bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of leaf margins for lung stereotactic body radiotherapy using a flattening filter‐free beam
Authors: Wakai Nobuhide , Sumida Iori , Otani Yuki , Suzuki Osamu , Seo Yuji , Isohashi Fumiaki , Yoshioka Yasuo , Hasegawa Masatoshi , Ogawa Kazuhiko 
Published: April 2015

Purpose:The authors sought to determine the optimal collimator leaf margins which minimize normal tissue dose while achieving high conformity and to evaluate differences between the use of a flattening filter‐free (FFF) beam and a flattening‐filtered (FF) beam.Methods:Sixteen lung cancer patients scheduled for stereotactic body radiotherapy underwent treatment planning for a 7 MV FFF and a 6 MV FF beams to the planning target volume (PTV) with a range of leaf margins (−3 to 3 mm). Forty grays per four fractions were prescribed as a PTV D95. For PTV, the heterogeneity index (HI), conformity index, modified gradient index (GI), defined as the 50% isodose volume divided by target volume, maximum dose (Dmax), and mean dose (Dmean) were calculated. Mean lung dose (MLD), V20 Gy, and V5 Gy for the lung (defined as the volumes of lung receiving at least 20 and 5 Gy), mean heart dose, and Dmax to the spinal cord were measured as doses to organs at risk (OARs). Paired t‐tests were used for statistical analysis.Results:HI was inversely related to changes in leaf margin. Conformity index and modified GI initially decreased as leaf margin width increased. After reaching a minimum, the two values then increased as leaf margin increased (“V” shape). The optimal leaf margins for conformity index and modified GI were −1.1 ± 0.3 mm (mean ± 1 SD) and −0.2 ± 0.9 mm, respectively, for 7 MV FFF compared to −1.0 ± 0.4 and −0.3 ± 0.9 mm, respectively, for 6 MV FF. Dmax and Dmean for 7 MV FFF were higher than those for 6 MV FF by 3.6% and 1.7%, respectively. There was a positive correlation between the ratios of HI, Dmax, and Dmean for 7 MV FFF to those for 6 MV FF and PTV size (R = 0.767, 0.809, and 0.643, respectively). The differences in MLD, V20 Gy, and V5 Gy for lung between FFF and FF beams were negligible. The optimal leaf margins for MLD, V20 Gy, and V5 Gy for lung were −0.9 ± 0.6, −1.1 ± 0.8, and −2.1 ± 1.2 mm, respectively, for 7 MV FFF compared to −0.9 ± 0.6, −1.1 ± 0.8, and −2.2 ± 1.3 mm, respectively, for 6 MV FF. With the heart inside the radiation field, the mean heart dose showed a V‐shaped relationship with leaf margins. The optimal leaf margins were −1.0 ± 0.6 mm for both beams. Dmax to the spinal cord showed no clear trend for changes in leaf margin.Conclusions:The differences in doses to OARs between FFF and FF beams were negligible. Conformity index, modified GI, MLD, lung V20 Gy, lung V5 Gy, and mean heart dose showed a V‐shaped relationship with leaf margins. There were no significant differences in optimal leaf margins to minimize these parameters between both FFF and FF beams. The authors’ results suggest that a leaf margin of −1 mm achieves high conformity and minimizes doses to OARs for both FFF and FF beams.
Whole-Genome Sequencing in Outbreak Analysis
Authors: Gilchrist Carol A. , Turner Stephen D. , Riley Margaret F. , Petri William A. , Hewlett Erik L. 
Published: April 2015

SUMMARYIn addition to the ever-present concern of medical professionals about epidemics of infectious diseases, the relative ease of access and low cost of obtaining, producing, and disseminating pathogenic organisms or biological toxins mean that bioterrorism activity should also be considered when facing a disease outbreak. Utilization of whole-genome sequencing (WGS) in outbreak analysis facilitates the rapid and accurate identification of virulence factors of the pathogen and can be used to identify the path of disease transmission within a population and provide information on the probable source. Molecular tools such as WGS are being refined and advanced at a rapid pace to provide robust and higher-resolution methods for identifying, comparing, and classifying pathogenic organisms. If these methods of pathogen characterization are properly applied, they will enable an improved public health response whether a disease outbreak was initiated by natural events or by accidental or deliberate human activity. The current application of next-generation sequencing (NGS) technology to microbial WGS and microbial forensics is reviewed.
Implementation of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry in Routine Clinical Laboratories Improves Identification of Coagulase-Negative Staphylococci and Reveals the Pathogenic Role of Staphylococcus lugdunensis
Authors: Argemi Xavier , Riegel Philippe , Lavigne Thierry , Lefebvre Nicolas , Grandpré Nicolas , Hansmann Yves , Jaulhac Benoit , Prévost Gilles , Schramm Frédéric 
Published: April 2015

