bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C Virus Genotypes in Clinical Specimens Tested at a National Reference Testing Laboratory in the United States
Authors: Germer Jeffrey J. , Mandrekar Jayawant N. , Bendel Jordan L. , Mitchell P. Shawn , Yao Joseph D. C. 
Published: May 2011

ABSTRACT

Hepatitis C virus (HCV) genotype (GT) distribution and frequency were studied among 22,407 unique specimens tested at a national reference testing laboratory. Subjects with HCV GT 3 were younger (
P
< 0.0001) than those with GT 1, 2, or 4, and the regional frequencies of HCV GT 2 and 3 ranged from 19.9% to 29.2%.
Comparison of Direct Colony Method versus Extraction Method for Identification of Gram-Positive Cocci by Use of Bruker Biotyper Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Alatoom Adnan A. , Cunningham Scott A. , Ihde Sherry M. , Mandrekar Jayawant , Patel Robin 
Published: May 2011

ABSTRACT

We evaluated Bruker Biotyper (version 2.0) matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) for the identification of 305 clinical isolates of staphylococci, streptococci, and related genera by comparing direct colony testing with preparatory extraction. Isolates were previously identified by use of phenotypic testing and/or 16S rRNA gene sequencing. Manufacturer-specified score cutoffs for genus- and species-level identification were used. After excluding 7 isolates not present in the Biotyper library, the Biotyper correctly identified 284 (95%) and 207 (69%) isolates to the genus and species levels, respectively, using extraction. By using direct colony testing, the Biotyper identified 168 (56%) and 60 (20%) isolates to the genus and species levels, respectively. Overall, more isolates were identified to the genus and species levels with preparatory extraction than with direct colony testing (
P
< 0.0001). The analysis was repeated after dividing the isolates into two subgroups, staphylococci, streptococci, and enterococci (
n
= 217) and “related genera” (
n
= 81). For the former subgroup, the extraction method resulted in the identification of 213 (98%) and 171 (79%) isolates to the genus and species levels, respectively, whereas the direct colony method identified 136 (63%) and 56 (26%) isolates to the genus and species levels, respectively. In contrast, for the subgroup of related genera, the extraction method identified 71 (88%) and 36 (44%) isolates to the genus and species levels, respectively, while the direct colony method identified 32 (40%) and 4 (5%) isolates to the genus and species levels, respectively. For both subgroups, preparatory extraction was superior to direct colony testing for the identification of isolates to the genus and species levels (
P
< 0.0001). Preparatory extraction is needed for the identification of a substantial proportion of Gram-positive cocci using the Biotyper method according to manufacturer-specified score cutoffs.
Unnatural Amino Acid Incorporation onto Adenoviral (Ad) Coat Proteins Facilitates Chemoselective Modification and Retargeting of Ad Type 5 Vectors
Authors: Banerjee Partha Sarathi , Ostapchuk Philomena , Hearing Patrick , Carrico Isaac Sheridan 
Published: May 2011

ABSTRACT
Surface modification of adenovirus vectors can improve tissue-selective targeting, attenuate immunogenicity, and enable imaging of particle biodistribution, thus significantly improving therapeutic potential. Currently, surface engineering is constrained by a combination of factors, including impact on viral fitness, limited access to functionality, or incomplete control over the site of modification. Here, we report a two-step labeling process involving an initial metabolic placement of a uniquely reactive unnatural amino acid, azidohomoalanine (Aha), followed by highly specific chemical modification. As genetic modification of adenovirus is unnecessary, vector production is exceedingly straightforward. Aha incorporation demonstrated no discernible impact on either virus production or infectivity of the resultant particles. “Click” chemical modification of surface-exposed azides was highly selective, allowing for the attachment of a wide range of functionality. Decoration of human adenovirus type 5 (hAd5) with folate, a known cancer-targeting moiety, provided an ∼20-fold increase in infection of murine breast cancer cells (4T1) in a folate receptor-dependent manner. This study demonstrates that incorporation of unnatural amino acids can provide a flexible, straightforward route for the selective chemical modification of adenoviral vectors.
Sterol Regulatory Element-Binding Protein 2 Couples HIV-1 Transcription to Cholesterol Homeostasis and T Cell Activation
Authors: Taylor Harry E. , Linde Michael E. , Khatua Atanu K. , Popik Waldemar , Hildreth James E. K. 
Published: May 2011

