bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Immunogenicity of DNA Prime and Modified Vaccinia Ankara Virus-HIV Subtype C Vaccine Boost in Healthy Adults
Authors: Hayes Peter , Gilmour Jill , von Lieven Andrea , Gill Dilbinder , Clark Lorna , Kopycinski Jakub , Cheeseman Hannah , Chung Amy , Alter Galit , Dally Len , Zachariah Devika , Lombardo Angela , Ackland James , Sayeed Eddy , Jackson Akil , Boffito Marta , Gazzard Brian , Fast Patricia E. , Cox Josephine H. , Laufer Dagna 
Published: January 2013

ABSTRACTA randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses of DNA vaccine (Advax) plus 1 dose of recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or 3 doses of TBC-M4 alone (groups A and B, respectively). Both vaccine regimens were found to be safe and well tolerated. Gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay responses were detected in 1/10 (10%) individuals in group A after three Advax primes and in 9/9 individuals (100%) after the MVA boost. In group B, IFN-γ ELISPOT responses were detected in 6/12 (50%) and 7/11 (64%) individuals after the second and third MVA vaccinations, respectively. Responses to all vaccine components, but predominantly to Env, were seen. The breadth and magnitude of the T cell response and viral inhibition were greater in group A than in group B, indicating that the quality of the T-cell response was enhanced by the DNA prime. Intracellular cytokine staining indicated that the T-cell responses were polyfunctional but were skewed toward Env with a CD4+phenotype. At 2 weeks after the last vaccination, HIV-specific antibody responses were detected in all (100%) group B and 1/11 (9.1%) group A vaccinees. Vaccinia virus-specific responses were detected in all (100%) group B and 2/11 (18.2%) group A vaccinees. In conclusion, HIV-specific T-cell responses were seen in the majority of volunteers in groups A and B but with a trend toward greater quality of the T-cell response in group A. Antibody responses were better in group B than in group A.
Microplate alamarBlue Assay for Paracoccidioides Susceptibility Testing
Authors: de Paula e Silva A. C. A. , Oliveira H. C. , Silva J. F. , Sangalli-Leite F. , Scorzoni L. , Fusco-Almeida A. M. , Mendes-Giannini M. J. S. 
Published: January 2013

ABSTRACT

CLSI method M27-A3 is not available for use with dimorphic fungi, such as those of the
Paracoccidioides
genus. In this study, we developed a microdilution method and added the alamarBlue reagent to test the responses of
Paracoccidioides brasiliensis
and
Paracoccidioides lutzii
against amphotericin B and itraconazole antifungals. The test proved to be sensitive, practical, and inexpensive and can be used to monitor the activity of low-growth microorganisms and their response to various drugs.
Activity and Mechanism of Action of HDVD, a Novel Pyrimidine Nucleoside Derivative with High Levels of Selectivity and Potency against Gammaherpesviruses
Authors: Coen N. , Singh U. , Vuyyuru V. , Van den Oord J. J. , Balzarini J. , Duraffour S. , Snoeck R. , Cheng Y. C. , Chu C. K. , Andrei G. 
Published: January 2013

ABSTRACT

A novel nucleoside analogue, 1-[(2
S
,4
S
-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1H,3H)-dione, or HDVD, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). HDVD had also a pronounced inhibitory activity against murine herpesvirus 68 (MHV-68) and herpes simplex virus 1 (HSV-1). In contrast, replication of herpesvirus saimiri (HVS), HSV-2, and varicella-zoster virus (VZV) was weakly inhibited by the compound, and no antiviral activity was determined against human cytomegalovirus (HCMV) and rhesus rhadinovirus (RRV). The HDVD-resistant virus phenotype contained point mutations in the viral thymidine kinase (TK) of HSV-1, MHV-68, and HVS isolates. These mutations conferred cross-resistance to other TK-dependent drugs, with the exception of an MHV-68 mutant (E358D) that exhibited resistance only to HDVD. HSV-1 and HVS TK-mutants isolated under selective pressure with bromovinyldeoxyuridine (BVDU) also showed reduced sensitivity to HDVD. Oral treatment with HDVD and BVDU was assessed in an intranasal model of MHV-68 infection in BALB/c mice. In contrast to BVDU treatment, HDVD-treated animals showed a reduction in viral DNA loads and diminished viral gene expression during acute viral replication in the lungs in comparison to levels in untreated controls. The valyl ester prodrug of HDVD (USS-02-71-44) suppressed the latent infection in the spleen to a greater extent than HDVD. In the present study, HDVD emerged as a highly potent antiviral with a unique spectrum of activity against herpesviruses, in particular, gammaherpesviruses, and may be of interest in the treatment of virus-associated diseases.
Manchester triage system version II and resource utilisation in the emergency department
Authors: Santos André Peralta , Freitas Paulo , Martins Henrique Manuel Gil 
Published: January 2013

