bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience of long-term use of non-invasive ventilation in motor neuron disease: an interpretative phenomenological analysis
Authors: Ando Hikari , Chakrabarti Biswajit , Angus Robert M , Cousins Rosanna , Thornton Everard W , Young Carolyn A 
Published: October 2013

ObjectiveAlthough non-invasive ventilation (NIV) can promote quality of life in motor neuron disease (MND), previous studies have disregarded the impact of progression of illness. This study explored how patients’ perceptions of NIV treatment evolve over time and how this was reflected in their adherence to NIV.MethodsFive patients with MND (male=4, mean age=59 years), from a bigger cohort who were prospectively followed, had multiple post-NIV semistructured interviews, covering more than 12 months, along with ventilator interaction data. The transcribed phenomenological data were analysed using qualitative methodology.ResultsThree themes emerged: experience of NIV, influence on attitudes and perceived impact of NIV on prognosis. The ventilator interaction data identified regular use of NIV by four participants who each gave positive account of their experience of NIV treatment, and irregular use by one participant who at interview revealed a negative attitude to NIV treatment and in whom MND induced feelings of hopelessness.ConclusionsThis exploratory study suggests that a positive coping style, adaptation and hope are key factors for psychological well-being and better adherence to NIV. More studies are needed to determine these relationships.
Duplication of radiology imaging studies in the emergency department: what is the cost?
Authors: Kamat Achyut B , Midgley Stephanie , Kimbrell Katherine 
Published: October 2013

ObjectiveTo quantify the rate of preventable duplication of imaging studies in the Emergency Department. Previously, to estimate potential savings from the Health Information Exchange, figures used to be based on expert opinion, as the actual rate of redundant imaging is unknown.Materials and methodsWe prospectively quantified the frequency of duplicate CT scans in tertiary care and community hospital emergency departments (ED) through a short questionnaire at the time the studies were ordered.ResultsDuring the study period, 9246 CT scans were performed with a preventable duplicate rate of 0.42%. Both sites had equivalent rates of preventable duplicates.Discussion and conclusionsWe used two EDs to quantify the rate of preventable duplicate CT scans ordered. Our results demonstrate that only 0.4% of CT scans performed in our EDs are preventable duplicates. Our rate of preventable duplicate studies was much lower than what experts and emergency practitioners suspected, which suggests that potential cost savings from elimination of preventable duplicates may also be much lower than currently estimated.
miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor
Authors: Pichler Martin , Winter Elke , Ress Anna Lena , Bauernhofer Thomas , Gerger Armin , Kiesslich Tobias , Lax Sigurd , Samonigg Hellmut , Hoefler Gerald 
Published: October 2013

AimsmiR-181a expression is frequently altered in different types of cancer. Members of the Wnt/β-catenin signalling pathway, which is commonly altered in colorectal cancer (CRC), have been reported as molecular interaction partners of miR-181. However, the role of miR-181a expression in CRC and its ability to predict survival and response to agents targeting the epidermal growth factor receptor (EGFR) have not been explored yet.MethodsIn this study, we analysed 80 patients with wild typeKRASCRC undergoing treatment with the EGFR-targeting monoclonal antibodies cetuximab and panitumumab for metastatic CRC. TheKRASmutational status was determined by pyrosequencing and miR-181a expression was measured by quantitative RT-PCR in CRC tumour tissue and corresponding non-neoplastic colon tissue. The microRNA expression levels were correlated with clinicopathological characteristics. Cancer-specific survival was calculated by univariate and multivariate analyses, and progression-free survival (PFS) during treatment with EGFR-targeting agents was also evaluated.ResultsA low miR-181a expression level was associated with poor differentiation of CRC (p=0.04). A Kaplan-Meier curve showed a decreased survival time for patients with low miR-181a expression (p=0.019). Low miR-181a expression was furthermore associated with poor PFS (p=0.015).ConclusionsIn conclusion, our data suggest that the miR-181a expression level is associated with poor survival in patients with CRC. Furthermore, miR-181a expression might predict PFS in EGFR-targeted therapy.
Exploring the social determinants of mental health service use using intersectionality theory and CART analysis
Authors: Cairney John , Veldhuizen Scott , Vigod Simone , Streiner David L , Wade Terrance J , Kurdyak Paul 
Published: October 2013

BACKGROUNDFewer than half of individuals with a mental disorder seek formal care in a given year. Much research has been conducted on the factors that influence service use in this population, but the methods generally used cannot easily identify the complex interactions that are thought to exist. In this paper, we examine predictors of subsequent service use among respondents to a population health survey who met criteria for a past-year mood, anxiety or substance-related disorder.METHODSTo determine service use, we use an administrative database including all physician consultations in the period of interest. To identify predictors, we use classification tree (CART) analysis, a data mining technique with the ability to identify unsuspected interactions. We compare results to those from logistic regression models.RESULTSWe identify 1213 individuals with past-year disorder. In the year after the survey, 24% (n=312) of these had a mental health-related physician consultation. Logistic regression revealed that age, sex and marital status predicted service use. CART analysis yielded a set of rules based on age, sex, marital status and income adequacy, with marital status playing a role among men and by income adequacy important among women. CART analysis proved moderately effective overall, with agreement of 60%, sensitivity of 82% and specificity of 53%.CONCLUSIONResults highlight the potential of data-mining techniques to uncover complex interactions, and offer support to the view that the intersection of multiple statuses influence health and behaviour in ways that are difficult to identify with conventional statistics. The disadvantages of these methods are also discussed.
Review of Mass Spectrometry–Based Metabolomics in Cancer Research
Authors: Liesenfeld David B. , Habermann Nina , Owen Robert W. , Scalbert Augustin , Ulrich Cornelia M. 
Published: October 2013

Abstract
Metabolomics, the systematic investigation of all metabolites present within a biologic system, is used in biomarker development for many human diseases, including cancer. In this review, we investigate the current role of mass spectrometry–based metabolomics in cancer research. A literature review was carried out within the databases PubMed, Embase, and Web of Knowledge. We included 106 studies reporting on 21 different types of cancer in 7 different sample types. Metabolomics in cancer research is most often used for case–control comparisons. Secondary applications include translational areas, such as patient prognosis, therapy control and tumor classification, or grading. Metabolomics is at a developmental stage with respect to epidemiology, with the majority of studies including less than 100 patients. Standardization is required especially concerning sample preparation and data analysis. In the second part of this review, we reconstructed a metabolic network of patients with cancer by quantitatively extracting all reports of altered metabolites: Alterations in energy metabolism, membrane, and fatty acid synthesis emerged, with tryptophan levels changed most frequently in various cancers. Metabolomics has the potential to evolve into a standard tool for future applications in epidemiology and translational cancer research, but further, large-scale studies including prospective validation are needed. Cancer Epidemiol Biomarkers Prev; 22(12); 2182–201. ©2013 AACR.
Contrasting Expression Patterns of Histone mRNA and microRNA 760 in Patients with Gastric Cancer
Authors: Iwaya Takeshi , Fukagawa Takeo , Suzuki Yutaka , Takahashi Yusuke , Sawada Genta , Ishibashi Masahisa , Kurashige Junji , Sudo Tomoya , Tanaka Fumiaki , Shibata Kohei , Endo Fumitaka , Katagiri Hirokatsu , Ishida Kaoru , Kume Kohei , Nishizuka Satoshi , Iinuma Hisae , Wakabayashi Go , Mori Masaki , Sasako Mitsuru , Mimori Koshi 
Published: October 2013

Abstract
Purpose: Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer.
Experimental Design: Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients.
Results: RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P = 0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNA and miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients.
Conclusion: Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer. Clin Cancer Res; 19(23); 6438–49. ©2013 AACR.
EZH2 Protein Expression Associates with the Early Pathogenesis, Tumor Progression, and Prognosis of Non–Small Cell Lung Carcinoma
Authors: Behrens Carmen , Solis Luisa M. , Lin Heather , Yuan Ping , Tang Ximing , Kadara Humam , Riquelme Erick , Galindo Hector , Moran Cesar A. , Kalhor Neda , Swisher Stephen G. , Simon George R. , Stewart David J. , Lee J. Jack , Wistuba Ignacio I. 
Published: October 2013

