bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a synthetic single‐crystal diamond detector for relative dosimetry on the Leksell Gamma Knife Perfexion radiosurgery system
Authors: Mancosu Pietro , Reggiori Giacomo , Stravato Antonella , Gaudino Anna , Lobefalo Francesca , Palumbo Valentina , Navarria Piera , Ascolese Anna , Picozzi Piero , Marinelli Marco , Verona‐Rinati Gianluca , Tomatis Stefano , Scorsetti Marta 
Published: August 2015

Purpose:To evaluate the new commercial PTW‐60019 synthetic single‐crystal microDiamond detector (PTW, Freiburg, Germany) for relative dosimetry measurements on a clinical Leksell Gamma Knife Perfexion radiosurgery system.Methods:Detector output ratios (DORs) for 4 and 8 mm beams were measured using a microDiamond (PTW‐60019), a stereotactic unshielded diode [IBA stereotactic field detector (SFD)], a shielded diode (IBA photon field detector), and GafChromic EBT3 films. Both parallel and transversal acquisition directions were considered for PTW‐60019 measurements. Measured DORs were compared to the new output factor reference values for Gamma Knife Perfexion (0.814 and 0.900 for 4 and 8 mm, respectively). Profiles in the three directions were also measured for the 4 mm beam to evaluate full width at half maximum (FWHM) and penumbra and to compare them with the corresponding Leksell GammaPlan profiles.Results:FWHM and penumbra for PTW‐60019 differed from the calculated values by less than 0.2 and 0.3 mm, for the parallel and transversal acquisitions, respectively. GafChromic films showed FWHM and penumbra within 0.1 mm. The output ratio obtained with the PTW‐60019 for the 4 mm field was 1.6% greater in transverse direction compared to the nominal value. Comparable differences up to 0.8% and 1.0% for, respectively, GafChromic films and SFD were found.Conclusions:The microDiamond PTW‐60019 is a suitable detector for commissioning and routine use of Gamma Knife with good agreement of both DORs and profiles in the three directions.
Hybrid detection of lung nodules on CT scan images
Authors: Lu Lin , Tan Yongqiang , Schwartz Lawrence H. , Zhao Binsheng 
Published: August 2015

Purpose:The diversity of lung nodules poses difficulty for the current computer‐aided diagnostic (CAD) schemes for lung nodule detection on computed tomography (CT) scan images, especially in large‐scale CT screening studies. We proposed a novel CAD scheme based on a hybrid method to address the challenges of detection in diverse lung nodules.Methods:The hybrid method proposed in this paper integrates several existing and widely used algorithms in the field of nodule detection, including morphological operation, dot‐enhancement based on Hessian matrix, fuzzy connectedness segmentation, local density maximum algorithm, geodesic distance map, and regression tree classification. All of the adopted algorithms were organized into tree structures with multi‐nodes. Each node in the tree structure aimed to deal with one type of lung nodule.Results:The method has been evaluated on 294 CT scans from the Lung Image Database Consortium (LIDC) dataset. The CT scans were randomly divided into two independent subsets: a training set (196 scans) and a test set (98 scans). In total, the 294 CT scans contained 631 lung nodules, which were annotated by at least two radiologists participating in the LIDC project. The sensitivity and false positive per scan for the training set were 87% and 2.61%. The sensitivity and false positive per scan for the testing set were 85.2% and 3.13%.Conclusions:The proposed hybrid method yielded high performance on the evaluation dataset and exhibits advantages over existing CAD schemes. We believe that the present method would be useful for a wide variety of CT imaging protocols used in both routine diagnosis and screening studies.
Technical Note: Estimation of lung tumor thickness from planar dual‐energy kV images
Authors: Jung Frederick , Patel Rakesh , Campana Maria , Panfil Joshua , Pankuch Mark , Roeske John C. 
Published: August 2015

Purpose:Dual‐energy (DE) imaging is a method that suppresses bony anatomy on planar kV images while enhancing soft tissue contrast. This technique has been used specifically in the chest to improve the visualization of small lung tumors. However, DE imaging may also provide quantitative information that has not been previously investigated. In this study, the aim was to establish a theoretical relationship between DE image contrast and tumor thickness and to observe this trend in phantom experiments.Methods:A phantom consisting cork (used to simulate lung), tissue‐equivalent material, and pork ribs was constructed to test for a relationship between DE image contrast and simulated tumor thickness. Fifteen phantom setups were used with various thicknesses of cork and tissue‐equivalent material. For each setup, high (120 kVp) and low (60 kVp) energy planar images were acquired and DE images were produced. The image contrast between the simulated tumor and surrounding tissue was then plotted against the known thicknesses and a linear regression was performed.Results:A linear regression of the contrast data vs simulated tumor thickness resulted in a slope of −0.0454 with an R2 = 0.9904. The expected uncertainty in the thickness measurements using the regression parameters and DE contrast standard deviation was 0.13 cm.Conclusions:Phantom data exhibited a linear relationship between DE image contrast and simulated tumor thickness. Future studies will investigate patient‐specific parameters so that this method can be used clinically to evaluate tumor thickness from planar kV images. Such an approach may have benefits for both adaptive and heavy ion therapies.
Australia and Other Nations Are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward
Authors: Straker Leon , Howie Erin Kaye , Cliff Dylan Paul , Davern Melanie T. , Engelen Lina , Gomersall Sjaan R. , Ziviani Jenny , Schranz Natasha K. , Olds Tim , Tomkinson Grant Ryan 
Published: August 2015

Background:Australia has joined a growing number of nations that have evaluated the physical activity and sedentary behavior status of their children. Australia received a “D minus” in the first Active Healthy Kids Australia Physical Activity Report Card.Methods:An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer 3 questions: (a) What are the main sedentary behaviors of children? (b) What are the potential mechanisms for sedentary behavior to impact child health and development? and (c) What are the effects of different types of sedentary behaviors on child health and development?Results:Neither sedentary time nor screen time is a homogeneous activity likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviors may positively or negatively affect cardiometabolic, neuromusculoskeletal, and psychosocial health, though the strength of evidence varies. National surveillance systems and mechanistic, longitudinal, and experimental studies are needed for Australia and other nations to improve their grade.Conclusions:Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviors are critical to the healthy growth, development, and wellbeing of children. Nations therefore need strategies to address these common behaviors.
The Effects of 8-Week Plyometric Training on Physical Performance in Young Tennis Players
Authors: Fernandez-Fernandez Jaime , De Villarreal Eduardo Sáez , Sanz-Rivas David , Moya Manuel 
Published: August 2015

Objectives:The aim of this study was to analyze the effects of an 8-week (conducted biweekly for a total of 16 sessions) plyometric training program (PT) (e.g., upper- and lower-body exercises) combined with regular tennis training on physical qualities in young tennis players.Design:Sixty tennis players between the ages of 12 and 13 years (age 12.5 ± 0.3 years, weight 44.2 ± 7.0 kg, height 156.6 ± 7.1 cm) were allocated to either the control group (standard in-season regimen) (CG; n = 30) or the experimental group, which received an additional PT (TG; n = 30) for 30–60 min as a substitute for some tennis training within the usual 90-min practice.Methods:Pre- and posttests included: anthropometric measures; vertical countermovement jump (CMJ); standing long jump (SLJ); 20 m sprint time (with 5 and 10 m splits); a modified 505 agility test; overhead medicine ball throw; and serve velocity test.Results:After the training intervention, the TG showed significant (p < .01) improvements in all the parameters analyzed, with percentages of change and effect sizes ranging from 3.1% to 10.1% and 0.4 (small) to 1.3 (moderate), respectively. No significant changes were observed in the CG after the training intervention.Conclusions:PT was shown as an important stimulus for enhancing explosive actions in young tennis players.
The Development of Activity Profiles in Adolescent Females and their Association with Adiposity
Authors: Dowd Kieran , Harrington Deidre , Hannigan Ailish , Purtill Helen , Kelly Sarah M. , Macken Alan P. , Moyna Niall , O’Gorman Clodagh S. , Donnelly Alan E. 
Published: August 2015

Objectives:This study aims to (1) use the objective activPAL activity monitor to assess physical activity behaviors, including sitting/lying, standing, and both light (LIPA) and moderate-to-vigorous physical activity (MVPA); (2) to develop distinct activity profiles based on time spent in each behavior in a sample of adolescent females; and (3) examine whether levels of adiposity differ across these activity profiles.Methods:Female adolescents (n = 195; 14–18 y) had body mass index (median = 21.7 [IQR = 5.2] kg/m2) and 4-site skinfold thickness (median 62.0 mm; IQR = 37.1) measured. Physical activity behaviors were measured using the activPAL. Hierarchical cluster analysis grouped participants into activity profiles based on similar physical activity characteristics. Linear mixed models explored differences in body composition across activity profiles.Results:Three activity profiles were identified, a low (n = 35), moderate (n = 110), and a high activity profile (n = 50). Significant differences across activity profiles were observed for skinfold thickness (p = .046), with higher values observed in the low activity profile compared with the high activity profile.Conclusions:Profiling free-living activity using behaviors from across the activity intensity continuum may account for more of the variability in energy expenditure then examining specific activity intensities, such as MVPA alone. The use of activity profiles may enable the identification of individuals with unhealthy activity behaviors, leading to the development and implementation of more targeted interventions.
The reusable holdout: Preserving validity in adaptive data analysis
Authors: Dwork Cynthia , Feldman Vitaly , Hardt Moritz , Pitassi Toniann , Reingold Omer , Roth Aaron 
Published: August 2015

Testing hypotheses privatelyLarge data sets offer a vast scope for testing already-formulated ideas and exploring new ones. Unfortunately, researchers who attempt to do both on the same data set run the risk of making false discoveries, even when testing and exploration are carried out on distinct subsets of data. Based on ideas drawn from differential privacy, Dworket al.now provide a theoretical solution. Ideas are tested against aggregate information, whereas individual data set components remain confidential. Preserving that privacy also preserves statistical inference validity.Science, this issue p.636
Multivalent Pneumococcal Protein Vaccines Comprising Pneumolysoid with Epitopes/Fragments of CbpA and/or PspA Elicit Strong and Broad Protection
Authors: Chen Austen , Mann Beth , Gao Geli , Heath Richard , King Janice , Maissoneuve Jeff , Alderson Mark , Tate Andrea , Hollingshead Susan K. , Tweten Rodney K. , Briles David E. , Tuomanen Elaine I. , Paton James C. 
Published: August 2015

ABSTRACT

Immunization with the pneumococcal proteins pneumolysin (Ply), choline binding protein A (CbpA), or pneumococcal surface protein A (PspA) elicits protective responses against invasive pneumococcal disease in animal models. In this study, we used different mouse models to test the efficacy of a variety of multivalent protein-based vaccines that comprised various combinations of full-length or peptide regions of the immunogens Ply, CbpA, or PspA: Ply toxoid with the L460D substitution (referred to herein as L460D); L460D fused with protective peptide epitopes from CbpA (YPT-L460D-NEEK [YLN]); L460D fused with the CD2 peptide containing the proline-rich region (PRR) of PspA (CD2-L460D); a combination of L460D and H70 (L460D+H70), a slightly larger PspA-derived peptide containing the PRR and the SM1 region; H70+YLN; and other combinations. Each mouse was immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) with three doses (at 2-week intervals) of the various antigen combinations in alum adjuvant and then challenged in mouse models featuring different infection routes with multiple
Streptococcus pneumoniae
strains. In the i.p. infection sepsis model, H70+YLN consistently provided significant protection against three different challenge strains (serotypes 1, 2, and 6A); the CD2+YLN and H70+L460D combinations also elicited significant protection. Protection against intravenous (i.v.) sepsis (type 3 and 6A challenge strains) was largely dependent on PspA-derived antigen components, and the most protection was elicited by H70 with or without L460D or YLN. In a type 4 intratracheal (i.t.) challenge model that results in progression to meningitis, antigen combinations that contained YLN elicited the strongest protection. Thus, the trivalent antigen combination of H70+YLN elicited the strongest and broadest protection in diverse pneumococcal challenge models.
Quantitative Microplate-Based Growth Assay for Determination of Antifungal Susceptibility of Histoplasma capsulatum Yeasts
Authors: Goughenour Kristie D. , Balada-Llasat Joan-Miquel , Rappleye Chad A. 
Published: August 2015

ABSTRACT

Standardized methodologies for determining the antifungal susceptibility of fungal pathogens is central to the clinical management of invasive fungal disease. Yeast-form fungi can be tested using broth macrodilution and microdilution assays. Reference procedures exist for
Candida
species and
Cryptococcus
yeasts; however, no standardized methods have been developed for testing the antifungal susceptibility of yeast forms of the dimorphic systemic fungal pathogens. For the dimorphic fungal pathogen
Histoplasma capsulatum
, susceptibility to echinocandins differs for the yeast and the filamentous forms, which highlights the need to employ
Histoplasma
yeasts, not hyphae, in antifungal susceptibility tests. To address this, we developed and optimized methodology for the 96-well microtiter plate-based measurement of
Histoplasma
yeast growth
in vitro
. Using optical density, the assay is quantitative for fungal growth with a dynamic range greater than 30-fold. Concentration and assay reaction time parameters were also optimized for colorimetric (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction) and fluorescent (resazurin reduction) indicators of fungal vitality. We employed this microtiter-based assay to determine the antifungal susceptibility patterns of multiple clinical isolates of
Histoplasma
representing different phylogenetic groups. This methodology fulfills a critical need for the ability to monitor the effectiveness of antifungals on
Histoplasma
yeasts, the morphological form present in mammalian hosts and, thus, the form most relevant to disease.
Hepatitis C Virus Envelope Glycoprotein E1 Forms Trimers at the Surface of the Virion
Authors: Falson Pierre , Bartosch Birke , Alsaleh Khaled , Tews Birke Andrea , Loquet Antoine , Ciczora Yann , Riva Laura , Montigny Cédric , Montpellier Claire , Duverlie Gilles , Pécheur Eve-Isabelle , le Maire Marc , Cosset François-Loïc , Dubuisson Jean , Penin François 
Published: August 2015

ABSTRACT
In hepatitis C virus (HCV)-infected cells, the envelope glycoproteins E1 and E2 assemble as a heterodimer. To investigate potential changes in the oligomerization of virion-associated envelope proteins, we performed SDS-PAGE under reducing conditions but without thermal denaturation. This revealed the presence of SDS-resistant trimers of E1 in the context of cell-cultured HCV (HCVcc) as well as in the context of HCV pseudoparticles (HCVpp). The formation of E1 trimers was found to depend on the coexpression of E2. To further understand the origin of E1 trimer formation, we coexpressed in bacteria the transmembrane (TM) domains of E1 (TME1) and E2 (TME2) fused to reporter proteins and analyzed the fusion proteins by SDS-PAGE and Western blotting. As expected for strongly interacting TM domains, TME1–TME2 heterodimers resistant to SDS were observed. These analyses also revealed homodimers and homotrimers of TME1, indicating that such complexes are stable species. The N-terminal segment of TME1 exhibits a highly conserved GxxxG sequence, a motif that is well documented to be involved in intramembrane protein-protein interactions. Single or double mutations of the glycine residues (Gly354 and Gly358) in this motif markedly decreased or abrogated the formation of TME1 homotrimers in bacteria, as well as homotrimers of E1 in both HCVpp and HCVcc systems. A concomitant loss of infectivity was observed, indicating that the trimeric form of E1 is essential for virus infectivity. Taken together, these results indicate that E1E2 heterodimers form trimers on HCV particles, and they support the hypothesis that E1 could be a fusion protein.

