bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlations among PPAR, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
Authors: Pazienza Valerio , Tavano Francesca , Benegiamo Giorgia , Vinciguerra Manlio , Burbaci Francesca Paola , Copetti Massimiliano , di Mola Fabio Francesco , Andriulli Angelo , di Sebastiano Pierluigi
Published: August 2012

Emerging evidence indicates that peroxisome proliferator-activated receptorγ(PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPARγactivation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues (), whereas PPARγand DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPARγand DNMT1 and between DNMT1 and DNMT3B were highly correlated ( and resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading () and resection margin status (), and a borderline association with perineural invasion () was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population ( 95%–0.895, ) and in the subgroup of patients without perineural invasion (; 95%–0.758; ), while such association was not observed in patients with tumor invasion into perineural structures (). In conclusion,in vitroandin vivoPPARγand DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.
Convergence of Implicit and Explicit Schemes for an Asymptotically Nonexpansive Mapping in q‐Uniformly Smooth and Strictly Convex Banach Spaces
Authors: Wen Meng , Hu Changsong , Wu Zhiyu
Published: August 2012

We introduce a new iterative scheme with Meir‐Keeler contractions for an asymptotically nonexpansive mapping in q‐uniformly smooth and strictly convex Banach spaces. We also proved the strong convergence theorems of implicit and explicit schemes. The results obtained in this paper extend and improve many recent ones announced by many others.
Hantavirus Regulation of Type I Interferon Responses
Authors: Matthys Valery , Mackow Erich R.
Published: August 2012

Hantaviruses primarily infect human endothelial cells (ECs) and cause two highly lethal human diseases. Early addition of Type I interferon (IFN) to ECs blocks hantavirus replication and thus for hantaviruses to be pathogenic they need to prevent early interferon induction. PHV replication is blocked in human ECs, but not inhibited in IFN deficient VeroE6 cells and consistent with this, infecting ECs with PHV results in the early induction of IFNβand an array of interferon stimulated genes (ISGs). In contrast, ANDV, HTNV, NY-1V and TULV hantaviruses, inhibit early ISG induction and successfully replicate within human ECs. Hantavirus inhibition of IFN responses has been attributed to several viral proteins including regulation by the Gn proteins cytoplasmic tail (Gn-T). The Gn-T interferes with the formation of STING-TBK1-TRAF3 complexes required for IRF3 activation and IFN induction, while the PHV Gn-T fails to alter this complex or regulate IFN induction. These findings indicate that interfering with early IFN induction is necessary for hantaviruses to replicate in human ECs, and suggest that additional determinants are required for hantaviruses to be pathogenic. The mechanism by which Gn-Ts disrupt IFN signaling is likely to reveal potential therapeutic interventions and suggest protein targets for attenuating hantaviruses.
The Sensitivity Analysis of a Lake Ecosystem with the Conditional Nonlinear Optimal Perturbation Method
Authors: Wang Bo , Zhang Peijun , Huo Zhenhua , Qi Qianqian
Published: August 2012

The instability and sensitivity of a lake ecosystem to the finite-amplitude perturbations related to the initial condition and the parameter correspondingly are studied. The CNOP-I and CNOP-P methods are adopted to investigate this nonlinear system. The numerical results with CNOP-I method show that the lake ecosystem can be nonlinearly unstable with finite-amplitude initial perturbations when the nutrient loading rate is between the two bifurcation points. A large enough finite amplitude initial perturbation, that is, CNOP-I, can induce a transition from an oligotrophic (eutrophic) state to an eutrophic (oligotrophic) state. With CNOP-P method, it is shown that the lake ecosystem can be transformed from an oligotrophic (eutrophic) state to an eutrophic (oligotrophic) state with a large enough finite amplitude parameter perturbation, that is, CNOP-P, no matter how large the nutrient loading rate is.
Evaluating Safer Conception Options for HIV-Serodiscordant Couples (HIV-Infected Female/HIV-Uninfected Male): A Closer Look at Vaginal Insemination
Authors: Mmeje Okeoma , Cohen Craig R. , Cohan Deborah
Published: August 2012

HIV serodiscordant couples represent at least half of all HIV-affected couples worldwide. Many of these couples have childbearing desires. Safer methods of conception may allow for pregnancy while minimizing the risk of sexual transmission of HIV. In serodiscordant partnerships with an HIV-infected female and HIV-uninfected male, vaginal insemination of a partner's semen during the fertile period coupled with 100% condom use may be the safest method of conception.
The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma
Authors: Burbelo Peter D. , Kovacs Joseph A. , Wagner Jason , Bayat Ahmad , Rhodes Craig S. , De Souza Yvonne , Greenspan John S. , Iadarola Michael J.
Published: August 2012

Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP), Kaposi's sarcoma (KS), or non-Hodgkin lymphoma (NHL). Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84%) showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94%) in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.
The Insulin and IGF-I Pathway in Endocrine Glands Carcinogenesis
Authors: Malaguarnera Roberta , Morcavallo Alaide , Belfiore Antonino
Published: August 2012

Endocrine cancers are a heterogeneous group of diseases that may arise from endocrine cells in any gland of the endocrine system. These malignancies may show an aggressive behavior and resistance to the common anticancer therapies. The etiopathogenesis of these tumors remains mostly unknown. The normal embryological development and differentiation of several endocrine glands are regulated by specific pituitary tropins, which, in adult life, control the function and trophism of the endocrine gland. Pituitary tropins act in concert with peptide growth factors, including the insulin-like growth factors (IGFs), which are considered key regulators of cell growth, proliferation, and apoptosis. While pituitary TSH is regarded as tumor-promoting factor for metastatic thyroid cancer, the role of other pituitary hormones in endocrine cancers is uncertain. However, multiple molecular abnormalities of the IGF system frequently occur in endocrine cancers and may have a role in tumorigenesis as well as in tumor progression and resistance to therapies. Herein, we will review studies indicating a role of IGF system dysregulation in endocrine cancers and will discuss the possible implications of these findings for tumor prevention and treatment, with a major focus on cancers from the thyroid, adrenal, and ovary, which are the most extensively studied.
Optimality Conditions for Infinite Order Distributed Parabolic Systems with Multiple Time Delays Given in Integral Form
Authors: G. M. Bahaa
Published: August 2012

The optimal boundary control problem for (n × n) infinite order distributed parabolic systems with multiple time delays given in the integral form both in the state equations and in the Neumann boundary conditions is considered. Constraints on controls are imposed. Necessary and suffacient optimality conditions for the Neumann problem with the quadratic performance functional are derived.
Successful Treatment of Hemifacial Myokymia and Dystonia Associated to Linear Scleroderma “En Coup de Sabre” with Repeated Botox Injections
Authors: Cañas Carlos A. , Orozco Jorge L. , Paredes Andrea Caicedo , Bonilla-Abadía Fabio
Published: August 2012

Linear scleroderma “en coup de sabre” (LSCS) is a form of localized scleroderma presents as band-like sclerotic lesions of the frontoparietal area. It has been reported in association with diverse neurological manifestations like seizures, migraine, neuromyotonia, dystonia and abnormalities in MRI and CT studies as cerebral atrophy, white matter lesions, intraparenchymal calcification, meningeocortical alterations, and skull atrophy. We describe a patient with LSCS associated with two abnormal movements: permanent myokimia of right masseter muscle and recurrent spasmodic retraction of right cigomatic and depressor labii inferioris muscles. He was initially treated with methotrexate and steroids without response, so later on he underwent repeated Botox injections with remarkable improvement.
Positive Solutions for (k,n−k) Conjugate Multipoint Boundary Value Problems in Banach Spaces
Authors: Zhao Yulin
Published: August 2012

By means of the fixed point index theory of strict-set contraction operator, we study the existence of positive solutions for the multipoint singular boundary value problem(-1)n-kun(t)=f(t,ut),0<t<1,n≥2,1≤k≤n-1,u(0)=∑i=1m-2‍aiu(ξi),u(i)(0)=u(j)(1)=θ,1≤i≤k−1,0≤j≤n−k−1in a real Banach spaceE, whereθis the zero element ofE,0<ξ1<ξ2<⋯<ξm-2<1,ai∈[0,+∞),i=1,2,…,m-2.As an application, we give two examples to demonstrate our results.
Receiver Design for Time-Based Ranging with IEEE 802.11b Signals
Authors: Exel Reinhard
Published: August 2012

This paper presents a ranging receiver architecture able to timestamp IEEE 802.11b Wireless LAN signals with sub-100 picosecond precision enabling time-based range measurements. Starting from the signal model, the performance of the proposed architecture is assessed in terms of statistical bounds when perturbed by zero-mean additive white Gaussian noise (AWGN) as well as in case of multipath propagation. Results of the proposed architecture, implemented in a Field Programmable Gate Array-(FPGA-) based prototype, are presented for different environments. For AWGN channels, the prototype system is able to attain an accuracy of 1.2 cm while the ranging accuracy degrades in dynamic multipath scenarios to about 0.6 m for 80% of the measurements due to the limited bandwidth of the signal.
N Point DCT VLSI Architecture for Emerging HEVC Standard
Authors: Ahmed Ashfaq , Shahid Muhammad Usman , Rehman Ata ur
Published: August 2012

