bluuebunny/crossref_metadata_2025_split huggingface dataset:
pHUSH: a single vector system for conditional gene expression
Authors: Gray Daniel C , Hoeflich Klaus P , Peng Li , Gu Zhenyu , Gogineni Alvin , Murray Lesley J , Eby Mike , Kljavin Noelyn , Seshagiri Somasekar , Cole Mary J , Davis David P 
Published: September 2007

Abstract

Background
Conditional expression vectors have become a valuable research tool to avoid artefacts that may result from traditional gene expression studies. However, most systems require multiple plasmids that must be independently engineered into the target system, resulting in experimental delay and an increased potential for selection of a cell subpopulation that differs significantly from the parental line. We have therefore developed pHUSH, an inducible expression system that allows regulated expression of shRNA, miRNA or cDNA cassettes on a single viral vector.

Results
Both Pol II and Pol III promoters have been successfully combined with a second expression cassette containing a codon-optimized tetracycline repressor and selectable marker. We provide examples of how pHUSH has been successfully employed to study the function of target genes in a number of cell types within in vitro and in vivo assays, including conditional gene knockdown in a murine model of brain cancer.

Conclusion
We have successfully developed and employed a single vector system that enables Doxycycline regulated RNAi or transgene expression in a variety of in vitro and in vivo model systems. These studies demonstrate the broad application potential of pHUSH for conditional genetic engineering in mammalian cells.
Biofortification in China: policy and practice
Authors: Campos-Bowers Monica H , Wittenmyer Brian F 
Published: September 2007

AbstractMicronutrient deficiency undernutrition, due to insufficient levels of vitamins and minerals in the diet, remains one of the most prevalent and preventable nutritional problems in the world today. Micronutrient undernutrition is the most common form of malnutrition. Compared to the 180 million children with protein-energy malnutrition, 3.5–5 billion persons are iron-deficient, and 140–250 million persons are vitamin A-deficient. Micronutrient deficiencies diminish physical, cognitive, and reproductive development. Undernutrition is both a cause and a result of poor human health and achievement.Middle-income nations, such as China, also suffer from micronutrient undernutrition's effects. In China's poor western provinces, despite supplementation and fortification efforts, stunting and underweight (symptoms of micronutrient undernutrition) remain common. In recent decades, nutritional adequacy, in terms of available food energy, improved immensely, as the government made food security a top priority. A potential next step for China could be to address specifically micronutrient undernutrition. The paper aims to provide a discussion of policy issues relevant to biofortification, if China were to consider the implementation of this intervention in its rural provinces.Traditional nutritional interventions currently employ four main strategies: dietary modification, supplementation, commercial fortification, and biofortification. Biofortification, a relatively new technique, involves selectively breeding staple plant varieties to increase specific nutrient levels in plant tissues. Biofortification has the potential to provide benefits to humans, plants, and livestock; nourish nutrient-depleted soils; and help increase crop yields per acre. Biofortification methods include selective breeding, reducing levels of anti-nutrients, and increasing levels of substances that promote nutrient absorption.If China were to implement biofortification programs, with help from government agencies and international organizations, several policy questions would need to be addressed. The paper discusses several policy questions that pertain to the relationship between biofortified and genetically modified crops, human health and safety concerns, labeling of biofortified crops for consumers, consumer rights, potential environmental impacts, intellectual property rights, seed disbursement, government investment, private-sector research, and additional agricultural and commercial regulations. Biofortification has the potential to help alleviate the suffering, death, disability, and failure to achieve full human potential that results from micronutrient undernutrition-related diseases.
Estimating uncertainty in observational studies of associations between continuous variables: example of methylmercury and neuropsychological testing in children
Authors: Goodman Michael , Barraj Leila M , Mink Pamela J , Britton Nicole L , Yager Janice W , Dana Flanders W , Kelsh Michael A 
Published: September 2007

Abstract
Background:
We suggest that the need to account for systematic error may explain the apparent lack of agreement among studies of maternal dietary methylmercury exposure and neuropsychological testing outcomes in children, a topic of ongoing debate.

