bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort
Authors: Pesch Beate , Gawrych Katarzyna , Rabstein Sylvia , Weiss Tobias , Casjens Swaantje , Rihs Hans-Peter , Ding Hui , Angerer Jürgen , Illig Thomas , Klopp Norman , Bueno-de-Mesquita Bas , Ros Martine M. , Kaaks Rudolf , Chang-Claude Jenny , Roswall Nina , Tjønneland Anne , Overvad Kim , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Dossus Laure , Boeing Heiner , Weikert Steffen , Trichopoulos Dimitrios , Palli Domenico , Sieri Sabina , Tumino Rosario , Panico Salvatore , Quirós José Ramón , González Carlos , Sánchez Mariá José , Dorronsoro Miren , Navarro Carmen , Barricarte Aurelio , Ljungberg Börje , Johansson Mattias , Ulmert David , Ehrnström Roy , Khaw Kay-Tee , Wareham Nick , Key Timothy J. , Ferrari Pietro , Romieu Isabelle , Riboli Elio , Brüning Thomas , Vineis Paolo 
Published: October 2013

AbstractBackground: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition.Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples.Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02–1.84, and OR = 1.50; 95% CI, 1.09–2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81–1.29).Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking.Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055–65. ©2013 AACR.
Randomized Controlled Trial of a Sun Protection Intervention for Children of Melanoma Survivors
Authors: Gritz Ellen R. , Tripp Mary K. , Peterson Susan K. , Prokhorov Alexander V. , Shete Sanjay S. , Urbauer Diana L. , Fellman Bryan M. , Lee Jeffrey E. , Gershenwald Jeffrey E. 
Published: October 2013

Abstract
Background: We studied whether a melanoma survivor–centered intervention was more effective than materials available to the general public in increasing children's sun protection.
Methods: In a randomized controlled trial, melanoma survivors (n = 340) who had a child ≤12 years received a targeted sun protection intervention (DVD and booklets) or standard education. Primary outcomes were children's sunburns, children's sun protection, and survivors' psychosocial factors at baseline and postintervention (1 and 4 months).
Results: The intervention increased children's sunscreen reapplication at 1 month (P = 0.002) and use of wide-brimmed hats at 4 months (P = 0.045). There were no effects on other behaviors or sunburns. The intervention improved survivors' hats/clothing self-efficacy at both follow-up assessments (P = 0.026, 0.009). At 4 months, the intervention improved survivors' clothing intentions (P = 0.029), knowledge (P = 0.010), and outcome expectations for hats (P = 0.002) and clothing (P = 0.037). Children's sun protection increased with survivors' intervention use. The intervention was less effective in survivors who were female or who had a family history, older children, or children with higher baseline sun protection scores.
Conclusions: A melanoma survivor–centered sun protection intervention can improve some child and survivor outcomes. The intervention may be more effective in survivors who have younger children or less experience with sun protection. Intervention delivery must be enhanced to maximize use.
Impact: This is the first study to examine a sun protection intervention for children of melanoma survivors. Findings will guide interventions for this important population at increased melanoma risk. Cancer Epidemiol Biomarkers Prev; 22(10); 1813–24. ©2013 AACR.
Plasma C-Peptide, Mammographic Breast Density, and Risk of Invasive Breast Cancer
Authors: Ahern Thomas P. , Hankinson Susan E. , Willett Walter C. , Pollak Michael N. , Eliassen A. Heather , Tamimi Rulla M. 
Published: October 2013

