bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced macrophage tropism of HIV in brain and lymphoid tissues is associated with sensitivity to the broadly neutralizing CD4 binding site antibody b12
Authors: Dunfee Rebecca L , Thomas Elaine R , Gabuzda Dana 
Published: July 2009

Abstract
Macrophages in the central nervous system (CNS) and other tissues are an important cellular reservoir for human immunodeficiency virus type 1 (HIV) infection, particularly in the later stages of disease. Macrophage-tropic HIV strains have an enhanced capacity to enter cells expressing low levels of CD4 through mechanisms that are not well understood. Here, we use a panel of primary HIV envelopes from brain and lymphoid tissues to examine the relationship between neutralization sensitivity to reagents targeting the CD4 binding site and virus entry into macrophages. Neutralization assays using pseudotyped viruses showed an association between the capacity of HIV to enter macrophages and increased sensitivity to the broadly neutralizing monoclonal antibody (mAb) b12, which recognizes a conserved epitope overlapping the CD4 binding site, but not sensitivity to soluble CD4 (sCD4) or b6, a non-neutralizing CD4 binding site mAb. Furthermore, loss of an N-linked glycosylation site at position 386 in the V4 region of Env enhanced macrophage tropism together with b12 sensitivity, but not neutralization by sCD4, b6, or a broadly neutralizing AIDS patient serum. These findings suggest that exposure of the b12 epitope, rather than exposure of the CD4 binding site per se, enhances HIV macrophage tropism, possibly by exposing a region on the outer domain of gp120 that is initially recognized by CD4. These findings suggest overlap between specific gp120 determinants in or near the b12 epitope and those conferring macrophage tropism.
High rate of unintended pregnancy among pregnant women in a maternity hospital in Córdoba, Argentina: a pilot study
Authors: Palena Celina , Bahamondes M Valeria , Schenk Verónica , Bahamondes Luis , Fernandez-Funes Julio 
Published: July 2009

Abstract

Background
Although Argentina has a new law on Reproductive Health, many barriers continue to exist regarding provision of contraceptive methods at public healthcare facilities.

Methods
We asked 212 pregnant women selected at random at the Maternity and Neonatal Hospital, Córdoba, Argentina, to participate in our descriptive study. Women were asked to complete a structured questionnaire. The objectives were to determine the rate of unintended pregnancies, reasons for not using contraception, past history of contraceptive use, and intended future use.

Results
Two hundred women responded to the questionnaire. Forty percent of the women stated that they had never used contraception and pregnancy was declared unintended by 65%. In the unintended pregnancy group, almost 50% of women said that they had not been using a contraceptive method because they were "unaware about contraception", and 25% stated that their contraceptive method had failed. Almost 85% of women stated that they intended to use contraception after delivery.

Conclusion
Approximately two-thirds of all pregnancies in this sample were unintended. Although the data is limited by the small sample size, our findings suggest that our government needs to invest in counseling and in improving the availability and access to contraceptive methods.
Higher activation of TLR9 in plasmacytoid dendritic cells by microbial DNA compared with self-DNA based on CpG-specific recognition of phosphodiester DNA
Authors: Coch Christoph , Busch Nicolas , Wimmenauer Vera , Hartmann Evelyn , Janke Markus , Abdel-Mottaleb Mona Mohamed Ahmed , Lamprecht Alf , Ludwig Janos , Barchet Winfried , Schlee Martin , Hartmann Gunther 
Published: July 2009

