bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implication of spot position error on plan quality and patient safety in pencil‐beam‐scanning proton therapy
Authors: Yu Juan , Beltran Chris J. , Herman Michael G. 
Published: July 2014

Purpose:To quantitatively and systematically assess dosimetric effects induced by spot positioning error as a function of spot spacing (SS) on intensity‐modulated proton therapy (IMPT) plan quality and to facilitate evaluation of safety tolerance limits on spot position.Methods:Spot position errors (PE) ranging from 1 to 2 mm were simulated. Simple plans were created on a water phantom, and IMPT plans were calculated on two pediatric patients with a brain tumor of 28 and 3 cc, respectively, using a commercial planning system. For the phantom, a uniform dose was delivered to targets located at different depths from 10 to 20 cm with various field sizes from 22 to 152 cm2. Two nominal spot sizes, 4.0 and 6.6 mm of 1 σ in water at isocenter, were used for treatment planning. The SS ranged from 0.5 σ to 1.5 σ, which is 2–6 mm for the small spot size and 3.3–9.9 mm for the large spot size. Various perturbation scenarios of a single spot error and systematic and random multiple spot errors were studied. To quantify the dosimetric effects, percent dose error (PDE) depth profiles and the value of percent dose error at the maximum dose difference (PDE [ΔDmax]) were used for evaluation.Results:A pair of hot and cold spots was created per spot shift. PDE[ΔDmax] is found to be a complex function of PE, SS, spot size, depth, and global spot distribution that can be well defined in simple models. For volumetric targets, the PDE [ΔDmax] is not noticeably affected by the change of field size or target volume within the studied ranges. In general, reducing SS decreased the dose error. For the facility studied, given a single spot error with a PE of 1.2 mm and for both spot sizes, a SS of 1σ resulted in a 2% maximum dose error; a SS larger than 1.25 σ substantially increased the dose error and its sensitivity to PE. A similar trend was observed in multiple spot errors (both systematic and random errors). Systematic PE can lead to noticeable hot spots along the field edges, which may be near critical structures. However, random PE showed minimal dose error.Conclusions:Dose error dependence for PE was quantitatively and systematically characterized and an analytic tool was built to simulate systematic and random errors for patient‐specific IMPT. This information facilitates the determination of facility specific spot position error thresholds.
Direct Inhibition of Choline Kinase by a Near-Infrared Fluorescent Carbocyanine
Authors: Arlauckas Sean P. , Popov Anatoliy V. , Delikatny Edward J. 
Published: July 2014

AbstractCholine kinase alpha (ChoK) expression is increasingly being recognized as an important indicator of breast cancer prognosis; however, previous efforts to noninvasively measure ChoK status have been complicated by the spectral limitations of in vivo magnetic resonance spectroscopy (MRS) and the complex network of enzymes involved in choline metabolism. The most effective ChoK inhibitors are symmetric and contain quaternary ammonium groups within heterocyclic head groups connected by an aliphatic spacer. Characterization of these bis-pyridinium and bis-quinolinium compounds has led to phase I clinical trials to assess small-molecule inhibitors of ChoK for solid tumor treatment. We report the development of a novel carbocyanine dye, JAS239, whose bis-indolium structure conforms to the parameters established for ChoK specificity and whose spacer length confers fluorescence in the near-infrared (NIR) window. Fluorimetry and confocal microscopy were used to demonstrate that JAS239 rapidly enters breast cancer cells independent of the choline transporters, with accumulation in the cytosolic space where ChoK is active. Radio-tracing and 1H MRS techniques were used to determine that JAS239 binds and competitively inhibits ChoK intracellularly, preventing choline phosphorylation while inducing cell death in breast cancer cell lines with similar efficacy to known ChoK inhibitors. Fluorescent molecules that report on ChoK status have potential use as companion diagnostics for noninvasive breast tumor staging, because NIR fluorescence allows for detection of real-time probe accumulation in vivo. Furthermore, their ability as novel ChoK inhibitors may prove effective against aggressive, therapy-resistant tumors. Mol Cancer Ther; 13(9); 2149–58. ©2014 AACR.
Identification of Kv11.1 Isoform Switch as a Novel Pathogenic Mechanism of Long-QT Syndrome
Authors: Gong Qiuming , Stump Matthew R. , Deng Vivianne , Zhang Li , Zhou Zhengfeng 
Published: July 2014

Background—

The
KCNH2
gene encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier current in the heart. The relative expression of the full-length Kv11.1a isoform and the C-terminally truncated Kv11.1a-USO isoform plays an important role in regulation of channel function. The formation of C-terminal isoforms is determined by competition between the splicing and alternative polyadenylation of
KCNH2
intron 9. It is not known whether changes in the relative expression of Kv11.1a and Kv11.1a-USO can cause long-QT syndrome.