Abstract
Background: Insulin may promote breast cancer directly by stimulating the insulin receptor or indirectly by increasing the plasma concentration of active sex hormones. The association between insulin and breast density, a strong breast cancer risk factor, has not been thoroughly studied. We measured associations between c-peptide (a molar marker of insulin secretion), breast cancer risk, and breast density measurements in case–control studies nested within the Nurses' Health Study and Nurses' Health Study II cohorts.
Methods: Breast cancer associations were estimated with multivariate logistic regression models and then pooled across cohorts (total n = 1,084 cases and 1,785 controls). Mammographic density associations (percent dense area, dense area, and nondense area) were estimated as the difference in least-square means of the density parameters between quartiles of c-peptide concentration in all breast cancer controls with available screening mammography films (n = 1,469).
Results: After adjustment for adiposity, c-peptide was not associated with any measure of breast density. However, c-peptide was associated with an approximately 50% increased risk of invasive breast cancer [top vs. bottom quartile, adjusted OR = 1.5, 95% confidence interval (CI), 1.1–2.0] that was robust to adjustment for plasma-free estradiol and sex hormone–binding globulin. The association was stronger for ER-negative disease (adjusted OR = 2.0; 95% CI, 1.2–3.6).
Conclusions: Our data suggest a positive association between hyperinsulinemia and breast cancer risk that occurs through nonestrogenic mechanisms, and that is not mediated by breast density.
Impact: Primary prevention of breast cancer in women with hyperinsulinemia may be possible by targeting insulin signaling pathways. Cancer Epidemiol Biomarkers Prev; 22(10); 1786–96. ©2013 AACR.
Impact of Rural Residence on Forgoing Healthcare after Cancer Because of Cost
Authors: Palmer Nynikka R.A. , Geiger Ann M. , Lu Lingyi , Case L. Douglas , Weaver Kathryn E. 
Published: October 2013

Abstract
Background: Routine follow-up care is recommended to promote the well-being of cancer survivors, but financial difficulties may interfere. Rural–urban disparities in forgoing healthcare due to cost have been observed in the general population; however, it is unknown whether this disparity persists among survivors. The purpose of this study was to examine rural–urban disparities in forgoing healthcare after cancer due to cost.
Methods: We analyzed data from 7,804 cancer survivors in the 2006 to 2010 National Health Interview Survey. Logistic regression models, adjusting for sociodemographic and clinical characteristics, were used to assess rural–urban disparities in forgoing medical care, prescription medications, and dental care due to cost, stratified by age (younger: 18–64, older: 65+).
Results: Compared with urban survivors, younger rural survivors were more likely to forgo medical care (P &lt; 0.001) and prescription medications (P &lt; 0.001) due to cost; older rural survivors were more likely to forgo medical (P &lt; 0.001) and dental care (P = 0.05). Rural–urban disparities did not persist among younger survivors in adjusted analyses; however, older rural survivors remained more likely to forgo medical [OR = 1.66, 95% confidence interval (CI) = 1.11–2.48] and dental care (OR = 1.54, 95%CI = 1.08–2.20).
Conclusions: Adjustment for health insurance and other sociodemographic characteristics attenuates rural–urban disparities in forgoing healthcare among younger survivors, but not older survivors. Financial factors relating to healthcare use among rural survivors should be a topic of continued investigation.
Impact: Addressing out-of-pocket costs may be an important step in reducing rural–urban disparities in healthcare, especially for older survivors. It will be important to monitor how healthcare reform efforts impact disparities observed in this vulnerable population. Cancer Epidemiol Biomarkers Prev; 22(10); 1668–76. ©2013 AACR.
Seroepidemiology of High-Risk HPV in HIV-Negative and HIV-Infected MSM: The H2M Study
Authors: Mooij Sofie H. , van der Klis Fiona R.M. , van der Sande Marianne A.B. , Schepp Rutger M. , Speksnijder Arjen G.C.L. , Bogaards Johannes A. , de Melker Hester E. , de Vries Henry J.C. , Snijders Peter J.F. , van der Loeff Maarten F. Schim 
Published: October 2013

