bluuebunny/crossref_metadata_2025 huggingface dataset:
PDLIM2 Inhibits T Helper 17 Cell Development and Granulomatous Inflammation Through Degradation of STAT3
Authors: Tanaka Takashi , Yamamoto Yu , Muromoto Ryuta , Ikeda Osamu , Sekine Yuichi , Grusby Michael J. , Kaisho Tsuneyasu , Matsuda Tadashi
Published: December 2011

An E3 ubiquitin ligase inhibits the development of inflammatory T cells involved in autoimmune diseases.
Protein Kinase C η Is Required for T Cell Activation and Homeostatic Proliferation
Authors: Fu Guo , Hu Jianfang , Niederberger-Magnenat Nathalie , Rybakin Vasily , Casas Javier , Yachi Pia P. , Feldstein Stephanie , Ma Bo , Hoerter John A. H. , Ampudia Jeanette , Rigaud Stephanie , Lambolez Florence , Gavin Amanda L. , Sauer Karsten , Cheroutre Hilde , Gascoigne Nicholas R. J.
Published: December 2011

Studies of knockout mice delineate specific and overlapping roles for different protein kinase C isoforms in T cell biology.
Cancer Cell Vulnerability
Authors: Ray L. Bryan
Published: December 2011

The glycolytic metabolism of cancers differs from normal tissues, allowing tumor cells to survive under oxidative stress.
Of Stress, Pain, Gender, and the Arginine Vasopressin Receptor
Authors: Adler Elizabeth M.
Published: December 2011

Variations in the vasopressin-1A receptor combine with stress level and gender to affect sensitivity to pain.
Age-Related Intimal Stiffening Enhances Endothelial Permeability and Leukocyte Transmigration
Authors: Huynh John , Nishimura Nozomi , Rana Kuldeepsinh , Peloquin John M. , Califano Joseph P. , Montague Christine R. , King Michael R. , Schaffer Chris B. , Reinhart-King Cynthia A.
Published: December 2011

Inhibiting endothelial cell contractility reverses the deleterious effects of age-related matrix stiffening on normal cell function, which could help prevent the development of atherosclerosis.
Improving Scientific Research and Writing Skills through Peer Review and Empirical Group Learning
Authors: Senkevitch Emilee , Smith Ann C. , Marbach-Ad Gili , Song Wenxia
Published: December 2011

Here we describe a semester-long, multipart activity called “Read and wRite to reveal the Research process” (R
3
) that was designed to teach students the elements of a scientific research paper. We implemented R
3
in an advanced immunology course. In R
3
, we paralleled the activities of reading, discussion, and presentation of relevant immunology work from primary research papers with student writing, discussion, and presentation of their own lab findings. We used reading, discussing, and writing activities to introduce students to the rationale for basic components of a scientific research paper, the method of composing a scientific paper, and the applications of course content to scientific research. As a final part of R
3
, students worked collaboratively to construct a Group Research Paper that reported on a hypothesis-driven research project, followed by a peer review activity that mimicked the last stage of the scientific publishing process. Assessment of student learning revealed a statistically significant gain in student performance on writing in the style of a research paper from the start of the semester to the end of the semester.
Microbes in Mascara: Hypothesis-Driven Research in a Nonmajor Biology Lab
Authors: Burleson Kathryn M. , Martinez-Vaz Betsy M.
Published: December 2011

In this laboratory exercise, students were taught concepts of microbiology and scientific process through an everyday activity — cosmetic use. The students’ goals for the lab were to develop a hypothesis regarding microbial contamination in cosmetics, learn techniques to culture and differentiate microorganisms from cosmetics, and propose best practices in cosmetics use based on their findings. Prior to the lab, students took a pretest to assess their knowledge of scientific hypotheses, microbiology, and cosmetic safety. In the first week, students were introduced to microbiological concepts and methodologies, and cosmetic terminology and safety. Students completed a hypothesis-writing exercise before formulating and testing their own hypotheses regarding cosmetic contamination. Students provided a cosmetic of their own and, in consultation with their lab group, chose one product for testing. Samples were serially diluted and plated on a variety of selective media. In the second week, students analyzed their plates to determine the presence and diversity of microbes and if their hypotheses were supported. Students completed a worksheet of their results and were given a posttest to assess their knowledge. Average test scores improved from 5.2 (pretest) to 7.8 (posttest), with p-values < 0.0001. Seventy-nine percent (79%) of students correctly identified hypotheses that were not falsifiable or lacked variables, and 89% of students improved their scores on questions concerning safe cosmetic use. Ninety-one percent (91%) of students demonstrated increased knowledge of microbial concepts and methods. Based on our results, this lab is an easy, yet effective, way to enhance knowledge of scientific concepts for nonmajors, while maintaining relevance to everyday life.
An Investigation of Bacterial Protein Interactions as a Primary Research Project in a Sophomore-Level Molecular Biology Course
Authors: Cardinale Jean A.
Published: December 2011

