bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of a Proapoptotic Peptide to Intratumorally Spreading Cancer Therapy
Authors: Chen Renwei , Braun Gary B. , Luo Xiuquan , Sugahara Kazuki N. , Teesalu Tambet , Ruoslahti Erkki 
Published: December 2012

Abstract
Bit1 is a proapoptotic mitochondrial protein associated with anoikis. Upon cell detachment, Bit1 is released into the cytoplasm and triggers caspase-independent cell death. Bit1 consists of 179 amino acids; for the C-terminal, two thirds of the molecule functions as a peptidyl-tRNA hydrolase, whereas the N-terminus contains a mitochondrial localization signal. Here, we localize the cell death domain (CDD) to the N-terminal 62 amino acids of Bit1 by transfecting cells with truncated Bit1 cDNA constructs. CDD was more potent in killing cells than the full-length Bit1 protein when equivalent amounts of cDNA were transfected. To develop Bit1 CDD into a cancer therapeutic, we engineered a recombinant protein consisting of the CDD fused to iRGD, which is a tumor-specific peptide with unique tumor-penetrating and cell-internalizing properties. iRGD-CDD internalized into cultured tumor cells through a neuropilin-1–activated pathway and triggered cell death. Importantly, iRGD-CDD spread extensively within the tumor when injected intratumorally into orthotopically implanted breast tumors in mice. Repeated treatment with iRGD-CDD strongly inhibited tumor growth, resulting in an average reduction of 77% in tumor volume and eradication of some tumors. The caspase independence of Bit1-induced cell death makes CDD a potentially attractive anticancer agent, because tumor resistance to the main mechanisms of apoptosis is circumvented. Using iRGD to facilitate the spreading of a therapeutic agent throughout the tumor mass may be a useful adjunct to local therapy for tumors that are surgically inoperable or difficult to treat systemically. Cancer Res; 73(4); 1352–61. ©2012 AACR.
Electrocardiographic PR Interval and Adverse Outcomes in Older Adults
Authors: Magnani Jared W. , Wang Na , Nelson Kerrie P. , Connelly Stephanie , Deo Rajat , Rodondi Nicolas , Schelbert Erik B. , Garcia Melissa E. , Phillips Caroline L. , Shlipak Michael G. , Harris Tamara B. , Ellinor Patrick T. , Benjamin Emelia J. ,   for the Health, Aging, and Body Composition Study
Published: December 2012

Background—
The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults.

Methods and Results—
The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02–1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04–1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11–1.93). PR interval was not associated with increased all-cause mortality.

Conclusions—
We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.
Association of Genome-Wide Variation With Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks
Authors: Yu Bing , Barbalic Maja , Brautbar Ariel , Nambi Vijay , Hoogeveen Ron C. , Tang Weihong , Mosley Thomas H. , Rotter Jerome I. , deFilippi Christopher R. , O’Donnell Christopher J. , Kathiresan Sekar , Rice Ken , Heckbert Susan R. , Ballantyne Christie M. , Psaty Bruce M. , Boerwinkle Eric 
Published: December 2012

Background—
High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels.

Methods and Results—

We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374;
P
=9.06×10
−9
) near the nuclear receptor coactivator 2 (
NCOA2
) gene. Overexpression of
NCOA2
can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445;
P
=4.73×10
−8
) in the gene
TNNT2
, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16;
P
=0.004).

Conclusions—

We identified 2 loci, near
NCOA2
and in the
TNNT2
gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results.
Effect of Valsartan on Systemic Right Ventricular Function
Authors: van der Bom Teun , Winter Michiel M. , Bouma Berto J. , Groenink Maarten , Vliegen Hubert W. , Pieper Petronella G. , van Dijk Arie P.J. , Sieswerda Gertjan T. , Roos-Hesselink Jolien W. , Zwinderman Aeilko H. , Mulder Barbara J.M. 
Published: December 2012

Background—
The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated.

Methods and Results—

We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass,

peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, −1.3% to 3.9%;
P
=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3–28 mL;
P
<0.01) and mass (8 g; 95% confidence interval, 2–14 g;
P
=0.01) in the placebo group than in the valsartan group.

