bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of budesonide MMX (Cortiment) for the treatment of mild-to-moderate active ulcerative colitis: study protocol for a prospective multicentre observational cohort study
Authors: Danese Silvio , Hart Ailsa , Dignass Axel , Louis Edouard , D'Haens Geert , Dotan Iris , Rogler Gerhard , D'Agay Laurence , Iannacone Claudio , Peyrin-Biroulet Laurent 
Published: May 2016

IntroductionA study has been developed to assess the use and effectiveness of budesonide MMX for mild-to-moderate active ulcerative colitis (UC) in routine clinical practice.Methods and analysisA prospective, multicentre, observational, cohort study of 300 patients prescribed budesonide MMX for the treatment of mild-to-moderate active UC will be conducted in Europe, Israel and Canada. Patients will be treated with budesonide MMX9 mg daily for induction of remission for ≤8 weeks. Data on effectiveness, including patient-reported outcomes, tolerability and use will be recorded at the end of treatment and at ≥2 weeks after. The primary outcome (improvement ≥3 point in the clinical subscores of the UC Disease Activity Index score at the end of treatment) will be compared in: patients who receive budesonide MMX added to mesalazine >2 weeks after increased/optimised mesalazine dose for the treatment of flare (late add-on); patients who receive budesonide MMX added to mesalazine ≤2 weeks since mesalazine increased/optimised for the treatment of flare, or without mesalazine dose modification (early add-on); and patients who receive budesonide MMX as monotherapy for the treatment of flare (mono). Propensity scoring will be used to minimise bias and confounding inherent in observational studies.Ethics and disseminationFirst ethical approval: Ethikkommission der Ärztekammer Hamburg (12/22/2015). The results will be published in full.DiscussionCompletion of primary data collection is expected in December 2017. Our results will provide further evidence on the effectiveness of budesonide MMX to support clinicians in their daily practice and inform therapeutic guidelines.Trial registration numberNCT02586259.
Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia
Authors: Pašara Vedran , Maksimović Bojana , Gunjača Mihaela , Mihovilović Karlo , Lončar Andrea , Kudumija Boris , Žabić Igor , Knotek Mladen 
Published: May 2016

ObjectivesStudies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se,or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA).DesignRetrospective cohort study.ParticipantsThis retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival.Primary outcome measuresPatient survival with respect to VA.ResultsThe cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3).ConclusionTDC may be an independent negative risk factor for HD patient survival.
Perceptions of coping with non-disease-related life stress for women with osteoarthritis: a qualitative analysis
Authors: Harris Melissa L , Byles Julie E , Townsend Natalie , Loxton Deborah 
Published: May 2016

ObjectiveCoping with arthritis-related stress has been extensively studied. However, limited evidence exists regarding coping with stress extraneous to the disease (life stress). This study explored life stress and coping in a subset of older women with osteoarthritis from a larger longitudinal study.SettingAn Australian regional university.DesignThis qualitative study involved semistructured telephone interviews. Potential participants were mailed a letter of invitation/participant information statement by the Australian Longitudinal Study on Women's Health (ALSWH). Invitations were sent out in small batches (primarily 10). Interviews were conducted until data saturation was achieved using a systematic process (n=19). Digitally recorded interviews were transcribed verbatim and deidentified. Data were thematically analysed.ParticipantsWomen who indicated being diagnosed or treated for arthritis in the previous 3 years in the fifth survey of the ALSWH (conducted in 2007) provided the sampling frame. Potential participants were randomly sampled by a blinded data manager using a random number generator.ResultsCoping with life stress involved both attitudinal coping processes developed early in life (ie, stoicism) and transient cognitive and support-based responses. Women also described a dualistic process involving a reduction in the ability to cope with ongoing stress over time, coupled with personal growth.ConclusionsThis is the first study to examine how individuals cope with non-arthritis-related stress. The findings add to the current understanding of stress and coping, and have implications regarding the prevention of arthritis in women. Importantly, this study highlighted the potential detrimental impact of persistent coping patterns developed early in life. Public health campaigns aimed at stress mitigation and facilitation of adaptive coping mechanisms in childhood and adolescence may assist with arthritis prevention.
Changes in poisonings among adolescents in the UK between 1992 and 2012: a population based cohort study
Authors: Tyrrell Edward G , Orton Elizabeth , Tata Laila J 
Published: May 2016

