bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of minimum monitor unit threshold on spot scanning proton plan quality
Authors: Howard Michelle , Beltran Chris , Mayo Charles S. , Herman Michael G. 
Published: August 2014

Purpose:To investigate the influence of the minimum monitor unit (MU) on the quality of clinical treatment plans for scanned proton therapy.Methods:Delivery system characteristics limit the minimum number of protons that can be delivered per spot, resulting in a min‐MU limit. Plan quality can be impacted by the min‐MU limit. Two sites were used to investigate the impact of min‐MU on treatment plans: pediatric brain tumor at a depth of 5–10 cm; a head and neck tumor at a depth of 1–20 cm. Three‐field, intensity modulated spot scanning proton plans were created for each site with the following parameter variations: min‐MU limit range of 0.0000–0.0060; and spot spacing range of 2–8 mm. Comparisons were based on target homogeneity and normal tissue sparing. For the pediatric brain, two versions of the treatment planning system were also compared to judge the effects of the min‐MU limit based on when it is accounted for in the optimization process (Eclipse v.10 and v.13, Varian Medical Systems, Palo Alto, CA).Results:The increase of the min‐MU limit with a fixed spot spacing decreases plan quality both in homogeneous target coverage and in the avoidance of critical structures. Both head and neck and pediatric brain plans show a 20% increase in relative dose for the hot spot in the CTV and 10% increase in key critical structures when comparing min‐MU limits of 0.0000 and 0.0060 with a fixed spot spacing of 4 mm. The DVHs of CTVs show min‐MU limits of 0.0000 and 0.0010 produce similar plan quality and quality decreases as the min‐MU limit increases beyond 0.0020. As spot spacing approaches 8 mm, degradation in plan quality is observed when no min‐MU limit is imposed.Conclusions:Given a fixed spot spacing of ≤4 mm, plan quality decreases as min‐MU increased beyond 0.0020. The effect of min‐MU needs to be taken into consideration while planning proton therapy treatments.
Effect of dosimeter type for commissioning small photon beams on calculated dose distribution in stereotactic radiosurgery
Authors: García‐Garduño O. A. , Rodríguez‐Ponce M. , Gamboa‐deBuen I. , Rodríguez‐Villafuerte M. , Galván de la Cruz O. O. , Rivera‐Montalvo T. 
Published: August 2014

Purpose:To assess the impact of the detector used to commission small photon beams on the calculated dose distribution in stereotactic radiosurgery (SRS).Methods:In this study, six types of detectors were used to characterize small photon beams: three diodes [a silicon stereotactic field diode SFD, a silicon diode SRS, and a silicon diode E], an ionization chamber CC01, and two types of radiochromic film models EBT and EBT2. These detectors were used to characterize circular collimated beams that were generated by a Novalis linear accelerator. This study was conducted in two parts. First, the following dosimetric data, which are of particular interest in SRS, were compared for the different detectors: the total scatter factor (TSF), the tissue phantom ratios (TPRs), and the off‐axis ratios (OARs). Second, the commissioned data sets were incorporated into the treatment planning system (TPS) to compare the calculated dose distributions and the dose volume histograms (DVHs) that were obtained using the different detectors.Results:The TSFs data measured by all of the detectors were in good agreement with each other within the respective statistical uncertainties: two exceptions, where the data were systematically below those obtained for the other detectors, were the CC01 results for all of the circular collimators and the EBT2 film results for circular collimators with diameters below 10.0 mm. The OAR results obtained for all of the detectors were in excellent agreement for all of the circular collimators. This observation was supported by the gamma‐index test. The largest difference in the TPR data was found for the 4.0 mm circular collimator, followed by the 10.0 and 20.0 mm circular collimators. The results for the calculated dose distributions showed that all of the detectors passed the gamma‐index test at 100% for the 3 mm/3% criteria. The aforementioned observation was true regardless of the size of the calculation grid for all of the circular collimators. Finally, the dose volume histogram results were independent of the size of the calculation grid used.Conclusions:The results of this study showed that all of the studied detectors produced similar commissioned data sets for the TPS dose calculations. However, this result only validated the dose distribution calculation in the TPS and could not be used to assess the dose delivery to the target in which the TFS data were used to calculate the monitor units (the TFS data were not used in the TPS dose distribution calculation). Therefore, this study could not be used to determine the most accurate detector commissioning data set; however, all of the detectors exhibited superior performance for the relative dosimetry of small photon beams.
Effect of Human Immunodeficiency Virus Infection on Plasma Bactericidal Activity against Salmonella enterica Serovar Typhimurium
Authors: Trebicka Estela , Shanmugam Nanda Kumar N. , Mikhailova Anastassia , Alter Galit , Cherayil Bobby J. 
Published: August 2014