Abstract
Mammalian genomic DNA complexed to the natural antimicrobial cationic peptide LL37 induces type I interferon but less than bacterial DNA or CG-dinucleotide containing oligodeoxynucleotides.
TLR9 detects DNA in endolysosomal compartments of human B cells and PDC. Recently, the concept of the CpG motif specificity of TLR9-mediated detection, specifically of natural phosphodiester DNA, has been challenged. Unlike in human B cells, CpG specificity of natural phosphodiester DNA recognition in human PDC has not been analyzed in the literature. Here, we found that the induction of IFN-α and TNF-α in human PDC by phosphodiester ODNs containing one or two CG dinucleotides was reduced to a lower level when the CG dinucleotides were methylated and was abolished if the CGs were switched to GCs. Consistent with a high frequency of unmethylated CG dinucleotides, bacterial DNA induced high levels of IFN-α in PDC; IFN-α was reduced but not abolished upon methylation of bacterial DNA. Mammalian DNA containing low numbers of CG dinucleotides, which are frequently methylated, induced IFN-α in PDC consistently but on a much lower level than bacterial DNA. For activation of PDC, phosphodiester ODNs and genomic DNA strictly required complexation with cationic molecules such as the keratinocyte-derived antimicrobial peptide LL37 or a scrambled derivative. In conclusion, we demonstrate that self-DNA complexed to cationic molecules activate PDC and thus, indeed, may function as DAMPs; nevertheless, the preference of PDC for CpG containing DNA provides the basis for the discrimination of microbial from self-DNA even if DNA is presented in the condensed form of a complex.
Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor Expression and Benefit From Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As First-Line Treatment in HER2-Negative or Unknown Metastatic Breast Cancer
Authors: Finn Richard S. , Press Michael F. , Dering Judy , Arbushites Michael , Koehler Maria , Oliva Cristina , Williams Lisa S. , Di Leo Angelo 
Published: July 2009

Purpose Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) with activity in HER2-amplified metastatic breast cancer (MBC). Its role in non–HER2-amplified MBC remains unclear. EGF30001, a phase III trial of lapatinib and paclitaxel versus paclitaxel and placebo, demonstrated lapatinib does not significantly benefit HER2-negative or HER2-unselected patients with MBC. Published data support interactions between steroid hormone and peptide growth factor signaling. We hypothesized that molecular subgroups may exist within EGF30001 that would benefit from lapatinib. Methods A blinded, retrospective biomarker evaluation was performed using immunohistochemistry to semiquantitate estrogen (ER), progesterone (PR), and EGFR expression. HER2 amplification was determined by fluorescent in situ hybridization. Effects of these biomarkers on event-free survival (EFS) were examined in patients with available tissue (n = 493). Results Lapatinib improved median EFS in HER2-amplified, ER- or PR-positive MBC (n = 36; 5.7 v 4.5 months; P = .351); benefit was greater and statistically significant in HER2-amplified, ER-negative, PR-negative MBC (n = 42; 8.3 v 5.0 months; P = .007). In HER2-negative, ER-positive MBC, median EFS improvement varied by degree of PR expression (H-score): no benefit if PR-strong (n = 133; 9.3 v 7.3 months; P = .373), benefit if PR-weak (n = 50; 7.3 v 2.4 months; P = .026), and potential antagonism if PR-negative (n = 40; 3.7 v 7.2 months; P = .004). No benefit was seen in triple-negative MBC (n = 131; median EFS, 4.6 v 4.8 months; P = .255). EGFR expression was not correlated with benefit from lapatinib. Conclusion Although subgroups are small, these analyses support the hypothesis that semiquantitative determination of hormone receptor status may be a surrogate for EGFR and/or HER2 dependency.
Absence of Progression As Assessed by Response Evaluation Criteria in Solid Tumors Predicts Survival in Advanced GI Stromal Tumors Treated With Imatinib Mesylate: The Intergroup EORTC-ISG-AGITG Phase III Trial
Authors: Le Cesne Axel , Van Glabbeke Martine , Verweij Jaap , Casali Paolo G. , Findlay Michael , Reichardt Peter , Issels Rolf , Judson Ian , Schoffski Patrick , Leyvraz Serge , Bui Binh , Hogendoorn Pancras C.W. , Sciot Raf , Blay Jean-Yves 
Published: July 2009

