bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral aneurysm wall thickness analysis using intraoperative microscopy: effect of size and gender on thin translucent regions
Authors: Kadasi Laith M , Dent Walter C , Malek Adel M 
Published: March 2012

ObjectiveWall thickness is a poorly documented characteristic of cerebral aneurysms which may provide insight into adaptive aneurysmal growth, aneurysm rupture risk and response to endovascular treatment. The distribution of aneurysm wall thickness, as observed by intraoperative video microscopy, is described.Methods54 unruptured saccular cerebral aneurysms were selected based on the availability of intraoperative video obtained from patients undergoing microsurgical clipping. Aneurysms were assessed for the distribution of wall thickness based on color translucence and quantitation of pixel values at superthin translucent, intermediate and thick regions of the dome. The data were analyzed with respect to aneurysm morphology, location and associated demographic factors.ResultsThe mean proportions of tissue characteristic among all domes analyzed were found to be 27% superthin, 65% intermediate, and 8% thick. Smaller aneurysms having a maximal dimension Dmax<7 mm had a higher proportion of superthin tissue (p=0.003) and lower thick tissue (p=0.001) content. Female gender was associated with a significantly higher proportion of superthin tissue at the aneurysm dome (p=0.038), with no statistical dependence seen with patient age, smoking status or anatomical location.ConclusionThe dome of unruptured aneurysms is a highly heterogeneous region with areas of variable thickness that appear to be intimately related to the process of aneurysm development. This inconstant property affects wall tensile stress, may play a role in aneurysm pathogenesis and focal rupture, and should be incorporated into future analyses of aneurysm rupture risk and mechanics.
A Galectin-3–Dependent Pathway Upregulates Interleukin-6 in the Microenvironment of Human Neuroblastoma
Authors: Silverman Ayaka M. , Nakata Rie , Shimada Hiroyuki , Sposto Richard , DeClerck Yves A. 
Published: March 2012

Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine with a broad range of physiologic and pathologic functions. Because in cancer, IL-6 contributes to a microenvironment that promotes tumor cell survival, angiogenesis, and inflammation, understanding the mechanism responsible for its production is important. In neuroblastoma, the second most common solid tumor in children, IL-6 is produced not by tumor cells but by stromal cells such as monocytes and bone marrow mesenchymal stem cells (BMMSC). Here we show that the production of IL-6 in BMMSCs is in part stimulated by galectin-3 binding protein (Gal-3BP) secreted by neuroblastoma cells. We identified a distal region of the IL-6 promoter that contains 3 CCATT/enhancer binding protein (C/EBP) binding domains involved in the transcriptional upregulation of IL-6 by Gal-3BP. Gal-3BP interacted with Galectin-3 (Gal-3) present in BMMSCs, and a Gal-3BP/Gal-3/Ras/MEK/ERK signaling pathway was responsible for the transcriptional upregulation of IL-6 in BMMSCs in which Gal-3 has a necessary function. In support of the role of this pathway in human neuroblastoma tumors, Gal-3BP was found to be present in tumor cells and in the adjacent extracellular matrix of 96% of 78 primary neuroblastoma tumor samples examined by immunohistochemistry. Considering the protumorigenic function of IL-6 in cancer, this tumor cell–stromal cell interactive pathway could be a target for anticancer therapy. Cancer Res; 72(9); 2228–38. ©2012 AACR.
A RASSF1A Polymorphism Restricts p53/p73 Activation and Associates with Poor Survival and Accelerated Age of Onset of Soft Tissue Sarcoma
Authors: Yee Karen S. , Grochola Lukasz , Hamilton Garth , Grawenda Anna , Bond Elisabeth E. , Taubert Helge , Wurl Peter , Bond Gareth L. , O'Neill Eric 
Published: March 2012

