bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of an analytic linear Boltzmann transport equation solver for high‐density inhomogeneities
Authors: Lloyd S. A. M. , Ansbacher W. 
Published: December 2012

Purpose:Acuros external beam (Acuros XB) is a novel dose calculation algorithm implemented through theECLIPSE treatment planning system. The algorithm finds a deterministic solution to the linear Boltzmann transport equation, the same equation commonly solved stochastically by Monte Carlo methods. This work is an evaluation of Acuros XB, by comparison with Monte Carlo, for dose calculation applications involving high‐density materials. Existing non‐Monte Carlo clinical dose calculation algorithms, such as the analytic anisotropic algorithm (AAA), do not accurately model dose perturbations due to increased electron scatter within high‐density volumes.Methods:Acuros XB, AAA, and EGSnrc based Monte Carlo are used to calculate dose distributions from 18 MV and 6 MV photon beams delivered to a cubic water phantom containing a rectangular high density (4.0–8.0 g/cm3) volume at its center. The algorithms are also used to recalculate a clinical prostate treatment plan involving a unilateral hip prosthesis, originally evaluated using AAA. These results are compared graphically and numerically using gamma‐index analysis. Radio‐chromic film measurements are presented to augment Monte Carlo and Acuros XB dose perturbation data.Results:Using a 2% and 1 mm gamma‐analysis, between 91.3% and 96.8% of Acuros XB dose voxels containing greater than 50% the normalized dose were in agreement with Monte Carlo data for virtual phantoms involving 18 MV and 6 MV photons, stainless steel and titanium alloy implants and for on‐axis and oblique field delivery. A similar gamma‐analysis of AAA against Monte Carlo data showed between 80.8% and 87.3% agreement. Comparing Acuros XB and AAA evaluations of a clinical prostate patient plan involving a unilateral hip prosthesis, Acuros XB showed good overall agreement with Monte Carlo while AAA underestimated dose on the upstream medial surface of the prosthesis due to electron scatter from the high‐density material. Film measurements support the dose perturbations demonstrated by Monte Carlo and Acuros XB data.Conclusions:Acuros XB is shown to perform as well as Monte Carlo methods and better than existing clinical algorithms for dose calculations involving high‐density volumes.
First Report of Human Acute Acalculous Cholecystitis Caused by the Fish Pathogen Lactococcus garvieae
Authors: Kim Ji Hyung , Go Jin , Cho Chong Rae , Kim Jae Il , Lee Myung Soo , Park Se Chang 
Published: December 2012

ABSTRACT

We report herein the first case of acute acalculous cholecystitis caused by
Lactococcus garvieae
, which is known as a fish pathogen. A 69-year-old fisherman underwent laparoscopic cholecystectomy due to severe inflammation in the gallbladder. The isolate obtained from the gallbladder was identified as
L. garvieae
by 16S rRNA and manganese-dependent superoxide dismutase (
sodA
) gene sequence analysis.
Spread of Multidrug-Resistant Pseudomonas aeruginosa Clones in a University Hospital
Authors: Koutsogiannou Maria , Drougka Eleanna , Liakopoulos Apostolos , Jelastopulu Eleni , Petinaki Efthimia , Anastassiou Evangelos D. , Spiliopoulou Iris , Christofidou Myrto 
Published: December 2012

ABSTRACT

An outbreak of multidrug-resistant
Pseudomonas aeruginosa
(MDRPA) infections in a university hospital is described. Phenotypic and genotypic analysis of 240 isolates revealed that 152 patients, mainly in the intensive care unit (ICU), were colonized or infected with MDRPA, the majority with O11. All metallo-β-lactamase (MBL)-positive isolates carried the
bla
VIM-2
or
bla
VIM-1
gene. One or more type III secretion system toxin genes were detected in most isolates. Five dominant pulsed-field gel electrophoresis (PFGE) types were characterized, associated with ST235, ST111, ST253, ST309, and ST639.
Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts
Authors: Puhan Milo A , Hansel Nadia N , Sobradillo Patricia , Enright Paul , Lange Peter , Hickson DeMarc , Menezes Ana M , Riet Gerben ter , Held Ulrike , Domingo-Salvany Antonia , Mosenifar Zab , Antó Josep M , Moons Karel G M , Kessels Alphons , Garcia-Aymerich Judith ,   for the International COPD Cohorts Collaboration Working Group
Published: December 2012

BackgroundLittle evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists.ObjectiveTo conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV1to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible.DesignIndividual subject data analysis of 10 European and American cohorts (n=13 914).SettingPopulation-based, primary, secondary and tertiary care.PatientsCOPD GOLD stages I–IV.MeasurementsWe validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses.Results1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV166% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p<0.001 for difference between predicted and observed risk). The updated ADO index (scores from 0 to 14) preserved excellent discrimination (area under curve 0.81, 95% CI 0.80 to 0.82) but showed much improved calibration with predicted 3-year risks from 0.7% (95% CI 0.6% to 0.9%, score of 0) to 64.5% (61.2% to 67.7%, score of 14). The ADO index showed higher net benefit in subjects at low-to-moderate risk of 3-year mortality than FEV1alone.InterpretationThe updated 15-point ADO index accurately predicts 3-year mortality across the COPD severity spectrum and can be used to inform patients about their prognosis, clinical trial study design or benefit harm assessment of medical interventions.
Snakebite enquiries to the UK National Poisons Information Service: 2004–2010
Authors: Coulson James Michael , Cooper Gillian , Krishna Channarayapatna , Thompson John Paul 
Published: December 2012

ObjectiveTo describe trends regarding snakebite enquiries to the UK National Poisons Information Service (NPIS) from 2004 to 2010.MethodsThe NPIS telephone enquiry database, the UK Poisons Information Database, was interrogated for enquiries to the four NPIS units from 2004 to 2010. Search terms used were ‘snake’ and ‘snakebite’. Information from the national dataset was available from Cardiff and Edinburgh units from 2004 onwards, Birmingham from June 2005 and Newcastle from September 2006.ResultsFive hundred and ten cases were identified, of which 69% were male and 31% female. Average age of cases was 32 years (±1 95% CI). The snake was identified as follows: British Adder in 52% of cases, an exotic species in 26%, unknown in 18% and another UK snake in 4%. 82% of cases occurred between the months of April and September. Cases peaked during August (19%). Forty-two per cent of enquiries involved features of envenoming. Eighty-five cases were assessed as requiring antivenom. Eighty-four cases received treatment with antivenom. No adverse reactions to the antivenom were reported and resolution of clinical features was reported in all treated cases. Advice to use an antidote was followed in 98.8% of cases.ConclusionsSnakebites account for one to two NPIS cases per week. Adder bites account for over half of cases. A quarter of cases were due to non-UK snakes kept in captivity within the UK. Envenoming was said to have occurred in just under half of all cases. Advice given by the NPIS appears to closely reflect national practice guidelines.
FGF-2 Disrupts Mitotic Stability in Prostate Cancer through the Intracellular Trafficking Protein CEP57
Authors: Cuevas Rolando , Korzeniewski Nina , Tolstov Yanis , Hohenfellner Markus , Duensing Stefan 
Published: December 2012

Abstract
Malignant tumors with deregulated FGF-2 expression such as prostate cancer are also frequently aneuploid. Aneuploidy can be caused by cell division errors due to extra centrosomes and mitotic spindle poles. However, a link between FGF-2 overexpression and chromosome missegregation has so far been elusive. Here, we show that FGF-2 rapidly uncouples centrosome duplication from the cell division cycle in prostate cancer cells through CEP57, an intracellular FGF-2–binding and trafficking factor. CEP57 was initially identified as a regulator of centriole overduplication in an RNA interference screen. We subsequently found that CEP57 rapidly stimulates centriole overduplication and mitotic defects when overexpressed and is required not only for FGF-2–induced centriole overduplication but also for normal centriole duplication. We provide evidence that CEP57 functions by modulating tubulin acetylation, thereby promoting daughter centriole stability. CEP57 was found to be overexpressed on the mRNA and protein level in a subset of prostate cancers, of which the vast majority also showed FGF-2 upregulation. Taken together, our results show an unexpected link between altered microenvironmental signaling cues such as FGF-2 overexpression and mitotic instability and provide a rationale for the therapeutic targeting of the FGF-2/FGFR1/CEP57 axis in prostate cancer. Cancer Res; 73(4); 1400–10. ©2012 AACR.
CCR2 Deficiency Prevents Neuronal Dysfunction and Cognitive Impairments Induced by Cranial Irradiation
Authors: Belarbi Karim , Jopson Timothy , Arellano Carla , Fike John R. , Rosi Susanna 
Published: December 2012

Abstract
Cranial irradiation can lead to long-lasting cognitive impairments in patients receiving radiotherapy for the treatment of malignant brain tumors. Recent studies have suggested inflammation as a major contributor to these deficits; we determined if the chemokine (C–C motif) receptor 2 (CCR2) was a mediator of cognitive impairments induced by irradiation. Two-month-old male Ccr2 knockout (−/−) and wild-type mice received 10 Gy cranial irradiation or sham-treatment. One month after irradiation, bromodeoxyuridine was injected intraperitoneally for seven consecutive days to label newly generated cells. At two months postirradiation, cognitive function was assessed by novel object recognition and Morris water maze. Our results show that CCR2 deficiency prevented hippocampus-dependent spatial learning and memory impairments induced by cranial irradiation. Hippocampal gene expression analysis showed that irradiation induced CCR2 ligands such as CCL8 and CCR2 deficiency reduced this induction. Irradiation reduced the number of adult-born neurons in both wild-type and Ccr2−/− mice, but the distribution pattern of the adult-born neurons through the granule cell layer was only altered in wild-type mice. Importantly, CCR2 deficiency normalized the fraction of pyramidal neurons expressing the plasticity-related immediate early gene Arc. These data offer new insight into the mechanism(s) of radiation-injury and suggest that CCR2 is a critical mediator of hippocampal neuronal dysfunction and hippocampal cognitive impairments after irradiation. Targeting CCR2 signaling could conceivably provide an effective approach to reduce or prevent the incidence and severity of this serious side effect of ionizing irradiation. Cancer Res; 73(3); 1201–10. ©2012 AACR.
Triptolide Inhibits MDM2 and Induces Apoptosis in Acute Lymphoblastic Leukemia Cells through a p53-Independent Pathway
Authors: Huang Mei , Zhang Hailong , Liu Tao , Tian Dan , Gu Lubing , Zhou Muxiang 
Published: December 2012

Abstract
Triptolide, a natural product derived from the Chinese plant Tripterygium wilfordii, is reported to exhibit antitumor effects in a broad range of cancers. The antitumor activity of triptolide is associated with its biologic activities, as it inhibits various proproliferative or antiapoptotic factors that are dominantly expressed in given types of cancer cells. Herein, we show that triptolide induced apoptosis in a subgroup of acute lymphoblastic leukemia (ALL) cells overexpressing the MDM2 oncoprotein by inhibiting MDM2 expression. More specifically, we found that triptolide inhibited MDM2 at the transcriptional level by suppressing its mRNA synthesis. This MDM2 inhibition led in turn to increased levels of p53 protein; however, p53 functionality was not activated due to the fact that triptolide-treated cells lacked induction of p21 and PUMA as well as in G1 cell-cycle arrest. Triptolide-mediated downregulation of MDM2 increased inhibition of X-linked inhibitor of apoptosis protein (XIAP), its translational target, in a manner distinct from reactions to cellular stress and DNA-damaging agent ionizing radiation that induce XIAP due to p53-activated MDM2. These results suggest that increased inhibition of XIAP due to downregulation of MDM2 may play a critical role in triptolide-induced apoptosis in MDM2-overexpressing cancers. Mol Cancer Ther; 12(2); 184–94. ©2012 AACR.
Dipyridamole decreases inflammatory metalloproteinase-9 expression and release by human monocytes
Authors: Carluccio Maria Annunziata , Pellegrino Mariangela , Calabriso Nadia , Storelli Carlo , Martines Giuseppe , Massaro Marika , Scoditti Egeria , De Caterina Raffaele 
Published: December 2012

SummaryMatrix metalloproteinase (MMP)-9 plays an important role in stroke by accelerating matrix degradation, disrupting the blood-brain barrier and increasing infarct size. Dipyridamole is an antiplatelet agent with recognised benefits in ischaemic stroke prevention. In addition to its antiplatelet properties, recent studies have reported that dipyridamole also features anti-inflammatory and anti-oxidant properties. We therefore investigated whether dipyridamole can ameliorate the proinflammatory profile of human monocytes, a source of MMP-9 in stroke, in terms of regulation of MMP-9 activity and expression, and explored underlying mechanisms. Human peripheral blood mononuclear cells (PBMC) and U937 cells were treated with increasing concentrations of dipyridamole (up to 10 µg/ml) for 60 minutes before stimulation with tumour necrosis factor (TNF)-α or phorbol myristate acetate (PMA). Exposure of PBMC and U937 to dipyridamole reduced TNF-α- and PMA-induced MMP-9 activity and protein release as well as MMP-9 mRNA, without significantly affecting the release of TIMP-1. This inhibitory effect was independent of dipyridamole-induced cyclic adeno-sine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) increase. Correspondingly, dipyridamole also significantly inhibited TNF-α-induced nuclear factor (NF)-κB activation and nuclear translocation of the p65 NF-κB subunit through a mechanism involving the inhibition of IkBα degradation and p38 MAPK activation. In conclusion, dipyridamole, at therapeutically achievable concentrations, reduces the expression and release of MMP-9 through a mechanism involving p38 MAPK and NF-κB inhibition. These results indicate that dipyridamole exerts anti-inflammatory properties in human monocytes that may favourably contribute to its actions in the secondary prevention of stroke, independent of its antiplatelet properties.
Integrin-substrate interactions underlying shear-induced inhibition of the inflammatory response of endothelial cells
Authors: Luu Thin , Egginton Stuart , Rainger Ed , Glen Katie , Nash Gerard 
Published: December 2012

SummaryConditioning of endothelial cells by shear stress suppresses their response to inflammatory cytokines. We questioned whether signalling through different integrin-matrix interactions, previously associated with the pathogenic effects of disturbed flow, supported the anti-inflammatory action of steady shear. Primary human endothelial cells were cultured on different substrates and exposed to shear stress (2.0Pa) for varying periods before stimulation with tumour necrosis factor-α (TNF). Shear-conditioning inhibited cytokine-induced recruitment of flowing neutrophils. However, the effect was similar for culture on collagen, laminin or fibronectin, even when seeding was reduced to 2hours, and shear to 3hours before TNF treatment (to minimise deposition of endothelial matrix). Nevertheless, in short- or longer- term cultures, reduction in expression of β1-integrin (but not β3-integrin) using siRNA essentially ablated the effect of shear-conditioning on neutrophil recruitment. Studies of focal adhesion kinase (FAK) phosphorylation, siRNA against FAK and a FAK-inhibitor (PF573228) indicated that FAK activity was an essential component downstream of β1-integrin. In addition, MAP-kinase p38 was phosphorylated downstream of FAK and also required for functional modification. Mechanotransduction through β1-integrins, FAK and p38 is required for anti-inflammatory effects of steady shear stress. Separation of the pathways which underlie pathological versus protective responses of different patterns of flow is required to enable therapeutic modification or mimicry, respectively.
Endothelial Acyl-CoA Synthetase 1 Is Not Required for Inflammatory and Apoptotic Effects of a Saturated Fatty Acid-Rich Environment
Authors: Li Xin , Gonzalez Oscar , Shen Xia , Barnhart Shelley , Kramer Farah , Kanter Jenny E. , Vivekanandan-Giri Anuradha , Tsuchiya Kyoichiro , Handa Priya , Pennathur Subramaniam , Kim Francis , Coleman Rosalind A. , Schaffer Jean E. , Bornfeldt Karin E. 
Published: December 2012

Objective—
Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo.