This work presents a flexible VLSI architecture to compute the N‐point DCT. Since HEVC supports different block sizes for the computation of the DCT, that is, 4 × 4 up to 32 × 32, the design of a flexible architecture to support them helps reducing the area overhead of hardware implementations. The hardware proposed in this work is partially folded to save area and to get speed for large video sequences sizes. The proposed architecture relies on the decomposition of the DCT matrices into sparse submatrices in order to reduce the multiplications. Finally, multiplications are completely eliminated using the lifting scheme. The proposed architecture sustains real‐time processing of 1080P HD video codec running at 150 MHz.
Cardiomyopathy Classification: Ongoing Debate in the Genomics Era
Authors: McCartan Charles , Mason Robert , Jayasinghe S. R. , Griffiths Lyn R.
Published: August 2012

Cardiomyopathies represent a group of diseases of the myocardium of the heart and include diseases both primarily of the cardiac muscle and systemic diseases leading to adverse effects on the heart muscle size, shape, and function. Traditionally cardiomyopathies were defined according to phenotypical appearance. Now, as our understanding of the pathophysiology of the different entities classified under each of the different phenotypes improves and our knowledge of the molecular and genetic basis for these entities progresses, the traditional classifications seem oversimplistic and do not reflect current understanding of this myriad of diseases and disease processes. Although our knowledge of the exact basis of many of the disease processes of cardiomyopathies is still in its infancy, it is important to have a classification system that has the ability to incorporate the coming tide of molecular and genetic information. This paper discusses how the traditional classification of cardiomyopathies based on morphology has evolved due to rapid advances in our understanding of the genetic and molecular basis for many of these clinical entities.
WNT10B Polymorphism in Korean Stroke Patients with Yin Deficiency Pattern
Authors: Ko Mi Mi , Park Tae-Yong , Lim Ji Hye , Cha Min Ho , Lee Myeong Soo
Published: August 2012

WNT10B has been indicated as a potential regulator of adipogenesisin vivoandin vitromodels of obesity. In this study, we analyzed the distribution of WNT10B polymorphism in elderly Korean subjects with cerebral infarction (CI) and Yin Deficiency pattern and Non-Yin Deficiency pattern. A total of 630 CI patients, including 75 with Yin Deficiency pattern and 555 with Non-Yin Deficiency pattern, participated in this study. SNP (G-607C) genotyping was conducted by primer extension using TaqMan probe; five percent of subjects were regenotyped by direct sequencing to confirm the accuracy of the genotyping. The results were analyzed using a multiple logistic regression model to evaluate the genetic association between the G-607C variant and Yin Deficiency pattern. The frequency of the CC genotype of G-607C in the Yin Deficiency pattern group (29.33%) was significantly higher than that in the Non-Yin Deficiency pattern group (23.96%) (P=0.0339,OR=2.005(1.054–3.814)) in a recessive model. This is the first study to demonstrate an association between a WNT10B polymorphism and the Yin Deficiency pattern of traditional Korean medicine (TKM) in a CI patient population. These results suggest that G-607C might be used as a diagnostic genetic marker for Yin Deficiency pattern in stroke patients and in the development of personalized medical care.
Evaluating the Performance of Taiwan Homestay Using Analytic Network Process
Authors: Hu Yi-Chung , Wang Jen-Hung , Wang Ru-Yu
Published: August 2012

Homestay industry in Taiwan is not only thriving, but also its operation is moving gradually toward elaboration strategy and in a specialized‐operation manner these years. Nevertheless, the evaluation frameworks of the earlier studies were sporadically constructed from an overall perspective of homestays. Moreover, the functions, operational model, and natures of homestays are dissimilar to those of hotels; therefore, if the evaluation criteria of homestays employ the ones of hotels, it would appear to be incoherent and incompatible. This study has accordingly developed and constructed a set of evaluation indicators tailor‐made for homestay sector through discussion of literatures and interviewing experts so that the evaluation framework would be more comprehensive and more practical. In the process of interviewing experts, it was discovered that dependences lay on the aspects and criteria. Consequently, this research chose the ANP (analytic network process) to get the weights and, further, to acquire the homestay business performance through fuzzy theory. The result reveals, as regards key aspects, homestay proprietors and customer groups both weight the surroundings of the building and features, service quality, operation, and management most. In respect to overall homestay performance, customer groups consider it has reached the satisfactory level.
The Structural Framework of the Erlangping Group in North Qinling, Central China
Authors: Zhang Hongyuan , Zhao Chunqiang , Xu Fanglei , Dong Yanlong
Published: August 2012

