bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained Reduction of Microbial Burden on Common Hospital Surfaces through Introduction of Copper
Authors: Schmidt Michael G. , Attaway Hubert H. , Sharpe Peter A. , John Joseph , Sepkowitz Kent A. , Morgan Andrew , Fairey Sarah E. , Singh Susan , Steed Lisa L. , Cantey J. Robert , Freeman Katherine D. , Michels Harold T. , Salgado Cassandra D. 
Published: May 2012

ABSTRACT

The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm
2
;
n
= 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm
2
). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm
2
;
n
= 2714 objects) compared to the controls (2,674 CFU/100 cm
2
;
n
= 2,831 objects [
P
< 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.
Early Serum Galactomannan Trend as a Predictor of Outcome of Invasive Aspergillosis
Authors: Chai Louis Y. A. , Kullberg Bart-Jan , Johnson Elizabeth M. , Teerenstra Steven , Khin Lay Wai , Vonk Alieke G. , Maertens Johan , Lortholary Olivier , Donnelly Peter J. , Schlamm Haran T. , Troke Peter F. , Netea Mihai G. , Herbrecht Raoul 
Published: May 2012

ABSTRACT

The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively;
P
= 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (
n
= 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (
P
= 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease
Authors: Görander Staffan , Harandi Ali M. , Lindqvist Madelene , Bergström Tomas , Liljeqvist Jan-Åke 
Published: May 2012

ABSTRACTThe envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4+T cells upon antigen restimulationin vitroand in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials.
LuIII Parvovirus Selectively and Efficiently Targets, Replicates in, and Kills Human Glioma Cells
Authors: Paglino Justin C. , Ozduman Koray , van den Pol Anthony N. 
Published: May 2012

ABSTRACT

Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineffective. The four viruses with the greatest oncolytic activity, LuIII, H-1, MVMp, and MVM-G52, were tested for the ability, at a low MOI, to progressively infect the culture over time, causing cell death at a rate higher than that of cell proliferation. LuIII alone was effective in all five human glioblastomas tested. H-1 progressively infected only two of five; MVMp and MVM-G52 were ineffective in all five. To investigate the underlying mechanism of LuIII's phenotype, we used recombinant parvoviruses with the LuIII capsid replacing the MVMp capsid or with molecular alteration of the P4 promoter. The LuIII capsid enhanced efficient replication and oncolysis in MO59J gliomas cells; other gliomas tested required the entire LuIII genome to exhibit enhanced infection. LuIII selectively infected glioma cells over normal glial cells
in vitro
. In mouse models, human glioblastoma xenografts were selectively infected by LuIII when administered intratumorally; LuIII reduced tumor growth by 75%. LuIII also had the capacity to selectively infect subcutaneous or intracranial gliomas after intravenous inoculation. Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia
in vivo
but showed a modest infection of developing neurons.
Seasonal Trivalent Inactivated Influenza Vaccine Protects against 1918 Spanish Influenza Virus Infection in Ferrets
Authors: Pearce Melissa B. , Belser Jessica A. , Gustin Kortney M. , Pappas Claudia , Houser Katherine V. , Sun Xiangjie , Maines Taronna R. , Pantin-Jackwood Mary J. , Katz Jacqueline M. , Tumpey Terrence M. 
Published: May 2012

ABSTRACT
The influenza virus H1N1 pandemic of 1918 was one of the worst medical catastrophes in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus [A(H1N1)pdm09], the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV), share cross-reactive antigenic determinants. In this study, we demonstrate that immunization with the 2010-2011 seasonal TIV induces neutralizing antibodies that cross-react with the reconstructed 1918 pandemic virus in ferrets. TIV-immunized ferrets subsequently challenged with the 1918 virus displayed significant reductions in fever, weight loss, and virus shedding compared to these parameters in nonimmune control ferrets. Seasonal TIV was also effective in protecting against the lung infection and severe lung pathology associated with 1918 virus infection. Our data demonstrate that prior immunization with contemporary TIV provides cross-protection against the 1918 virus in ferrets. These findings suggest that exposure to A(H1N1)pdm09 through immunization may provide protection against the reconstructed 1918 virus which, as a select agent, is considered to pose both biosafety and biosecurity threats.
Corneal Replication Is an Interferon Response-Independent Bottleneck for Virulence of Herpes Simplex Virus 1 in the Absence of Virion Host Shutoff
Authors: Pasieka Tracy Jo , Menachery Vineet D. , Rosato Pamela C. , Leib David A. 
Published: May 2012

ABSTRACTHerpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.
Partial Escape of HIV-1 from Cytotoxic T Lymphocytes during Chronic Infection
Authors: Lewis Martha J. , Dagarag Mirabelle , Khan Basim , Ali Ayub , Yang Otto O. 
Published: May 2012

ABSTRACTViral mutational escape from CD8+cytotoxic T lymphocytes (CTLs) is typically considered to be a dichotomous process and uncommon during chronic HIV-1 infection.Ex vivopassaging of HIV-1 from persons with chronic infection, however, revealed the evolution of many fixed substitutions within and around CTL-targeted regions, with an associated increase in replicative capacity. This indicates an evolution of mutations during chronic HIV-1 infection that trade replicative fitness for incomplete evasion of CTLs, or “partial escape.”
Recombinant Canine Distemper Virus Strain Snyder Hill Expressing Green or Red Fluorescent Proteins Causes Meningoencephalitis in the Ferret
Authors: Ludlow M. , Nguyen D. T. , Silin D. , Lyubomska O. , de Vries R. D. , von Messling V. , McQuaid S. , De Swart R. L. , Duprex W. P. 
Published: May 2012

ABSTRACT

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV
SH
) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV
SH
(rCDV
SH
) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread
in vivo
. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV
5804P
and the prototypic wild-type CDV
R252
showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV
SH
-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the
in vivo
spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.
Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys
Authors: Mir Kiran D. , Bosinger Steven E. , Gasper Melanie , Ho On , Else James G. , Brenchley Jason M. , Kelvin David J. , Silvestri Guido , Hu Shiu-lok , Sodora Donald L. 
Published: May 2012

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent viral replication in the context of CD4+T cell depletion and elevated immune activation associated with disease progression. In contrast, simian immunodeficiency virus (SIV) infection of African-origin sooty mangabeys (SM) generally does not result in simian AIDS despite high viral loads and therefore affords a unique model in which to study the immunologic contributions to a nonpathogenic lentiviral disease outcome. A key feature of these natural SIV infections is the maintenance of low levels of immune activation during chronic infection. Our goal was to delineate the contribution of monocytes to maintaining low levels of immune activation in SIV-infected SM. Utilizing anex vivowhole-blood assay, proinflammatory cytokine production was quantified in monocytes in response to multiple Toll-like receptor (TLR) ligands and a specific, significant reduction in the tumor necrosis factor alpha (TNF-α) response to lipopolysaccharide (LPS) was observed in SIV-infected SM. In contrast, monocytes from hosts of pathogenic infections (HIV-infected humans and SIV-infected Asian macaques) maintained a robust TNF-α response. In SIV-infected SM, monocyte TNF-α responses to low levels of LPS could be augmented by the presence of plasma from uninfected control animals. The impact of LPS-induced TNF-α production on immune activation was demonstratedin vitro, as TNF-α blocking antibodies inhibited downstream CD8+T cell activation in a dose-dependent manner. These data demonstrate an association between nonpathogenic SIV infection of SM and a reduced monocyte TNF-α response to LPS, and they identify a role for monocytes in contributing to the suppressed chronic immune activation observed in these natural hosts.
Autophagic Clearance of Sin Nombre Hantavirus Glycoprotein Gn Promotes Virus Replication in Cells
Authors: Hussein Islam T. M. , Cheng Erdong , Ganaie Safder S. , Werle Michael J. , Sheema Sheema , Haque Absarul , Mir Muhammad A. 
Published: May 2012

