bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbon monoxide poisoning in patients presenting to the emergency department with a headache in winter months
Authors: Zorbalar Nilay , Yesilaras Murat , Aksay Ersin 
Published: October 2013

BackgroundCarbon monoxide (CO) poisoning is an important reason for emergency department (ED) visits during winter months, but because there are no specific symptoms it can be difficult to diagnose. We aimed to determine the frequency of CO poisoning in patients presenting to the ED with headaches during winter months and evaluate the ability of non-invasive carboxyhaemoglobin measurement (SpCO) to screen for CO poisoning in these patients.MethodsSpCO measurement values of adult patients were measured non-invasively with a Rad-57 Pulse CO-Oximeter. Patients whose initial SpCO reading was over 10% underwent a venous blood draw for laboratory determination of invasive carboxyhaemoglobin (COHb) measurement. Patients with a invasive COHb level of over 10% were diagnosed with CO poisoning. Percentage of screened patients with suspected and occult CO poisoning, the distribution of patients with CO poisoning by time of day of the ED visit and the positive predictive value of SpCO to detect CO poisoning were calculated.Results483 patients presenting with headaches were screened with SpCO measurement. Thirty-eight had a mean SpCO value of over 10%, 31 (6.4% of the study population) of which had elevated COHb confirmed by laboratory determination. SpCO measurement, therefore, had a positive predictive value of 82% for CO poisoning. Twenty-four (77%) of the CO poisoning cases were suspected and seven (23%) were occult. CO poisoning was detected more frequently in patients visiting the ED after midnight and during morning hours.ConclusionsCO poisoning should be kept in mind in patients presenting to the ED with a headache. SpCO is an effective screening tool to detect CO poisoning in these patients.
Characterizing the Temporal Dynamics of Human Papillomavirus DNA Detectability Using Short-Interval Sampling
Authors: Liu Su-Hsun , Cummings Derek A.T. , Zenilman Jonathan M. , Gravitt Patti E. , Brotman Rebecca M. 
Published: October 2013

AbstractBackground: Variable detection of human papillomavirus (HPV) DNA can result in misclassification of infection status, but the extent of misclassification has not been quantitatively evaluated.Methods: In 2005–2007, 33 women of ages 22 to 53 years self-collected vaginal swabs twice per week for 16 consecutive weeks. Each of the 955 swabs collected was tested for 37 HPV types/subtypes. Assuming that a woman's underlying infection status did not change over the short study period, biases in prevalence estimates obtained from single versus multiple swabs were calculated. Using event history analysis methods, time to recurrent gain and loss of at least one HPV type was determined, separately. Baseline any-type and high risk–type HPV prevalence was 60.6% and 24.2%, respectively. Cumulative any-HPV and high-risk HPV prevalence over the 16-week period was 84.8% and 60.6%, separately.Results: Overall, there were 319 events of detection and 313 events of loss of detection. Median times to a recurrent detection and loss of detection were 11 and seven days, respectively. Neither vaginal sex nor condom use during follow-up was associated with recurrent viral detection or loss of detection. Assuming the cumulative 16-week prevalence reflects the true prevalence of infection, the baseline any-HPV prevalence underestimated infection status by 24.2%, with a bootstrapped mean of 20.2% [95% confidence interval (CI), 8.9%–29.6%].Conclusions: These findings suggest that a substantial proportion of HPV-infected women are misclassified as being uninfected when using a single-time DNA measurement.Impact: Short-term variation in detectable HPV DNA needs to be considered while interpreting the natural history of infections using single samples collected at long intervals. Cancer Epidemiol Biomarkers Prev; 23(1); 200–8. ©2013 AACR.
Maté Drinking and Esophageal Squamous Cell Carcinoma in South America: Pooled Results from Two Large Multicenter Case–Control Studies
Authors: Lubin Jay H. , De Stefani Eduardo , Abnet Christian C. , Acosta Gisele , Boffetta Paolo , Victora Cesar , Graubard Barry I. , Muñoz Nubia , Deneo-Pellegrini Hugo , Franceschi Silvia , Castellsagué Xavier , Ronco Alvaro L. , Dawsey Sanford M. 
Published: October 2013

