bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifetime risk of developing coronary heart disease in Aboriginal Australians: a cohort study
Authors: Wang Zhiqiang , Hoy Wendy E 
Published: February 2013

ObjectivesLifetime risk of coronary heart disease (CHD) is an important yardstick by which policy makers, clinicians and the general public can assess and promote the awareness and prevention of CHD. The lifetime risk in Aboriginal people is not known. Using a cohort with up to 20 years of follow-up, we estimated the lifetime risk of CHD in Aboriginal people.DesignA cohort study.SettingA remote Aboriginal region.Participants1115 Aboriginal people from one remote tribal group who were free from CHD at baseline were followed for up to 20 years.Main outcome measuresDuring the follow-up period, new CHD incident cases were identified through hospital and death records. We estimated the lifetime risks of CHD with and without adjusting for the presence of competing risk of death from non-CHD causes.ResultsParticipants were followed up for 17 126 person-years, during which 185 developed CHD and 144 died from non-CHD causes. The average age at which the first CHD event occurred was 48 years for men and 49 years for women. The risk of developing CHD increased with age until 60 years and then decreased with age. Lifetime cumulative risk without adjusting for competing risk was 70.7% for men and 63.8% for women. Adjusting for the presence of competing risk of death from non-CHD causes, the lifetime risk of CHD was 52.6% for men and 49.2% for women.ConclusionsLifetime risk of CHD is as high as one in two in both Aboriginal men and women. The average age of having first CHD events was under 50 years, much younger than that reported in non-Aboriginal populations. Our data provide useful knowledge for health education, screening and prevention of CHD in Aboriginal people.
Periostin expression correlates with pT-stage, grading and tumour size, and independently predicts cancer-specific survival in surgically treated penile squamous cell carcinomas
Authors: Gunia Sven , Jain Anjun , Koch Stefan , Denzinger Stefan , Götz Stefanie , Niessl Nina , May Matthias 
Published: February 2013

AimsOverexpression of periostin, a secreted cell adhesion molecule, has been reported to enhance invasion and angiogenesis in squamous cell carcinomas (SCCs) derived from different anatomic sites. We studied the so far neglected periostin expression profiles in penile SCCs and evaluated its association with pertinent clinicopathologic variables.MethodsParaffin-embedded tissues from 89 patients with surgically treated penile SCCs were subjected to a central histopathologic review performed by one pathologist. Then, tissue microarray technique was employed for periostin immunostaining which was evaluated by two independent raters. Kappa (κ)-statistics were used to assess interobserver variability. Spearman correlations as well as uni- and multivariable Cox proportional hazards analysis were applied to assess the association between periostin expression and clinicopathologic parameters. Mean postsurgical follow-up was 31.5 months (IQR 6–66).ResultsPeriostin expression was recorded in 39/89 penile SCCs (44%). K-statistics disclosed substantial interobserver agreement for epithelial and stromal staining evaluation (K-values 0.76 vs 0.83, p values <0.001). High periostin expression in either stroma or tumour epithelia showed a significant positive correlation with tumour size, histologic grade and pT-stage. In the multivariable Cox models including pT-stage, pN status, grading and the patients’ age at the time of surgery, periostin expression independently predicted cancer-specific survival (CSS).ConclusionsImmunohistochemically, periostin is not infrequently expressed in penile cancer, and might become a valuable tool to independently predict CSS after surgical treatment. Further studies should clarify the so far unresolved usefulness of periostin to be employed as a possible molecular target in antineoplastic therapy in metastasised penile SCCs.
Initial experience with the coaxial dual-lumen Scepter C balloon catheter for endovascular management of cerebral vasospasm from subarachnoid hemorrhage
Authors: John Seby , Spiotta Alejandro M , Turner Raymond M , Chaudry M Imran , Turk Aquilla S , Hui Ferdinand 
Published: February 2013