Longer term research activities that may be incorporated in undergraduate courses are a powerful tool for promoting student interest and learning, developing cognitive process skills, and allowing undergraduates to experience real research activities in which they may not otherwise have the opportunity to participate. The challenge to doing so in lower-level courses is that students may have not fully grasped the scientific concepts needed to undertake such research endeavors, and that they may be discouraged if activities are perceived to be too challenging. The paper describes how a bacterial protein:protein interaction detection system was adapted and incorporated into the laboratory component of a sophomore-level Molecular Cell Biology course. The project was designed to address multiple learning objectives connecting course content to the laboratory activities, as well as teach basic molecular biology laboratory skills and procedures in the context of a primary research activity. Pre- and posttesting and student surveys both suggest that the laboratory curriculum resulted in significant learning gains, as well as being well received and valued by the students.
Journal Watch
Authors: Herzog Jennifer A.
Published: December 2011

The Journal Watch section highlights published journal articles which discuss recent developments and new technology used in microbiology and related fields.
A Review of
Virology: Molecular Biology and Pathogenesis
Review of:
Virology: Molecular Biology and Pathogenesis,
1st ed.; Leonard C. Norkin; (2010). ASM Press, Washington DC. Hardcover, 725 pages. ISBN-10: 1555814530.
Authors: Godfrey Susan
Published: December 2011

Review of:
Virology: Molecular Biology and Pathogenesis,
1st ed.; Leonard C. Norkin; (2010). ASM Press, Washington DC. Hardcover, 725 pages. ISBN-10: 1555814530.
A Comparative Review of Four Photographic Atlases for Microbiology
A Photographic Atlas for the Microbiology Laboratory,
Fourth Edition; Michael J. Leboffe and Burton E. Pierce; (2011). Morton Publishing Company, Englewood, CO. 256 pages.
Microbiology: A Photographic Atlas for the Laboratory
; Steven K. Alexander and Dennis Strete; (2001). Pearson Education, Inc., Upper Saddle River, NJ. 193 pages.
Microbiology Perspectives: A Photographic Survey of the Microbial World
, Second Edition; George Wistreich; (2007). Pearson Education, Inc., Upper Saddle River, NJ. 232 pages.
Authors: Tobiason Deborah
Published: December 2011

Review of: four photographic atlases for microbiology, including:

A Photographic Atlas for the Microbiology Laboratory, Fourth Edition;
Michael J. Leboffe and Burton E. Pierce; (2011) . Morton Publishing Company, Englewood, CO. 256 pages.

Microbiology: A Photographic Atlas for the Laboratory ; Steven K. Alexander and Dennis Strete;
(2001) . Pearson Education, Inc., Upper Saddle River, NJ. 193 pages.

Microbiology Perspectives: A Photographic Survey of the Microbial World , Second Edition;
George Wistreich; (2007) . Pearson Education, Inc., Upper Saddle River, NJ. 232 pages.

and

ASM’s MicrobeLibrary Atlas.
Do urology journals enforce trial registration? A cross-sectional study of published trials
Authors: Kunath Frank , Grobe Henrik R , Keck Bastian , Rücker Gerta , Wullich Bernd , Antes Gerd , Meerpohl Joerg J
Published: December 2011

Objectives

(1) To assess endorsement of trial registration in author instructions of urology-related journals and (2) to assess whether randomised controlled trials (RCTs) in the field of urology were effectively registered.

Design

Cross-sectional study of author instructions and published trials.

Setting

Journals publishing in the field of urology.

Participants

First, the authors analysed author instructions of 55 urology-related journals indexed in ‘Journal Citation Reports 2009’ (12/2010). The authors divided these journals in two groups: those requiring and those not mentioning trial registration as a precondition for publication. Second, the authors chose the five journals with the highest impact factor (IF) from each group.

Intervention

MEDLINE search to identify RCTs published in these 10 journals in 2009 (01/2011); search of the clinical trials meta-search interface of WHO (International Clinical Trials Registry Platform) for RCTs that lacked information about registration (01–03/2011). Two authors independently assessed the information.

Outcome measures

Proportion of journals providing advice about trial registration and proportion of trials registered.

Results

Of 55 journals analysed, 26 (47.3%) provided some editorial advice about trial registration. Journals with higher IFs were more likely to mention trial registration explicitly (p=0.015). Of 106 RCTs published in 2009, 63 were registered (59.4%) with a tendency to an increase after 2005 (83.3%, p=0.035). 71.4% (30/42) of the RCTs that were published in journals mentioning and requiring registration, and 51.6% (33/64) of the RCTs that were published in journals that did not mention trial registration explicitly were registered. This difference was statistically significant (p=0.04).