Emergency department (ED) triage systems aim to direct the best clinical assistance to those who are in the greatest urgency and guarantee that resources are efficiently applied.The study's purpose was to determine whether the Manchester Triage System (MTS) second version is a useful instrument for determining the risk of hospital admission, intrahospital death and resource utilisation in ED and to compare it with the MTS first version.This was a prospective study of patients that attended the ED at a large hospital. It comprised a total of 25 218 cases that were triaged between 11 July and 13 October 2011. The MTS codes were grouped into two clusters: red and orange into a ‘high acuity/priority’ (HP) cluster, and yellow, green and blue into a ‘low acuity/priority’ cluster.The risk of hospital admission in the HP cluster was 4.86 times that of the LP cluster for both admission route and ages. The percentage of patient hospital admission between medical and surgical specialties, in high and low priority clusters, was similar. We found the risk of death in the HP cluster to be 5.58 times that of the risk of the low acuity/priority cluster. The MTS had an inconsistent association relative to the utilisation of x-ray, while it seemed to portray a consistent association between ECG and laboratory utilisation and MTS cluster.There were no differences between medical and surgical specialities risk of admission. This suggests that improvements were made in the second version of MTS, particularly in the discriminators of patients triaged to surgical specialties, because this was not true for the first version of MTS.
Evolved design makes ThoraQuik safe and user friendly in the management of pneumothorax and pleural effusion
Authors: Rathinam Sridhar , Grobler Sophia , Bleetman Antony , Kink Thomas , Steyn Richard 
Published: January 2013

BackgroundWe have previously described the utility of ThoraQuik, a device designed to be fit for purpose for aspirations of pneumothorax and pleural effusions. We evaluated the safety, efficacy and operator handling of the evolved prototype, ThoraQuik II, which has a lesser profile and a spring loaded Veres needle for added safety.MethodsA prospective, observational clinical trial with ethics and MHRA approval was conducted in a single centre. Patients with diagnosed pneumothorax (including tension pneumothorax) and pleural effusion were consented and recruited. The ease of device introduction, penetration and ease of use were evaluated. Clinical and radiological improvements were the clinical endpoints and operator feedback was analysed.Results20 procedures were performed on patients (mean age: 63.4 years (range: 30–90 years) with 75% male subjects) recruited between September 2008 and August 2009. Nine patients had pneumothorax (tension pneumothorax n=4) and 11 had pleural effusions. 19 patients completed the study with symptomatic and radiological resolution. One patient was withdrawn due to poor pain threshold disproportionate to the procedure. No complications were encountered. 68% had complete clinical and radiological resolution and 32% had partial resolution (these patients needed a definitive drain and hence were not aspirated to completion). The operator feedback in the study rated the device as very good or excellent in 90% patients.ConclusionsOur study found the use of ThoraQuik II to be safe and easy in draining pneumothorax and pleural effusions. The changes to ThoraQuik II made it more user friendly.
Use of prothrombin complex concentrates: 4-year experience of a national aeromedical retrieval service servicing remote and rural areas
Authors: Robertson Laura Catriona , McKinlay Jayne A C , Munro Philip T , Hearns Stephen 
Published: January 2013

