bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombosomes: a platelet‐derived hemostatic agent for control of noncompressible hemorrhage
Authors: Fitzpatrick G. Michael , Cliff Richard , Tandon Narendra 
Published: January 2013

BackgroundUncontrolled hemorrhage is responsible for ∼80% of the potentially survivable deaths in combat and over 40% of early mortality in the under 65 age group in the United States. Providing an easily used infusible hemostatic agent to first responders could significantly reduce these fatalities. We report on an infusible lyophilized platelet‐derived hemostatic agent stabilized with trehalose and polysucrose prior to and during lyophilization.Study Design and MethodsCharacterization included determining the particle population size range, surface marker expression GPIb, GPIIbIIIa, and Annexin V binding. Function was assessed by aggregation, thromboelastography, and thrombin generation. Pharmacokinetics, biodistribution, and immunogenicity established using Indium111 labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman primates.ResultsThrombosomes retained GPIIbIIIa expression (98.71% ± 0.18 of the rehydrated particles), a reduced expression of GPIb (47.77% ± 6.65), and Annexin V binding (86.05% ± 2.65). Aggregation to all agonists except thrombin in buffer (78.15% ± 2.5) was <50%. Thrombin generation and thromboelastography results demonstrated a concentration gradient that was consistent from lot to lot. There were no observed adverse events in any safety study and blood loss was reduced by >80% in the thrombocytopenic ear bleed model.ConclusionOur in vitro characterization studies in conjunction with preclinical animal safety and efficacy studies demonstrated lot consistency in manufacturing, maintenance of hemostatic functions of Thrombosomes, safety at high dose concentrations, and the potential to provide an effective hemostatic agent at the site of injury.
Development of a riboflavin and ultraviolet light‐based device to treat whole blood
Authors: Reddy Heather L. , Doane Suzann K. , Keil Shawn D. , Marschner Susanne , Goodrich Raymond P. 
Published: January 2013

BackgroundIn the United States, blood components are commonly used for patients in need of massive transfusion after blood loss. In combat situations, when severe traumatic injuries occur far from a hospital, fresh whole blood is a valuable transfusion therapy because components may not be available. The risk of infectious or immunological complications from fresh whole blood transfusions could be mitigated by a system that reduces pathogen loads and inactivates white blood cells (WBCs). Such a system is in development and utilizes riboflavin and ultraviolet light to provide pathogen reduction and WBC inactivation.Study Design and MethodsThe system has been tested with in vitro and in vivo animal studies to evaluate WBC inactivation and pathogen reduction, and with in vitro studies to assess the function of the treated blood products.ResultsElimination of viable WBCs with the system is equivalent to gamma‐irradiation. Results have been reported for reduction of Babesia microti, Trypanosoma cruzi, HIV, and bacteria, and preliminary results for Babesia divergens are available. Treated whole blood, platelets, and plasma maintain coagulation function. Treated red blood cell components exhibit low hemolysis and high adenosine triphosphate levels at the end of storage.ConclusionsTreatment with riboflavin and ultraviolet light is a promising alternative to gamma‐irradiation. Effectiveness of the system against a variety of pathogens has been established, and further studies are planned. The in vitro studies of function indicate that treated whole blood, as well as components from treated whole blood, will provide acceptable hemostasis and perform well in the next phase of in vivo studies.
Evolution and the Bible: The Hermeneutical Question
Authors: Dawes Gregory W. 
Published: January 2013

Theistic evolutionists suggest that evolutionary theory is not necessarily in conflict with biblical teaching. But in fact conflict is avoided only by reinterpreting Genesis 1–3. Is such a reinterpretation justified? There exists a hermeneutical tradition that dates back to St Augustine which offers guidelines regarding apparent conflicts between biblical teaching and natural philosophy (or ‘science’). These state that the literal meaning of the text may be abandoned only if the natural-philosophical conclusions are established beyond doubt. But no large-scale scientific theory, such as Darwin’s, can claim this degree of certainty. It follows that to justify their reinterpretation of Genesis 1–3, Christians must either argue that the literal sense of the biblical text can be maintained or accept that this view of biblical authority is untenable. Three alternative views are discussed: a first that limits the scope of biblical authority, a second that distinguishes between the Bible and the Word of God, and a third that abandons the idea that religious faith offers certain knowledge. While the third view seems the most defensible, it comes at a cost: the recognition that, as John Locke put it, “reason must be our last judge and guide in everything.”
Single-Tube Multiplexed Molecular Detection of Endemic Porcine Viruses in Combination with Background Screening for Transboundary Diseases
Authors: Wernike Kerstin , Hoffmann Bernd , Beer Martin 
Published: January 2013

