bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Nuclear Antigen 1 Replication and Segregation Functions in Nasopharyngeal Carcinoma Cell Lines
Authors: Sivachandran Nirojini , Thawe Natalia N. , Frappier Lori 
Published: July 2011

ABSTRACT
Nasopharyngeal carcinomas (NPC) are usually Epstein-Barr virus (EBV) positive, but, with the exception of C666-1 cells, these cells lose the EBV genomes when grown in culture. Maintenance of EBV requires the viral EBV nuclear antigen 1 (EBNA1) protein, which ensures the replication and mitotic segregation of the genomes through interactions with OriP. Here we compare the abilities of C666-1 and NPC cells that have lost EBV genomes to replicate and segregate OriP plasmids. We found that either cell line can replicate and maintain OriP plasmids for extended periods under conditions where low levels of EBNA1 are expressed but that high EBNA1 levels selectively interfered with mitotic segregation.
Estimating person-based injury incidence: accuracy of an algorithm to identify readmissions from hospital discharge data
Authors: Davie Gabrielle , Samaranayaka Ari , Langley John D , Barson Dave 
Published: July 2011

BackgroundEffective use of routinely collected hospital discharge data (HDD) to estimate injury incidence requires a separate identification of new injuries from readmissions for a previous injury. The aim was to determine the accuracy of a computerised algorithm to identify injury readmissions in HDD.MethodsA random sample of 2000 events (‘key events’) were selected from the 2006 injury subset of New Zealand's HDD. Discharge histories from 1989 to 2007 were extracted for individuals and manually reviewed by at least two people to determine the ‘gold standard’ readmission status of each key event. The algorithm relies on four variables: unique national person identifier, dates of injury, admission and discharge. Reviewers were provided with these variables as well as additional discharge information (eg, discharge type and external cause code narrative) recorded in the HDD. Results of the manual review were compared to those obtained from the algorithm.ResultsThe algorithm assigned 1811 (90.6%) as incident admissions compared to 1800 (90.0%) classified by the gold standard. Agreement was 97.9%, and accuracy measures (sensitivity, specificity, negative predictive value and positive predictive value) ranged from 87% to 99%. No statistically significant differences between readmission assignation by the algorithm and the gold standard were observed by age, nature of injury, external cause of injury or body region.ConclusionsAny country with electronic HDD could readily identify readmissions and, thus, accurately estimate injury incidence from HDD, providing that a unique person identifier and the date of injury were included in addition to the obligatory dates of admission and discharge.
Treatment of high risk symptomatic intracranial atherosclerosis with balloon mounted coronary stents and Wingspan stents: single center experience over a 10 year period
Authors: Tarlov Nicholas , Jahan Reza , Saver Jeffrey L , Sayre James W , Ali Latisha K , Kim Doojin , Duckwiler Gary R , Tateshima Satoshi , Viñuela Fernando , Liebeskind David S 
Published: July 2011

BackgroundStenting of symptomatic intracranial atherosclerosis remains under investigation, yet this option to potentially avert subsequent stroke has been offered at select centers under humanitarian device exemption and off-label use for several years.MethodsRetrospective case series of consecutive patients undergoing stenting with Wingspan and balloon mounted coronary stents for symptomatic intracranial atherosclerosis at a single institution. Recurrent symptomatic ischemia in the territory of the stented artery was ascertained. Rates of recurrent ischemic stroke were calculated per patient-year of follow-up and were compared with medically treated patients in the Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial.ResultsDuring the 10 year study period, 41 cases of intracranial stenting were identified. Stenoses were severe (>70%) in 88% of patients. Stenting procedures occurred a median of 14 days from the most recent symptomatic event. 19 Wingspan stents and 22 balloon mounted coronary stents were deployed. Four strokes occurred within 24 h of stenting, seven within 1 month and eight within 3 months. By 3 months after stenting, no further strokes occurred during up to 2 years of follow-up. Patients had 0.194 ischemic strokes per person-year of follow-up, compared with 0.083 ischemic strokes per person-year of follow-up in the aspirin arm of WASID and 0.065 ischemic strokes per person-year of follow-up in the warfarin arm of WASID.ConclusionsStenting of symptomatic intracranial atherosclerosis in a high risk subset of cases with advanced degree of luminal stenosis may be associated with an increased early risk of recurrent ischemic stroke.
Farming, growing up on a farm, and haematological cancer mortality
Authors: Mannetje Andrea 't , Eng Amanda , Pearce Neil 
Published: July 2011

ObjectivesOccupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm.MethodsNew Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex.ResultsGrowing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used.ConclusionsThese results could suggest a role for early life biological exposures in the development of haematological cancers.
Haematological analysis of calves with bovine neonatal pancytopenia
Authors: Witt K. , Weber C. N. , Meyer J. , Buchheit‐Renko S. , Müller K. E. 
Published: July 2011

Blood was obtained from 61 neonatal Holstein calves originating from a farm in Germany with a high incidence of bovine neonatal pancytopenia (BNP). In order to detect alterations that might be related to BNP, selected haematological analytes were determined. Haematological examinations demonstrated alterations in at least two of the three cell lineages in 10 calves (16.39 per cent). Six animals (9.84 per cent) developed a bleeding disorder indicative of BNP at approximately two weeks of age. None of these animals showed alterations in complete blood cell count at sampling in the first week of life. In weeks when calves with BNP were born, an increase in the number of apparently healthy calves demonstrating decreases in blood cell counts was observed.
Combinatorial Treatments That Overcome PDGFRβ-Driven Resistance of Melanoma Cells to V600EB-RAF Inhibition
Authors: Shi Hubing , Kong Xiangju , Ribas Antoni , Lo Roger S. 
Published: July 2011

Abstract
V600EB-RAF mutation is found in 50% to 60% of melanomas, and the novel agents PLX4032/vemurafenib and GSK2118436 that inhibit the V600EB-RAF kinase achieve a remarkable clinical response rate. However, as might be expected, acquired clinical resistance to these agents arises in most melanoma patients. PLX4032/vemurafenib resistance that arises in vivo in tumor matched short-term cultures or in vitro in melanoma cell lines is not caused by acquisition of secondary mutations in V600EB-RAF but rather is caused by upregulating platelet-derived growth factor receptor β (PDGFRβ) or N-RAS which results in resistance or sensitivity to mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK) kinase inhibitors, respectively. In this study, we define a targeted combinatorial strategy to overcome PLX4032/vemurafenib resistance in melanoma cell lines or short-term culture where the resistance is driven by PDGFRβ upregulation, achieving synergistic growth inhibition and cytotoxicity. PDGFRβ-upregulated, PLX4032-resistant (PPRM) cell lines show dual phospho (p)-ERK and p-AKT upregulation, and their growth inhibitory responses to specific small molecule inhibitors correlated with p-ERK, p-AKT, and p-p70S6K levels. Coordinate inhibition of V600EB-RAF inhibition and the RTK–PI3K–AKT–mTORC axis led to functionally significant rebound signaling, illustrating a robust and dynamic network connectivity. Combined B-RAF, phosphoinositide 3-kinase (PI3K), and mTORC1/2 inhibition suppressed both immediate early and delayed compensatory signaling, resulting in a highly synergistic growth inhibitory response but less efficient cytotoxic response. In contrast, the combination of MEK1/2, PI3K, and mTORC1/2 inhibitors consistently triggered apoptosis in a highly efficient manner. Together, our findings offer a rational strategy to guide clinical testing in preidentified subsets of patients who relapse during treatment with V600EB-RAF inhibitors. Cancer Res; 71(15); 5067–74. ©2011 AACR.
Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists
Authors: Marchesi Chiara , Pierfranceschi Matteo , Crowther Mark , Garcia David , Hylek Elaine , Witt Daniel , Clark Nathan , Squizzato Alessandro , Imberti Davide , Ageno Walter , Dentali Francesco 
Published: July 2011

SummaryProthrombin complex concentrates (PCCs) are recommended as the treatment of choice in warfarin-related coagulopathy. However, the risk of thromboembolic complications associated with their use is not well defined. We performed a meta-analysis to estimate the rate of thromboembolic complications in patients receiving vitamin K antagonists (VKAs) treated with PCCs for bleeding or before urgent surgery. Medline and Embase databases were searched. Two reviewers performed study selection and extracted data independently. Studies providing data on incidence of thromboembolic complications in VKA-treated patients were eligible for the study. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Twenty-seven studies (1,032 patients) were included. Seven studies used 3-factor, and 20 4-factor PCCs. Twelve patients had a thromboembolic complication (weighted mean 1.4%; 95% CI 0.8–2.1), of which two were fatal. The incidence of thromboembolic events was 1.8% (95% CI 1.0–3.0) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0–2.4) in patients treated with 3-factor PCCs. Total mortality rate was 10.6% (95% CI 5.9–16.6). In conclusion, our results suggest there is a low but quantifiable risk of thromboembolism in VKA-treated patients receiving PCCs for anticoagulation reversal. These findings should be confirmed in randomised, controlled trials.
Plaque Distribution of Stenotic Middle Cerebral Artery and Its Clinical Relevance
Authors: Xu Wei-Hai , Li Ming-Li , Gao Shan , Ni Jun , Zhou Li-Xin , Yao Ming , Peng Bin , Feng Feng , Jin Zheng-Yu , Cui Li-Ying 
Published: July 2011