Methods and Results—

We identified a novel
KCNH2
splice site mutation in a large family. The mutation, IVS9-2delA, is a deletion of the A in the AG dinucleotide of the 3′ acceptor site of intron 9. We designed an intron-containing full-length
KCNH2
gene construct to study the effects of the mutation on the relative expression of Kv11.1a and Kv11.1a-USO at the mRNA, protein, and functional levels. We found that this mutation disrupted normal splicing and resulted in exclusive polyadenylation of intron 9, leading to a switch from the functional Kv11.1a to the nonfunctional Kv11.1a-USO isoform in HEK293 cells and HL-1 cardiomyocytes. We also showed that IVS9-2delA caused isoform switch in the mutant allele of mRNA isolated from patient lymphocytes.

Conclusions—
Our findings indicate that the IVS9-2delA mutation causes a switch in the expression of the functional Kv11.1a isoform to the nonfunctional Kv11.1a-USO isoform. Kv11.1 isoform switch represents a novel mechanism in the pathogenesis of long-QT syndrome.
Socioeconomic Status Inconsistency and Risk of Stroke Among Japanese Middle-Aged Women
Authors: Honjo Kaori , Iso Hiroyasu , Inoue Manami , Sawada Norie , Tsugane Shoichiro 
Published: July 2014

Background and Purpose—
Little research has been conducted to examine the effect of inconsistencies in socioeconomic status on cardiovascular health. In particular, no studies have been reported in Asian countries, including Japan, which is thought to have high socioeconomic status inconsistency among women.

Methods—
We examined the effect of status inconsistency between education level and occupation on stroke risk in a prospective 20-year study of 14 742 middle-aged Japanese women included in the prospective Japan Public Health Center-based (JPHC) Study Cohort I in 1990. Status inconsistency between education level and occupation was determined (qualified, overqualified, and underqualified), and the association with risk of stroke was examined. Cox proportional regression analysis was used to determine hazard ratios, which were adjusted for age, marital status, and geographical area.

Results—
Adjusted hazard ratio for stroke in overqualified compared with qualified women was 2.06 (95% confidence interval, 1.13–3.78). Adjusted hazard ratios for stroke among highly educated manual workers and workers in service industry were 3.47 (95% confidence interval, 1.54–7.84) and 3.21 (95% confidence interval, 1.49–6.90), respectively, when compared with highly educated professionals/managers.

Conclusions—
High academic qualifications without an appropriate job could be a risk factor for stroke among Japanese women. Our result suggests that status inconsistency could be a potential explanation for the increased stroke risk among highly educated women.
Morphology of Susceptibility Vessel Sign Predicts Middle Cerebral Artery Recanalization After Intravenous Thrombolysis
Authors: Yan Shenqiang , Hu Haitao , Shi Zhenghao , Zhang Xuting , Zhang Sheng , Liebeskind David S. , Lou Min 
Published: July 2014

Background and Purpose—
We aimed to evaluate the predictive value of susceptibility vessel sign (SVS) burden and morphology in middle cerebral artery recanalization.

Methods—
We retrospectively examined clinical and imaging data from 72 consecutive patients with acute ischemic stroke with middle cerebral artery occlusion and examined the association of recanalization with SVS length and shape.

Results—

None of the patients with a middle cerebral artery SVS >20 mm in length achieved recanalization. For patients with a relatively short SVS (length <20 mm), irregular shape was a strong independent predictor for no recanalization (odds ratio, 6.891; 95% confidence interval, 1.441–32.950;
P
=0.016).

Conclusions—
Irregular shape and long length (>20 mm) of SVS decrease the potential to recanalize the occluded middle cerebral artery with intravenous thrombolysis.
Experiments on Differential Scalar Mixing in Turbulence in a Sheared, Stratified Flow
Authors: Jackson P. Ryan , Rehmann Chris R. 
Published: July 2014