Purpose From February 2001 to February 2002, 946 patients with advanced GI stromal tumors (GISTs) treated with imatinib were included in a controlled EORTC/ISG/AGITG (European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group) trial. This analysis investigates whether the response classification assessed by RECIST (Response Evaluation Criteria in Solid Tumors), predicts for time to progression (TTP) and overall survival (OS). Patients and Methods Per protocol, the first three disease assessments were done at 2, 4, and 6 months. For the purpose of the analysis (landmark method), disease response was subclassified in six categories: partial response (PR; > 30% size reduction), minor response (MR; 10% to 30% reduction), no change (NC) as either NC− (0% to 10% reduction) or NC+ (0% to 20% size increase), progressive disease (PD; > 20% increase/new lesions), and subjective PD (clinical progression). Results A total of 906 patients had measurable disease at entry. At all measurement time points, complete response (CR), PR, and MR resulted in similar TTP and OS; this was also true for NC− and NC+, and for PD and subjective PD. Patients were subsequently classified as responders (CR/PR/MR), NC (NC+/NC−), or PD. This three-class response categorization was found to be highly predictive of further progression or survival for the first two measurement points. After 6 months of imatinib, responders (CR/PR/MR) had the same survival prognosis as patients classified as NC. Conclusion RECIST perfectly enables early discrimination between patients who benefited long term from imatinib and those who did not. After 6 months of imatinib, if the patient is not experiencing PD, the pattern of radiologic response by tumor size criteria has no prognostic value for further outcome. Imatinib needs to be continued as long as there is no progression according to RECIST.
The Impact of the Privacy Rule on Cancer Research: Variations in Attitudes and Application of Regulatory Standards
Authors: Goss Elizabeth , Link Michael P. , Bruinooge Suanna S. , Lawrence Theodore S. , Tepper Joel E. , Runowicz Carolyn D. , Schilsky Richard L. 
Published: July 2009

Purpose The American Society of Clinical Oncology (ASCO) Cancer Research Committee designed a qualitative research project to assess the attitudes of cancer researchers and compliance officials regarding compliance with the US Privacy Rule and to identify potential strategies for eliminating perceived or real barriers to achieving compliance. Methods A team of three interviewers asked 27 individuals (13 investigators and 14 compliance officials) from 13 institutions to describe the anticipated approach of their institutions to Privacy Rule compliance in three hypothetical research studies. Results The interviews revealed that although researchers and compliance officials share the view that patients' cancer diagnoses should enjoy a high level of privacy protection, there are significant tensions between the two groups related to the proper standards for compliance necessary to protect patients. The disagreements are seen most clearly with regard to the appropriate definition of a “future research use” of protected health information in biospecimen and data repositories and the standards for a waiver of authorization for disclosure and use of such data. Conclusion ASCO believes that disagreements related to compliance and the resulting delays in certain projects and abandonment of others might be eased by additional institutional training programs and consultation on Privacy Rule issues during study design. ASCO also proposes the development of best practices documents to guide 1) creation of data repositories, 2) disclosure and use of data from such repositories, and 3) the design of survivorship and genetics studies.
The obscuring object of race: Clinical breast exams and coping styles in ethnic subpopulations of women
Authors: Kudadjie‐Gyamfi Elizabeth K. , Magai Carol , Consedine Nathan S. 
Published: July 2009

