bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target‐specific optimization of four‐dimensional cone beam computed tomography
Authors: Ahmad Moiz , Pan Tinsu 
Published: August 2012

Purpose:Under‐sampling artifacts are a major problem in four‐dimensional cone‐beam computed tomography (4D‐CBCT) and may compromise evaluation of target motion. Several studies have addressed scan parameter selection for minimizing under‐sampling artifacts; however, the role of the target characteristics in scan parameter selection has not been investigated. In this work, the authors evaluated 4D‐CBCT performance by assessing the accuracy of target motion measurements for various target sizes and motions. The results may serve as patient‐specific guidelines for scan parameters selection in 4D‐CBCT.Methods:The authors acquired 4D‐CBCT scans of a moving phantom consisting of six water‐filled sphere targets of sizes 10–37 mm, using various scan times ranging from 30 s to 3 min., setting the motion to 3‐s and 6‐s periods. The authors used automatic image registration to extract the target motion trajectories and evaluated these measurements for various target sizes and motions over various combinations of scan parameters including scan time, detector configuration, number of respiration phases, and reconstruction filters.Results:The most important object parameter to 4D‐CBCT performance was the period of motion. Measurements for the 6‐s motion were always systematically less accurate than measurements for the 3‐s motion for 34 of 36 objects of various sizes and periods of motion. The 6‐s motion required a greater scan time than the 3‐s motion for equivalent measurement accuracy. The second most influential parameter was the target size. For the 3‐s period of motion, objects larger than 13 mm were tracked with sub‐millimeter accuracy with a 1‐min scan time. For the 6‐s period of motion, objects larger than 22‐mm were tracked with sub‐millimeter accuracy with a 1.5‐min scan time. For all sizes and motions, temporal blurring was observed when the number of phases was fewer than 8. Offset detector configuration provided the same performance as centered detector except for small targets (20 mm.) at short scan times (≤1 min). Finally, reconstruction filtering and number of respiratory phases did not affect performance.Conclusions:Scan time should be set according to target size and motion. The authors have provided figures that provide the minimum scan time needed to achieve the particular motion measurement accuracy for a particular size and motion period.
Effects of Olympic-style taekwondo kicks on an instrumented head-form and resultant injury measures
Authors: Fife Gabriel P , O'Sullivan David M , Pieter Willy , Cook David P , Kaminski Thomas W 
Published: August 2012

ObjectiveThe objective of this study was to assess the effect of taekwondo kicks and peak foot velocity (FVEL) on resultant head linear acceleration (RLA), head injury criterion (HIC15) and head velocity (HVEL).MethodsEach subject (n=12) randomly performed five repetitions of the turning kick (TK), clench axe kick (CA), front leg axe kick, jump back kick (JB) and jump spinning hook kick (JH) at the average standing head height for competitors in their weight division. A Hybrid II Crash Test Dummy head was fitted with a protective taekwondo helmet and instrumented with a triaxial accelerometer and fixed to a height-adjustable frame. Resultant head linear acceleration, HVEL, FVEL data were captured and processed using Qualysis Track Manager.ResultsThe TK (130.11±51.67 g) produced a higher RLA than the CA (54.95±20.08 g, p<0.001, d=1.84) and a higher HIC15 than the JH (672.74±540.89 vs 300.19±144.35, p<0.001, ES=0.97). There was no difference in HVEL of the TK (4.73±1.67 m/s) and that of the JB (4.43±0.78 m/s; p=0.977, ES<0.01).ConclusionsThe TK is of concern because it is the most common technique and cause of concussion in taekwondo. Future studies should aim to understand rotational accelerations of the head.
Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial
Authors: Steunebrink Mirjam , Zwerver Johannes , Brandsema Ruben , Groenenboom Petra , Akker-Scheek Inge van den , Weir Adam 
Published: August 2012