Abstract
RASSF1A (Ras association domain containing family 1A), a tumor suppressor gene that is frequently inactivated in human cancers, is phosphorylated by ataxia telangiectasia mutated (ATM) on Ser131 upon DNA damage, leading to activation of a p73-dependent apoptotic response. A single-nucleotide polymorphism located in the region of the key ATM activation site of RASSF1A predicts the conversion of alanine (encoded by the major G allele) to serine (encoded by the minor T allele) at residue 133 of RASSF1A (p.Ala133Ser). Secondary protein structure prediction studies suggest that an alpha helix containing the ATM recognition site is disrupted in the serine isoform of RASSF1A (RASSF1A-p.133Ser). In this study, we observed a reduced ability of ATM to recruit and phosphorylate RASSF1A-p.133Ser upon DNA damage. RASSF1A-p.133Ser failed to activate the MST2/LATS pathway, which is required for YAP/p73-mediated apoptosis, and negatively affected the activation of p53, culminating in a defective cellular response to DNA damage. Consistent with a defective p53 response, we found that male soft tissue sarcoma patients carrying the minor T allele encoding RASSF1A-p.133Ser exhibited poorer tumor-specific survival and earlier age of onset compared with patients homozygous for the major G allele. Our findings propose a model that suggests a certain subset of the population have inherently weaker p73/p53 activation due to inefficient signaling through RASSF1A, which affects both cancer incidence and survival. Cancer Res; 72(9); 2206–17. ©2012 AACR.
Molecular Pathways: Fibroblast Growth Factor Signaling: A New Therapeutic Opportunity in Cancer
Authors: Brooks A. Nigel , Kilgour Elaine , Smith Paul D. 
Published: March 2012

Abstract
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis plays an important role in normal organ, vascular, and skeletal development. Deregulation of FGFR signaling through genetic modification or overexpression of the receptors (or their ligands) has been observed in numerous tumor settings, whereas the FGF/FGFR axis also plays a key role in driving tumor angiogenesis. A growing body of preclinical data shows that inhibition of FGFR signaling can result in antiproliferative and/or proapoptotic effects, both in vitro and in vivo, thus confirming the validity of the FGF/FGFR axis as a potential therapeutic target. In the past, development of therapeutic approaches to target this axis has been hampered by our inability to develop FGFR-selective agents. With the advent of a number of new modalities for selectively inhibiting FGF/FGFR signaling, we are now in a unique position to test and validate clinically the many hypotheses that have been generated preclinically. Clin Cancer Res; 18(7); 1855–62. ©2012 AACR.
Developmental Endothelial Locus-1 (Del-1) Mediates Clearance of Platelet Microparticles by the Endothelium
Authors: Dasgupta Swapan Kumar , Le Anhquyen , Chavakis Triantafyllos , Rumbaut Rolando E. , Thiagarajan Perumal 
Published: March 2012

Background—
Phosphatidylserine-expressing microparticles circulate in blood with a short half-life of <10 minutes. We tested the role of an endothelium-derived phosphatidylserine-binding opsonin, developmental endothelial locus-1 (Del-1), in the uptake of platelet microparticles.

Methods and Results—

Cultured human umbilical vein and microvascular endothelial cells avidly engulf BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-
s
-indacene)-maleimide–labeled platelet microparticles. Microparticle uptake was inhibited by a monoclonal antibody to Del-1 (
P
=0.027) and by annexin A5 (
P
=0.027), abciximab (
P
=0.027), a monoclonal antibody to integrin αVβ3 (
P
=0.027), and chlorpromazine (
P
=0.027). These results suggest that Del-1 mediates phosphatidylserine- and integrin-dependent endothelial uptake of microparticles by endocytosis. To assess the in vivo significance, we infused fluorescent platelet microparticles into the inferior vena cava of mice and harvested endothelial cells from the pulmonary and systemic circulation. Compared with their wild-type littermates, Del-1–deficient mice had decreased uptake in endothelial cells in lung (3.07±1.9 versus 1.09±1.3,
P
=0.02) and liver (2.85±1.1 versus 1.35±0.92,
P
=0.01). Furthermore, after endotoxin administration, Del-1–deficient mice displayed an increase in the level of microparticles compared with wild-type mice (
P
=0.02).