Abstract
Background: Men who have sex with men (MSM), in particular HIV-infected MSM, are at increased risk for diseases related to human papilloma virus (HPV). Our goal was to assess the effect of HIV status on the presence of type-specific antibodies against seven high-risk HPV types in HPV-unvaccinated MSM. Moreover, we compared determinants of HPV seropositivity between HIV-negative and HIV-infected MSM.
Methods: MSM ≥18 years of age were recruited from the Amsterdam Cohort Studies, a sexually transmitted infection clinic, and an HIV-treatment center in Amsterdam, the Netherlands. Participants completed a risk-factor questionnaire; serum samples were analyzed using a fluorescent bead-based multiplex assay.
Results: MSM (n = 795) were recruited in 2010 to 2011; 758 MSM were included in this analysis. Median age was 40.1 years (interquartile range 34.8–47.5) and 308 MSM (40.6%) were HIV-infected. Seroprevalence of HPV-16 was 37.1% in HIV-negative and 62.7% in HIV-infected MSM (P &lt; 0.001); seroprevalence of HPV-18 was 29.1% in HIV-negative MSM and 42.5% in HIV-infected MSM (P &lt; 0.001). Similar patterns of seroprevalence were observed for HPV types 31, 33, 45, 52, and 58. In multivariable analyses, HPV seropositivity was associated with HIV infection [adjusted OR = 2.1; 95% confidence interval, 1.6–2.6]. In multivariable analyses stratified by HIV status, increasing age and number of lifetime male sex partners were significantly associated with HPV seropositivity in HIV-negative, but not HIV-infected MSM.
Conclusions: Seroprevalence of high-risk HPV types is high among unvaccinated MSM.
Impact: HIV infection is a strong and independent determinant for HPV seropositivity, which we hypothesize is because of increased persistence of HPV infection in HIV-infected MSM. Cancer Epidemiol Biomarkers Prev; 22(10); 1698–708. ©2013 AACR.
The Impact of a Community-Based Clinical Trial Educational Intervention among Underrepresented Chinese Americans
Authors: Ma Grace X. , Tan Yin , Blakeney Natasha C. , Seals Brenda F. , Ma Xiang S. , Zhai Shumenghui , Liu Amy , Tai Yanfei , Michaels Margo 
Published: October 2013

Abstract
Background: Clinical trials are a critical resource for the discovery of new prevention, diagnostic, and treatment methods for cancer. The most effective prevention and treatment modalities are based on previous clinical trial results. However, participation in clinical trials is underrepresented by racial/ethnic minority populations, Asian Americans in particular. Asian Americans are the least represented of any ethnic groups in clinical trials. The purpose of this study is to develop and evaluate a culturally and linguistically appropriate community-based educational intervention to increase knowledge of and intent to participate in cancer clinical trials among underrepresented Chinese Americans.
Methods: Community-Based Participatory Research approach was used to guide the development, cultural tailoring, implementation, and evaluation of clinical trial intervention. First, 22 Asian community representatives were recruited as community health educators (CHE) who received 12-hour training on clinical trial education. Second, 262 members were recruited from 11 Chinese community organizations. Of those recruited, a total of 247 eligible Chinese enrolled and participated in the clinical trial education delivered by trained CHEs. Participants completed pretest before and posttest after the intervention.
Results: Fifteen of 21 measures of clinical trial knowledge showed significant changes post the intervention (P &lt; 0.05). Education remained the sole demographic factor increasing clinical trial knowledge in multivariate analysis.
Conclusion: Clinical trial education should emphasize both benefits to science and the larger Asian community. This community-based clinical trial intervention demonstrated promising results and has potential to enhance recruitment and participation in clinical trial research among the underrepresented Asian Americans.
Impact: Improving clinical trial participation in the fast-growing Asian American population is key to dissemination of health innovations targeted to diminish health disparities.
See all articles in this CEBP Focus section, “Community Network Program Centers.”
Cancer Epidemiol Biomarkers Prev; 23(3); 424–32. ©2013 AACR.
Target-Based Therapeutic Matching in Early-Phase Clinical Trials in Patients with Advanced Colorectal Cancer and PIK3CA Mutations
Authors: Ganesan Prasanth , Janku Filip , Naing Aung , Hong David S. , Tsimberidou Apostolia M. , Falchook Gerald S. , Wheler Jennifer J. , Piha-Paul Sarina A. , Fu Siqing , Stepanek Vanda M. , Lee J. Jack , Luthra Rajyalakshmi , Overman Michael J. , Kopetz E. Scott , Wolff Robert A. , Kurzrock Razelle 
Published: October 2013