Methods:
These sensitivity analyses address the possible role of systematic error on reported associations between low-level prenatal exposure to methylmercury and neuropsychological test results in two well known, but apparently conflicting cohort studies: the Faroe Islands Study (FIS) and the Seychelles Child Development Study (SCDS). We estimated the potential impact of confounding, selection bias, and information bias on reported results in these studies using the Boston Naming Test (BNT) score as the outcome variable.

Results:
Our findings indicate that, assuming various degrees of bias (in either direction) the corrected regression coefficients largely overlap. Thus, the reported effects in the two studies are not necessarily different from each other.

Conclusion:
Based on our sensitivity analysis results, it is not possible to draw definitive conclusions about the presence or absence of neurodevelopmental effects due to in utero methylmercury exposure at levels reported in the FIS and SCDS.
Recent changes in breast cancer incidence and risk factor prevalence in San Francisco Bay area and California women: 1988 to 2004
Authors: Keegan Theresa HM , Chang Ellen T , John Esther M , Horn-Ross Pamela L , Wrensch Margaret R , Glaser Sally L , Clarke Christina A 
Published: September 2007

Abstract
Introduction
Historically, the incidence rate of breast cancer among non-Hispanic white women living in the San Francisco Bay area (SFBA) of California has been among the highest in the world. Substantial declines in breast cancer incidence rates have been documented in the United States and elsewhere during recent years. In light of these reports, we examined recent changes in breast cancer incidence and risk factor prevalence among non-Hispanic white women in the SFBA and other regions of California.

Methods
Annual age-adjusted breast cancer incidence and mortality rates (1988 to 2004) were obtained from the California Cancer Registry and analyzed using Joinpoint regression. Population-based risk factor prevalences were calculated using two data sources: control subjects from four case-control studies (1989 to 1999) and the 2001 and 2003 California Health Interview Surveys.

Results
In the SFBA, incidence rates of invasive breast cancer increased 1.3% per year (95% confidence interval [CI], 0.7% to 2.0%) in 1988–1999 and decreased 3.6% per year (95% CI, 1.6% to 5.6%) in 1999–2004. In other regions of California, incidence rates of invasive breast cancer increased 0.8% per year (95% CI, 0.4% to 1.1%) in 1988–2001 and decreased 4.4% per year (95% CI, 1.4% to 7.3%) in 2001–2004. In both regions, recent (2000–2001 to 2003–2004) decreases in invasive breast cancer occurred only in women 40 years old or older and in women with all histologic subtypes and tumor sizes, hormone receptor-defined types, and all stages except distant disease. Mortality rates declined 2.2% per year (95% CI, 1.8% to 2.6%) from 1988 to 2004 in the SFBA and the rest of California. Use of estrogen-progestin hormone therapy decreased significantly from 2001 to 2003 in both regions. In 2003–2004, invasive breast cancer incidence remained higher (4.2%) in the SFBA than in the rest of California, consistent with the higher distributions of many established risk factors, including advanced education, nulliparity, late age at first birth, and alcohol consumption.

Conclusion
Ongoing surveillance of breast cancer occurrence patterns in this high-risk population informs breast cancer etiology through comparison of trends with lower-risk populations and by highlighting the importance of examining how broad migration patterns influence the geographic distribution of risk factors.
Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation
Authors: Schlange Thomas , Matsuda Yutaka , Lienhard Susanne , Huber Alexandre , Hynes Nancy E 
Published: September 2007

Abstract
Background
De-regulation of the wingless and integration site growth factor (WNT) signaling pathway via mutations in APC and Axin, proteins that target β-catenin for destruction, have been linked to various types of human cancer. These genetic alterations rarely, if ever, are observed in breast tumors. However, various lines of evidence suggest that WNT signaling may also be de-regulated in breast cancer. Most breast tumors show hypermethylation of the promoter region of secreted Frizzled-related protein 1 (sFRP1), a negative WNT pathway regulator, leading to downregulation of its expression. As a consequence, WNT signaling is enhanced and may contribute to proliferation of human breast tumor cells. We previously demonstrated that, in addition to the canonical WNT/β-catenin pathway, WNT signaling activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mouse mammary epithelial cells via epidermal growth factor receptor (EGFR) transactivation.