BackgroundPoisonings are a common cause of morbidity and mortality among adolescents. Yet surveillance data indicating current incidence rates (IRs) and time trends are lacking, making policy development and service planning difficult. We utilised population based primary care data to estimate adolescent poisoning rates according to intent across the UK.MethodsA cohort study of 1 311 021 adolescents aged 10–17 years, between 1992 and 2012, was conducted using routine primary care data from The Health Improvement Network. IRs and adjusted IRRs with 95% CIs were calculated for all poisonings, intentional, unintentional, unknown intent and alcohol related poisonings, by age, sex, calendar time and socioeconomic deprivation.ResultsOverall poisoning incidence increased by 27% from the period 1992–1996 to 2007–2012, with the largest increases in intentional poisonings among females aged 16–17 years (IR 391.4/100 000 person years (PY), CI 328.9 to 465.7 for age 17 years in 1992–1996; 767.0/100 000 PY, CI 719.5 to 817.7 in 2007–2012) and alcohol related poisonings in females aged 15–16 years (IR 65.7/100 000 PY, CI 43.3 to 99.8 rising to 130.0/100 000 PY, CI 110.0 to 150.0 for age 15 years). A strong socioeconomic gradient for all poisonings persisted over time, with higher rates among the more deprived (IRR 2.63, CI 2.41 to 2.88 for the most vs least deprived quintile in 2007–2012).ConclusionsAdolescent poisonings, especially intentional poisonings, have increased substantially over time and remain associated with health inequalities. Social and psychological support for adolescents should be targeted at more deprived communities, and child and adolescent mental health and alcohol support service provision should be commissioned to reflect the changing need.
Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study
Authors: Childs Erica J. , Chaffee Kari G. , Gallinger Steven , Syngal Sapna , Schwartz Ann G. , Cote Michele L. , Bondy Melissa L. , Hruban Ralph H. , Chanock Stephen J. , Hoover Robert N. , Fuchs Charles S. , Rider David N. , Amundadottir Laufey T. , Stolzenberg-Solomon Rachael , Wolpin Brian M. , Risch Harvey A. , Goggins Michael G. , Petersen Gloria M. , Klein Alison P. 
Published: May 2016

Abstract
Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13–1.63; P = 9.29 × 10−4; 7p13, rs17688601: OR = 0.76; 95% CI, 0.63–0.93; P = 6.59 × 10−3). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P &lt; 5 × 10−5) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185–91. ©2016 AACR.
ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI
Authors: Gerstner Elizabeth R. , Zhang Zheng , Fink James R. , Muzi Mark , Hanna Lucy , Greco Erin , Prah Melissa , Schmainda Kathleen M. , Mintz Akiva , Kostakoglu Lale , Eikman Edward A. , Ellingson Benjamin M. , Ratai Eva-Maria , Sorensen A. Gregory , Barboriak Daniel P. , Mankoff David A. 
Published: May 2016

Abstract
Purpose: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma.
Experimental Design: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival.
Results: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59–0.91], nRCBV (AUC = 0.72; 95% CI, 0.56–0.89), and nCBF (AUC = 0.72; 95% CI, 0.56–0.89) were predictive of survival at 1 year.
Conclusions: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079–86. ©2016 AACR.
Intratumor Heterogeneity Affects Gene Expression Profile Test Prognostic Risk Stratification in Early Breast Cancer
Authors: Gyanchandani Rekha , Lin Yan , Lin Hui-Min , Cooper Kristine , Normolle Daniel P. , Brufsky Adam , Fastuca Michael , Crosson Whitney , Oesterreich Steffi , Davidson Nancy E. , Bhargava Rohit , Dabbs David J. , Lee Adrian V. 
Published: May 2016