BackgroundPost-hemorrhagic cerebral vasospasm accounts for significant morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Intra-arterial therapies including vasodilator administration and/or balloon angioplasty are used when medical management fails. The Scepter C is a newer dual coaxial lumen temporary occlusion balloon catheter used for the treatment of post-hemorrhagic cerebral vasospasm.ObjectiveTo report our early experience with the use of Scepter C for the treatment of post-hemorrhagic cerebral vasospasm.MethodsWe reviewed cases from two institutions where the Scepter C balloon catheter was used for the treatment of cerebral vasospasm related to SAH.ResultsSeven patients were identified who underwent endovascular treatment with the Scepter C balloon catheter for treatment of SAH-related cerebral vasospasm. All patients had cerebral vasospasm that was refractory to medical management and it was technically feasible to use the catheter for this indication. Compared with larger double-lumen catheters, the Scepter C catheter was more trackable given the presence of a more steerable microwire. There were no complications or large vessel vasospasm recurrence after the procedure requiring repeat intra-arterial therapy.ConclusionsEndovascular treatment for post-hemorrhagic cerebral vasospasm is used when medical management fails or because of complications of medical therapies. With continuing advancements in the development of endovascular devices and techniques, more options are available for the management of cerebral vasospasm. Our initial experience with the dual coaxial lumen Scepter C occlusion balloon catheter demonstrates its feasibility in the treatment of cerebral vasospasm.
The rarity ofTrichomonas vaginalisin urban Australia
Authors: Bygott Jeanine M , Robson Jenny M 
Published: February 2013

ObjectivesInfection withTrichomonas vaginalishas declined dramatically in urban Australia but remains endemic in some predominantly indigenous rural regions. The objective was to determineT vaginalispositivity rates in clinical specimens by PCR detection, from a large community-based private pathology laboratory servicing rural and urban Australian populations.MethodsRetrospective analysis of data from 44 464 specimens referred forT vaginalisPCR testing over 8 years from 2004 to 2011.Results44 464 consecutive specimens (37 137 female, 7242 male, 85 sex-unspecified) were analysed:T vaginaliswas detected in 633 specimens. The overall communityT vaginalispositivity rate was 1.4% (95% CI 1.3% to 1.5%). Overall rates were 2.1-fold higher in women than in men (1.5% vs 0.7%). Positivity rates were highest in the 10–14 year age group (p<0.0001). Referrals from urban areas of South-East Queensland accounted for 52% of specimens (23 121): theT vaginalispositivity rate in this urban cohort was 0.7% (95% CI 0.6% to 0.8%). Referrals identified to be from indigenous patients accounted for 48% of positive cases (304/633), and came from predominantly rural and regional areas of northern Queensland. Where follow-up testing was available 21% of patients (14/66) remainedT vaginalisPCR positive when tested again within 3 months and 25% (26/101) within 6 months of the initial diagnosis.ConclusionsThis study confirms thatT vaginalisis rare in the urban non-indigenous Australian setting. Guidelines need to be developed to allow targeted testing. Follow-up testing 3 months after treatment should be considered.
A NEW CHARACTERIZATION OF PGL(2, p)
Authors: ASBOEI ALIREZA KHALILI 
Published: February 2013

Let G be a finite group and πe(G) be the set of element orders of G. Let k ∈ πe(G) and mk be the number of elements of order k in G. Set nse (G) ≔ {mk ∣ k ∈ πe(G)}. In this paper, it is proved if G is a group with the following properties, then G ≅ PGL (2, p). (1) p > 3 is prime divisor of ∣G∣ but p2 does not divide ∣G∣. (2) nse (G) = nse ( PGL (2, p)).
NUMERICAL SIMULATION AND PARAMETRIC STUDIES FOR EVALUATION OF BALANCED VENTILATION AND EARTH AIR EXCHANGERS SYSTEM COUPLED TO A DOMESTIC BUILDING
Authors: KARTACHI YOUNES , MECHAQRANE ABDELLAH 
Published: February 2013