As one major unit of the North Qinling tectonic belt, and being located in the north side of the UHP belt between the Yangtze block and the North China block, the Erlangping Group has become one hot research spot because it still keeps records of both plate and inner-continent evolution histories. Three aspects of the Erlangping Group are reviewed. (1) Research history are concluded into three stages, including the determination of rock assemblages before the late 1980s, the regional metamorphism laws solution in the 1990s, and the formation time and tectonic background discussion in the 2000s. (2) Five major controversies and frontier scientific problems have been offered, such as, the deformation ages determination, the Cretaceous tectonic event definition, the determination of the deformation mechanisms and conditions, the kinematic and dynamic nature of the Zhuyangguan-Xiaguan shear zone, and the reconstruction of the evolution and exhumation history. (3) Structural framework of the Erlangping Group is divided into five parts according to our field and laboratory study, including the Erjingou slab, the Damiao-Wantan shear zone, the Huoshenmiao slab, the Xiaozhai-Erlangping shear zone, and the Baoshuping slab. Only the Xiaozhai-Erlangping shear zone has clear kinematic marks of left lateral slip.
The SS-SCR Scheme for Dynamic Spectrum Access
Authors: Thumar Vinay , Nadkar Taskeen , Desai U. B. , Merchant S. N.
Published: August 2012

We integrate the two models ofCognitive Radio (CR), namely, the conventionalSense-and-Scavenge (SS) Model and Symbiotic Cooperative Relaying (SCR). The resultant scheme, calledSS-SCR, improves the efficiency of spectrum usage and reliability of the transmission links.SS-SCRis enabled by a suitable cross-layer optimization problem in a multihop multichannel CR network. Its performance is compared for different PU activity patterns with those schemes which considerSSandSCRseparately and perform disjoint resource allocation. Simulation results depict the effectiveness of the proposedSS-SCRscheme. We also indicate the usefulness of cloud computing for a practical deployment of the scheme.
Development of a Control Banding Tool for Nanomaterials
Authors: Riediker M. , Ostiguy C. , Triolet J. , Troisfontaine P. , Vernez D. , Bourdel G. , Thieriet N. , Cadène A.
Published: August 2012

Control banding (CB) can be a useful tool for managing the potential risks of nanomaterials. The here proposed CB, which should be part of an overall risk control strategy, groups materials by hazard and emission potential. The resulting decision matrix proposes control bands adapted to the risk potential levels and helps define an action plan. If this plan is not practical and financially feasible, a full risk assessment is launched. The hazard banding combines key concepts of nanomaterial toxicology: translocation across biological barriers, fibrous nature, solubility, and reactivity. Already existing classifications specific to the nanomaterial can be used “as is.” Otherwise, the toxicity of bulk or analogous substances gives an initial hazard band, which is increased if the substance is not easily soluble or if it has a higher reactivity than the substance. The emission potential bands are defined by the nanomaterials′ physical form and process characteristics. Quantities, frequencies, and existing control measures are taken into account during the definition of the action plan. Control strategies range from room ventilation to full containment with expert advice. This CB approach, once validated, can be easily embedded in risk management systems. It allows integrating new toxicity data and needs no exposure data.
“Incidentaloma” of the Liver: Management of a Diagnostic and Therapeutic Dilemma
Authors: Ehrl Denis , Rothaug Katharina , Herzog Peter , Hofer Bernhard , Rau Horst-Günter
Published: August 2012