Abstract
Target-matched treatment with PI3K/AKT/mTOR pathway inhibitors in patients with diverse advanced cancers with PIK3CA mutations have shown promise. Tumors from patients with colorectal cancer were analyzed for PIK3CA, KRAS, and BRAF mutations. PIK3CA-mutated tumors were treated, whenever feasible, with agents targeting the PI3K/AKT/mTOR pathway. Of 194 patients analyzed, 31 (16%) had PIK3CA mutations and 189 (97%) were assessed for KRAS mutations. Patients with PIK3CA mutations had a higher prevalence of simultaneous KRAS mutations than patients with wild-type PIK3CA (71%, 22/31 vs. 43%, 68/158; P = 0.006). Of 31 patients with PIK3CA mutations, 17 (55%) were treated with protocols containing PI3K/AKT/mTOR pathway inhibitors [median age, 57 years; median number of prior therapies, 4; mTORC1 inhibitors (11), phosphoinositide 3-kinase (PI3K) inhibitors (5), or an AKT inhibitor (1)]. None (0/17) had a partial or complete response (PR/CR) and only 1 [6%, 95% confidence interval (CI), 0.01–0.27] had stable disease 6 months or more, which was not significantly different from a stable disease ≥6 month/PR/CR rate of 16% (11/67; 95% CI, 0.09–0.27) in patients with colorectal cancer without PIK3CA mutations treated with PI3K/AKT/mTOR pathway inhibitors (P = 0.44). Median progression-free survival was 1.9 months (95% CI, 1.5–2.3). In conclusion, our data provide preliminary evidence that in heavily pretreated patients with PIK3CA-mutant advanced colorectal cancer, protocols incorporating PI3K/AKT/mTOR inhibitors have minimal activity. PIK3CA mutations are associated with simultaneous KRAS mutations, possibly accounting for therapeutic resistance. Mol Cancer Ther; 12(12); 2857–63. ©2013 AACR.
HDAC Inhibitor Entinostat Restores Responsiveness of Letrozole-Resistant MCF-7Ca Xenografts to Aromatase Inhibitors through Modulation of Her-2
Authors: Sabnis Gauri J. , Goloubeva Olga G. , Kazi Armina A. , Shah Preeti , Brodie Angela H. 
Published: October 2013

AbstractWe previously showed that in innately resistant tumors, silencing of the estrogen receptor (ER) could be reversed by treatment with a histone deacetylase (HDAC) inhibitor, entinostat. Tumors were then responsive to aromatase inhibitor (AI) letrozole. Here, we investigated whether ER in the acquired letrozole-resistant tumors could be restored with entinostat. Ovariectomized athymic mice were inoculated with MCF-7Ca cells, supplemented with androstenedione (Δ4A), the aromatizable substrate. When the tumors reached about 300 mm3, the mice were treated with letrozole. After initial response to letrozole, the tumors eventually became resistant (doubled their initial volume). The mice then were grouped to receive letrozole, exemestane (250 μg/d), entinostat (50 μg/d), or the combination of entinostat with letrozole or exemestane for 26 weeks. The growth rates of tumors of mice treated with the combination of entinostat with letrozole or exemestane were significantly slower than with the single agent (P &lt; 0.05). Analysis of the letrozole-resistant tumors showed entinostat increased ERα expression and aromatase activity but downregulated Her-2, p-Her-2, p-MAPK, and p-Akt. However, the mechanism of action of entinostat in reversing acquired resistance did not involve epigenetic silencing but rather included posttranslational as well as transcriptional modulation of Her-2. Entinostat treatment reduced the association of the Her-2 protein with HSP-90, possibly by reducing the stability of Her-2 protein. In addition, entinostat also reduced Her-2 mRNA levels and its stability. Our results suggest that the HDAC inhibitor may reverse letrozole resistance in cells and tumors by modulating Her-2 expression and activity. Mol Cancer Ther; 12(12); 2804–16. ©2013 AACR.
Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids
Authors: Camont Laurent , Lhomme Marie , Rached Fabiana , Le Goff Wilfried , Nègre-Salvayre Anne , Salvayre Robert , Calzada Catherine , Lagarde Michel , Chapman M. John , Kontush Anatol 
Published: October 2013