In this study, we analyze the impact of ventilation heat recovery with the heating and cooling potential of earth air heat exchanger in real climatic conditions in domestic buildings in the Middle Atlas region. In our case study, we calculate the primary energy used by a domestic building built as per the conventional house design parameters required by the Moroccan regulation. We use climate data for the city of Fes in Northern Moroccan. Three system configurations were considered. The first was the mechanical extract ventilation system both with and without heat recovery. The second was the mechanical extract ventilation system with earth to air heat exchanger system (EAHEX), and the third system was the mechanical balanced ventilation system coupled with EAHEX system. Primary energy use strongly influences natural resources efficiency and the environmental impacts of energy supply activities. In this study we explore the primary energy implications of the mechanical balanced ventilation system coupled with the EAHEX system in residential buildings. The results of this study shows that the use of a balanced ventilation system, with a high efficiency instead of a mechanical extract ventilation system, decreases the final and primary energy consumption. Moreover, it decreases or increases the CO2 emission depending on the primary energy sources.
AMPK Activation by Oncogenesis Is Required to Maintain Cancer Cell Proliferation in Astrocytic Tumors
Authors: Ríos Marcos , Foretz Marc , Viollet Benoit , Prieto Angel , Fraga Máximo , Costoya Jose A. , Señarís Rosa 
Published: February 2013

Abstract
5′-AMP-activated protein kinase (AMPK) is an energy sensor that controls cell metabolism, and it has been related to apoptosis and cell-cycle arrest. Although its role in metabolic homeostasis is well documented, its function in cancer is much less clear. In this study, we examined the role of AMPK in a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We also evaluated the activity and role of AMPK in human glioblastoma cells and xenografts. AMPK was constitutively activated in astrocytes expressing oncogenic H-RasV12 in parallel with high cell division rates. Genetic deletion of AMPK or attenuation of its activity in these cells was sufficient to reduce cell proliferation. The levels of pAMK were always related to the levels of phosphorylated retinoblastoma (Rb) at Ser804, which may indicate an AMPK-mediated phosphorylation of Rb. We confirmed this AMPK–Rb relationship in human glioblastoma cell lines and xenografts. In clinical specimens of human glioblastoma, elevated levels of activated AMPK appeared especially in areas of high proliferation surrounding the blood vessels. Together, our findings indicate that the initiation and progression of astrocytic tumors relies upon AMPK-dependent control of the cell cycle, thereby identifying AMPK as a candidate therapeutic target in this setting. Cancer Res; 73(8); 2628–38. ©2013 AACR.
Oncogenic Activation of Pak1-Dependent Pathway of Macropinocytosis Determines BCG Entry into Bladder Cancer Cells
Authors: Redelman-Sidi Gil , Iyer Gopa , Solit David B. , Glickman Michael S. 
Published: February 2013

Abstract
Bacille Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that is used widely as a vaccine for tuberculosis and is used as an effective treatment for superficial bladder carcinoma. Despite being the most successful cancer biotherapy, its mechanism of action and response determinants remain obscure. Here, we establish a model system to analyze BCG interaction with bladder cancer cells, using it to show that these cells vary dramatically in their susceptibility to BCG infection. Unexpectedly, the uptake of BCG by bladder cancer cells occurs by macropinocytosis rather than phagocytosis. BCG entry into bladder cancer cells relied upon Rac1, Cdc42, and their effector kinase Pak1. The difference in susceptibility between BCG-permissive and -resistant bladder cancer cells was due to oncogenic activation of signaling pathways that activate macropinocytosis, with phosphoinositide 3-kinase inhibitor activation stimulating BCG uptake independently of Akt. Similarly, activated Ras strongly activated Pak1-dependent uptake of BCG. These results reveal that oncogenic activation of macropinocytosis determines BCG uptake by bladder cancer cells, implying that tumor responsiveness to BCG may be governed by the specific mutations present in the treated cancer cell. Cancer Res; 73(3); 1156–67. ©2013 AACR.
HDAC6 Inhibition Restores Ciliary Expression and Decreases Tumor Growth
Authors: Gradilone Sergio A. , Radtke Brynn N. , Bogert Pamela S. , Huang Bing Q. , Gajdos Gabriella B. , LaRusso Nicholas F. 
Published: February 2013

