bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoerythropoietin Is 10-Times More Effective Than Regular Erythropoietin in Neuroprotection in a Neonatal Rat Model of Hypoxia and Ischemia
Authors: Chen Han , Spagnoli Frédéric , Burris Michael , Rolland William B. , Fajilan Adriel , Dou Huanyu , Tang Jiping , Zhang John H. 
Published: December 2011

Background and Purpose—
Erythropoietin (EPO) has been demonstrated to possess significant neuroprotective effects in stroke. We determined if the nano-drug form of human recombinant EPO (PLGA-EPO nanoparticles [PLGA-EPO-NP]) can enhance neuroprotection at lower dosages versus human recombinant EPO (r-EPO).

Methods—
Established neonatal rat model of unilateral ischemic stroke was used to compare r-EPO, PLGA-EPO-NP and phosphate-buffered saline, given by daily intraperitoneal injections, followed by infarction volume and Rotarod Performance Test assessment.

Results—
PLGA-EPO-NP significantly reduced infarction volumes 72 hours after injury compared with the same concentrations of r-EPO. Functional deficits were significantly reduced by 300 U/kg PLGA-EPO-NP versus controls, with deficit attenuation apparent at significantly lower dosages of PLGA-EPO-NP versus r-EPO.

Conclusions—
PLGA-EPO-NP is neuroprotective and beneficial against deficits after brain ischemia, at significantly reduced dosages versus r-EPO.
Public Awareness of Stroke in Korea
Authors: Kim Young Seo , Park Sang-Soon , Bae Hee-Joon , Heo Ji Hoe , Kwon Sun U. , Lee Byung-Chul , Lee Seung-Hoon , Oh Chang Wan , Yoon Byung-Woo 
Published: December 2011

Background and Purpose—
To date, no large study has been conducted to investigate baseline stroke awareness within a nationally representative sample of the Korean population.

Methods—
A total of 1000 residents were randomly sampled according to regional demographic characteristics and were interviewed in person by trained interviewers. Structured, open-ended and close-ended questions were asked to assess stroke awareness.

Results—
Among the respondents, 62% reported at least 1 stroke symptom and 56% reported at least 1 risk factor for stroke in open-ended questioning. Multivariate analysis revealed that completion of ≥12 years of education was independently associated with knowledge of symptoms (OR, 1.527; 95% CI, 1.146–2.034) and risk factors (OR, 1.577; 95% CI, 1.175–2.115). Approximately 31% and 33% of respondents, respectively, had some knowledge of thrombolysis and the proper action (call emergency medical services). Compared with subjects aged 20 to 39 years, those aged 40 to 59 years were more knowledgeable about thrombolysis (OR, 1.433; 95% CI, 1.045–1.964) and proper action (OR, 2.291; 95% CI, 1.646–3.188). The major source of information about stroke was television (59%), and the most reliable source was the respondents' physicians (55%). Among respondents 20 to 39 years of age, the Internet (37%) was the second greatest source of information.

Conclusions—
Stroke awareness was suboptimal in Korea, especially among younger citizens and those with less education. To improve their knowledge, physicians should exert greater efforts to educate the public about stroke using mass media and the Internet.
Dehydration in Hospital-Admitted Stroke Patients
Authors: Rowat Anne , Graham Catriona , Dennis Martin 
Published: December 2011

Background and Purpose—
We aimed to determine the frequency of dehydration, risk factors, and associations with outcomes at hospital discharge after stroke.

Methods—
We linked clinical data from stroke patients in 2 prospective hospital registers with routine blood urea and creatinine results. Dehydration was defined by a blood urea-to-creatinine ratio >80.

Results—

Of 2591 patients registered, 1606 (62%) were dehydrated at some point during their admission. Independent risk factors for dehydration included older age, female gender, total anterior circulation syndrome, and prescribed diuretics (all
P
<0.001). Patients with dehydration were significantly more likely be dead or dependent at hospital discharge than those without (χ
2
=170.5; degrees of freedom=2;
P
<0.0001).

Conclusions—
Dehydration is common and associated with poor outcomes. Further work is required to establish if these associations are causal and if preventing or treating dehydration improves outcomes.
Does Helicopter Emergency Medical Service Transfer Offer Benefit to Patients With Stroke?
Authors: Olson Michael D. , Rabinstein Alejandro A. 
Published: December 2011

Background and Purpose—
Helicopter transportation of patients with acute stroke who have received recombinant tissue-type plasminogen activator is commonly considered the best option. We evaluated if transportation by helicopter can reduce complications and improve clinical outcomes in patients with acute stroke.

Methods—
We conducted a review of consecutive patients with acute ischemic stroke transferred to our hospital after intravenous thrombolysis initiated at a referral center.

Results—

A total of 122 patient transportations were analyzed, 94 by air and 28 by ground. Time from activation of the transport system to arrival at our hospital was significantly shorter with air transportation (53 versus 68 minutes,
P
=0.04). Two complications were noted in the air group and no complications were noted in the ground group (
P
=1.0). All other outcome measures were not significantly different between groups.

Conclusions—
Air transfer of patients with acute ischemic stroke treated with thrombolysis does not seem to impart any benefit to patient outcomes when compared with ground transport. Therefore, ground transport should be considered for these patients unless they are being considered for emergency endovascular rescue therapy.
Quantification of the Impact of Nauru Island on ARM Measurements
Authors: Long Charles N. , McFarlane Sally A. 
Published: December 2011

AbstractNauru Island at times generates low clouds that impact low-level cloud statistics and downwelling shortwave radiation measurements made at the Atmospheric Radiation Measurement Program (ARM) site. This study uses five years of Nauru data to quantify the island impact on the site measurements. The results indicate that the solar-heating-produced Nauru island effect occurs about 11% of the time during daylight hours. The island effect increases the 500–1000-m cloud base occurrence by 15%–20% when clouds occur, but because the island effect only occurs 11% of the time the overall increase in daylight low-cloud statistics is 2%, or 1% for 24-h statistics. In a similar way, the island effect produces a reduction of about 17% in the downwelling shortwave (SW) radiation across the daylight hours during the 11% of the time it occurs, an overall 2% daylight (or 1% for 24 h) average reduction. The island effect produces frequent positive downwelling SW cloud effects, in particular during the morning, which tend to somewhat mitigate the overall decrease in downwelling SW radiation that is due to clouds. This produces 17 W m−2 less daylight average SW cloud effect relative to non-island-effect times, in particular for the convectively suppressed regime that typifies island-effect-producing conditions. For long-term overall statistical studies such as model and satellite comparisons, the 2% daylight (or 1% per 24 h) average increase in low-level cloud occurrence and decrease in downwelling SW are not of large concern as long as researchers are aware of them. For shorter-term studies, however, or those that separate data by conditions such as convectively active/suppressed regimes, the Nauru island effect can have significant impacts.
Convective Momentum Transport by Rainbands within a Madden–Julian Oscillation in a Global Nonhydrostatic Model with Explicit Deep Convective Processes. Part I: Methodology and General Results
Authors: Miyakawa Tomoki , Takayabu Yukari N. , Nasuno Tomoe , Miura Hiroaki , Satoh Masaki , Moncrieff Mitchell W. 
Published: December 2011

Abstract
The convective momentum transport (CMT) properties of 13 215 rainbands within a Madden–Julian oscillation (MJO) event simulated by a global nonhydrostatic model are examined. CMT vectors, which represent horizontal accelerations to the mean winds due to momentum flux convergences of deviation winds, are derived for each rainband. The CMT vectors are composited according to their locations relative to the MJO center.
While a similar number of rainbands are detected in the eastern and western halves of the MJO convective envelope, CMT vectors with large zonal components are most plentiful between 0° and 20° to the west of the MJO center. The zonal components of the CMT vectors exhibit a coherent directionality and have a well-organized three-layer structure: positive near the surface, negative in the low to midtroposphere, and positive in the upper troposphere. In the low to midtroposphere, where the longitudinal difference in the mean zonal wind across the MJO is 10 m s−1 on average, the net acceleration due to CMT contributes about −16 m s−1.
Possible roles of the CMT are proposed. First, the CMT delays the eastward progress of the low- to midtroposphere westerly wind, hence delaying the eastward migration of the convectively favorable region and reducing the propagation speed of the entire MJO. Second, the CMT tilts the MJO flow structure westward with height. Furthermore, the CMT counteracts the momentum transport due to large-scale flows that result from the tilted structure.
A Cloud-Resolving Simulation Study on the Merging Processes and Effects of Topography and Environmental Winds
Authors: Fu Danhong , Guo Xueliang 
Published: December 2011

Abstract
The cloud-resolving fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) was used to study the cloud interactions and merging processes in the real case that generated a mesoscale convective system (MCS) on 23 August 2001 in the Beijing region. The merging processes can be grouped into three classes for the studied case: isolated nonprecipitating and precipitating cell merging, cloud cluster merging, and echo core or updraft core merging within cloud systems.
The mechanisms responsible for the multiscale merging processes were investigated. The merging process between nonprecipitating cells and precipitating cells and that between clusters is initiated by forming an upper-level cloud bridge between two adjacent clouds due to upper-level radial outflows in one vigorous cloud. The cloud bridge is further enhanced by a favorable middle- and upper-level pressure gradient force directed from one cloud to its adjacent cloud by accelerating cloud particles being horizontally transported from the cloud to its adjacent cloud and induce the redistribution of condensational heating, which destabilizes the air at and below the cloud bridge and forms a favorable low-level pressure structure for low-level water vapor convergence and merging process. The merging of echo cores within the mesoscale cloud happens because of the interactions between low-level cold outflows associated with the downdrafts formed by these cores.
Further sensitivity studies on the effects of topography and large-scale environmental winds suggest that the favorable pressure gradient force from one cloud to its adjacent cloud and stronger low-level water vapor convergence produced by the topographic lifting of large-scale low-level airflow determine further cloud merging processes over the mountain region.
Size and Strength of Tropical Cyclones as Inferred from QuikSCAT Data
Authors: Chan Kelvin T. F. , Chan Johnny C. L. 
Published: December 2011

A comprehensive statistical climatology of the size and strength of the tropical cyclones (TCs) occurring over the western North Pacific (WNP; including the South China Sea) and the North Atlantic (NA; including the Gulf of Mexico and the Caribbean Sea) between 1999 and 2009 is constructed based on Quick Scatterometer (QuikSCAT) data. The size and strength of a TC are defined, respectively, as the azimuthally averaged radius of 17 m s−1 of ocean-surface winds (R17) and the azimuthally averaged tangential wind within 1°–2.5°-latitude radius from the TC center (outer-core wind strength, OCS). The mean TC size and strength are found to be 2.13° latitude and 19.6 m s−1, respectively, in the WNP, and 1.83° latitude and 18.7 m s−1 in the NA. While the correlation between size and strength is strong (r ≈ 0.9), that between intensity and either size or strength is weak. Seasonally, midsummer (July) and late-season (October) TCs are significantly larger in the WNP, while the mean size is largest in September in the NA. The percentage frequency of TCs having large size or high strength is also found to vary spatially and seasonally. In addition, the interannual variation of TC size and strength in the WNP correlate significantly with the TC lifetimes and the effect of El Niño over the WNP. TC lifetime and seasonal subtropical ridge activities are shown to be potential factors that affect TC size and strength.
Receptor mechanisms of antipsychotic drug action in bipolar disorder – focus on asenapine
Authors: Reynolds Gavin P 
Published: December 2011

The atypical antipsychotic drugs are considered a first-line treatment for mania in bipolar disorder with many having a proven superiority to the classical mood stabilisers. This review addresses the pharmacological mechanisms underlying this therapeutic efficacy, as well as those mechanisms considered responsible for the adverse effects of antipsychotic drugs, with a particular focus on the recently introduced asenapine. The high efficacy in bipolar mania of haloperidol, a relatively selective dopamine D2-like receptor antagonist, indicates that the one common receptor mechanism underlying antipsychotic effects on mania is antagonism at the D2 receptor. Serotonin receptors are implicated in antidepressant response, and relief of depressed mood in mixed states is likely to involve drug effects at one, or more likely several interacting, serotonin receptors. Asenapine shows a unique breadth of action at these sites, with potential effects at clinical doses at 5HT1A, 1B, 2A, 2C, 6 and 7 receptors. Antagonism at alpha2 adrenoceptors may also be involved. Adverse effects include those classically associated with dopamine D2 receptor blockade, the extrapyramidal side effects (EPS), and which are relatively diminished in the atypical (in comparison with the conventional) antipsychotics. A variety of protective mechanisms against EPS associated with different drugs include low D2 affinity, D2 partial agonism, high 5-HT2A and 2C antagonism. Similar effects at the D2 and 5-HT2C receptors may underlie the low propensity for hyperprolactinaemia of the atypicals, although the strong prolactin-elevating effect of risperidone reflects its relatively high blood/brain concentration ratio, a consequence of it being a substrate for the p-glycoprotein pump. Weight gain is a further concern of antipsychotic treatment of bipolar disorder which is particularly severe with olanzapine. Histamine H1, alpha1 adrenergic and particularly 5-HT2C receptors are implicated in this effect, although the lower propensity for weight gain shown by asenapine which, like olanzapine, binds to these receptors, indicates that other protective receptor mechanisms, or subtle differences in the 5-HT2C receptor-mediated effects, may be important. Of other peripheral and central effects, the pharmacological basis of sedation (H1 receptors) and postural hypotension (alpha1 adrenoceptors) are rather better understood. The relative benefits of atypical antipsychotics like asenapine can be understood from their receptor pharmacology, and this understanding is key to the future development of improved treatment for bipolar disorder.
Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine
Authors: Lavelle Donald , Vaitkus Kestis , Ling Yonghua , Ruiz Maria A. , Mahfouz Reda , Ng Kwok Peng , Negrotto Soledad , Smith Nicola , Terse Pramod , Engelke Kory J. , Covey Joseph , Chan Kenneth K. , DeSimone Joseph , Saunthararajah Yogen 
Published: December 2011