Abstract
Background: Maté tea is a nonalcoholic infusion widely consumed in southern South America, and may increase risk of esophageal squamous cell carcinoma (ESCC) and other cancers due to polycyclic aromatic hydrocarbons (PAH) and/or thermal injury.
Methods: We pooled two case–control studies: a 1988 to 2005 Uruguay study and a 1986 to 1992 multinational study in Argentina, Brazil, Paraguay, and Uruguay, including 1,400 cases and 3,229 controls. We computed ORs and fitted a linear excess OR (EOR) model for cumulative maté consumption in liters/day–year (LPDY).
Results: The adjusted OR for ESCC with 95% confidence interval (CI) by ever compared with never use of maté was 1.60 (1.2–2.2). ORs increased linearly with LPDY (test of nonlinearity; P = 0.69). The estimate of slope (EOR/LPDY) was 0.009 (0.005–0.014) and did not vary with daily intake, indicating maté intensity did not influence the strength of association. EOR/LPDY estimates for consumption at warm, hot, and very hot beverage temperatures were 0.004 (−0.002–0.013), 0.007 (0.003–0.013), and 0.016 (0.009–0.027), respectively, and differed significantly (P &lt; 0.01). EOR/LPDY estimates were increased in younger (&lt;65) individuals and never alcohol drinkers, but these evaluations were post hoc, and were homogeneous by sex.
Conclusions: ORs for ESCC increased linearly with cumulative maté consumption and were unrelated to intensity, so greater daily consumption for shorter duration or lesser daily consumption for longer duration resulted in comparable ORs. The strength of association increased with higher maté temperatures.
Impact: Increased understanding of cancer risks with maté consumption enhances the understanding of the public health consequences given its purported health benefits. Cancer Epidemiol Biomarkers Prev; 23(1); 107–16. ©2013 AACR.
The Effect of VEGF-Targeted Therapy on Biomarker Expression in Sequential Tissue from Patients with Metastatic Clear Cell Renal Cancer
Authors: Sharpe Kevin , Stewart Grant D. , Mackay Alan , Van Neste Christophe , Rofe Charlotte , Berney Dan , Kayani Irfan , Bex Axel , Wan Elaine , O'Mahony Fiach C. , O'Donnell Marie , Chowdhury Simon , Doshi Rukma , Ho-Yen Colan , Gerlinger Marco , Baker Dawn , Smith Neil , Davies Barry , Sahdev Anju , Boleti Ekaterini , De Meyer Tim , Van Criekinge Wim , Beltran Luis , Lu Yong-Jie , Harrison David J. , Reynolds Andrew R. , Powles Tom 
Published: October 2013

Abstract
Purpose: To investigate how biologically relevant markers change in response to antiangiogenic therapy in metastatic clear cell renal cancer (mRCC) and correlate these changes with outcome.
Experimental Design: The study used sequential tumor tissue and functional imaging (taken at baseline and 12–16 weeks) obtained from three similar phase II studies. All three studies investigated the role of VEGF tyrosine kinase inhibitors (TKI) before planned nephrectomy in untreated mRCC (n = 85). The effect of targeted therapy on ten biomarkers was measured from sequential tissue. Comparative genomic hybridization (CGH) array and DNA methylation profiling (MethylCap-seq) was performed in matched frozen pairs. Biomarker expression was correlated with early progression (progression as best response) and delayed progression (between 12–16 weeks).
Results: VEGF TKI treatment caused a significant reduction in vessel density (CD31), phospho-S6K expression, PDL-1 expression, and FOXP3 expression (P &lt; 0.05 for each). It also caused a significant increase in cytoplasmic FGF-2, MET receptor expression in vessels, Fuhrman tumor grade, and Ki-67 (P &lt; 0.05 for each). Higher levels of Ki-67 and CD31 were associated with delayed progression (P &lt; 0.05). Multiple samples (n = 5) from the same tumor showed marked heterogeneity of tumor grade, which increased significantly with treatment. Array CGH showed extensive intrapatient variability, which did not occur in DNA methylation analysis.
Conclusion: TKI treatment is associated with dynamic changes in relevant biomarkers, despite significant heterogeneity in chromosomal and protein, but not epigenetic expression. Changes to Ki-67 expression and tumor grade indicate that treatment is associated with an increase in the aggressive phenotype of the tumor. Clin Cancer Res; 19(24); 6924–34. ©2013 AACR.
IGFBP2/FAK Pathway Is Causally Associated with Dasatinib Resistance in Non–Small Cell Lung Cancer Cells
Authors: Lu Haibo , Wang Li , Gao Wen , Meng Jieru , Dai Bingbing , Wu Shuhong , Minna John , Roth Jack A. , Hofstetter Wayne L. , Swisher Stephen G. , Fang Bingliang 
Published: October 2013

