bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonal change in bone, muscle and fat in professional rugby league players and its relationship to injury: a cohort study
Authors: Georgeson Erin C , Weeks Benjamin K , McLellan Chris , Beck Belinda R 
Published: November 2012

ObjectivesTo examine the anthropometric characteristics of an Australian National Rugby League team and identify the relationship to type and incidence of injuries sustained during a professional season. It was hypothesised that body composition would not change discernibly across a season and that injury would be negatively related to preseason bone and muscle mass.DesignA repeated measure, prospective, observational, cohort study.SettingGriffith University, Gold Coast, Australia.Participants37 professional male Australian National Rugby League players, 24.3 (3.8) years of age were recruited for preseason 1 testing, of whom 25 were retested preseason 2.Primary and secondary outcome measuresPrimary outcome measures included biometrics; body composition (bone, muscle and fat mass; dual-energy x-ray absorptiometry; XR800, Norland Medical Systems, Inc); bone geometry and strength (peripheral quantitative CT; XCT 3000, Stratec); calcaneal broadband ultrasound attenuation (BUA; QUS-2, Quidel); diet and physical activity history. Secondary outcome measures included player injuries across a single playing season.ResultsLean mass decreased progressively throughout the season (pre=81.45(7.76) kg; post=79.89(6.72) kg; p≤0.05), while whole body (WB) bone mineral density (BMD) increased until mid-season (pre=1.235(0.087) g/cm2; mid=1.296(0.093) g/cm2; p≤0.001) then decreased thereafter (post=1.256(0.100); p≤0.001). Start-of-season WB BMD, fat and lean mass, weight and tibial mass measured at the 38% site predicted bone injury incidence, but no other relationship was observed between body composition and injury.ConclusionsSignificant anthropometric changes were observed in players across a professional rugby league season, including an overall loss of muscle and an initial increase, followed by a decrease in bone mass. Strong relationships between anthropometry and incidence of injury were not observed. Long-term tracking of large rugby league cohorts is indicated to obtain more injury data in order to examine anthropometric relationships with greater statistical power.
Clinical application of UF-1000i in combination with AX-4280 for the screening test ability of urinary formed elements
Authors: Zhao Feng , Jin Yi , Chen Xiaoyan , Xie Xinyou 
Published: November 2012

AimsTo evaluate the screening test ability of UF-1000i combination with AX-4280 for major pathological urinary formed elements and to establish screening rules suitable for our laboratory.MethodsA total of 2220 cases of urine samples were collected from out-patients and inpatients. The sample tests were finished within 4 h after collection. The results were verified and corroborated with microscopic tests.ResultsIn ‘both-negative’ group, the negative predictive values for red blood cell, white blood cell and cast were 99.12%, 99.56% and 100%, respectively, and the false negative rates were 0.87%, 0.44% and 0%, respectively. In ‘both-positive’ group, the positive predictive values for red blood cell, white blood cell and cast were 69.18%, 74.41% and 33.33%, respectively, and the false positive rates were 30.82%, 25.59% and 66.67%, respectively. In ‘U positive/A negative’ group, the positive predictive values for red blood cell, white blood cell and cast were 32.47%, 23.67% and 8.57%, respectively, and the false positive rates were 67.53%, 76.36% and 91.43%, respectively. In ‘U negative/A positive’ group, the positive predictive values for red blood cell, white blood cell and cast were 8.18%, 19.50% and 4.67%, respectively, and the false positive rates were 91.82%, 50.50% and 95.24%, respectively.ConclusionsWhen the results of the red blood cell, white blood cell and cast tested by UF-1000i were all negative, and the results of the red blood cell, white blood cell and protein tested by AX-4280 were negative, an automatic report stating ‘normal microscopic appearance’ was generated, and then the microscopic test rate was reduced by 37.6%. However, if any automated parameter measurement was out of the reference range, corroboration by manual microscopy was advisable.
HIV testing for acute medical admissions: evaluation of a pilot study in Leicester, England
Authors: Palfreeman Adrian , Nyatsanza Farai , Farn Helen , McKinnon Graham , Schober Paul , McNally Paul 
Published: November 2012

ObjectivesThe 2008 UK National Guidelines for HIV testing recommended HIV testing should be offered to all general medical admissions aged 16–60 years in high prevalence areas, and that this should be evaluated to ensure this was effective in diagnosing previously undiagnosed HIV.MethodsHIV testing was introduced as a routine test for all patients admitted to the acute medical admissions unit, comparisons were made between the testing rates before, during and after this intervention.ResultsThe pilot was initiated in August 2009. Prior to the pilot the unit was carrying out 15 tests per month. However, when the pilot was introduced 82 tests were being carried out per month with a total of 10 new diagnoses since the start of the pilot. The proportion of patients tested versus those eligible for testing remained low varying between 6% and 22% month by month. 10 patients we found to be HIV positive with a prevalence of approximately 1%, 10 fold higher than the cut off for cost effectiveness used in the guidelines.ConclusionsOverall the pilot showed that HIV testing could be delivered without the use of extra resources and is acceptable to patients.
Patterns and mechanisms of fluvial sediment flux and accumulation in two subarctic fjords: Nachvak and Saglek Fjords, Nunatsiavut, Canada
Authors: Bentley Samuel J. , Kahlmeyer Elisabeth 
Published: November 2012