Conclusions—
These studies show a physiological role for Del-1 in the clearance of phosphatidylserine-expressing microparticles by endothelium.
Multidecadal Covariability of North Atlantic Sea Surface Temperature, African Dust, Sahel Rainfall, and Atlantic Hurricanes
Authors: Wang Chunzai , Dong Shenfu , Evan Amato T. , Foltz Gregory R. , Lee Sang-Ki 
Published: March 2012

Abstract
Most studies of African dust and North Atlantic climate have been limited to the short time period since the satellite era (1980 onward), precluding the examination of their relationship on longer time scales. Here a new dust dataset with the record extending back to the 1950s is used to show a multidecadal covariability of North Atlantic SST and aerosol, Sahel rainfall, and Atlantic hurricanes. When the North Atlantic Ocean was cold from the late 1960s to the early 1990s, the Sahel received less rainfall and the tropical North Atlantic experienced a high concentration of dust. The opposite was true when the North Atlantic Ocean was warm before the late 1960s and after the early 1990s. This suggests a novel mechanism for North Atlantic SST variability—a positive feedback between North Atlantic SST, African dust, and Sahel rainfall on multidecadal time scales. That is, a warm (cold) North Atlantic Ocean produces a wet (dry) condition in the Sahel and thus leads to low (high) concentration of dust in the tropical North Atlantic, which in turn warms (cools) the North Atlantic Ocean. An implication of this study is that coupled climate models need to be able to simulate this aerosol-related feedback in order to correctly simulate climate variability in the North Atlantic. Additionally, it is found that dust in the tropical North Atlantic varies inversely with the number of Atlantic hurricanes on multidecadal time scales because of the multidecadal variability of both direct and indirect influences of dust on vertical wind shear in the hurricane main development region.
Increase in Mean Platelet Volume in Patients With Myocardial Bridge
Authors: Bilen Emine , Tanboga Ibrahim Halil , Kurt Mustafa , Kocak Umran , Ayhan Huseyin , Keleş Telat , Bozkurt Engin 
Published: March 2012

Aim: Myocardial bridge is associated with atherosclerosis altered in shear stress and endothelial dysfunction. Mean platelet volume (MPV), a determinant of platelet activation, is shown to be related with atherosclerosis and endothelial dysfunction. In this study, we aimed to evaluate platelet function assessed by MPV in patients with myocardial bridge. Methods: Forty-two patients with myocardial bridge in the left anterior descending artery (LAD) and 43 age- and gender-matched healthy participants were included in the study. Myocardial bridging was defined as an intramyocardial systolic compression or milking of a segment of an epicardial coronary artery on angiography. For the entire study population, MPV was measured using an automatic blood counter. Results: The study population consisted of 42 patients with myocardial bridge (52.7 ± 10.2, 76.2% male) and 43 age- and sex-matched healthy control participants (52.1 ± 10.4, 74.4% male). Compared to the control group, MPV value was significantly higher in patients with myocardial bridge (8.9 ± 1.24 vs 8.3 ± 0.78; P = .01). Further, there were no significant differences between groups regarding hemoglobin level, platelet count, fasting blood glucose, and creatinine levels. Conclusions: Our study findings indicated that myocardial bridge is associated with elevated MPV values. Our results might partly explain the increased cardiovascular events in patients with myocardial bridge.
Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography
Authors: Albrecht P , Ringelstein M , Müller AK , Keser N , Dietlein T , Lappas A , Foerster A , Hartung HP , Aktas O , Methner A 
Published: March 2012

Background: Optical coherence tomography can be used to assess retinal degeneration in multiple sclerosis (MS). Thinning of the retinal nerve fibre layer and macular thickness have been well characterized, but newer devices allow quantification of all retinal layers. Objectives: The objective of this study was to evaluate the thickness of the paramacular retina, peripapillary retinal nerve fibre layer, and deeper paramacular layers in MS patient subgroups, using state-of-the-art optical coherence tomography. Methods: Using a Heidelberg Engineering Spectralis device, we performed paramacular volumetric retinal scans and circular peripapillary fibre-layer scans, manually segmenting different retinal layers into single horizontal foveal scans in 95 patients with definite MS (42 relapsing–remitting, 41 secondary progressive, 12 primary progressive), plus 91 age- and sex-matched controls. Results: Even without a history of optic neuritis, all MS subgroups had significant thinning of the peripapillary retinal nerve fibre layer, the paramacular retinal thickness and the retinal ganglion cell- and inner plexiform layer. Only in primary progressive MS was the inner nuclear layer significantly reduced. Conclusions: Our findings indicate a primary retinal pathology involving the inner nuclear layer in primary progressive MS. Results in eyes without history of optic neuritis suggest possible subclinical episodes of optic neuritis or retrograde trans-synaptic degeneration of retinal ganglion cells and their axons.
Abnormal cervical cord function contributes to fatigue in multiple sclerosis
Authors: Rocca MA , Absinta M , Valsasina P , Copetti M , Caputo D , Comi G , Filippi M 
Published: March 2012