Abstract
Purpose: To examine the effect of intratumor heterogeneity (ITH) on detection of genes within gene expression panels (GEPs) and the subsequent ability to predict prognostic risk.
Experimental Design: Multiplexed barcoded RNA analysis was used to measure the expression of 141 genes from five GEPs (Oncotype Dx, MammaPrint, PAM50, EndoPredict, and Breast Cancer Index) in breast cancer tissue sections and tumor-rich cores from 71 estrogen receptor (ER)-positive node-negative tumors, on which clinical Oncotype Dx testing was previously performed. If the tumor had foci of high Ki67 (n = 26), low/negative progesterone receptor (PR; n = 13), or both (n = 5), additional cores were obtained. In total, 181 samples were processed. Oncotype Dx recurrence scores were calculated from NanoString nCounter gene expression data.
Results: Hierarchical clustering using all GEP genes showed that majority (61 of 71) of tumor samples clustered by patient, indicating greater interpatient heterogeneity (IPH) than ITH. We found a strikingly high correlation between Oncotype Dx recurrence scores obtained from whole sections versus tumor-rich cores (r = 0.94). However, high Ki67 and low PR cores had slightly higher but not statistically significant recurrence scores. For 18 of 71 (25%) patients, scores were divergent between sections and cores and crossed the boundaries for low, intermediate, and high risk.
Conclusions: Our study indicates that in patients with highly heterogeneous tumors, GEP recurrence scores from a single core could under- or overestimate prognostic risk. Hence, it may be a useful strategy to assess multiple samples (both representative and atypical cores) to fully account for the ITH-driven variation in risk prediction. Clin Cancer Res; 22(21); 5362–9. ©2016 AACR.
TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Authors: Jeselsohn Rinath , Barry William T. , Migliaccio Ilenia , Biagioni Chiara , Zhao Jin , De Tribolet-Hardy Jonas , Guarducci Cristina , Bonechi Martina , Laing Naomi , Winer Eric P. , Brown Myles , Leo Angelo Di , Malorni Luca 
Published: May 2016

AbstractPurpose: Fulvestrant is an estrogen receptor (ER) antagonist and an approved treatment for metastatic estrogen receptor–positive (ER+) breast cancer. With the exception of ER levels, there are no established predictive biomarkers of response to single-agent fulvestrant. We attempted to identify a gene signature of response to fulvestrant in advanced breast cancer.Experimental Design: Primary tumor samples from 134 patients enrolled in the phase III CONFIRM study of patients with metastatic ER+ breast cancer comparing treatment with either 250 mg or 500 mg fulvestrant were collected for genome-wide transcriptomic analysis. Gene expression profiling was performed using Affymetrix microarrays. An exploratory analysis was performed to identify biologic pathways and new signatures associated with response to fulvestrant.Results: Pathway analysis demonstrated that increased EGF pathway and FOXA1 transcriptional signaling is associated with decreased response to fulvestrant. Using a multivariate Cox model, we identified a novel set of 37 genes with an expression that is independently associated with progression-free survival (PFS). TFAP2C, a known regulator of ER activity, was ranked second in this gene set, and high expression was associated with a decreased response to fulvestrant. The negative predictive value of TFAP2C expression at the protein level was confirmed by IHC.Conclusions: We identified biologic pathways and a novel gene signature in primary ER+ breast cancers that predicts for response to treatment in the CONFIRM study. These results suggest potential new therapeutic targets and warrant further validation as predictive biomarkers of fulvestrant treatment in metastatic breast cancer. Clin Cancer Res; 22(23); 5755–64. ©2016 AACR.
Noninvasive Detection of Metastases and Follicle Density in Ovarian Tissue Using Full-Field Optical Coherence Tomography
Authors: Peters Inge T.A. , Stegehuis Paulien L. , Peek Ronald , Boer Florine L. , van Zwet Erik W. , Eggermont Jeroen , Westphal Johan R. , Kuppen Peter J.K. , Trimbos J. Baptist , Hilders Carina G.J.M. , Lelieveldt Boudewijn P.F. , van de Velde Cornelis J.H. , Bosse Tjalling , Dijkstra Jouke , Vahrmeijer Alexander L. 
Published: May 2016