ABSTRACTIndividuals with human immunodeficiency virus (HIV) infection have increased susceptibility to invasive disease caused bySalmonella entericaserovar Typhimurium. Studies from Africa have suggested that this susceptibility is related in part to the development of a high level of lipopolysaccharide (LPS)-specific IgG that is able to inhibit the killing ofS. Typhimurium by bactericidal antibodies in healthy individuals. To explore this issue further, we examined the bactericidal activity againstS. Typhimurium using serum and plasma samples from healthy controls and various clinical subgroups of HIV-infected adults in the United States. We found that the bactericidal activity in the samples from HIV-positive elite controllers was comparable to that from healthy individuals, whereas it was significantly reduced in HIV-positive viremic controllers and untreated chronic progressors. As demonstrated previously for healthy controls, the bactericidal activity of the plasma from the elite controllers was inhibited by preincubation withS. Typhimurium LPS, suggesting that it was mediated by anti-LPS antibodies.S. Typhimurium LPS-specific IgG was significantly reduced in all subgroups of HIV-infected individuals. Interestingly, and in contrast to the healthy controls, plasma from all HIV-positive subgroups inhibitedin vitrokilling ofS. Typhimurium by plasma from a healthy individual. Our results, together with the findings from Africa, suggest that multiple mechanisms may be involved in the HIV-induced dysregulation of humoral immunity toS. Typhimurium.
Apolipoprotein E Likely Contributes to a Maturation Step of Infectious Hepatitis C Virus Particles and Interacts with Viral Envelope Glycoproteins
Authors: Lee Ji-Young , Acosta Eliana G. , Stoeck Ina Karen , Long Gang , Hiet Marie-Sophie , Mueller Birthe , Fackler Oliver T. , Kallis Stephanie , Bartenschlager Ralf 
Published: August 2014

ABSTRACT
The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to components of the very-low-density lipoprotein (VLDL) pathway. We and others have shown that apolipoprotein E (ApoE) plays a major role in production of infectious HCV particles. However, the mechanism by which ApoE contributes to virion assembly/release and how it gets associated with the HCV particle is poorly understood. We found that knockdown of ApoE reduces titers of infectious intra- and extracellular HCV but not of the related dengue virus. ApoE depletion also reduced amounts of extracellular HCV core protein without affecting intracellular core amounts. Moreover, we found that ApoE depletion affected neither formation of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step of assembly, such as particle maturation and infectivity. Importantly, we demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably E2. This interaction did not require any other viral proteins and depended on the transmembrane domain of E2 that also was required for recruitment of HCV envelope glycoproteins to detergent-resistant membrane fractions. These results suggest that ApoE plays an important role in HCV particle maturation, presumably by direct interaction with viral envelope glycoproteins.

IMPORTANCE
The HCV replication cycle is tightly linked to host cell lipid pathways and components. This is best illustrated by the dependency of HCV assembly on lipid droplets and the VLDL component ApoE. Although the role of ApoE for production of infectious HCV particles is well established, it is still poorly understood how ApoE contributes to virion formation and how it gets associated with HCV particles. Here, we provide experimental evidence that ApoE likely is required for an intracellular maturation step of HCV particles. Moreover, we demonstrate that ApoE associates with the viral envelope glycoproteins. This interaction appears to be dispensable for envelopment of virus particles but likely contributes to the quality control of secreted infectious virions. These results shed new light on the exploitation of host cell lipid pathways by HCV and the link of viral particle assembly to the VLDL component ApoE.
Stearoyl Coenzyme A Desaturase 1 Is Associated with Hepatitis C Virus Replication Complex and Regulates Viral Replication
Authors: Nguyen Lam N. , Lim Yun-Sook , Pham Long V. , Shin Hae-Young , Kim Yong-Sun , Hwang Soon B. 
Published: August 2014

ABSTRACT
The hepatitis C virus (HCV) life cycle is tightly regulated by lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have recently screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet formation using cell culture-grown HCV (HCVcc)-infected cells. We selected and characterized the gene encoding stearoyl coenzyme A (CoA) desaturase 1 (SCD1). siRNA-mediated knockdown or pharmacological inhibition of SCD1 abrogated HCV replication in both subgenomic replicon and Jc1-infected cells, while exogenous supplementation of either oleate or palmitoleate, products of SCD1 activity, resurrected HCV replication in SCD1 knockdown cells. SCD1 was coimmunoprecipitated with HCV nonstructural proteins and colocalized with both double-stranded RNA (dsRNA) and HCV nonstructural proteins, indicating that SCD1 is associated with HCV replication complex. Moreover, SCD1 was fractionated and enriched with HCV nonstructural proteins at detergent-resistant membrane. Electron microscopy data showed that SCD1 is required for NS4B-mediated intracellular membrane rearrangement. These data further support the idea that SCD1 is associated with HCV replication complex and that its products may contribute to the proper formation and maintenance of membranous web structures in HCV replication complex. Collectively, these data suggest that manipulation of SCD1 activity may represent a novel host-targeted antiviral strategy for the treatment of HCV infection.

IMPORTANCE
Stearoyl coenzyme A (CoA) desaturase 1 (SCD1), a liver-specific enzyme, regulates hepatitis C virus (HCV) replication through its enzyme activity. HCV nonstructural proteins are associated with SCD1 at detergent-resistant membranes, and SCD1 is enriched on the lipid raft by HCV infection. Therein, SCD1 supports NS4B-mediated membrane rearrangement to provide a suitable microenvironment for HCV replication. We demonstrated that either genetic or chemical knockdown of SCD1 abrogated HCV replication in both replicon cells and HCV-infected cells. These findings provide novel mechanistic insights into the roles of SCD1 in HCV replication.
Probing the Functions of the Paramyxovirus Glycoproteins F and HN with a Panel of Synthetic Antibodies
Authors: Welch Brett D. , Paduch Marcin , Leser George P. , Bergman Zachary , Kors Christopher A. , Paterson Reay G. , Jardetzky Theodore S. , Kossiakoff Anthony A. , Lamb Robert A. 
Published: August 2014

ABSTRACTParamyxoviruses are enveloped negative-strand RNA viruses that are significant human and animal pathogens. Most paramyxoviruses infect host cells via the concerted action of a tetrameric attachment protein (variously called HN, H, or G) that binds either sialic acid or protein receptors on target cells and a trimeric fusion protein (F) that merges the viral envelope with the plasma membrane at neutral pH. F initially folds to a metastable prefusion conformation that becomes activated via a cleavage event during cellular trafficking. Upon receptor binding, the attachment protein, which consists of a globular head anchored to the membrane via a helical tetrameric stalk, triggers a major conformation change in F which results in fusion of virus and host cell membranes. We recently proposed a model for F activation in which the attachment protein head domains move following receptor binding to expose HN stalk residues critical for triggering F. To test the model in the context of wild-type viral glycoproteins, we used a restricted-diversity combinatorial Fab library and phage display to rapidly generate synthetic antibodies (sAbs) against multiple domains of the paramyxovirus parainfluenza 5 (PIV5) pre- and postfusion F and HN. As predicted by the model, sAbs that bind to the critical F-triggering region of the HN stalk do not disrupt receptor binding or neuraminidase (NA) activity but are potent inhibitors of fusion. An inhibitory prefusion F-specific sAb recognized a quaternary antigenic site and may inhibit fusion by preventing F refolding or by blocking the F-HN interaction.IMPORTANCEThe paramyxovirus family of negative-strand RNA viruses cause significant disease in humans and animals. The viruses bind to cells via their receptor binding protein and then enter cells by fusion of their envelope with the host cell plasma membrane, a process mediated by a metastable viral fusion (F) protein. To understand the steps in viral membrane fusion, a library of synthetic antibodies to F protein and the receptor binding protein was generated in bacteriophage. These antibodies bound to different regions of the F protein and the receptor binding protein, and the location of antibody binding affected different processes in viral entry into cells.
Anal heterosex among young people and implications for health promotion: a qualitative study in the UK
Authors: Marston C , Lewis R 
Published: August 2014

ObjectiveTo explore expectations, experiences and circumstances of anal sex among young people.DesignQualitative, longitudinal study using individual and group interviews.Participants130 men and women aged 16–18 from diverse social backgrounds.Setting3 contrasting sites in England (London, a northern industrial city, rural southwest).ResultsAnal heterosex often appeared to be painful, risky and coercive, particularly for women. Interviewees frequently cited pornography as the ‘explanation’ for anal sex, yet their accounts revealed a complex context with availability of pornography being only one element. Other key elements included competition between men; the claim that ‘people must like it if they do it’ (made alongside the seemingly contradictory expectation that it will be painful for women); and, crucially, normalisation of coercion and ‘accidental’ penetration. It seemed that men were expected to persuade or coerce reluctant partners.ConclusionsYoung people's narratives normalised coercive, painful and unsafe anal heterosex. This study suggests an urgent need for harm reduction efforts targeting anal sex to help encourage discussion about mutuality and consent, reduce risky and painful techniques and challenge views that normalise coercion.
Risk factors of falls in inpatients and their practical use in identifying high-risk persons at admission: Fukushima Medical University Hospital cohort study
Authors: Hayakawa Takehito , Hashimoto Shigeatsu , Kanda Hideyuki , Hirano Noriko , Kurihara Yumi , Kawashima Takako , Fukushima Tetsuhito 
Published: August 2014