Methods and Results—
Saturated fatty acids caused increased inflammatory activation, endoplasmic reticulum stress, and apoptosis in mouse microvascular endothelial cells. Forced ACSL1 overexpression exacerbated the effects of saturated fatty acids on apoptosis and endoplasmic reticulum stress. However, endothelial ACSL1 deficiency did not protect against the effects of saturated fatty acids in vitro, nor did it protect insulin-resistant mice fed a saturated fatty acid-rich diet from macrophage adipose tissue accumulation or increased aortic adhesion molecule expression.

Conclusion—
Endothelial ACSL1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.
Human Apolipoprotein A-II Protects Against Diet-Induced Atherosclerosis in Transgenic Rabbits
Authors: Wang Yao , Niimi Manabu , Nishijima Kazutoshi , Waqar Ahmed Bilal , Yu Ying , Koike Tomonari , Kitajima Shuji , Liu Enqi , Inoue Tomohiro , Kohashi Masayuki , Keyamura Yuka , Yoshikawa Tomohiro , Zhang Jifeng , Ma Loretta , Zha Xiaohui , Watanabe Teruo , Asada Yujiro , Chen Y. Eugene , Fan Jianglin 
Published: December 2012

Objective—
Apolipoprotein (apo) A-II is the second major apo of high-density lipoproteins, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and, if so, to elucidate the mechanism involved.

Methods and Results—
We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates, while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells, and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma C-reactive protein and blood leukocytes compared with non-Tg rabbits, and high-density lipoproteins of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than high-density lipoproteins isolated from non-Tg rabbits. In addition, β-very-low-density lipoproteins of Tg rabbits were less sensitive to copper-induced oxidation than β-very-low-density lipoproteins of non-Tg rabbits.

Conclusion—
These results suggest that enrichment of apo A-II in high-density lipoprotein particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.
Reduced Mural Cell Coverage and Impaired Vessel Integrity After Angiogenic Stimulation in the
Alk1
-deficient Brain
Authors: Chen Wanqiu , Guo Yi , Walker Espen J. , Shen Fanxia , Jun Kristine , Oh S. Paul , Degos Vincent , Lawton Michael T. , Tihan Tarik , Davalos Dimitrios , Akassoglou Katerina , Nelson Jeffrey , Pile-Spellman John , Su Hua , Young William L. 
Published: December 2012

Objective—

Vessels in brain arteriovenous malformations are prone to rupture. The underlying pathogenesis is not clear. Hereditary hemorrhagic telangiectasia type 2 patients with activin receptor-like kinase 1 (
Alk1
) mutation have a higher incidence of brain arteriovenous malformation than the general population. We tested the hypothesis that vascular endothelial growth factor impairs vascular integrity in the
Alk1
-deficient brain through reduction of mural cell coverage.

Methods and Results—

Adult
Alk1
1f/2f
mice (loxP sites flanking exons 4–6) and wild-type mice were injected with 2×10
7
PFU adenovious-cre recombinase and 2×10
9
genome copies of adeno-associated virus-vascular endothelial growth factor to induce focal homozygous
Alk1
deletion (in
Alk1
1f/2f
mice) and angiogenesis. Brain vessels were analyzed 8 weeks later. Compared with wild-type mice, the
Alk1
-deficient brain had more fibrin (99±30×10
3
pixels/mm
2
versus 40±13×10
3
;
P
=0.001), iron deposition (508±506 pixels/mm
2
versus 6±49;
P
=0.04), and Iba1
+
microglia/macrophage infiltration (888±420 Iba1
+
cells/mm
2
versus 240±104 Iba1
+
;
P
=0.001) after vascular endothelial growth factor stimulation. In the angiogenic foci, the
Alk1
-deficient brain had more α-smooth muscle actin negative vessels (52±9% versus 12±7%,
P
<0.001), fewer vascular-associated pericytes (503±179/mm
2
versus 931±115,
P
<0.001), and reduced platelet-derived growth factor receptor-β expression.

Conclusion—
Reduction of mural cell coverage in response to vascular endothelial growth factor stimulation is a potential mechanism for the impairment of vessel wall integrity in hereditary hemorrhagic telangiectasia type 2-associated brain arteriovenous malformation.