Background/Objective We aimed to investigate whether cervical cord damage and dysfunction is associated with the presence and severity of fatigue in multiple sclerosis (MS) using a multiparametric magnetic resonance (MR) approach. Methods: Cervical cord functional magnetic resonance imaging (fMRI) during a tactile stimulation of the right hand, and structural brain and cord MRI were acquired from 20 controls, 15 MS patients without fatigue (NF) and 20 MS patients with fatigue (F). Between-group differences in the extent of focal lesions and diffusivity abnormalities in the brain and cord, cord-normalized cross-sectional area (CSAn) and fMRI activity were assessed. Results: All structural MRI measures differed significantly among groups, except for cord lesion number and CSAn. Compared with controls, NF-MS patients experienced higher cord recruitment ( p=0.04). Compared with F-MS, NF-MS patients had a lower brain normal-appearing white matter average fractional anisotropy ( p=0.001) and increased cord recruitment ( p=0.02). In patients with MS, the extent of cord recruitment was correlated with the severity of fatigue ( r=-0.34, p=0.04). Compared with the other two groups, F-MS patients had a more diffuse recruitment of cord quadrants on the axial and longitudinal planes. Conclusions: Abnormalities of function, but not of structure, of the cervical cord are likely to contribute to the pathogenesis of fatigue in MS.
Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study
Authors: Czuczman Myron S. , Fayad Luis , Delwail Vincent , Cartron Guillaume , Jacobsen Eric , Kuliczkowski Kazimierz , Link Brian K. , Pinter-Brown Lauren , Radford John , Hellmann Andrzej , Gallop-Evans Eve , DiRienzo Christine G. , Goldstein Nancy , Gupta Ira , Jewell Roxanne C. , Lin Thomas S. , Lisby Steen , Schultz Martin , Russell Charlotte A. , Hagenbeek Anton 
Published: March 2012

AbstractNew treatments are required for rituximab-refractory follicular lymphoma (FL). In the present study, patients with rituximab-refractory FL received 8 weekly infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg; N = 116). The median age of these patients was 61 years, 47% had high-risk Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy-refractory, and the median number of prior therapies was 4. The overall response rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27 patients refractory to rituximab monotherapy, the overall response rate was 22%. The median progression-free survival was 5.8 months. Forty-six percent of patients demonstrated tumor reduction 3 months after therapy initiation, and the median progression-free survival for these patients was 9.1 months. The most common adverse events included infections, rash, urticaria, fatigue, and pruritus. Three patients experienced grade 3 infusion-related reactions, none of which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia, and thrombocytopenia occurred in a subset of patients. Ofatumumab was well tolerated and modestly active in this heavily pretreated, rituximab-refractory population and is therefore now being studied in less refractory FL and in combination with other agents in various B-cell neoplasms. The present study was registered at www.clinicaltrials.gov as NCT00394836.
Enhancing performance of ZnO dye-sensitized solar cells by incorporation of multiwalled carbon nanotubes
Authors: Chang Wei-Chen , Cheng Yao-Yi , Yu Wan-Chin , Yao Yih-Chun , Lee Chia-Hua , Ko Hung-Han 
Published: March 2012

Abstract
A low-temperature, direct blending procedure was used to prepare composite films consisting of zinc oxide [ZnO] nanoparticles and multiwalled carbon nanotubes [MWNTs]. The mesoporous ZnO/MWNT films were fabricated into the working electrodes of dye-sensitized solar cells [DSSCs]. The pristine MWNTs were modified by an air oxidation or a mixed acid oxidation treatment before use. The mixed acid treatment resulted in the disentanglement of MWNTs and facilitated the dispersion of MWNTs in the ZnO matrix. The effects of surface property and loading of MWNTs on DSSC performance were investigated. The performance of DSSCs was found to depend greatly on the type and the amount of MWNTs incorporated. At a loading of 0.01 wt%, the acid-treated MWNTs were able to increase the power conversion efficiency of fabricated cells from 2.11% (without MWNTs) to 2.70%.
Therapy for metastatic melanoma: the past, present, and future
Authors: Finn Laura , Markovic Svetomir N , Joseph Richard W 
Published: March 2012

