bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the removal of point-of-sale tobacco displays in Ireland
Authors: McNeill Ann , Lewis Sarah , Quinn Casey , Mulcahy Maurice , Clancy Luke , Hastings Gerard , Edwards Richard 
Published: November 2010

AimTo evaluate the short-term impacts of removing point-of-sale tobacco displays in Ireland, implemented in July 2009.MethodsRetailer compliance was assessed using audit surveys in 2007, 2008 and 2009. Using a monthly survey of 1000 adults carried out since 2002, changes in smoking prevalence were assessed; attitudes were measured using extra questions added for a 10-month period before and after the law. Youth responses were assessed using a cohort of 180 13–15 year olds, interviewed in June and August 2009.ResultsImmediately following implementation, compliance was 97%. Support for the law increased among adults after implementation (58% Apr-Jun vs 66% Jul-Dec, p<0.001). Recall of displays decreased significantly for adults (49% to 22%; p<0.001), more so among teenagers (81% to 22%; p<0.001). There were no significant short-term changes in prevalence among youths or adults. The proportion of youths believing more than a fifth of children their age smoked decreased from 62% to 46%, p<0.001). Post-legislation, 14% of adult smokers thought the law had made it easier to quit smoking and 38% of teenagers thought it would make it easier for children not to smoke.ConclusionsCompliance was very high and the law was well supported. Recall of displays dropped significantly among adults and teenagers post-legislation and there were encouraging signs that the law helped de-normalise smoking.
Eroding Australia: rates and processes from Bega Valley to Arnhem Land
Authors: Heimsath Arjun M. , Chappell John , Fifield Keith 
Published: November 2010

Abstract

We report erosion rates determined from
in situ
produced cosmogenic
10
Be across a spectrum of Australian climatic zones, from the soil-mantled SE Australian escarpment through semi-arid bedrock ranges of southern and central Australia, to soil-mantled ridges at a monsoonal tropical site near the Arnhem escarpment. Climate has a major effect on the balance between erosion and transport and also on erosion rate: the highest rates, averaging 35 m Ma
−1
, were from soil-mantled, transport-limited spurs in the humid temperate region around the base of the SE escarpment; the lowest, averaging about 1.5 m Ma
−1
, were from the steep, weathering-limited, rocky slopes of Kings Canyon and Mt Sonder in semi-arid central Australia. Between these extremes, other factors come into play including rock-type, slope, and recruitment of vegetation. We measured intermediate average erosion rates from rocky slopes in the semi-arid Flinders and MacDonnell ranges, and from soil-mantled sites at both semi-arid Tyler Pass in central Australia and the tropical monsoonal site. At soil-mantled sites in both the SE and tropical north, soil production generally declines exponentially with increasing soil thickness, although at the tropical site this relationship does not persist under thin soil thicknesses and the relationship here is ‘humped’. Results from Tyler Pass show uniform soil thicknesses and soil production rates of about 6.5 m Ma
−1
, supporting a longstanding hypothesis that equilibrium, soil-mantled hillslopes erode in concert with stream incision and form convex-up spurs of constant curvature. Moreover, weathering-limited slopes and spurs also occur in the same region: the average erosion rate for rocky sandstone spurs at Glen Helen is 7 m Ma
−1
, similar to the Tyler Pass soil-mantled slopes, whereas the average rate for high, quartzite spurs at Mount Sonder is 1.8 m Ma
−1
. The extremely low rates measured across bedrock-dominated landscapes suggest that the ridge–valley topography observed today is likely to have been shaped as long ago as the Late Miocene. These rates and processes quantified across different, undisturbed landscapes provide critical data for landscape evolution models.
Breaking through a Plateau in Renal Cell Carcinoma Therapeutics: Development and Incorporation of Biomarkers
Authors: Pal Sumanta Kumar , Kortylewski Marcin , Yu Hua , Figlin Robert A. 
Published: November 2010

AbstractWith the Food and Drug Administration approval of 6 novel targeted agents since December 2005 and limited comparative trials to discern relative efficacy, the treatment of metastatic renal cell carcinoma (RCC) has become immensely complex. The research community must look to novel ways in which to identify appropriate candidates for selected targeted therapies; one potential strategy is the use of clinical and molecular biomarkers. A growing body of knowledge-related von Hippel Lindau-driven pathways in this disease has highlighted the potential role of hypoxia-inducible factor subtypes in distinguishing RCC patients clinically. Techniques applied in other malignancies, such as gene expression and proteomic profiling, may also ultimately allow for clinical stratification. An emerging understanding of immunologic phenomena that may affect cancer progression (i.e., tumor infiltration by CD68 lymphocytes, memory T-cells, etc.) has unveiled a number of other potential biomarkers of response. Several vascular endothelial growth factor receptor-directed therapies classically thought to function as antiangiogenics may also have complex effects upon the tumor microenvironment including the associated immune cell milieu. As such, immunologic parameters could potentially predict response to current therapies. Finally, clinical biomarkers, such as hypertension, may predict the efficacy of several currently available targeted agents, although implementation of such biomarkers remains challenging. Herein, the clinical relevance of putative RCC biomarkers is examined in detail. Mol Cancer Ther; 9(12); 3115–25. ©2010 AACR.
The Bilirubin-Increasing Drug Atazanavir Improves Endothelial Function in Patients With Type 2 Diabetes Mellitus
Authors: Dekker Douwe , Dorresteijn Mirrin J. , Pijnenburg Margot , Heemskerk Suzanne , Rasing-Hoogveld Anja , Burger David M. , Wagener Frank A.D.T.G. , Smits Paul 
Published: November 2010