The continuous development of highly sensitive clinical imaging increased the detection of focal lesions of the liver. These accidentally detected liver tumors without liver-specific symptoms such as cholestasis have been named “incidentalomas.” Diagnostic tools such as sonography, computed tomography, or magnetic resonance imaging are used increasingly in asymptomatic individuals without defined suspected diagnoses in the setting of general prevention or followup after a history of malignancy. But despite continuous improvement of diagnostics, some doubt regarding the benign or malign behavior of a tumor remains. In case an asymptomatic hemangioma or FNH can be preoperatively detected with certainty, the indication for surgery must be very strict. In case of symptomatic liver lesions surgical resection should only be indicated with tumor-specific symptoms. In the remaining cases of benign lesions of the liver, a “watch and wait” strategy is recommended. In case of uncertain diagnosis, especially in patients with positive history of a malignant tumor or the suspected diagnosis of hepatocellular adenoma, surgical resection is indicated. Due to the continuous improvement of surgical techniques, liver resection should be done in the laparoscopic technique. Laparoscopic surgery has lower morbidity and shorter hospitalization than open technique.
Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection
Authors: Shenoy K. V. , Solomides C. , Cordova F. , Rogers T. J. , Ciccolella D. , Criner G. J.
Published: August 2012

Background. Bronchus-associated lymphoid tissue (BALT) has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection.Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT) criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations.Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate.Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection.
Device Characteristics and Capabilities Discovery for Multimedia Content
Authors: Ibrahim Mohd Faisal , Yahya Saadiah , Taib Mohd Nasir
Published: August 2012

The rapid growth of web and mobile technologies has allowed people to access multimedia content from a wide range of heterogeneous client devices that have different characteristics and capabilities. In order to deliver the best presentation of content requested, the web system must possess a mechanism that is able to accurately discover the characteristics and capabilities of a client’s device. Existing content negotiation techniques mainly focus on static profiling approach without considering the combination of static and dynamic approaches that are capable of overcoming the device scalability issues. In view of these issues, we propose a hybrid approach for recognizing devices and their capabilities using token-based method. By proposing such solution, we can provide flexible, extensible, and scalable method that provides more accurate information in resolving the content negotiation issues. To validate the effectiveness of the proposed method, we construct a laboratory and field studies to investigate its performance and accuracy. The experimental results show that the proposed hybrid approach has better performances in several aspects compared to the static profiling.
Simulation of Outer Rotor Permanent Magnet Brushless DC Motor Using Finite Element Method for Torque Improvement
Authors: Kumaravelu Uma Devi , Mohamed Yakub Sanavullah
Published: August 2012

A method of simulation and modeling outer rotor permanent magnet brushless DC (ORPMBLDC) motor under dynamic conditions using finite element method by FEMM 4.2 software package is presented. In the proposed simulation, the torque developed at various positions of the rotor, under a complete cycle of excitation of the stator, is analysed. A novel method of sinusoidal excitation is proposed to enhance the overall torque development of ORPMBLDC motor.
On Subspaces of an Almost -Lagrange Space
Authors: Pandey P. N. , Shukla Suresh K.
Published: August 2012

We discuss the subspaces of an almost -Lagrange space (APL space in short). We obtain the induced nonlinear connection, coefficients of coupling, coefficients of induced tangent and induced normal connections, the Gauss-Weingarten formulae, and the Gauss-Codazzi equations for a subspace of an APL-space. Some consequences of the Gauss-Weingarten formulae have also been discussed.
Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study
Authors: Hyde Zoë , Flicker Leon , McCaul Kieran A. , Almeida Osvaldo P. , Hankey Graeme J. , Chubb S.A. Paul , Yeap Bu B.
Published: August 2012

Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer.

Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010.

Results: During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00–1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21–1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53–5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers.

Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer.

Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy. Cancer Epidemiol Biomarkers Prev; 21(8); 1319–29. ©2012 AACR.
The Oncogenic Role of miR-155 in Breast Cancer
Authors: Mattiske Sam , Suetani Rachel J. , Neilsen Paul M. , Callen David F.
Published: August 2012

miR-155 is an oncogenic miRNA with well described roles in leukemia. However, additional roles of miR-155 in breast cancer progression have recently been described. A thorough literature search was conducted to review all published data to date, examining the role of miR-155 in breast cancer. Data on all validated miR-155 target genes was collated to identify biologic pathways relevant to miR-155 and breast cancer progression. Publications describing the clinical relevance, functional characterization, and regulation of expression of miR-155 in the context of breast cancer are reviewed. A total of 147 validated miR-155 target genes were identified from the literature. Pathway analysis of these genes identified likely roles in apoptosis, differentiation, angiogenesis, proliferation, and epithelial–mesenchymal transition. The large number of validated miR-155 targets presented here provide many avenues of interest as to the clinical potential of miR-155. Further investigation of these target genes will be required to elucidate the specific mechanisms and functions of miR-155 in breast cancer. This is the first review examining the role of miR-155 in breast cancer progression. The collated data of target genes and biologic pathways of miR-155 identified in this review suggest new avenues of research for this oncogenic miRNA. Cancer Epidemiol Biomarkers Prev; 21(8); 1236–43. ©2012 AACR.
Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project
Authors: Caan Bette J. , Kwan Marilyn L. , Shu Xiao Ou , Pierce John P. , Patterson Ruth E. , Nechuta Sarah J. , Poole Elizabeth M. , Kroenke Candyce H. , Weltzien Erin K. , Flatt Shirley W. , Quesenberry Charles P. , Holmes Michelle D. , Chen Wendy Y.
Published: August 2012

Background: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI).