ABSTRACT
Hantavirus glycoprotein precursor (GPC) is posttranslationally cleaved into two glycoproteins, Gn and Gc. Cells transfected with plasmids expressing either GPC or both Gn and Gc revealed that Gn is posttranslationally degraded. Treatment of cells with the autophagy inhibitors 3-methyladenine, LY-294002, or Wortmanin rescued Gn degradation, suggesting that Gn is degraded by the host autophagy machinery. Confocal microscopic imaging showed that Gn is targeted to autophagosomes for degradation by an unknown mechanism. Examination of autophagy markers LC3-I and LC3-II demonstrated that both Gn expression and Sin Nombre hantavirus (SNV) infection induce autophagy in cells. To delineate whether induction of autophagy and clearance of Gn play a role in the virus replication cycle, we downregulated autophagy genes BCLN-1 and ATG7 using small interfering RNA (siRNA) and monitored virus replication over time. These studies revealed that inhibition of host autophagy machinery inhibits Sin Nombre virus replication in cells, suggesting that autophagic clearance of Gn is required for efficient virus replication. Our studies provide mechanistic insights into viral pathogenesis and reveal that SNV exploits the host autophagy machinery to decrease the intrinsic steady-state levels of an important viral component for efficient replication in host cells.
The subsurface record of the Late Palaeozoic glaciation in the Chaco Basin, Bolivia
Authors: Bache F. , Moreau J. , Rubino J. L. , Gorini C. , Van-Vliet Lanoë B. 
Published: May 2012

Abstract

The Late Palaeozoic glaciation was the longest of the Phanerozoic era. It is recorded in numerous Gondwanan basins, with some, such as the Chaco Basin, having a high petroleum potential. In this basin, the quality of the available seismic, well and outcrop data permits us to characterize the Late Palaeozoic glacial record. Palaeovalleys that are
c
. 500 m deep and
c
. 7 km wide have been analysed here. Focusing on the glaciogenic Carboniferous deposits, seismic data with well ties and outcrop analogues provide new sedimentological insights. The palaeovalley infill is imaged as a chaotic seismic facies overlain by an aggrading–prograding prism, interpreted as tillites covered by a fluvio-deltaic system. Tillites form both under the ice and during rapid ice recession, whereas fluvio-deltaic systems can only originate from a stable ice margin and last until the ice sheets withdraw inland. These two depositional modes are repeated several times, generating a progressive burial of the Carboniferous palaeovalleys. This succession of erosions and fills records major glacial stages, including a series of glacial and interglacial phases from the Late Devonian to the Early Permian. Depicting the Late Palaeozoic glacial history of the Chaco Basin seems crucial for the localization of potential good reservoirs.
HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells
Authors: Nishizawa Satoshi , Hirohashi Yoshihiko , Torigoe Toshihiko , Takahashi Akari , Tamura Yasuaki , Mori Takashi , Kanaseki Takayuki , Kamiguchi Kenjiro , Asanuma Hiroko , Morita Rena , Sokolovskaya Alice , Matsuzaki Junichi , Yamada Ren , Fujii Reona , Kampinga Harm H. , Kondo Toru , Hasegawa Tadashi , Hara Isao , Sato Noriyuki 
Published: May 2012

AbstractCancer stem–like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB8 overexpression increased the percentage of side population (SP) cells representing CSCs in RCC cells, enhancing their tumor-initiating ability. Conversely, attenuation of DNAJB8 decreased SP cells and reduced tumor-initiating ability. The utility of DNAJB8 as an immunologic target was established in DNA vaccination experiments. Compared with immunization with the tumor-associated antigen survivin, which was expressed in both CSCs and non-CSCs in RCC, immunization with Dnajb8 expression plasmids yielded stronger antitumor effects. Together, our findings suggest that DNAJB8 plays a role in CSC maintenance and that it offers a candidate for CSC-targeting immunotherapy in RCC. Cancer Res; 72(11); 2844–54. ©2012 AACR.
Combination Therapy with HSP90 Inhibitor 17-DMAG Reconditions the Tumor Microenvironment to Improve Recruitment of Therapeutic T cells
Authors: Rao Aparna , Taylor Jennifer L. , Chi-Sabins Nina , Kawabe Mayumi , Gooding William E. , Storkus Walter J. 
Published: May 2012