Abstract
Laboratory experiments were performed to measure differential diffusion of temperature and salinity across a sheared density interface. The eddy diffusivity of temperature KT exceeded the eddy diffusivity of salinity KS by as much as 1.5 orders of magnitude at low ε/νN2, where ε is the rate of dissipation of turbulent kinetic energy, ν is the kinematic viscosity, and N is the buoyancy frequency in the pycnocline. The diffusivity ratio d = KS/KT increased from about 0.05 to 1 over the range 0.1 &lt; ε/νN2 &lt; 40. These differences made the eddy diffusivity of density depend on the density ratio. The trend of d with ε/νN2 was consistent with trends found in other experiments, simulations, and theory, and the collapse of several datasets allowed the diffusivity ratio to be expressed as a function of ε/νN2. However, shear decreased differential diffusion less in the experiments than predicted by theory for homogeneous turbulence subjected to constant shear and stratification. No strong effect of the density ratio on the diffusivity ratio was apparent. Because many flows in oceanography and limnology have values of ε/νN2 low enough to exhibit significant differential diffusion, accounting for differential diffusion in interpreting measurements and modeling stratified water bodies is recommended.
Influence of the Barotropic Mean Flow on the Width and the Structure of the Atlantic Equatorial Deep Jets
Authors: Claus Martin , Greatbatch Richard J. , Brandt Peter 
Published: July 2014

AbstractA representation of an equatorial basin mode excited in a shallow-water model for a single high-order baroclinic vertical normal mode is used as a simple model for the equatorial deep jets. The model is linearized about both a state of rest and a barotropic mean flow corresponding to the observed Atlantic Equatorial Intermediate Current System. It was found that the eastward mean flow associated with the North and South Intermediate Counter Currents (NICC and SICC, respectively) effectively shields the equator from off-equatorial Rossby waves. The westward propagation of these waves is blocked, and focusing on the equator due to beta dispersion is prevented. This leads to less energetic jets along the equator. On the other hand, the westward barotropic mean flow along the equator reduces the gradient of absolute vorticity and hence widens the cross-equatorial structure of the basin mode. Increasing lateral viscosity predominantly affects the width of the basin modes’ Kelvin wave component in the presence of the mean flow, while the Rossby wave is confined by the flanking NICC and SICC. Independent of the presence of the mean flow, the application of sufficient lateral mixing also hinders the focusing of off-equatorial Rossby waves, which is hence an unlikely feature of a low-frequency basin mode in the real ocean.
Development of a non-dairy probiotic fermented product based on almond milk and inulin
Authors: Bernat Neus , Cháfer Maite , Chiralt Amparo , González-Martínez Chelo 
Published: July 2014

A new fermented almond “ milk” that combined the properties of both almonds and probiotics was considered to cover the current versatile health-promoting foods’ demand. Almond milk fermentation with probiotic Lactobacillus reuteri and Streptococcus thermophilus was studied by using a Central Composite design with response surface methodology, and different factors (glucose, fructose, inulin and starters) were optimised to assure high probiotic survivals in the final product. The optimal formulation was physicochemically characterised throughout cold storage (28 days) and both probiotic survivals to in vitro digestion and proteolysis were quantified. Results showed that a high probiotic population (>107 cfu/mL) was obtained in the previously optimised almond milk throughout storage time, which correspond to the addition of 0.75 g of glucose/100 mL, 0.75 g of fructose/100 mL, 2 g/100 mL inulin and 6 mL/100 mL inoculum. Glucose was used as the main nutrient and the production of mannitol by L. reuteri was detected. The fermentation process increased the viscosity values, forming a weak gel structure, whose physical properties hardly changed. Probiotic bacteria notably survived (51%) to the in vitro digestion, surely related to the inulin presence, which would add value to the developed product by enhancing the potential health benefits of its consumption.
Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus
Authors: Dimopoulos Meletios A. , Kastritis Efstathios , Owen Roger G. , Kyle Robert A. , Landgren Ola , Morra Enrica , Leleu Xavier , García-Sanz Ramón , Munshi Nikhil , Anderson Kenneth C. , Terpos Evangelos , Ghobrial Irene M. , Morel Pierre , Maloney David , Rummel Mathias , Leblond Véronique , Advani Ranjana H. , Gertz Morie A. , Kyriakou Charalampia , Thomas Sheeba K. , Barlogie Bart , Gregory Stephanie A. , Kimby Eva , Merlini Giampaolo , Treon Steven P. 
Published: July 2014

Abstract
Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.
RETRACTED ARTICLE: Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats
Authors: Ahmed Danish , Kumar Vikas , Verma Amita , Gupta Pushpraj S , Kumar Hemant , Dhingra Vishal , Mishra Vatsala , Sharma Manju 
Published: July 2014

Abstract
Background
Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats.

Methods
The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats.

Results
Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p < 0.05) decreased the level of TC, TG, and LDL-c, VLDL-c. While it increases the level of HDL-c to a significant (p < 0.05) level. The treatment also resulted in a marked increase in reduced glutathione, glutathione Peroxidase, catalase and superoxide dismutase and diminished level of lipid peroxidation in liver and kidney of STZ induced diabetic rats. Histopathological studies suggest the diminution in the pancreatic, liver and cardiac muscle damage.