IMPORTANCE
HCV glycoproteins E1 and E2 play an essential role in virus entry into liver cells as well as in virion morphogenesis. In infected cells, these two proteins form a complex in which E2 interacts with cellular receptors, whereas the function of E1 remains poorly understood. However, recent structural data suggest that E1 could be the protein responsible for the process of fusion between viral and cellular membranes. Here we investigated the oligomeric state of HCV envelope glycoproteins. We demonstrate that E1 forms functional trimers after virion assembly and that in addition to the requirement for E2, a determinant for this oligomerization is present in a conserved GxxxG motif located within the E1 transmembrane domain. Taken together, these results indicate that a rearrangement of E1E2 heterodimer complexes likely occurs during the assembly of HCV particles to yield a trimeric form of the E1E2 heterodimer. Gaining structural information on this trimer will be helpful for the design of an anti-HCV vaccine.
Identification of Host Cell Factors Associated with Astrovirus Replication in Caco-2 Cells
Authors: Murillo Andrea , Vera-Estrella Rosario , Barkla Bronwyn J. , Méndez Ernesto , Arias Carlos F. 
Published: August 2015

ABSTRACT

Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (
DHCR7
,
CYP51A1
) and fatty acid (
FASN
) synthesis, phosphatidylinositol (
PI4KIIIβ
) and inositol phosphate (
ITPR3
) metabolism, and RNA helicase activity (
DDX23
) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles.

IMPORTANCE
Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients. More recently, they have been associated with neurological diseases in mammals, including humans, and are also responsible for different pathologies in birds. In this work, we provide evidence that astrovirus RNA replication and virus assembly occur in contact with cell membranes potentially derived from multiple cell organelles and show that membrane-associated cellular proteins involved in lipid metabolism are required for efficient viral replication. Our findings provide information to enhance our knowledge of astrovirus biology and provide information that might be useful for the development of therapeutic interventions to prevent virus replication.
Turnover Rate of NS3 Proteins Modulates Bluetongue Virus Replication Kinetics in a Host-Specific Manner
Authors: Ftaich Najate , Ciancia Claire , Viarouge Cyril , Barry Gerald , Ratinier Maxime , van Rijn Piet A. , Breard Emmanuel , Vitour Damien , Zientara Stephan , Palmarini Massimo , Terzian Christophe , Arnaud Frédérick 
Published: August 2015

ABSTRACT

Bluetongue virus (BTV) is an arbovirus transmitted to livestock by midges of the
Culicoides
family and is the etiological agent of a hemorrhagic disease in sheep and other ruminants. In mammalian cells, BTV particles are released primarily by virus-induced cell lysis, while in insect cells they bud from the plasma membrane and establish a persistent infection. BTV possesses a ten-segmented double-stranded RNA genome, and NS3 proteins are encoded by segment 10 (Seg-10). The viral nonstructural protein 3 (NS3) plays a key role in mediating BTV egress as well as in impeding the
in vitro
synthesis of type I interferon in mammalian cells. In this study, we asked whether genetically distant NS3 proteins can alter BTV-host interactions. Using a reverse genetics approach, we showed that, depending on the NS3 considered, BTV replication kinetics varied in mammals but not in insects. In particular, one of the NS3 proteins analyzed harbored a proline at position 24 that leads to its rapid intracellular decay in ovine but not in
Culicoides
cells and to the attenuation of BTV virulence in a mouse model of disease. Overall, our data reveal that the genetic variability of Seg-10/NS3 differentially modulates BTV replication kinetics in a host-specific manner and highlight the role of the host-specific variation in NS3 protein turnover rate.

IMPORTANCE
BTV is the causative agent of a severe disease transmitted between ruminants by biting midges of
Culicoides
species. NS3, encoded by Seg-10 of the BTV genome, fulfills key roles in BTV infection. As Seg-10 sequences from various BTV strains display genetic variability, we assessed the impact of different Seg-10 and NS3 proteins on BTV infection and host interactions. In this study, we revealed that various Seg-10/NS3 proteins alter BTV replication kinetics in mammals but not in insects. Notably, we found that NS3 protein turnover may vary in ovine but not in
Culicoides
cells due to a single amino acid residue that, most likely, leads to rapid and host-dependent protein degradation. Overall, this study highlights that genetically distant BTV Seg-10/NS3 influence BTV biological properties in a host-specific manner and increases our understanding of how NS3 proteins contribute to the outcome of BTV infection.