ABSTRACTCholesterol plays an essential role in the life cycle of several enveloped viruses. Many of these viruses manipulate host cholesterol metabolism to facilitate their replication. HIV-1 infection of CD4+T cells activates the sterol regulatory element-binding protein 2 (SREBP2) transcriptional program, which includes genes involved in cholesterol homeostasis. However, the role of SREBP2-dependent transcription in HIV-1 biology has not been fully examined. Here, we identify TFII-I, a gene critical for HIV-1 transcription in activated T cells, as a novel SREBP2 target gene. We found TFII-I expression increased after HIV-1 infection or activation of human primary CD4+T cells. We show that inhibition of SREBP2 activity reduced TFII-I induction in response to these stimuli. More importantly, small interfering RNA (siRNA)-mediated gene silencing of either SREBP2 or TFII-I significantly reduced HIV-1 production in CD4+T cells. We also found that TFII-I potentiates Tat-dependent viral gene expression, consistent with a role at the level of HIV-1 transcription. Collectively, our results demonstrate for the first time that HIV-1 transcription in T cells is linked to cholesterol homeostasis through control of TFII-I expression by SREBP2.
Genus-Specific Substitution Rate Variability among Picornaviruses
Authors: Hicks Allison L. , Duffy Siobain 
Published: May 2011

ABSTRACT

Picornaviruses have some of the highest nucleotide substitution rates among viruses, but there have been no comparisons of evolutionary rates within this broad family. We combined our own Bayesian coalescent analyses of VP1 regions from four picornaviruses with 22 published VP1 rates to produce the first within-family meta-analysis of viral evolutionary rates. Similarly, we compared our rate estimates for the RNA polymerase 3D
pol
gene from five viruses to four published 3D
pol
rates. Both a structural and a nonstructural gene show that enteroviruses are evolving, on average, a half order of magnitude faster than members of other genera within the
Picornaviridae
family.
Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals
Authors: Chopera D. R. , Mlotshwa M. , Woodman Z. , Mlisana K. , de Assis Rosa D. , Martin D. P. , Abdool Karim S. , Gray C. M. , Williamson C. ,   the CAPRISA 002 Study Team
Published: May 2011

ABSTRACT

Molecular epidemiology studies have identified HLA-B*58:01 as a protective HIV allele. However, not all B*58:01-expressing persons exhibit slow HIV disease progression. We followed six HLA-B*58:01-positive, HIV subtype C-infected individuals for up to 31 months from the onset of infection and observed substantial variability in their clinical progression despite comparable total breadths of T cell responses. We therefore investigated additional immunological and virological factors that could explain their different disease trajectories. Cytotoxic T-lymphocyte (CTL) responses during acute infection predominantly targeted the TW10 and KF9 epitopes in p24
Gag
and Nef, respectively. Failure to target the TW10 epitope in one B*58:01-positive individual was associated with low CD4
+
counts and rapid disease progression. Among those targeting TW10, escape mutations arose within 2 to 15 weeks of infection. Rapid escape was associated with preexisting compensatory mutations in the transmitted viruses, which were present at a high frequency (69%) in the study population. At 1 year postinfection, B*58:01-positive individuals who targeted and developed escape mutations in the TW10 epitope (
n
= 5) retained significantly higher CD4
+
counts (
P
= 0.04), but not lower viral loads, than non-B*58:01-positive individuals (
n
= 17). The high population-level frequency of these compensatory mutations may be limiting the protective effect of the B*58:01 allele.
Attitudes towards the extension of smoking restrictions to selected outdoor areas in Italy
Authors: Gallus Silvano , Rosato Valentina , Zuccaro Piergiorgio , Pacifici Roberta , Colombo Paolo , Manzari Marco , La Vecchia Carlo 
Published: May 2011

