bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypofractionated proton therapy for prostate cancer: Dose delivery uncertainty due to interfractional motion
Authors: Wang Yi , Efstathiou Jason A. , Lu Hsiao‐Ming , Sharp Gregory C. , Trofimov Alexei 
Published: June 2013

Purpose:The α‐to‐β (α/β) ratio for prostate tumor is likely lower than that for the surrounding normal organs, such as rectum and bladder (∼3 Gy). As a result, hypofractionation is expected to improve the therapeutic ratio in prostate radiation therapy. However, with the use of fewer, larger fractions, the accuracy of treatment dose delivery becomes more influenced by the physical uncertainties resulting from motion and radiobiological uncertainties in the α/β ratio of the prostate tumor. The purpose of this study is to evaluate the impact of interfractional motion on treatment dose delivery within the likely range of the tumor α/β ratio.Methods:Serial CT images acquired at simulation and daily treatment for three prostate patients were studied retrospectively. A conventional 3D‐conformal proton plan was created for each patient, delivering 25 fractions of 2 Gy to ITV1 (internal target volume, expanded from the prostate and clinically involved seminal vesicles) followed by 14 fractions to ITV2 (expanded from the prostate). The plans were renormalized for a series of hypofractionated protocols of between five and 28 fractions. The fractional doses were computed on daily CT and were mapped onto simulation CT using deformable registration. In each course, the doses from the fractions with the lowest D97% of the ITV2 were summed to approximate the lower limit (worst case) of target coverage. The uncertainty in dose and coverage was estimated as the deviation of the worst case from the nominal plan.Results:For treatments in 28 to five fractions, the uncertainty arising from interfractional motion ranged from ∼1% to 4% for V100% and ∼2% to 6% for D100% of the ITV2. The uncertainties in V95% and D95% were both minimal (<1%) for all protocols. For tumors with a low α/β of 1.0 Gy, the treatment in five fractions could deliver an additional 21.0 and 17.4 GyEQD2 to 95% and 100% of the ITV2, respectively, compared to that in 28 fractions. This advantage disappeared for tumors with α/β > 2.5 Gy, assuming the worst case for interfractional motion.Conclusions:In hypofractionated proton therapy for prostate cancer, the dosimetric uncertainties due to interfractional motion were minimal for the ITV2 coverage at 95% isodose level and the dose received by 95% of the ITV2. Although hypofractionation could yield an increase in equivalent dose to the target for tumors with low α/β, the gain was cancelled out by the uncertainty due to interfractional motion for tumors with α/β > 2.5 Gy.
Draft Genome Sequence of Streptococcus agalactiae PR06
Authors: MZ Irma Syakina , Teh L. K. , Salleh M. Z. 
Published: June 2013

ABSTRACT

Streptococcus agalactiae
(group B streptococcus [GBS]) is a Gram-positive bacterium that was first recognized as a causative agent of bovine mastitis.
S. agalactiae
has subsequently emerged as a significant cause of human diseases. Here, we report the draft genome sequence of
S. agalactiae
PR06, which was isolated from a septicemic patient in a local hospital in Malaysia.
Foot pronation is not associated with increased injury risk in novice runners wearing a neutral shoe: a 1-year prospective cohort study
Authors: Nielsen Rasmus Oestergaard , Buist Ida , Parner Erik Thorlund , Nohr Ellen Aagaard , Sørensen Henrik , Lind Martin , Rasmussen Sten 
Published: June 2013