Objective—
In type 2 diabetes mellitus (T2DM), oxidative stress gives rise to endothelial dysfunction. Bilirubin, a powerful endogenous antioxidant, significantly attenuates endothelial dysfunction in preclinical experiments. The Gilbert syndrome is accompanied by a mild and lifelong hyperbilirubinemia and associated with only one third of the usual cardiovascular mortality risk. The hyperbilirubinemia caused by atazanavir treatment closely resembles the Gilbert syndrome. We thus hypothesized that treatment with atazanavir would ameliorate oxidative stress and vascular inflammation and improve endothelial function in T2DM.

Methods and Results—

In a double-blind, placebo-controlled crossover design, we induced a moderate hyperbilirubinemia by a 3-day atazanavir treatment in 16 subjects experiencing T2DM. On the fourth day, endothelial function was assessed by venous occlusion plethysmography. Endothelium-dependent and endothelium-independent vasodilation were assessed by intraarterial infusion of acetylcholine and nitroglycerin, respectively. Atazanavir treatment induced an increase in average bilirubin levels from 7 μmol/L (0.4 mg/dL) to 64 μmol/L (3.8 mg/dL). A significant improvement in plasma antioxidant capacity (
P
<0.001) and endothelium-dependent vasodilation (
P
=0.036) and a decrease in plasma von Willebrand factor (
P
=0.052) were observed.

Conclusion—
Experimental hyperbilirubinemia is associated with a significant improvement of endothelial function in T2DM.
High-Mobility Group Box Protein 1 Neutralization Reduces Development of Diet-Induced Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Kanellakis Peter , Agrotis Alex , Kyaw Tin Soe , Koulis Christine , Ahrens Ingo , Mori Shuji , Takahashi Hideo K. , Liu Keyue , Peter Karlheinz , Nishibori Masahiro , Bobik Alex 
Published: November 2010

Objective—
High-mobility group box protein 1 (HMGB1) is a DNA-binding protein and cytokine highly expressed in atherosclerotic lesions, but its pathophysiological role in atherosclerosis is unknown. We investigated its role in the development of atherosclerosis in ApoE−/− mice.

Methods and Results—
Apolipoprotein E–deficient (ApoE−/−) mice fed a high-fat diet were administered a monoclonal anti-HMGB1 neutralizing antibody, and the effects on lesion size, immune cell accumulation, and proinflammatory mediators were assessed using Oil Red O, immunohistochemistry, and real-time polymerase chain reaction. As with human atherosclerotic lesions, lesions in ApoE−/− mice expressed HMGB1. Treatment with the neutralizing antibody attenuated atherosclerosis by 55%. Macrophage accumulation was reduced by 43%, and vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression was attenuated by 48% and 72%, respectively. CD11c+ dendritic cells were reduced by 65%, and the mature (CD83+) population was reduced by 60%. Treatment also reduced CD4+ cells by nearly 50%. mRNAs in lesions encoding tumor necrosis factor-α and interleukin-1β tended to be reduced. Mechanistically, HMGB1 stimulated macrophage migration in vitro and in vivo; in vivo, it markedly augmented the accumulation of F4/80+Gr-1(Ly-6C)+ macrophages and also increased F4/80+CD11b+ macrophage numbers.

Conclusion—
HMGB1 exerts proatherogenic effects augmenting lesion development by stimulating macrophage migration, modulating proinflammatory mediators, and encouraging the accumulation of immune and smooth muscle cells.
Prevalence of Coronary Atherosclerosis in Patients With Cerebral Infarction
Authors: Amarenco Pierre , Lavallée Philippa C. , Labreuche Julien , Ducrocq Gregory , Juliard Jean-Michel , Feldman Laurent , Cabrejo Lucie , Meseguer Elena , Guidoux Celine , Adraï Valérie , Ratani Samina , Kusmierek Jérôme , Lapergue Bertrand , Klein Isabelle F. , Gongora-Rivera Fernando , Jaramillo Arturo , Mazighi Mikael , Touboul Pierre-Jean , Steg Philippe Gabriel 
Published: November 2010

Background and Purpose—
There is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is no known history of coronary heart disease.

Methods—
We consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6–11) after stroke onset.

Results—
Coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval [CI], 56.5–67.3) and coronary stenoses ≥50% were found in 25.7% (95% CI, 20.9–30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58–2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92–9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%.

Conclusions—
There is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.
Delayed Anti-Nogo-A Therapy Improves Function After Chronic Stroke in Adult Rats
Authors: Tsai Shih-Yen , Papadopoulos Catherine M. , Schwab Martin E. , Kartje Gwendolyn L. 
Published: November 2010

Background and Purpose—
We have shown that anti-Nogo-A immunotherapy to neutralize the neurite growth inhibitory protein Nogo-A results in functional improvement and enhanced plasticity after ischemic stroke in the adult rat. The present study investigated whether functional improvement and neuronal plasticity can be induced by this immunotherapy when administered to the chronic stroke-impaired rat.

Methods—
Adult rats were trained to perform the skilled forelimb reaching test, followed by permanent middle cerebral artery occlusion to impair the preferred forelimb. Nine weeks after stroke, animals showing a profound deficit were randomly distributed to 3 groups: no treatment, control antibody, or anti-Nogo-A antibody (11C7). Animals were tested weekly after stroke surgery and daily after antibody treatment until the end of the study. Biotin dextran amine tracing was injected into the nonlesioned forelimb motor cortex at the end of behavioral testing to determine axonal plasticity.

Results—
All rats showed similar forelimb impairment before treatment. Animals treated with anti-Nogo-A immunotherapy started to show improvement 3 weeks after treatment. Such improvement became significantly better than stroke-only control and control Ab-treated animals, and persisted to the end of the study. Biotin dextran amine-labeled axonal fiber analysis also showed significant enhanced corticorubral axonal sprouting from the contralesional forelimb motor cortex to the deafferented red nucleus in the anti-Nogo-A immunotherapy rats.

Conclusions—
These results indicate that improvement of chronic neurological deficits and enhancement of neuronal plasticity can be induced in the adult rat with anti-Nogo-A immunotherapy, and that this therapy may be used to restore function even when administered long after ischemic brain damage has occurred.
Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma
Authors: Sung Chang Ohk , Kim Sang Cheol , Karnan Sivasundaram , Karube Kennosuke , Shin Hyung Jin , Nam Do-Hyun , Suh Yeon-Lim , Kim Seok-Hyung , Kim Ji Yeon , Kim Seok Jin , Kim Won Seog , Seto Masao , Ko Young-Hyeh 
Published: November 2010

Abstract
Of the genetic changes in primary central nervous system lymphoma (PCNSL), little is known. To detect copy number alterations and differentially expressed genes in PCNSL, we analyzed a total of 12 PCNSL samples with high-resolution array-based comparative genomic hybridization and performed expression profiling in 7 of the 12 samples. The most frequent deletion found in 8 patients (66.7%) occurred in 9p21.3 containing CDKN2A. We compiled the top 96 genes (family-wise error rate, P < .05) showing the greatest differential expression between PCNSL and normal lymph node tissues. From these, we selected 8 candidate genes (NPFFR2, C4orf7, OSMR, EMCN, TPO, FNDC1, COL12A1, and MSC) in which expression changes were associated with copy number aberrations. All 8 genes showed both down-regulation in expression microarray and deletion in array-based comparative genomic hybridization analyses. These genes participate in cell signaling or cell adhesion. In addition, low mRNA expression of C4orf7 was significantly associated with poor survival (P = .0425). Using gene set enrichment analysis, we identified several signal transduction pathways, such as Janus kinase-signal transducers and activators of transcription pathway and adhesion-related pathways, which may be involved in pathogenesis of PCNSL. In conclusion, this study identified novel tumor suppressor genes that may serve as therapeutic targets of PCNSL.
A single mutation results in diploid gamete formation and parthenogenesis in a Drosophila yemanuclein-alpha meiosis I defective mutant
Authors: Meyer Régis E , Delaage Michèle , Rosset Roland , Capri Michèle , Aït-Ahmed Ounissa 
Published: November 2010

Abstract

Background
Sexual reproduction relies on two key events: formation of cells with a haploid genome (the gametes) and restoration of diploidy after fertilization. Therefore the underlying mechanisms must have been evolutionary linked and there is a need for evidence that could support such a model.

Results
We describe the identification and the characterization of yem

1
, the first yem-alpha mutant allele (V478E), which to some extent affects diploidy reduction and its restoration. Yem-alpha is a member of the Ubinuclein/HPC2 family of proteins that have recently been implicated in playing roles in chromatin remodeling in concert with HIRA histone chaperone. The yem

1
mutant females exhibited disrupted chromosome behavior in the first meiotic division and produced very low numbers of viable progeny. Unexpectedly these progeny did not display paternal chromosome markers, suggesting that they developed from diploid gametes that underwent gynogenesis, a form of parthenogenesis that requires fertilization.

Conclusions
We focus here on the analysis of the meiotic defects exhibited by yem

1
oocytes that could account for the formation of diploid gametes. Our results suggest that yem

1
affects chromosome segregation presumably by affecting kinetochores function in the first meiotic division.
This work paves the way to further investigations on the evolution of the mechanisms that support sexual reproduction.
A tritrophic signal that attracts parasitoids to host-damaged plants withstands disruption by non-host herbivores
Authors: Erb Matthias , Foresti Nicolas , Turlings Ted CJ 
Published: November 2010

Abstract

Background
Volatiles emitted by herbivore-infested plants are highly attractive to parasitoids and therefore have been proposed to be part of an indirect plant defense strategy. However, this proposed function of the plant-provided signals remains controversial, and it is unclear how specific and reliable the signals are under natural conditions with simultaneous feeding by multiple herbivores. Phloem feeders in particular are assumed to interfere with plant defense responses. Therefore, we investigated how attack by the piercing-sucking cicadellid Euscelidius variegatus influences signaling by maize plants in response to the chewing herbivore Spodoptera littoralis.

Results
The parasitoid Cotesia marginiventris strongly preferred volatiles of plants infested with its host S. littoralis. Overall, the volatile emissions induced by S. littoralis and E. variegatus were similar, but higher levels of certain wound-released compounds may have allowed the wasps to specifically recognize plants infested by hosts. Expression levels of defense marker genes and further behavioral bioassays with the parasitoid showed that neither the physiological defense responses nor the attractiveness of S. littoralis infested plants were altered by simultaneous E. variegatus attack.

Conclusions
Our findings imply that plant defense responses to herbivory can be more robust than generally assumed and that ensuing volatiles convey specific information about the type of herbivore that is attacking a plant, even in complex situations with multiple herbivores. Hence, the results of this study support the notion that herbivore-induced plant volatiles may be part of a plant's indirect defense stratagem.
Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen
Authors: Cimica Velasco , Smith Melissa E , Zhang Zhikai , Mathur Deepti , Mani Sridhar , Kalpana Ganjam V 
Published: November 2010

Abstract

Background
Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam) in order to reduce the concentration of flavopiridol needed for inhibition of RTs.

Methods
The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i) cell survival assays, ii) FACS analysis, iii) caspase activity assays, and iv) immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA) analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined.

Results
We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G2 arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G2 arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G2 arrest, but enhanced flavopiridol- (but not 4OH-Tam-) mediated apoptosis, by enhancing caspase 2 and 3 activities.

Conclusions
Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was enhanced by abrogation of p53. Our results warrant further studies investigating the combinatorial effects of flavopiridol and 4OH-Tam as a novel therapeutic strategy for RTs and other tumors that have been shown to respond to flavopiridol.
Determinants of delay in malaria treatment-seeking behaviour for under-five children in south-west Ethiopia: a case control study
Authors: Getahun Alemayehu , Deribe Kebede , Deribew Amare 
Published: November 2010

Abstract

Background
Prompt diagnosis and timely treatment of malaria within 24 hours after onset of first symptoms can reduce illness progression to severe stages and therefore, decrease mortality. The reason why mothers/caretakers delay in malaria diagnosis and treatment for under-five children is not well studied in Ethiopia. The objective of this study was to assess determinants of malaria treatment delay in under-five children in three districts of south-west Ethiopia.

Methods
A case control study was conducted from March 15 to April 20, 2010. Cases were under-five children who had clinical malaria and sought treatment after 24 hours of developing sign and symptom, and controls were under-five children who had clinical malaria and sought treatment within 24 hours of developing sign and symptom of malaria. Data were collected by trained enumerators using structured questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using SPSS version 16.0. To identify determinants, multiple logistic regression was done.

Results
A total of 155 mothers of cases and 155 mothers of controls were interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41, 95% CI: 1.39, 8.34), who complained about the side effects of anti-malarial drugs (OR = 4.96, 95% CI: 1.21, 20.36), who had no history of child death (OR = 3.50, 95% CI: 1.82, 6.42) and who complained about the higher cost of transportation to reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45) were more likely to be late for the treatment of malaria in under-five children.

Conclusion
Effective malaria control programmes should address reducing delayed presentation of children for treatment. Efforts to reduce delay should address transport cost, decentralization of services and increasing awareness of the community on early diagnosis and treatment.