bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformation-Selective Methylation of Geminivirus DNA
Authors: Paprotka T. , Deuschle K. , Metzler V. , Jeske H. 
Published: August 2011

ABSTRACT
Geminiviruses with small circular single-stranded DNA genomes replicate in plant cell nuclei by using various double-stranded DNA (dsDNA) intermediates: distinct open circular and covalently closed circular as well as heterogeneous linear DNA. Their DNA may be methylated partially at cytosine residues, as detected previously by bisulfite sequencing and subsequent PCR. In order to determine the methylation patterns of the circular molecules, the DNAs of tomato yellow leaf curl Sardinia virus (TYLCSV) and Abutilon mosaic virus were investigated utilizing bisulfite treatment followed by rolling circle amplification. Shotgun sequencing of the products yielded a randomly distributed 50% rate of C maintenance after the bisulfite reaction for both viruses. However, controls with unmethylated single-stranded bacteriophage DNA resulted in the same level of C maintenance. Only one short DNA stretch within the C2/C3 promoter of TYLCSV showed hyperprotection of C, with the protection rate exceeding the threshold of the mean value plus 1 standard deviation. Similarly, the use of methylation-sensitive restriction enzymes suggested that geminiviruses escape silencing by methylation very efficiently, by either a rolling circle or recombination-dependent replication mode. In contrast, attempts to detect methylated bases positively by using methylcytosine-specific antibodies detected methylated DNA only in heterogeneous linear dsDNA, and methylation-dependent restriction enzymes revealed that the viral heterogeneous linear dsDNA was methylated preferentially.
The effect of community and family interventions on young people's physical activity levels: a review of reviews and updated systematic review
Authors: van Sluijs Esther M F , Kriemler Susi , McMinn Alison M 
Published: August 2011

BackgroundNext to the school environment, the family and community environment are key for young people's behaviour and for promoting physical activity (PA).MethodsA review of reviews was conducted, after which a literature search was conducted (in PubMed, Scopus and PsychInfo) from August 2007 (search date of the most recent review) to October 2010. Inclusion criteria were study population aged 18 years or younger, controlled trial, no PA control condition, PA promotion intervention and reported analyses of a PA-related outcome. Methodological quality was assessed, and data on intervention details, methods and effects on primary and secondary outcomes (PA, body composition and fitness) were extracted.ResultsThree previous reviews were reviewed, including 13 family-based and three community-based interventions. Study inclusion differed for each review, but all concluded that the evidence was limited, although the potential of family-based interventions delivered in the home and including self-monitoring was highlighted. A further six family-based and four community-based interventions were included in the updated review, with a methodological quality score ranging from 2 to 10 and five studies scoring 6 or higher. Significant positive effects on PA were observed for one community-based and three family-based studies. No distinctive characteristics of the effective interventions compared with those that were ineffective were identified.ConclusionsThe effect of family- and community-based interventions remains uncertain despite improvements in study quality. Of the little evidence of effectiveness, most comes from those targeted at families and set in the home. Further detailed research is needed to identify key approaches for increasing young people's PA levels in family and community settings.
What proportion of youth are physically active? Measurement issues, levels and recent time trends
Authors: Ekelund Ulf , Tomkinson Grant , Armstrong Neil 
Published: August 2011

AimThe aim of this review is to summarise issues surrounding the measurement of physical activity (PA) by self-report and accelerometry in youth (2–18 years old). Current levels and temporal trends in PA and sport participation and the effect of assessment method on data interpretation will be summarised.MethodsRelevant papers were extracted from a computerised literature search of MEDLINE and personal databases. Additional papers were extracted from reference lists of recently published reviews.ResultsThe criterion validity (direct comparison with an objective method) of self-reported instruments is low to moderate, with correlation coefficients generally between 0.3 and 0.4. Self-report instruments overestimate the intensity and duration of PA and sport participation. The interpretation of PA data from accelerometry is a challenge, and specific issues include the definition of intensity thresholds and the influence of age on intensity thresholds.Recent data on self-reported PA in youth suggest that between 30% and 40% are sufficiently active. Prevalence values for sufficiently active youth measured by accelerometry range between 1% and 100%, depending on the intensity thresholds used. Sport participation is likely to contribute to higher levels of PA. The available evidence does not support the notion that PA levels and sport participation in youth have declined in recent decades.ConclusionThe number of youth meeting current PA guidelines varies by assessment method and the intensity thresholds used when PA is measured by accelerometry. The available evidence does not firmly support the notion that PA in young people has declined during the last decades. It is unlikely that any self-report method is sufficiently accurate for examining cross-cultural differences and temporal trends in young people's PA and sport participation over time. Surveillance systems therefore need to strive for an international standardisation using objective measurements of PA to complement existing self-report instruments.
The Model for Understanding Success in Quality (MUSIQ): building a theory of context in healthcare quality improvement
Authors: Kaplan Heather C , Provost Lloyd P , Froehle Craig M , Margolis Peter A 
Published: August 2011

