bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfemoral venous approach for Onyx embolization of anterior fossa dural arteriovenous fistulae
Authors: Spiotta Alejandro M , Hawk Harris , Kellogg Ryan T , Turner Raymond D , Chaudry M Imran , Turk Aquilla S 
Published: March 2013

BackgroundDural arteriovenous fistulae (dAVF) of the anterior fossa have a malignant course since they exclusively drain into cortical frontal veins and warrant aggressive treatment. Classically, these lesions have been treated with microsurgical clipping of the fistulous connection. We describe a transvenous approach for Onyx embolization of these lesions that relies on distal venous access using a flexible new-generation guide catheter.MethodsA retrospective review was performed of all patients with an anterior fossa dAVF treated at the Medical University of South Carolina since 2010. Charts, procedural records, angiographic images and follow-up were reviewed. Three patients were identified.ResultsTransfemoral venous access and distal transvenous sinus access was obtained in a retrograde fashion to at least the level of the right transverse sinus. Once a distal guide catheter position was obtained within the venous sinus system, a microcatheter was advanced into the predominant draining anterior frontal cortical vein in preparation for embolization. Onyx 34 embolization was then initiated from this position with the objective of achieving penetration across the vascular shunt.ConclusionsOur experience demonstrates that transvenous Onyx embolization offers an effective and safe alternative to the classic neurosurgical treatment of anterior fossa dAVF.
Targeted Inhibition of the Molecular Chaperone Hsp90 Overcomes ALK Inhibitor Resistance in Non–Small Cell Lung Cancer
Authors: Sang Jim , Acquaviva Jaime , Friedland Julie C. , Smith Donald L. , Sequeira Manuel , Zhang Chaohua , Jiang Qin , Xue Liquan , Lovly Christine M. , Jimenez John-Paul , Shaw Alice T. , Doebele Robert C. , He Suqin , Bates Richard C. , Camidge D. Ross , Morris Stephan W. , El-Hariry Iman , Proia David A. 
Published: March 2013

Abstract
EML4–ALK gene rearrangements define a unique subset of patients with non–small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy. Here, we show that the Hsp90 inhibitor ganetespib induced loss of EML4–ALK expression and depletion of multiple oncogenic signaling proteins in ALK-driven NSCLC cells, leading to greater in vitro potency, superior antitumor efficacy, and prolonged animal survival compared with results obtained with crizotinib. In addition, combinatorial benefit was seen when ganetespib was used with other targeted ALK agents both in vitro and in vivo. Importantly, ganetespib overcame multiple forms of crizotinib resistance, including secondary ALK mutations, consistent with activity seen in a patient with crizotinib-resistant NSCLC. Cancer cells driven by ALK amplification and oncogenic rearrangements of ROS1 and RET kinase genes were also sensitive to ganetespib exposure. Taken together, these results highlight the therapeutic potential of ganetespib for ALK-driven NSCLC.
Significance: In addition to direct kinase inhibition, pharmacologic blockade of the molecular chaperone Hsp90 is emerging as a promising approach for treating tumors driven by oncogenic rearrangements of ALK. The bioactivity profile of ganetespib presented here underscores a new therapeutic opportunity to target ALK and overcome multiple mechanisms of resistance in patients with ALK-positive NSCLC. Cancer Discov; 3(4); 430–43. ©2013 AACR.
This article is highlighted in the In This Issue feature, p. 363
Dextran sulphate induces fibrinogen receptor activation through a novel Syk-independent PI-3 kinase-mediated tyrosine kinase pathway in platelets
Authors: Getz Todd M. , Manne Bhanu , Buitrago Lorena , Mao Yingying , Kunapuli Satya P. 
Published: March 2013

