bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of p53 activity by IκBα: Evidence suggesting a common phylogeny between NF-κB and p53 transcription factors
Authors: Dreyfus David H , Nagasawa Masayuki , Gelfand Erwin W , Ghoda Lucy Y 
Published: June 2005

Abstract
Background
In this work we present evidence that the p53 tumor suppressor protein and NF-κB transcription factors could be related through common descent from a family of ancestral transcription factors regulating cellular proliferation and apoptosis. P53 is a homotetrameric transcription factor known to interact with the ankyrin protein 53BP2 (a fragment of the ASPP2 protein). NF-κB is also regulated by ankyrin proteins, the prototype of which is the IκB family. The DNA binding sequences of the two transcription factors are similar, sharing 8 out of 10 nucleotides. Interactions between the two proteins, both direct and indirect, have been noted previously and the two proteins play central roles in the control of proliferation and apoptosis.

Results
Using previously published structure data, we noted a significant degree of structural alignment between p53 and NF-κB p65. We also determined that IκBα and p53 bind in vitro through a specific interaction in part involving the DNA binding region of p53, or a region proximal to it, and the amino terminus of IκBα independently or cooperatively with the ankyrin 3 domain of IκBα In cotransfection experiments, κBα could significantly inhibit the transcriptional activity of p53. Inhibition of p53-mediated transcription was increased by deletion of the ankyrin 2, 4, or 5 domains of IκBα Co-precipitation experiments using the stably transfected ankyrin 5 deletion mutant of κBα and endogenous wild-type p53 further support the hypothesis that p53 and IκBα can physically interact in vivo.

Conclusion
The aggregate results obtained using bacterially produced IκBα and p53 as well as reticulocyte lysate produced proteins suggest a correlation between in vitro co-precipitation in at least one of the systems and in vivo p53 inhibitory activity. These observations argue for a mechanism involving direct binding of IκBα to p53 in the inhibition of p53 transcriptional activity, analogous to the inhibition of NF-κB by κBα and p53 by 53BP2/ASPP2. These data furthermore suggest a role for ankyrin proteins in the regulation of p53 activity. Taken together, the NFκB and p53 proteins share similarities in structure, DNA binding sites and binding and regulation by ankyrin proteins in support of our hypothesis that the two proteins share common descent from an ancestral transcriptional factor.
The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour
Authors: Teich Niels , Kleeff Jörg , Lochs Herbert , Mössner Joachim , Keim Volker , Friess Helmut , Ockenga Johann 
Published: June 2005

Abstract

Background
The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass.

Methods
Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured.

Results
The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively.

Conclusion
Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy.
Insufficient neutralization in testing a chlorhexidine-containing ethanol-based hand rub can result in a false positive efficacy assessment
Authors: Kampf Günter , Shaffer Marc , Hunte Corrine 
Published: June 2005

Abstract

Background
Effective neutralization in testing hand hygiene preparations is considered to be a crucial element to ensure validity of the test results, especially with the difficulty to neutralize chlorhexidine gluconate. Aim of the study was to measure the effect of chemical neutralization under practical test conditions according to EN 1500.

Methods
We have investigated two ethanol-based hand rubs (product A, based on 61% ethanol and 1% chlorhexidine gluconate; product B, based on 85% ethanol). The efficacy of products (application of 3 ml for 30 s) was compared to 2-propanol 60% (v/v) (two 3 ml rubs of 30 s each) on hands artificially contaminated with Escherichia coli using a cross-over design with 15 volunteers. Pre-values were obtained by rubbing fingertips for 1 minute in liquid broth. Post-values were determined by sampling immediately after disinfection in liquid broth with and without neutralizers (0.5% lecithin, 4% polysorbate 20).

Results
The neutralizers were found to be effective and non-toxic. Without neutralization in the sampling fluid, the reference disinfection reduced the test bacteria by 3.7 log10, product B by 3.3 log10 and product A by 4.8 log10 (P = 0.001; ANOVA). With neutralization the reference disinfection reduced the test bacteria by 3.5 log10, product B by 3.3 log10 and product A by 2.7 log10 (P = 0.011; ANOVA). In comparison to the reference treatment Product B lead to a lower mean reduction than the reference disinfection but the difference was not significant (P > 0.1; Wilcoxon-Wilcox test). Without neutralizing agents in the sampling fluid, product A yielded a significantly higher reduction of test bacteria (4.8; P = 0.02) as compared to the situation with neutralizing agents (2.7; P = 0.033).