IntroductionProthrombin complex concentrates (PCCs) are recommended as first-line treatment for acquired or congenital factor II, VII, IX and X deficiencies in situations of major haemorrhage. The Emergency Medical Retrieval Service (EMRS) provides critical care and aeromedical retrieval to patients in remote and rural Scotland. It has an important role in the care of these patients.MethodWe sought to determine the incidence of haemorrhage requiring PCC administration in our cohort of patients, and to assess compliance with current national guidelines regarding their storage and use. We searched our database for all patients that received PCCs, or met current guidelines for their administration, and followed them through to hospital discharge. We also conducted a telephone survey of all hospitals served by the EMRS to determine compliance with national standards.ResultsDuring the 42-month study period, 1170 retrieval missions were conducted. Twenty-six retrieved patients had a congenital or acquired clotting factor deficiency and seven met criteria for PCC administration. Of these, only three received PCCs prior to transfer to definitive care. Telephone survey revealed that all the rural general hospitals were served by the EMRS stock PCCs, but only one out of 15 GP-led community hospitals had access to PCCs.ConclusionsIn the remote and rural setting where access to definitive care may be limited or delayed, timely administration of PCCs in appropriate patients may improve outcomes. As many rural hospitals do not have access to PCCs, the ability of the EMRS to provide this treatment may improve patient care.
Prognostic significance of serum microRNA-221 expression in human epithelial ovarian cancer
Authors: Hong Fanzhen , Li Yuyang , Xu Yongping , Zhu Lin 
Published: January 2013

Objective To evaluate the feasibility of using serum microRNA (miR)-221 as a noninvasive diagnostic and prognostic biomarker in epithelial ovarian cancer (EOC). Methods In this retrospective study, real-time reverse transcription–polymerase chain reaction was used to measure miR-221 expression in serum samples from patients with EOC and healthy age-matched controls. Correlations between serum miR-221 levels and clinicopathological factors and prognosis were explored. Results Serum miR-221 was upregulated in patients with EOC ( n = 96) compared with healthy controls ( n = 35). The level of serum miR-221 expression was significantly associated with International Federation of Gynecology and Obstetrics stage, and tumour grade. Furthermore, multivariate analysis of overall survival showed that high serum miR-221 expression was an independent unfavourable prognostic factor in EOC. Conclusions These findings indicate that serum miR-221 may have a role as a novel diagnostic and prognostic marker, and may have potential as a therapeutic target in EOC.
Adiponectin/leptin ratio and insulin resistance in pregnancy
Authors: Skvarca A , Tomazic M , Blagus R , Krhin B , Janez A 
Published: January 2013

Objective Pregnancy is characterized by progressive insulin resistance. The present study evaluated whether the adiponectin/leptin ratio is associated with insulin resistance in pregnancy, since this ratio has been shown to be associated with insulin resistance in obesity, type 2 diabetes mellitus, metabolic syndrome and polycystic ovary syndrome. Methods In this cross-sectional study, adiponectin and leptin concentrations were measured in pregnant women using enzyme-linked immunosorbent assays. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA–IR). Results Mean ± SD age of the participants ( n = 74) was 30.76 ± 4.27 years, mean ± SD gestational age was 26.81 ± 3.52 weeks and median body mass index (BMI) before pregnancy was 22.68 kg/m2 (interquartile range 20.75–26.79 kg/m2). There was a significant correlation between the HOMA–IR and leptin concentration, but not between the HOMA–IR and adiponectin concentration. There was a significant inverse correlation between the HOMA–IR and adiponectin/leptin ratio. The adiponectin/leptin ratio was inversely correlated with BMI before pregnancy. Conclusion The adiponection/leptin ratio inversely correlates with HOMA–IR in pregnancy.
Development of a checklist of quality indicators for clinical trials in resource-limited countries: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) experience
Authors: Hanna Mina , Minga Albert , Fao Paulin , Borand Laurence , Diouf Assane , Mben Jean-Marc , Gad Rita R , Anglaret Xavier , Bazin Brigitte , Chene Geneviève ,   and the [Quali-PED] ANRS 12175 Study Group
Published: January 2013