SummaryIn our attempt to find a physiological agonist that activates PAR3 receptors, we screened several coagulation proteases using PAR4 null platelets. We observed that FXIIa and heat inactivated FXIIa, but not FXII, caused platelet aggregation. We have identified a contaminant activating factor in FXIIa preparation as dextran sulfate (DxS), which caused aggregation of both human and mouse platelets. DxS-induced platelet aggregation was unaffected by YM254890, a Gq inhibitor, but abolished by pan-Src family kinase (SFK) inhibitor PP2, suggesting a role for SFKs in this pathway. However, DxS-induced platelet aggregation was unaffected in FcRγ-chain null murine platelets, ruling out the possibility of glycoprotein VI-mediated events. More interesting, OXSI-2 and Go6976, two structurally unrelated inhibitors shown to affect Syk, had only a partial effect on DxS-induced PAC-1 binding. DxS-induced platelet aggregation and intracellular calcium increases were abolished by the pan PI-3 kinase inhibitor LY294002, or an isoform-specific PI-3 kinase β inhibitor TGX-221. Pretreatment of platelets with Syk inhibitors or ADP receptor antagonists had little effect on Akt phosphorylation following DxS stimulation. These results, for the first time, establish a novel tyrosine kinase pathway in platelets that causes fibrinogen receptor activation in a PI-3 kinase-dependent manner without a crucial role for Syk.
The electrolytic inferior vena cava model (EIM) to study thrombogenesis and thrombus resolution with continuous blood flow in the mouse
Authors: Alvarado Christine M. , Wrobleski Shirley K. , Slack Dallas W. , Hawley Angela E. , Farris Diana M. , Henke Peter K. , Wakefield Thomas W. , Myers Daniel D. , Diaz Jose A. 
Published: March 2013

SummaryPreviously, we presented the electrolytic inferior vena cava (IVC) model (EIM) during acute venous thrombosis (VT). Here, we present our evaluation of the EIM for chronic VT time points in order to determine whether this model allows for the study of thrombus resolution. C57BL/6 mice (n=191) were utilised. In this model a copper-wire, inserted into a 25-gauge needle, is placed in the distal IVC and another subcutaneously. An electrical current (250 Amp/15 minutes) activates the endothelial cells, inducing thrombogenesis. Ultrasound, thrombus weight (TW), vein wall leukocyte counts, vein wall thickness/ fibrosis scoring, thrombus area and soluble P-selectin (sP-sel) were performed at baseline, days 1, 2, 4, 6, 9, 11 and 14, post EIM. A correlation between TW and sP-sel was also determined. A thrombus formed in each mouse undergoing EIM. Blood flow was documented by ultrasound at all time points. IVC thrombus size increased up to day 2 and then decreased over time, as shown by ultrasound, TW, and sP-sel levels. TW and sP-sel showed a strong positive correlation (r=0.48, p<0.0002). Vein wall neutrophils were the most common cell type present in acute VT (up to day 2) with monocytes becoming the most prevalent in chronic VT (from day 6 to day 14). Thrombus resolution was demonstrated by ultrasound, TW and thrombus area. In conclusion, the EIM produces a non-occlusive and consistent IVC thrombus, in the presence of constant blood flow, allowing for the study of VT at both acute and chronic time points. Thrombus resolution was demonstrated by all modalities utilised in this study.Note: Results were presented, in part, at the 24th American Venous Forum Annual Meeting 2012 in Orlando, FL, USA.
Pregnancy Loss and Later Risk of Atherosclerotic Disease
Authors: Ranthe Mattis Flyvholm , Andersen Elisabeth A. Wreford , Wohlfahrt Jan , Bundgaard Henning , Melbye Mads , Boyd Heather A. 
Published: March 2013

Background—
Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension.

Methods and Results—
Among women pregnant at least once between 1977 and 2008, we identified a cohort of women with miscarriages, stillbirths, or live singleton births. These women were followed from the end of pregnancy for incident myocardial infarction, cerebral infarction, and renovascular hypertension. Using Poisson regression, we estimated incidence rate ratios for each of the outcomes by history of miscarriage and stillbirth. Among 1 031 279 women followed for >15 928 900 person-years, we identified 27 98 myocardial infarctions, 40 53 cerebral infarctions, and 1269 instances of renovascular hypertension. Women with stillbirths had 2.69 (95% confidence interval, 2.06–3.50), 1.74 (1.32–2.28), and 2.42 (1.59–3.69) times the rates of myocardial infarction, cerebral infarction, and renovascular hypertension, respectively, as women with no stillbirths. Compared with women with no miscarriages, women with miscarriages had 1.13 (1.03–1.24), 1.16 (1.07–1.25), and 1.20 (1.05–1.38) times the rates of these same outcomes, respectively; these associations were dose dependent, with each additional miscarriage increasing the rates of myocardial and cerebral infarction and renovascular hypertension by 9% (3% to 16%), 13% (7% to 19%), and 19% (9% to 30%), respectively. Associations were strongest in younger women (<35 years).