Abstract
Primary cilia are multisensory organelles recently found to be absent in some tumor cells, but the mechanisms of deciliation and the role of cilia in tumor biology remain unclear. Cholangiocytes, the epithelial cells lining the biliary tree, normally express primary cilia and their interaction with bile components regulates multiple processes, including proliferation and transport. Using cholangiocarcinoma as a model, we found that primary cilia are reduced in cholangiocarcinoma by a mechanism involving histone deacetylase 6 (HDAC6). The experimental deciliation of normal cholangiocyte cells increased the proliferation rate and induced anchorage-independent growth. Furthermore, deciliation induced the activation of mitogen-activated protein kinase and Hedgehog signaling, two important pathways involved in cholangiocarcinoma development. We found that HDAC6 is overexpressed in cholangiocarcinoma and overexpression of HDAC6 in normal cholangiocytes induced deciliation and increased both proliferation and anchorage-independent growth. To evaluate the effect of cilia restoration on tumor cells, we targeted HDAC6 by short hairpin RNA (shRNA) or by the pharmacologic inhibitor, tubastatin-A. Both approaches restored the expression of primary cilia in cholangiocarcinoma cell lines and decreased cell proliferation and anchorage-independent growth. The effects of tubastatin-A were abolished when cholangiocarcinoma cells were rendered unable to regenerate cilia by stable transfection of IFT88-shRNA. Finally, inhibition of HDAC6 by tubastatin-A also induced a significant decrease in tumor growth in a cholangiocarcinoma animal model. Our data support a key role for primary cilia in malignant transformation, provide a plausible mechanism for their involvement, and suggest that restoration of primary cilia in tumor cells by HDAC6 targeting may be a potential therapeutic approach for cholangiocarcinoma. Cancer Res; 73(7); 2259–70. ©2013 AACR.
Aire Deficiency Promotes TRP-1–Specific Immune Rejection of Melanoma
Authors: Zhu Meng-Lei , Nagavalli Anil , Su Maureen A. 
Published: February 2013

Abstract
The thymic transcription factor autoimmune regulator (Aire) prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1–specific T cells without affecting thymic numbers of regulatory T cells. Aire-deficient mice displayed elevated T-cell immune responses that were associated with suppression of melanoma outgrowth. Furthermore, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wild-type host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma and how manipulating TRP-1–specific T-cell negative selection may offer a logical strategy to enhance immune rejection of melanoma. Cancer Res; 73(7); 2104–16. ©2013 AACR.
The Ability of Plasma Cotinine to Predict Nicotine and Carcinogen Exposure is Altered by Differences in CYP2A6: the Influence of Genetics, Race, and Sex
Authors: Zhu Andy Z.X. , Renner Caroline C. , Hatsukami Dorothy K. , Swan Gary E. , Lerman Caryn , Benowitz Neal L. , Tyndale Rachel F. 
Published: February 2013

Abstract
Background: Cotinine, a nicotine metabolite, is a biomarker of tobacco, nicotine, and carcinogen exposure. However, a given cotinine level may not represent the same tobacco exposure; for example, African-Americans have higher cotinine levels than Caucasians after controlling for exposure.
Methods: Cotinine levels are determined by the amount of cotinine formation and the rate of cotinine removal, which are both mediated by the enzyme CYP2A6. Because CYP2A6 activity differs by sex (estrogen induces CYP2A6) and genotype, their effect on cotinine formation and removal was measured in nonsmoking Caucasians (Study 1, n = 181) infused with labeled nicotine and cotinine. The findings were then extended to ad libitum smokers (Study 2, n = 163).
Results: Study 1: Reduced CYP2A6 activity altered cotinine formation less than cotinine removal resulting in ratios of formation to removal of 1.31 and 1.12 in CYP2A6 reduced and normal metabolizers (P = 0.01), or 1.39 and 1.12 in males and females (P = 0.001), suggesting an overestimation of tobacco exposure in slower metabolizers. Study 2: Cotinine again overestimated tobacco and carcinogen exposure by 25% or more in CYP2A6 reduced metabolizers (≈2-fold between some genotypes) and in males.
Conclusions: In people with slower relative to faster CYP2A6 activity, cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure.
Impact: Cotinine levels may be misleading when comparing those with differing CYP2A6 genotypes within a race, between races with differing frequencies of CYP2A6 gene variants (i.e., African-Americans have higher frequencies of reduced function variants contributing to their higher cotinine levels), or between the sexes. Cancer Epidemiol Biomarkers Prev; 22(4); 708–18. ©2013 AACR.
Efficacy of Low-Dose Oral Metronomic Dosing of the Prodrug of Gemcitabine, LY2334737, in Human Tumor Xenografts
Authors: Pratt Susan E. , Durland–Busbice Sara , Shepard Robert L. , Donoho Gregory P. , Starling James J. , Wickremsinhe Enaksha R. , Perkins Everett J. , Dantzig Anne H. 
Published: February 2013

