–brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system.
Methylation of WNT target genes AXIN2 and DKK1 as robust biomarkers for recurrence prediction in stage II colon cancer
Authors: Kandimalla R , Linnekamp J F , van Hooff S , Castells A , Llor X , Andreu M , Jover R , Goel A , Medema J P 
Published: April 2017

AbstractStage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2 and LGR5 are silenced by DNA methylation and could serve as prognostic markers in stage II CC patients using methylation-specific PCR. Here, we have extended our discovery cohort AMC90-AJCC-II (N=65) and methylation was analyzed by quantitative pyrosequencing. Subsequently, we validated the results in an independent EPICOLON1 CC cohort (N=79). Methylation of WNT target genes is negatively correlated to mRNA expression. A combination of AXIN2 and DKK1 methylation significantly predicted recurrences in univariate (area under the curve (AUC)=0.83, confidence interval (CI): 0.72–0.94, P<0.0001) analysis in stage II microsatellite stable (MSS) CC patients. This two marker combination showed an AUC of 0.80 (CI: 0.68–0.91, P<0.0001) in the EPICOLON1 validation cohort. Multivariate analysis in the Academic Medical Center (AMC) cohort revealed that both WNT target gene methylation and consensus molecular subtype 4 (CMS4) are significantly associated with poor recurrence-free survival (hazard ratio (HR)methylation: 3.84, 95% CI: 1.14–12.43; HRCMS4: 3.73, 95% CI: 1.22–11.48). CMS4 subtype tumors with WNT target methylation showed worse prognosis. Combining WNT target gene methylation and CMS4 subtype lead to an AUC of 0.89 (0.791–0.982, P<0.0001) for recurrence prediction. Notably, we observed that methylation of DKK1 is high in BRAF mutant and CIMP (CpG island methylator phenotype)-positive cancers, whereas AXIN2 methylation appears to be associated with CMS4. Methylation of AXIN2 and DKK1 were found to be robust markers for recurrence prediction in stage II MSS CC patients. Further validation of these findings in a randomized and prospective manner could pave a way to identify poor prognosis patients of stage II CC for AT.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells
Authors: Rupp Levi J. , Schumann Kathrin , Roybal Kole T. , Gate Rachel E. , Ye Chun J. , Lim Wendell A. , Marson Alexander 
Published: April 2017

AbstractImmunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.
Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease
Authors: Skjørringe Tina , Amstrup Pedersen Per , Salling Thorborg Sidsel , Nissen Poul , Gourdon Pontus , Birk Møller Lisbeth 
Published: April 2017

AbstractMenkes disease (MD) is caused by mutations in ATP7A, encoding a copper-transporting P-type ATPase which exhibits copper-dependent trafficking. ATP7A is found in the Trans-Golgi Network (TGN) at low copper concentrations, and in the post-Golgi compartments and the plasma membrane at higher concentrations. Here we have analyzed the effect of 36 ATP7A missense mutations identified in phenotypically different MD patients. Nine mutations identified in patients with severe MD, virtually eliminated ATP7A synthesis, in most cases due to aberrant RNA splicing. A group of 21 predominantly severe mutations led to trapping of the protein in TGN and displayed essentially no activity in a yeast-based functional assay. These were predicted to inhibit the catalytic phosphorylation of the protein. Four mutants showed diffuse post-TGN localization, while two displayed copper dependent trafficking. These six variants were identified in patients with mild MD and typically displayed activity in the yeast assay. The four post-TGN located mutants were presumably affected in the catalytic dephosphorylation of the protein. Together these results indicate that the severity of MD correlate with cellular localization of ATP7A and support previous studies indicating that phosphorylation is crucial for the exit of ATP7A from TGN, while dephosphorylation is crucial for recycling back to TGN.
Identification of a six-lncRNA signature associated with recurrence of ovarian cancer
Authors: Yang Kai , Hou Yan , Li Ang , Li Zhenzi , Wang Wenjie , Xie Hongyu , Rong Zhiwei , Lou Ge , Li Kang 
Published: April 2017