Conclusions

The existence of a statement about trial registration in author instructions resulted in a higher proportion of registered RCTs in those journals. Journals with higher IFs were more likely to mention trial registration.
Stream salmonids as opportunistic foragers: the importance of terrestrial invertebrates along a stream-size gradient
Authors: Syrjänen J. , Korsu K. , Louhi P. , Paavola R. , Muotka T.
Published: December 2011

Terrestrial invertebrates have been reported to be positively selected by stream salmonids. We assessed the importance of terrestrial and aquatic invertebrates to salmonid diets in 25 streams in Finland, with the hypothesis that terrestrial prey would be important in only the smallest forest streams. Several measures of prey availability were used, including proportional abundance in benthic or drift samples, compared with a trait-based approach, to predict diet composition. Across all 25 streams in autumn, blackfly and caddis larvae were the most important prey items. Terrestrial invertebrates were of moderate importance in all streams, including the smallest. Pure availability predicted diet best and provided, in most cases, a significant fit with the observed diet. In a quantitative literature review, the mean proportion of terrestrial prey in salmonid diets was 17%, being highest for the largest fish (≥15 cm). Species of the genus Salmo consumed significantly less terrestrials than did other salmonid genera. The proportion of terrestrial prey was highest in streams flowing through deciduous forests, but it was only weakly correlated with channel width.
Response of trout populations in five Colorado streams two decades after habitat manipulation
Authors: White Shannon L. , Gowan Charles , Fausch Kurt D. , Harris Josh G. , Saunders W. Carl
Published: December 2011

Evaluating the effectiveness of instream structures for increasing trout populations is complicated by a paucity of long-term studies. We report on a study spanning 23 years to assess the effect of installing log weirs on stream habitat and trout abundance. Structures were installed in a randomly selected half of a 500 m study reach in six small Colorado, USA, mountain streams in 1988, and habitat and trout abundance and biomass were measured annually from 1987 to 1994. When five of the streams were resampled in 2009, none of the 53 logs had moved, and all but one were functioning properly. Pool volume remained more than three times higher in treatment sections than in adjacent controls, and mean depth was also greater. Adult trout abundance increased rapidly after structures were installed and remained 53% higher in treatment sections than in controls 21 years later. Effects on juvenile trout abundance were not detected, probably because fry recruitment is strongly influenced by effects of snowmelt runoff, which vary annually among basins. This evaluation shows that instream structures placed in small, stable channels can function for more than two decades when properly installed and can cause long-lasting increases in trout abundance when habitat is limiting.
GENE EXPRESSION DATA ANALYSIS USING PSEUDO STANDARD DEVIATION MINIMIZATION FEATURE FUSION METHOD FOR CANCER DIAGNOSIS
Authors: PIAO HAIYAN
Published: December 2011

Over the past years applications of fusion technique have been growing rapidly. However, very few applications of the technique to microarray data have been reported. In this paper, we propose a new fusion method based on pseudo standard deviation minimization (PSDM) for the feature selection of microarray. This new method provides a more accurate set of features. Therefore the classification can be performed and functional meaning from the features can also be revealed. The new method is actually obtained through a combination of two different feature selection methods (FSMs). It is shown that it can explore nonperfect correlation between gene expression profile and cancer classes or feature detection algorithms. To evaluate its effectiveness, it is tested on lymphoma and leukemia microarray expression datasets and then compared with the existing methods. Self-organizing map (SOM) is used for feature classification. It can be seen through the comparison that the classification accuracy of the new fusion method is at least 2% ~ 3% higher than others.
GAIT SYMMETRY ANALYSIS PROTOCOL FOR WHOLE LEG MOVEMENT SYMMETRY EVALUATION
Authors: JANG IK GYU , NAM KYOUNG WON , PARK HONG SEONG , JO YUNG HO , KANG HYUN GUY , PARK JEONG YUN , KIM KWANG GI
Published: December 2011

Objective and accurate evaluation of patients who underwent lower limb operation is important in determining a proper rehabilitation process according to the patient's recovery status. Gait symmetry analysis is a common protocol that is used to evaluate lower limb function; however, most studies have focused only on the terminal symmetry of lower limb during gait motion and were unable to provide information about detailed motions of the whole leg. To more accurately analyze mutual symmetry of the left and right leg during gait motion, measurement of motions of the whole left and right leg including the pelvis, hip, knee, and ankle is required. Eight patients (mean [standard deviation]: age = 22.87 [6.05] years; height = 167.81 [5.86] cm; weight = 629.52 [133.63] Newtons) who underwent limbsalvage surgery and eight normal volunteers (age = 28.87 [3.79] years; height = 167 [8.36] cm; weight = 657.46 [157.02] Newtons) participated in this study. Using motion capture cameras arranged around each subject, real-time gait motion of each participant was recorded and moving trajectories of 12 submotion elements were extracted. Mutual symmetry of the motion between the left and right leg was then calculated using a Pearson correlation method, while a nonparametric Mann-Whitney test was performed for group comparison. Experimental results showed that the moving trajectories of the left and right leg were similar in the normal group (r = 0.8114[0.22]) but were critically different in the patient group (r = 0.624286[0.15]). In addition, there was statistically significant difference (p = 0.0162) in gait symmetry between the normal group and the patient group (95% confidence level). We conclude that the proposed protocol can provide a useful evaluation tool for patient recovery condition and that it could be helpful in establishing an effective postoperative treatment protocol for lower limb patients.
EFFECTS OF FLUID SHEAR STRESS AND CIGLITAZONE ON OSTEOBLASTS
Authors: SUN LIJUN , WANG HAOYU , XU HAO , WEI JINHONG , SHI LIANG , LIU XIAOGANG , ZHANG JIANBAO
Published: December 2011