ObjectivesTo estimate the attitudes of Italians on the extension of the smoking ban to selected public outdoor areas.MethodsThe authors considered data from two Italian surveys on smoking conducted in 2009 and 2010 on a total sample of 6233 individuals, representative of the Italian population aged 15 years or over.Results64.6% of Italians supported smoke-free policies in public parks, 68.5% in sports stadiums, 62.1% in beaches, 85.9% in school courtyards and 79.9% in outdoor areas surrounding hospitals. Among current smokers, the corresponding estimates were 32.9% for parks, 38.2% for stadiums, 31.2% for beaches, 67.6% for schools and 55.3% for hospitals.ConclusionsExtension of the smoking ban to selected outdoor areas is supported by the large majority of the Italian population. The overwhelming majority of support for smoke-free school grounds and outdoor areas surrounding hospitals indicates that legislative action is required.
Changed cycling of P, N, Si, and DOC in Danish Lake Nordborg after aluminum treatment
Authors: Egemose Sara , de Vicente Inmaculada , Reitzel Kasper , Flindt Mogens R. , Andersen Frede Ø. , Lauridsen Torben L. , Søndergaard Martin , Jeppesen Erik , Jensen Henning S. 
Published: May 2011

Loading, retention, and in-lake cycling of phosphorus (P), nitrogen, silica, and dissolved organic carbon (DOC) were studied 1 year before and 3 years after P-inactivation by aluminum (Al) hydroxide in Danish Lake Nordborg in 2006. Simultaneously, external P loading was reduced by 40% via establishment of precipitation ponds in two inlets. After Al treatment, the internal P loading (sediment P release) during summer declined 90%–94%, owing to adsorption to aluminum hydroxide. Also, silicate regeneration from the sediment was reduced by 69%–76%, and sediment oxygen uptake as well as ammonium release declined markedly. Consequently, lake water total P, dissolved inorganic P, silicate, and DOC decreased by 73%, 97%, 87%, and 46%, respectively. The Secchi depth increased in the summer period during the first post-treatment year, but declined afterwards to pre-treatment levels, even though the mean lake-water total P concentration during summer was reduced from ∼240 µg·L–1before treatment to 26–65 µg·L–1in the first three post-treatment years. We conclude that a further reduction in external P loading is needed to obtain the full effect of the Al treatment in Lake Nordborg.
SPARC Stimulates Neuronal Differentiation of Medulloblastoma Cells via the Notch1/STAT3 Pathway
Authors: Bhoopathi Praveen , Chetty Chandramu , Dontula Ranadheer , Gujrati Meena , Dinh Dzung H. , Rao Jasti S. , Lakka Sajani S. 
Published: May 2011

Abstract
Secreted protein acidic and rich in cysteine (SPARC) participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell–matrix interactions. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we show that adenoviral-mediated overexpression of SPARC cDNA (Ad-DsRed-SP) elevated the expression of the neuronal markers NeuN, nestin, neurofilament, and MAP-2 in medulloblastoma cells and induced neuron-like differentiation. SPARC overexpression decreased STAT3 phosphorylation; constitutive expression of STAT3 reversed SPARC-mediated expression of neuronal markers. We also show that Notch signaling is suppressed in the presence of SPARC, as well as the Notch effector basic helix-loop-helix (bHLH) transcription factor hairy and enhancer of split 1 (HES1). Notch signaling was found to be responsible for the decreased STAT3 phosphorylation in response to SPARC expression. Furthermore, expression of SPARC decreased the production of interleukin 6 (IL-6) and supplemented IL-6–abrogated, SPARC-mediated suppression of Notch signaling and expression of neuronal markers. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed increased immunoreactivity for the neuronal markers and a decrease in Notch1 expression and phosphorylation of STAT3. Taken together, our results suggest that SPARC induces expression of neuronal markers in medulloblastoma cells through its inhibitory effect on IL-6–regulated suppression of Notch pathway–mediated STAT3 signaling, thus giving further support to the potential use of SPARC as a therapeutic candidate for medulloblastoma treatment. Findings show that SPARC-induced neuronal differentiation can sensitize medulloblastoma cells for therapy. Cancer Res; 71(14); 4908–19. ©2011 AACR.
Determination of age-specific and sex-specific familial risks for the different manifestations of venous thromboembolism: A nationwide family study in Sweden
Authors: Li Xinjun , Sundquist Jan , Sundquist Kristina , Zöller Bengt 
Published: May 2011