Recent marine sedimentary deposits and river discharge in two subarctic fjords in Nunatsiavut (Northern Labrador, Canada) have been studied to elucidate patterns and mechanisms of fluvial sediment transfer and accumulation in the fjords, to further our understanding of the longer-term sedimentary record. Multibeam and sub-bottom acoustic data and sediment cores were collected in Nachvak and Saglek fjords, within Canada’s Torngat Mountains National Park, as part of the most extensive study of the park’s marine resources to date. Cores were subsampled for X-radiography, grain size, and 210Pb/137Cs geochronology. Muddy basin sediments within each fjord are bioturbated, indicating circulation of oxygenated bottom water. Depositional fluxes and inventories of 210Pb indicate efficient marine scavenging of 210Pb by fine suspended sediments. In Nachvak Fjord, with small rivers and steep, presently glaciated catchments, postglacial and recent sediment accumulation rates are similar, implying relatively constant sedimentation over time. In Saglek Fjord, fed by larger rivers with more extensive catchments that lack glaciers, recent sediment accumulation is more rapid than that averaged over postglacial time. Present mass accumulation rates for the Nachvak Fjord basin are on average 39 000 t·year–1 for the entire basin, and for Saglek 43 000 t·year–1 for the entire basin, with sediment-gravity flows being one likely mechanism for sediment delivery to deep basins. Results collectively suggest that both marine basins are excellent natural sediment traps. Comparison of accumulation rates from 137Cs and 210Pb suggest that sediment fluxes to Nachvak Fjord may have decreased slightly over the past ∼130 years.
Human interference on soft cliff retreat: examples from Christchurch Bay, UK
Authors: Brown S. , Barton M. E. , Nicholls R. J. 
Published: November 2012

Human interference in soft coastal cliff retreat causes problems worldwide. Building defences alters the sediment budget, frequently causing a sediment deficit down-drift resulting in increased retreat rates. Subsequently, undefended shorelines become set back from protection works, often causing excessive and unexpected land and infrastructure loss, prompting defence extensions. Down-drift of groynes, this is known as the terminal groyne effect. From case studies, this paper determines the effects of human interference on soft cliffs, and investigates excessive land loss and likely future coastal response.
Using 10.5 km of soft cliffs in Christchurch Bay, UK as a study region, a historical shoreline analysis from the mid 19th century to the present day was undertaken. Detailed analysis was conducted at three case study sites to determine whether retreat rates had increased down-drift after the construction of protection works. After defence construction, increased retreat occurred at all three sites, albeit for only a few hundred metres down-drift, as propagation was limited owing to a headland or large sediment volumes. Set-backs can lead to artificial headland formation, making the coast more challenging and costly to defend. Shoreline management plans advocating protection or realignment should take account of natural features to enhance engineering design and reduce excess land loss.
Genomic Profiling of Isolated Circulating Tumor Cells from Metastatic Breast Cancer Patients
Authors: Magbanua Mark Jesus M. , Sosa Eduardo V. , Roy Ritu , Eisenbud Lauren E. , Scott Janet H. , Olshen Adam , Pinkel Dan , Rugo Hope S. , Park John W. 
Published: November 2012

Abstract
Molecular characterization of circulating tumor cells (CTC) from blood is technically challenging because cells are rare and difficult to isolate. We developed a novel approach to isolate CTCs from blood via immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE–FACS). Isolated CTCs were subjected to genome-wide copy number analysis via array comparative genomic hybridization (aCGH). In clinical studies, CTCs were isolated from 181 patients with metastatic breast cancer, 102 of which were successfully profiled, including matched archival primary tumor from five patients. CTCs revealed a wide range of copy number alterations including those previously reported in breast cancer. Comparison with two published aCGH datasets of primary breast tumors revealed similar frequencies of recurrent genomic copy number aberrations. In addition, serial testing of CTCs confirmed reproducibility and indicated genomic change over time. Comparison of CTCs with matched archival primary tumors confirmed shared lineage as well as some divergence. We showed that it is feasible to isolate CTCs away from hematopoietic cells with high purity through IE–FACS and profile them via aCGH analysis. Our approach may be used to explore genomic events involved in cancer progression and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively noninvasive manner. Cancer Res; 73(1); 30–40. ©2012 AACR.
Overexpression of the Mitochondrial Folate and Glycine–Serine Pathway: A New Determinant of Methotrexate Selectivity in Tumors
Authors: Vazquez Alexei , Tedeschi Philip M. , Bertino Joseph R. 
Published: November 2012