Methods
Using the WNT modulator sFRP1 and short interfering RNA-mediated Dishevelled (DVL) knockdown, we interfered with autocrine WNT signaling at the ligand-receptor level. The impact on proliferation was measured by cell counting, YOPRO, and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay; β-catenin, EGFR, ERK1/2 activation, and PARP (poly [ADP-ribose]polymerase) cleavages were assessed by Western blotting after treatment of human breast cancer cell lines with conditioned media, purified proteins, small-molecule inhibitors, or blocking antibodies.

Results
Phospho-DVL and stabilized β-catenin are present in many breast tumor cell lines, indicating autocrine WNT signaling activity. Interfering with this loop decreases active β-catenin levels, lowers ERK1/2 activity, blocks proliferation, and induces apoptosis in MDA-MB-231, BT474, SkBr3, JIMT-1, and MCF-7 cells. The effects of WNT signaling are mediated partly by EGFR transactivation in human breast cancer cells in a metalloprotease- and Src-dependent manner. Furthermore, Wnt1 rescues estrogen receptor-positive (ER+) breast cancer cells from the anti-proliferative effects of 4-hydroxytamoxifen (4-HT) and this activity can be blocked by an EGFR tyrosine kinase inhibitor.

Conclusion
Our data show that interference with autocrine WNT signaling in human breast cancer reduces proliferation and survival of human breast cancer cells and rescues ER+ tumor cells from 4-HT by activation of the canonical WNT pathway and EGFR transactivation. These findings suggest that interference with WNT signaling at the ligand-receptor level in combination with other targeted therapies may improve the efficiency of breast cancer treatments.
Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression
Authors: Beane Jennifer , Sebastiani Paola , Liu Gang , Brody Jerome S , Lenburg Marc E , Spira Avrum 
Published: September 2007

Abstract
Background
Tobacco use remains the leading preventable cause of death in the US. The risk of dying from smoking-related diseases remains elevated for former smokers years after quitting. The identification of irreversible effects of tobacco smoke on airway gene expression may provide insights into the causes of this elevated risk.

Results
Using oligonucleotide microarrays, we measured gene expression in large airway epithelial cells obtained via bronchoscopy from never, current, and former smokers (n = 104). Linear models identified 175 genes differentially expressed between current and never smokers, and classified these as irreversible (n = 28), slowly reversible (n = 6), or rapidly reversible (n = 139) based on their expression in former smokers. A greater percentage of irreversible and slowly reversible genes were down-regulated by smoking, suggesting possible mechanisms for persistent changes, such as allelic loss at 16q13. Similarities with airway epithelium gene expression changes caused by other environmental exposures suggest that common mechanisms are involved in the response to tobacco smoke. Finally, using irreversible genes, we built a biomarker of ever exposure to tobacco smoke capable of classifying an independent set of former and current smokers with 81% and 100% accuracy, respectively.

Conclusion
We have categorized smoking-related changes in airway gene expression by their degree of reversibility upon smoking cessation. Our findings provide insights into the mechanisms leading to reversible and persistent effects of tobacco smoke that may explain former smokers increased risk for developing tobacco-induced lung disease and provide novel targets for chemoprophylaxis. Airway gene expression may also serve as a sensitive biomarker to identify individuals with past exposure to tobacco smoke.
Aberrant dendritic cell differentiation initiated by theMll-Eenfusion gene does not require leukemic transformation
Authors: Sun Q , Kong C T , Huang F P , Chan L C 
Published: September 2007

AbstractDendritic cells (DCs), as specialized APCs, play a key role in the induction of anti-tumor immunity. They originate from bone marrow (BM) progenitors, which are frequently the targets of chromosomal translocations leading to development of leukemia. Aberrant DC differentiation and functions have been observed and are widely reported in patients with leukemia. It is not clear, however, whether such defects are a direct effect of a leukemic fusion gene or simply an outcome of the clinical disease. In this study, we demonstrate for the first time that knockin of the Mll-Een fusion gene can affect myeloid DC differentiation and functions directly, independent of the leukemic disease activities. We showed that the Mll-Een-expressing BM cells [enhanced green fluorescent protein+ (EGFP+)] from leukemic and nonleukemic mice had similarly impaired DC differentiation capacities with functional abnormalities. In contrast, BM cells without Mll-Een expression (EGFP−) showed normal DC differentiation and functions. A reduction in the frequency of CD11c+ DCs was also observed within the EGFP+ population in spleen and lymph nodes, and these cells were dysfunctional. Taken together, our findings suggest that the Mll-Een fusion gene can affect myeloid DC differentiation directly and functions in a cell-autonomous manner, where fully leukemic transformation of the hematopoietic progenitors is not required exclusively. Therefore, the study provides evidence for a direct causal relationship between leukemic gene fusion and abnormal DC differentiation, possibly contributing to the development of leukemia.
Adding Long‐acting β‐agonists to Inhaled Corticosteroids after Discharge from the Emergency Department for Acute Asthma: A Randomized Controlled Trial
Authors: Rowe Brian H. , Wong Eric , Blitz Sandra , Diner Barry , Mackey Duncan , Ross Scott , Senthilselvan Ambikaipakan 
Published: September 2007

Background: Relapses of asthma following emergency department discharge can be reduced with oral and inhaled corticosteroids (ICSs), but the benefits of long‐acting β‐agonists (LABAs) are unclear.Objectives: To determine whether the addition of a LABA reduces relapses in patients with acute asthma.Methods: This was a randomized, controlled, double‐blind trial of 137 patients, aged 18–55 years, conducted in four Canadian EDs. Patients receiving high‐dose ICSs or oral corticosteroids, and those who were medically unstable, were excluded. Patients were randomized to either fluticasone 1,000 μg/day with salmeterol 100 μg/day or fluticasone 1,000 μg/day alone. All patients were discharged on seven days of oral prednisone. The main outcome measure was relapse at 21 days.Results: Both groups had similar baseline characteristics. After 21 days, seven of 69 patients (10.1%) treated with fluticasone/salmeterol and ten of 68 patients (14.7%) treated with fluticasone experienced a relapse (p = 0.42). Prior intubation, female gender, and prior use of ICSs were associated with relapse. There were no clinically or statistically significant differences in overall quality of life and individual domain scores. Fluticasone/salmeterol improved quality of life (p < 0.05) and relapses (24% to 13%; p = 0.35) in patients receiving ICSs at the time of emergency admission.Conclusions: Outpatient treatment with a short course of systemic corticosteroids combined with ICSs is adequate for most patients with asthma discharged from the emergency department; those already receiving ICS agents may benefit from ICS/LABA combination therapy to improve quality of life. Larger studies are needed to confirm the role of inhaled LABAs in acute asthma.
Training Retention of Level C Personal Protective Equipment Use by Emergency Medical Services Personnel
Authors: Northington William E. , Mahoney G. Michael , Hahn Michael E. , Suyama Joe , Hostler Dave 
Published: September 2007

Objectives: To assess the six‐month training retention for out‐of‐hospital providers donning and doffing Level C personal protective equipment (PPE).Methods: In this prospective observational study, 36 out‐of‐hospital providers enrolled in a paramedic program were trained in Level C (chemical‐resistant coverall, butyl gloves, and boots and an air‐purifying respirator) PPE use. A standardized training module and checklist of critical actions developed by a hazardous materials (hazmat) technician were used to evaluate donning and doffing. Students were trained until they were able to correctly don and doff the Level C PPE. An investigator used the checklist accompanying the training module to assess proficiency and remediate mistakes. Six months after initial training, the subjects were reassessed using the same investigator and checklist. Errors were designated as either critical (resulted in major self‐contamination of the airway, such as early removal of the respirator) or noncritical (potentially resulted in minor self‐contamination not involving the airway).Results: Only five subjects (14.3%) were able to don and doff PPE without committing a critical error. The most common critical errors were premature removal of the respirator (65.7%; n= 23) and actions allowing the contaminated suit to touch the body (54.3%; n= 19). The most common noncritical error was possible self‐contamination due to the boots not being removed before exposing other body parts (37.1%; n= 13). Of the seven subjects (20%) with additional prior hazmat training, only two donned and doffed PPE without committing a critical error.Conclusions: Retention of proper donning and doffing techniques in paramedic students is poor at six months after initial training. Even in subjects with previous hazmat, firefighter, and emergency medical services training, critical errors were common, suggesting that current training may be inadequate to prevent harmful exposures in emergency medical services personnel working at a hazmat or weapons of mass destruction incident.
National Study on the Quality of Emergency Department Care in the Treatment of Acute Myocardial Infarction and Pneumonia
Authors: Pham Julius Cuong , Kelen Gabor D. , Pronovost Peter J. 
Published: September 2007

Objectives: To measure the quality of emergency department (ED) care for patients with acute myocardial infarction (AMI) and pneumonia (PNA) and to estimate the number of preventable deaths in these patients.Methods: The authors performed a cross sectional study of ED visits with the diagnosis of AMI or PNA from 1998 to 2004. Data from the National Hospital Ambulatory Medical Care Survey were used. The study involved 544 EDs across the United States. The authors measured the proportion of patients receiving recommended therapies for AMI (aspirin and β‐blockers [BBs]) and PNA (appropriate antibiotics and pulse oximetry). The excess deaths associated with current care were estimated.Results: Aspirin was administered to 40% and BBs to 17% of patients with AMI. Recommended antibiotics were administered to 69% and pulse oximetry was measured in 46% of patients with PNA. During the study period, the percentage receiving BBs and recommended antibiotics increased. There were more than 2.7 million opportunities to improve care and 22,000 excess deaths per year associated with current treatment of AMI and PNA.Conclusions: Quality of care in the ED management of AMI and PNA is below national goals. This deficiency accounts for significant preventable deaths.
Communicating in the “Gray Zone”: Perceptions about Emergency Physician–hospitalist Handoffs and Patient Safety
Authors: Apker Julie , Mallak Larry A. , Gibson Scott C. 
Published: September 2007

Objectives: To identify the perceptions of emergency physicians (EPs) and hospitalists regarding interservice handoff communication as patients are transferred from the emergency department to the inpatient setting.Methods: Investigators conducted individual interviews with 12 physicians (six EPs and six hospitalists). Data evaluation consisted of using the steps of constant comparative, thematic analysis.Results: Physicians perceived handoff communication as a gray zone characterized by ambiguity about patients' conditions and treatment. Two major themes emerged regarding the handoff gray zone. The first theme, poor communication practices and conflicting communication expectations, presented barriers that exacerbated physicians' information ambiguity. Specifically, handoffs consisting of insufficient information, incomplete data, omissions, and faulty information flow exacerbated gray zone problems and may negatively affect patient outcomes. EPs and hospitalists had different expectations about handoffs, and those expectations influenced their interactions in ways that may result in communication breakdowns. The second theme illustrated how poor handoff communication contributes to boarding‐related patient safety threats for boarders and emergency department patients alike. Those interviewed talked about the systemic failures that lead to patient boarding and how poor handoffs exacerbated system flaws.Conclusions: Handoffs between EPs and hospitalists both reflect and contribute to the ambiguity inherent in emergency medicine. Poor handoffs, consisting of faulty communication behaviors and conflicting expectations for information, contribute to patient boarding conditions that can pose safety threats. Pragmatic conclusions are drawn regarding physician–physician communication in patient transfers, and recommendations are offered for medical education.