Objectives. Differences in breast cancer screening rates have been linked to many factors including race, access to healthcare, and breast cancer knowledge and beliefs; less frequently studied has been the role of characteristic styles of coping. In this study, we examined ethnicity and the role of coping with a possible breast cancer diagnosis in the context of whether or not women obtained clinical breast examinations (CBE).Design. To measure coping, a stressor, in the form of a vignette asking participants to imagine they had just received a breast diagnosis upon a doctor's visit, was used.Method. Three hundred and eight women from seven ethnic subpopulations (and from three racial groups) in the USA were interviewed regarding frequency of breast screening, as well as how they would likely cope with a diagnosis of breast cancer.Results. CBE rates were similar across groups and were differentially predicted by the different coping styles. Analysing the results using typical racial categories (rather than distinct ethnic groupings) obscured these results. Furthermore, avoidance predicted CBE and mammogram rates differently, specifically, predicting mammogram rates differentially for each group, with no relation to CBE rates.Conclusion. Recognition of the roles of problem solving, social support, and avoidance in coping with a possible breast cancer diagnosis may guide the development and provision of interventions that are more sensitive to the characteristics of specific groups of women. Examinations of psychological variables in preventive health behaviours must begin to analyse diversity by paying attention to ethnic specificity, rather than race, as well as to the underlying nature of the screening task.
Self‐reported health, self‐reported fitness, and all‐cause mortality: Prospective cohort study
Authors: Phillips Anna C. , Der Geoff , Carroll Douglas 
Published: July 2009

Objectives. Self‐reported health has a well established relationship to later mortality, although the reasons are not entirely understood. This study examined the association of a similar self‐reported measure of fitness with mortality and compared it to that of self‐reported health.Design. The study had a prospective cohort design with multiple sampling points.Methods. Participants were 858 men and women from Glasgow and the surrounding area of Scotland, aged 59 when self‐reported health and fitness data were first collected in 1991/92. They were re‐interviewed at age 64 and 69 and mortality was tracked for 16.5 years in total. Hazard ratios for all cause mortality were estimated for those that reported poor health or poor fitness relative to others their age, taking into account a range of covariates, some of which were also time varying.Results. In both unadjusted and covariate adjusted models, self‐reported fitness was at least as good a predictor of mortality as self‐reported health. In a mutually adjusted model, both again emerged as significant predictors. Poor subjective health with poor subjective fitness appeared to be a particularly lethal combination.Conclusion. Both self‐reported health and self‐reported fitness were independent predictors of mortality. Where the objective assessment of aerobic fitness is not feasible, a simple measure of subjective fitness could prove a useful alternative.
Tribocharging of Particle Contaminants Evaluated as an Ignition Source in Oxygen-Enriched Environments
Authors: Oza Aditi , Ghosh Sudipto , Chowdhury Kanchan 
Published: July 2009

Abstract
Contamination particles make an oxygen system more vulnerable to fire hazard as they provide a large surface area with reduced minimum energy of ignition. Adiabatic compression, resonance, solid friction, flow friction, and promoted ignition have acted as the source of ignition in oxygen systems. In this paper, static electricity generated in solid particles is proposed to be another possible source of ignition. It is known that the movement of particles in a system results in the buildup of static charges in them. This static electricity, if supported by suitable geometric configuration and grounding of metal projections, may lead to propagating brush discharge (PBD) and provide the energy needed for initiation of fire. Particles with low auto-ignition temperature, particularly in dispersed state, may help in initiating the fire, while metal particles may aid the propagation because of their high combustion energy. In this paper, we have determined the velocity profile utilizing the FLUENT code and calculated the charge generated in particles, exploring the ignition probability of equipment in oxygen environment through electrostatic discharge. We have also attempted to perform preliminary calculation to determine charge density and the electric field strength required for brush discharge. Computational fluid dynamics analyses on globe valves reveal the presence of probable areas of particulate accumulation in the valve. The decrease in minimum ignition energy (MIE) in the environment of high pressure, high temperature, high purity of oxygen, low humidity, small particles, high dielectric constant, low thickness of insulating layer, and high resistance of the deposited dust layer facilitates occurrence of PBD, which may cause ignition. Adiabatic heating may aid combustion by lowering the MIE of particles. Experiments have been proposed for verification of the hypothesis and analytical calculations presented by the authors. The paper may give a new insight into the possible causes of oxygen fire.
Additive Genetic Variability and the Bayesian Alphabet
Authors: Gianola Daniel , de los Campos Gustavo , Hill William G , Manfredi Eduardo , Fernando Rohan 
Published: July 2009