Abstract
Previous studies have documented the roles of transport via the reduced folate carrier, retention via polyglutamylation, and increased levels of the target enzyme, dihydrofolate reductase in sensitivity to methotrexate. Recent studies have shown that the mitochondrial enzymes in the cellular metabolism of serine, folate, and glycine are overexpressed in a subset of human cancers and that their expression is required for tumor maintenance. In this Perspective article, we propose that the expression of mitochondrial enzymes in the metabolism of serine and glycine, in addition to those involved in folate metabolism, are determinants of the response to methotrexate. Furthermore, we show that myc activation in tumors is associated with upregulation of these enzymes. We propose that patients whose tumors show this phenotype will be sensitive to folate antagonists targeting thymidylate or purine biosynthesis. Cancer Res; 73(2); 478–82. ©2012 AACR.
Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis
Authors: Nahon Pierre , Amathieu Roland , Triba Mohamed N. , Bouchemal Nadia , Nault Jean-Charles , Ziol Marianne , Seror Olivier , Dhonneur Gilles , Trinchet Jean-Claude , Beaugrand Michel , Le Moyec Laurence 
Published: November 2012

Abstract
Purpose: Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC).
Experimental Design: The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components.
Results: The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up.
Conclusions: Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis. Clin Cancer Res; 18(24); 6714–22. ©2012 AACR.
Expression Profiling of Archival Tumors for Long-term Health Studies
Authors: Waldron Levi , Ogino Shuji , Hoshida Yujin , Shima Kaori , McCart Reed Amy E. , Simpson Peter T. , Baba Yoshifumi , Nosho Katsuhiko , Segata Nicola , Vargas Ana Cristina , Cummings Margaret C. , Lakhani Sunil R. , Kirkner Gregory J. , Giovannucci Edward , Quackenbush John , Golub Todd R. , Fuchs Charles S. , Parmigiani Giovanni , Huttenhower Curtis 
Published: November 2012

Abstract
Purpose: More than 20 million archival tissue samples are stored annually in the United States as formalin-fixed, paraffin-embedded (FFPE) blocks, but RNA degradation during fixation and storage has prevented their use for transcriptional profiling. New and highly sensitive assays for whole-transcriptome microarray analysis of FFPE tissues are now available, but resulting data include noise and variability for which previous expression array methods are inadequate.
Experimental Design: We present the two largest whole-genome expression studies from FFPE tissues to date, comprising 1,003 colorectal cancer (CRC) and 168 breast cancer samples, combined with a meta-analysis of 14 new and published FFPE microarray datasets. We develop and validate quality control (QC) methods through technical replication, independent samples, comparison to results from fresh-frozen tissue, and recovery of expected associations between gene expression and protein abundance.
Results: Archival tissues from large, multicenter studies showed a much wider range of transcriptional data quality relative to smaller or frozen tissue studies and required stringent QC for subsequent analysis. We developed novel methods for such QC of archival tissue expression profiles based on sample dynamic range and per-study median profile. This enabled validated identification of gene signatures of microsatellite instability and additional features of CRC, and improved recovery of associations between gene expression and protein abundance of MLH1, FASN, CDX2, MGMT, and SIRT1 in CRC tumors.
Conclusions: These methods for large-scale QC of FFPE expression profiles enable study of the cancer transcriptome in relation to extensive clinicopathological information, tumor molecular biomarkers, and long-term lifestyle and outcome data. Clin Cancer Res; 18(22); 6136–46. ©2012 AACR.
Targeted MET Inhibition in Castration-Resistant Prostate Cancer: A Randomized Phase II Study and Biomarker Analysis with Rilotumumab plus Mitoxantrone and Prednisone
Authors: Ryan Charles J. , Rosenthal Mark , Ng Siobhan , Alumkal Joshi , Picus Joel , Gravis Gwenaëlle , Fizazi Karim , Forget Frédéric , Machiels Jean-Pascal , Srinivas Sandy , Zhu Min , Tang Rui , Oliner Kelly S. , Jiang Yizhou , Loh Elwyn , Dubey Sarita , Gerritsen Winald R. 
Published: November 2012

