bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient perceptions of caring and association with emergency department activity and access block
Authors: Limbourn Sarah , Celenza Antonio 
Published: February 2011

AbstractObjective:  To develop and validate a questionnaire isolating patients' perceptions of caring as individuals provided by ED doctors. This tool was then applied to explore the relationship between ED activity and patient perceptions of caring.Methods:  Following questionnaire development and reliability analysis, a prospective, cross‐sectional study was performed of ED patients who completed the written questionnaire regarding perceptions of caring. The ED tracking database obtained demographic data, patient visit characteristics and markers of departmental activity. Spearman's rho evaluated associations between perceptions of caring and activity. Free text responses were analysed thematically.Results:  In reliability testing the questionnaire demonstrated Kappa 0.679, Cronbach's alpha 0.891. The survey was completed by 467 patients. Over 95% of patients agreed that ED doctors: identified themselves; took the problem seriously; treated patients with respect; were courteous and considerate; and demonstrated an overall caring attitude towards patients. Lower agreement occurred with doctors: not distracted by other issues; patient involvement in decisions about care; respect for cultural or religious needs; and doctors going out of their way to help. There were no significant differences in the proportion of patients recruited from different days of the week, shifts or sex. No clinically important associations were demonstrated between perceptions of caring and departmental activity. Least liked aspects of ED care related to system issues rather than the interpersonal relationship with the ED doctors.Conclusions:  This study has validated a questionnaire isolating caring attributes. ED activity was not associated with patients' perceptions of being cared for by ED doctors.
State Boards of Health: Governance and Politics
Authors: Hughes Richard , Ramdhanie Korisha , Wassermann Travis , Moscetti Craig 
Published: February 2011

The governance structures of state public health systems vary as much as the states themselves, including the existence and role of state boards of health. Understanding these differences is essential to a complete understanding of the governmental public health enterprise. State boards of health are obvious vehicles for public health policy development in some states, where they work closely with or oversee state health agencies. In other states they do not exist or serve only in a non-binding advisory capacity.In this article, we distinguish and identify state boards of health and state public health advisory boards, examine state boards of health in practice, and discuss their role in advocacy and policy development in the context of state politics. We used a set of mixed qualitative methods, including a literature review, online research of state statutes establishing state board of health authorities, and key informant interviews. Informants were five current and former state board of health members, four current and former state health officers, and nine state health agency senior policy staff, spanning 13 states.
Treacherous Objects: Towards a Theory of Jacobite Material Culture
Authors: PITTOCK MURRAY 
Published: February 2011

AbstractThis article examines the importance of material objects and their circulation, decor, cant and code as means of avoiding prosecution under sedition or treason legislation in the period from 1680 to 1760. It seeks to move the discussion of the use of such material in communicative and associative strategies beyond the realms of antiquarianism and connoisseurship to develop a theory of Jacobite material culture. The study concludes with an examination of the work of James Gibbs and a discussion of interior plasterwork in Scotland and England, notably at the House of Dun.
Needleless Vaccine Delivery Using Micro-Shock Waves
Authors: Jagadeesh Gopalan , Prakash G. Divya , Rakesh S. G. , Allam Uday Sankar , Krishna M. Gopala , Eswarappa Sandeepa M. , Chakravortty Dipshikha 
Published: February 2011

ABSTRACT

Shock waves are one of the most efficient mechanisms of energy dissipation observed in nature. In this study, utilizing the instantaneous mechanical impulse generated behind a micro-shock wave during a controlled explosion, a novel nonintrusive needleless vaccine delivery system has been developed. It is well-known that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery. Unfortunately, needle-free devices for epidermal delivery have inherent problems from the perspective of the safety and comfort of the patient. The penetration depth of less than 100 μm in the skin can elicit higher immune response without any pain. Here we show the efficient utilization of our needleless device (that uses micro-shock waves) for vaccination. The production of liquid jet was confirmed by high-speed microscopy, and the penetration in acrylamide gel and mouse skin was observed by confocal microscopy.
Salmonella enterica
serovar Typhimurium vaccine strain pmrG-HM-D (DV-STM-07) was delivered using our device in the murine salmonellosis model, and the effectiveness of the delivery system for vaccination was compared with other routes of vaccination. Vaccination using our device elicits better protection and an IgG response even at a lower vaccine dose (10-fold less) compared to other routes of vaccination. We anticipate that our novel method can be utilized for effective, cheap, and safe vaccination in the near future.
Molecular Analysis of a Novel Simian Virus 40 (SV40) Type in Rhesus Macaques and Evidence for Double Infections with the Classical SV40 Type
Authors: Fagrouch Zahra , Karremans Kevin , Deuzing Ilona , van Gessel Sabine , Niphuis Henk , Bogers Willy , Verschoor Ernst J. 
Published: February 2011