Background Since 1994, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) has funded research sites in resource-limited countries (RLCs). These sites implement research on human immunodeficiency virus (HIV) infection and Hepatitis C. In parallel, international regulations and recommendations for clinical trials have evolved and proliferated. However, little guidance exists on how these should be interpreted and applied within academic trials and in the context of RLCs. After developing a specific Ethical Charter for research in developing countries in 2002, ANRS developed a set of quality indicators (QIs) as a monitoring tool for assessing compliance to international guidelines. Purpose We describe here the development process, QIs adopted, and areas for improvement. Methods In 2008, a group of experts was convened that included a researcher representing each ANRS site (Cote d’Ivoire, Senegal, Cameroun, Burkina Faso, Egypt, and Cambodia). Our structuring interaction development process combined evidence and expert opinion in two nominal group meetings to identify (1) clinical trial processes involved, (2) issues specific to RLCs in terms of Good Clinical Practice (GCP) and the application of ethical recommendations, and (3) checklists of QIs adapted to clinical trials conducted in RLCs. Results The trial process reviewed and proposed for RLCs was mostly similar to the one produced in wealthier countries. The scheme generated by our work group added two further processes: ‘drug management’ and ‘biological investigations’. Specific issues regarding trial management in RLCs were therefore described for eight trial steps (1) protocol conception and seeking authorizations, (2) participant enrollment and follow-up, (3) site monitoring, (4) drug management, (5) biological investigations, (6) record management, (7) data management, and (8) site closeout. A total of 58 indicators were identified with at least one indicator for each trial process. Limitations Some trial activities require further consideration, that is, in the case of vulnerable participants (children, pregnant women). Proposed indicators are the result of expert consensus and reflect their experience in the HIV field. Relevance to existing trials and extrapolation to other fields must be assessed. Conclusions This innovative program allowed ANRS sites located in RLCs to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. The next step is to collect data from ongoing HIV and hepatitis C trials in these settings and will assess the relevance of these indicators to document current quality of performance among trials in resource-limited settings.
Optimizing patient derived mesenchymal stem cells as virus carriers for a Phase I clinical trial in ovarian cancer
Authors: Mader Emily K , Butler Greg , Dowdy Sean C , Mariani Andrea , Knutson Keith L , Federspiel Mark J , Russell Stephen J , Galanis Evanthia , Dietz Allan B , Peng Kah-Whye 
Published: January 2013

Abstract

Background
Mesenchymal stem cells (MSC) can serve as carriers to deliver oncolytic measles virus (MV) to ovarian tumors. In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach.

Methods
MSC from adipose tissues of healthy donors (hMSC) and nine ovarian cancer patients (ovMSC) were characterized for susceptibility to virus infection and tumor homing abilities.

Results
Adipose tissue (range 0.16-3.96 grams) from newly diagnosed and recurrent ovarian cancer patients yielded about 7.41×106 cells at passage 1 (range 4–9 days). Phenotype and doubling times of MSC were similar between ovarian patients and healthy controls. The time to harvest of 3.0×108 cells (clinical dose) could be achieved by day 14 (range, 9–17 days). Two of nine samples tested had an abnormal karyotype represented by trisomy 20. Despite receiving up to 1.6×109 MSC/kg, no tumors were seen in SCID beige mice and MSC did not promote the growth of SKOV3 human ovarian cancer cells in mice. The ovMSC migrated towards primary ovarian cancer samples in chemotaxis assays and to ovarian tumors in athymic mice. Using non-invasive SPECT-CT imaging, we saw rapid co-localization, within 5–8 minutes of intraperitoneal administration of MV infected MSC to the ovarian tumors. Importantly, MSC can be pre-infected with MV, stored in liquid nitrogen and thawed on the day of infusion into mice without loss of activity. MV infected MSC, but not virus alone, significantly prolonged the survival of measles immune ovarian cancer bearing animals.

Conclusions
These studies confirmed the feasibility of using patient derived MSC as carriers for oncolytic MV therapy. We propose an approach where MSC from ovarian cancer patients will be expanded, frozen and validated to ensure compliance with the release criteria. On the treatment day, the cells will be thawed, washed, mixed with virus, briefly centrifuged and incubated for 2 hours with virus prior to infusion of the virus/MSC cocktail into patients.
Interaction of members of the heat shock protein-70 family with the macrophage mannose receptor
Authors: Yang Seungchan , Vigerust David J , Shepherd Virginia L 
Published: January 2013