AbstractThe deoxycytidine analog decitabine (DAC) can deplete DNA methyl-transferase 1 (DNMT1) and thereby modify cellular epigenetics, gene expression, and differentiation. However, a barrier to efficacious and accessible DNMT1-targeted therapy is cytidine deaminase, an enzyme highly expressed in the intestine and liver that rapidly metabolizes DAC into inactive uridine counterparts, severely limiting exposure time and oral bioavailability. In the present study, the effects of tetrahydrouridine (THU), a competitive inhibitor of cytidine deaminase, on the pharmacokinetics and pharmacodynamics of oral DAC were evaluated in mice and nonhuman primates. Oral administration of THU before oral DAC extended DAC absorption time and widened the concentration-time profile, increasing the exposure time for S-phase–specific depletion of DNMT1 without the high peak DAC levels that can cause DNA damage and cytotoxicity. THU also decreased interindividual variability in pharmacokinetics seen with DAC alone. One potential clinical application of DNMT1-targeted therapy is to increase fetal hemoglobin and treat hemoglobinopathy. Oral THU-DAC at a dose that would produce peak DAC concentrations of less than 0.2μM administered 2×/wk for 8 weeks to nonhuman primates was not myelotoxic, hypomethylated DNA in the γ-globin gene promoter, and produced large cumulative increases in fetal hemoglobin. Combining oral THU with oral DAC changes DAC pharmacology in a manner that may facilitate accessible noncytotoxic DNMT1-targeted therapy.
Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)
Authors: Kantarjian Hagop M. , Shah Neil P. , Cortes Jorge E. , Baccarani Michele , Agarwal Mohan B. , Undurraga María Soledad , Wang Jianxiang , Kassack Ipiña Juan Julio , Kim Dong-Wook , Ogura Michinori , Pavlovsky Carolina , Junghanss Christian , Milone Jorge H. , Nicolini Franck E. , Robak Tadeusz , Van Droogenbroeck Jan , Vellenga Edo , Bradley-Garelik M. Brigid , Zhu Chao , Hochhaus Andreas 
Published: December 2011

Abstract
Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg (n = 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to ≤ 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247.
Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p
Authors: Neben Kai , Lokhorst Henk M. , Jauch Anna , Bertsch Uta , Hielscher Thomas , van der Holt Bronno , Salwender Hans , Blau Igor W. , Weisel Katja , Pfreundschuh Michael , Scheid Christof , Dührsen Ulrich , Lindemann Walter , Schmidt-Wolf Ingo G. H. , Peter Norma , Teschendorf Christian , Martin Hans , Haenel Mathias , Derigs Hans G. , Raab Marc S. , Ho Anthony D. , van de Velde Helgi , Hose Dirk , Sonneveld Pieter , Goldschmidt Hartmut 
Published: December 2011

Abstract
In patients with multiple myeloma (MM), risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches. In the present study, we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Because of the 2-arm design of the study, we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation (arm B) compared with standard treatment without bortezomib (arm A). For allanalyzed chromosomal aberrations, progression-free survival (PFS) and overall survival (OS) were at least equal or superior in the bortezomib arm compared with the standard arm. Strikingly, patients with del(17p13) benefited the most from the bortezomib-containing treatment: the median PFS in arm A was 12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A was 17% and for arm B it was 69% (P = .028). After multivariate analysis, del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in arm A, whereas no statistically significant effect on PFS (P = .28) or OS (P = .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13). This trial is registered at the International Standard Randomised Controlled Trial Number Register as ISRCTN64455289.
EGFL7: a unique angiogenic signaling factor in vascular development and disease
Authors: Nichol Donna , Stuhlmann Heidi 
Published: December 2011

AbstractEGFL7 is a secreted angiogenic factor that is highly conserved in vertebrates. Most secreted angiogenic signaling molecules, including VEGF and fibroblast growth factor-2, are mainly expressed by nonendothelial cell types such as fibroblasts. In contrast, EGFL7 is unique because it is almost exclusively expressed by and acts on endothelial cells. Egfl7 expression is highest when the endothelium is in an active, proliferating state. This factor acts as a chemoattractant for endothelial cells and binds to components of the extracellular matrix. In vivo, Egfl7 is important for regulating tubulogenesis in zebrafish and for controlling vascular patterning and integrity in mice. Its function in blood vessel development is mediated, at least in part, through modulation of Notch signaling. In this review, we summarize the findings that support a role for Egfl7 in developmental and postnatal angiogenesis and describe the EGFL7-signaling pathways that underlie these processes. In addition, we discuss a potential role for EGFL7 in vascular repair and its possible use as a therapeutic target for treatment of hypoxia-induced injury. Finally, we consider EGFL7 action during tumorigenesis and its potential as an antiangiogenic agent.