bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort
Authors: Woolcott Christy G , Maskarinec Gertraud , Haiman Christopher A , Verheus Martijn , Pagano Ian S , Le Marchand Loïc , Henderson Brian E , Kolonel Laurence N 
Published: February 2009

Abstract
Introduction
Mammographic density is a strong risk factor for breast cancer. Our objective was to examine its association with polymorphisms identifying breast cancer susceptibility loci that were ascertained in recent genome-wide association studies.

Methods
Subjects were 825 women who participated in previous case–control studies of mammographic density and genetic factors nested within the Multiethnic Cohort study and were from three ethnic groups (White, Japanese American, Native Hawaiian). Eight polymorphisms (rs2981582 in FGFR2, rs3803662 and rs12443621in TOX3, rs3817198 in LSP1, rs981782 and rs10941679 near HCN1/MRPS30, rs889312 in MAP3K1, and rs13387042 at 2q) were examined. Mammographic density was quantified with a computer-assisted method as the percent dense area: the area of radiologically dense fibroglandular tissue relative to the total breast area that also includes radiologically lucent fatty tissue.

Results
The polymorphism rs12443621 in TOX3 was associated with percent dense area; women with at least one G allele (previously associated with increased breast cancer risk) had 3% to 4% higher densities than women with two A alleles. The polymorphism rs10941679 near HCN1/MRPS30 was also associated with percent dense area; women who were homozygous for the G allele (previously associated with increased breast cancer risk) had 4% to 5% lower densities than women with at least one A allele. The other polymorphisms were not associated with percent dense area.

Conclusions
The available data suggest that the effects of most of these polymorphisms on breast cancer are not mediated by mammographic density. Some effects may have been too small to be detected. The association with rs12443621 may provide clues as to how variation in TOX3 influences breast cancer risk.
Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis
Authors: Flierl Michael A , Stahel Philip F , Rittirsch Daniel , Huber-Lang Markus , Niederbichler Andreas D , Hoesel L Marco , Touban Basel M , Morgan Steven J , Smith Wade R , Ward Peter A , Ipaktchi Kyros 
Published: February 2009

Abstract
Introduction
Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis.

Methods
Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls.

Results
Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group.

Conclusions
Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.
Contrast enhancement of stimulus intermittency in a primary olfactory network and its behavioral significance
Authors: Lei Hong , Riffell Jeffrey A , Gage Stephanie L , Hildebrand John G 
Published: February 2009

Abstract
Background
An animal navigating to an unseen odor source must accurately resolve the spatiotemporal distribution of that stimulus in order to express appropriate upwind flight behavior. Intermittency of natural odor plumes, caused by air turbulence, is critically important for many insects, including the hawkmoth, Manduca sexta, for odor-modulated search behavior to an odor source. When a moth's antennae receive intermittent odor stimulation, the projection neurons (PNs) in the primary olfactory centers (the antennal lobes), which are analogous to the olfactory bulbs of vertebrates, generate discrete bursts of action potentials separated by periods of inhibition, suggesting that the PNs may use the binary burst/non-burst neural patterns to resolve and enhance the intermittency of the stimulus encountered in the odor plume.

Results
We tested this hypothesis first by establishing that bicuculline methiodide reliably and reversibly disrupted the ability of PNs to produce bursting response patterns. Behavioral studies, in turn, demonstrated that after injecting this drug into the antennal lobe at the effective concentration used in the physiological experiments animals could no longer efficiently locate the odor source, even though they had detected the odor signal.

Conclusions
Our results establish a direct link between the bursting response pattern of PNs and the odor-tracking behavior of the moth, demonstrating the behavioral significance of resolving the dynamics of a natural odor stimulus in antennal lobe circuits.
M. bovisBCG induced expression of COX-2 involves nitric oxide-dependent and -independent signaling pathways
Authors: Bansal Kushagra , Narayana Yeddula , Patil Shripad A , Balaji Kithiganahalli N 
Published: February 2009

