bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging
Authors: Russo Paolo , Curion Assunta S. , Mettivier Giovanni , Esposito Michela , Aurilio Michela , Caracò Corradina , Aloj Luigi , Lastoria Secondo 
Published: March 2011

Purpose:The authors assembled a prototype compact gamma‐ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera.Methods:The room‐temperature CdTe pixel detector (1 mm thick) has square pixels arranged with a pitch (sensitive area ), coupled pixel‐by‐pixel via bump‐bonding to the Medipix2 photon‐counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife‐edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin‐to‐collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low‐energy threshold of about 20 keV.Results:For, at 50 mm distance, a background‐subtracted sensitivity of and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq and prior localization with standard gamma camera lymphoscintigraphy.Conclusions:The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.
On the relationships between electron spot size, focal spot size, and virtual source position in Monte Carlo simulations
Authors: Sterpin E. , Chen Y. , Lu W. , Mackie T. R. , Olivera G. H. , Vynckier S. 
Published: March 2011

Purpose:Every year, new radiotherapy techniques including stereotactic radiosurgery using linear accelerators give rise to new applications of Monte Carlo (MC) modeling. Accurate modeling requires knowing the size of the electron spot, one of the few parameters to tune in MC models. The resolution of integrated megavoltage imaging systems, such as the tomotherapy system, strongly depends on the photon spot size which is closely related to the electron spot. The aim of this article is to clarify the relationship between the electron spot size and the photon spot size (i.e., thefocal spot size) for typical incident electron beam energies and target thicknesses.Methods:Three electron energies (3, 5.5, and 18 MeV), four electron spot sizes (, 0.5, 1, and 1.5 mm), and two tungsten target thicknesses (0.15 and 1 cm) were considered. The formation of the photon beam within the target was analyzed through electron energy deposition with depth, as well as photon production at several phase‐space planes placed perpendicular to the beam axis, where only photons recorded for the first time were accounted for. Photon production was considered for “newborn” photons intersecting a plane at the isocenter (85 cm from source). Finally, virtual source position and “effective” focal spot size were computed by backprojecting all the photons from the bottom of the target intersecting a plane. The virtual source position and focal spot size were estimated at the plane position where the latter is minimal.Results:In the relevant case of considering only photons intersecting the plane, the results unambiguously showed that the effective photon spot is created within the first 0.25 mm of the target and that electron and focal spots may be assumed to be equal within 3–4%.Conclusions:In a good approximation photon spot size equals electron spot size for high energy X‐ray treatments delivered by linear accelerators.
Investigation of a breathing surrogate prediction algorithm for prospective pulmonary gating
Authors: White Benjamin M. , Low Daniel A. , Zhao Tianyu , Wuenschel Sara , Lu Wei , Lamb James M. , Mutic Sasa , Bradley Jeffrey D. , El Naqa Issam 
Published: March 2011

Purpose:A major challenge of four dimensional computed tomography (4DCT) in treatment planning and delivery has been the lack of respiration amplitude and phase reproducibility during image acquisition. The implementation of a prospective gating algorithm would ensure that images would be acquired only during user‐specified breathing phases. This study describes the development and testing of an autoregressive moving average (ARMA) model for human respiratory phase prediction under quiet respiration conditions.Methods:A total of 47 4DCT patient datasets and synchronized respiration records was utilized in this study. Three datasets were used in model development and were removed from further evaluation of the ARMA model. The remaining 44 patient datasets were evaluated with the ARMA model for prediction time steps from 50 to 1000 ms in increments of 50 and 100 ms. Thirty‐five of these datasets were further used to provide a comparison between the proposed ARMA model and a commercial algorithm with a prediction time step of 240 ms.Results:The optimal number of parameters for the ARMA model was based on three datasets reserved for model development. Prediction error was found to increase as the prediction time step increased. The minimum prediction time step required for prospective gating was selected to be half of the gantry rotation period. The maximum prediction time step with a conservative 95% confidence criterion was found to be 0.3 s. The ARMA model predicted peak inhalation and peak exhalation phases significantly better than the commercial algorithm. Furthermore, the commercial algorithm had numerous instances of missed breath cycles and falsely predicted breath cycles, while the proposed model did not have these errors.Conclusions:An ARMA model has been successfully applied to predict human respiratory phase occurrence. For a typical CT scanner gantry rotation period of 0.4 s (0.2 s prediction time step), the absolute error was relatively small, at peak inhalation and at peak exhalation. The application of the ARMA model for prospective pulmonary gating has been demonstrated.
Patient radiation dose audits for fluoroscopically guided interventional procedures
Authors: Balter Stephen , Rosenstein Marvin , Miller Donald L. , Schueler Beth , Spelic David 
Published: March 2011