ObjectiveTo investigate if running distance to first running-related injury varies between foot postures in novice runners wearing neutral shoes.DesignA 1-year epidemiological observational prospective cohort study.SettingDenmark.ParticipantsA total of 927 novice runners equivalent to 1854 feet were included. At baseline, foot posture on each foot was evaluated using the foot-posture index and categorised into highly supinated (n=53), supinated (n=369), neutral (n=1292), pronated (n=122) or highly pronated (n=18). Participants then had to start running in a neutral running shoe and to use global positioning system watch to quantify the running distance in every training session.Main outcome measureA running-related injury was defined as any musculoskeletal complaint of the lower extremity or back caused by running, which restricted the amount of running for at least 1 week.ResultsDuring 1 year of follow-up, the 1854 feet included in the analyses ran a total of 326 803 km until injury or censoring. A total of 252 participants sustained a running-related injury. Of these, 63 were bilateral injuries. Compared with a neutral foot posture, no significant body mass index-adjusted cumulative risk differences (RD) were found after 250 km of running for highly supinated feet (RD=11.0% (−10% to 32.1%), p=0.30), supinated feet (RD=−1.4% (−8.4% to 5.5%), p=0.69), pronated feet (RD=−8.1% (−17.6% to 1.3%), p=0.09) and highly pronated feet (RD=9.8% (−19.3% to 38.8%), p=0.51). In addition, the incidence-rate difference/1000 km of running, revealed that pronators had a significantly lower number of injuries/1000 km of running of −0.37 (−0.03 to −0.70), p=0.03 than neutrals.ConclusionsThe results of the present study contradict the widespread belief that moderate foot pronation is associated with an increased risk of injury among novice runners taking up running in a neutral running shoe. More work is needed to ascertain if highly pronated feet face a higher risk of injury than neutral feet.
miRNA Landscape in Stage I Epithelial Ovarian Cancer Defines the Histotype Specificities
Authors: Calura Enrica , Fruscio Robert , Paracchini Lara , Bignotti Eliana , Ravaggi Antonella , Martini Paolo , Sales Gabriele , Beltrame Luca , Clivio Luca , Ceppi Lorenzo , Di Marino Mariacristina , Fuso Nerini Ilaria , Zanotti Laura , Cavalieri Duccio , Cattoretti Giorgio , Perego Patrizia , Milani Rodolfo , Katsaros Dionyssios , Tognon Germana , Sartori Enrico , Pecorelli Sergio , Mangioni Costantino , D'Incalci Maurizio , Romualdi Chiara , Marchini Sergio 
Published: June 2013

Abstract
Purpose: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic diseases, with survival rate virtually unchanged for the past 30 years. EOC comprises different histotypes with molecular and clinical heterogeneity, but up till now the present gold standard platinum-based treatment has been conducted without any patient stratification. The aim of the present study is to generate microRNA (miRNA) profiles characteristic of each stage I EOC histotype, to identify subtype-specific biomarkers to improve our understanding underlying the tumor mechanisms.
Experimental Design: A collection of 257 snap-frozen stage I EOC tumor biopsies was gathered together from three tumor tissue collections and stratified into independent training (n = 183) and validation sets (n = 74). Microarray and quantitative real-time PCR (qRT-PCR) were used to generate and validate the histotype-specific markers. A novel dedicated resampling inferential strategy was developed and applied to identify the highest reproducible results. mRNA and miRNA profiles were integrated to identify novel regulatory circuits.
Results: Robust miRNA markers for clear cell and mucinous histotypes were found. Specifically, the clear cell histotype is characterized by a five-fold (log scale) higher expression of miR-30a and miR-30a*, whereas mucinous histotype has five-fold (log scale) higher levels of miR-192/194. Furthermore, a mucinous-specific regulatory loop involving miR-192/194 cluster and a differential regulation of E2F3 in clear cell histotype were identified.
Conclusions: Our findings showed that stage I EOC histotypes have their own characteristic miRNA expression and specific regulatory circuits. Clin Cancer Res; 19(15); 4114–23. ©2013 AACR.
Microglia and Interleukin-1β in Ischemic Retinopathy Elicit Microvascular Degeneration Through Neuronal Semaphorin-3A
Authors: Rivera José Carlos , Sitaras Nicholas , Noueihed Baraa , Hamel David , Madaan Ankush , Zhou Tianwei , Honoré Jean-Claude , Quiniou Christiane , Joyal Jean-Sébastien , Hardy Pierre , Sennlaub Florian , Lubell William , Chemtob Sylvain 
Published: June 2013