Abstract
Purpose: Enhancer of zeste homolog 2 (EZH2) promotes carcinogenesis by epigenetically silencing tumor suppressor genes. We studied EZH2 expression by immunohistochemistry in a large series of non–small cell lung carcinomas (NSCLC) in association with tumor characteristics and patient outcomes.
Experimental Design: EZH2 immunohistochemistry expression was analyzed in 265 normal and premalignant bronchial epithelia, 541 primary NSCLCs [221 squamous cell carcinomas (SCC) and 320 adenocarcinomas] and 36 NSCLCs with paired brain metastases. An independent set of 91 adenocarcinomas was also examined. EZH2 expression was statistically correlated with clinico-pathological information, and EGFR/KRAS mutation status.
Results: EZH2 expression was significantly (P &lt; 0.0001) higher in SCCs compared with adenocarcinomas and in brain metastasis relative to matched primary tumors (P = 0.0013). EZH2 expression was significantly (P &lt; 0.0001) elevated in bronchial preneoplastic lesions with increasing severity. In adenocarcinomas, higher EZH2 expression significantly correlated with younger age, cigarette smoking, and higher TNM stage (P = 0.02 to P &lt; 0.0001). Higher EZH2 expression in adenocarcinoma was associated with worse recurrence-free survival (RFS; P = 0.025; HR = 1.54) and overall survival (OS; P = 0.0002; HR = 1.96). Furthermore, lung adenocarcinomas with low EZH2 levels and high expression of the lineage-specific transcription factor, TTF-1, exhibited significantly improved RFS (P = 0.009; HR = 0.51) and OS (P = 0.0011; HR = 0.45), which was confirmed in the independent set of 91 adenocarcinomas.
Conclusion: In lung, EZH2 expression is involved in early pathogenesis of SCC and correlates with a more aggressive tumor behavior of adenocarcinoma. When EZH2 and TTF-1 expressions are considered together, they serve as a prognostic marker in patients with surgically resected lung adenocarcinomas. Clin Cancer Res; 19(23); 6556–65. ©2013 AACR.
Effects of Adjuvant Chemoradiotherapy on the Frequency and Function of Regulatory T Cells in Patients with Head and Neck Cancer
Authors: Schuler Patrick J. , Harasymczuk Malgorzata , Schilling Bastian , Saze Zenichiro , Strauss Laura , Lang Stephan , Johnson Jonas T. , Whiteside Theresa L. 
Published: October 2013

Abstract
Purpose: Regulatory T cells (Treg) accumulate in tumor tissues and the peripheral blood of cancer patients and may persist after therapies. This cross-sectional study examines effects of adjuvant chemoradiotherapy (CRT) on Treg numbers and function in head and neck squamous cell carcinoma (HNSCC) patients.
Experimental Design: The frequency and absolute numbers of CD4+, ATP-hydrolyzing CD4+CD39+ and CD8+ T cells, and expression levels of CD39, CD25, TGF-β–associated LAP and GARP on Treg were measured by flow cytometry in 40 healthy donors (NC) and 71 HNSCC patients [29 untreated with active disease (AD); 22 treated with surgery; 20 treated with CRT]. All treated subjects had no evident disease (NED) at the time of phlebotomy. In an additional cohort of 40 subjects with AD (n = 15), NED (n = 10), and NC (n = 15), in vitro sensitivity of CD4+ T-cell subsets to cisplatin and activation-induced cell death (AICD) was tested in Annexin V–binding assays.
Results: CRT decreased the frequency of circulating CD4+ T cells (P &lt; 0.002) but increased that of CD4+CD39+ Treg (P ≤ 0.001) compared with untreated or surgery-only patients. Treg frequency remained elevated for &gt;3 years. CRT increased surface expression of LAP, GARP, and CD39 on Treg. In vitro Treg were resistant to AICD or cisplatin but conventional CD4+ T cells (Tconv) were not. CRT-induced Treg from AD or NC subjects upregulated prosurvival proteins whereas Tconv upregulated proapoptotic Bax.
Conclusions: Highly suppressive, cisplatin-resistant Treg increase in frequency and persist after CRT and could be responsible for suppression of antitumor immune responses and recurrence in HNSCC. Clin Cancer Res; 19(23); 6585–96. ©2013 AACR.
Interleukin-7 Mediates Selective Expansion of Tumor-redirected Cytotoxic T Lymphocytes (CTLs) without Enhancement of Regulatory T-cell Inhibition
Authors: Perna Serena K. , Pagliara Daria , Mahendravada Aruna , Liu Hao , Brenner Malcolm K. , Savoldo Barbara , Dotti Gianpietro 
Published: October 2013