ABSTRACT
Detection of several pathogens with multiplexed real-time quantitative PCR (qPCR) assays in a one-step setup allows the simultaneous detection of two endemic porcine and four different selected transboundary viruses. Reverse transcription (RT)-qPCR systems for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), two of the most economically important pathogens of swine worldwide, were combined with a screening system for diseases notifiable to the World Organization of Animal Health, namely, classical and African swine fever, foot-and-mouth disease, and Aujeszky's disease. Background screening was implemented using the identical fluorophore for all four different RT-qPCR assays. The novel multiplex RT-qPCR system was validated with a large panel of different body fluids and tissues from pigs and other animal species. Both reference samples and clinical specimens were used for a complete evaluation. It could be demonstrated that a highly sensitive and specific parallel detection of the different viruses was possible. The assays for the notifiable diseases were even not affected by the simultaneous amplification of very high loads of PRRSV- and PCV2-specific sequences. The novel broad-spectrum multiplex assay allows in a unique form the routine investigation for endemic porcine pathogens with exclusion diagnostics of the most important transboundary diseases in samples from pigs with unspecific clinical signs, such as fever or hemorrhages. The new system could significantly improve early detection of the most important notifiable diseases of swine and could lead to a new approach in syndromic surveillance.
Functional Comparison of SCARB2 and PSGL1 as Receptors for Enterovirus 71
Authors: Yamayoshi Seiya , Ohka Seii , Fujii Ken , Koike Satoshi 
Published: January 2013

ABSTRACT
Human scavenger receptor class B, member 2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL1) have been identified to be the cellular receptors for enterovirus 71 (EV71). We compared the EV71 infection efficiencies of mouse L cells that expressed SCARB2 (L-SCARB2) and PSGL1 (L-PSGL1) and the abilities of SCARB2 and PSGL1 to bind to the virus. L-SCARB2 cells bound a reduced amount of EV71 compared to L-PSGL1 cells. However, EV71 could infect L-SCARB2 cells more efficiently than L-PSGL1 cells. The results suggested that the difference in the binding capacities of the two receptors was not the sole determinant of the infection efficiency and that SCARB2 plays an essential role after attaching to virions. Therefore, we examined the viral entry into L-SCARB2 cells and L-PSGL1 cells by immunofluorescence microscopy. In both cells, we detected internalized EV71 virions that colocalized with an early endosome marker. We then performed a sucrose density gradient centrifugation analysis to evaluate viral uncoating. After incubating the EV71 virion with L-SCARB2 cells or soluble SCARB2 under acidic conditions below pH 6.0, we observed that part of the native virion was converted into an empty capsid that lacked both genomic RNA and VP4 capsid proteins. The results suggested that the uncoating of EV71 requires both SCARB2 and an acidic environment and occurs after the internalization of the virus-receptor complex into endosomes. However, the empty capsid formation was not observed after incubation with L-PSGL1 cells or soluble PSGL1 under any of the tested pH conditions. These results indicated that SCARB2 is capable of viral binding, viral internalization, and viral uncoating and that the low infection efficiency of L-PSGL1 cells is due to the inability of PSGL1 to induce viral uncoating. The characterization of SCARB2 as an uncoating receptor greatly contributes to the understanding of the early steps of EV71 infection.
In Vivo
Selection of H1N2 Influenza Virus Reassortants in the Ferret Model
Authors: Angel Matthew , Kimble J. Brian , Pena Lindomar , Wan Hongquan , Perez Daniel R. 
Published: January 2013

