bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy and completeness of mortality data in the Department of Veterans Affairs
Authors: Sohn Min-Woong , Arnold Noreen , Maynard Charles , Hynes Denise M 
Published: April 2006

Abstract

Background
One of the national mortality databases in the U.S. is the Beneficiary Identification and Record Locator Subsystem (BIRLS) Death File that contains death dates of those who have received any benefits from the Department of Veterans Affairs (VA). The completeness of this database was shown to vary widely from cohort to cohort in previous studies. Three other sources of death dates are available in the VA that can complement the BIRLS Death File. The objective of this study is to evaluate the completeness and accuracy of death dates in the four sources available in the VA and to examine whether these four sources can be combined into a database with improved completeness and accuracy.

Methods
A random sample of 3,000 was drawn from 8.3 million veterans who received benefits from the VA between 1997 and 1999 and were alive on January 1, 1999 according to at least one source. Death dates found in BIRLS Death File, Medical SAS Inpatient Datasets, Medicare Vital Status, and Social Security Administration (SSA) Death Master File were compared with dates obtained from the National Death Index. A combined dataset from these sources was also compared with National Death Index dates.

Results
Compared with the National Death Index, sensitivity (or the percentage of death dates correctly recorded in a source) was 77.4% for BIRLS Death File, 12.0% for Medical SAS Inpatient Datasets, 83.2% for Medicare Vital Status, and 92.1% for SSA Death Master File. Over 95% of death dates in these sources agreed exactly with dates from the National Death Index. Death dates in the combined dataset demonstrated 98.3% sensitivity and 97.6% exact agreement with dates from the National Death Index.

Conclusion
The BIRLS Death File is not an adequate source of mortality data for the VA population due to incompleteness. When the four sources of mortality data are carefully combined, the resulting dataset can provide more timely data for death ascertainment than the National Death Index and has comparable accuracy and completeness.
Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host
Authors: Demma LJ , Vanderford TH , Logsdon JM , Feinberg MB , Staprans SI 
Published: April 2006

AbstractBackgroundThe ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time.ResultsSIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS.ConclusionPositive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.
Inhibition of constitutively active Jak-Stat pathway suppresses cell growth of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells
Authors: Tomita Mariko , Kawakami Hirochika , Uchihara Jun-nosuke , Okudaira Taeko , Masuda Masato , Matsuda Takehiro , Tanaka Yuetsu , Ohshiro Kazuiku , Mori Naoki 
Published: April 2006

AbstractBackgroundHuman T-cell leukemia virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL), induces cytokine-independent proliferation of T-cells, associated with the acquisition of constitutive activation of Janus kinases (Jak) and signal transducers and activators of transcription (Stat) proteins. Our purposes in this study were to determine whether activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells, and to explore mechanisms by which inhibition of Jak-Stat pathway kills ATL cells.ResultsConstitutive activation of Stat3 and Stat5 was observed in HTLV-1-infected T-cell lines and primary ATL cells, but not in HTLV-1-negative T-cell lines. Using AG490, a Jak-specific inhibitor, we demonstrated that the activation of Stat3 and Stat5 was mediated by the constitutive phosphorylation of Jak proteins. AG490 inhibited the growth of HTLV-1-infected T-cell lines and primary ATL cells by inducing G1cell-cycle arrest mediated by altering the expression of cyclin D2, Cdk4, p53, p21, Pim-1 and c-Myc, and by apoptosis mediated by the reduced expression of c-IAP2, XIAP, survivin and Bcl-2. Importantly, AG490 did not inhibit the growth of normal peripheral blood mononuclear cells.ConclusionOur results indicate that activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells. Inhibition of this pathway may provide a new approach for the treatment of ATL.
Variation at APOE and STH loci and Alzheimer's disease
Authors: Zuo Lingjun , van Dyck Christopher H , Luo Xingguang , Kranzler Henry R , Yang Bao-zhu , Gelernter Joel 
Published: April 2006

Abstract

Background
The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH) gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between APOE and AD, and between STH and AD in our sample.

Methods
The functional polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the ε 2, ε 3, and ε 4 alleles), and the Q7R SNP in the STH gene, were genotyped in 369 patients with AD and 289 healthy European-Americans. The associations between these two genes and AD were analyzed in a case-control design.