Abstract
Members of the heat shock protein 70 family bind to the macrophage mannose receptor, potentially contributing to appropriate localization and trafficking.
The macrophage MR has been the subject of investigation for over 20 years, and several important physiological functions have been described. However, the molecular mechanisms that regulate MR signaling and trafficking during these processes still remain elusive. The focus of the current paper was to identify potential cellular MR-interacting proteins. An initial screen of binding proteins in MR-expressing cells was performed using coimmunoprecipitation, followed by identification of matching peptide sequences using proteomics and MS. The major class of binding proteins identified belonged to the heat shock family of proteins. The specific interaction of the MR with HSP70 family members was validated by Western blot analysis, ligand binding assays, and intracellular colocalization using confocal microscopy. Additional studies indicated that inhibition of the HSP BiP by treatment of cells with EGCG reduced BiP interaction with and surface expression of the MR. Studies of possible motifs within the cytoplasmic tail of the receptor suggested that a juxtamembrane dibasic sequence may contribute to the interaction with BiP. These findings suggest that the molecular association of the MR with HSP70 family members via the receptor cytoplasmic tail may contribute to MR trafficking in macrophages.
Crystal structure of N-succinimidyl-4-fluorobenzoate, C11H8FNO4
Authors: Liu Ya-Ling , Zou Pei , Wu Jun , Wang Hong-Yong , Luo Shi-Neng 
Published: January 2013

Abstract C11H8FNO4, monoclinic, P21/n (no. 14), a = 9.177(3) Å, b = 5.472(2) Å, c = 22.414(7) Å, β = 95.264(4)°, V = 1120.7 Å3, Z = 4, Rgt(F) = 0.0493, wRref(F2) = 0.1195, T = 203 K.
A Patient-Centered Approach to Counseling Patients With Head and Neck Cancer Undergoing Human Papillomavirus Testing: A Clinician's Guide
Authors: Chu Amy , Genden Eric , Posner Marshall , Sikora Andrew 
Published: January 2013

Abstract
The International Agency for Research on Cancer and the National Cancer Institute have acknowledged human papillomavirus (HPV)-16 as an independent risk factor for oropharyngeal cancer (OPC). HPV-positive oropharyngeal cancer (HPVOPC) is a sexually transmitted entity that is on the rise; within the next 10 years, the annual number of HPV-associated OPC cases is projected to exceed the annual number of cervical cancer cases in the United States. Recognition of HPV status in OPC has broad implications beyond the traditional oncological concerns of timely diagnosis, accurate staging, and appropriate treatment of cancer patients. The National Comprehensive Cancer Network recommends testing the tumor site for HPV-status during OPC management; it is likely this will become a standard component of care for patients with high-probability tumors of the oropharynx. As the practice of HPV testing becomes more common, it behooves providers to be able to adequately address the concerns of patients with HPVOPC. Although there are currently few relevant studies focusing on this population, existing literature on HPV-infected women and patients with cervical cancer strongly supports the concept that patients with HPVOPC need education to optimally address concerns such as self-blame, guilt, intimacy, and interpersonal relationships. When HPV testing is done, it should be accompanied by evidence-driven and patient-centered counseling to best minimize negative psychosocial outcomes and ensure optimum health promotion. Based on the current state of the literature, this article is intended to be a reference for physicians to effectively manage psychosocial outcomes when diagnosing patients with HPV-associated OPC.
Proteasomal Degradation of Herpes Simplex Virus Capsids in Macrophages Releases DNA to the Cytosol for Recognition by DNA Sensors
Authors: Horan Kristy A. , Hansen Kathrine , Jakobsen Martin R. , Holm Christian K. , Søby Stine , Unterholzner Leonie , Thompson Mikayla , West John A. , Iversen Marie B. , Rasmussen Simon B. , Ellermann-Eriksen Svend , Kurt-Jones Evelyn , Landolfo Santo , Damania Blossom , Melchjorsen Jesper , Bowie Andrew G. , Fitzgerald Katherine A. , Paludan Søren R. 
Published: January 2013

Abstract
The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9 and that nonimmune tissue cells can sense herpesvirus DNA in the nucleus. However, it remains unknown how and where myeloid cells, such as macrophages and conventional dendritic cells, detect infections with herpesviruses. In this study, we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors. In this context, the DNA sensor IFN-γ–inducible 16 is important for induction of IFN-β in human macrophages postinfection with HSV-1 and CMV. Viral DNA localized to the same cytoplasmic regions as did IFN-γ–inducible 16, with DNA sensing being independent of viral nuclear entry. Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors.