bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Long Non‐Coding RNA Growth Arrest‐Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease
Authors: Lucafò Marianna , Di Silvestre Alessia , Romano Maurizio , Avian Alice , Antonelli Roberta , Martelossi Stefano , Naviglio Samuele , Tommasini Alberto , Stocco Gabriele , Ventura Alessandro , Decorti Giuliana , De Iudicibus Sara 
Published: July 2017

AbstractGlucocorticoids (GCs) are widely employed in inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first‐line treatment for inducing remission in inflammatory bowel disease (IBD). Given the high incidence of suboptimal response, associated with a significant number of side‐effects, that are particularly severe in paediatric patients, the identification of subjects that are most likely to respond poorly to GCs is extremely important. Recent evidence suggests that the long non‐coding RNA (lncRNA) GAS5 could be a potential marker of GC resistance. To address this issue, we evaluated the association between the lncRNA GAS5 and the efficacy of steroids, in terms of inhibition of proliferation, in two cell lines derived from colon and ovarian cancers, to confirm the sensitivity and specificity of these lncRNAs. These cells showed a different sensitivity to GCs and revealed differential expression of GAS5 after treatment. GAS5 was up‐regulated in GC‐resistant cells and accumulated more in the cytoplasm compared to the nucleus in response to the drug. The functions of GAS5 were assessed by silencing, and we found that GAS5 knock‐down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and we demonstrated an up‐regulation of the lncRNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.
A Local Agreement Pattern Measure Based on Hazard Functions for Survival Outcomes
Authors: Dai Tian , Guo Ying , Peng Limin , Manatunga Amita K. 
Published: July 2017

Summary
Assessing agreement is often of interest in biomedical and clinical research when measurements are obtained on the same subjects by different raters or methods. Most classical agreement methods have been focused on global summary statistics, which cannot be used to describe various local agreement patterns. The objective of this work is to study the local agreement pattern between two continuous measurements subject to censoring. In this article, we propose a new agreement measure based on bivariate hazard functions to characterize the local agreement pattern between two correlated survival outcomes. The proposed measure naturally accommodates censored observations, fully captures the dependence structure between bivariate survival times and provides detailed information on how the strength of agreement evolves over time. We develop a nonparametric estimation method for the proposed local agreement pattern measure and study theoretical properties including strong consistency and asymptotical normality. We then evaluate the performance of the estimator through simulation studies and illustrate the method using a prostate cancer data example.
Renal-infiltrating CD11c+ cells are pathogenic in murine lupus nephritis through promoting CD4+ T cell responses
Authors: Liao X , Ren J , Reihl A , Pirapakaran T , Sreekumar B , Cecere T E , Reilly C M , Luo X M 
Published: July 2017

SummaryLupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE), causing morbidity and mortality in 40–60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c+ myeloid cell population in LN. These CD11c+ cells accumulated in the kidneys of lupus-prone mice as LN progressed. Surface markers of this population suggest their dendritic cell identity and differentiation from lymphocyte antigen 6 complex (Ly6C)low mature monocytes. The cytokine/chemokine profile of these renal-infiltrating CD11c+ cells suggests their roles in promoting LN, which was confirmed further in a loss-of-function in-vivo study by using an antibody-drug conjugate (ADC) strategy targeting CX3CR1, a chemokine receptor expressed highly on these CD11c+ cells. However, CX3CR1 was dispensable for the homing of CD11c+ cells into lupus nephritic kidneys. Finally, we found that these CD11c+ cells co-localized with infiltrating T cells in the kidney. Using an ex- vivo co-culture system, we showed that renal-infiltrating CD11c+ cells promoted the survival, proliferation and interferon-γ production of renal-infiltrating CD4+ T cells, suggesting a T cell-dependent mechanism by which these CD11c+ cells promote LN. Together, our results identify a pathogenic kidney-infiltrating CD11c+ cell population promoting LN progression, which could be a new therapeutic target for the treatment of LN.
Countering resistance to protected‐area extension
Authors: Lindenmayer David , Thorn Simon , Noss Reed 
Published: July 2017

AbstractThe establishment of protected areas is a critical strategy for conserving biodiversity. Key policy directives like the Aichi targets seek to expand protected areas to 17% of Earth's land surface, with calls by some conservation biologists for much more. However, in places such as the United States, Germany, and Australia, attempts to increase protected areas are meeting strong resistance from communities, industry groups, and governments. We examined case studies of such resistance in Victoria, Australia, Bavaria, Germany, and Florida, United States. We considered 4 ways to tackle this problem. First, broaden the case for protected areas beyond nature conservation to include economic, human health, and other benefits, and translate these into a persuasive business case for protected areas. Second, better communicate the conservation values of protected areas. This should include highlighting how many species, communities, and ecosystems have been conserved by protected areas and the counterfactual (i.e., what would have been lost without protected area establishment). Third, consider zoning of activities to ensure the maintenance of effective management. Finally, remind citizens to think about conservation when they vote, including holding politicians accountable for their environmental promises. Without tackling resistance to expanding the protected estate, it will be impossible to reach conservation targets, and this will undermine attempts to stem the global extinction crisis.
Beyond glycaemic control: A cross‐over, double‐blinded, 24‐week intervention with liraglutide in type 1 diabetes
Authors: Dubé Marie‐Christine , D'Amours Martin , Weisnagel S. John 
Published: July 2017

AimsTo investigate the effects of 24 weeks of treatment with liraglutide added to basal/bolus insulin on anthropometric and metabolic parameters in overweight participants with type 1 diabetes.MethodsIn a double‐blinded cross‐over fashion, 15 participants were randomly assigned (1:1) to receive placebo (saline solution) or liraglutide for 24 weeks including a 1‐month titration period from 0.6 to 1.2 to 1.8 mg, in addition to their insulin. The treatment was followed by a 1‐month wash‐out period. Participants were then assigned to the other treatment for another 24 weeks. Paired rank tests were used to compare the metabolic parameters.ResultsThere was no treatment effect on HbA1c nor on insulin dose. Heart rate was increased by about 8 beats per minute with liraglutide. There were significant reductions in metabolic measures: weight, body mass index, waist and hip circumferences, body fatness, computed tomography scan abdominal and mid‐thigh measurements, systolic and diastolic blood pressures (all P ≤ .05). There was no increase in time spent in hypoglycaemia with liraglutide.ConclusionsThe addition of liraglutide to basal/bolus insulin therapy for 24 weeks in overweight/obese individuals with type 1 diabetes improved the anthropometric and metabolic profiles without an increase in hypoglycaemia.Clinical Trials.gov No: NCT01787916.
Development of a cardiovascular diseases risk prediction model and tools for Chinese patients with type 2 diabetes mellitus: A population‐based retrospective cohort study
Authors: Wan Eric Yuk Fai , Fong Daniel Yee Tak , Fung Colman Siu Cheung , Yu Esther Yee Tak , Chin Weng Yee , Chan Anca Ka Chun , Lam Cindy Lo Kuen 
Published: July 2017

AimsEvidence‐based cardiovascular diseases (CVD) risk prediction models and tools specific for Chinese patients with type 2 diabetes mellitus (T2DM) are currently unavailable. This study aimed to develop and validate a CVD risk prediction model for Chinese T2DM patients.MethodsA retrospective cohort study was conducted with 137 935 Chinese patients aged 18 to 79 years with T2DM and without prior history of CVD, who had received public primary care services between January 1, 2010 and December 31, 2010. Using the derivation cohort over a median follow‐up of 5 years, the interaction effect between predictors and age were derived using Cox proportional hazards regression with a forward stepwise approach. Harrell's C statistic and calibration plot were used on the validation cohort to assess the discrimination and calibration of the models. The web calculator and chart were developed based on the developed models.ResultsFor both genders, predictors for higher risk of CVD were older age, smoking, longer diabetes duration, usage of anti‐hypertensive drug and insulin, higher body mass index, haemoglobin A1c (HbA1c), systolic and diastolic blood pressure, a total cholesterol to high‐density lipoprotein‐cholesterol (TC/HDL‐C) ratio and urine albumin to creatinine ratio, and lower estimated glomerular filtration rate. Interaction factors with age demonstrated a greater weighting of TC/HDL‐C ratio in both younger females and males, and smoking status and HbA1c in younger males.ConclusionThe developed models, translated into a web calculator and color‐coded chart, served as evidence‐based visual aids that facilitate clinicians to estimate quickly the 5‐year CVD risk for Chinese T2DM patients and to guide intervention.
ADAM10 modulates calcitriol‐regulated RAGE in cardiomyocytes
Authors: Lee Ting‐Wei , Kao Yu‐Hsun , Lee Ting‐I , Chen Yi‐Jen 
Published: July 2017

AbstractBackgroundReceptor for advanced glycation end products (RAGE) signalling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression. This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes.Materials and methodsWestern blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N‐terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL‐1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor‐κB (NF‐κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 h.ResultsCalcitriol (10 nM) significantly reduced RAGE protein expression and increased sRAGE concentrations in HL‐1 cardiomyocytes compared with control cells. These changes were associated with increased protein expression and enzyme activity of ADAM10 and higher mRNA expression of esRAGE. In the presence of ADAM10 inhibitor, however, the suppressive effect of calcitriol on RAGE was diminished. Methylglyoxal (500 μM for 10 min)‐mediated JNK phosphorylation was attenuated in the presence of calcitriol (10 nM). Moreover, control and NF‐κB inhibitor‐treated HL‐1 cells had similar RAGE and sRAGE expression, suggesting that calcitriol‐mediated RAGE modulation was independent of NF‐κB signalling.ConclusionsWe showed that RAGE downregulation and increased sRAGE production by calcitriol were mediated through ADAM10 activation in cardiomyocytes. The results suggest that calcitriol has therapeutic potential in treating RAGE‐mediated cardiovascular complications.
The role of plant phenology in stomatal ozone flux modeling
Authors: Anav Alessandro , Liu Qiang , De Marco Alessandra , Proietti Chiara , Savi Flavia , Paoletti Elena , Piao Shilong 
Published: July 2017