Conclusions—
Pregnancy losses were associated with subsequent risks of myocardial infarction, cerebral infarction, and renovascular hypertension, consistent with either shared etiology or the initiation of pathological processes by a pregnancy loss leading to atherosclerosis.
The Meaning of Play for Young People with Physical Disabilities
Authors: Pollock Nancy , Stewart Debra , Law Mary , Sahagian-Whalen Sandra , Harvey Susan , Toal Coleen 
Published: March 2013

As a primary area of occupation, play is central to the lives of children. Emerging views of play reflect the complexity of the area, and focus on the relationship between the person and the environment during play. This paper reports the results of a qualitative study of twenty adolescents with and without physical disabilities. The participants were interviewed about their perceptions and personal experiences of play. Through a textual analysis of the data, significant themes related to the nature of play, environmental barriers and supports, and personal influences on play were identified. Clinical implications are discussed in relation to these themes.
Dose rounding of ipilimumab in adult metastatic melanoma patients results in significant cost savings
Authors: Jarkowski Anthony , Nestico Jill S , Vona Karen L , Khushalani Nikhil I 
Published: March 2013

Purpose To assess cost savings incurred with a dose rounding process that was implemented for ipilimumab. Secondarily, to assess response rates, patient tolerance, and adverse effects associated with ipilimumab upon implementation of dose rounding. Methods All patients with a diagnosis of metastatic melanoma and who received at least one dose ipilimumab were included for analysis. Doses of ipilimumab were calculated based upon the actual body weight (in kg) of the patient at the FDA approved regimen of 3 mg/kg every 21 days × 4 doses. The exact total mg dose was then rounded to the nearest 50 mg vial size. The potential effect on cost was calculated in US dollars for both the calculated and rounded doses. Waste, in mg, was defined as the amount of drug that may have been discarded if the calculated dose was used for therapy. The acquisition cost applied was US$120 per mg. Results 22 patients have received at least one dose of ipilimumab. 11 patients have completed therapy and received all four induction doses. 9 patients discontinued therapy early and 2 patients were still actively receiving induction at the time of this analysis. A total of 63 doses were given. The maximum potential cost savings by giving ipilimumab to the nearest 50 mg over the period was 155,400. Conclusions Dose rounding of ipilimumab to the nearest 50 mg has the potential to result in a significant cost savings by eliminating drug waste.
Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion
Authors: Zhang YanPing , Kawedia Jitesh D , Myers Alan L , McIntyre Chelsey M , Anderson Peter M , Kramer Mark A , Culotta Kirk S 
Published: March 2013

Purpose Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. Methods Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. Results Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). Conclusions Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.
Oral chemotherapy handling and storage practices among Veterans Affairs oncology patients and caregivers
Authors: Trovato James A , Tuttle Laura A 
Published: March 2013

Purpose This questionnaire-based study was designed to identify the oral chemotherapy medication handling, storage, and disposal practices among cancer patients and their caregivers. Methods This was a single-center observational survey study approved by the Investigational Review Board and VA Research & Development Committee. Patients were eligible for inclusion if they had an active order for an oral antineoplastic medication and an appointment at the oncology clinic. A questionnaire related to the storage, handling, disposal, patient education and counseling, and patients’ perception of safety of oral antineoplastic medications was developed and given to patients in the clinic. Survey responses were analyzed using descriptive statistics. Results A total of 45 surveys were given to eligible patients in the oncology clinic and 42 surveys were returned to the study team. The majority, 40 participants (95%) were male. Participants ranged in age from 51 to 85 years (median, 65 years). Thirty-eight patients (90.5%) responded that the medication was stored away from extreme heat, cold, and humidity. Thirty-two patients (76%) reported keeping their medications in the original container. Hand washing was not a consistent practice among patients. Eleven patients (26%) reported always washing their hands after handling their anticancer medication; another 6 (14%) responded “sometimes”. Of the 42 participants who answered, only 6 patients (14%) reported always or sometimes wearing gloves. Conclusion The majority of patients responding to this survey store their oral anticancer medications appropriately, but patients’ and caregivers’ handling and disposal practices are inconsistent and frequently do not follow the published recommendations.
Non-negative matrix factorization by maximizing correntropy for cancer clustering
Authors: Wang Jim Jing-Yan , Wang Xiaolei , Gao Xin 
Published: March 2013