ABSTRACT
The incidence of simian virus 40 (SV40) infections in rhesus macaques infected with simian-human immunodeficiency viruses (SHIV) and in uninfected animals was determined using PCR. Rates varied from 5% in peripheral blood mononuclear cells of uninfected monkeys to 19.6% in SHIV-infected macaques. Much higher detection rates, up to 75%, were found in lymph nodes and spleen samples of SHIV-infected animals. Sequence analysis of PCR amplicons revealed that they form two genetic clusters, one containing the majority of known SV40 strains and the other formed by variants with 7% genetic difference. Based on this difference, we propose two SV40 types: “type 1” or “classical type” for the majority of SV40 strains and “type 2” for the novel SV40 variants. The genome of one variant, SV40-Ri257, was completely sequenced and analyzed. The agnogene of SV40-Ri257 extends into the VP2 open reading frame and encodes a typical agnoprotein fused to a C-terminal hydrophobic region. The transcriptional control region (TCR) of SV40-Ri257 is the least conserved region compared to type 1 viruses. Particularly, the 3′ end of the TCR, containing the early promoter and enhancer region, exhibits considerable variation. Further analysis of SHIV-infected macaques with type-specific PCRs revealed that the TCR of type 1 was completely conserved, whereas this region in type 2 varied considerably within the early enhancer region. We provide evidence here for the existence of a novel SV40 type in rhesus macaques and show that double infections with both types frequently occur.
Strain Variation among Bordetella pertussis Isolates Circulating in Poland after 50 Years of Whole-Cell Pertussis Vaccine Use
Authors: Mosiej Ewa , Augustynowicz Ewa , Zawadka Monika , Dąbrowski Waldemar , Lutyńska Anna 
Published: February 2011

ABSTRACT

In the present study, clinical isolates of
Bordetella pertussis
collected in Poland from 1960 to 2005 were analyzed by pulsed-field gel electrophoresis (PFGE) according to protocols recommended in previous studies. Among the 110 isolates from 1995 to 2005, 59 PFGE patterns were found, most of which were different from those currently circulating in other European Union (EU) countries for which data are available. The PFGE patterns of currently disseminating
B. pertussis
clones were found within PFGE groups III and IV, as elsewhere in the EU, and in newly identified clusters A and C. Up to 70, 26, and 4%, respectively, of the currently isolated strains in Poland harbored
ptxA1-prn1
,
ptxA1-prn2
, and
ptxA1-prn3
allele combinations, and most (82%) were found to be of the Fim2 phenotype. Differences in the extent of heterogeneity estimated by PFGE typing in
B. pertussis
populations circulating in Poland in comparison to other EU countries may be due to the different vaccine composition strategy, since routine pertussis vaccination was initiated in Poland in 1960.
TaqMan Real-Time Reverse Transcription-PCR Assay for Universal Detection and Quantification of Avian Hepatitis E Virus from Clinical Samples in the Presence of a Heterologous Internal Control RNA
Authors: Troxler Salome , Marek Ana , Prokofieva Irina , Bilic Ivana , Hess Michael 
Published: February 2011

ABSTRACT

Avian hepatitis E virus (HEV) isolates could be separated into at least three genotypes. In this study, the development of the first duplex TaqMan real-time reverse transcription-PCR (RT-PCR) assay for detection and quantification of avian HEV is presented. Primers and probes binding within relatively conserved open reading frame 3 (ORF3) were designed. Tenfold dilution series of
in vitro
-transcribed avian HEV RNA were used as the standard for quantification. A 712-bp region of the green fluorescent protein gene was transcribed
in vitro
and used as a heterologous internal control for both RNA isolation and real-time RT-PCR. The duplex real-time RT-PCR for avian HEV had an efficiency of 1.04, a regression squared value of 0.996, and a sensitivity of approximately 3.6 × 10
3
copies per reaction mixture when
in vitro
-transcribed RNA was used as the template. The presence of
in vitro
-transcribed heterologous internal control RNA did not affect amplification of avian HEV RNA compared to that achieved by the single assay. The sensitivity of the real-time RT-PCR assay was comparable to that of conventional RT-PCR, and it was shown to be highly specific, as tissues from uninfected chickens, mammalian HEVs, and other viral genomes did not produce positive signals. All tested field samples with virus belonging to different avian HEV genotypes were successfully detected with this new duplex TaqMan real-time RT-PCR assay.
Immune-Induced Evolutionary Selection Focused on a Single Reading Frame in Overlapping Hepatitis B Virus Proteins
Authors: Maman Yaakov , Blancher Antoine , Benichou Jennifer , Yablonka Adi , Efroni Sol , Louzoun Yoram 
Published: February 2011

ABSTRACTViruses employ various means to evade immune detection. Reduction of CD8+T cell epitopes is one of the common strategies used for this purpose. Hepatitis B virus (HBV), a member of theHepadnaviridaefamily, has four open reading frames, with about 50% overlap between the genes they encode. We computed the CD8+T cell epitope density within HBV proteins and the mutations within the epitopes. Our results suggest that HBV accumulates escape mutations that reduce the number of epitopes. These mutations are not equally distributed among genes and reading frames. While the highly expressed core and X proteins are selected to have low epitope density, polymerase, which is expressed at low levels, does not undergo the same selection. In overlapping regions, mutations in one protein-coding sequence also affect the other protein-coding sequence. We show that mutations lead to the removal of epitopes in X and surface proteins even at the expense of the addition of epitopes in polymerase. The total escape mutation rate for overlapping regions is lower than that for nonoverlapping regions. The lower epitope replacement rate for overlapping regions slows the evolutionary escape rate of these regions but leads to the accumulation of mutations more robust in the transfer between hosts, such as mutations preventing proteasomal cleavage into epitopes.
eEF-2 Kinase Dictates Cross-Talk between Autophagy and Apoptosis Induced by Akt Inhibition, Thereby Modulating Cytotoxicity of Novel Akt Inhibitor MK-2206
Authors: Cheng Yan , Ren Xingcong , Zhang Yi , Patel Rajesh , Sharma Arati , Wu Hao , Robertson Gavin P. , Yan Li , Rubin Eric , Yang Jin-Ming 
Published: February 2011

Abstract
Inhibition of the survival kinase Akt can trigger apoptosis, and also has been found to activate autophagy, which may confound tumor attack. In this study, we investigated regulatory mechanisms through which apoptosis and autophagy were modulated in tumor cells subjected to Akt inhibition by MK-2206, the first allosteric small molecule inhibitor of Akt to enter clinical development. In human glioma cells, Akt inhibition by MK-2206 or siRNA-mediated attenuation strongly activated autophagy, whereas silencing of eukaryotic elongation factor-2 (eEF-2) kinase, a protein synthesis regulator, blunted this autophagic response. Suppression of MK-2206–induced autophagy by eEF-2 silencing was accompanied by a promotion of apoptotic cell death. Similarly, siRNA-mediated inhibition of eEF-2 kinase potentiated the efficacy of MK-2206 against glioma cells. Together, these results showed that blunting autophagy and augmenting apoptosis by inhibition of eEF-2 kinase could modulate the sensitivity of glioma cells to Akt inhibition. Our findings suggest that targeting eEF-2 kinase may reinforce the antitumor efficacy of Akt inhibitors such as MK-2206. Cancer Res; 71(7); 2654–63. ©2011 AACR.
HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care
Authors: Fabi Alessandra , Di Benedetto Anna , Metro Giulio , Perracchio Letizia , Nisticò Cecilia , Di Filippo Franco , Ercolani Cristiana , Ferretti Gianluigi , Melucci Elisa , Buglioni Simonetta , Sperduti Isabella , Papaldo Paola , Cognetti Francesco , Mottolese Marcella 
Published: February 2011