Abstract
Insulin-like growth factor (IGF)-binding protein-2 (IGFBP2) expression is increased in various types of cancers, including in a subset of patients with lung cancer. Because IGFBP2 is involved in signal transduction of some critical cancer-related pathways, we analyzed the association between IGFBP2 and response to pathway-targeted agents in seven human non–small cell lung cancer (NSCLC) cell lines. Western blot analysis and ELISA showed that four of the seven NSCLC cell lines analyzed expressed high levels of IGFBP2, whereas the remaining three had barely detectable IGFBP2. Susceptibilities of those seven cell lines to nine anticancer agents targeting to IGF1R, Src, FAK, MEK, and AKT were determined by a dose-dependent cell viability assay. The results showed that high IGFBP2 levels were associated with resistance to dasatinib and, to a lesser degree, to sacaratinib, but not to other agents. Ectopic IGFBP2 overexpression or knockdown revealed that changing IGFBP2 expression levels reversed dasatinib susceptibility phenotype, suggesting a causal relationship between IGFBP2 expression and dasatinib resistance. Molecular characterization revealed that focal adhesion kinase (FAK) activation was associated with increased IGFBP2 expression and partially contributed to IGFBP2-mediated dasatinib resistance. Treatment with a combination of dasatinib and FAK inhibitor led to enhanced antitumor activity in IGFBP2-overexpressing and dasatinib-resistant NSCLC cells in vitro and in vivo. Our results showed that the IGFBP2/FAK pathway is causally associated with dasatinib resistance and may be used as biomarkers for identification of dasatinib responders among patients with lung cancer. Simultaneous targeting on Src and FAK will likely improve the therapeutic efficacy of dasatinib for treatment of lung cancer. Mol Cancer Ther; 12(12); 2864–73. ©2013 AACR.
Cytoreductive Chemotherapy Improves the Biodistribution of Antibodies Directed against Tumor Necrosis in Murine Solid Tumor Models
Authors: Jang Julie K. , Khawli Leslie A. , Park Ryan , Wu Brian W. , Li Zibo , Canter David , Conti Peter S. , Epstein Alan L. 
Published: October 2013

AbstractCurrent strategies in cancer treatment employ combinations of different treatment modalities, which include chemotherapy, radiotherapy, immunotherapy, and surgery. Consistent with that approach, the present study demonstrates how chemotherapeutic agents can potentiate the delivery of radiolabeled, necrosis-targeting antibodies (chTNT-3, NHS76) to tumor. All chemotherapeutics in this study (5-fluorouracil, etoposide, vinblastine, paclitaxel, and doxorubicin) resulted in statistically significant increases in tumor uptake of radiolabeled antibodies and their F(ab')2 fragments compared to no pretreatment with chemotherapy. Labeled antibodies were administered at various time points following a single dose of chemotherapy in multiple tumor models, and the biodistribution of the antibodies was determined by measuring radioactivity in harvested tissues. MicroPET/CT was also done to demonstrate clinical relevancy of using chemotherapy pretreatment to increase antibody uptake. Results of biodistribution and imaging data reveal specific time frames following chemotherapy when necrosis-targeting antibodies are best delivered, either for imaging or radiotherapy. Thus, the present work offers the prospect of using cytoreductive chemotherapy to increase tumor accumulation of select therapeutic antibodies, especially when combined with other forms of immunotherapy, for the successful treatment of solid tumors. Mol Cancer Ther; 12(12); 2827–36. ©2013 AACR.
Differential and Common DNA Repair Pathways for Topoisomerase I- and II-Targeted Drugs in a Genetic DT40 Repair Cell Screen Panel
Authors: Maede Yuko , Shimizu Hiroyasu , Fukushima Toru , Kogame Toshiaki , Nakamura Terukazu , Miki Tsuneharu , Takeda Shunichi , Pommier Yves , Murai Junko 
Published: October 2013