SummaryThis nationwide study aimed to determine whether differences exist in age-specific and sex-specific familial risks for pulmonary embolism (PE), venous thrombosis of the lower limbs (VT) and other forms of venous thromboembolism (OVTE) among offspring, siblings and spouses of affected individuals. The Swedish Multi-Generation Register was linked to the Hospital Discharge Register data for the period 1987–2007. Standardised incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalised for venous thromboembolism (VTE), as determined by the International Classification of Diseases (ICD), and those whose relatives were unaffected by VTE. The total number of hospitalised VTE patients was 45,362. All VTE patients were categorised as PE, VT or OVTE according to ICD at first hospitalisation. For example, the parental SIRs for PE, VT and OVTE in offspring at age 10–19 years were 2.89 (95% CI 1.48–5.06), 4.99 (95% CI 3.22–6.10) and 3.89 (95% CI 2.51–5.75), respectively. The low spousal risks of PE (1.08; 95% CI 1.02–1.13), VT (1.06; 95% CI 1.011.12) and OVTE (1.07; 95% CI 1.00–1.15) suggest the familial risks to be largely genetic. In both men and women, familial relative risks were increased for all the different manifestations of VTE with the exception of those older than 70 years. Familial history is a risk indicator in both sexes, and is potentially useful for clinical risk assessment for the different manifestations of VTE.
Use of statins and recurrence of atrial fibrillation after catheter ablation or electrical cardioversion
Authors: Dentali Francesco , Gianni Monica , Squizzato Alessandro , Ageno Walter , Castiglioni Luana , Maroni Lorenzo , Hylek Elaine M. , Grandi Anna Maria , Cazzani Eugenio , Venco Achille , Guasti Luigina 
Published: May 2011

SummaryStatins have important pleiotropic effects and have been shown to reduce vascular inflammation. Some evidence suggests that statins may have a role in the primary prevention of atrial fibrillation (AF), whereas little is know on the role of statins in patients with existing AF. We performed a meta-analysis of the literature to assess the effect of statins on the recurrence of AF after electrical cardioversion or ablation. MEDLINE and EMBASE databases were searched up to January 2010. Relative risks (RR) and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Sixteen studies were included in our systematic review. Statins did not reduce the risk of AF recurrence after ablation (four studies including 750 patients; RR, 1.04; 95% CI, 0.85–1.28, p=0.71; I2 = 34%). Conversely, the use of statins was associated with a significantly reduced risk of AF recurrence after electrical cardioversion (12 studies including 1790 patients; RR, 0.78; 95% CI, 0.67–0.90, p=0.0003; I2 = 34%). This reduction was not statistically significant when the analysis was restricted to randomised controlled trials (RCTs) only (five studies, 458 patients, RR, 0.76; 95% CI, 0.48–1.20). In conclusion, statins may lower the risk of AF recurrence after electrical cardioversion, but not ablation. However, this finding should be considered with caution, and larger RCTs are warranted to confirm our preliminary results.
Ischaemic stroke and bleeding rates in ‘real-world’ atrial fibrillation patients
Authors: Ogilvie Isla M. , Cowell Warren , Lip Gregory Y. H. , Welner Sharon A. 
Published: May 2011