Methods: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I–III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%–<10% and ≥10% loss and gain] with mortality were estimated using Cox proportional hazards models.

Results: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14–1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a nonsignificant increased risk of death.

Conclusions: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality.

Impact: Weight control strategies for breast cancer survivors should be personalized to the individual's medical history. Cancer Epidemiol Biomarkers Prev; 21(8); 1260–71. ©2012 AACR.
External Validation of Medicare Claims Codes for Digital Mammography and Computer-Aided Detection
Authors: Fenton Joshua J. , Zhu Weiwei , Balch Steven , Smith-Bindman Rebecca , Lindfors Karen K. , Hubbard Rebecca A.
Published: August 2012

Background: While Medicare claims are a potential resource for clinical mammography research or quality monitoring, the validity of key data elements remains uncertain. Claims codes for digital mammography and computer-aided detection (CAD), for example, have not been validated against a credible external reference standard.

Methods: We matched Medicare mammography claims for women who received bilateral mammograms from 2003 to 2006 to corresponding mammography data from the Breast Cancer Surveillance Consortium (BCSC) registries in four U.S. states (N = 253,727 mammograms received by 120,709 women). We assessed the accuracy of the claims-based classifications of bilateral mammograms as either digital versus film and CAD versus non-CAD relative to a reference standard derived from BCSC data.

Results: Claims data correctly classified the large majority of film and digital mammograms (97.2% and 97.3%, respectively), yielding excellent agreement beyond chance (κ = 0.90). Claims data correctly classified the large majority of CAD mammograms (96.6%) but a lower percentage of non-CAD mammograms (86.7%). Agreement beyond chance remained high for CAD classification (κ = 0.83). From 2003 to 2006, the predictive values of claims-based digital and CAD classifications increased as the sample prevalences of each technology increased.

Conclusion: Medicare claims data can accurately distinguish film and digital bilateral mammograms and mammograms conducted with and without CAD.

Impact: The validity of Medicare claims data regarding film versus digital mammography and CAD suggests that these data elements can be useful in research and quality improvement. Cancer Epidemiol Biomarkers Prev; 21(8); 1344–7. ©2012 AACR.
The Role of Obesity in Cancer Survival and Recurrence
Authors: Demark-Wahnefried Wendy , Platz Elizabeth A. , Ligibel Jennifer A. , Blair Cindy K. , Courneya Kerry S. , Meyerhardt Jeffrey A. , Ganz Patricia A. , Rock Cheryl L. , Schmitz Kathryn H. , Wadden Thomas , Philip Errol J. , Wolfe Bruce , Gapstur Susan M. , Ballard-Barbash Rachel , McTiernan Anne , Minasian Lori , Nebeling Linda , Goodwin Pamela J.
Published: August 2012

Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions. Cancer Epidemiol Biomarkers Prev; 21(8); 1244–59. ©2012 AACR.
Confirmation of the HOXB13 G84E Germline Mutation in Familial Prostate Cancer
Authors: Breyer Joan P. , Avritt T. Grant , McReynolds Kate M. , Dupont William D. , Smith Jeffrey R.
Published: August 2012

Background: A recent study of familial and early onset prostate cancer reported a recurrent rare germline mutation of HOXB13 among men of European descent. The gene resides within the 17q21 hereditary prostate cancer linkage interval.

Methods: We evaluated the G84E germline mutation (rs138213197) of HOXB13 in a case–control study of familial prostate cancer at Vanderbilt University (Nashville, TN) to independently evaluate the association of the mutation with familial prostate cancer. We genotyped 928 familial prostate cancer probands and 930 control probands without a personal or family history of prostate cancer.