Abstract
Purpose: Autotransplantation of ovarian tissue can be used to restore fertility in patients with cancer following gonadotoxic treatment. Whether this procedure is safe remains unclear, as current tumor detection methods render the ovarian tissue unsuitable for transplantation. Full-field optical coherence tomography (FF-OCT) is an imaging modality that rapidly produces high-resolution histology-like images without the need to fix, freeze, or stain the tissue. In this proof-of-concept study, we investigated whether FF-OCT can be used to detect metastases in ovarian tissue, thereby increasing the safety of ovarian tissue autotransplantation. We also evaluated whether cortical ovarian tissue and follicles remain viable following FF-OCT imaging.
Experimental Design: Formalin-fixed, paraffin-embedded tissue samples were obtained from seven normal ovaries and fourteen ovaries containing metastases and/or micrometastases. These samples were deparaffinized and imaged using FF-OCT. The FF-OCT images were then compared with corresponding hematoxylin and eosin–stained tissue sections. Finally, we examined the effect of FF-OCT imaging on the viability of ovarian tissues and follicles in fresh bovine ovarian tissue using a glucose uptake and neutral red staining, respectively.
Results: FF-OCT illustrated both normal structures and metastases in ovarian tissue within minutes. Primordial follicles were readily identifiable. Finally, tissues and follicles remained viable following FF-OCT imaging for up to 180 and 60 minutes, respectively.
Conclusions: FF-OCT imaging is a promising method for the noninvasive detection of metastases, including micrometastases, in ovarian tissue. Moreover, this method facilitates the selection of cortical ovarian tissue with the highest density of primordial follicles, potentially increasing the likelihood of restoring ovarian function following ovarian tissue autotransplantation. Clin Cancer Res; 22(22); 5506–13. ©2016 AACR.
The Effect of F877L and T878A Mutations on Androgen Receptor Response to Enzalutamide
Authors: Prekovic Stefan , van Royen Martin E. , Voet Arnout R.D. , Geverts Bart , Houtman Rene , Melchers Diana , Zhang Kam Y.J. , Van den Broeck Thomas , Smeets Elien , Spans Lien , Houtsmuller Adriaan B. , Joniau Steven , Claessens Frank , Helsen Christine 
Published: May 2016

Abstract
Treatment-induced mutations in the ligand-binding domain of the androgen receptor (AR) are known to change antagonists into agonists. Recently, the F877L mutation has been described to convert enzalutamide into an agonist. This mutation was seen to co-occur in the endogenous AR allele of LNCaP cells, next to the T878A mutation. Here, we studied the effects of enzalutamide on the F877L and T878A mutants, as well as the double-mutant AR (F877L/T878A). Molecular modeling revealed favorable structural changes in the double-mutant AR that lead to a decrease in steric clashes for enzalutamide. Ligand-binding assays confirmed that the F877L mutation leads to an increase in relative binding affinity for enzalutamide, but only the combination with the T878A mutation resulted in a strong agonistic activity. This correlated with changes in coregulator recruitment and chromatin interactions. Our data show that enzalutamide is only a very weak partial agonist of the AR F877L, and a strong partial agonist of the double-mutant AR. Mol Cancer Ther; 15(7); 1702–12. ©2016 AACR.
Chromatin Regulators as a Guide for Cancer Treatment Choice
Authors: Gurard-Levin Zachary A. , Wilson Laurence O.W. , Pancaldi Vera , Postel-Vinay Sophie , Sousa Fabricio G. , Reyes Cecile , Marangoni Elisabetta , Gentien David , Valencia Alfonso , Pommier Yves , Cottu Paul , Almouzni Geneviève 
Published: May 2016

Abstract
The limited capacity to predict a patient's response to distinct chemotherapeutic agents is a major hurdle in cancer management. The efficiency of a large fraction of current cancer therapeutics (radio- and chemotherapies) is influenced by chromatin structure. Reciprocally, alterations in chromatin organization may affect resistance mechanisms. Here, we explore how the misexpression of chromatin regulators—factors involved in the establishment and maintenance of functional chromatin domains—can inform about the extent of docetaxel response. We exploit Affymetrix and NanoString gene expression data for a set of chromatin regulators generated from breast cancer patient-derived xenograft models and patient samples treated with docetaxel. Random Forest classification reveals specific panels of chromatin regulators, including key components of the SWI/SNF chromatin remodeler, which readily distinguish docetaxel high-responders and poor-responders. Further exploration of SWI/SNF components in the comprehensive NCI-60 dataset reveals that the expression inversely correlates with docetaxel sensitivity. Finally, we show that loss of the SWI/SNF subunit BRG1 (SMARCA4) in a model cell line leads to enhanced docetaxel sensitivity. Altogether, our findings point toward chromatin regulators as biomarkers for drug response as well as therapeutic targets to sensitize patients toward docetaxel and combat drug resistance. Mol Cancer Ther; 15(7); 1768–77. ©2016 AACR.