Purpose:Quality management for any use of medical x‐ray imaging should include monitoring of radiation dose. Fluoroscopically guided interventional (FGI) procedures are inherently clinically variable and have the potential for inducing deterministic injuries in patients. The use of a conventional diagnostic reference level is not appropriate for FGI procedures. A similar but more detailed quality process for management of radiation dose in FGI procedures is described.Methods:A method that takes into account both the inherent variability of FGI procedures and the risk of deterministic injuries from these procedures is suggested. The substantial radiation dose level (SRDL) is an absolute action level (with regard to patient follow‐up) below which skin injury is highly unlikely and above which skin injury is possible. The quality process for FGI procedures collects data from all instances of a given procedure from a number of facilities into an advisory data set (ADS). An individual facility collects a facility data set (FDS) comprised of all instances of the same procedure at that facility. The individual FDS is then compared to the multifacility ADS with regard to the overall shape of the dose distributions and the percent of instances in both the ADS and the FDS that exceed the SRDL.Results:Samples of an ADS and FDS for percutaneous coronary intervention, using the dose metric of reference air kerma (i.e., the cumulative air kerma at the reference point), are used to illustrate the proposed quality process for FGI procedures. Investigation is warranted whenever the FDS is noticeably different from the ADS for the specific FGI procedure and particularly in two circumstances: (1) When the facility's local median exceeds the 75th percentile of the ADS and (2) when the percent of instances where exceeds the facility‐selected SRDL is greater for the FDS than for the ADS.Conclusions:Analysis of the two data sets (ADS and FDS) and of the percent of instances that exceed the SRDL provides a means for the facility to better manage radiation dose (and therefore both deterministic and stochastic radiation risk) to the patient during FGI procedures.
Quantification of prostate deformation due to needle insertion during TRUS‐guided biopsy: Comparison of hand‐held and mechanically stabilized systems
Authors: De Silva Tharindu , Fenster Aaron , Bax Jeffrey , Romagnoli Cesare , Izawa Jonathan , Samarabandu Jagath , Ward Aaron D. 
Published: March 2011

Purpose:Prostate biopsy is the clinical standard for the definitive diagnosis of prostate cancer. To overcome the limitations of 2D TRUS‐guided biopsy systems when targeting preplanned locations, systems have been developed with 3D guidance to improve the accuracy of cancer detection. Prostate deformation due to needle insertion and biopsy gun firing is a potential source of error that can cause target misalignments during biopsies.Methods:The authors used nonrigid registration of 2D TRUS images to quantify the deformation that occurs during the needle insertion and the biopsy gun firing procedure and compare this effect in biopsies performed using a hand‐held TRUS probe to those performed using a mechanically assisted 3D TRUS‐guided biopsy system. The authors calculated a spatially varying 95% confidence interval on the prostate tissue motion and analyzed this motion both as a function of distance to the biopsy needle and as a function of distance to the lower piercing point of the prostate. The former is relevant because biopsy targets lie along the needle axis, and the latter is of particular importance due to the reported high concentration of prostate cancer in the peripheral zone, a substantial portion of which lies on the posterior side of the prostate where biopsy needles enter the prostate after penetrating the rectal wall during transrectal biopsy.Results:The results show that for both systems, the tissue deformation is such that throughout the length of the needle axis, including regions proximal to the lower piercing point, spherical tumors with a radius of 2.1 mm or more can be sampled with 95% confidence under the assumption of zero error elsewhere in the biopsy system. More deformation was observed in the direction orthogonal to the needle axis compared to the direction parallel to the needle axis; this is of particular importance given the long, narrow shape of the biopsy core. The authors measured lateral tissue motion proximal to the needle axis of not more than 1.5 mm, with 95% confidence. The authors observed a statistically significant and clinically insignificant maximum difference of 0.38 mm in the deformation, resulting from the hand‐held and mechanically assisted systems along the needle axis, and the mechanical system resulted in a lower relative increase in deformation proximal to the needle axis during needle insertion, as well as lower variability of deformation during biopsy gun firing.Conclusions:Given the clinical need to biopsy tumors of volume greater than or equal to, corresponding to spherical tumors with a radius of 5 mm or more, the tissue motion induced by needle insertion and gun firing is an important consideration when setting the design specifications for TRUS‐guided prostate biopsy systems.
Longitudinal Analysis of Pneumococcal Antibodies during Community-Acquired Pneumonia Reveals a Much Higher Involvement of Streptococcus pneumoniae than Estimated by Conventional Methods Alone
Authors: van Mens Suzan P. , Meijvis Sabine C. A. , Endeman Henrik , van Velzen-Blad Heleen , Biesma Douwe H. , Grutters Jan C. , Vlaminckx Bart J. M. , Rijkers Ger T. 
Published: March 2011