Results: Our study confirmed the association between the G84E mutation of HOXB13 and risk of prostate cancer among subjects of European descent. We observed the mutation in 16 familial cases and in two controls, each as heterozygotes. The odds ratio (OR) for prostate cancer was 7.9 [95% confidence interval, (CI) 1.8–34.5, P = 0.0062] among carriers of the mutation. The carrier rate was 1.9% among all familial case probands and 2.7% among probands of pedigrees with ≥3 affected. In a separate case series of 268 probands of European descent with no additional family history of prostate cancer, the carrier rate was 1.5%.

Conclusions: The germline mutation G84E of HOXB13 is a rare but recurrent mutation associated with elevated risk of prostate cancer in men of European descent, with an effect size that is greater than observed for previously validated risk variants of genome wide association studies.

Impact: This study independently confirms the association of a germline HOXB13 mutation with familial prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(8); 1348–53. ©2012 AACR.
Common Genetic Variants in the MicroRNA Biogenesis Pathway Are Not Associated with Breast Cancer Risk in Asian Women
Authors: Sung Hyuna , Zhang Ben , Choi Ji-Yeob , Long Jirong , Park Sue K. , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Zheng Wei , Kang Daehee
Published: August 2012

Background: Although the role of miRNA in cancer development and progression has been well established, the association between genetic variants in miRNA biogenesis pathway genes and breast cancer risk has been yet unclear.

Methods: We analyzed data from two genome-wide association studies conducted in East Asian women including 5,066 cases and 4,337 controls. Among the single-nucleotide polymorphisms (SNP), which were directly genotyped or imputed, we selected 237 SNPs in 32 genes involved in miRNA biogenesis pathway and its regulation.

Results: Although eight SNPs were nominally associated with breast cancer risk in combined samples (P < 0.05), none of them were significant after adjustment for multiple comparisons.

Conclusions: The common genetic variants in miRNA biogenesis pathway genes may not be associated with breast cancer risk.

Impact: This study suggests no association between the polymorphisms in miRNA biogenesis pathway genes and breast cancer risk. Studies with large sample size and more genetic variants should be warranted to adequately evaluate the potential association. Cancer Epidemiol Biomarkers Prev; 21(8); 1385–7. ©2012 AACR.
Individual Patient-Specific Immunity against High-Grade Glioma after Vaccination with Autologous Tumor Derived Peptides Bound to the 96 KD Chaperone Protein
Authors: Crane Courtney A. , Han Seunggu J. , Ahn Brian , Oehlke Jessica , Kivett Valerie , Fedoroff Anne , Butowski Nicholas , Chang Susan M. , Clarke Jennifer , Berger Mitchel S. , McDermott Michael W. , Prados Michael D. , Parsa Andrew T.
Published: August 2012

Purpose: Cancer immunotherapy offers hope of a highly specific nontoxic adjuvant treatment. Heat shock protein peptide complexes (HSPPCs) found in cancer cells carry tumor-specific antigenic proteins and can facilitate adaptive and innate immune responses. Here we show that peptides bound to a 96 kD chaperone protein (HSP-96) from brain tissue containing glioblastoma multiforme (GBM) can be used to safely immunize patients with recurrent GBM.

Experimental Design: Multimodality immunomonitoring was completed on 12 patients with recurrent GBM before and after immunization with an autologous HSPPC vaccine derived from surgically resected tumor. Clinical endpoints included safety assessments and overall survival.

Results: No adverse events attributable to the vaccine were found. Testing of peripheral blood leukocytes before and after vaccination revealed a significant peripheral immune response specific for the peptides bound to HSP-96, in 11 of the 12 patients treated. Brain biopsies of immune responders after vaccination revealed focal CD4, CD8, and CD56 IFNγ positive cell infiltrates, consistent with tumor site specific immune responses. Immune responders had a median survival of 47 weeks after surgery and vaccination, compared with 16 weeks for the single nonresponder.

Conclusions: These data provide the first evidence in humans of individual patient-specific immune responses against autologous tumor derived peptides bound to HSP-96. Clin Cancer Res; 19(1); 205–14. ©2012 AACR.
Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy
Authors: Hu Lingmin , Wu Chen , Zhao Xueying , Heist Rebecca , Su Li , Zhao Yang , Han Baohui , Cao Songyu , Chu Minjie , Dai Juncheng , Dong Jing , Shu Yongqian , Xu Lin , Chen Yijiang , Wang Yi , Lu Feng , Jiang Yue , Yu Dianke , Chen Hongyan , Tan Wen , Ma Hongxia , Chen Jiaping , Jin Guangfu , Wu Tangchun , Lu Daru , Christiani David C. , Lin Dongxin , Hu Zhibin , Shen Hongbing
Published: August 2012

Purpose: Genetic variation may influence chemotherapy response and overall survival in cancer patients.