AbstractIn a multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) by Mycobacterium bovis bacillus Calmette-Guerin (BCG) may act as an important influencing factor for the effective host immunity. We here demonstrate that M. bovis BCG-triggered TLR2-dependent signaling leads to COX-2 and PGE2 expression in vitro in macrophages and in vivo in mice. Further, the presence of PGE2 could be demonstrated in sera or cerebrospinal fluid of tuberculosis patients. The induced COX-2 expression in macrophages is dependent on NF-κB activation, which is mediated by inducible NO synthase (iNOS)/NO-dependent participation of the members of Notch1-PI-3K signaling cascades as well as iNOS-independent activation of ERK1/2 and p38 MAPKs. Inhibition of iNOS activity abrogated the M. bovis BCG ability to trigger the generation of Notch1 intracellular domain (NICD), a marker for Notch1 signaling activation, as well as activation of the PI-3K signaling cascade. On the contrary, treatment of macrophages with 3-morpholinosydnonimine, a NO donor, resulted in a rapid increase in generation of NICD, activation of PI-3K pathway, as well as the expression of COX-2. Stable expression of NICD in RAW 264.7 macrophages resulted in augmented expression of COX-2. Further, signaling perturbations suggested the involvement of the cross-talk of Notch1 with members with the PI-3K signaling cascade. These results implicate the dichotomous nature of TLR2 signaling during M. bovis BCG-triggered expression of COX-2. In this perspective, we propose the involvement of iNOS/NO as one of the obligatory, early, proximal signaling events during M. bovis BCG-induced COX-2 expression in macrophages.
The influence of swing phase load on the electrochemical response, friction, and ion release of metal-on-metal hip prostheses in a friction simulator
Authors: Yan Y , Neville A , Dowson D , Williams S , Fisher J 
Published: February 2009

Second-generation metal-on-metal (MoM) hip replacements have been considered as an alternative to commonly used polyethylene-on-metal joint prostheses due to polyethylene wear debris-induced osteolysis. However, the role of corrosion is still not fully understood. Bench tests have been carried out to characterize the relationship and interactions between electrochemical reactions ( corrosion), mechanical damage ( wear), and biological environments. An investigation of the corrosion response of MoM hip replacements has been conducted in a friction simulator in an initial attempt to reveal the tribocorrosion behaviour of clinically used metallic hip implants. These are the first reported results where electrochemical measurements have been made in-situ in a joint simulator. A ProSim friction simulator was used with an integrated electrochemical cell in this study of biotribocorrosion. Peak loads of 2 kN with three different swing phase loads, 25, 100, and 300 N were used to determine the effect of different swing loads on the corrosion processes (through electrochemical measurements and the release of metal ions). The three lubricants, NaCl solution, 25 per cent serum, and bovine synovial fluid, were employed as lubricants in this study. All femoral heads of the tested hip implants were 36 mm in diameter and made from a CoCrMo alloy. The open circuit potential (OCP) was monitored while implants were subjected to dynamic loading cycles. The link between swing phase load, lubricant, and ion release is discussed in relation to corrosion processes occurring at the tribological interface.
A longitudinal analysis of family migration and the gender gap in earnings in the united states and great britain
Authors: Cooke Thomas J. , Boyle Paul , Couch Kenneth , Feijten Peteke 
Published: February 2009

Abstract
This article uses longitudinal data for the United States and Great Britain to examine the impact of residential mobility and childbirth on the earnings of women, their family earnings, and the related division of earnings by gender. This project is the _ rst to compare explicitly the impact of childbirth and family migration on women’s earnings, and it extends prior cross-sectional and longitudinal studies on isolated countries by providing a direct contrast between two major industrialized nations, using comparable measures. The results indicate that families respond in similar ways in both countries to migration and childbirth. In response to both migration and childbirth, women’s earnings fall at the time of the event and recover slowly afterward, but the magnitude of the impact is roughly twice as large for childbirth as for migration. However, migration but not the birth of a child is also associated with a significant increase in total family earnings because of increased husbands’ earnings. As a result, the effect of migration on the relative earnings of wives to husbands is similar to the effect of childbirth. These results suggest that family migration should be given consideration in the literature on the gender earnings gap.
Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics
Authors: Shen Yiping , Wu Bai-Lin 
Published: February 2009

Abstract
Background: Microarray-based genomic DNA profiling (MGDP) technologies are rapidly moving from translational research to clinical diagnostics and have revolutionized medical practices. Such technologies have shown great advantages in detecting genomic imbalances associated with genomic disorders and single-gene diseases.
Content: We discuss the development and applications of the major array platforms that are being used in both academic and commercial laboratories. Although no standardized platform is expected to emerge soon, comprehensive oligonucleotide microarray platforms—both comparative genomic hybridization arrays and genotyping hybrid arrays—are rapidly becoming the methods of choice for their demonstrated analytical validity in detecting genomic imbalances, for their flexibility in incorporating customized designs and updates, and for the advantage of being easily manufactured. Copy number variants (CNVs), the form of genomic deletions/duplications detected through MGDP, are a common etiology for a variety of clinical phenotypes. The widespread distribution of CNVs poses great challenges in interpretation. A broad survey of CNVs in the healthy population, combined with the data accumulated from the patient population in clinical laboratories, will provide a better understanding of the nature of CNVs and enhance the power of identifying genetic risk factors for medical conditions.
Summary: MGDP technologies for molecular diagnostics are still at an early stage but are rapidly evolving. We are in the process of extensive clinical validation and utility evaluation of different array designs and technical platforms. CNVs of currently unknown importance will be a rich source of novel discoveries.
Coamplification at Lower Denaturation Temperature-PCR Increases Mutation-Detection Selectivity of TaqMan-Based Real-Time PCR
Authors: Li Jin , Wang Lilin , Jänne Pasi A , Makrigiorgos G Mike 
Published: February 2009