BackgroundQuality improvement (QI) efforts have become widespread in healthcare, however there is significant variability in their success. Differences in context are thought to be responsible for some of the variability seen.ObjectiveTo develop a conceptual model that can be used by organisations and QI researchers to understand and optimise contextual factors affecting the success of a QI project.Methods10 QI experts were provided with the results of a systematic literature review and then participated in two rounds of opinion gathering to identify and define important contextual factors. The experts subsequently met in person to identify relationships among factors and to begin to build the model.ResultsThe Model for Understanding Success in Quality (MUSIQ) is organised based on the level of the healthcare system and identifies 25 contextual factors likely to influence QI success. Contextual factors within microsystems and those related to the QI team are hypothesised to directly shape QI success, whereas factors within the organisation and external environment are believed to influence success indirectly.ConclusionsThe MUSIQ framework has the potential to guide the application of QI methods in healthcare and focus research. The specificity of MUSIQ and the explicit delineation of relationships among factors allows a deeper understanding of the mechanism of action by which context influences QI success. MUSIQ also provides a foundation to support further studies to test and refine the theory and advance the field of QI science.
Comparison of a chlorhexidine and a benzoyl peroxide shampoo as sole treatment in canine superficial pyoderma
Authors: Loeffler A. , Cobb M. A. , Bond R. 
Published: August 2011

The clinical and antibacterial efficacy of two shampoos used as a sole antibacterial treatment in dogs with superficial pyoderma were investigated and compared. In a randomised, partially blinded study, a 3 per cent chlorhexidine gluconate shampoo (Chlorhex 3; Leo Animal Health) was compared against a 2.5 per cent benzoyl peroxide shampoo (Paxcutol; Virbac) in 22 dogs with superficial pyoderma. Dogs were washed two to three times weekly with a 10‐minute contact time over 21 days. Clinical scores and bacterial counts were assessed on days 1, 8 and 22 and compared within and between treatment groups; overall response was assessed at the end of the study. Twenty dogs completed the study; 15 (68.2 per cent) showed an overall clinical improvement and the clinical signs resolved in three chlorhexidine‐treated dogs. In the chlorhexidine‐treated group, scores for papules/pustules (P<0.001), investigator‐assessed pruritus (P=0.003), total bacterial counts (P=0.003) and counts for coagulase‐positive staphylococci (P=0.003) were reduced after three weeks. Scores and bacterial counts did not vary significantly in the benzoyl peroxide‐treated group.
Use of radiography to identify keel bone fractures in laying hens and assess healing in live birds
Authors: Richards G. J. , Nasr M. A. , Brown S. N. , Szamocki E. M. G. , Murrell J. , Barr F. , Wilkins L. J. 
Published: August 2011

The aim of this study was to use radiography to assess and characterise naturally occurring keel bone fractures in laying hens and monitor live birds over several weeks to examine the healing process. Twenty‐four Lohmann brown commercial laying hens with varying degrees of keel bone fracture were used in the study. Birds were radiographed regularly over six weeks and the radiographic features and changing appearance of keel bone fractures were evaluated. The radiographic characteristics of old and new fractures were categorised and indicated that 80 per cent of birds entering the study with new fractures had healed after 35 days and five birds had incurred new fractures irrespective of their original fracture status.
Review of seven cases of granulosa cell tumour of the equine ovary
Authors: Crabtree J. 
Published: August 2011

This paper reviews the equine granulosa cell tumour (GCT) and describes the clinicopathological features, treatment and outcome in seven cases of GCT in mares. Mares were presented with unilateral ovarian enlargement during the 2007 to 2010 breeding seasons. The mean (sd) age of the mares was 11.7 (5.96) years. Three mares were multiparous barren, three were nulliparous and one was primigravida. Behaviour at presentation was 57 per cent anoestrus, 28 per cent with stallion‐like behaviour and 14 per cent with persistent oestrus. All mares had unilateral ovarian enlargement. Six non‐pregnant mares had a small and inactive contralateral ovary; the pregnant mare had a single small corpus luteum on the contralateral ovary and was at three‐and‐a‐half months' gestation. Enlarged ovaries measured 7 cm to an estimated 30 cm in diameter. 28 per cent had a multicystic ultrasound appearance, 57 per cent were dense structures and 14 per cent were of mixed appearance. Mean concentrations of progesterone were <1 ng/ml, oestrone sulphate 3.06 (2.32) ng/ml and testosterone 0.58 (0.64) nmol/l in non‐pregnant mares. Inhibin was elevated in all non‐pregnant cases at 7.6 (12.45) ng/ml. The pregnant mare had concentrations of progesterone 2.5 ng/ml, oestrone sulphate 81.0 ng/ml, testosterone 1.9 nmol/l and inhibin 1.31 ng/ml. Mares demonstrating stallion‐like behaviour had a significantly higher (P<0.001) testosterone concentration (1.85 [0.07] nmol/l) than those that did not (0.34 [0.26] nmol/l). Three mares underwent unilateral ovariectomy and resumed cyclic ovarian activity within nine months of surgery.
A Phase 1 Dose Escalation, Pharmacokinetic, and Pharmacodynamic Evaluation of eIF-4E Antisense Oligonucleotide LY2275796 in Patients with Advanced Cancer
Authors: Hong David S. , Kurzrock Razelle , Oh Yun , Wheler Jennifer , Naing Aung , Brail Les , Callies Sophie , André Valérie , Kadam Sunil K. , Nasir Aejaz , Holzer Timothy R. , Meric-Bernstam Funda , Fishman Mayer , Simon George 
Published: August 2011

Abstract
Purpose: The antisense oligonucleotide LY2275796 blocks expression of cap-binding protein eukaryotic initiation factor 4E (eIF-4E), an mRNA translation regulator upregulated in tumors. This phase I study sought an appropriate LY2275796 dose in patients with advanced tumors.
Experimental Design: A 3-day loading dose, then weekly maintenance doses, were given to 1 to 3 patient cohorts, beginning with 100 mg and escalating. Plasma samples were collected to determine LY2275796 concentrations and tumor biopsies to quantify eIF-4E mRNA/protein.
Results: Thirty patients with stage 4 disease received 1 or more LY2275796 dose. A dose-limiting toxicity was observed at 1,200 mg, with 1,000 mg the maximum-tolerated dose. Across all dose levels, most patients (87%) had only grade 1 to 2 toxicities. LY2275796 pharmacokinetics supported the dosing regimen. Comparison of pre- and postdose biopsies showed eIF-4E decreased in most patients. Fifteen patients had progressive disease, and 7 patients achieved stable disease (minimum of 6 weeks) as best response, with 2 patients on therapy for more than 3 months (one with melanoma, one with cystadenocarcinoma of the head/neck).
Conclusions: LY2275796 was well tolerated up to 1,000 mg. Because tumor eIF-4E expression was decreased, but no tumor response observed, LY2275796 should be studied combined with other treatment modalities. Clin Cancer Res; 17(20); 6582–91. ©2011 AACR.
Phase I Dose-Finding Study of Pazopanib in Hepatocellular Carcinoma: Evaluation of Early Efficacy, Pharmacokinetics, and Pharmacodynamics
Authors: Yau Thomas , Chen Pei-Jer , Chan Pierre , Curtis C. Martin , Murphy Philip S. , Suttle A. Benjamin , Gauvin Jennifer , Hodge Jeffrey P. , Dar Mohammed M. , Poon Ronnie T. 
Published: August 2011

Abstract
Background: A phase I dose-escalating study of pazopanib was conducted to determine the maximum tolerated dose (MTD), pharmacokinetic/pharmacodynamic relationships, and clinical activity in patients with advanced hepatocellular carcinoma (HCC).
Experimental Design: Asian patients (N = 28) were dose escalated on pazopanib (200–800 mg) once daily (QD) on 21-day cycles, with MTD as the primary endpoint using a modified 3 + 3 design. Changes in tumor vasculature were evaluated by dynamic contrast-enhanced MRI (DCE—MRI).
Results: Two of five patients at the 800-mg dose level experienced dose-limiting toxicities [grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevations and grade 3 malaise]. The MTD in patients with HCC (Child–Pugh class A) was 600 mg QD. Diarrhea, skin hypopigmentation, and AST elevation were the most commonly reported adverse events at the MTD. Mean Cmax and area under the concentration-time curve (AUC0–6) of pazopanib and its metabolites did not increase dose proportionally across the 200 to 800 mg range. Reductions in IAUGC and Ktrans were shown at all pazopanib doses evaluated, with the greatest reductions at 600 and 800 mg. Although larger DCE-MRI parameter decreases were associated with larger C24 and Cmax values, there was no constant relationship between tumor perfusion decreases measured by DCE-MRI and plasma pazopanib pharmacokinetic parameters. Overall, 19 patients (73%) had either partial response or stable disease.
Conclusion: Pazopanib has a manageable safety profile in patients with advanced HCC, and 600 mg was chosen for further development of pazopanib in advanced HCCs. Moreover, pazopanib reduced tumor vessel leakage, as shown by DCE-MRI, indicating a direct effect on HCC vasculature that might be associated with its antitumor activity. Clin Cancer Res; 17(21); 6914–23. ©2011 AACR.
CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin
Authors: Mine Naoki , Yamamoto Sayaka , Saito Naoya , Yamazaki Satoshi , Suda Chikako , Ishigaki Machiyo , Kufe Donald W. , Von Hoff Daniel D. , Kawabe Takumi 
Published: August 2011

AbstractCBP501 is an anticancer drug currently in randomized phase II clinical trials for patients with non–small cell lung cancer and malignant pleural mesothelioma. CBP501 was originally described as a unique G2 checkpoint-directed agent that binds to 14-3-3, inhibiting the actions of Chk1, Chk2, mitogen-activated protein kinase-activated protein kinase 2, and C-Tak1. However, unlike a G2 checkpoint inhibitor, CBP501 clearly enhances the accumulation of tumor cells at G2–M phase that is induced by cisplatin or bleomycin at low doses and short exposure. By contrast, CBP501 does not similarly affect the accumulation of tumor cells at G2–M that is induced by radiation, doxorubicin, or 5-fluorouracil treatment. Our recent findings point to an additional mechanism of action for CBP501. The enhanced accumulation of tumor cells at G2–M upon combined treatment with cisplatin and CBP501 results from an increase in intracellular platinum concentrations, which leads to increased binding of platinum to DNA. The observed CBP501-enhanced platinum accumulation is negated in the presence of excess Ca2+. Some calmodulin inhibitors behave similarly to, although less potently than, CBP501. Furthermore, analysis by surface plasmon resonance reveals a direct, high-affinity molecular interaction between CBP501 and CaM (Kd = 4.62 × 10−8 mol/L) that is reversed by Ca2+, whereas the Kd for the complex between CBP501 and 14-3-3 is approximately 10-fold weaker and is Ca2+ independent. We conclude that CaM inhibition contributes to CBP501′s activity in sensitizing cancer cells to cisplatin or bleomycin. This article presents an additional mechanism of action which might explain the clinical activity of the CBP501–cisplatin combination. Mol Cancer Ther; 10(10); 1929–38. ©2011 AACR.
BRCA Mutation Status and Determinant of Outcome in Women with Recurrent Epithelial Ovarian Cancer Treated with Pegylated Liposomal Doxorubicin
Authors: Safra Tamar , Borgato Lucia , Nicoletto Maria Ornella , Rolnitzky Linda , Pelles-Avraham Sharon , Geva Ravit , Donach Martin Edward , Curtin John , Novetsky Akiva , Grenader Tal , Lai Wei-Chu V. , Gabizon Alberto , Boyd Leslie , Muggia Franco 
Published: August 2011