Experimental design: We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA).

Results: Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population.

Conclusion: In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients. Clin Cancer Res; 18(19); 5507–14. ©2012 AACR.
Occurrence of Septic Shock in a Patient Submitted to Emergency Cerclage following a Negative Amniocentesis: Report of a Case
Authors: Ghi T. , Bellussi F. , Curti A. , Youssef A. , Bianchi A. , De Eccher L. , Turchi G. , Rainaldi M.P. , De Iaco P. , Pilu G. , Rizzo N.
Published: August 2012

Background: Second trimester emergency cerclage is an option for pregnant women presenting bulging fetal membranes. Despite a significant prolongation of pregnancy might be achieved, serious fetal and maternal events have been reported. Exclusion of infections through preprocedure amniocentesis has been proposed. Methods: A 37-year-old woman, gravida 4 para 1, was admitted at 21 weeks of gestation to our University Hospital due to bulging fetal membranes. An amniocentesis was performed in order to exclude an actual amniotic infection. Our Microbiology Department found a negative amniotic culture for bacteria and Mycoplasma and a normal glucose and interleukin-6 level, so a cervical cerclage was performed. The patient was discharged home on oral erythromycin. Results: After 48 h, the patient complained of hyperpyrexia, shivers and reduced fetal movements. Ultrasound at admission showed absent cardiac activity and after cerclage removal a non-viable fetus was delivered vaginally. Piperacillin and tazobactam were started, but the clinical course of the patient deteriorated and she developed a cold septic shock and was submitted to hysterectomy and transferred to the ICU of our hospital. Conclusion: This report heralds that even after negative amniocentesis, a life-threatening infection may not be excluded in women candidate for emergency cerclage due to bulging fetal membranes.
Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change
Authors: Kidokoro Kengo , Satoh Minoru , Nagasu Hajime , Sakuta Takeo , Kuwabara Atsunori , Yorimitsu Daisuke , Nishi Yuko , Tomita Naruya , Sasaki Tamaki , Kashihara Naoki
Published: August 2012

Background/Aims: The immunosuppressive drug tacrolimus (FK506) is used clinically to reduce the rejection rate in patients with kidney transplantation; however, the resultant nephrotoxicity remains a serious problem. In the present study we attempted to elucidate the mechanisms of glomerular injury induced by FK506 and the renoprotective effects of the angiotensin II receptor blocker telmisartan. Methods: Seven-week-old male Wistar rats were divided into three groups: vehicle group, FK506 group, and FK506 + telmisartan group. After 8 weeks, we assessed kidney function and renal morphological changes including oxidative stress. We also assessed the effect of FK506 in human glomerular endothelial cells (hGECs) with regard to reactive oxygen species (ROS). Results: FK506 induced ROS production via activation of NAD(P)H oxidase in the glomeruli. Expression of ICAM mRNA was increased in glomeruli from the FK506 group. These effects resulted in macrophage infiltration into the glomeruli. FK506 directly promoted NAD(P)H oxidase activity and accelerated production of ROS in hGECs. Conversely, cotreatment with telmisartan inhibited both NAD(P)H oxidase activity and production of ROS. Conclusion: These findings suggest that glomerular injury resulting from FK506 is caused by oxidative stress mediated by activation of NAD(P)H oxidase and that telmisartan exerts a renoprotective effect via antioxidative activity.
No Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin 2 Receptor Blocker Intake with Acute Kidney Injury in Patients Undergoing Kidney Biopsy
Authors: Friedl Alexander , Peric Slobodan , Masghati Salome , Wolzt Michael , Hörl Walter H. , Soleiman Afschin , Fuhrmann Valentin , Haider Dominik G.
Published: August 2012

Background: Treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin 2 receptor blockers (ARBs) is associated with an increased risk for acute kidney injury after cardiovascular interventions. However, for patients undergoing kidney biopsy, no data is available. Methods: Four hundred and sixty-six patients undergoing kidney biopsy were retrospectively analyzed of whether or not concomitant intake of ACEIs or ARBs impairs kidney function. Results: Three hundred and twenty-three patients received ACEIs or ARBs or both before kidney biopsy. ACEI/ARB intake had no effect on kidney function compared to patients without this medication (all p > 0.05). Conclusion: Treatment with ACEIs or ARBs is not associated with risk of acute kidney injury in subjects undergoing kidney biopsy.