Long-term use of thiazolidinedione (TZD) antidiabetic agents in patients with type 2 diabetes mellitus has been shown to increase the incidence of osteoporosis. Mechanical loading can enhance bone mass by promoting bone formation and suppressing bone resorption, which may be beneficial to patients with TZD-induced osteoporosis. In this study, we examined the cooperative effect of fluid shear stress (FSS) and ciglitazone (CIG), a type of TZD, on osteoblasts. The proliferation, osteoblast differentiation-related mRNA expression and translocation of nuclear factor κB (NFκB) of osteoblasts were assessed. The results show that CIG significantly decreased the proliferation of osteoblasts, inhibited the translocation of NFκB to the nucleus and reduced the mRNA expression of COX-2, IGF, Runx2 and OCN. At the same time, CIG also increased the mRNA expression of PPARγ. Conversely, FSS significantly increased the proliferation of osteoblasts, promoted the translocation of NFκB to the nucleus and increased the mRNA expression of COX-2, IGF, Runx2 and OCN but decreased the mRNA expression of PPARγ. When FSS and CIG were combined, FSS counteracted the effects of CIG on osteoblasts. Taken together, the current results suggest that FSS is able to arrest the effects of CIG on the proliferation and differentiation of osteoblasts.
Predominant Dissemination of PVL-Negative CC89 MRSA with SCCmecType II in Children with Impetigo in Japan
Authors: Kikuta H. , Shibata M. , Nakata S. , Yamanaka T. , Sakata H. , Akizawa K. , Kobayashi K.
Published: December 2011

Background. The ratio of CA-MRSA in children with impetigo has been increasing in Japan.Methods. Antimicrobial susceptibilities of 136S. aureusisolates from children with impetigo were studied. Furthermore, molecular epidemiological analysis and virulence gene analysis were performed.Results. Of the 136S. aureusisolates, 122 (89.7%) were MSSA and 14 (10.3%) were MRSA. Of the 14 MRSA strains, 11 belonged to CC89 (ST89, ST91, and ST2117) and carried diverse types of SCCmec: type II (IIb: 3 strains; unknown subtype: 4 strains), type IVa (2 strains), and unknown type (2 strains). The remaining three strains exhibited CC8 (ST-8)-SCCmectype VIa, CC121 (ST121)-SCCmectype V, and CC5 (ST5)-nontypeable SCCmecelement, respectively. None werelukS-PV-lukF-PV gene positive. Gentamicin- and clarithromycin-resistant strains were frequently found in both MRSA and MSSA.Conclusions. PVL-negative CC89-SCCmectype II strains are the most predominant strains among the CA-MRSA strains circulating in the community in Japan.
Nonlinear Magnetoconvection in a Sparsely Packed Porous Medium
Authors: Babu A. Benerji , Ravi Ragoju , Tagare S. G.
Published: December 2011

Linear and weakly nonlinear properties of magnetoconvection in a sparsely packed porous medium are investigated. We have obtained the values of Takens-Bogdanov bifurcation points and codimension two bifurcation points by plotting graphs of neutral curves corresponding to stationary and oscillatory convection for different values of physical parameters relevant to magnetoconvection in a sparsely packed porous medium near a supercritical pitchfork bifurcation. We have derived a nonlinear two-dimensional Ginzburg-Landau equation with real coefficients by using Newell-Whitehead (1969) method. The effect of the parameter values on the stability mode is investigated and shown the occurrence of secondary instabilities namely, Eckhaus and Zigzag instabilities. We have studied Nessult number contribution at the onset of stationary convection. We have also derived two nonlinear one-dimensional coupled Ginzburg-Landau-type equations with complex coefficients near the onset of oscillatory convection at a supercritical Hopf bifurcation and discussed the stability regions of standing and travelling waves.
Robust Design of Biological Circuits: Evolutionary Systems Biology Approach
Authors: Chen Bor-Sen , Hsu Chih-Yuan , Liou Jing-Jia
Published: December 2011

Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.
Construction of Compactly Supported Refinable Componentwise Polynomial Functions in ℝ2
Authors: Xue Yanmei , Bi Ning
Published: December 2011

We provide a sufficient condition for constructing a class of
compactly supported refinable functions with componentwise polynomial property in ℝ2. An iteration algorithm is developed to compute the polynomial on each component of the functions′ support. Finally, two examples for constructing the symmetric refinable componentwise polynomial functions are given.
Peroxisome Proliferator-Activated Receptor-αActivation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension
Authors: Lee Dexter L. , Wilson Justin L. , Duan Rong , Hudson Tamaro , El-Marakby Ahmed
Published: December 2011

Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-αactivation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-αactivation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-αactivation protects the kidney against renal injury via decreased COX-2 expression.
Maternal Obesity and the Early Origins of Childhood Obesity: Weighing Up the Benefits and Costs of Maternal Weight Loss in the Periconceptional Period for the Offspring
Authors: Zhang Song , Rattanatray Leewen , Morrison Janna L. , Nicholas Lisa M. , Lie Shervi , McMillen I. Caroline
Published: December 2011