AbstractPlant phenology plays a pivotal role in the climate system as it regulates the gas exchange between the biosphere and the atmosphere. The uptake of ozone by forest is estimated through several meteorological variables and a specific function describing the beginning and the termination of plant growing season; actually, in many risk assessment studies, this function is based on a simple latitude and topography model. In this study, using two satellite datasets, we apply and compare six methods to estimate the start and the end dates of the growing season across a large region covering all Europe for the year 2011. Results show a large variability between the green‐up and dormancy dates estimated using the six different methods, with differences greater than one month. However, interestingly, all the methods display a common spatial pattern in the uptake of ozone by forests with a marked change in the magnitude, up to 1.9 TgO3/year, and corresponding to a difference of 25% in the amount of ozone that enters the leaves. Our results indicate that improved estimates of ozone fluxes require a better representation of plant phenology in the models used for O3 risk assessment.
A unifying explanation for variation in ozone sensitivity among woody plants
Authors: Feng Zhaozhong , Büker Patrick , Pleijel Håkan , Emberson Lisa , Karlsson Per Erik , Uddling Johan 
Published: July 2017

AbstractTropospheric ozone is considered the most detrimental air pollutant for vegetation at the global scale, with negative consequences for both provisioning and climate regulating ecosystem services. In spite of recent developments in ozone exposure metrics, from a concentration‐based to a more physiologically relevant stomatal flux‐based index, large‐scale ozone risk assessment is still complicated by a large and unexplained variation in ozone sensitivity among tree species. Here, we explored whether the variation in ozone sensitivity among woody species can be linked to interspecific variation in leaf morphology. We found that ozone tolerance at the leaf level was closely linked to leaf dry mass per unit leaf area (LMA) and that whole‐tree biomass reductions were more strongly related to stomatal flux per unit leaf mass (r2 = 0.56) than to stomatal flux per unit leaf area (r2 = 0.42). Furthermore, the interspecific variation in slopes of ozone flux–response relationships was considerably lower when expressed on a leaf mass basis (coefficient of variation, CV = 36%) than when expressed on a leaf area basis (CV = 66%), and relationships for broadleaf and needle‐leaf species converged when using the mass‐based index. These results show that much of the variation in ozone sensitivity among woody plants can be explained by interspecific variation in LMA and that large‐scale ozone impact assessment could be greatly improved by considering this well‐known and easily measured leaf trait.
Sensory strategies of postural sway during quiet stance in patients with haemophilic arthropathy
Authors: Cruz‐Montecinos C. , De la Fuente C. , Rivera‐Lillo G. , Morales‐Castillo S. , Soto‐Arellano V. , Querol F. , Pérez‐Alenda S. 
Published: July 2017

IntroductionThe sensory strategies of postural control in adult haemophilic arthropathy patients are still poorly understood.AimTo determine sensorial posture‐control strategies through postural sway frequency analysis when in a bipedal quiet stance with and without visual stimulus deprivation in healthy subjects and patients with haemophilic arthropathy. Secondarily, to determine the irregularity of postural balance control through sample entropy (SampEn).MethodsA triaxial accelerometer attached at the L3 level determined the displacement and acceleration of the centre of mass (DCoM and ACoM, respectively) under open‐ and closed‐eyes conditions. Sensorial strategies were studied by spectral analysis of the DCoM signal, divided into low, medium and high frequencies for visual/vestibular, cerebellum and somatosensory strategies respectively. DCoM irregularity was also analysed by SampEn.ResultsFifteen young, healthy subjects and fifteen young, haemophilia patients were included. The mediolateal DCoM and anteroposterior ACoM differed between groups. During the open‐eyes condition, haemophiliacs presented limited high and medium frequencies, and more low frequency bands as compared to non‐haemophiliacs (P<.05). In the closed‐eyes condition, haemophiliacs had a minor percentage of high frequencies but an elevated percentage of low frequencies as compared to non‐haemophiliacs (P<.05). Non‐haemophiliacs had higher SampEn than haemophiliacs in the mediolateral axis with open‐ and closed‐eyes (P<.05 and <.001, respectively).ConclusionsThe presented results indicate that patients with haemophilic arthropathy, as compared to healthy subjects, have less postural control irregularity and poor somatosensory system contributions that are compensated by more vestibular inputs.
Add‐on effects of fluvastatin in simeprevir/pegylated‐interferon/ribavirin combination therapy for patients with genotype 1 hepatitis C virus infection: A randomized controlled study
Authors: Suda Goki , Ito Jun , Nagasaka Atsushi , Yamamoto Yoshiya , Furuya Ken , Okamoto Munenori , Terashita Katsumi , Kobayashi Tomoe , Tsunematsu Izumi , Yoshida Junichi , Meguro Takashi , Ohara Masatsugu , Kawagishi Naoki , Kimura Megumi , Umemura Machiko , Izumi Takaaki , Tsukuda Yoko , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Morikawa Kenichi , Ogawa Koji , Sakamoto Naoya ,   for the NORTE Study Group
Published: July 2017