Abstract

Background
Non-negative matrix factorization (NMF) has been shown to be a powerful tool for clustering gene expression data, which are widely used to classify cancers. NMF aims to find two non-negative matrices whose product closely approximates the original matrix. Traditional NMF methods minimize either the l
2 norm or the Kullback-Leibler distance between the product of the two matrices and the original matrix. Correntropy was recently shown to be an effective similarity measurement due to its stability to outliers or noise.

Results
We propose a maximum correntropy criterion (MCC)-based NMF method (NMF-MCC) for gene expression data-based cancer clustering. Instead of minimizing the l
2 norm or the Kullback-Leibler distance, NMF-MCC maximizes the correntropy between the product of the two matrices and the original matrix. The optimization problem can be solved by an expectation conditional maximization algorithm.

Conclusions
Extensive experiments on six cancer benchmark sets demonstrate that the proposed method is significantly more accurate than the state-of-the-art methods in cancer clustering.
The pattern of Phosphate transporter 1 genes evolutionary divergence in Glycine maxL.
Authors: Fan Chengming , Wang Xu , Hu Ruibo , Wang Yahui , Xiao Chaowen , Jiang Ying , Zhang Xiaomei , Zheng Changying , Fu Yong-Fu 
Published: March 2013

Abstract

Background
The Phosphate transporter 1 (PHT1) gene family has crucial roles in phosphate uptake, translocation, remobilization, and optimization of metabolic processes using of Pi. Gene duplications expand the size of gene families, and subfunctionalization of paralog gene pairs is a predominant tendency after gene duplications. To date, experimental evidence for the evolutionary relationships among different paralog gene pairs of a given gene family in soybean is limited.

Results
All potential Phosphate transporter 1 genes in Glycine max L. (GmPHT1) were systematically analyzed using both bioinformatics and experimentation. The soybean PHT1 genes originated from four distinct ancestors prior to the Gamma WGT and formed 7 paralog gene pairs and a singleton gene. Six of the paralog gene pairs underwent subfunctionalization, and while GmPHT1;4 paralog gene experienced pseudogenization. Examination of long-term evolutionary changes, six GmPHT1 paralog gene pairs diverged at multiple levels, in aspects of spatio-temporal expression patterns and/or quanta, phosphates affinity properties, subcellular localization, and responses to phosphorus stress.

Conclusions
These characterized divergences occurred in tissue- and/or development-specific modes, or conditional modes. Moreover, they have synergistically shaped the evolutionary rate of GmPHT1 family, as well as maintained phosphorus homeostasis at cells and in the whole plant.
Plasmodium falciparum susceptibility to anti-malarial drugs in Dakar, Senegal, in 2010: an ex vivo and drug resistance molecular markers study
Authors: Fall Bécaye , Pascual Aurélie , Sarr Fatoumata D , Wurtz Nathalie , Richard Vincent , Baret Eric , Diémé Yaya , Briolant Sébastien , Bercion Raymond , Wade Boubacar , Tall Adama , Pradines Bruno 
Published: March 2013

Abstract

Background
In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, there have been very few reports on the level of resistance of P. falciparum to anti-malarial drugs. To determine whether parasite susceptibility has been affected by the new anti-malarial policies, an ex vivo susceptibility and drug resistance molecular marker study was conducted on local isolates obtained from the Centre de santé Elizabeth Diouf (Médina, Dakar, Senegal).

Methods
The prevalence of genetic polymorphisms in genes associated with anti-malarial drug resistance, i.e., pfcrt, pfdhfr, pfdhps and pfmdr1, were evaluated for a panel of 165 isolates collected from patients recruited from 17 August 2010 to 6 January 2011. The malaria isolates were assessed for susceptibility to chloroquine (CQ); quinine (QN); monodesethylamodiaquine (MDAQ), the active metabolite of amodiaquine; mefloquine (MQ); lumefantrine (LMF); dihydroartemisinin (DHA), the active metabolite of artemisinin derivatives; and doxycycline (DOX) using the Plasmodium lactate dehydrogenase (pLDH) ELISA.