ABSTRACT
Although the ferret model has been extensively used to study pathogenesis and transmission of influenza viruses, little has been done to determine whether ferrets are a good surrogate animal model to study influenza virus reassortment. It has been previously shown that the pandemic 2009 H1N1 (H1N1pdm) virus was able to transmit efficiently in ferrets. In coinfection studies with either seasonal H1N1 or H3N2 strains (H1N1s or H3N2s, respectively), the H1N1pdm virus was able to outcompete these strains and become the dominant transmissible virus. However, lack of reassortment could have been the result of differences in the cell or tissue tropism of these viruses in the ferret. To address this issue, we performed coinfection studies with recombinant influenza viruses carrying the surface genes of a seasonal H3N2 strain in the background of an H1N1pdm strain and vice versa. After serial passages in ferrets, a dominant H1N2 virus population was obtained with a constellation of gene segments, most of which, except for the neuraminidase (NA) and PB1 segments, were from the H1N1pdm strain. Our studies suggest that ferrets recapitulate influenza virus reassortment events. The H1N2 virus generated through this process resembles similar viruses that are emerging in nature, particularly in pigs.
Airway Delivery of an Adenovirus-Based Ebola Virus Vaccine Bypasses Existing Immunity to Homologous Adenovirus in Nonhuman Primates
Authors: Richardson Jason S. , Pillet Stéphane , Bello Alexander J. , Kobinger Gary P. 
Published: January 2013

ABSTRACT
Anti-adenovirus serotype 5 antibodies are capable of neutralizing adenovirus serotype 5-based vaccines. In mice and guinea pigs, intranasal delivery of adenovirus serotype 5-based vaccine bypasses induced adenovirus serotype 5 preexisting immunity, resulting in protection against species-adapted Ebola virus challenge. In this study, nonhuman primates were vaccinated with adenovirus serotype 5-based vaccine either intramuscularly or via the airway route (intranasally/intratracheally) in the presence or absence of adenovirus serotype 5 preexisting immunity. Immune responses were evaluated to determine the effect of both the vaccine delivery route and preexisting immunity before and after a lethal Ebola virus (Zaïre strain Kikwit 95) challenge. Intramuscular vaccination fully protected nonhuman primates in the absence of preexisting immunity, whereas the presence of preexisting immunity abrogated vaccine efficacy and resulted in complete mortality. In contrast, the presence of preexisting immunity to adenovirus serotype 5 did not alter the survival rate of nonhuman primates receiving the adenovirus serotype 5-based Ebola virus vaccine in the airway. This study shows that airway vaccination with adenovirus serotype 5-based Ebola virus vaccine can efficiently bypass preexisting immunity to adenovirus serotype 5 and induce protective immune responses, albeit at lower efficacy than that using an intramuscular vaccine delivery route.
The First-aid Advice and Safety Training (FAST) parents programme for the prevention of unintentional injuries in preschool children: a protocol
Authors: Mytton Julie A , Towner Elizabeth ML , Kendrick Denise , Stewart-Brown Sarah , Emond Alan , Ingram Jenny , Blair Peter S , Powell Jane , Mulvaney Caroline , Thomas James , Deave Toity , Potter Barbara 
Published: January 2013

BackgroundUnintentional injury is the leading cause of preventable death in children in the UK, and 0–4-year-olds frequently attend emergency departments following injuries in the home. Parenting programmes designed to support parents, promote behaviour change and enhance parent–child relationships have been shown to improve health outcomes in children. It is not known whether group-based parenting programmes have the potential to prevent unintentional injuries in preschool children.MethodsA study to develop a group-based parenting programme to prevent unintentional home injuries in preschool children, and assess the feasibility of evaluation through a cluster-randomised controlled trial. The intervention, designed for parents of children who have sustained a medically attended injury, will be developed with two voluntary sector organisations. The feasibility study will assess ability to recruit parents, deliver the programme and follow-up participants. Participants will complete questionnaires at baseline, 3 months and 6 months, and report injuries in their preschool children using a tool designed and validated for this study. Qualitative methods will assess user and deliverer perceptions of the programme.DiscussionThis study will develop the first group-based parenting programme to prevent injuries in preschool children, and design tools for parent-reported injury outcomes. A key challenge will be to recruit parents to participate in a manner that is non-stigmatising, and does not result in feelings of guilt or belief that they are perceived to be a bad parent. The findings will be used to prepare a trial to assess the effectiveness and cost-effectiveness of the intervention.
CONGRUENCES CONCERNING LEGENDRE POLYNOMIALS III
Authors: SUN ZHI-HONG 
Published: January 2013