Results
Consistent with previously reported results, the frequencies of the APOE ε 4 allele, ε 4/ε 4 genotype and ε 3/ε 4 genotype were significantly higher in AD cases than controls; the ε 4/ε 4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the ε 2 allele, ε 3 allele, ε 3/ε 3 genotype and ε 2/ε 3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs+) of APOE alleles and genotypes increased in a linear trend with the number of ε 4 alleles and decreased in a linear trend with the number of ε 2 or ε 3 alleles. There was no significant difference in the STH allele and genotype frequency distributions between AD cases and controls.

Conclusion
This study confirmed that the ε 4 allele is a dose-response risk factor for AD and the ε 4/ε 4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the ε 2 allele was a dose-response protective factor for AD and the ε 3 allele exerted a weaker dose-response protective effect for risk of AD compared with ε 2. In a clinical setting, APOE genotyping could offer additional biological evidence of whether a subject may develop AD, but it is not robust enough to serve as an independent screening or predictive test in the diagnosis of AD. STH variation was not significantly associated with AD in our sample.
Initial breastfeeding attitudes and practices of women born in Turkey, Vietnam and Australia after giving birth in Australia
Authors: McLachlan Helen L , Forster Della A 
Published: April 2006

AbstractBackgroundCultural variations exist in the proportion of women who breastfeed. For some cultural groups, migration to a new country is associated with a reduction in the initiation and duration of breastfeeding. This paper describes the initial breastfeeding attitudes and practices of women born in Vietnam, Turkey and Australia who gave birth in Australia.MethodsThe study included 300 women: 100 hundred Turkish-born, 100 Vietnamese-born and 100 Australian-born women who had given birth in a large public, tertiary referral maternity hospital between January 1998 and May 1999 in Melbourne, Australia. Women were interviewed in hospital, between 24 hours after the birth and discharge from hospital. Data were collected using a structured questionnaire with some open-ended questions. Only women who had a normal vaginal birth and who gave birth to a healthy baby were included in the study.ResultsAlmost all Turkish women initiated breastfeeding (98%) compared with 84% of Australian women. Vietnamese women had the lowest rate of breastfeeding initiation (75%), perceived their partners to be more negative about breastfeeding and did not value the health benefits of colostrum to the same extent as the other two groups. Forty percent of Vietnamese women gave their baby formula in hospital. The results of this study add to the previously reported finding that immigrant Vietnamese women have low breastfeeding rates compared with other groups.ConclusionDespite the Baby Friendly status of the hospital where the study was conducted, major differences were found in breastfeeding initiation. Future research should develop and test interventions aimed at increasing breastfeeding initiation in Vietnamese women where initiation is low.
Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone
Authors: Sloan Erica K , Pouliot Normand , Stanley Kym L , Chia Jenny , Moseley Jane M , Hards Daphne K , Anderson Robin L 
Published: April 2006

Abstract
Introduction
Studies in xenograft models and experimental models of metastasis have implicated several β3 integrin-expressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumor-specific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear.

Methods
We used a syngeneic orthotopic model of spontaneous breast cancer metastasis to test whether exogenous expression of αvβ3 in a mammary carcinoma line (66cl4) that metastasizes to the lung, but not to bone, was sufficient to promote its spontaneous metastasis to bone from the mammary gland. The tumor burden in the spine and the lung following inoculation of αvβ3-expressing 66cl4 (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was analyzed by real-time quantitative PCR. The ability of these cells to grow and form osteolytic lesions in bone was determined by histology and tartrate-resistant acid phosphatase staining of bone sections following intratibial injection of tumor cells. The adhesive, migratory and invasive properties of 66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays.

Results
The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in the spine compared with 66cl4pBabe. A similar trend in lung metastasis was observed. αvβ3 did not increase the proliferation of 66cl4 cells in vitro or in the mammary gland in vivo. Similarly, αvβ3 is not required for the proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3 proliferated to the same extent when injected directly into the tibia. 66cl4beta3 tumor growth in the tibia, however, increased osteoclast recruitment and bone resorption compared with 66cl4 tumors. Moreover, αvβ3 increased 66cl4 tumor cell adhesion and αvβ3-dependent haptotactic migration towards bone matrix proteins, as well as their chemotactic response to bone-derived soluble factors in vitro.