Conclusion
The crucial step of neutralization lies in the sampling fluid itself in order to stop any residual bacteriostatic or bactericidal activity immediately after the application of the preparation, especially with chlorhexidine gluconate-containing preparations. This is particularly important at short application times such as the 30 s.
P-cadherin expression and survival rate in oral squamous cell carcinoma:an immunohistochemical study
Authors: Lo Muzio Lorenzo , Campisi Giuseppina , Farina Antonio , Rubini Corrado , Pannone Giuseppe , Serpico Rosario , Laino Gregorio , De Lillo Alfredo , Carinci Francesco 
Published: June 2005

Abstract

Background
P-cadherin (P-cad) is a transmembrane molecule involved in the cell-cell adhesion and similar to E-cadherin (E-cad), but less investigated in oncology, especially in in vivo studies. Aims of the present study were to assess the prevalence of P-cad expression in oral squamous cell carcinoma (OSCC) and to verify whether P-cad can be considered a marker of prognosis in patients with OSCC.

Methods
In a retrospective study, a cohort of 67 OSCC patients was investigated for P-cad expression and its cellular localization by immunohistochemistry; some respective healthy margins of resection were similarly investigated as standard controls. After grouping for P-cad expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, Staging, and overall survival rate. Univariate and multivariate analyses were performed.

Results
37 cases (55.2%) of OSCC showed membranous/cytoplasmic positivity for P-cad, whereas 30 (44.8 %) were negative. Although with some differences in membranous vs cytoplasmic localization of P-cad in OSCC with different G, no statistical association was found between P-cad expression and any variables considered at baseline. In terms of prognostic significance, P-cad non expression was found to have an independent association with poorer overall survival rate than P-cad expressing group (P = 0.056); moreover, among P-cad +ve patients the best prognosis was for those OSCC with membranous (P < 0.0001) than those with cytoplasmic P-cad expression.

Conclusion
On the basis of these results, it is possible to suggest P-cad as an early marker of poor prognosis. The abnormal or lack of P-cad expression could constitute an hallmark of aggressive biological behavior in OSCC
Bone mineral density measurement and osteoporosis treatment after a fragility fracture in older adults: regional variation and determinants of use in Quebec
Authors: Vanasse Alain , Dagenais Pierre , Niyonsenga Théophile , Grégoire Jean-Pierre , Courteau Josiane , Hemiari Abbas 
Published: June 2005

Abstract
Background
Osteoporosis (OP) is a skeletal disorder characterized by reduced bone strength and predisposition to increased risk of fracture, with consequent increased risk of morbidity and mortality. It is therefore an important public health problem. International and Canadian associations have issued clinical guidelines for the diagnosis and treatment of OP. In this study, we identified potential predictors of bone mineral density (BMD) testing and OP treatment, which include place of residence.

Methods
Our study was a retrospective population-based cohort study using data from the Quebec Health Insurance Board. The studied population consisted of all individuals 65 years and older for whom a physician claimed a consultation for a low velocity vertebral, hip, wrist, or humerus fracture in 1999 and 2000. Individuals were considered to have undergone BMD testing if there was a claim for such a procedure within two years following a fracture. They were considered to have received an OP treatment if there was at least one claim to Quebec's health insurance plan (RAMQ) for OP treatment within one year following a fracture. We performed descriptive analyses and logistic regressions by gender. Predictors included age, site of fracture, social status, comorbidity index, prior BMD testing, prior OP treatment, long-term glucocorticoid use, and physical distance to BMD device.

Results
The cohort, 77% of which was female, consisted of 25,852 individuals with fragility fractures. BMD testing and OP treatment rates were low and gender dependent (BMD: men 4.6%; women 13.1%; OP treatment: men 9.9%; women 29.7%). There was an obvious regional variation, particularly in BMD testing, ranging from 0 to 16%. Logistic regressions demonstrate that individuals living in long term care facilities received less BMD testing. Patients who had suffered from vertebral fractures, or who had received prior OP treatment or BMD testing, regardless of gender, subsequently received more BMD testing and OP treatments. Furthermore, increasing the distance between a patient's residence and BMD facility precluded likelihood of BMD testing.

Conclusion
BMD testing rate was extremely low but not completely explained by reduced physical access; gender, age, social status, prior BMD testing and OP treatment were all important predictors for future BMD testing and OP treatment.
Adenosine infusion increases plasma levels of VEGF in humans
Authors: Adair Thomas H , Cotten Reid , Gu Jian-Wei , Pryor Janelle S , Bennett Kenneth R , McMullan Michael R , McDonnell Preston , Montani Jean-Pierre 
Published: June 2005

Abstract

Background
Many in vitro studies have shown that adenosine (Ado) can induce vascular endothelial growth factor (VEGF) mRNA and protein expression and stimulate endothelial proliferation. In the present study, we seek to determine whether Ado can increase circulating levels of VEGF protein in the intact human.