Suppose that p is an odd prime and d is a positive integer. Let x and y be integers given by p = x2+dy2 or 4p = x2+dy2. In this paper we determine x( mod p) for many values of d. For example, [Formula: see text] where x is chosen so that x ≡ 1 ( mod 3). We also pose some conjectures on supercongruences modulo p2 concerning binary quadratic forms.
Designing and Developing S100P Inhibitor 5-Methyl Cromolyn for Pancreatic Cancer Therapy
Authors: Arumugam Thiruvengadam , Ramachandran Vijaya , Sun Duoli , Peng Zhenghong , Pal Ashutosh , Maxwell David S. , Bornmann William G. , Logsdon Craig D. 
Published: January 2013

Abstract
We have previously shown that the antiallergic drug cromolyn blocks S100P interaction with its receptor receptor for advanced glycation end product (RAGE) and improves gemcitabine effectiveness in pancreatic ductal adenocarcinoma (PDAC). However, the concentration required to achieve its effectiveness was high (100 μmol/L). In this study, we designed and synthesized analogs of cromolyn and analyzed their effectiveness compared with the parent molecule. An ELISA was used to confirm the binding of S100P with RAGE and to test the effectiveness of the different analogs. Analog 5-methyl cromolyn (C5OH) blocked S100P binding as well as the increases in NF-κB activity, cell growth, and apoptosis normally caused by S100P. In vivo C5OH systemic delivery reduced NF-κB activity to a greater extent than cromolyn and at 10 times lesser dose (50 mg vs. 5 mg). Treatment of mice-bearing syngeneic PDAC tumors showed that C5OH treatment reduced both tumor growth and metastasis. C5OH treatment of nude mice bearing orthotopic highly aggressive pancreatic Mpanc96 cells increased the overall animal survival. Therefore, the cromolyn analog, C5OH, was found to be more efficient and potent than cromolyn as a therapeutic for PDAC. Mol Cancer Ther; 12(5); 654–62. ©2013 AACR.
A Companion Animal in a Work Simulation: The Roles of Task Difficulty and Prior Companion-Animal Guardianship in State Anxiety
Authors: Stewart Anna , Strickland Oriel 
Published: January 2013

Abstract
Human-animal interactions often have positive physiological and psychological outcomes for humans. The current study extended research in this area by studying three variables that have never directly been examined together within a laboratory setting: task difficulty level (moderate versus extreme), the human-animal interaction (present or absent), and participants’ companion-animal guardianship status (yes or no) to determine whether a companion dog would reduce self-reported state anxiety. The participants were undergraduate students from a large western university in the United States who performed timed paper-and-pencil tasks either with or without the presence of a companion dog under varying degrees of task difficulty. Spielberger’s State/Trait anxiety measures were used to assess reactions to the work setting. Results indicated that although the mere presence of a dog is not enough to lower state anxiety for all participants, the interaction of companion-animal guardianship status and task difficulty was significant. Companion animals may assist in stress relief for people in average-stress jobs who already have positive feelings toward companion animals but may have no effect for people in high-stress jobs or who do not already enjoy the company of animals.
Information about assisted dying: an evaluation of web-based information resources
Authors: Haigh Carol , Costa Cristina 
Published: January 2013