ABSTRACTIn up to half of all cases of community-acquired pneumonia (CAP), no pathogen can be identified with conventional diagnostic methods. The most common identified causative agent isStreptococcus pneumoniae. In this study, pneumococcal antibody responses during CAP were analyzed to estimate the contribution of the pneumococcus to all cases of CAP for epidemiological purposes. Pneumococcal antibodies against 14 different serotypes were measured in serum of hospitalized CAP patients. Patients participated in one of two consecutive clinical trials in a general 600-bed teaching hospital in the Netherlands (between October 2004 and June 2009). A significant pneumococcal immune response was defined as at least a 2-fold increase in antibody concentrations against a single serotype between an early (day 1) and a late (day 30) serum sample of each patient with an end concentration above 0.35 μg/ml. A total of 349 adult CAP patients participated in two consecutive clinical trials. For 200 patients, sufficient serum samples were available to determine antibody responses: 62 pneumococcal pneumonia patients, 57 nonpneumococcal pneumonia patients, and 81 patients with an unidentified causative agent. A significant immune response was detected in 45% (28/62 patients) of pneumococcal pneumonia patients, in 5% (3/57) of nonpneumococcal pneumonia patients, and in 28% (23/81) of patients with an unidentified causative agent. The estimated contribution of pneumococci in patients with an unidentified causative agent was calculated to be 57% (95% confidence interval, 36 to 86%). A substantial fraction of pneumococcal pneumonia patients do not elicit a serotype-specific immune response.
Immunodominance of HLA-A2-Restricted Hepatitis C Virus-Specific CD8
+
T Cell Responses Is Linked to Naïve-Precursor Frequency
Authors: Schmidt Julia , Neumann-Haefelin Christoph , Altay Tayibe , Gostick Emma , Price David A. , Lohmann Volker , Blum Hubert E. , Thimme Robert 
Published: March 2011

ABSTRACT

The impact of naïve-precursor frequency on human virus-specific CD8
+
T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor frequencies across three HLA-A2-restricted hepatitis C virus (HCV)-specific epitopes. Importantly, the NS3
1406
epitope with the highest naïve-precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both
ex vivo
and after
in vitro
stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve-precursor frequency.
Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1 Viremia and on Intensified Antiretroviral Therapy Are Identical to Replicating Viral RNAs Recovered from Circulating Resting CD4
+
T Cells
Authors: Anderson Jeffrey A. , Archin Nancie M. , Ince William , Parker Daniel , Wiegand Ann , Coffin John M. , Kuruc JoAnn , Eron Joseph , Swanstrom Ronald , Margolis David M. 
Published: March 2011

ABSTRACT

Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4
+
T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing of HIV-1
env
from LLV plasma was performed, and the sequences were compared to sequences recovered from limiting-dilution outgrowth assays of resting CD4
+
T cells. The circulating LLV virus clone was identical to virus recovered from outgrowth assays from pools of millions of resting CD4
+
T cells. Understanding the sources of LLV requires evaluation of all possible reservoirs of persistent HIV infection.
Transmission of Murine Cytomegalovirus in Breast Milk: a Model of Natural Infection in Neonates
Authors: Wu Carol A. , Paveglio Sara A. , Lingenheld Elizabeth G. , Zhu Li , Lefrançois Leo , Puddington Lynn 
Published: March 2011

ABSTRACT
Vertical transmission of viruses in breast milk can expose neonates to infectious pathogens at a time when the capacity of their immune system to control infections is limited. We developed a mouse model to study the outcomes of acquisition of murine cytomegalovirus (MCMV) when neonates are breastfed by mothers with acute or latent infection. Breast milk leukocytes collected from lactating mice were examined for the presence of MCMV IE-1 mRNA by reverse transcription-PCR (RT-PCR) with Southern analysis. As determined by this criterion, breast milk leukocytes from both acute and latent mothers were positive for MCMV. This mimics the outcome seen in humans with latent cytomegalovirus infection, where reactivation of virus occurs specifically in the lactating mammary gland. Interestingly, intraperitoneal injection of breast milk collected from mothers with latent infection was sufficient to transfer MCMV to neonatal mice, demonstrating that breast milk was a source of virus. Furthermore, we found that MCMV was transmitted from infected mothers to breastfed neonates, with MCMV IE-1 mRNA or infectious virus present in multiple organs, including the brain. In fact, 1 day of nursing was sufficient to transmit MCMV from latent mothers to breastfed neonatal mice. Together, these data validate this mouse model of vertical transmission of MCMV from mothers with acute or latent MCMV infection to breastfed neonates. Its relevance to human disease should prove useful in future studies designed to elucidate the immunological and pathological ramifications of neonatal infection acquired via this natural route.
FUSE Binding Protein 1 Interacts with Untranslated Regions of Japanese Encephalitis Virus RNA and Negatively Regulates Viral Replication
Authors: Chien Hsu-Ling , Liao Ching-Len , Lin Yi-Ling 
Published: March 2011