ObjectivesTo assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone.MethodsRandomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised estimated equation was used to analyse the treatment, time and treatment×time effect. Analyses were performed following the intention-to-treat principle.ResultsVISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.80). Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.38). Patient satisfaction showed no difference between GTN and placebo groups (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash.ConclusionIt seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy.
The prevalence and clinicopathological profile of IgM nephropathy in children with steroid-resistant nephrotic syndrome at a single centre in Pakistan
Authors: Shakeel Shaheera , Mubarak Muhammed , Kazi Javed I , Lanewala Ali 
Published: August 2012

BackgroundThere is little information on the clinicopathological characteristics of IgM nephropathy (IgMN) in paediatric steroid-resistant nephrotic syndrome (SRNS) and its response to calcineurin inhibitors (CNI).Material and MethodsThis study was conducted at Sindh Institute of Urology and Transplantation, from January 2009 to August 2011. All SRNS children who received renal biopsies were included. Relevant data were compared among minimal change disease (MCD) and IgMN. The response to CNI was analysed in detail in IgMN by groups (group 1: complete or partial remission; group 2: no response).ResultsThe frequency of IgMN in 147 children with SRNS was 13.6%. Compared with MCD, there was a male preponderance in IgMN. Blood urea and serum creatinine both at presentation and at last follow-up were significantly higher in IgMN. Regarding subgroups of IgMN, systolic blood pressure (SBP), blood urea and serum creatinine were significantly higher in group 2 at presentation, while at last follow-up, SBP, diastolic blood pressure and proteinuria were higher in group 2. The prevalence and degree of mesangial proliferation, global glomerulosclerosis, interstitial fibrosis and tubular atrophy were significantly higher in group 2.ConclusionsIgMN is a common cause of paediatric SRNS and is significantly different from MCD. There is also a significant difference in clinical and laboratory parameters among responders and non-responders to CNI in IgMN.
Higher-order bud production increases tillering capacity in the perennial caespitose grass Scribner’s Panicum (Dichanthelium oligosanthes)
Authors: Ott Jacqueline P. , Hartnett David C. 
Published: August 2012

The persistence and dynamics of perennial grass populations strongly depend on tiller recruitment from the bud bank. Because of the structural organization of grasses as populations of phytomers, bud production and tillering are constrained by morphology. An infrequent trait observed in only a few caespitose grasses is the branching of buds to produce higher-order buds prior to tiller development. We studied bud bank dynamics in Dichanthelium oligosanthes (Schult.) Gould a C3 perennial caespitose grass widely distributed in the eastern Great Plains. A hierarchy of bud development occurred in D. oligosanthes, with primary buds branching to produce secondary, tertiary, and quaternary buds. This higher-order bud production increased the overwintering propagule supply for spring recruitment by 4.5 times, and more than half of successful tiller recruits originated as higher-order buds. The temporal patterns of higher-order bud production and development suggest that growing season length may be an important factor determining the extent of higher-order bud production and subsequent year tiller natality in D. oligosanthes. Higher-order bud production likely has important consequences for the population dynamics of grasses. It may increase bud bank densities and tillering capacity, buffer population dynamics, and increase intraclonal tiller densities and resource consolidation in caespitose grasses.
Leaf epidermal characters of Brazilian species of Solanum section Torva as taxonomic evidence
Authors: Nurit-Silva Kiriaki , Costa-Silva Rafael , Basílio Ionaldo J.L.D. , Agra Maria de Fátima 
Published: August 2012

To evaluate their taxonomic significance, the yet unknown epidermal characters of the leaves of 10 species of Solanum section Torva Nees (Solanaceae) from Brazil were determined using light and scanning electron microscopy. Our results indicated that the leaf epidermis showed epidermal cells of straight to wavy outlines. The curved pattern of anticlinal cell walls was predominant on the adaxial surface, and the wave pattern was predominant on the abaxial surface. Leaves are amphistomatic in six species ( Solanum acutilobum Dunal, Solanum bonariense L., Solanum guaraniticum A. St.-Hil., Solanum metrobotryon Dunal, Solanum scuticum M. Nee, and Solanum torvum Sw.) and hypostomatic in four species ( Solanum adspersum Witasek, Solanum paniculatum L., Solanum subumbellatum Vell., and Solanum variabile Mart.). Four different types of stomata (anisocytic, anomocytic, paracytic, and diacytic) were recognized, with the anisocytic type predominant on adaxial and abaxial surfaces. The combination of some micro-morphological characters such as density, distribution and type of stellate trichomes, the anticlinal walls of epidermal cells, and also the type and distribution of stomata proved to be the most useful and distinctive characters for the separation of species. This set of characters also may help as additional support in quality control of species having medicinal importance.
Geomechanical mechanisms involving faults and fractures for observed correlations between fluctuations in flowrates at wells in North Sea oilfields
Authors: Heffer Kes J. 
Published: August 2012