ObjectivesTo clarify the risk factors for falls in hospital settings and to propose the use of such factors to identify high-risk persons at admission.DesignProspective cohort study.SettingFukushima Medical University Hospital, Japan, from August 2008 and September 2009.Participants9957 adult consecutive inpatients admitted to our hospital.MethodsInformation was collected at admission from clinical records obtained from a structured questionnaire conducted in face-to-face interviews with subjects by nurses and doctors and fall events were collected from clinical records.ResultsThe proportion of patients who fell during follow-up was 2.5% and the incidence of falls was 3.28 per 100 person-days. There were significant differences in age, history of falling, cognitive dysfunction, planned surgery, wheelchair use, need for help to move, use of a remote caring system, rehabilitation, use of laxative, hypnotic or psychotropic medications and need for help with activities of daily living (ADL) between patients who did and did not fall. Multivariable adjusted ORs for falls showed that age, history of falls and need for help with ADL were common risk factors in both men and women. Using psychotropic medication also increased the risk of falling in men while cognitive dysfunction and use of hypnotic medication increased the risk of falling in women. Planned surgery was associated with a low risk of falls in women.ConclusionsTo prevent falls in inpatients it is important to identify high-risk persons. Age, history of falling and the need for help with ADL are the most important pieces of information to be obtained at admission. Care plans for patients including fall prevention should be clear and considered.
Relative risk values of age, acrolein, IL-6 and CRP as markers of periventricular hyperintensities: a cross-sectional study
Authors: Abe Arata , Nishiyama Yasuhiro , Harada-Abe Mina , Okubo Seiji , Ueda Masayuki , Mishina Masahiro , Katayama Yasuo 
Published: August 2014

ObjectiveBrain white matter hyperintensities can be divided into periventricular hyperintensity (PVH) and deep-and-subcortical white matter hyperintensity (DSWMH); the former contributes more to cognitive dysfunction and infarction risk. We conducted the present investigation to define the relationship between PVH and DSWMH.DesignCross-sectional study.SettingUniversity hospital.ParticipantsWe prospectively enrolled 228 healthy Japanese volunteers with relative risk values (RRVs) >0.5.Primary outcome measuresWe investigated whether it is possible to use the RRV to predict PVH and DSWMH.ResultsAmong 228 volunteers, 103 (45.1%) and 157 (68.8%) exhibited PVH and DSWMH, respectively. Age, body mass index and PVH were significant independent determinants of RRV. A significant OR for PVH was noted in the highest RRV tertile compared with the lowest, after adjusting for potential confounding factors. A significant OR for high predicted PVH risk was found for RRV levels as well.ConclusionsElevated RRV levels were significantly associated with increased predicted PVH, suggesting that measuring the plasma protein-conjugated acrolein, interleukin 6 and C reactive protein levels may be useful for identifying Japanese at high risk for PVH.
NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions
Authors: Bowers Laura W. , Maximo Ilane X.F. , Brenner Andrew J. , Beeram Muralidhar , Hursting Stephen D. , Price Ramona S. , Tekmal Rajeshwar R. , Jolly Christopher A. , deGraffenried Linda A. 
Published: August 2014

AbstractObesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor α (ERα)–positive breast cancer recurrence in obese and overweight women. Retrospective review of data from ERα-positive patients with an average body mass index of &gt;30 revealed that NSAID users had a 52% lower recurrence rate and a 28-month delay in time to recurrence. To examine the mechanisms that may be mediating this effect, we conducted in vitro studies that utilized sera from obese and normal-weight patients with breast cancer. Exposure to sera from obese patients stimulated greater macrophage COX-2 expression and PGE2 production. This was correlated with enhanced preadipocyte aromatase expression following incubation in conditioned media (CM) collected from the obese-patient, sera-exposed macrophages, an effect neutralized by COX-2 inhibition with celecoxib. In addition, CM from macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated greater breast cancer cell ERα activity, proliferation, and migration compared with sera from normal-weight patients, and these differences were eliminated or reduced by the addition of an aromatase inhibitor during CM generation. Prospective studies designed to examine the clinical benefit of NSAID use in obese patients with breast cancer are warranted. Cancer Res; 74(16); 4446–57. ©2014 AACR.