Abstract
Background: DNA genotyping with mutation-specific TaqMan® probes (Applied Biosystems) is broadly used in detection of single-nucleotide polymorphisms but is less so for somatic mutations because of its limited selectivity for low-level mutations. We recently described coamplification at lower denaturation temperature-PCR (COLD-PCR), a method that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences during the PCR. We demonstrate that combining COLD-PCR with TaqMan technology provides TaqMan genotyping with the selectivity needed to detect low-level somatic mutations.
Methods: Minor-groove binder-based or common TaqMan probes were designed to contain a nucleotide that matches the desired mutation approximately in the middle of the probe. The critical denaturation temperature (Tc) of each amplicon was then experimentally determined. COLD-PCR/TaqMan genotyping was performed in 2 steps: denaturation at the Tc, followed by annealing and extension at a single temperature (fast COLD-PCR). The threshold cycle was used to identify mutations on the basis of serial dilutions of mutant DNA into wild-type DNA and to identify TP53 (tumor protein p53) and EGFR [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)] mutations in tumors.
Results: COLD-PCR/TaqMan genotyping identified G&gt;A mutations within TP53 exon 8 (codon 273 mutation hot spot) and C&gt;T mutations within the EGFR gene (drug-resistance mutation T790M) with a selectivity improvement of 15- to 30-fold over regular PCR/TaqMan genotyping. A second round of COLD-PCR/TaqMan genotyping improved the selectivity by another 15- to 30-fold and enabled detection of 1 mutant in 2000 wild-type alleles. Use of COLD-PCR/TaqMan genotyping allowed quantitative identification of low-level TP53 and T790 mutations in colon tumor samples and in non-small-cell lung cancer cell lines treated with kinase inhibitors.
Conclusions: The major improvement in selectivity provided by COLD-PCR enables the popular TaqMan genotyping method to become a powerful tool for detecting low-level mutations in clinical samples.
mRNA Expression and BRAF Mutation in Circulating Melanoma Cells Isolated from Peripheral Blood with High Molecular Weight Melanoma-Associated Antigen-Specific Monoclonal Antibody Beads
Authors: Kitago Minoru , Koyanagi Kazuo , Nakamura Takeshi , Goto Yasufumi , Faries Mark , O'Day Steven J , Morton Donald L , Ferrone Soldano , Hoon Dave S B 
Published: February 2009

Abstract
Background: The detection of circulating tumor cells (CTCs) in the peripheral blood of melanoma patients by quantitative real-time reverse-transcription PCR (qRT-PCR) analysis correlates with a poor prognosis. The assessment of CTCs from blood has been difficult because of lack of a good monoclonal antibody (mAb) directed against surface cell antigens to capture melanoma cells.
Methods: Blood was collected prospectively from 57 melanoma patients (43 test and 14 test-development cases) and 5 healthy donors. High molecular weight melanoma-associated antigen (HMW-MAA)-specific mAbs bound to immunomagnetic beads were used to isolate CTCs. mRNA and/or DNA were extracted from CTCs. Testing for the expression of a melanoma-associated gene panel (MLANA, MAGEA3, and MITF) with qRT-PCR and for the presence of BRAFmt (a BRAF gene variant encoding the V600E mutant protein) verified the beads-isolated CTCs to be melanoma cells. A peptide nucleic acid-clamping PCR assay was used for BRAFmt analysis.
Results: Spiking of peripheral blood cells (PBCs) with melanoma cells showed that the beads-based detection assay can detect approximately 1 melanoma cell in 5 × 106 PBCs. qRT-PCR analysis detected MLANA, MAGEA3, and MITF expression in 19 (44%), 29 (67%), and 19 (44%) of the patients, respectively. At least one biomarker of the panel was positive in 40 (93%) of the 43 melanoma patients. BRAFmt was detected in 17 (81%) of the 21 assessed stage IV melanoma patients.
Conclusion: The assay of bead capture coupled with the PCR has utility for assessing CTCs in melanoma patients, which can then be characterized for both genomic and transcriptome expression.
Circulating Prostate Tumor Cells Detected by Reverse Transcription-PCR in Men with Localized or Castration-Refractory Prostate Cancer: Concordance with CellSearch Assay and Association with Bone Metastases and with Survival
Authors: Helo Pauliina , Cronin Angel M , Danila Daniel C , Wenske Sven , Gonzalez-Espinoza Rita , Anand Aseem , Koscuiszka Michael , Väänänen Riina-Minna , Pettersson Kim , Chun Felix K-H , Steuber Thomas , Huland Hartwig , Guillonneau Bertrand D , Eastham James A , Scardino Peter T , Fleisher Martin , Scher Howard I , Lilja Hans 
Published: February 2009