Abstract
The use of all available molecular markers in statistical models for prediction of quantitative traits has led to what could be termed a genomic-assisted selection paradigm in animal and plant breeding. This article provides a critical review of some theoretical and statistical concepts in the context of genomic-assisted genetic evaluation of animals and crops. First, relationships between the (Bayesian) variance of marker effects in some regression models and additive genetic variance are examined under standard assumptions. Second, the connection between marker genotypes and resemblance between relatives is explored, and linkages between a marker-based model and the infinitesimal model are reviewed. Third, issues associated with the use of Bayesian models for marker-assisted selection, with a focus on the role of the priors, are examined from a theoretical angle. The sensitivity of a Bayesian specification that has been proposed (called “Bayes A”) with respect to priors is illustrated with a simulation. Methods that can solve potential shortcomings of some of these Bayesian regression procedures are discussed briefly.
The Complex Tale of the achaete–scute Complex: A Paradigmatic Case in the Analysis of Gene Organization and Function During Development
Authors: García-Bellido Antonio , de Celis Jose F 
Published: July 2009

Abstract
The achaete–scute gene complex (AS-C) contains four genes encoding transcription factors of the bHLH family, achaete, scute, lethal of scute, and asense located in 40 kb of DNA containing multiple cis-regulatory position-specific enhancers. These genes play a key role in the commitment of epidermal cells toward a neural fate, promoting the formation of both sensory organs in the peripheral nervous system (bristles) of the adult and of neuroblasts in the central nervous system of the embryo. The analysis of the AS-C initially focused on the variations in positional specificity of effects of achaete (ac) and scute (sc) alleles on macrochaete bristle pattern in the Drosophila adult epidermis, and from there it evolved as a key entry point into understanding the molecular bases of pattern formation and cell commitment. In this perspective, we describe how the study of the AS-C has contributed to the understanding of eukaryotic gene organization and the dissection of the developmental mechanisms underlying pattern formation.
Expanded Newborn Screening: Outcome in Screened and Unscreened Patients at Age 6 Years
Authors: Wilcken Bridget , Haas Marion , Joy Pamela , Wiley Veronica , Bowling Francis , Carpenter Kevin , Christodoulou John , Cowley David , Ellaway Carolyn , Fletcher Janice , Kirk Edwin P. , Lewis Barry , McGill Jim , Peters Heidi , Pitt James , Ranieri Enzo , Yaplito-Lee Joy , Boneh Avihu 
Published: July 2009

OBJECTIVE: Tandem mass spectrometry is widely applied to routine newborn screening but there are no long-term studies of outcome. We studied the clinical outcome at six years of age in Australia.
METHODS: In a cohort study, we analyzed the outcome at 6 years for patients detected by screening or by clinical diagnosis among &gt;2 million infants born from 1994 to 1998 (1 017 800, all unscreened) and 1998 to 2002 (461 500 screened, 533 400 unscreened) recording intellectual and physical condition, school placement, other medical problems, growth, treatment, diet, and hospital admissions. Results were analyzed separately for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and other disorders, and grouped patients as those who presented clinically or died in the first 5 days of life; patients presented later or diagnosed by screening, and those with substantially benign disorders.
RESULTS: Inborn errors, excluding phenylketonuria, were diagnosed in 116 of 1 551 200 unscreened infants (7.5/100 000 births) and 70 of 461 500 screened infants (15.2/100 000 births). Excluding MCADD, 21 unscreened patients with metabolic disorders diagnosed after 5 days of life died or had a significant intellectual or physical handicap (1.35/100 000 population) compared with 2 of the screened cohort (0.43/100 000; odds ratio: 3.1 [95% CI: 0.73–13.32]). Considering the likely morbidity or mortality among the expected number of never-diagnosed unscreened patients, there would be a significant difference. Growth distribution was normal in all cohorts.
CONCLUSION: Screening by tandem mass spectrometry provides a better outcome for patients at 6 years of age, with fewer deaths and fewer clinically significant disabilities.