Abstract
Purpose: The antitumor activity of chimeric antigen receptor (CAR)–redirected CTLs should be enhanced if it were possible to increase their proliferation and function after adoptive transfer without concomitantly increasing the proliferation and function of regulatory T cells (Treg). Here, we explored whether the lack of IL-7Rα in Treg can be exploited by the targeted manipulation of the interleukin-7 (IL-7) cytokine–cytokine receptor axis in CAR-engrafted Epstein–Barr Virus–specific CTLs (EBV-CTLs) to selectively augment their growth and antitumor activity even in the presence of Treg.
Experimental Design: We generated a bicistronic retroviral vector encoding a GD2-specific CAR and the IL-7Rα subunit, expressed the genes in EBV-CTLs, and assessed their capacity to control tumor growth in the presence of Treg in vitro and in vivo when exposed to either interleukin-2 (IL-2) or IL-7 in a neuroblastoma xenograft.
Results: We found that IL-7, in sharp contrast with IL-2, supports the proliferation and antitumor activity of IL-7Rα.CAR-GD2+ EBV-CTLs both in vitro and in vivo even in the presence of fully functional Treg.
Conclusions: IL-7 selectively favors the survival, proliferation, and effector function of IL-7Rα-transgenic/CAR-redirected EBV-CTLs in the presence of Treg both in vitro and in vivo. Thus, IL-7 can have a significant impact in sustaining expansion and persistence of adoptively CAR-redirected CTLs. Clin Cancer Res; 20(1); 131–9. ©2013 AACR.
A Phase I Trial of Imetelstat in Children with Refractory or Recurrent Solid Tumors: A Children's Oncology Group Phase I Consortium Study (ADVL1112)
Authors: Thompson Patrick A. , Drissi Rachid , Muscal Jodi A. , Panditharatna Eshini , Fouladi Maryam , Ingle Ashish M. , Ahern Charlotte H. , Reid Joel M. , Lin Tong , Weigel Brenda J. , Blaney Susan M. 
Published: October 2013

Abstract
Purpose: Imetelstat is a covalently-lipidated 13-mer thiophosphoramidate oligonucleotide that acts as a potent specific inhibitor of telomerase. It binds with high affinity to the template region of the RNA component of human telomerase (hTERC) and is a competitive inhibitor of telomerase enzymatic activity. The purpose of this study was to determine the recommended phase II dose of imetelstat in children with recurrent or refractory solid tumors.
Experimental Design: Imetelstat was administered intravenously more than two hours on days 1 and 8, every 21 days. Dose levels of 225, 285, and 360 mg/m2 were evaluated, using the rolling-six design. Imetelstat pharmacokinetic and correlative biology studies were also performed during the first cycle.
Results: Twenty subjects were enrolled (median age, 14 years; range, 3–21). Seventeen were evaluable for toxicity. The most common toxicities were neutropenia, thrombocytopenia, and lymphopenia, with dose-limiting myelosuppression in 2 of 6 patients at 360 mg/m2. Pharmacokinetics is dose dependent with a lower clearance at the highest dose level. Telomerase inhibition was observed in peripheral blood mononuclear cells at 285 and 360 mg/m2. Two confirmed partial responses, osteosarcoma (n = 1) and Ewing sarcoma (n = 1), were observed.
Conclusions: The recommended phase II dose of imetelstat given on days 1 and 8 of a 21-day cycle is 285 mg/m2. Clin Cancer Res; 19(23); 6578–84. ©2013 AACR.
Loss of NAPRT1 Expression by Tumor-Specific Promoter Methylation Provides a Novel Predictive Biomarker for NAMPT Inhibitors
Authors: Shames David S. , Elkins Kristi , Walter Kimberly , Holcomb Thomas , Du Pan , Mohl Dane , Xiao Yang , Pham Thinh , Haverty Peter M. , Liederer Bianca , Liang Xiaorong , Yauch Robert L. , O'Brien Thomas , Bourgon Richard , Koeppen Hartmut , Belmont Lisa D. 
Published: October 2013