There is a need to understand the separate or interdependent contributions of maternal prepregnancy BMI, gestational weight gain, glycaemic control, and macronutrient intake on the metabolic outcomes for the offspring. Experimental studies highlight that there may be separate influences of maternal obesity during the periconceptional period and late gestation on the adiposity of the offspring. While a period of dietary restriction in obese mothers may ablate the programming of obesity, it is associated with an activation of the stress axis in the offspring. Thus, maternal obesity may result in epigenetic changes which predict the need for efficient fat storage in postnatal life, while maternal weight loss may lead to epigenetic changes which predict later adversity. Thus, development of dietary interventions for obese mothers during the periconceptional period requires a greater evidence base which allows the effective weighing up of the metabolic benefits and costs for the offspring.
Screening ofα-Glucosidase Inhibitory Activity from Some Plants of Apocynaceae, Clusiaceae, Euphorbiaceae, and Rubiaceae
Authors: Elya Berna , Basah Katrin , Mun'im Abdul , Yuliastuti Wulan , Bangun Anastasia , Septiana Eva Kurnia
Published: December 2011

Diabetes mellitus (DM) is recognized as a serious global health problem that is characterized by high blood sugar levels. Type 2 DM is more common in diabetic populations. In this type of DM, inhibition ofα-glucosidase is a useful treatment to delay the absorption of glucose after meals. As a megabiodiversity country, Indonesia still has a lot of potential unexploited forests to be developed as a medicine source, including as theα-glucosidase inhibitor. In this study, we determine theα-glucosidase inhibitory activity of 80% ethanol extracts of leaves and twigs of some plants from the Apocynaceae, Clusiaceae, Euphorbiaceae, and Rubiaceae. Inhibitory activity test of theα-glucosidase was performedin vitrousing spectrophotometric methods. Compared with the control acarbose (IC50117.20 μg/mL), thirty-seven samples of forty-five were shown to be more potentα-glucosidase inhibitors with IC50values in the range 2.33–112.02 μg/mL.
The Effect of Traditional Cupping on Pain and Mechanical Thresholds in Patients with Chronic Nonspecific Neck Pain: A Randomised Controlled Pilot Study
Authors: Lauche Romy , Cramer Holger , Hohmann Claudia , Choi Kyung-Eun , Rampp Thomas , Saha Felix Joyonto , Musial Frauke , Langhorst Jost , Dobos Gustav
Published: December 2011

Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP) and mechanical sensory thresholds.Methods. Fifty CNP patients were randomly assigned to treatment (TG,n=25) or waiting list control group (WL,n=25). TG received a single cupping treatment. Pain at rest (PR), pain related to movement (PM), quality of life (SF-36), Neck Disability Index (NDI), mechanical detection (MDT), vibration detection (MDT), and pressure pain thresholds (PPT) were measured before and three days after a single cupping treatment. Patients also kept a pain and medication diary (PaDi, MeDi) during the study.Results. Baseline characteristics were similar in the two groups. After cupping TG reported significantly less pain (PR: −17.9 mm VAS, 95%CI −29.2 to −6.6; PM: −19.7, 95%CI −32.2 to −7.2; PaDi: −1.5 points on NRS, 95%CI −2.5 to −0.4; allP<0.05) and higher quality of life than WL (SF-36, Physical Functioning: 7.5, 95%CI 1.4 to 13.5; Bodily Pain: 14.9, 95%CI 4.4 to 25.4; Physical Component Score: 5.0, 95%CI 1.4 to 8.5; allP<0.05). No significant effect was found for NDI, MDT, or VDT, but TG showed significantly higher PPT at pain-areas than WL (in lg(kPa); pain-maximum: 0.088, 95%CI 0.029 to 0.148, pain-adjacent: 0.118, 95%CI 0.038 to 0.199; bothP<0.01).Conclusion. A single application of traditional cupping might be an effective treatment for improving pain, quality of life, and hyperalgesia in CNP.
Analysis of Longitudinal and Survival Data: Joint Modeling, Inference Methods, and Issues
Authors: Wu Lang , Liu Wei , Yi Grace Y. , Huang Yangxin
Published: December 2011

In the past two decades, joint models of longitudinal and survival data have received much attention in the literature. These models are often desirable in the following situations: (i) survival models with measurement errors or missing data in time-dependent covariates, (ii) longitudinal models with informative dropouts, and (iii) a survival process and a longitudinal process are associated via latent variables. In these cases, separate inferences based on the longitudinal model and the survival model may lead to biased or inefficient results. In this paper, we provide a brief overview of joint models for longitudinal and survival data and commonly used methods, including the likelihood method and two-stage methods.
Genetic Variants in Oxidative Stress–Related Genes Predict Chemoresistance in Primary Breast Cancer: A Prospective Observational Study and Validation
Authors: Yu Ke-Da , Huang A-Ji , Fan Lei , Li Wen-Feng , Shao Zhi-Ming
Published: December 2011

