bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Note on Using Regression Models to Analyze Randomized Trials: Asymptotically Valid Hypothesis Tests Despite Incorrectly Specified Models
Authors: Kim Jane Paik 
Published: September 2012

SummaryIn the context of randomized trials, Rosenblum and van der Laan (2009, Biometrics 63, 937–945) considered the null hypothesis of no treatment effect on the mean outcome within strata of baseline variables. They showed that hypothesis tests based on linear regression models and generalized linear regression models are guaranteed to have asymptotically correct Type I error regardless of the actual data generating distribution, assuming the treatment assignment is independent of covariates. We consider another important outcome in randomized trials, the time from randomization until failure, and the null hypothesis of no treatment effect on the survivor function conditional on a set of baseline variables. By a direct application of arguments in Rosenblum and van der Laan (2009), we show that hypothesis tests based on multiplicative hazards models with an exponential link, i.e., proportional hazards models, and multiplicative hazards models with linear link functions where the baseline hazard is parameterized, are asymptotically valid under model misspecification provided that the censoring distribution is independent of the treatment assignment given the covariates. In the case of the Cox model and linear link model with unspecified baseline hazard function, the arguments in Rosenblum and van der Laan (2009) cannot be applied to show the robustness of a misspecified model. Instead, we adopt an approach used in previous literature (Struthers and Kalbfleisch, 1986, Biometrika 73, 363–369) to show that hypothesis tests based on these models, including models with interaction terms, have correct type I error.
Does soil nitrogen availability mediate the response of grassland composition to water regime?
Authors: Araya Yoseph N. , Gowing David J. , Dise N. 
Published: September 2012

AbstractQuestionsHow is the composition of wet meadow plant communities influenced by water regime? What controls soil nitrogen (N) availability along a gentle soil water regime gradient? Is vegetation response to subtle changes in soil water regime mediated by N availability?LocationCricklade, Wiltshire, southwest England.MethodsA field survey of community composition and soil N availability was conducted along a gentle gradient of water table depth (mean water table depth between 25 and 70 cm) at a species‐rich hay meadow in southwest England. This study was complemented by a controlled mescosm study undertaken at water table depths between 5 and 45 cm, and a controlled laboratory N mineralization study with water tension varying between 0 and 100 cm (0–10 kPa), the latter augmented with a microbial community study.ResultsThe field, mesocosm and laboratory studies showed that the soil N mineralization rate and N availability responded to water regime. In particular, the N mineralization rate strongly declined when the soil air‐filled pore space dropped below 10% of total soil volume. In the field, plant cover distribution (individual species as well as functional groups) correlated with increase in soil water table depth (r = −0.86 and r = 0.89 for graminoids and forbs, respectively) and soil N availability (r = 0.77 and r = −0.85, respectively). A switch in dominance between forbs and graminoids occurred at a mean water table depth of 55 cm and mean soil inorganic N of 20 mg·kg−1). Study of the soil microbial community composition in the mesocosms, using phospholipid fatty acid (PLFA) signatures, showed that microbial community composition was also significantly influenced by soil water status.ConclusionsWe show that soil moisture content and soil aeration control the availability of N, a limiting nutrient, in species‐rich wet meadows. The mechanism is linked to changes in suitability of the soil water regime for microbially mediated N mineralization. Maintaining the water regime is therefore critical because adjustment of the hydrological niche also conditions species' responses along the N availability gradient. This could subsequently prove a useful tool for conservation managers trying to sustain a target vegetation type.
Rural Roadway Safety Perceptions Among Rural Teen Drivers Living in and Outside of Towns
Authors: Ramirez Marizen , Roth Lisa , Young Tracy , Peek‐Asa Corinne 
Published: September 2012

AbstractPurpose: To compare perceptions about rural road and general driving behaviors between teens who live in‐ and out‐of‐town from rural communities in Iowa.Methods: A cross‐sectional survey was conducted with 160 teens anticipating their Intermediate License within 3 months upon enrollment into this study. Self‐administered surveys were used to collect demographics and driving exposures (eg, frequency of driving, age when first drove unsupervised). Two Likert scales were included to measure agreement with safe driving behaviors on rural roads and general safe driving behaviors (eg, speeding, seat belt use). T‐tests were calculated comparing mean composite scores between in‐ and out‐of‐town teens, and between mean rural road and general driving safety attitude scores. A linear regression multivariable model was constructed to identify predictors of the rural road score.Results: While the majority of teens endorsed rural road and general safe driving behaviors, up to 40% did not. Thirty‐two percent did not believe the dangers of animals on rural roads, and 40% disagreed that exceeding the speed limit is dangerous. In‐town teens were less safety conscious about rural road hazards with a significantly lower mean composite score (4.4) than out‐of‐town teens (4.6); mean scores for general driving behaviors were similar. Living out‐of‐town and owning one's own car were significant predictors of increased rural road safety scores.Conclusion: Rural, in‐town teens have poorer safety attitudes about rural roadway hazards compared with out‐of‐town teens. Interventions that involve education, parental supervision, and practice on rural roads are critical for preventing teen crashes on rural roads.
Activated hepatic stellate cells mediate the differentiation of macrophages
Authors: Chang Jonathan , Hisamatsu Tadakazu , Shimamura Katsuyoshi , Yoneno Kazuaki , Adachi Masayuki , Naruse Hiroshi , Igarashi Toru , Higuchi Hajime , Matsuoka Katsuyoshi , Kitazume Mina T. , Ando Setsu , Kamada Nobuhiko , Kanai Takanori , Hibi Toshifumi 
Published: September 2012

AimLiver macrophages play integral roles in both the progression and resolution of hepatic inflammation and fibrosis, comprising opposing functions that largely coincide with the activation state of nearby hepatic stellate cells (HSC). While cross‐talk between HSC and macrophages may be essential at various stages of inflammation and fibrogenesis, many facets of this interaction have yet to be thoroughly explored. Here, we examine the potential roles of HSC‐derived signaling molecules as mediators of liver macrophage differentiation.MethodsHuman peripheral blood mononuclear cells (PBMC) were differentiated to macrophages in the presence or absence of cultured HSC‐derived conditioned media. The phenotype of resulting macrophages was characterized by examination of cell surface marker expression, antigen‐presenting capabilities and cytokine secretion.ResultsConditioned media from activated human HSC promoted the differentiation of a unique set of macrophages that differed in morphology and function from both classical (M1) and alternative (M2) macrophages, expressing increased levels of CD14 and CD16, as well as a distinct interleukin (IL)‐6high/IL‐10low/transforming growth factor (TGF)‐βhigh expression profile. These macrophages expressed high levels of CD206, CD209, CD80 and human leukocyte antigen DR, though no significant increases in antigen presentation were apparent. HSC‐derived macrophages exhibited specific activation of p38 mitogen‐activated protein kinase, and inhibition of this activation by p38 inhibitors during differentiation effectively reversed increases in IL‐6 and TGF‐β.ConclusionThe present results suggest that HSC‐derived signaling molecules promote differentiation of liver macrophages with both pro‐inflammatory and profibrotic functions. Furthermore, these effects appear to be mediated, at least partially, in a p38‐dependent manner.
The Impact of an Online Learning Community Project on University Chinese as a Foreign Language Students’ Motivation
Authors: Cai Shengrong , Zhu Wei 
Published: September 2012

AbstractThis study investigated the impact of an online learning community project on university students’ motivation in learning Chinese as a foreign language. A newly proposed second language (L2) motivation theory—the L2 motivational self system (Dörnyei, 2005, 2009)—guided this study. A concurrent transformative mixed‐methods design was employed to collect both quantitative and qualitative data through the pre‐ and posttest of a questionnaire. Results from paired t tests indicated a significant difference in the L2 learning experience aspect of motivation before and after the online project, while there was no significant difference in the other two aspects of motivation (i.e., the ideal L2 self and the ought‐to L2 self). Specific motivating and demotivating features of the online project were identified from participants’ responses to an open‐ended question.
Population‐based trends in overweight and obesity: a comparative study of 2 148 342 Israeli male and female adolescents born 1950–1993
Authors: Meydan C. , Afek A. , Derazne E. , Tzur D. , Twig G. , Gordon B. , Shamiss A. 
Published: September 2012

Summary
What is already known about this subject?
Obesity is rising among children and adolescents in Israel and as a global trend.
Obesity during adolescence correlates to morbidity in adulthood.
Socio‐demographic and ethnic factors are risk modifiers for obesity.

What this study adds?
Temporal trends of obesity in adolescents in a large study with measured physical dimensions.
A descriptive case study of obesity trends in a country that shifted from developing to booming.
Elucidation of risk factors for obesity in adolescents, including socioeconomic status, geographical origin and education.
Exploration of gender disparities.
BackgroundThe epidemic of obesity has been identified as a major source of morbidity, not just in developed countries but globally, in adults as well as at younger ages.ObjectiveThe aims of this study were to describe trends in obesity and overweight in Israeli adolescents and observe temporal changes and association by risk factors.MethodsThe research analyzed records of 2 148 342 Jewish adolescents, over a span of 44 years and included data for individual body measurements, place of residence, area of origin and education levels. Body mass index (BMI) was measured by professionals, calculated and categorized as overweight or obesity according to age‐ and gender‐specific BMI curves established in recent years. We processed the data in multinomial logistic regression model and calculated odds ratios for various risk factors.ResultsObesity and overweight are on the rise for male and female adolescents born from the mid‐1960s onwards, and especially for men from the 1980s onwards. Risk factors for male adolescents include lower socioeconomic status, inferior education levels and Western origins (vs. Asian, African or Israeli origins). Risk modifiers for women were similar, except for African origins, which were associated with increased risk rather than decreased risk. Asian and Israeli origins were protective for both genders, and education was more strongly associated with obesity for women.ConclusionsWe recommend stronger preventive efforts directed at adolescents as a whole, and particularly vulnerable groups with lower education levels and poverty, or those with specific geographical origins. Gender disparities are evident and should be considered in these efforts and in further research.
Guided gingival fibroblast attachment to titanium surfaces: an in vitro study
Authors: Kearns Victoria R , Williams Rachel L. , Mirvakily Felora , Doherty Patrick J. , Martin Nicolas 
Published: September 2012

AbstractAimTo assess the potential of gingival fibroblasts to attach in a predetermined linear orientation to a nano‐topography of aligned fibres on titanium surfaces and determine the ability of such cells to deposit aligned collagen fibre matrix.Materials and Methodssmooth glass and rough titanium substrates were coated with polytetrafluoroethylene (PTFE) nano‐fibres. Ammonia plasma treatment was used to modify the surface chemistry. Human gingival fibroblasts were cultured on substrates and orientation and collagen deposition was assessed.ResultsStraight, unidirectional, parallel PTFE nano‐fibres were deposited over the titanium features. By 7 days, the majority of cells were observed to orient to untreated fibres despite the presence of competing titanium surface features. On plasma‐treated fibre‐coated titanium substrates, cell orientation was mixed. On uncoated substrates, the majority of cells oriented to the titanium surface features. On fibre‐coated glass substrates, cells oriented themselves with untreated and plasma‐treated fibres and secreted collagen in the same direction after 1 week. On uncoated glass substrates, there was no preferred direction of collagen orientation.ConclusionPolytetrafluoroethylene nano‐fibres induced cell and collagen orientation. Surface chemistry appeared only to affect cell behaviour at early time points. An implant surface that controls cell orientation may also influence the orientation of collagen, providing improved gingival support.
A randomised titrated crossover study comparing two oral appliances in the treatment for mild to moderate obstructive sleep apnoea/hypopnoea syndrome
Authors: Zhou J. , Liu Y.H. 
Published: September 2012

SummaryThe objective of this study was to compare the efficiency of two oral appliances in patients with mild to moderate obstructive sleep apnoea/hypopnoea syndrome (OSAHS) by the analysis of objective and subjective evaluations and measurement of upper airway parameter. A randomised crossover design trial was carried out on 16 patients with OSAHS. Two different types of oral appliances were tested in each patient, a one‐piece monoblock and the SILENT NITE® (GlideWell Laboratories, Newport Beach, CA, USA), a two‐piece appliance. Each oral appliance needed to be worn for two 3‐month periods separated by a 2‐week wash‐out period in between. The objective and subjective efficiency and upper airway parameters associated with the oral appliances were assessed. One‐way analysis of variance (anova) test was performed to compare the changes in upper airway morphology and the treatment efficiency between the appliances. The monoblock and SILENT NITE® (GlideWell Laboratories) appliances reduced Apnoea Hypopnoea Index (AHI) from 26·38 ± 4·13 to 7·58 ± 2·28 (P < 0·001) and 8·87 ± 2·88 (P < 0·001), respectively. The monoblock appliance was statistically more efficient in reducing AHI and Apnoea Index (AI) than the SILENT NITE® (GlideWell Laboratories) (P < 0·05). The scores on Epworth's Sleepiness Scale (ESS) and Snoring Scale (SS) were improved significantly by both appliances. The upper airway spaces showed considerable enlargement by both mandibular advancement appliances (MAAs) (P < 0·05), while no significant differences were found between the two appliances (P > 0·05). Both MAAs showed good efficacy in the treatment for mild to moderate OSAHS. Use of the monoblock appliance should be considered when patients with OSAHS choose MAA treatment, as it was more efficient in reducing the AHI and AI compared to the two‐piece appliance and was preferred by most patients. Long‐term efficiency should be evaluated in future prospective studies.
Topology of the microsomal glycerol‐3‐phosphate acyltransferase Gpt2p/Gat1p of Saccharomyces cerevisiae
Authors: Pagac Martin , Vazquez Hector M. , Bochud Arlette , Roubaty Carole , Knöpfli Cécile , Vionnet Christine , Conzelmann Andreas 
Published: September 2012

SummaryAll glycerophospholipids are made from phosphatidic acid, which, according to the traditional view, is generated at the cytosolic surface of the ER. In yeast, phosphatidic acid is synthesized de novo by two acyl‐CoA‐dependent acylation reactions. The first is catalysed by one of the two homologous glycerol‐3‐phosphate acyltransferases Gpt2p/Gat1p and Sct1p/Gat2p, the second by one of the two 1‐acyl‐sn‐glycerol‐3‐phosphate acyltransferases Slc1p and Ale1p/Slc4p. To study the biogenesis and topology of Gpt2p we observed the location of dual topology reporters inserted after various transmembrane helices. Moreover, using microsomes, we probed the accessibility of natural and substituted cysteine residues to a membrane impermeant alkylating agent and tested the protease sensitivity of various epitope tags inserted into Gpt2p. Finally, we assayed the sensitivity of the acyltransferase activity to membrane impermeant agents targeting lysine residues. By all these criteria we find that the most conserved motifs of Gpt2p and its functionally relevant lysines are oriented towards the ER lumen. Thus, the first step in biosynthesis of phosphatidic acid in yeast seems to occur in the ER lumen and substrates may have to cross the ER membrane.
Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets
Authors: Sá MA , Andrade VB , Mendes RM , Caliari MV , Ladeira LO , Silva EE , Silva GAB , Corrêa‐Júnior JD , Ferreira AJ 
Published: September 2012