Abstract
Metastatic melanoma is the most aggressive form of skin cancer with a median overall survival of less than one year. Advancements in our understanding of how melanoma evades the immune system as well as the recognition that melanoma is a molecularly heterogeneous disease have led to major improvements in the treatment of patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved two novel therapies for advanced melanoma: a BRAF inhibitor, vemurafenib, and an immune stimulatory agent, ipilimumab. The success of these agents has injected excitement and hope into patients and clinicians and, while these therapies have their limitations, they will likely provide excellent building blocks for the next generation of therapies. In this review we will discuss the advantages and limitations of the two new approved agents, current clinical trials designed to overcome these limitations, and future clinical trials that we feel hold the most promise.
Macroautophagy in sporadic and the genetic form of Parkinson's disease with the A53T α-synuclein mutation
Authors: Huang Yue , Chegini Fariba , Chua Germaine , Murphy Karen , Gai Weiping , Halliday Glenda M 
Published: March 2012

Abstract

Background
The A53T mutation in the α-synuclein gene causes autosomal-dominant Lewy body Parkinson's disease (PD). Cultured cell models have linked this mutation to increased cell macroautophagy, although evidence of enhanced macroautophagy in patients with this mutation has not been assessed.

Objective
To determine whether macroautophagy is increased by the A53T α-synuclein gene mutation in PD patients and cell models.

Methods
Formalin-fixed paraffin-embedded 10 μm-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T α-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain Bank. Lewy bodies were isolated from frontal cortex of a case with late stage PD (recruited from South Australian Brain Bank). Immunohistochemistry was performed for α-synuclein and the macroautophagy markers autophagy-specific gene (ATG) 5, ATG6/Beclin1 and ATG8/LC3. SH-SY5Y cells were transfected with wild type or A53T mutant α-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western blotting.

Results
α-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients, and perinuclear cytoplasmic α-synuclein aggregates were observed in the α-synuclein A53T gene transfected SH-SY5Y cells compared to wild type transfections. All PD patients (with or without A53T mutations) had increased immunohistochemical evidence for macroautophagy compared with controls, and the levels of the ATG5 complex were equally increased in wild type and A53T α-synuclein gene transfected cells compared to controls.

Conclusion
Despite increased α-synuclein accumulation with A53T mutations, macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type α-synuclein, suggesting that mutated α-synuclein protein is not removed by macroautophagy.
Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study
Authors: Zampeli Evangelia , Protogerou Athanase , Stamatelopoulos Kimon , Fragiadaki Kalliopi , Katsiari Christina G , Kyrkou Katerina , Papamichael Christos M , Mavrikakis Myron , Nightingale Peter , Kitas George D , Sfikakis Petros P 
Published: March 2012

Abstract
Introduction
Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to both classical risk factors and chronic inflammation. We assessed longitudinally the factors associated with new carotid plaques in nondiabetic RA patients and apparently healthy individuals.

Methods
In our present prospective observational study, carotid plaques were identified by ultrasonography at baseline and follow-up end, separated by an average of 3.6 ± 0.2 years, in 64 patients (mean age 59.2 ± 12.0 and disease duration at baseline 7.8 ± 6.2 years, 83% women, clinical and laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients were matched 1:1 for traditional cardiovascular risk factors with 'healthy' controls and were studied in parallel.

Results
New atherosclerotic plaques formed in 30% of patients (first plaque in 9%) who were significantly older than the remaining patients. Tobacco use, blood pressure, body mass index, average cumulative low-density lipoprotein, high-sensitivity C-reactive protein, erythrocyte sedimentation rate level, RA stage, functional class, disease duration and treatment modalities during follow-up did not differ significantly between subgroups after application of the Bonferroni correction. RA was in clinical remission, on average, for approximately 70% of the follow-up time and was not different between subgroups. Multivariate analysis including all the above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration of low-dose corticosteroid use (P = 0.016) associated independently with new plaque formation. RA patients displayed similar numbers of newly formed carotid plaques to the tightly matched for traditional cardiovascular risk factors 'healthy' controls, although more patients than controls had carotid plaques at baseline.

Conclusions
Formation of new atherosclerotic plaques in this small cohort of patients with well-controlled RA depended mainly on traditional cardiovascular risk factors and corticosteroid use, whereas an adverse effect of residual systemic inflammation was not readily detectable.