Conclusion
Our research exertion clearly indicates the considerable antihyperglycemic, antihyperlipidemic, antioxidant & pancreas/renal/hepatic/cardiac protective action of ALEx.
Sublobar resection versus lobectomy in solid-type, clinical stage IA, non-small cell lung cancer
Authors: Jeon Hyun Woo , Kim Young-Du , Kim Kyung Soo , Sung Sook Whan , Park Hyung Joo , Park Jae Kil 
Published: July 2014

Abstract

Background
Recent studies have demonstrated that sublobar resection is not inferior to lobectomy for peripheral early lung cancer with ground-glass opacification. However, the effect of sublobar resection on solid-type early lung cancer is controversial. The aim of this study was to compare clinical outcomes of patients who have undergone sublobar resection or lobectomy for solid-type, early-stage, non-small cell lung cancer (NSCLC).

Methods
This study was a retrospective review of the records of patients who underwent lobectomy or sublobar resection between March 2000 and September 2010 for clinical stage IA NSCL. Patients with pure ground-glass opacities or death within 30 days after surgery were excluded. Disease-free interval, survival, and prognostic factors were analyzed.

Results
Thirty-one patients and 133 patients underwent sublobar resection and lobectomy, respectively. There were significant differences in age (P <0.001), cardiovascular disease (P = 0.001), and diffusing capacity of the lung for carbon monoxide (DLCO) (P <0.001). The patients with lobectomy had a significantly longer disease-free interval (P <0.001) and survival (P = 0.001). By multivariate analysis, sublobar resection (P = 0.011), lymphatic vessel invasion (P = 0.006), and number of positive lymph nodes (P = 0.028) were predictors for survival. Sublobar resection (P <0.001), visceral pleural invasion (P = 0.002), and lymphatic vessel invasion (P <0.001) were predictors for disease-free interval.

Conclusions
Lobectomy should remain the standard surgical procedure for solid-type, clinical stage IA, NSCLC.
Targeting of viral interleukin-10 with an antibody fragment specific to damaged arthritic cartilage improves its therapeutic potency
Authors: Hughes Chris , Sette Angelica , Seed Michael , D’Acquisto Fulvio , Manzo Antonio , Vincent Tonia L , Lim Ngee Han , Nissim Ahuva 
Published: July 2014

Abstract
Introduction
We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to demonstrate the superior efficacy of anti-inflammatory cytokines when targeted to inflamed arthritic joints by the anti-ROS modified CII (anti-ROS-CII) scFv in a mouse model of arthritis.

Methods
Viral interleukin-10 (vIL-10) was fused to anti-ROS-CII scFv (1-11E) with a matrix-metalloproteinase (MMP) cleavable linker to create 1-11E/vIL-10 fusion. Binding of 1-11E/vIL-10 to ROS-CII was determined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immune-staining of arthritic cartilage, whereas vIL-10 bioactivity was evaluated in vitro by using an MC-9 cell-proliferation assay. Specific in vivo localization and therapeutic efficacy of 1-11E/vIL-10 was tested in the mouse model of antigen-induced arthritis.

Results
1-11E/vIL-10 bound specifically to ROS-CII and to damaged arthritic cartilage. Interestingly, the in vitro vIL-10 activity in the fusion protein was observed only after cleavage with MMP-1. When systemically administered to arthritic mice, 1-11E/vIL-10 localized specifically to the arthritic knee, with peak accumulation observed after 3 days. Moreover, 1-11E/vIL-10 reduced inflammation significantly quicker than vIL-10 fused to the control anti-hen egg lysozyme scFv (C7/vIL10).

Conclusions
Targeted delivery of anti-inflammatory cytokines potentiates their anti-arthritic action in a mouse model of arthritis. Our results further support the hypothesis that targeting biotherapeutics to arthritic joints may be extended to include anti-inflammatory cytokines that lack efficacy when administered systemically.
Albumin administration in the acutely ill: what is new and where next?
Authors: Vincent Jean-Louis , Russell James A , Jacob Matthias , Martin Greg , Guidet Bertrand , Wernerman Jan , Roca Ricard Ferrer , McCluskey Stuart A , Gattinoni Luciano 
Published: July 2014

AbstractAlbumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has become the subject of criticism and debate in more recent years. Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of patients are most likely to benefit from their use. However, many questions remain related to where exactly albumin fits within our fluid choices. Here, we briefly summarize some of the physiology and history of albumin use in intensive care before offering some evidence-based guidance for albumin use in critically ill patients.