Background and Purpose—
Microanatomy studies reveal that most penetrating branches of middle cerebral artery (MCA) arise from the dorsal–superior surface of the trunk. Using high-resolution MRI, we sought to explore the plaque distribution of MCA atherosclerosis and its clinical relevance in relation to the orifices of penetrating arteries.

Methods—
We retrospectively analyzed the imaging and clinical data of 86 patients with atherosclerotic MCA stenosis. On high-resolution MRI, plaques were categorized based on the involvement of the superior, inferior, ventral, or dorsal MCA wall. The relationship of plaque distribution and clinical presentation was analyzed.

Results—

A total of 92 stenotic MCAs (40 symptomatic and 52 asymptomatic) on 828 image slices were studied. Overall, of the 251 slices with identified plaques, plaques were more frequently located at the ventral (44.8%) and inferior (31.7%) wall as compared with the superior (14.3%) and dorsal wall (9.0%;
P
<0.001). Symptomatic MCA stenosis had more superior (
P
=0.016) and less inferior (
P
=0.023) wall plaques than asymptomatic stenosis. Within the group of symptomatic MCA stenosis, vessels with penetrating artery infarctions had more superior (
P
=0.001) but less ventral (
P
=0.038) and inferior (
P
=0.024) plaques than without penetrating artery infarctions.

Conclusions—
MCA plaques tend to locate opposite to the orifices of penetrating arterial branches. Further studies are required to investigate whether MCA plaque distribution is an independent determinant of stroke occurrence and its subtypes.
Effects of Extending the Time Window of Thrombolysis to 4.5 Hours
Authors: Asplund Kjell , Glader Eva-Lotta , Norrving Bo , Eriksson Marie ,   for the Riks-Stroke Collaboration
Published: July 2011

Background and Purpose—
The European Cooperative Acute Stroke Study (ECASS) III trial and Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) data were published in 2008. Riks-Stroke, the Swedish Stroke Register, was used to explore how thrombolysis in the 3- to 4.5-hour window has been spread in different hospitals and patient groups and what effects this has had on treatment within 3 hours.

Methods—
All 76 hospitals in Sweden admitting patients with acute stroke participate in Riks-Stroke. During the study period, January 2003 to June 2010, 92 150 18- to 80-year-old patients were hospitalized for acute ischemic stroke.

Results—

After the publication of the ECASS III results in the third quarter of 2008, thrombolysis in the 3- to 4.5-hour window increased from 0.5% before publication to 2.1% in 2010. Thrombolysis in the 3- to 4.5-hour window spread somewhat faster in men than women (
P
=0.04) but at a similar rate in different age groups. The use of thrombolysis within 3 hours after onset of symptoms increased successively from 0.9% in 2003 to 6.6% in late 2008 and then it stabilized at 6%. The median time from arrival to the hospital to start of treatment remained unchanged at 66 to 69 minutes before and after 2008 (
P
=0.06).

Conclusions—
Since the end of 2008, there has been a rapid nationwide dissemination of thrombolysis in the 3- to 4.5-hour window, whereas rates in the <3-hour window have leveled off. The extended time window has not affected door-to-needle time.
Notch1 controls macrophage recruitment and Notch signaling is activated at sites of endothelial cell anastomosis during retinal angiogenesis in mice
Authors: Outtz Hasina H. , Tattersall Ian W. , Kofler Natalie M. , Steinbach Nicole , Kitajewski Jan 
Published: July 2011