Abstract
Purpose: We sought to identify predictive biomarkers for a novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor.
Experimental Design: We use a NAMPT inhibitor, GNE-617, to evaluate nicotinic acid rescue status in a panel of more than 400 cancer cell lines. Using correlative analysis and RNA interference (RNAi), we identify a specific biomarker for nicotinic acid rescue status. We next determine the mechanism of regulation of expression of the biomarker. Finally, we develop immunohistochemical (IHC) and DNA methylation assays and evaluate cancer tissue for prevalence of the biomarker across indications.
Results: Nicotinate phosphoribosyltransferase (NAPRT1) is necessary for nicotinic acid rescue and its expression is the major determinant of rescue status. We demonstrate that NAPRT1 promoter methylation accounts for NAPRT1 deficiency in cancer cells, and NAPRT1 methylation is predictive of rescue status in cancer cell lines. Bisulfite next-generation sequencing mapping of the NAPRT1 promoter identified tumor-specific sites of NAPRT1 DNA methylation and enabled the development of a quantitative methylation-specific PCR (QMSP) assay suitable for use on archival formalin-fixed paraffin-embedded tumor tissue.
Conclusions: Tumor-specific promoter hypermethylation of NAPRT1 inactivates one of two NAD salvage pathways, resulting in synthetic lethality with the coadministration of a NAMPT inhibitor. NAPRT1 expression is lost due to promoter hypermethylation in most cancer types evaluated at frequencies ranging from 5% to 65%. NAPRT1-specific immunohistochemical or DNA methylation assays can be used on archival formalin paraffin-embedded cancer tissue to identify patients likely to benefit from coadministration of a Nampt inhibitor and nicotinic acid. Clin Cancer Res; 19(24); 6912–23. ©2013 AACR.
A Phase 1, Dose-Escalation, Pharmacokinetic and Pharmacodynamic Study of BIIB021 Administered Orally in Patients with Advanced Solid Tumors
Authors: Saif Muhammad Wasif , Takimoto Chris , Mita Monica , Banerji Udai , Lamanna Nicole , Castro Januario , O'Brien Susan , Stogard Christopher , Von Hoff Daniel 
Published: October 2013

Abstract
Purpose: BIIB021 is the first oral, synthetic, non-geldanamycin–based HSP90 inhibitor that showed activity in preclinical models at low nanomolar concentrations. We performed a phase 1 trial of BIIB021 administered to subjects with advanced solid tumors.
Experimental Design: Sixty patients received BIIB021 capsules orally on days 1, 4, 8, 11, 15, and 18 of each course in schedule 1, and on days 1, 4, 8, 11, 15, 18, 22, and 25 of each course in schedule 2. The treatment schedules were repeated every 28 days. In addition to determining the MTD, we evaluated pharmacokinetics of BIIB021 and pharmacodynamic effects of BIIB021 [Hsp70, HER2 extracellular domain (HER2-ECD)].
Results: The MTD was 700 mg twice weekly when BIIB021 was dosed for 3 weeks out of each 4-week course. The MTD for continuous dosing regimen was established at 600 mg twice weekly. Gastrointestinal (nausea, vomiting), hot flashes, and neurologic (dizziness) events characterize the safety profile of BIIB021 dosed twice weekly, with events mostly mild or moderate. Plasma exposure to BIIB021 was dose-dependent. Cmax occurred at approximately 90 minutes and t1/2 was approximately 1 hour across dosing cohorts of 25 to 800 mg BIIB021 twice weekly. The biologic activity of BIIB021 was demonstrated in serum, PBMCs, and tumor tissue. Hsp70 levels were increased (&gt;150% from baseline) and serum HER2-ECD was significantly decreased (&gt;15% inhibition from baseline).
Conclusions: BIIB021 twice weekly, given with or without the 1 of 4-week rest period was tolerated in subjects with advanced solid tumors at doses that are pharmacodynamically active. Clin Cancer Res; 20(2); 445–55. ©2013 AACR.