SummaryStroke prevention guidelines recommend oral anticoagulants (OAC) for atrial fibrillation (AF) patients at moderate/high risk of stroke, and antiplatelet or no therapy for those at low/moderate risk. Outcomes for AF patients receiving antiplatelet/no therapy in ‘real-life’ clinical practice were explored. This study compared clinical event rates (stroke/bleeding) for AF patients treated with OAC therapy, antiplatelets or no therapy in usual clinical practice to event rates in OAC-treated AF patients from optimally-monitored ‘real-life’ settings (anticoagulation clinics). We searched biomedical literature (1994–2010) using PubMed to identify ‘real-world’ studies of clinical event rates for AF patients receiving OAC therapy, antiplatelets, or no therapy; event rates were extracted for each treatment and setting. We identified 136 studies of thromboembolic events and 86 of bleeding events. Ischaemic stroke rates (30 studies) were higher for AF patients receiving no therapy (median: 4.45/100 person-years; range: 0.25–5.9) or antiplatelet-therapy (median: 4.45/100 person-years; range: 2.0–10) compared to OACtreated patients monitored in anticoagulation clinics (median: 1.72/100 person-years; range: 0.97–2.00), or from a non-specialized setting (median 1.66/100 person-years; range: 0–4.9). Major bleeding rates (32 studies) for patients receiving antiplatelet/no therapy were similar to OAC-treated patients from both clinical settings. As in randomised clinical trials, AF patients in ‘real-world’ clinical practice receiving antiplatelet/no therapy have higher rates of ischaemic stroke than OAC-treated patients. Antiplatelet/no therapy was associated with similar bleeding rates to OAC therapy. Increasing utilisation of anticoagulants in clinical practice could improve patient outcomes.
Atorvastatin reduces thrombin generation and expression of tissue factor, P-selectin and GPIIIa on platelet-derived microparticles in patients with peripheral arterial occlusive disease
Authors: Mobarrez Fariborz , He Shu , Bröijersen Anders , Wiklund Björn , Antovic Aleksandra , Antovic Jovan , Egberg Nils , Jörneskog Gun , Wallén Håkan 
Published: May 2011

SummaryWe investigated the effects of statin treatment on platelet-derived microparticles (PMPs) and thrombin generation in atherothrombotic disease. Nineteen patients with peripheral arterial occlusive disease were randomised to eight weeks of treatment with atorvastatin or placebo in a cross-over fashion. Expression of GPIIIa (CD61), P-selectin (CD62P), tissue factor (TF, CD142) and phosphatidylserine (PS; annexin-V or lactadherin binding) was assessed on PMPs. Thrombin generation in vivo was assessed by measurement of prothrombin fragment 1+2 in plasma (F1+2) and ex vivo by using the calibrated automated thrombogram (CAT). During atorvastatin treatment, expression of TF, P-selectin and GPIIIa was significantly reduced vs. placebo (p<0.001 for all). No effect on annexin-V or lactadherin binding was seen. Thrombin generation was significantly reduced during atorvastatin as assessed by both the CAT assay (p<0.001) and by measurements of F1+2 (p<0.01). Subsequent in vitro experiments showed that when TF on microparticles (MPs) was blocked by antibodies, the initiation of thrombin generation was slightly but significantly delayed. Blocking PS on MPs using annexin-V or lactadherin resulted in almost complete inhibition of thrombin generation. In conclusion, atorvastatin reduces thrombin generation and expression of TF, GPIIIa and P-selectin on PMPs in patients with peripheral vascular disease. Microparticle-bound TF slightly enhances initiation of thrombin generation whereas negatively charged surfaces provided by MPs or lipoproteins could reinforce thrombin generation. Statins may inhibit initiation of thrombin generation partly through a microparticle dependent mechanism but the main effect is probably through reduction of lipoprotein levels.
Prognostic significance of mean platelet volume on admission in an unselected cohort of patients with non ST-segment elevation acute coronary syndrome
Authors: Saia Francesco , Rapezzi Claudio , Marrozzini Cinzia , Reggiani Maria Letizia Bacchi , Palmerini Tullio , Ortolani Paolo , Melandri Giovanni , Rosmini Stefania , Cinti Laura , Alessi Laura , Vagnarelli Fabio , Villani Caterina , Branzi Angelo , Marzocchi Antonio , Taglieri Nevio 
Published: May 2011

SummaryMean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5–8.0; Q3=8.1–8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06–1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06–1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06–1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.