Chemotherapy response in patients with primary breast cancer is difficult to predict and the role of host genetic factors has not been thoroughly investigated. We hypothesized that polymorphisms in oxidative stress (OS)-related genes, including estrogen–quinone metabolizing enzymes NQO2 and GSTM1-5, may influence disease progression and treatment response. In this prospective observational study, nineteen polymorphisms tagging known variations in candidate genes were genotyped and analyzed in 806 patients with primary breast cancer. Three functional polymorphisms, which were shown to affect gene expression levels in experiments in vitro and ex vivo, modified the effect of chemotherapy on disease-free survival. There were significant interactions between chemotherapy and individual polymorphisms or combined genotypes (designated as genetic score). Patients harboring high genetic score had a 75% reduction in the hazard of disease progression compared with patients with low genetic score when no chemotherapy was administered (HR = 0.25, 95% CI: 0.10–0.63, P = 0.005); however, they received much less survival benefit from adjuvant chemotherapy compared with patients with low genetic score when chemotherapy was administered (HR = 4.60 for interaction, 95% CI: 1.63–13.3, P = 0.004). These findings were validated in another population (n = 339). In conclusion, germline polymorphisms in OS-related genes affect chemotherapy sensitivity in breast cancer patients. Although reduced OS levels might prevent breast cancer progression, they probably compromise the effectiveness of adjuvant chemotherapy. Our findings also indicate that host-related factors must be considered for individualized chemotherapy. Cancer Res; 72(2); 408–19. ©2011 AACR.
Common Polymorphisms in the Adiponectin and Its Receptor Genes, Adiponectin Levels and the Risk of Prostate Cancer
Authors: Dhillon Preet K. , Penney Kathryn L. , Schumacher Fredrick , Rider Jennifer R. , Sesso Howard D. , Pollak Michael , Fiorentino Michelangelo , Finn Stephen , Loda Massimo , Rifai Nader , Mucci Lorelei A. , Giovannucci Edward , Stampfer Meir J. , Ma Jing
Published: December 2011

Background: Adiponectin, an insulin-sensitizing adipokine, is inversely associated with adiposity and prostate cancer risk and progression. However, the role of genetic variation in the adiponectin (ADIPOQ) and receptor genes (ADIPOR1/R2) in prostate cancer is largely unknown.

Methods: In a nested case–control study of 1,286 cases and 1,267 controls within the Physicians' Health Study, we evaluated 29 common single-nucleotide polymorphisms (SNP) in ADIPOQ (n = 13), ADIPOR1 (n = 5), and ADIPOR2 (n = 11) in relation to the risk of prostate cancer. In subgroups, we also evaluated the association of genotype and circulating adiponectin levels (n = 951) and prostate tumor expression of insulin receptor (IR) and insulin-like growth factor 1 (IGF-IR) receptor (n = 181).

Results: Among the 12 tagging polymorphisms in ADIPOQ, four (rs266729, rs182052, rs822391, and rs2082940) were significantly associated (P < 0.05) with overall prostate cancer risk, with no significant difference by tumor grade or clinical stage. Two of the risk SNPs (rs266729 and rs182052) plus four other SNPs (rs16861209, rs17366568, rs3774261, and rs7639352) were also associated with plasma adiponectin levels, and three of these (rs1686109, rs17366568, and rs3774261) were also significantly associated with IR expression in prostate tumor tissue. One additional SNP was associated with IGFI-R tumor tissue expression (rs16861205). None of the 16 variants in ADIPOR1/R2 were related to cancer risk or circulating adiponectin levels.

Conclusions: Common variants in the adiponectin gene were associated with prostate cancer risk, plasma adiponectin levels, and IR or IGF-IR expression in the prostate tumor.

Impact: These genotype–phenotype associations support the biological relevance of adiponectin for prostate carcinogenesis, particularly in earlier stages of development. Cancer Epidemiol Biomarkers Prev; 20(12); 2618–27. ©2011 AACR.
Prenatal Smoke Exposure and Genomic DNA Methylation in a Multiethnic Birth Cohort
Authors: Flom Julie D. , Ferris Jennifer S. , Liao Yuyan , Tehranifar Parisa , Richards Clara Belessiotis , Cho Yoon Hee , Gonzalez Karina , Santella Regina M. , Terry Mary Beth
Published: December 2011

Background: Exposure to prenatal tobacco smoke (PTS) has been associated with a number of health outcomes in the offspring, including some childhood cancers. Lower levels of genomic DNA methylation have also been associated with several types of cancers. We investigated whether PTS was associated with global DNA methylation levels in the offspring.

Methods: Our sample was drawn from a birth cohort of women born between 1959 and 1963 in New York City (n = 90). We measured methylation of repetitive elements (Sat2, Alu, LINE-1) from peripheral blood granulocytes. We combined prospectively collected data on PTS with adult epidemiologic data and blood samples collected in 2001 to 2007 (mean age, 43 years). We used linear regression to assess the association between PTS and repetitive element methylation.

Results: Thirty-six percent of mothers smoked during pregnancy. We observed an inverse association between PTS and Sat2 methylation. This inverse association remained even after adjustment for potential mediators including child environmental tobacco smoke exposure, birth size, postnatal weight and height changes, and adult smoking status and alcohol intake (β = −0.22, 95% confidence interval = −0.40 to −0.03 for ever exposed to PTS vs. never exposed using models of log-transformed methylation levels). PTS exposure was not statistically significantly associated with LINE-1 or Alu methylation.