ObjectiveWe evaluated the effects of sodium hyaluronate (HY) and carbon nanotubes functionalized with HY (HY‐CNT) on bone repair in the tooth sockets of diabetic rats.Materials and MethodsDiabetes was induced by streptozotocin (50 mg kg−1 i.v.), and the sockets were divided into normal control, diabetic control, diabetic treated with HY (1%), and diabetic treated with HY‐CNT (100 μg ml−1) groups. The sockets were analyzed according to the percentage of bone formation and the number of cell nuclei.ResultsThe percentage of bone trabeculae was lower in diabetic control animals (11.16 ± 5.10% vs 41.92 ± 6.34% in normal animals) after 14 days. Treating diabetic animals with HY or HY‐CNT significantly increased the percentage of neoformed trabeculae (HY: 29.43 ± 3.29%; HY‐CNT: 36.90 ± 3.07%). Moreover, the sockets of diabetic animals had an increased number of cell nuclei and HY or HY‐CNT reduced this parameter.ConclusionOur results indicate that HY and HY‐CNT restore bone repair in the tooth sockets of diabetic rats, suggesting that these biomaterials are potential adjuvant therapies for the management of diabetes.
TBX2 expression is regulated by PAX3 in the melanocyte lineage
Authors: Liu Fang , Cao Juxiang , Lv Jinghu , Dong Liang , Pier Eric , Xu George X. , Wang Rui‐an , Xu Zhixiang , Goding Colin , Cui Rutao 
Published: September 2012

SummaryThe paired box homeotic gene 3 (PAX3) is a crucial regulator for the maintenance of melanocytic progenitor cells and has a poorly defined role in melanoma. To understand how PAX3 affects melanocyte and melanoma proliferation, we identified potential PAX3 downstream targets through gene expression profiling. Here, we identify T‐box 2 (TBX2), a key developmental regulator of cell identity and an antisenescence factor in melanoma, as a directly regulated PAX3 target. We also found that TBX2 is involved in the survival of melanoma cells and is overexpressed in some melanoma specimens. The identification of TBX2 as a target for PAX3 provides a key insight into how PAX3 may contribute to melanoma evolution and may provide opportunities for prosenescence therapeutic intervention aimed at disrupting the ability of PAX3 to regulate TBX2.
Vitamin D in Dialysis: Defining Deficiency and Rationale for Supplementation
Authors: Singer Richard Francis 
Published: September 2012

AbstractVitamin D status is determined by the serum concentration of one of its metabolites, 25‐hydroxy‐D. Defining vitamin D deficiency based on its classical roles in gut calcium absorption and bone mineralization is problematic in dialysis patients and, until recently, was ignored in the nephrology literature. The newly recognized nonclassical functions of vitamin D include effects on the immune system, cardiovascular disease, and cancer. The nonclassical effects are likely to be equally relevant in the dialysis population, but suffer from a lack of strong evidence on which to base therapeutic targets. Past medical opinion in the nondialysis population warned that higher dose vitamin D supplementation may be toxic and was unnecessary. This is because older supplementation recommendations were based on early twentieth century studies using cod‐liver oil to treat rickets. The clinical resolution of rickets requires a relatively low dose of vitamin D. Current vitamin D guidelines generally target higher 25‐hydroxy‐D levels of 30 ng/ml, based on optimizing markers of bone health. This results in very high estimates of 50–100% for the prevalence of vitamin D deficiency in dialysis patients. This review examines the relevance of data on the classical and nonclassical effects of vitamin D in dialysis patients. An evidence‐based dosing regimen for use in dialysis patients is suggested to safely and reliably achieve vitamin D sufficiency.
Imaging a relic of complex tectonics: the lithosphere‐asthenosphere structure in the Eastern Mediterranean
Authors: ElGabry Mohamed N. , Panza Giuliano Francesco , Badawy Ahmed A. , Korrat Ibrahim M. 
Published: September 2012

Terra Nova, 25, 102–109, 2013AbstractThe crust and upper mantle structure of the Eastern Mediterranean is investigated through the nonlinear inversion of Raleigh wave dispersion curves extracted from broadband records in the region along two profiles crossing the Hellenic and Cyprian arcs. Corresponding density models are constructed, consistent with the observed gravity anomalies. The modelled profiles exhibit a continental crust type overlain by a thick sedimentary cover and underlain by a thick lithospheric mantle. The lithosphere‐asthenosphere system exhibits features, which suggest the presence of upducted asthenosphere exhumed to the north of the Hellenic arc, where the slab extension is limited to depths of about 220 km.