Abstract
Background: Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival.
Methods: KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch™; Veridex) approved for clinical use.
Results: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (≥80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%–85%) and correlated (Kendall τ, 0.60–0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status.
Conclusions: Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.
Ice Hockey Facility Safety: Litigated Case Studies Involving Ice Hockey Injuries
Authors: Lucenko Leonard K. 
Published: February 2009

Abstract
This paper will discuss the duties facility owners and operators owe participants and spectators in the ice skating and ice hockey environment. These duties have been established by case law, standards in the industry, and the safety and risk management literature in sports and recreation. There will also be a discussion of court cases that illustrate the importance of incorporating risk management principles and industry standards into operating procedures. The consequences, when these principles are not followed, will also be addressed based on results of litigated cases.
Comparison of CANDU Fuel Bundle Finite Element Model with Unirradiated Mechanical Load Experiments
Authors: Lampman Timothy J. , Popescu Adrian , Freire-Canosa Jose 
Published: February 2009

Abstract
A requirement of spent nuclear fuel is to maintain its structural integrity at all times to enable its safe and efficient handling during storage, transportation, and placement in a deep geological repository. In Canada, commercial spent fuel is currently stored in light water pools for about ten years before being transferred to dry storage where storage may extend up to 100 years. Investigations on the fuel structural integrity evolution during dry storage are being performed for spent CANDU fuel bundles. A CANDU nuclear fuel bundle is a cylindrical assembly approximately 0.1 m in diameter and 0.5 m in length made of 28 or 37 fuel elements held together by welding two endplates at both ends. The welds have a circular notch of less than 10 μm diameter. Significant hydraulic, mechanical, and thermal loads during bundle irradiation in the reactor may lead to bundle deformation, which when coupled with the sharp weld notch can result in significant stress enhancement at the notch tip and possibly activate delayed hydride cracking (DHC) during dry storage. To better understand the stress levels in CANDU fuel during dry storage, a finite element model of CANDU fuel bundles is under development. The stress distribution in the bundle and the stress intensity factor at each weld notch can be evaluated by the model for the spent fuel geometry and dry storage conditions. This paper discusses the agreement between the finite element model and validation experiments using unirradiated 28-element CANDU fuel bundles tested in the elastic and plastic regime.
Association of serum fetuin A with truncal obesity and dyslipidemia in non-diabetic hemodialysis patients
Authors: Chen Hung-Yuan , Chiu Yen-Lin , Hsu Shih-Ping , Pai Mei-Fen , Lai Chun-Fu , Peng Yu-Sen , Kao Tze-Wah , Hung Kuan-Yu , Tsai Tun-Jun , Wu Kwan-Dun 
Published: February 2009

BackgroundFetuin A, a predictor of cardio-vascular (CV) mortality in dialysis patients has been associated with dyslipidemia in non-diabetic coronary artery disease. Truncal obesity is linked to dyslipidemia and also predicts CV mortality. This study had aimed to investigate the associations among fetuin A, truncal obesity, and dyslipidemia in hemodialysis (HD) patients.MethodsOne hundred and nine non-diabetic HD patients were evaluated. Waist circumference, highly sensitive C-reactive protein (hs-CRP), fetuin A, and lipoprotein levels (i.e. total cholesterol (T-CHO), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-HDL-C, and triglyceride (TG)) were measured for analysis of correlations. The patients were divided into tertiles by fetuin A concentrations.ResultsData from 63 women and 46 men aged 60±13 years were analyzed. Patients in the highest tertile of fetuin A (0.33–0.51 g/l) had higher serum creatinine, albumin, T-CHO, LDL-C, non-HDL-C, and TG, more truncal obesity and lower hs-CRP than patients in the lowest tertile (allP<0.05). In multi-variable linear regression analysis, fetuin A was independently associated with TG level and total iron binding capacity after adjustments for age, hemoglobin, albumin, calcium, body mass index, and hs-CRP. Patients in the highest fetuin A tertile had 3.2- and 4.4-fold higher incidence of truncal obesity (P=0.038) and hyper-triglyceridemia (P=0.015) independent of nutritional status and inflammation.ConclusionFetuin A is positively associated with truncal obesity and dyslipidemia, which are independent of malnutrition and inflammation. It may predict visceral adiposity and dyslipidemia, especially TG and TG-rich lipoproteins, in HD patients.