Objective—
Proinflammatory cytokines contribute to the development of retinal vasculopathies. However, the role of these factors and the mechanisms by which they elicit their effects in retina are not known. We investigated whether activated microglia during early stages of ischemic retinopathy produces excessive interleukin-1β (IL-1β), which elicits retinal microvascular degeneration not directly but rather by triggering the release of the proapoptotic/repulsive factor semaphorin-3A (Sema3A) from neurons.

Approach and Results—

Sprague Dawley rats subjected to retinopathy induced by hyperoxia (80% O
2
; O
2
-induced retinopathy) exhibited retinal vaso-obliteration associated with microglial activation, NLRP3 upregulation, and IL-1β and Sema3A release; IL-1β was mostly generated by microglia. Intraperitoneal administration of IL-1 receptor antagonists (Kineret, or rytvela [101.10]) decreased these effects and enhanced retinal revascularization; knockdown of Sema3A resulted in microvessel preservation and, conversely, administration of IL-1β caused vaso-obliteration. In vitro, IL-1β derived from activated primary microglial cells, cultured under hyperoxia, stimulated the release of Sema3A in retinal ganglion cells-5, which in turn induced apoptosis of microvascular endothelium; antagonism of IL-1 receptor decreased microglial activation and on retinal ganglion cells-5 abolished the release of Sema3A inhibiting ensuing endothelial cell apoptosis. IL-1β was not directly cytotoxic to endothelial cells.

Conclusions—

Our findings suggest that in the early stages of O
2
-induced retinopathy, retinal microglia are activated to produce IL-1β, which sustains the activation of microglia and induces microvascular injury through the release of Sema3A from adjacent neurons. Interference with IL-1 receptor or Sema3A actions preserves the microvascular bed in ischemic retinopathies and, consequently, decreases ensued pathological preretinal neovascularization.
Visual–Motor Interactions during Action Observation Are Shaped by Cognitive Context
Authors: Bortoletto Marta , Baker Katharine S. , Mattingley Jason B. , Cunnington Ross 
Published: June 2013

Abstract
Interactions between the visual system and the motor system during action observation are important for functions such as imitation and action understanding. Here, we asked whether such processes might be influenced by the cognitive context in which actions are performed. We recorded ERPs in a delayed go/no-go task known to induce bidirectional interference between the motor system and the visual system (visuomotor interference). Static images of hand gestures were presented as go stimuli after participants had planned either a matching (congruent) or nonmatching (incongruent) action. Participants performed the identical task in two different cognitive contexts: In one, they focused on the visual image of the hand gesture shown as the go stimulus (image context), whereas in the other, they focused on the hand gesture they performed (action context). We analyzed the N170 elicited by the go stimulus to test the influence of action plans on action observation (motor-to-visual priming). We also analyzed movement-related activity following the go stimulus to examine the influence of action observation on action planning (visual-to-motor priming). Strikingly, the context manipulation reversed the direction of the priming effects: We found stronger motor-to-visual priming in the action context compared with the image context and stronger visual-to-motor priming in the image context compared with the action context. Taken together, our findings indicate that neural interactions between motor and visual processes for executed and observed actions can change depending on task demands and are sensitive to top–down control according to the context.
Vascular Risk Moderates Associations between Hippocampal Subfield Volumes and Memory
Authors: Bender Andrew R. , Daugherty Ana M. , Raz Naftali 
Published: June 2013

Abstract
Advanced age and vascular risk negatively affect episodic memory. The hippocampus (HC) is a complex structure, and little is known about the roles of different HC regions in age-related memory declines. Using data from an ongoing longitudinal study, we investigated whether memory functions are related to volumes of specific HC subregions (CA1-2, CA3-4/dentate gyrus, and subiculum). Furthermore, we inquired if arterial hypertension, a common age-related vascular risk factor, modifies age-related differences in HC regional volumes, concurrent memory performance, and improvement in memory over multiple administrations. Healthy adults (n = 49, 52–82 years old) completed associative recognition and free recall tasks. In grouped path models, covariance structures differed between hypertensive and normotensive participants. Whereas larger CA3-4/dentate gyrus volumes predicted greater improvement in associative memory over repeated tests regardless of vascular risk, CA1-2 volumes were associated with improvement in noun recall only in hypertensive participants. Only among hypertensive participants, CA1-2 volumes negatively related to age and CA3-4/dentate gyrus and CA1-2 volumes were associated with performance at the last measurement occasion. These findings suggest that relatively small regions of the HC may play a role in age-related memory declines and that vascular risk factors associated with advanced age may modify that relationship.
Influence of display cabinet cooling on performance of supermarket buildings
Authors: Hill Frances , Edwards Rodger , Levermore Geoffrey 
Published: June 2013

Energy demand attributable to the operation of supermarkets is thought to be responsible for 1% of UK greenhouse gas emissions. Current building regulations in the UK require the “building related” energy use of new commercial buildings to comply with particular requirements. Supermarket buildings are therefore modelled in considerable detail, according to these protocols to establish their predicted energy demand. Lighting, occupancy, and small electrical energy impacts are included in this modelling. However, a large gap is found between the design outputs of this modelling and the energy performance of the store in operation. One reason for this is that thermal interactions at the refrigeration cabinets are not included in this modelling, as refrigeration is classified as “process energy” rather than “building related.” This paper explores the comparative energy demands of supermarket retail floors simulated both with and without the cooling effect of refrigeration cabinets included in the simulation. The retail floor of a recently built supermarket is modelled using EnergyPlus. Practical applications: It has been shown that the energy demand of the retail floor of a new store could be reduced by 25% by improvement of the envelope, by halving ventilation rates and doubling insulation levels. This has been shown by simulation of the building energy flows with refrigeration cabinets included in the modelling (whereas these are currently excluded as process energy). Changes in modelling protocols, and regulations, to encompass refrigeration energy transfers, could reduce the national load, due to supermarkets, by at least 140 MW in 5 years. Energy costs to the retailer would be reduced by 20%. Additionally, the simulation has shown the contribution of rooflights to the reduction of energy demand to be lower than previously predicted, saving only around 1/3 of design expectations.
The diagnostic role for susceptibility-weighted MRI during sporadic hemiplegic migraine
Authors: Fedak Erin M , Zumberge Nicholas A , Heyer Geoffrey L 
Published: June 2013

Background Hemiplegic migraine is a rare form of migraine with aura that includes motor weakness. Diagnosis during the first episode can be difficult to make and costly, especially with the sporadic form. Cases Our study evaluates the ictal magnetic resonance imaging (MRI) features of four sequential pediatric patients during a first-time, sporadic hemiplegic migraine. Susceptibility-weighted imaging (SWI) revealed cerebral venous prominence and increased magnetic susceptibility affecting brain regions that corresponded with each patient’s neurologic deficits. Repeat MRI (performed in three patients) following migraine recovery demonstrated resolution of all susceptibility abnormalities. Conclusion When combined with conventional MRI sequences, SWI has diagnostic value in the acute setting of motor weakness and with clinical features consistent with hemiplegic migraine. The sequence may help to further characterize ictal cerebral blood flow changes during the hemiplegic migraine aura.
Glucose-induced gradual phenotypic modulation of cultured human glomerular epithelial cells may be independent of Wilms’ tumor 1 (WT1)
Authors: Tsotakos Nikolaos E , Sagnou Marina , Kotsopoulou Eleni S , Tsilibary Effie C , Drossopoulou Garyfalia I 
Published: June 2013

Abstract

Background
Renal podocytes form the main filtration barrier possessing a unique phenotype maintained by proteins including podocalyxin and nephrin, the expression of which is suppressed in pathological conditions. We used an in vitro model of human glomerular epithelial cells (HGEC) to investigate the role of high glucose in dysregulating the podocytic epithelial phenotype and determined the time needed for this change to occur.

Results
In our in vitro podocyte system changes indicating podocyte dedifferentiation in the prolonged presence of high glucose included loss of podocalyxin, nephrin and CD10/CALLA concomitant with upregulation of mesenchymal vimentin. Our study demonstrates for the first time that podocyte-specific markers undergo changes of expression at different time intervals, since glucose-mediated podocalyxin downregulation is a progressive process that precedes downregulation of nephrin expression. Finally we demonstrate that high glucose permanently impaired WT1 binding to the podocalyxin gene promoter region but did not affect WT1 binding on the nephrin gene promoter region.

Conclusion
The presence of high glucose induced a phenotypic conversion of podocytes resembling partial dedifferentiation. Our study demonstrates that dysregulation of the normal podocytic phenotype is an event differentially affecting the expression of function-specific podocytic markers, exhibiting downregulation of the epithelial marker CD10/CALLA and PC first, followed by stably downregulated nephrin. Furthermore, it is herein suggested that WT1 may not be directly involved with upregulation of previously reduced PC and nephrin expression.
Boolean network-based model of the Bcl-2 family mediated MOMP regulation
Authors: Tokar Tomas , Turcan Zdenko , Ulicny Jozef 
Published: June 2013

Abstract

Background
Mitochondrial outer membrane permeabilization (MOMP) is one of the most important points in the majority of apoptotic signaling cascades and it is controlled by a network of interactions between the members of the Bcl-2 family.

Methods
To understand the role of individual members of this family within the MOMP regulation, we have constructed a Boolean network-based model of interactions between the Bcl-2 proteins.

Results
Computational simulations have revealed the existence of trapping states which, independently from the incoming stimuli, block the occurrence of MOMP. Our results emphasize the role of the antiapoptotic protein Mcl-1 in the majority of these configurations. We demonstrate here the importance of the Bid and Bim for activation of effectors Bax and Bak, and the irreversibility of this activation. The model further points to the antiapoptotic protein Bcl-w as a key factor preventing Bax activation.

Conclusions
In spite of relative simplicity, the Boolean network-based model provides useful insight into main functioning logic of the Bcl-2 switch, consistent with experimental findings.
Gene delivery in a mouse xenograft of a retargeted retrovirus to a solid 143B osteosarcoma
Authors: Zhang Xia , Sarangi Anindita , Wu Dai-Tze , Kanduri Jaya , Roth Monica J 
Published: June 2013

Abstract

Background
Osteosarcomas are the most common primary bone malignancies found in children and adolescents. An optimized system was developed for efficient retroviral gene delivery into solid 143B osteosarcoma tumors in mice using a retargeted Env. In these studies, the viral Env CP was isolated from an in vitro screen of a library of feline leukemia virus Env randomized in the receptor-binding domain and maintained high titer on human 143B osteosarcoma cell line.

Findings
The vector developed to express the random Env libraries encoded the drug selectable marker neo. To adapt this for studies in live animals, the murine based vector was modified to express the luciferase gene. The bicistronic vector developed expressed both the CP Env and luciferase in the presence of either the MPMV CTE or a WPRE element. Virus bearing the CP FeLV Env variant maintained high titers after concentration allowing for direct visualization of delivery of the luciferase gene in subcutaneous 143B osteosarcoma tumors.

Conclusion
This system serves as a proof-of-concept for the use of novel FeLV Env pseudotyped MLV particles for in vivo gene delivery. Gene delivery and expression of lucerifase from viral particles bearing the CP Env was readily detected in live mice after a single round of intratumor injection.