Conclusions—
There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN52352170.
Computing Sources of Epileptic Discharges Using the Novel BMA Approach
Authors: Bravo Elena Cuspineda , Martínez-Montes Eduardo , Farach-Fumero Miguel , Machado-Curbelo Calixto 
Published: December 2012

Electroencephalography (EEG) source localization in epileptology continues to be a challenge for neuroscientists. A number of inverse solution (IS) methodologies have been proposed to solve this problem, and their advantages and limitations have been described. In the present work, a previously developed IS approach called Bayesian model averaging (BMA) is introduced in clinical practice in order to improve the localization accuracy of epileptic discharge sources. For this study, 31 patients with the diagnosis of partial epilepsies were studied: 14 had benign childhood epilepsy with centrotemporal spikes and 17 had temporal lobe epilepsy (TLE). The underlying epileptic sources were localized using the BMA approach, and the results were compared with those expected from the clinical diagnosis. Additional comparisons with results obtained from 3 of the most commonly used distributed IS methods for these purposes (minimum norm [MN], weighted minimum norm [WMN], and low-resolution electromagnetic tomography [LORETA]) were carried out in terms of source localization accuracy and spatial resolutions. The BMA approach estimated discharge sources that were consistent with the clinical diagnosis, and this method outperformed LORETA, MN, and WMN in terms of both localization accuracy and spatial resolution. The BMA was able to localize deeper generators with high accuracy. In conclusion, the BMA methodology has a great potential for the noninvasive accurate localization of epileptic sources, even those located in deeper structures. Therefore, it could be a promising tool for clinical practice in epileptology, although additional studies in other types of epileptic syndromes are necessary.
Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract
Authors: Badiali Luca , Cedernaes Jonathan , Olszewski Pawel K , Nylander Olof , Vergoni Anna V , Schiöth Helgi B 
Published: December 2012

Abstract

Background
G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.

Methods
Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.

Results
We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

Conclusions
Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.
Effect of low-dose gaseous ozone on pathogenic bacteria
Authors: Fontes Belchor , Cattani Heimbecker Ana Maria , de Souza Brito Glacus , Costa Silvia F , van der Heijden Inneke M , Levin Anna S , Rasslan Samir 
Published: December 2012

Abstract

Background
Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes.

Methods
A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5min under atmospheric pressure was selected. In the 2nd phase, eight bacterial strains with well characterized resistance patterns were evaluated in vitro using agar-blood in adapted Petri dishes (105 bacteria/dish). The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O3/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used.

Results
The selected ozone dose was applied to the following eight strains: Escherichia coli, oxacillin-resistant Staphylococcus aureus, oxacillin-susceptible Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, Acinetobacter baumannii susceptible only to carbapenems, and Pseudomonas aeruginosa susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups.

Conclusion
A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents.
Aspects of functioning and environmental factors in medical work capacity evaluations of persons with chronic widespread pain and low back pain can be represented by a combination of applicable ICF Core Sets
Authors: Schwegler Urban , Anner Jessica , Boldt Christine , Glässel Andrea , Lay Veronika , De Boer Wout Ernst Lodewijk , Stucki Gerold , Trezzini Bruno 
Published: December 2012

Abstract

Background
Medical work capacity evaluations play a key role in social security schemes because they usually form the basis for eligibility decisions regarding disability benefits. However, the evaluations are often poorly standardized and lack transparency as decisions on work capacity are based on a claimant’s disease rather than on his or her functional capacity. A comprehensive and consistent illustration of a claimant’s lived experience in relation to functioning, applying the International Classification of Functioning, Disability and Health (ICF) and the ICF Core Sets (ICF-CS), potentially enhances transparency and standardization of work capacity evaluations. In our study we wanted to establish whether and how the relevant content of work capacity evaluations can be captured by ICF-CS, using disability claimants with chronic widespread pain (CWP) and low back pain (LBP) as examples.

Methods
Mixed methods study, involving a qualitative and quantitative content analysis of medical reports. The ICF was used for data coding. The coded categories were ranked according to the percentage of reports in which they were addressed. Relevance thresholds at 25% and 50% were applied. To determine the extent to which the categories above the thresholds are represented by applicable ICF-CS or combinations thereof, measures of the ICF-CS’ degree of coverage (i.e. content validity) and efficiency (i.e. practicability) were defined.