AbstractOvarian cancer (OvCa) is the leading cause of death among all gynecological malignancies, and recurrent OvCa is almost always incurable. In this study, we developed a signature based on long non-coding RNAs (lncRNAs) associated with OvCa recurrence to facilitate personalized OvCa therapy. lncRNA expression data were extracted from GSE9891 and GSE30161. LASSO (least absolute shrinkage and selection operator) penalized regression was used to identify an lncRNA-based signature using the GSE9891 training cohort. The signature was then validated in GSE9891 internal and GSE30161 external validation cohorts. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to explore the possible functions of identified lncRNAs. A six-lncRNA signature (RUNX1-IT1, MALAT1, H19, HOTAIRM1, LOC100190986 and AL132709.8) was identified in the training cohort and validated in internal and external validation cohorts using the LASSO method (P < 0.05). This signature was also independent of other clinical factors according to multivariate and sub-group analyses. The identified lncRNAs are involved in cancer-related biological processes and pathways. We selected a highly reliable signature based on six lncRNAs associated with OvCa recurrence. This six-lncRNA signature is a promising method to personalize ovarian cancer therapy and may improve patient quality of life quality according to patients’ condition in the future.
Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
Authors: Chan Sherwin , Ch’ng Jun-Hong , Wahlgren Mats , Thutkawkorapin Jessada 
Published: April 2017

AbstractPlasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons that are negatively associated to protein translation efficiency. Despite this, one third of all codons in the genome are GU wobble codons, suggesting that codon usage in P. falciparum has not been driven to maximize translation efficiency, but may have evolved as translational regulatory mechanism. Particularly, asparagine homorepeats are generally encoded by locally clustered GU wobble AAT codons, we demonstrated that this GU wobble-rich codon context is the determining factor that causes reduction of protein level. Moreover, insertion of clustered AAT codons also causes destabilization of the transcripts. Interestingly, more frequent asparagine homorepeats insertion is seen in single-exon genes, suggesting transcripts of these genes may have been programmed for rapid mRNA decay to compensate for the inefficiency of mRNA surveillance regulation on intronless genes. To our knowledge, this is the first study that addresses P. falciparum codon usage in vitro and provides new insights on translational regulation and genome evolution of this parasite.
The Vernix Caseosa is the Main Site of Dioxin Excretion in the Human Foetus
Authors: Morokuma Seiichi , Tsukimori Kiyomi , Hori Tsuguhide , Kato Kiyoko , Furue Masutaka 
Published: April 2017

AbstractDioxins are highly toxic to foetuses and prenatal exposure leads to adverse health effects; however, the metabolic pathways involved in dioxin excretion are poorly understood. We determined the dynamics of maternal-to-foetal dioxin transfer during normal pregnancy and how foetuses eliminate polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls. Dioxin levels in maternal blood, cord blood, placenta, vernix caseosa, meconium, and amniotic fluid were analysed by high-resolution gas chromatography/mass spectrometry. The average levels of total dioxins, expressed as picograms of toxic equivalency quantity per gram of lipid and in parentheses, dioxin fraction, with maternal blood levels arbitrarily set as 100%, were as follows: maternal blood, 15.8 (100%); placenta, 12.9 (81.5%); cord blood, 5.9 (37.2%); vernix caseosa, 8.4 (53.2%); meconium, 2.9 (18.2%); and amniotic fluid, 1.5 (9.2%). Similar proportions were observed for each dioxin congener. Thus, the highest content of foetal dioxins was observed in the vernix caseosa, indicating that this is the major site of dioxin excretion in human foetuses.
High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma
Authors: Xu Yi , Zheng Zhousan , Gao Ying , Duan Shiyu , Chen Cui , Rong Jian , Wang Kebing , Yun Miao , Weng Huiwen , Ye Sheng , Zhang Jiaxing 
Published: April 2017

AbstractInosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1. IMPDH2 protein expression was markedly higher in NPC tissues than in adjacent non-tumorous tissues. Moreover, IMPDH2 expression in NPC correlated with several clinicopathological parameters, including T classification (P = 0.023), TNM stage (P = 0.020), distant metastasis (P = 0.001) and death (P = 0.002). Further Cox regression analysis suggested that IMPDH2 expression was an independent prognostic factor for overall survival (P = 0.001) and disease-free survival (P < 0.001). In addition, stratified survival analysis showed that high expression of IMPDH2 could be a prognostic factor for NPC patients with TNM stage I/II (OS: P = 0.012; DMFS: P = 0.007), TNM stage III/IV (OS: P = 0.028; DMFS: P = 0.020). Our study demonstrates IMPDH2 may be served as an independent prognostic biomarker for NPC patients, in which high IMPDH expression suggests poor prognosis of NPC patients.
Characteristics of the heme catabolic pathway in mild unconjugated hyperbilirubinemia and their associations with inflammation and disease prevention
Authors: Mölzer Christine , Wallner Marlies , Kern Carina , Tosevska Anela , Zadnikar René , Doberer Daniel , Marculescu Rodrig , Wagner Karl-Heinz 
Published: April 2017

AbstractHeme catabolism exerts physiological functions that impact health through depressing inflammation. Upon reactive pathway progression, as in Gilbert’s Syndrome (GS; UGT1A1*28 polymorphism), aggravated health effects have been determined. Based on lower inflammation and improved metabolic health reported for GS, inter-group differences in heme catabolism were explored. Therefore, a case-control study including 120 fasted, healthy, age- and gender matched subjects with/without GS, was conducted. Genetic expressions of HMOX-1 and BLVRA were measured. Additionally participants were genotyped for those polymorphisms that are known (UGT1A1*28) or likely (HMOX-1 microsatellites) to impact bilirubinemia. Intracellular interleukins (IL-6, IL-1β, TNFα), circulatory C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hpt) were analysed as inflammatory markers. To assess intracellular heme oxygenase 1 (HO-1) isolated PBMCs were used. In GS vs. C, inflammation markers were significantly decreased. This was supported by an altered heme catabolism, indirectly reflecting in elevated unconjugated bilirubin (UCB; main phenotypic feature of GS) and iron, decreased hemopexin (Hpx) and Hpt and in up-regulated biliverdin reductase (BLVRA) gene expressions. Moreover, HMOX (GT)n short alleles were non-significantly more prominent in female GS individuals. Herewith, we propose a concept to elucidate why GS individuals encounter lower inflammation, and are thus less prone to oxidative-stress mediated diseases.
Power-scalable subcycle pulses from laser filaments
Authors: Voronin A.A. , Zheltikov A.M. 
Published: April 2017

AbstractCompression of optical pulses to ultrashort pulse widths using methods of nonlinear optics is a well-established technology of modern laser science. Extending these methods to pulses with high peak powers, which become available due to the rapid progress of laser technologies, is, however, limited by the universal physical principles. With the ratio P/Pcr of the peak power of an ultrashort laser pulse, P, to the critical power of self-focusing, Pcr, playing the role of the fundamental number-of-particles integral of motion of the nonlinear Schrödinger equation, keeping this ratio constant is a key principle for the power scaling of laser-induced filamentation. Here, we show, however, that, despite all the complexity of the underlying nonlinear physics, filamentation-assisted self-compression of ultrashort laser pulses in the regime of anomalous dispersion can be scaled within a broad range of peak powers against the principle of constant P/Pcr. We identify filamentation self-compression scaling strategies whereby subcycle field waveforms with almost constant pulse widths can be generated without a dramatic degradation of beam quality within a broad range of peak powers, varying from just a few to hundreds of Pcr.