Abstract
LY2334737, an oral prodrug of gemcitabine, is cleaved in vivo, releasing gemcitabine and valproic acid. Oral dosing of mice results in absorption of intact prodrug with slow systemic hydrolysis yielding higher plasma levels of LY2334737 than gemcitabine and prolonged gemcitabine exposure. Antitumor activity was evaluated in human colon and lung tumor xenograft models. The dose response for efficacy was examined using 3 metronomic schedules, once-a-day dosing for 14 doses, every other day for 7 doses, and once a day for 7 doses, 7 days rest, followed by an additional 7 days of once-a-day dosing. These schedules gave significant antitumor activity and were well tolerated. Oral gavage of 6 mg/kg LY2334737 daily for 21 days gave equivalent activity to i.v. 240 mg/kg gemcitabine. HCl administered once a week for 3 weeks to mice bearing a patient mesothelioma tumor PXF 1118 or a non–small cell lung cancer tumor LXFE 937. The LXFE 397 tumor possessed elevated expression of the equilibrative nucleoside transporter-1 (ENT1) important for gemcitabine uptake but not prodrug uptake and responded significantly better to treatment with LY2334737 than gemcitabine (P ≤ 0.001). In 3 colon xenografts, antitumor activity of LY2334737 plus a maximally tolerated dose of capecitabine, an oral prodrug of 5-fluorouracil, was significantly greater than either monotherapy. During treatment, the expression of carboxylesterase 2 (CES2) and concentrative nucleoside transporter-3 was induced in HCT-116 tumors; both are needed for the activity of the prodrugs. Thus, metronomic oral low-dose LY2334737 is efficacious, well tolerated, and easily combined with capecitabine for improved efficacy. Elevated CES2 or ENT1 expression may enhance LY2334737 tumor response. Mol Cancer Ther; 12(4); 481–90. ©2013 AACR.
The HSP70 and Autophagy Inhibitor Pifithrin-μ Enhances the Antitumor Effects of TRAIL on Human Pancreatic Cancer
Authors: Monma Hiroyuki , Harashima Nanae , Inao Touko , Okano Shinji , Tajima Yoshitsugu , Harada Mamoru 
Published: February 2013

Abstract
TRAIL and agonistic death receptor-specific antibodies can induce apoptosis in cancer cells with little cytotoxicity to normal cells. To improve TRAIL-induced antitumor effects, we tested its effectiveness in combination with pifithrin (PFT)-μ, which has the potential to inhibit HSP70 function and autophagy, both of which participate in TRAIL resistance in cancer cells. Among the four human pancreatic cancer cell lines tested, MiaPaca-2, Panc-1, and BxPC-3 cells showed varying sensitivities to TRAIL. In MiaPaca-2 and Panc-1 cells, knockdown of HSP70 or beclin-1, the latter an autophagy-related molecule, by RNA interference augmented TRAIL-induced antitumor effects, decreasing cell viability, and increasing apoptosis. On the basis of these findings, we next determined whether the TRAIL-induced antitumor effects could be augmented by its combination with PFT-μ. The combination of TRAIL plus PFT-μ significantly decreased the viability and colony-forming ability of MiaPaca-2 and Panc-1 cells compared with cells treated with either agent alone. When applied alone, PFT-μ increased Annexin V+ cells in both caspase-dependent and -independent manners. It also promoted TRAIL-induced apoptosis and arrested cancer cell growth. Furthermore, PFT-μ antagonized TRAIL-associated NF-κB activation in cancer cells. In a xenograft mouse model, combination therapy significantly inhibited MiaPaca-2 tumor growth compared with treatment with either agent alone. The results of this study suggest protective roles for HSP70 and autophagy in TRAIL resistance in pancreatic cancer cells and suggest that PFT-μ is a promising agent for use in therapies intended to enhance the antitumor effects of TRAIL. Mol Cancer Ther; 12(4); 341–51. ©2013 AACR.