Results
Focusing on the 25% threshold and combining the Brief ICF-CS for CWP, LBP and depression for CWP reports, the coverage ratio reached 49% and the efficiency ratio 70%. Combining the Brief ICF-CS for LBP, CWP and obesity for LBP reports led to a coverage of 47% and an efficiency of 78%.

Conclusions
The relevant content of work capacity evaluations involving CWP and LBP can be represented by a combination of applicable ICF-CS. A suitable standard for documenting such evaluations could consist of the Brief ICF-CS for CWP, LBP, and depression or obesity, augmented by additional ICF categories relevant for this particular context. In addition, the unique individual experiences of claimants have to be considered in order to assess work capacity comprehensively.
The R0 package: a toolbox to estimate reproduction numbers for epidemic outbreaks
Authors: Obadia Thomas , Haneef Romana , Boëlle Pierre-Yves 
Published: December 2012

Abstract

Background
Several generic methods have been proposed to estimate transmission parameters during an outbreak, especially the reproduction number. However, as of today, no dedicated software exists that implements these methods and allow comparisons.

Results
A review of generic methods used to estimate transmissibility parameters during outbreaks was carried out. Most methods used the epidemic curve and the generation time distribution. Two categories of methods were available: those estimating the initial reproduction number, and those estimating a time dependent reproduction number. We implemented five methods as an R library, developed sensitivity analysis tools for each method and provided numerical illustrations of their use. A comparison of the performance of the different methods on simulated datasets is reported.

Conclusions
This software package allows a standardized and extensible approach to the estimation of the reproduction number and generation interval distribution from epidemic curves.
Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
Authors: Hernestål-Boman Jenny , Norberg Margareta , Jansson Jan-Hakan , Eliasson Mats , Eriksson Jan W , Lindahl Bernt , Johansson Lars 
Published: December 2012

Abstract

Background
Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM.

Methods
We conducted a prospective incident case-referent study within the Västerbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L).

Results
After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments.

Conclusions
Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance.
Assessment of local wood species used for the manufacture of cookware and the perception of chemical benefits and chemical hazards associated with their use in Kumasi, Ghana
Authors: Mensah John Kenneth , Adei Evans , Adei Dina , Owusu Ansah Gwendolyn 
Published: December 2012

AbstractBackgroundHistorical proven wood species have no reported adverse health effect associated with its past use. Different historical proven species have traditionally been used to manufacture different wooden food contact items. This study uses survey questionnaires to assess suppliers’, manufacturers’, retailers’ and consumers’ (end-users’) preferences for specific wood species, to examine the considerations that inform these preferences and to investigate the extent of awareness of the chemical benefits and chemical hazards associated with wooden food contact material use.MethodsThrough the combined use of a cross sectional approach and a case study design, 25 suppliers, 25 manufacturers, 25 retailers and 125 consumers (end-users) of wooden food contact materials in four suburbs in Kumasi Metropolitan Area (Anloga junction, Ahinsan Bus Stop, Ahwia-Pankrono and Race Course) and Ashanti Akyim Agogo in the Ashanti Akyim North District of the Ashanti Region were administered with closed ended questionnaires. The questionnaires were prepared in English, but local language, Twi, was used to translate and communicate the content of the questionnaire where necessary.ResultsSuppliers’, manufacturers’ and retailers’ preferences for specific wood species for most wooden cookware differed from that of consumers (end-users). But all respondent groups failed to indicate any awareness of chemical benefits or chemical hazards associated with either the choice of specific wood species for specific wooden cookware or with the general use of wooden food contact materials. The lack of appreciation of chemical benefits or hazards associated with active principles of wooden cookware led to heavy reliance of consumers (end-users) on the wood density, price, attractive grain pattern and colour or on the judgement of retailers in their choice of specific species for a wooden cookware.ConclusionThis study contributes some practical suggestions to guide national policy development on improvement in quality of available wooden food contact materials in Ghana.