Abstract
Notch is a critical regulator of angiogenesis, vascular differentiation, and vascular integrity. We investigated whether Notch signaling affects macrophage function during retinal angiogenesis in mice. Retinal macrophage recruitment and localization in mice with myeloid-specific loss of Notch1 was altered, as these macrophages failed to localize at the leading edge of the vascular plexus and at vascular branchpoints. Furthermore, these retinas were characterized by elongated endothelial cell sprouts that failed to anastomose with neighboring sprouts. Using Notch reporter mice, we demonstrate that retinal macrophages localize between Dll4-positive tip cells and at vascular branchpoints, and that these macrophages had activated Notch signaling. Taken together, these data demonstrate that Notch signaling in macrophages is important for their localization and interaction with endothelial cells during sprouting angiogenesis.
Erythrocyte peripheral type benzodiazepine receptor/voltage-dependent anion channels are upregulated by Plasmodium falciparum
Authors: Bouyer Guillaume , Cueff Anne , Egée Stéphane , Kmiecik Justyna , Maksimova Yelena , Glogowska Edyta , Gallagher Patrick G. , Thomas Serge L. Y. 
Published: July 2011

Abstract
Plasmodium falciparum relies on anion channels activated in the erythrocyte membrane to ensure the transport of nutrients and waste products necessary for its replication and survival after invasion. The molecular identity of these anion channels, termed “new permeability pathways” is unknown, but their currents correspond to up-regulation of endogenous channels displaying complex gating and kinetics similar to those of ligand-gated channels. This report demonstrates that a peripheral-type benzodiazepine receptor, including the voltage dependent anion channel, is present in the human erythrocyte membrane. This receptor mediates the maxi-anion currents previously described in the erythrocyte membrane. Ligands that block this peripheral-type benzodiazepine receptor reduce membrane transport and conductance in P falciparum-infected erythrocytes. These ligands also inhibit in vitro intraerythrocytic growth of P falciparum. These data support the hypothesis that dormant peripheral-type benzodiazepine receptors become the “new permeability pathways” in infected erythrocytes after up-regulation by P falciparum. These channels are obvious targets for selective inhibition in anti-malarial therapies, as well as potential routes for drug delivery in pharmacologic applications.
Differences in cortical response to acupressure and electroacupuncture stimuli
Authors: Witzel Thomas , Napadow Vitaly , Kettner Norman W , Vangel Mark G , Hämäläinen Matti S , Dhond Rupali P 
Published: July 2011

AbstractBackgroundFMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP). We further assessed how brain response changed during the course of stimulation.ResultsEvoked brain response to EA differed from AP in its temporal dynamics by showing clear contralateral M20/M30 peaks while the latter demonstrated temporal dispersion. Both EA and AP demonstrated significantly decreased response amplitudes following five minutes of stimulation. However, the latency of these decreases were earlier in EA (~30 ms post-stimulus) than AP (> 100 ms). Time-frequency responses demonstrated early onset, event related synchronization (ERS), within the gamma band at ~70-130 ms and the theta band at ~50-200 ms post-stimulus. A prolonged event related desynchronization (ERD) of alpha and beta power occurred at ~100-300 ms post-stimulus. There was decreased beta ERD at ~100-300 ms over the course of EA, but not AP.ConclusionBoth EA and AP demonstrated conditioning of SI response. In conjunction with their subcortical effects on endogenous pain regulation, these therapies show potential for affecting S1 processing and possibly altering maladaptive neuroplasticity. Thus, further investigation in neuropathic populations is needed.
Wide cross-reactivity between Anopheles gambiae and Anopheles funestus SG6 salivary proteins supports exploitation of gSG6 as a marker of human exposure to major malaria vectors in tropical Africa
Authors: Rizzo Cinzia , Ronca Raffaele , Fiorentino Gabriella , Mangano Valentina D , Sirima Sodiomon B , Nèbiè Issa , Petrarca Vincenzo , Modiano David , Arcà Bruno 
Published: July 2011

Abstract

Background
The Anopheles gambiae gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector A. gambiae. However, malaria transmission in tropical Africa is sustained by three main vectors (A. gambiae, Anopheles arabiensis and Anopheles funestus) and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the A. gambiae species complex whereas the A. funestus homologue, fSG6, is more divergent (80% identity with gSG6). The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6.

Methods
The A. funestus SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large A. gambiae prevalence (>75%). Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed.

Results
According to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level.

Conclusions
Comparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission and evaluate vector control measures, especially in conditions of low malaria transmission and/or reduced vector density. The Anopheles stephensi SG6 protein also shares 80% identity with gSG6, suggesting the attractive possibility that the A. gambiae protein may also be useful to assess human exposure to several Asian malaria vectors.