Abstract
Clinical topoisomerase I (Top1) and II (Top2) inhibitors trap topoisomerases on DNA, thereby inducing protein-linked DNA breaks. Cancer cells resist the drugs by removing topoisomerase-DNA complexes, and repairing the drug-induced DNA double-strand breaks (DSB) by homologous recombination and nonhomologous end joining (NHEJ). Because numerous enzymes and cofactors are involved in the removal of the topoisomerase-DNA complexes and DSB repair, it has been challenging to comprehensively analyze the relative contribution of multiple genetic pathways in vertebrate cells. Comprehending the relative contribution of individual repair factors would give insights into the lesions induced by the inhibitors and genetic determinants of response. Ultimately, this information would be useful to target specific pathways to augment the therapeutic activity of topoisomerase inhibitors. To this end, we put together 48 isogenic DT40 mutant cells deficient in DNA repair and generated one cell line deficient in autophagy (ATG5). Sensitivity profiles were established for three clinically relevant Top1 inhibitors (camptothecin and the indenoisoquinolines LMP400 and LMP776) and three Top2 inhibitors (etoposide, doxorubicin, and ICRF-193). Highly significant correlations were found among Top1 inhibitors as well as Top2 inhibitors, whereas the profiles of Top1 inhibitors were different from those of Top2 inhibitors. Most distinct repair pathways between Top1 and Top2 inhibitors include NHEJ, TDP1, TDP2, PARP1, and Fanconi Anemia genes, whereas homologous recombination seems relevant especially for Top1 and, to a lesser extent, for Top2 inhibitors. We also found and discuss differential pathways among Top1 inhibitors and Top2 inhibitors. Mol Cancer Ther; 13(1); 214–20. ©2013 AACR.
Black Raspberries Protectively Regulate Methylation of Wnt Pathway Genes in Precancerous Colon Tissue
Authors: Wang Li-Shu , Kuo Chieh-Ti , Huang Tim H.-M. , Yearsley Martha , Oshima Kiyoko , Stoner Gary D. , Yu Jianhua , Lechner John F. , Huang Yi-Wen 
Published: October 2013

Abstract
Ulcerative colitis is frequently an intermediate step to colon cancer. The interleukin-10 knockout mouse is a genetic model of this progression. We report that knockout mice fed 5% black raspberries (BRB) had significantly less colonic ulceration as compared with knockout mice that consumed the control diet. Dysfunction of the Wnt signaling pathway is a key event in ulcerative colitis–associated colon carcinogenesis. Therefore, we investigated the effects of BRBs on the Wnt pathway and found that the BRB-fed knockout mice exhibited a significantly lower level of β-catenin nuclear translocation. We followed-up this observation by evaluating the effect of BRBs on selected Wnt pathway antagonists. The mRNA expression levels of wif1, sox17, and qki were diminished in the knockout mice, whereas they were expressed at normal levels in knockout mice that were fed BRBs. The lower mRNA expression of these genes in the colon from the knockout mice correlated with hypermethylation of their promoter regions; BRBs decreased their promoter methylation and increased mRNA expression of these genes. This hypomethylation was associated with elevated protein expression of key proteins/enzymes that augment methylation, for example, dnmt3b, hdac1, hdac2, and mbd2 in the knockout mice; in addition, BRBs decreased the protein expression of these proteins/enzymes. The knockout mouse model recapitulates what occurs in human ulcerative colitis. Promoter methylation of CDH1 and SFRP1 was significantly higher in human ulcerative colitis tissues compared with their adjacent normal tissues. In conclusion, our results suggest that BRBs inhibit colonic ulceration and, ultimately, colon cancer partly through inhibiting aberrant epigenetic events that dysregulate Wnt signaling. Cancer Prev Res; 6(12); 1317–27. ©2013 AACR.
Pilot Study on the Impact of Evidence-Based Data on Oncology Pharmacists’ Perceptions
Authors: Renet Sophie , Lebel Denis , Prot-Labarthe Sonia , Therrien Roxane , Bourdon Olivier , Bussières Jean-François 
Published: October 2013