Abstract
Ineffective recognition of tumor cells by CD8+ T cells is a limitation of cancer immunotherapy. Therefore, treatment regimens that coordinately promote enhanced antitumor CD8+ T-cell activation, delivery, and target cell recognition should yield greater clinical benefit. Using an MCA205 sarcoma model, we show that in vitro treatment of tumor cells with the HSP90 inhibitor 17-DMAG results in the transient (proteasome-dependent) degradation of the HSP90 client protein EphA2 and the subsequent increased recognition of tumor cells by Type-1 anti-EphA2 CD8+ T cells. In vivo administration of 17-DMAG to tumor-bearing mice led to slowed tumor growth, enhanced/prolonged recognition of tumor cells by anti-EphA2 CD8+ T cells, reduced levels of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment, and activation of tumor-associated vascular endothelial cells in association with elevated levels of Type-1 tumor-infiltrating lymphocytes. When combined with EphA2-specific active vaccination or the adoptive transfer of EphA2-specific CD8+ T cells, 17-DMAG cotreatment yielded a superior tumor therapeutic regimen that was capable of rendering animals free of disease. Taken together, our findings indicate that 17-DMAG functions as an immune adjuvant in the context of vaccines targeting EphA2. Cancer Res; 72(13); 3196–206. ©2012 AACR.
Chemokine (C-X-C Motif) Ligand 12 Is Associated with Gallbladder Carcinoma Progression and Is a Novel Independent Poor Prognostic Factor
Authors: Lee Hyun Jung , Lee Kyungmin , Lee Dong Gwang , Bae Kwang-Hee , Kim Jang-Seong , Liang Zhe Long , Huang Song Mei , Suk Oh Yoon , Kim Ha Yon , Jo Deog Yeon , Min Jeong-Ki , Kim Jin-Man , Lee Hyo Jin 
Published: May 2012

Abstract
Purpose: Although recent studies have suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) is important in the progression of various malignancies, its role in gallbladder carcinoma (GBC) remains unknown. We investigated CXCL12 expression in GBC and its biologic and prognostic role in GBC tumorigenesis.
Experimental Design: We examined CXCL12 expression in tumor specimens from 72 patients with GBC by immunohistochemistry and analyzed the correlation between CXCL12 expression and clinicopathologic factors or survival. The functional significance of CXCL12 expression was investigated by CXCL12 treatment and suppression of CXCR4, a major receptor of CXCL12, as well as by CXCL12 overexpression in in vitro and in vivo studies.
Results: CXCL12 was differentially expressed in GBC tissues. CXCL12 expression was significantly associated with a high histologic grade (P = 0.042) and nodal metastasis (P = 0.015). Multivariate analyses showed that CXCL12 expression (HR, 8.675; P = 0.014) was an independent risk factor for patient survival. CXCL12 significantly increased anchorage-dependent and -independent growth, migration, invasion, adhesiveness, and survival of GBC cells in vitro, and these effects were dependent on CXCR4. Consistent with these results, overexpression of CXCL12 significantly promoted GBC tumorigenicity in a xenograft model.
Conclusions: Our results indicate that GBC cells express both CXCL12 and its receptor CXCR4, and CXCL12 may have a role in GBC progression through an autocrine mechanism. In addition, CXCL12 is a novel independent poor prognostic factor in patients with GBCs. Thus, targeting CXCL12 and CXCR4 may provide a novel therapeutic strategy for GBC treatment. Clin Cancer Res; 18(12); 3270–80. ©2012 AACR.