Methods
Five outpatients 49.3 ± 6.7 years of age and weighing 88.2 ± 8.5 kg were selected. They were given a 6 min intravenous infusion of Ado (0.14 mg kg-1 min-1) in conjunction with sestamibi myocardial perfusion scans. Mean blood pressure (MBP, calculated from systolic and diastolic values) and heart rate (HR) were determined before Ado infusion and every 2 min for the next 10 min. Plasma VEGF concentrations (ELISA) were determined immediately before Ado infusion and 1 h, 2 h, and 8 h after the infusion.

Results
Plasma VEGF concentration averaged 20.3 ± 2.0 pg ml-1 prior to Ado infusion, and increased to 62.7 ± 18.1 pg ml-1 at 1 h post- infusion (p < 0.01). VEGF plasma concentration returned to basal levels 2 h after infusion (23.3 ± 3.4 pg ml-1). MBP averaged 116 ± 7 mmHg and heart rate averaged 70 ± 7 prior to Ado infusion. MBP decreased by a maximum of ~22% and HR increased by a maximum of ~17% during the infusion.

Conclusion
We conclude from these preliminary findings that intravenous infusion of adenosine can increase plasma levels of VEGF in humans.
Evidence-based patient choice: a prostate cancer decision aid in plain language
Authors: Holmes-Rovner Margaret , Stableford Sue , Fagerlin Angela , Wei John T , Dunn Rodney L , Ohene-Frempong Janet , Kelly-Blake Karen , Rovner David R 
Published: June 2005

Abstract
Background
Decision aids (DA) to assist patients in evaluating treatment options and sharing in decision making have proliferated in recent years. Most require high literacy and do not use plain language principles. We describe one of the first attempts to design a decision aid using principles from reading research and document design. The plain language DA prototype addressed treatment decisions for localized prostate cancer. Evaluation assessed impact on knowledge, decisions, and discussions with doctors in men newly diagnosed with prostate cancer.

Methods
Document development steps included preparing an evidence-based DA in standard medical parlance, iteratively translating it to emphasize shared decision making and plain language in three formats (booklet, Internet, and audio-tape). Scientific review of medical content was integrated with expert health literacy review of document structure and design. Formative evaluation methods included focus groups (n = 4) and survey of a new sample of men newly diagnosed with prostate cancer (n = 60), compared with historical controls (n = 184).

Results
A transparent description of the development process and design elements is reported. Formative evaluation among newly diagnosed prostate cancer patients found the DA to be clear and useful in reaching a decision. Newly diagnosed patients reported more discussions with doctors about treatment options, and showed increases in knowledge of side effects of radiation therapy.

Conclusion
The plain language DA presenting medical evidence in text and numerical formats appears acceptable and useful in decision-making about localized prostate cancer treatment. Further testing should evaluate the impact of all three media on decisions made and quality of life in the survivorship period, especially among very low literacy men.
A Severe Acute Respiratory Syndrome extranet: supporting local communication and information dissemination
Authors: Valaitis Ruta K , Akhtar-Danesh Noori , Kealey Cathy M , Brunetti Glenn M , Thomas Helen 
Published: June 2005

Abstract
Background
The objective of this study was to explore the use and perceptions of a local Severe Acute Respiratory Syndrome (SARS) Extranet and its potential to support future information and communication applications. The SARS Extranet was a single, managed electronic and limited access system to manage local, provincial and other SARS control information.

Methods
During July, 2003, a web-based and paper-based survey was conducted with 53 SARS Steering Committee members in Hamilton. It assessed the use and perceptions of the Extranet that had been built to support the committee during the SARS outbreak. Before distribution, the survey was user-tested based on a think-aloud protocol, and revisions were made. Quantitative and qualitative questions were asked related to frequency of use of the Extranet, perceived overall usefulness of the resource, rationale for use, potential barriers, strengths and limitations, and potential future uses of the Extranet.

Results
The response rate was 69.4% (n = 34). Of all respondents, 30 (88.2%) reported that they had visited the site, and rated it highly overall (mean = 4.0; 1 = low to 5 = high). However, the site was rated 3.4 compared with other communications strategies used during the outbreak. Almost half of all respondents (44.1%) visited the site at least once every few days. The two most common reasons the 30 respondents visited the Extranet were to access SARS Steering Committee minutes (63.3%) and to access Hamilton medical advisories (53.3%). The most commonly cited potential future uses for the Extranet were the sending of private emails to public health experts (63.3%), and surveillance (63.3%). No one encountered personal barriers in his or her use of the site, but several mentioned that time and duplication of email information were challenges.

Conclusion
Despite higher rankings of various communication strategies during the SARS outbreak, such as email, meetings, teleconferences, and other web sites, users generally perceived a local Extranet as a useful support for the dissemination of local information during public health emergencies.
Real time spatial cluster detection using interpoint distances among precise patient locations
Authors: Olson Karen L , Bonetti Marco , Pagano Marcello , Mandl Kenneth D 
Published: June 2005

Abstract
Background
Public health departments in the United States are beginning to gain timely access to health data, often as soon as one day after a visit to a health care facility. Consequently, new approaches to outbreak surveillance are being developed. When cases cluster geographically, an analysis of their spatial distribution can facilitate outbreak detection. Our method focuses on detecting perturbations in the distribution of pair-wise distances among all patients in a geographical region. Barring outbreaks, this distribution can be quite stable over time. We sought to exemplify the method by measuring its cluster detection performance, and to determine factors affecting sensitivity to spatial clustering among patients presenting to hospital emergency departments with respiratory syndromes.

Methods
The approach was to (1) define a baseline spatial distribution of home addresses for a population of patients visiting an emergency department with respiratory syndromes using historical data; (2) develop a controlled feature set simulation by inserting simulated outbreak data with varied parameters into authentic background noise, thereby creating semisynthetic data; (3) compare the observed with the expected spatial distribution; (4) establish the relative value of different alarm strategies so as to maximize sensitivity for the detection of clustering; and (5) measure factors which have an impact on sensitivity.

Results
Overall sensitivity to detect spatial clustering was 62%. This contrasts with an overall alarm rate of less than 5% for the same number of extra visits when the extra visits were not characterized by geographic clustering. Clusters that produced the least number of alarms were those that were small in size (10 extra visits in a week, where visits per week ranged from 120 to 472), diffusely distributed over an area with a 3 km radius, and located close to the hospital (5 km) in a region most densely populated with patients to this hospital. Near perfect alarm rates were found for clusters that varied on the opposite extremes of these parameters (40 extra visits, within a 250 meter radius, 50 km from the hospital).

Conclusion
Measuring perturbations in the interpoint distance distribution is a sensitive method for detecting spatial clustering. When cases are clustered geographically, there is clearly power to detect clustering when the spatial distribution is represented by the M statistic, even when clusters are small in size. By varying independent parameters of simulated outbreaks, we have demonstrated empirically the limits of detection of different types of outbreaks.
Immediate transfection of patient-derived leukemia: a novel source for generating cell-based vaccines
Authors: Gershan Jill A , Johnson Bryon D , Weber James , Schauer Dennis W , Natalia Natalia , Behnke Stephanie , Burns Karen , Maloney Kelly W , Warwick Anne B , Orentas Rimas J 
Published: June 2005

Abstract

Background
The production of cell-based cancer vaccines by gene vectors encoding proteins that stimulate the immune system has advanced rapidly in model systems. We sought to develop non-viral transfection methods that could transform patient tumor cells into cancer vaccines, paving the way for rapid production of autologous cell-based vaccines.

Methods
As the extended culture and expansion of most patient tumor cells is not possible, we sought to first evaluate a new technology that combines electroporation and chemical transfection in order to determine if plasmid-based gene vectors could be instantaneously delivered to the nucleus, and to determine if gene expression was possible in a cell-cycle independent manner. We tested cultured cell lines, a primary murine tumor, and primary human leukemia cells from diagnostic work-up for transgene expression, using both RFP and CD137L expression vectors.

Results
Combined electroporation-transfection directly delivered plasmid DNA to the nucleus of transfected cells, as demonstrated by confocal microscopy and real-time PCR analysis of isolated nuclei. Expression of protein from plasmid vectors could be detected as early as two hours post transfection. However, the kinetics of gene expression from plasmid-based vectors in tumor cell lines indicated that optimal gene expression was still dependent on cell division. We then tested to see if pediatric acute lymphocytic leukemia (ALL) would also display the rapid gene expression kinetics of tumor cells lines, determining gene expression 24 hours after transfection. Six of 12 specimens showed greater than 17% transgene expression, and all samples showed at least some transgene expression.

Conclusion
Given that transgene expression could be detected in a majority of primary tumor samples analyzed within hours, direct electroporation-based transfection of primary leukemia holds the potential to generate patient-specific cancer vaccines. Plasmid-based gene therapy represents a simple means to generate cell-based cancer vaccines and does not require the extensive infrastructure of a virus-based vector system.