Abstract
Purpose: To analyze HER2 status in primary breast cancer (PBC) compared with correspondent metachronous metastases and to investigate whether BC phenotype may be predictive of change in HER2 expression.
Experimental Design: HER2 was investigated by immunohistochemistry, silver in situ hybridization (SISH), and FISH, in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single PBC and metastatic (MBC) on the same slide.
Results: HER2 status was discordant in 14 cases (10%): 12 negative in PBC and positive in metastases and two positive in PBC and negative in metastases (P = 0.04). These findings were confirmed by a PCR based test termed Multiplex Ligation-dependent Probe Amplification (MLPA). HER2 status changed in hormone receptor-positive BC more frequently than in negative ones (P = 0.002). In addition, we evaluated HER2 gene and chromosome 17 copy number by SISH in the 123 cases with unchanged HER2 status during progression. We found consistent HER2 gene copy number stability in the 100 nonamplified cases. Conversely, of the 23 amplified PBC, 13 (57%) demonstrated a significant increase in the HER2 gene and chromosome 17 copy number in their paired metastases (P = 0.01), as defined by SISH (k = 0.54, P &lt; 0.0001) and MLPA. Patients who changed HER2 status from negative to positive, presented significant longer time to progression when treated with trastuzumab compared to those who were untreated (P = 0.04).
Conclusions: When feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from primary hormone receptor-positive BC. Clin Cancer Res; 17(7); 2055–64. ©2011 AACR.
A Pathobiological Role of the Insulin Receptor in Chronic Lymphocytic Leukemia
Authors: Saiya-Cork Kamlai , Collins Roxane , Parkin Brian , Ouillette Peter , Kuizon Erlene , Kujawski Lisa , Erba Harry , Campagnaro Erica , Shedden Kerby , Kaminski Mark , Malek Sami N. 
Published: February 2011

Abstract
Purpose: The chromosomal deletion 11q affects biology and clinical outcome in chronic lymphocytic leukemia (CLL) but del11q-deregulated genes remain incompletely characterized.
Experimental Design: We have employed integrated genomic profiling approaches on CLL cases with and without del11q to identify 11q-relevant genes.
Results: We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (∼10-fold higher mean levels than other genomic categories) was confirmed by quantitative PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through flow cytometry, compared with measurements in normal CD19+ B cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels. INSR stimulation by insulin in CLL cells ex vivo resulted in the activation of canonical INSR signaling pathways, including the AKT-mTOR and Ras/Raf/Erk pathways, and INSR activation partially abrogated spontaneous CLL cell apoptosis ex vivo. Higher INSR levels correlated with shorter time to first therapy and shorter overall survival (OS). In bivariate analysis, INSR expression predicted for rapid initial disease progression and shorter OS in ZAP-70–low/negative CLL. Finally, in multivariate analysis (ZAP-70 status, IgVH status, and INSR expression), we detected elevated HRs and trends for short OS for CLL cases with high INSR expression (analyzed inclusive or exclusive of cases with del11q).
Conclusions: Our aggregate biochemical and clinical outcome data suggest biologically meaningful elevated INSR expression in a substantial subset of all CLL cases, including many cases with del11q. Clin Cancer Res; 17(9); 2679–92. ©2011 AACR.
Second-Generation Tyrosine Kinase Inhibitors: The Future of Frontline CML Therapy
Authors: Kantarjian Hagop M. , Baccarani Michele , Jabbour Elias , Saglio Giuseppe , Cortes Jorge E. 
Published: February 2011

Abstract
All available data from ongoing studies of second-generation tyrosine kinase inhibitors (TKIs) for treatment of patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) were reviewed. In two nilotinib phase 2 trials, the speed and depth of molecular and cytogenetic responses were greater than responses to imatinib. Furthermore, only one patient in each study progressed to accelerated or blastic phase. In the phase 3 ENESTnd study, molecular and cytogenetic responses to nilotinib were superior to imatinib, and more patients achieved undetectable levels of disease with nilotinib. Nilotinib also demonstrated significantly lower progression than did imatinib. In the ongoing phase 2 study of dasatinib, the speed and depth of molecular and cytogenetic responses were higher compared with expected responses to imatinib; no patient to date has progressed. In the phase 3 DASISION study, molecular and cytogenetic responses to dasatinib were superior to those of imatinib and fewer patients progressed. The results suggest that second-generation TKIs have the potential to replace imatinib as the standard of care for patients with early CML-CP. Future CML therapy might include earlier use of these agents to help more patients achieve complete molecular response and may be a path to a CML cure. Clin Cancer Res; 17(7); 1674–83. ©2011 AACR.
Bcr is a substrate for Transglutaminase 2 cross-linking activity
Authors: Yi Sun-Ju , Groffen John , Heisterkamp Nora 
Published: February 2011