Conclusions: PTS exposure, measured at the time of pregnancy and not retrospectively reported, was associated with a decrease in Sat2 methylation but not LINE-1 or Alu methylation.

Impact: If replicated in larger studies, this study supports a persistent effect of PTS on DNA methylation levels, as measured by Sat2, in adulthood. Cancer Epidemiol Biomarkers Prev; 20(12); 2518–23. ©2011 AACR.
Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management
Authors: Bandiera Elisabetta , Romani Chiara , Specchia Claudia , Zanotti Laura , Galli Claudio , Ruggeri Giuseppina , Tognon Germana , Bignotti Eliana , Tassi Renata A. , Odicino Franco , Caimi Luigi , Sartori Enrico , Santin Alessandro D. , Pecorelli Sergio , Ravaggi Antonella
Published: December 2011

Background: The aim of this work was to analyze the diagnostic and prognostic value of serum human epididymis protein 4 (HE4) and Risk for Ovarian Malignancy Algorithm (ROMA) in epithelial ovarian cancer (EOC).

Methods: Preoperative serum samples of 419 women (140 healthy controls, 131 ovarian benign cysts, 34 endometriosis, and 114 EOC) were tested for CA125 and HE4 using fully automated methods (Abbott ARCHITECT) and validated cutoff values.

Results: For the discrimination of benign masses from EOC, in premenopausal women, the sensitivity and specificity were 92.3% and 59.4% for CA125, 84.6% and 94.2% for HE4, and 84.6% and 81.2% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 94.3% and 82.3% for CA125, 78.2% and 99.0% for HE4, and 93.1% and 84.4% for ROMA. In patients with EOC, elevated CA125, HE4, and ROMA levels were associated with advanced Federation of Gynaecologists and Obstetricians (FIGO) stage, suboptimally debulking, ascites, positive cytology, lymph node involvement, and advanced age (all P ≤ 0.05). Elevated HE4 and ROMA (both P ≤ 0.01), but not CA125 (P = 0.0579), were associated with undifferentiated tumors. In multivariable analysis, elevated HE4 and ROMA (all P ≤ 0.05) were independent prognostic factors for shorter overall, disease-free, and progression-free survival.

Conclusions and Impact: This study underlines the high specificity of HE4 in discriminating endometriosis and ovarian benign cysts from EOC and the high sensitivity of CA125 in detecting EOC. We showed HE4 and ROMA as independent prognostic factors. Multicenter studies are needed to draw firm conclusions about the applicability of HE4 and ROMA in clinical practice. Cancer Epidemiol Biomarkers Prev; 20(12); 2496–506. ©2011 AACR.
Genetic Variants of Toll-Like Receptor 2 and 5, Helicobacter Pylori Infection, and Risk of Gastric Cancer and Its Precursors in a Chinese Population
Authors: Zeng Hong-Mei , Pan Kai-Feng , Zhang Yang , Zhang Lian , Ma Jun-Ling , Zhou Tong , Su Hui-Juan , Li Wen-Qing , Li Ji-You , Gerhard Markus , Classen Meinhard , You Wei-Cheng
Published: December 2011

Background: Genetic polymorphisms of Toll-like receptors (TLR) may influence the outcome of Helicobacter pylori infection and play important roles in gastric carcinogenesis. To screen the genetic variants of TLR2 and TLR5, and evaluate their associations with gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shandong Province, China.

Methods: Genetic variants were identified by PCR-based denaturing high-performance liquid chromatography and PCR-restriction fragment length polymorphism analysis in 248 GC cases, 846 subjects with advanced gastric lesions including 350 dysplasia and 496 intestinal metaplasia, and 496 superficial gastritis/mild chronic atrophic gastritis controls.

Results: Nine allelic variants each were detected within the promoter and exons of TLR2 and TLR5. Among those, TLR2 c. −196 to −174 del carriers (ins/del+del/del) showed a significantly decreased risk of GC (adjusted OR, 0.66; 95% CI: 0.48–0.90), whereas TLR5 rs5744174 C carriers (TC+CC) had an increased risk of GC (OR, 1.43; 95% CI: 1.03–1.97). Further analysis indicated an elevated risk of GC in subjects with the TLR5 rs5744174 TC+CC genotype and H. pylori infection (OR, 3.35; 95% CI: 2.13–5.26), and a significant interaction between rs5744174 and H. pylori infection was observed (OR, 2.15; 95% CI: 1.12–4.16).

Conclusion: These findings suggest that TLR2 c. −196 to −174 ins > del, TLR5 rs5744174 and interaction between rs5744174 and H. pylori infection were associated with the development of GC.

Impact: TLR2 and TLR5 polymorphisms may play important roles in the process of H. pylori-related gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(12); 2594–602. ©2011 AACR.
Prospective Seroepidemiologic Study of Human Papillomavirus and Other Risk Factors in Cervical Cancer
Authors: Arnheim Dahlström Lisen , Andersson Kristin , Luostarinen Tapio , Thoresen Steinar , Ögmundsdottír Helga , Tryggvadottír Laufey , Wiklund Fredrik , Skare Gry B. , Eklund Carina , Sjölin Kia , Jellum Egil , Koskela Pentti , Wadell Göran , Lehtinen Matti , Dillner Joakim
Published: December 2011

Background: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects.