AbstractPurpose: To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients with castration-resistant prostate cancer (CRPC).Experimental Design: This double-blinded phase II study randomized (1:1:1) patients with progressive, taxane-refractory CRPC to receive MP (12 mg/m2 i.v. day 1, 5 mg twice a day orally days 1–21, respectively) plus 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab, or placebo (i.v. day 1) every 3 weeks. The primary endpoint was overall survival (OS).Results: One hundred and forty-four patients were randomized. Median OS was 12.2 versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82–1.48] in the combined rilotumumab versus control arms. Median progression-free survival was 3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79–1.31). Treatment appeared well tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab. A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment. Soluble MET levels increased in all treatment arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab showed linear pharmacokinetics when co-administered with MP.Conclusions: Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study. High tumor MET expression may identify patients with CRPC with poorer prognosis. Clin Cancer Res; 19(1); 215–24. ©2012 AACR.
Is There a Link Between Genome-Wide Hypomethylation in Blood and Cancer Risk?
Authors: Brennan Kevin , Flanagan James M. 
Published: November 2012

Abstract
Cancer cells display widespread genetic and epigenetic abnormalities, but the contribution to disease risk, particularly in normal tissue before disease, is not yet established. Genome-wide hypomethylation occurs frequently in tumors and may facilitate chromosome instability, aberrant transcription and transposable elements reactivation. Several epidemiologic case–control studies have reported genomic hypomethylation in peripheral blood of cancer patients, suggesting a systemic effect of hypomethylation on disease predisposition, which may be exploited for biomarker development. However, more recent studies have failed to reproduce this. Here, we report a meta-analysis, indicating a consistent inverse association between genomic 5-methylcytosine levels and cancer risk [95% confidence interval (CI), 1.2–6.1], but no overall risk association for studies using surrogates for genomic methylation, including methylation at the LINE-1 repetitive element (95% CI, 0.8–1.7). However, studies have been highly heterogeneous in terms of experimental design, assay type, and analytical methods. We discuss the limitations of the current approaches, including the low interindividual variability of surrogate assays such as LINE1 and the importance of using prospective studies to investigate DNA methylation in disease risk. Insights into genomic location of hypomethylation, from recent whole genome, high-resolution methylome maps, will help address this interesting and clinically important question. Cancer Prev Res; 5(12); 1345–57. ©2012 AACR.
Is higher choroid plexus ‘load’ an aetiologic factor in idiopathic intracranial hypertension? A clinico-imaging morphometric correlative study
Authors: Horsburgh Avril , Massoud Tarik F 
Published: November 2012

Background Idiopathic intracranial hypertension (IIH) is a condition of raised cerebrospinal fluid (CSF) pressure with normal ventricular size. Although the pathogenesis of IIH remains controversial, increased CSF formation may be important. We hypothesised that if increased CSF formation was an aetiologic factor, it might result in a macroscopic increase in size of the choroid plexus (CP). Method We retrospectively studied 50 patients with IIH. Total size of the CP was estimated on computed tomography (CT) venograms from the sum of axial areas measured at three locations. Results were compared with the CP load of 50 matched controls on post-contrast head CTs. Evans Index was measured to exclude ventriculomegaly. Results were analysed using a Student’s t test for independent samples ( p < 0.05), and the effect of ICP was tested on the dependent variable (area of CP) using regression analysis. Results There was no significant difference in the size of the CP glomus, total axial areas of the CP between IIH patients (183 mm2) and controls (178 mm2) and no correlation between the ‘load’ of CP and the degree of intracranial pressure (ICP) ( R2 < 0.02). Conclusion If increased CSF formation is an aetiologic factor in IIH, this is not reflected in a corresponding raised ‘load’ of CP.
Change in intraindividual ICHD-II headache diagnosis over time: A follow-up of the DMKG headache study
Authors: Khil Laura , Straube Andreas , Evers Stefan , Berger Klaus 
Published: November 2012

Background Change in headache diagnoses over time within the same individual is not well studied in the adult population. In this study, we prospectively examined the individual variation of migraine and tension-type headache (TTH) diagnoses over time. Methods As part of the epidemiological Deutsche Migräne und Kopfschmerzgesellschaft (DMKG) headache study, 1312 participants were personally interviewed and 1122 responded to a second mailed questionnaire 2.2 years later. Headaches were assigned to migraine or TTH at two different points in time using the International Headache Classification, ICHD-II. We used broad (definite and probable subtypes) and strict (only definite type) definitions of migraine and TTH. Results Using the broad definition increased the reproducibility of migraine diagnosis from 48.0% to 62.0% and of TTH from 59.0% to 65.0%. A constant TTH diagnosis was related to a higher social status (OR 2.81; 95% CI 1.43–5.53) a higher level of education (OR 1.96; 95% CI 1.00–3.85) and physical inactivity (OR 2.28; 95% CI 1.16–4.49). A constant diagnosis of definite migraine was associated with severe headache (OR 2.64; 95% CI 0.97–7.21) and frequent use of headache medication (OR 4.73; 95% CI 0.95–23.60). The result that coexisting TTH decreased the likelihood of a constant migraine (OR 0.29; 95% CI 0.10–0.85) is assumed to indicate response variability. Conclusions In epidemiological studies, definite and probable subtypes should be included in the diagnosis to increase the diagnostic accuracy.