BackgroundThe Japan Society of Hepatology guidelines indicate that hepatitis C virus (HCV) protease inhibitor combination therapy with simeprevir (SMV), pegylated‐interferon (Peg‐IFN), and ribavirin (RBV) is a therapeutic option for patients who fail to respond to a direct direct‐acting antiviral‐containing regimen. However, treatment outcomes have room for improvement. Fluvastatin (FLV) add‐on treatment in Peg‐IFN and RBV combination therapy for HCV‐infected patients significantly improved the sustained virologic response (SVR), but the add‐on effect of FLV on SMV combination therapy is not well understood.MethodsThis was a prospective, randomized, multicenter study in which a total of 61 HCV genotype 1b‐infected patients were recruited and 60 eligible patients were randomly allocated to two groups that received 12 weeks of SMV/Peg‐IFN/RBV followed by 12 weeks of Peg‐IFN/RBV with or without 24 weeks of FLV. The SVR rate and adverse events were compared between the two groups.ResultsThirty‐one patients were allocated to the FLV add‐on group and 29 patients were allocated to the control group. Baseline clinical factors, including median age, baseline platelet count, alanine aminotransferase level, HCV RNA titer, Fibrosis‐4 index, and rate of IL28B minor genotype, were all similar between the two groups. The rapid virologic response, end‐of‐treatment response rates, SVR rates at 24 weeks after treatment, and safety profiles were also similar between the two groups.ConclusionsThis prospective, randomized, multicenter study indicated that FLV had no add‐on effect when given with SMV/Peg‐IFN/RBV combination therapy for genotype 1b HCV‐infected patients.
Food Security at Whose Expense? A Critique of the Canadian Temporary Farm Labour Migration Regime and Proposals for Change
Authors: Weiler Anelyse M. , McLaughlin Janet , Cole Donald C. 
Published: July 2017

AbstractTemporary farm labour migration schemes in Canada have been justified on the premise that they bolster food security for Canadians by addressing agricultural labour shortages, while tempering food insecurity in the Global South via remittances. Such appeals hinge on an ideology defining migrants as racialized outsiders to Canada. Drawing on qualitative interviews and participant observation in Mexico, Jamaica and Canada, we critically analyse how Canada's Seasonal Agricultural Worker Program is tied to ideological claims about national food security and agrarianism, and how it purports to address migrant workers’ own food insecurity. We argue remittances only partially, temporarily mitigate food insecurity and fail to strengthen migrant food sovereignty. Data from our clinical encounters with farm workers illustrate structural barriers to healthy food access and negative health consequences. We propose an agenda for further research, along with policies to advance food security and food sovereignty for both migrants and residents of Canada.
Usefulness of fragmented QRS in hypertensive patients in the absence of left ventricular hypertrophy
Authors: Eyuboglu Mehmet , Karabag Yavuz , Karakoyun Suleyman , Senarslan Omer , Tanriverdi Zulkif , Akdeniz Bahri 
Published: July 2017

In the absence of left ventricular hypertrophy, importance of fragmented QRS complex (fQRS) in individuals with hypertension is unknown. The authors aimed to evaluate the relationship between blood pressure levels and fQRS in the absence of left ventricular hypertrophy. A total of 548 never‐treated patients who underwent 24‐hour ambulatory blood pressure monitoring were enrolled. The frequency of fQRS was significantly higher in patients with hypertension than normotension (36.4% vs 17.6%, P<.05). Multivariate logistic regression analysis revealed that systolic blood pressure is significantly associated with presence of fQRS on electrocardiography (odds ratio, 0.931; 95% CI, 0.910–0.9521 [P<.001]) even after adjusting for other confounding factors. Receiver operating characteristic analysis revealed a cutoff value of 147.65 mm Hg for systolic blood pressure to predict presence of fQRS (sensitivity: 51%, specificity: 99%, area under the curve=0.764; 95% CI, 0.717–0.811 [P<.001]). fQRS may be a sign of increased blood pressure and may predict higher fibrotic burden in patients with hypertension.