Aim This paper is a report of a study of the quality of information that is available on the World Wide Web around the topic of assisted dying by sampling information from a number of web pages about assisted dying with a view to evaluating the nature, content and rigour of the information they contain. Background The Internet is seen as one of the first places people will go for information about their health or health-related topics. However, whilst it would appear that, as a source of factual health-related information, the Internet has a degree of reliability and credibility, there is a dearth of information about how the information may contribute to opinion formation and attitudes around important health debates. Methods The study used content analysis of web-based material to evaluate the nature, content, currency and rigour of the information they contained against 27 criteria. Each website was independently assessed by two people, and discrepancies were resolved by discussion. In addition the readability and reading age level of each site was evaluated objectively using ‘The Readability Test Tool’ website (Simpson, 2009). The web page data were collected on three separate days in November 2010. Results/Findings The majority of sites showed accuracy (76%, n = 43) with 7 (14%) being assessed as highly accurate. This was reflected in the completeness of the site evaluated. All sites were readable with 12 pages (24%) being rated at 3. Conclusion There is a discrepancy between web-based information that is aimed at ‘scholars’ and that aimed at the general public. This does have implications for those service users who wish to make health-related decisions based upon reliable information.
Transcriptional profiling of Chinese medicinal formula Si-Wu-Tang on breast cancer cells reveals phytoestrogenic activity
Authors: Liu Mandy , Fan Jeffery , Wang Steven , Wang Zhijun , Wang Charles , Zuo Zhong , Chow Moses SS , Shi Leming , Wen Zhining , Huang Ying 
Published: January 2013

Abstract

Background
Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women’s diseases. In our previous study, the microarray gene expression profiles of SWT on breast cancer cell line MCF-7 were found similar to the effect of β-estradiol (E2) on MCF-7 cells in the Connectivity Map database.

Methods
Further data analysis was conducted to find the main similarities and differences between the effects of SWT and E2 on MCF-7 gene expression. The cell proliferation assay on MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) cells were used to examine such estrogenic activity. The estrogenic potency of SWT was further confirmed by estrogen-responsive element (ERE) luciferase reporter assay in MCF-7 cells.

Results
Many estrogen regulated genes strongly up-regulated by E2 were similarly up-regulated by SWT, e.g., GREB1, PGR and EGR3. Of interest with regard to safety of SWT, the oncogenes MYBL1 and RET were strongly induced by E2 but not by SWT. Quantitative RT-PCR analysis revealed a highly concordant expression change in selected genes with data obtained by microarrays. Further supporting SWT’s estrogenic activity, in MCF-7 but not in MDA-MB-231 cells, SWT stimulated cell growth at lower concentrations (< 3.0 mg/ml), while at high concentrations, it inhibits the growth of both cell lines. The growth inhibitory potency of SWT was significantly higher in MDA-MB-231 than in MCF-7 cells. The SWT-induced cell growth of MCF-7 could be blocked by addition of the estrogen receptor antagonist tamoxifen. In addition, SWT was able to activate the ERE activity at lower concentrations. The herbal components Angelicae, Chuanxiong and Rehmanniae at lower concentrations (< 3.0 mg/ml) also showed growth-inducing and ERE-activating activity in MCF-7 cells.

Conclusions
These results revealed a new mechanism to support the clinical use of SWT for estrogen related diseases and possibly for cancer prevention. This study also demonstrated the feasibility of using microarray transcriptional profiling to discover phytoestrogenic components that are present in natural products.
Control of epitaxial relationships of ZnO/SrTiO3 heterointerfaces by etching the substrate surface
Authors: Jia Caihong , Chen Yonghai , Liu Xianglin , Yang Shaoyan , Zhang Weifeng , Wang Zhanguo 
Published: January 2013

Abstract
Wurtzite ZnO thin films with different epitaxial relationships are obtained on as-received and etched (001), (011), and (111) SrTiO3 (STO) by metal-organic chemical vapor deposition (MOCVD). ZnO films exhibit nonpolar (1120) orientation with in-plane orientation relationship of <0001>ZnO//<110>STO on as-received (001) STO, and polar c-axis growth with <1100>ZnO//<110>STO on etched (001) STO substrates. ZnO films change from polar (0001) to semipolar (1012) oriented on as-received and etched (011) STO. On as-received and etched (111) STO, ZnO films show the same growing direction of polar (0001), but different in-plane orientations with 30° rotation. The change of epitaxial relationship of ZnO films on as-received and etched (001), (011), and (111) STO substrates is accompanied with the increase of lattice mismatch, decrease of bond density, and increase of substrate surface roughness. In other words, the epitaxial relationships of ZnO/STO heterointerfaces can be controlled by etching the substrates. These results show that polar, nonpolar, and semipolar ZnO films for different applications can be grown epitaxially on STO substrates by MOCVD.