Abstract
The hydraulic conductivities of faults and fractures in reservoirs can be influenced by geomechanical perturbations due to production operations. It is anticipated that such dynamic permeabilities will be manifest as changes in flowrates at production and injection wells. Statistical correlations in flowrate fluctuations between wells from fields in the North Sea appear to bear out this expectation; they are characterized by high correlations over very large separation distances between wells, and appear to be stress-related and fault-related. This paper discusses possible geomechanical mechanisms that might explain orientational characteristics of correlations relative to stress state: (1) creation of new Andersonian, bimodal faults; (2) shear slip on pre-existing structural features according to slip tendencies; (3) polymodal faulting more consistent with three-dimensional strain; and (4) dilatation or compaction of aligned compliant (micro-)fractures at near-critical densities arranged in en echelon patterns. Mechanism 4 is currently preferred in that it is consistent with: (a) established theory of the nucleation of shear failure; (b) interpretations of widespread microfractures in the lithosphere from observations of shear-wave splitting; (c) (as shown in this paper) the observed frequencies of directionalities in oilfield flooding schemes, an independent empirical feature of production data.
Targeting the EWSR1-FLI1 Oncogene-Induced Protein Kinase PKC-β Abolishes Ewing Sarcoma Growth
Authors: Surdez Didier , Benetkiewicz Magdalena , Perrin Virginie , Han Zhi-Yan , Pierron Gaëlle , Ballet Stelly , Lamoureux François , Rédini Françoise , Decouvelaere Anne-Valérie , Daudigeos-Dubus Estelle , Geoerger Birgit , de Pinieux Gonzague , Delattre Olivier , Tirode Franck 
Published: August 2012

Abstract
Ewing sarcoma is a rare but aggressive disease most common in young adults. This cancer is driven by a unique chimeric fusion oncogene but targeted strategies have been elusive. Here we report the identification of the protein kinase PKC-ß (PRKCB) as a disease-specific druggable target for treatment of Ewing sarcoma. We found that transcriptional activation of PRKCB was directly regulated by the chimeric fusion oncogene EWSR1-FLI1 that drives this cancer. PRKCB phosphorylated histone H3T6 to permit global maintenance of H3K4 trimethylation at a variety of gene promoters. PRKCB loss induced apoptosis in vitro and prevented tumor growth in vivo. Gene expression profiling revealed a strong overlap between genes modulated by EWSR1-FLI1 and PRKCB in regulating crucial signaling pathways. Taken together, our findings offer a preclinical proof-of-concept for PRKCB as a promising therapeutic target in Ewing sarcoma. Cancer Res; 72(17); 4494–503. ©2012 AACR.
Prognostic Significance of Promoter DNA Methylation in Patients with Childhood Neuroblastoma
Authors: Lau Diana T. , Hesson Luke B. , Norris Murray D. , Marshall Glenn M. , Haber Michelle , Ashton Lesley J. 
Published: August 2012