ABSTRACT
The untranslated regions (UTRs) located at the 5′ and 3′ ends of the Japanese encephalitis virus (JEV) genome, a positive-sense RNA, are involved in viral translation, the initiation of RNA synthesis, and the packaging of nascent virions. The cellular and viral proteins that participate in these processes are expected to interact with the UTRs. In this study, we used biotinylated RNA-protein pulldown and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analyses to identify that the far upstream element (FUSE) binding protein 1 (FBP1) binds with JEV 5′ and 3′ UTRs. The impact of FBP1 on JEV infection was determined in cells with altered FBP1 expression. JEV replication was enhanced by knockdown and reduced by the overexpression of FBP1, indicating a negative role for FBP1 in JEV infection. FBP1, a nuclear protein, was redistributed to the perinuclear region and appeared as cytoplasmic foci that partially colocalized with JEV RNA in the early stage of JEV infection. By using a JEV replicon reporter assay, FBP1 appeared to suppress JEV protein expression mediated by the 5′ and 3′ UTRs. Thus, we suggest that FBP1 binds with the JEV UTR RNA and functions as a host anti-JEV defense molecule by repressing viral protein expression.
Human Adenovirus Type 5 Induces Cell Lysis through Autophagy and Autophagy-Triggered Caspase Activity
Authors: Jiang Hong , White Erin J. , Ríos-Vicil Christian I. , Xu Jing , Gomez-Manzano Candelaria , Fueyo Juan 
Published: March 2011

ABSTRACT

Oncolytic adenoviruses, such as Delta-24-RGD, are promising therapies for patients with brain tumor. Clinical trials have shown that the potency of these cancer-selective adenoviruses should be increased to optimize therapeutic efficacy. One potential strategy is to increase the efficiency of adenovirus-induced cell lysis, a mechanism that has not been clearly described. In this study, for the first time, we report that autophagy plays a role in adenovirus-induced cell lysis. At the late stage after adenovirus infection, numerous autophagic vacuoles accompany the disruption of cellular structure, leading to cell lysis. The virus induces a complete autophagic process from autophagosome initiation to its turnover through fusion with the lysosome although the formation of the autophagosome is sufficient for virally induced cell lysis. Importantly, downmodulation of autophagy genes (
ATG5
or
ATG10
) rescues the infected cells from being lysed by the virus. Moreover, autophagy triggers caspase activity via the extrinsic FADD/caspase 8 pathway, which also contributes to adenovirus-mediated cell lysis. Therefore, our study implicates autophagy and caspase activation as part of the mechanism for cell lysis induced by adenovirus and suggests that manipulation of the process is a potential strategy to optimize clinical efficacy of oncolytic adenoviruses.
Protein pUL128 of Human Cytomegalovirus Is Necessary for Monocyte Infection and Blocking of Migration
Authors: Straschewski Sarah , Patrone Marco , Walther Paul , Gallina Andrea , Mertens Thomas , Frascaroli Giada 
Published: March 2011

ABSTRACTWe have previously shown that only endotheliotropic strains of human cytomegalovirus (HCMV), such as TB40E, infect monocytes and impair their chemokine-driven migration. The proteins encoded by the UL128-131A region (UL128, UL130, and UL131A) of the HCMV genome, which assemble into a pentameric gH-gL-UL128-UL130-UL131A envelope complex, have been recognized as determinants for HCMV endothelial cell tropism. The genes for these proteins are typically inactivated by mutations in all fibroblast-adapted strains that have lost the diversified tropism of clinical isolates. By using mutant HCMV reconstituted from TB40E-derived bacterial artificial chromosomes (BAC) encoding a wild-type (wt) or mutated form of UL128, we show here that UL128-131A products are essential determinants of infection in monocytes and that pUL128, in particular, can block chemokine-driven motility. The virus BAC4, encoding wt UL128, established infection in monocytes, induced the intracellular retention of several chemokine receptors, and rendered monocytes unresponsive to different chemokines. In contrast, the virus BAC1, encoding a mutated UL128, failed to infect monocytes and to downregulate chemokine receptors. BAC1-exposed monocytes did not express immediate-early (IE) products, retained virions in cytoplasmic vesicles, and exhibited normal chemokine responsiveness. A potential role of second-site mutations in the observed phenotype was excluded by using the revertant viruses BAC1rep and BAC4mut. By incubating noninfected monocytes with soluble recombinant pUL128, we observed both the block of migration and the chemokine receptor internalization. We propose that among the gH-gL-UL128-UL130-UL131A complex subunits, the UL128 protein is the one that triggers monocyte paralysis.