Objective—
High-density lipoprotein (HDL) displays multiple atheroprotective activities and is highly heterogeneous in structure, composition, and function; the molecular determinants of atheroprotective functions of HDL are incompletely understood. Because phospholipids represent a major bioactive lipid component of HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL subpopulations and related it to HDL functionality.

Approach and Results—
Using an original liquid chromatography–mass spectrometry/mass spectrometry methodology for phospholipid and sphingolipid profiling, 162 individual molecular lipid species were quantified across the 9 lipid subclasses, in the order of decreasing abundance, phosphatidylcholine>sphingomyelin>lysophosphatidylcholine>phosphatidylethanolamine>phosphatidylinositol>ceramide>phosphatidylserine>phosphatidylglycerol>phosphatidic acid. When data were expressed relative to total lipid, the contents of lysophosphatidylcholine and of negatively charged phosphatidylserine and phosphatidic acid increased progressively with increase in hydrated density of HDL, whereas the proportions of sphingomyelin and ceramide decreased. Key biological activities of HDL subpopulations, notably cholesterol efflux capacity from human THP-1 macrophages, antioxidative activity toward low-density lipoprotein oxidation, antithrombotic activity in human platelets, cell-free anti-inflammatory activity, and antiapoptotic activity in endothelial cells, were predominantly associated with small, dense, protein-rich HDL3. The biological activities of HDL particles were strongly intercorrelated, exhibiting significant correlations with multiple components of the HDL phosphosphingolipidome. Specifically, the content of phosphatidylserine revealed positive correlations with all metrics of HDL functionality, reflecting enrichment of phosphatidylserine in small, dense HDL3.

Conclusions—
Our structure–function analysis thereby reveals that the HDL lipidome may strongly affect atheroprotective functionality.
Transition of European Cooperative Acute Stroke Study III Results to Clinical Practice
Authors: Cronin Carolyn A. , Langenberg Patricia , Dutta Tara M. , Kittner Steven J. 
Published: October 2013

Background and Purpose—
The European Cooperative Acute Stroke Study (ECASS) III showed benefit of intravenous tissue-type plasminogen activator for acute ischemic stroke 3 to 4.5 hours from onset in selected patients from Europe, with this extended treatment subsequently recommended by the American Stroke Association. We prospectively enrolled patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator, during the time this recommendation was being applied in clinical practice to determine safety and efficacy in a representative cohort from the United States.

Methods—
Patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator were enrolled at 18 primary stroke centers throughout Maryland, including community hospitals and academic medical centers. Patients grouped by time to treatment (≤3 versus 3–4.5 hours) were compared for the presence of exclusion criteria from ECASS III that are not standard practice in the United States for ≤3 hours (age, >80 years; history of stroke and diabetes mellitus; oral anticoagulant treatment; and National Institutes of Health Stroke Scale, >25). Outcomes included good function at 90 days (modified Rankin Scale, 0–1 and 0–2), mortality, and symptomatic intracerebral hemorrhage.

Results—
In the 3- to 4.5-hour treatment group, there were significantly fewer patients aged >80 years and no patients with the combination of stroke and diabetes mellitus. There were no statistically significant differences by time to treatment in symptomatic intracerebral hemorrhage, mortality, or functional outcome.

Conclusions—
For patients treated with intravenous tissue-type plasminogen activator 3 to 4.5 hours from onset in everyday practice in the United States, there is no evidence for increased risk or worse outcomes compared with standard treatment ≤3 hours.