AbstractPurpose: To characterize the clinical significance of promoter methylation in a cohort of primary neuroblastoma tumors and investigate the association between DNA methylation and clinical outcome.Experimental Design: A customized Illumina GoldenGate methylation assay was used to assess methylation status of 96 CpG sites within 48 candidate genes in primary neuroblastoma tumors obtained from 131 children diagnosed in Australia. Genes were selected on the basis of previous reports of altered DNA methylation in embryonal cancers. Levels of DNA methylation were validated in a subset of 48 patient samples using combined bisulfite restriction analysis (CoBRA) and bisulfite sequencing. A Cox proportional hazards model was used to investigate the association between promoter hypermethylation and the risk of relapse/death within 5 years of diagnosis, while adjusting for known prognostic factors including MYCN amplification, age, and stage at diagnosis.Results: Levels of promoter methylation of DNAJC15, neurotrophic tyrosine kinase receptor 1 or TrkA (NTRK1), and tumor necrosis factor receptor superfamily, member 10D (TNFRSF10D), were higher in older patients at diagnosis (P &lt; 0.01), whereas higher levels of methylation of DNAJC15, NTRK1, and PYCARD were observed in patients with MYCN amplification (P &lt; 0.001). In multivariate analysis, hypermethylation of folate hydrolase (FOLH1), myogenic differentiation-1 (MYOD1), and thrombospondin-1 (THBS1) remained significant independent predictors of poorer clinical outcome after adjusting for known prognostic factors (P ≤ 0.017). Moreover, more than 30% of patients displayed hypermethylation in 2 genes or more and were at least 2 times more likely to relapse or die (HR = 2.72, 95% confidence interval = 1.55–4.78, P = 0.001), independent of MYCN status, age, and stage at diagnosis.Conclusions: Our findings highlight the potential use of methylation profiling to identify additional prognostic markers and detect new therapeutic targets for selected patient subsets. Clin Cancer Res; 18(20); 5690–700. ©2012 AACR.
CCT244747 Is a Novel Potent and Selective CHK1 Inhibitor with Oral Efficacy Alone and in Combination with Genotoxic Anticancer Drugs
Authors: Walton Mike I. , Eve Paul D. , Hayes Angela , Valenti Melanie R. , De Haven Brandon Alexis K. , Box Gary , Hallsworth Albert , Smith Elizabeth L. , Boxall Kathy J. , Lainchbury Michael , Matthews Thomas P. , Jamin Yann , Robinson Simon P. , Aherne G. Wynne , Reader John C. , Chesler Louis , Raynaud Florence I. , Eccles Suzanne A. , Collins Ian , Garrett Michelle D. 
Published: August 2012

Abstract
Purpose: Many tumors exhibit defective cell-cycle checkpoint control and increased replicative stress. CHK1 is critically involved in the DNA damage response and maintenance of replication fork stability. We have therefore discovered a novel potent, highly selective, orally active ATP-competitive CHK1 inhibitor, CCT244747, and present its preclinical pharmacology and therapeutic activity.
Experimental Design: Cellular CHK1 activity was assessed using an ELISA assay, and cytotoxicity a SRB assay. Biomarker modulation was measured using immunoblotting, and cell-cycle effects by flow cytometry analysis. Single-agent oral CCT244747 antitumor activity was evaluated in a MYCN-driven transgenic mouse model of neuroblastoma by MRI and in genotoxic combinations in human tumor xenografts by growth delay.
Results: CCT244747 inhibited cellular CHK1 activity (IC50 29–170 nmol/L), significantly enhanced the cytotoxicity of several anticancer drugs, and abrogated drug-induced S and G2 arrest in multiple tumor cell lines. Biomarkers of CHK1 (pS296 CHK1) activity and cell-cycle inactivity (pY15 CDK1) were induced by genotoxics and inhibited by CCT244747 both in vitro and in vivo, producing enhanced DNA damage and apoptosis. Active tumor concentrations of CCT244747 were obtained following oral administration. The antitumor activity of both gemcitabine and irinotecan were significantly enhanced by CCT244747 in several human tumor xenografts, giving concomitant biomarker modulation indicative of CHK1 inhibition. CCT244747 also showed marked antitumor activity as a single agent in a MYCN-driven neuroblastoma.
Conclusion: CCT244747 represents the first structural disclosure of a highly selective, orally active CHK1 inhibitor and warrants further evaluation alone or combined with genotoxic anticancer therapies. Clin Cancer Res; 18(20); 5650–61. ©2012 AACR.
Perillyl Alcohol for the Treatment of Temozolomide-Resistant Gliomas
Authors: Cho Hee-Yeon , Wang Weijun , Jhaveri Niyati , Torres Shering , Tseng Joshua , Leong Michelle N. , Lee David Jungpa , Goldkorn Amir , Xu Tong , Petasis Nicos A. , Louie Stan G. , Schönthal Axel H. , Hofman Florence M. , Chen Thomas C. 
Published: August 2012