Methods: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI.

Results: Exposure to HPV16 was the strongest risk factor for cervical cancer [OR = 2.4; 95% confidence interval (CI), 2.0–3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2–3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3–4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9–1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8–1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5–2.3).

Conclusions: A large prospective study has assessed the role of different STIs in cervical cancer.

Impact: Prospective evidence supports cofactor role of some STI in cervical cancer. Cancer Epidemiol Biomarkers Prev; 20(12); 2541–50. ©2011 AACR.
Family History of Breast Cancer in Relation to Tumor Characteristics and Mortality in a Population-Based Study of Young Women with Invasive Breast Cancer
Authors: Malone Kathleen E. , Daling Janet R. , Doody David R. , O'Brien Cecilia , Resler Alexa , Ostrander Elaine A. , Porter Peggy L.
Published: December 2011

Background: Inherited predisposition may be associated with distinctive breast cancer phenotypes and/or mortality. Past studies have had inconsistent results and little is known about the contributions of screening and treatment.

Methods: Within a population-based cohort of 1,260 women diagnosed with invasive breast cancer before age 46, we assessed how family history of breast cancer relates to mortality and tumor characteristics. Analyses were repeated excluding BRCA1/BRCA2 carriers. Medical records were reviewed for treatment history and tumors were centrally reviewed and tested. Cox proportional hazard modeling was used to assess the risk of dying in relation to family history; logistic regression was used to assess the association of family history to tumor characteristics.

Results: Compared with women with no family history, women with first-degree family history of breast cancer had a 40% reduction (95% CI: 0.5–0.8) in the risk of dying. Mortality in women with only a second-degree family history was similar to those with no family history. The risk of dying was further reduced in those with a greater number of affected relatives. These relationships did not seem to be attributable to differences in screening, detection method, or treatment. Tumors in women with a first-degree family history had generally more favorable prognostic profiles.

Conclusion: Our findings suggest that breast cancer patients with a first-degree family history, compared with their counterparts without such a profile, may have a better prognosis.

Impact: These findings support the need for future research directed at replicating these results and identifying factors underlying this possible relationship. Cancer Epidemiol Biomarkers Prev; 20(12); 2560–71. ©2011 AACR.
Telomere Length and TERT Functional Polymorphisms Are Not Associated with Risk of Squamous Cell Carcinoma of the Head and Neck
Authors: Liu Zhensheng , Ma Hongxia , Wei Sheng , Li Guojun , Sturgis Erich M. , Wei Qingyi
Published: December 2011

Background: Recent studies reported associations of the relative telomere length (RTL) and TERT variants with risk of several cancers, which have not been comprehensively investigated in squamous cell carcinoma of the head and neck (SCCHN).

Methods: We detected RTL in peripheral blood lymphocytes and genotyped six selected functional single-nucleotide polymorphisms (SNP) of the TERT gene in 888 SCCHN cases and 885 cancer-free controls of non-Hispanic whites.

Results: Overall, we did not observe significant associations between RTL and SCCHN risk (adjusted OR = 0.97; 95% CI = 0.80–1.17 for below versus above the median; Ptrend = 0.618) nor between the six TERT SNPs and SCCHN risk. We also found no associations between RTL and TERT SNPs.

Conclusions: Our results suggest that RTL and TERT functional polymorphisms may not play a major role in the etiology of SCCHN. Large prospective studies are needed to validate our findings.

Impact: Although our results suggest no association among RTL, TERT functional polymorphisms, and SCCHN risk, this study may contribute to future meta-analysis. Cancer Epidemiol Biomarkers Prev; 20(12); 2642–5. ©2011 AACR.
Yolk Sac Diameter in Early Pregnancy in Maternal Diabetes Mellitus
Authors: Papaioannou George I. , Syngelaki Argyro , Maiz Nerea , Ross Jackie A. , Nicolaides Kypros H.
Published: December 2011

Aims: To investigate the possible association between maternal diabetes mellitus and increased yolk sac diameter (YSD). Methods: We searched the Early Pregnancy Unit database to identify singleton pregnancies with measurements of embryonic crown-rump length (CRL) and YSD at 6–10 weeks of gestation and subsequent delivery of phenotypically normal neonates. We compared the YSD in patients with pre-gestational and gestational diabetes with those who were unaffected by diabetes. Results: A total of 3,686 cases were identified including 43 (1.2%) with type 1 diabetes, 31 (0.8%) with type 2 diabetes and 71 (1.9%) who subsequently developed gestational diabetes. The measured YSD in both the diabetic and non-diabetic groups were expressed as differences from the expected normal mean for CRL (Δ values). There were no significant differences in ΔYSD between the groups. The median (IQR) ΔYSD was 0.01 (–0.33 to 0.37) mm in the unaffected group, 0.01 (–0.35 to 0.51) mm in type 1 diabetes, –0.02 (–3.44 to 0.27) mm in type 2 diabetes and 0.01 (–0.28 to 0.35) mm in gestational diabetes. Conclusion: After exclusion of miscarriages and embryopathies, pre-gestational and gestational diabetes are not associated with altered YSD.