Abstract
Epithelial ovarian cancer (EOC) patients with BRCA mutations (BRCA +) benefit from platinum-based treatment more than noncarriers. Impaired ability to repair DNA by homologous recombination increases their chemosensitivity. We investigated whether BRCA + predicts for improved outcome following pegylated liposomal doxorubicin (PLD) for recurrence. Recurrent EOC patients receiving second- or third-line PLD from 1998 to 2009 in 4 institutions (Tel Aviv, New York, Padua, and Jerusalem) were subjected to retrospective comparisons between 40 (25.8%) patients who were BRCA +, and 115 (74.2%) deemed nonhereditary (NH). Median age was 59 years (range 31–83); 111 (72%) had a platinum-free interval more than 6 months [PLD alone (n = 65) and PLD plus platinum (n = 90)]; 104 received PLD in second-line and 51 in third-line. BRCA + versus NH comparisons: median time to treatment failure (TTF) 15.8 months [95% confidence interval (CI): 11.4–21.6] versus 8.1 months (95% CI: 6.1–10.3; P = 0.009); overall survival (OS) 56.8 months (95% CI: 32.5–indeterminate) versus 22.6 months (95% CI: 17.0–34.1; P = 0.002). In multivariate Cox models BRCA status was significantly associated with TTF (HR = 1.66; 95% CI: 1.08–2.55; P = 0.02) and OS (adjusted HR 2.07; 95% CI: 1.18–3.60; P = 0.01). Adjusted HR relating platinum sensitivity to OS was 1.58 (95% CI: 0.93–2.68; P = 0.09); no significant association found with age at diagnosis, line of PLD or combinations, or institution. In this retrospective analysis, recurrent EOC BRCA mutation carriers treated with PLD had an improved outcome, and this result seemed to be independent of platinum sensitivity. Tumors arising in a background of defective BRCA function are more sensitive than other EOCs to DNA-damaging agents such as PLD, even after acquiring platinum resistance. Mol Cancer Ther; 10(10); 2000–7. ©2011 AACR.
Dietary Folate Deficiency Blocks Prostate Cancer Progression in the TRAMP Model
Authors: Bistulfi Gaia , Foster Barbara A. , Karasik Ellen , Gillard Bryan , Miecznikowski Jeff , Dhiman Vineet K. , Smiraglia Dominic J. 
Published: August 2011

Abstract
Dietary folate is essential in all tissues to maintain several metabolite pools and cellular proliferation. Prostate cells, due to specific metabolic characteristics, have increased folate demand to support proliferation and prevent genetic and epigenetic damage. Although several studies have found that dietary folate interventions can affect colon cancer biology in rodent models, its impact on prostate is unknown. The purpose of this study was to determine whether dietary folate manipulation, possibly being of primary importance for prostate epithelial cell metabolism, could significantly affect prostate cancer progression. Strikingly, mild dietary folate depletion arrested prostate cancer progression in 25 of 26 transgenic adenoma of the mouse prostate (TRAMP) mice, in which tumorigenesis is prostate-specific and characteristically aggressive. The significant effect on prostate cancer growth was characterized by size, grade, proliferation, and apoptosis analyses. Folate supplementation had a mild, nonsignificant, beneficial effect on grade. In addition, characterization of folate pools (correlated with serum), metabolite pools (polyamines and nucleotides), genetic and epigenetic damage, and expression of key biosynthetic enzymes in prostate tissue revealed interesting correlations with tumor progression. These findings indicate that prostate cancer is highly sensitive to folate manipulation and suggest that antifolates, paired with current therapeutic strategies, might significantly improve treatment of prostate cancer, the most commonly diagnosed cancer in American men. Cancer Prev Res; 4(11); 1825–34. ©2011 AACR.
Monitoring low dose recombinant factor VIIa therapy in patients with severe factor XI deficiency undergoing surgery
Authors: Riddell Anne , Abdul-Kadir Rezan , Pollard Debra , Tuddenham Edward , Gomez Keith 
Published: August 2011

SummaryAlthough factor XI (FXI) concentrate is an effective replacement therapy in severe FXI deficiency without inhibitors, some patients are unwilling to receive it because it is plasma-derived. We report on the use and monitoring of low dose, recombinant factor VIIa (rFVIIa, NovoSeven®), to cover surgery (caesarean section, cholecystectomy and abdominoplasty) in four female patients (FXI:C 2–4 IU/dl, aged 32–51 years) who wished to avoid exposure to plasma. None of our patients had inhibitors to FXI. Our aim was to find the optimal dose of rFVIIa by in vitro spiking of patient samples and to correlate this with the response to rFVIIa in vivo. Prior to surgery, venous blood was collected into sodium citrate with corn trypsin inhibitor and spiked with 0.25–1.0 μg/ml rFVIIa in vitro, equivalent to a 15–70 μg/kg dose of rFVIIa in vivo. Analysis using thromboelastometry and thrombin generation assays, triggered with tissue factor, showed that the thrombin generation assay was insufficiently sensitive to the haemostatic defect in these patients. A concentration of 0.5 μg/ml was as effective as 1.0 μg/ml FVIIa in normalising thromboelastometry in vitro in all four patients. Therefore, patients received 15–30 μg/kg rFVIIa at 2–4 hourly intervals with tranexamic acid 1g every six hours. Post treatment samples were taken at 10–240 minutes and showed initial normalisation of thromboelastometry with gradual return to baseline after 2–4 hours. In conclusion, low-dose rFVIIa therapy was successfully used in four patients with severe FXI deficiency undergoing surgery to prevent bleeding and can be monitored using thromboelastometry.