Abstract

Background
Breakpoint cluster region (Bcr) is a multi-domain protein that contains a C-terminal GTPase activating protein (GAP) domain for Rac. Transglutaminase 2 (TG2) regulates Bcr by direct binding to its GAP domain. Since TG2 has transglutaminase activity that has been implicated in the response to extreme stress, we investigated if Bcr can also act as a substrate for TG2.

Results
We here report that activation of TG2 by calcium caused the formation of covalently cross-linked Bcr. Abr, a protein related to Bcr but lacking its N-terminal oligomerization domain, was not cross-linked by TG2 even though it forms a complex with it. A Bcr mutant missing the first 62 amino acid residues remained monomeric in the presence of activated TG2, showing that this specific domain is necessary for the cross-linking reaction. Calcium influx induced by a calcium ionophore in primary human endothelial cells caused cross-linking of endogenous Bcr, which was inhibited by the TG2 inhibitor cystamine. Treatment of cells with cobalt chloride, a hypoxia-mimetic that causes cellular stress, also generated high molecular weight Bcr complexes. Cross-linked Bcr protein appeared in the TritonX-100-insoluble cell fraction and further accumulated in cells treated with a proteasome inhibitor.

Conclusions
Bcr thus represents both an interacting partner under non-stressed conditions and a target of transglutaminase activity for TG2 during extreme stress.
Modification of genetic regulation of a heterologous chitosanase gene in Streptomyces lividans TK24 leads to chitosanase production in the absence of chitosan
Authors: Dubeau Marie-Pierre , Guay Isabelle , Brzezinski Ryszard 
Published: February 2011

Abstract

Background
Chitosanases are enzymes hydrolysing chitosan, a β-1,4 linked D-glucosamine bio-polymer. Chitosan oligosaccharides have numerous emerging applications and chitosanases can be used for industrial enzymatic hydrolysis of chitosan. These extracellular enzymes, produced by many organisms including fungi and bacteria, are well studied at the biochemical and enzymatic level but very few works were dedicated to the regulation of their gene expression. This is the first study on the genetic regulation of a heterologous chitosanase gene (csnN106) in Streptomyces lividans.

Results
Two S. lividans strains were used for induction experiments: the wild type strain and its mutant (ΔcsnR), harbouring an in-frame deletion of the csnR gene, encoding a negative transcriptional regulator. Comparison of chitosanase levels in various media indicated that CsnR regulates negatively the expression of the heterologous chitosanase gene csnN106. Using the ΔcsnR host and a mutated csnN106 gene with a modified transcription operator, substantial levels of chitosanase could be produced in the absence of chitosan, using inexpensive medium components. Furthermore, chitosanase production was of higher quality as lower levels of extracellular protease and protein contaminants were observed.

Conclusions
This new chitosanase production system is of interest for biotechnology as only common media components are used and enzyme of high degree of purity is obtained directly in the culture supernatant.
Dispersion of single-walled carbon nanotubes modified with poly-l-tyrosine in water
Authors: Kojima Mio , Chiba Tomoka , Niishima Junichiro , Higashi Toshiaki , Fukuda Takahiro , Nakajima Yoshikata , Kurosu Shunji , Hanajiri Tatsuro , Ishii Koji , Maekawa Toru , Inoue Akira 
Published: February 2011

AbstractIn this study, complexes composed of poly-l-tyrosine (pLT) and single-walled carbon nanotubes (SWCNTs) were produced and the dispersibility of the pLT/SWCNT complexes in water by measuring the ζ potential of the complexes and the turbidity of the solution were investigated. It is found that the absolute value of the ζ potential of the pLT/SWCNT complexes is as high as that of SWCNTs modified with double-stranded DNA (dsDNA) and that the complexes remain stably dispersed in the water at least for two weeks. Thermogravimetry analysis (TGA) and visualization of the surface structures of pLT/SWCNT complexes using an atomic force microscope (AFM) were also carried out.