Results
The prevalence of the in vitro resistant isolates, or isolates with reduced susceptibility, was 62.1% for MQ, 24.2% for CQ, 10.3% for DOX, 11.8% MDAQ, 9.7% for QN, 2.9% for LMF and 0% for DHA. The Pfcrt 76T mutation was identified in 43.6% of the samples. The pfmdr1 86Y, 184F and 1246Y mutations were found in 16.2%, 50.0% and 1.6% of the samples, respectively. The pfdhfr 108N, 51I and 59R mutations were identified in 81.9%, 77.4% and 79.4% of the samples, respectively. The double mutant (108N and 51I) was detected in 75.5% of the isolates, and the triple mutant (108N, 51I and 59R) was detected in 73.6% of the isolates. The pfdhps 437G, 436A and 613S mutations were found in 54.4%, 38.6% and 1.2% of the samples, respectively. There was only one double mutant, 437G and 540E, and one quintuple mutant, pfdhfr 108N, 51I and 59R and pfdhps 437G and 540E. The prevalence of the quadruple mutant (pfdhfr 108N, 51I and 59R and pfdhps 437G) was 36.7%.

Conclusions
The results of this study indicate that an intensive surveillance of the in vitro P. falciparum susceptibility to anti-malarial drugs must be conducted in Senegal.
The roles of integrin β1 in phenotypic maintenance and dedifferentiation in chondroid cells differentiated from human adipose-derived stem cells
Authors: Luo Simin , Shi Qiping , Zha Zhengang , Yao Ping , Lin Hongsheng , Liu Ning , Wu Hao , Cai Jiye , Sun Shangyun 
Published: March 2013

Abstract

Objective
The aim of this study is to probe the intrinsic mechanism of chondroid cell dedifferentiation in order to provide a feasible solution for this in cell culture.

Methods
Morphological and biomechanical properties of cells undergoing chondrogenic differentiation from human adipose-derived stem cells (ADSCs) were measured at the nanometer scale using atomic force microscopy and laser confocal scanning microscopy. Gene expression was determined by real-time quantitative polymerase chain reaction.

Results
The expression of COL II, SOX9, and Aggrecan mRNA began to increase gradually at the beginning of differentiation and reach a peak similar to that of normal chondrocytes on the 12th day, then dropped to the level of the 6th day at 18th day. Cell topography and mechanics trended resembled those of the genes’ expression. Integrin β1 was expressed in ADSCs and rapidly upregulated during differentiation but downregulated after reaching maturity.

Conclusions
The amount and distribution of integrin β1 may play a critical role in mediating both chondroid cell maturity and dedifferentiation. Integrin β1 is a possible new marker and target for phenotypic maintenance in chondroid cells.
Novel approaches to minimize ventilator-induced lung injury
Authors: Fan Eddy , Villar Jesus , Slutsky Arthur S 
Published: March 2013

Abstract
Despite over 40 years of research, there is no specific lung-directed therapy for the acute respiratory distress syndrome (ARDS). Although much has evolved in our understanding of its pathogenesis and factors affecting patient outcome, supportive care with mechanical ventilation remains the cornerstone of treatment. Perhaps the most important advance in ARDS research has been the recognition that mechanical ventilation, although necessary to preserve life, can itself aggravate or cause lung damage through a variety of mechanisms collectively referred to as ventilator-induced lung injury (VILI). This improved understanding of ARDS and VILI has been important in designing lung-protective ventilatory strategies aimed at attenuating VILI and improving outcomes. Considerable effort has been made to enhance our mechanistic understanding of VILI and to develop new ventilatory strategies and therapeutic interventions to prevent and ameliorate VILI with the goal of improving outcomes in patients with ARDS. In this review, we will review the pathophysiology of VILI, discuss a number of novel physiological approaches for minimizing VILI, therapies to counteract biotrauma, and highlight a number of experimental studies to support these concepts.