Conclusion
These results demonstrate for the first time that tumor-specific αvβ3 contributes to spontaneous metastasis of breast tumors to bone and suggest a critical role for this receptor in mediating chemotactic and haptotactic migration towards bone factors.
The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome – a randomized controlled study [ISRCTN35655335]
Authors: von Heymann Christian , Sander Michael , Foer Achim , Heinemann Anja , Spiess Bruce , Braun Jan , Krämer Michael , Grosse Joachim , Dohmen Pascal , Dushe Simon , Halle Jürgen , Konertz Wolfgang F , Wernecke Klaus-Dieter , Spies Claudia 
Published: April 2006

Abstract
Introduction
Cardiopulmonary bypass (CPB) induces hemodilutional anemia, which frequently requires the transfusion of blood products. The objective of this study was to evaluate oxygen delivery and consumption and clinical outcome in low risk patients who were allocated to an hematocrit (Hct) of 20% versus 25% during normothermic CPB for elective coronary artery bypass graft (CABG) surgery.

Methods
This study was a prospective, randomized and controlled trial. Patients were subjected to normothermic CPB (35 to 36°C) and were observed until discharge from the intensive care unit (ICU). Outcome measures were calculated whole body oxygen delivery, oxygen consumption and clinical outcome. A nonparametric multivariate analysis of variance for repeated measurements and small sample sizes was performed.

Results
In a total of 54 patients (25% Hct, n = 28; 20% Hct, n = 26), calculated oxygen delivery (p = 0.11), oxygen consumption (p = 0.06) and blood lactate (p = 0.60) were not significantly different between groups. Clinical outcomes were not different between groups.

Conclusion
These data indicate that an Hct of 20% during normothermic CPB maintained calculated whole body oxygen delivery above a critical level after elective CABG surgery in low risk patients. The question of whether a transfusion trigger in excess of 20% Hct during normothermic CPB is still supported requires a larger prospective and randomized trial.
A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion
Authors: Matot Idit , Weiniger Carolyn F , Zeira Evelyne , Galun Eithan , Joshi Bhalchandra V , Jacobson Kenneth A 
Published: April 2006

AbstractIntroductionAlthough activation of A3adenosine receptors attenuates reperfusion lung injury and associated apoptosis, the signaling pathway that mediates this protection remains unclear. Adenosine agonists activate mitogen-activated protein kinases, and these kinases have been implicated in ischemia/reperfusion injury; the purpose of this study was therefore to determine whether A3adenosine receptor stimulation with reperfusion modulates expression of the different mitogen-activated protein kinases. In addition, we compared the effect of the A3adenosine agonist IB-MECA with the newly synthesized, highly selective A3adenosine receptor agonist MRS3558 on injury in reperfused lung.MethodStudies were performed in anin vivospontaneously breathing cat model, in which the left lower lobe of the lung was isolated and subjected to 2 hours of ischemia and 3 hours of reperfusion. The selective A3adenosine receptor agonists IB-MECA (0.05 mg/kg, 0.1 mg/kg, or 0.3 mg/kg) and MRS3558 (0.05 mg/kg or 0.1 mg/kg) were administered before reperfusion.ResultsBoth A3adenosine receptor agonists administered before reperfusion markedly (P< 0.01) attenuated indices of injury and apoptosis, including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, TUNEL (in situTdT-mediated dUTP nick end labeling)-positive cells, and caspase 3 activity and expression. The more pronounced effects at low doses were observed with MRS3558. Increases in phosphorylated c-Jun amino-terminal protein kinase (JNK), p38, and extracellular signal-regulated kinase (ERK)1/2 levels were observed by the end of reperfusion compared with controls. Pretreatment with the A3agonists upregulated phosphorylated ERK1/2 levels but did not modify phosphorylated JNK and p38 levels.ConclusionThe protective effects of A3adenosine receptor activation are mediated in part through upregulation of phosphorylated ERK. Also, MRS3558 was found to be more potent than IB-MECA in attenuating reperfusion lung injury. The results suggest not only that enhancement of the ERK pathway may shift the balance between cell death and survival toward cell survival, but also that A3agonists have potential as an effective therapy for ischemia/reperfusion-induced lung injury.
Intensive care acquired infection is an independent risk factor for hospital mortality: a prospective cohort study
Authors: Ylipalosaari Pekka , Ala-Kokko Tero I , Laurila Jouko , Ohtonen Pasi , Syrjälä Hannu 
Published: April 2006

Abstract
Introduction
The aim of this study was to elucidate the impact of intensive care unit (ICU)-acquired infection on hospital mortality.

Methods
Patients with a longer than 48 hour stay in a mixed 10 bed ICU in a tertiary-level teaching hospital were prospectively enrolled between May 2002 and June 2003. Risk factors for hospital mortality were analyzed with a logistic regression model.

Results
Of 335 patients, 80 developed ICU-acquired infection. Among the patients with ICU-acquired infections, hospital mortality was always higher, regardless of whether or not the patients had had infection on admission (infection on admission group (IAG), 35.6% versus 17%, p = 0.008; and no-IAG, 25.7% versus 6.1%, p = 0.023). In IAG (n = 251), hospital stay was also longer in the presence of ICU-acquired infection (median 31 versus 16 days, p < 0.001), whereas in no-IAG (n = 84), hospital stay was almost identical with and without the presence of ICU-acquired infection (18 versus 17 days). In univariate analysis, the significant risk factors for hospital mortality were: Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, sequential organ failure assessment (SOFA) score >8, ICU-acquired infection, age ≥ 65, community-acquired pneumonia, malignancy or immunosuppressive medication, and ICU length of stay >5 days. In multivariate logistic regression analysis, ICU-acquired infection remained an independent risk factor for hospital mortality after adjustment for APACHE II score and age (odds ratio (OR) 4.0 (95% confidence interval (CI): 2.0–7.9)) and SOFA score and age (OR 2.7 (95% CI: 2.9–7.6)).

Conclusion
ICU-acquired infection was an independent risk factor for hospital mortality even after adjustment for the APACHE II or SOFA scores and age.
Differential responsiveness to IFN-α and IFN-β of human mature DC through modulation of IFNAR expression
Authors: Severa Martina , Remoli Maria Elena , Giacomini Elena , Ragimbeau Josiane , Lande Roberto , Uzé Gilles , Pellegrini Sandra , Coccia Eliana M 
Published: April 2006

Abstract
In human monocyte-derived dendritic cells (DC), infection with Mycobacterium tuberculosis and viruses or stimulation with Toll-like receptor type 3 and 4 agonists causes the release of type I interferon (IFN). Here, we describe that the IFN-β released upon stimulation with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) is responsible for a rapid and sustained signal transducer and activator of transcription 1 and 2 activation and expression of IFN-stimulated genes, such as the transcription factor IFN regulatory factor 7 and the chemokine CXC chemokine ligand 10. The autocrine production of IFN-β from LPS and poly I:C-matured DC (mDC) induced a temporary saturation of the response to type I IFN and a marked decline in the level of the two IFN receptor (IFNAR) subunits. It is interesting that we found that upon clearing of the released cytokines, LPS-stimulated DC reacquired full responsiveness to IFN-β but only partial responsiveness to IFN-α, and their maturation process was unaffected. Monitoring of surface and total levels of the receptor subunits showed that maximal expression of IFNAR2 resumed within 24 h of clearing, and IFNAR1 expression remained low. Thus, mDC can modulate their sensitivity to two IFN subtypes through a differential regulation of the IFNAR subunits.
Two-Stage Designs in Case–Control Association Analysis
Authors: Zuo Yijun , Zou Guohua , Zhao Hongyu 
Published: April 2006

Abstract
DNA pooling is a cost-effective approach for collecting information on marker allele frequency in genetic studies. It is often suggested as a screening tool to identify a subset of candidate markers from a very large number of markers to be followed up by more accurate and informative individual genotyping. In this article, we investigate several statistical properties and design issues related to this two-stage design, including the selection of the candidate markers for second-stage analysis, statistical power of this design, and the probability that truly disease-associated markers are ranked among the top after second-stage analysis. We have derived analytical results on the proportion of markers to be selected for second-stage analysis. For example, to detect disease-associated markers with an allele frequency difference of 0.05 between the cases and controls through an initial sample of 1000 cases and 1000 controls, our results suggest that when the measurement errors are small (0.005), ∼3% of the markers should be selected. For the statistical power to identify disease-associated markers, we find that the measurement errors associated with DNA pooling have little effect on its power. This is in contrast to the one-stage pooling scheme where measurement errors may have large effect on statistical power. As for the probability that the disease-associated markers are ranked among the top in the second stage, we show that there is a high probability that at least one disease-associated marker is ranked among the top when the allele frequency differences between the cases and controls are not &lt;0.05 for reasonably large sample sizes, even though the errors associated with DNA pooling in the first stage are not small. Therefore, the two-stage design with DNA pooling as a screening tool offers an efficient strategy in genomewide association studies, even when the measurement errors associated with DNA pooling are nonnegligible. For any disease model, we find that all the statistical results essentially depend on the population allele frequency and the allele frequency differences between the cases and controls at the disease-associated markers. The general conclusions hold whether the second stage uses an entirely independent sample or includes both the samples used in the first stage and an independent set of samples.