AbstractPerillyl alcohol (POH) is a monoterpene that has been used orally for the treatment of systemic cancer. However, when used orally significant gastrointestinal side effects and lack of overall efficacy were documented. Recently, in a phase II trial in Brazil for the treatment of temozolomide (TMZ)-resistant malignant gliomas, POH was well tolerated when administered intranasally. The present study explores the effects and mechanisms of POH on TMZ-sensitive and TMZ-resistant glioma cells. In vitro studies showed that POH was cytotoxic to TMZ-resistant as well as TMZ-sensitive glioma cells, and this effect was independent of O6-methylguanine-DNA methyltransferase expression. POH induced cytotoxicity, in part, through the endoplasmic reticulum (ER) stress pathway as shown by the increased expression of glucose-regulated protein-78 (GRP78), activating transcription factor 3, and C/EBP-homologous protein. In addition, POH impeded survival pathways, such as mTOR and Ras. As well, POH reduced the invasive capacity of sensitive and resistant glioma cells. POH alone and/or in combination with other ER stress–inducing cytotoxic drugs (i.e., 2, 5-dimethyl-celecoxib, nelfinavir) further induced apoptosis in TMZ-sensitive and TMZ-resistant glioma cells. To show whether intranasal delivery of POH was effective for the treatment of TMZ-resistant gliomas, animals bearing intracranial tumors were given POH intranasally. Animals treated through intranasal administration of POH exhibited a decrease in tumor growth and an increase in survival. Our data show that POH is an effective anti-glioma cytotoxic agent for TMZ-resistant gliomas when administered intranasally. Mol Cancer Ther; 11(11); 2462–72. ©2012 AACR.
Genome-wide DNA Methylation Events in TMPRSS2–ERG Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with miR-26a Hypermethylation
Authors: Börno Stefan T. , Fischer Axel , Kerick Martin , Fälth Maria , Laible Mark , Brase Jan C. , Kuner Ruprecht , Dahl Andreas , Grimm Christina , Sayanjali Behnam , Isau Melanie , Röhr Christina , Wunderlich Andrea , Timmermann Bernd , Claus Rainer , Plass Christoph , Graefen Markus , Simon Ronald , Demichelis Francesca , Rubin Mark A. , Sauter Guido , Schlomm Thorsten , Sültmann Holger , Lehrach Hans , Schweiger Michal R. 
Published: August 2012

Abstract
Prostate cancer is the second most common cancer among men worldwide. Alterations in the DNA methylation pattern can be one of the leading causes for prostate cancer formation. This study is the first high-throughput sequencing study investigating genome-wide DNA methylation patterns in a large cohort of 51 tumor and 53 benign prostate samples using methylated DNA immunoprecipitation sequencing. Comparative analyses identified more than 147,000 cancer-associated epigenetic alterations. In addition, global methylation patterns show significant differences based on the TMPRSS2–ERG rearrangement status. We propose the hypermethylation of miR-26a as an alternative pathway of ERG rearrangement-independent EZH2 activation. The observed increase in differential methylation events in fusion–negative tumors can explain the tumorigenic process in the absence of genomic rearrangements.
Significance: In contrast to TMPRSS2–ERG-rearranged tumors, the pathomechanism for gene fusion–negative tumors is completely unclear. Using a sequencing-based approach, our work uncovers significant global epigenetic alterations in TMPRSS2–ERG gene fusion–negative tumors and provides a mechanistic explanation for the tumor formation process. Cancer Discov; 2(11); 1024–35. ©2012 AACR.
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