Objectives: The main objective was to evaluate whether the level of agreement of oncology hospital pharmacists with statements on their impact is influenced by the presence or absence of evidence-based data. The secondary objective was to evaluate the relative importance of evidence-based data among factors that may have contributed to oncology pharmacy practice evolution. Methods: Oncology pharmacists’ answered a Web questionnaire to measure their level of agreement with statements regarding their impact. Respondents answered the questionnaire before (pre) and after (post) being informed whether supporting evidence was available for each statement. Respondents were also asked to rank all of the factors in order of their perceived contribution to oncology pharmacy practice evolution. Results: A total of 64 questionnaires were obtained. Respondents reported a high level of agreement with statements regarding their impact on oncology pharmacy practice (mean agreement of 95.9% pre vs 93.8% post). A statistically significant diminution in the level of agreement was observed for 3 statements after respondents were informed that no supporting evidence was available for these statements. Respondents assigned a high importance to factors related to the perception of positive outcomes of pharmaceutical activities on patient safety, health care costs, and clinical results but a low importance to the use of evidence-based data.
Acrolein exposure suppresses antigen-induced pulmonary inflammation
Authors: Spiess Page C , Kasahara David , Habibovic Aida , Hristova Milena , Randall Matthew J , Poynter Matthew E , van der Vliet Albert 
Published: October 2013

AbstractBackgroundAdverse health effects of tobacco smoke arise partly from its influence on innate and adaptive immune responses, leading to impaired innate immunity and host defense. The impact of smoking on allergic asthma remains unclear, with various reports demonstrating that cigarette smoke enhances asthma development but can also suppress allergic airway inflammation. Based on our previous findings that immunosuppressive effects of smoking may be largely attributed to one of its main reactive electrophiles, acrolein, we explored the impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic asthma.MethodsC57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7, and challenged with aerosolized OVA on days 14–16. In some cases, mice were also exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14–17. Lung tissues or brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were measured in BALF, and lung tissue samples were collected for analysis of mucus and Th1/Th2 cytokine expression, determination of protein alkylation, cellular thiol status and transcription factor activity.ResultsExposure to acrolein following OVA challenge of OVA-sensitized mice resulted in markedly attenuated allergic airway inflammation, demonstrated by decreased inflammatory cell infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2 pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and induction of Nrf2-target genes such as HO-1. Additionally, analysis of inflammatory signaling pathways showed suppressed activation of NF-κB and marginally reduced activation of JNK in acrolein-exposed lungs, associated with increased carbonylation of RelA and JNK.ConclusionAcrolein inhalation suppresses Th2-driven allergic inflammation in sensitized animals, due to direct protein alkylation resulting in activation of Nrf2 and anti-inflammatory gene expression, and inhibition of NF-κB or JNK signaling. Our findings help explain the paradoxical anti-inflammatory effects of cigarette smoke exposure in allergic airways disease.
Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology
Authors: Staneva Rada , Rukova Blaga , Hadjidekova Savina , Nesheva Desislava , Antonova Olga , Dimitrov Plamen , Simeonov Valeri , Stamenov Georgi , Cukuranovic Rade , Cukuranovic Jovana , Stefanovic Vladislav , Polenakovic Momir , Dimova Ivanka , Hlushchuk Ruslan , Djonov Valentin , Galabov Angel , Toncheva Draga 
Published: October 2013

Abstract

Background
Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries.
DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood.

Methods
We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions.

Results
Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles.

SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders.

Conclusion
Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.