ABSTRACT

The use of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for staphylococcal identification is now considered routine in laboratories compared with the conventional phenotypical methods previously used. We verified its microbiological relevance for identifying the main species of coagulase-negative staphylococci (CoNS) by randomly selecting 50 isolates. From 1 January 2007 to 31 August 2008, 12,479 staphylococci were isolated with phenotypic methods, of which 4,594 were identified as
Staphylococcus aureus
and 7,885 were coagulase negative staphylococci. Using MALDI-TOF MS from 1 January 2011 to 31 August 2012, 14,913 staphylococci were identified, with 5,066 as
S. aureus
and 9,847 as CoNS. MALDI-TOF MS allowed the identification of approximately 85% of the CoNS strains, whereas only 14% of the CoNS strains were identified to the species level with phenotypic methods because they were often considered contaminants. Furthermore, the use of MALDI-TOF MS revealed the occurrence of recently characterized
Staphylococcus
species, such as
S. pettenkoferi
,
S. condimenti
, and
S. piscifermentans
. Microbiological relevance analysis further revealed that some species displayed a high rate of microbiological significance, i.e., 40% of the
S. lugdunensis
strains included in the analysis were associated with infection risk. This retrospective microbiological study confirms the role of MALDI-TOF MS in clinical settings for the identification of staphylococci with clinical consequences. The species distribution reveals the occurrence of the recently identified species
S. pettenkoferi
and putative virulent species, including
S. lugdunensis
.
Development and Validation of a Laboratory-Developed Multiplex Real-Time PCR Assay on the BD Max System for Detection of Herpes Simplex Virus and Varicella-Zoster Virus DNA in Various Clinical Specimens
Authors: Pillet Sylvie , Verhoeven Paul O. , Epercieux Amélie , Bourlet Thomas , Pozzetto Bruno 
Published: April 2015

ABSTRACT
A multiplex real-time PCR (quantitative PCR [qPCR]) assay detecting herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA together with an internal control was developed on the BD Max platform combining automated DNA extraction and an open amplification procedure. Its performance was compared to those of PCR assays routinely used in the laboratory, namely, a laboratory-developed test for HSV DNA on the LightCycler instrument and a test using a commercial master mix for VZV DNA on the ABI7500fast system. Using a pool of negative cerebrospinal fluid (CSF) samples spiked with either calibrated controls for HSV-1 and VZV or dilutions of a clinical strain that was previously quantified for HSV-2, the empirical limit of detection of the BD Max assay was 195.65, 91.80, and 414.07 copies/ml for HSV-1, HSV-2, and VZV, respectively. All the samples from HSV and VZV DNA quality control panels (Quality Control for Molecular Diagnostics [QCMD], 2013, Glasgow, United Kingdom) were correctly identified by the BD Max assay. From 180 clinical specimens of various origins, 2 CSF samples were found invalid by the BD Max assay due to the absence of detection of the internal control; a concordance of 100% was observed between the BD Max assay and the corresponding routine tests. The BD Max assay detected the PCR signal 3 to 4 cycles earlier than did the routine methods. With results available within 2 h on a wide range of specimens, this sensitive and fully automated PCR assay exhibited the qualities required for detecting simultaneously HSV and VZV DNA on a routine basis.
Electronic-cigarette use among young people in Wales: evidence from two cross-sectional surveys
Authors: Moore Graham , Hewitt Gillian , Evans John , Littlecott Hannah J , Holliday Jo , Ahmed Nilufar , Moore Laurence , Murphy Simon , Fletcher Adam 
Published: April 2015

ObjectivesTo examine the prevalence of electronic(e)-cigarette use, prevalence of e-cigarette and tobacco use by age, and associations of e-cigarette use with sociodemographic characteristics, tobacco and cannabis use among young people in Wales.DesignData from two nationally-representative cross-sectional surveys undertaken in 2013–2014. Logistic regression analyses, adjusting for school-level clustering, examined sociodemographic characteristics of e-cigarette use, and associations between e-cigarette use and smoking.SettingPrimary and secondary schools in Wales.ParticipantsPrimary-school children aged 10–11 (n=1601) and secondary-school students aged 11–16 (n=9055).ResultsPrimary-school children were more likely to have used e-cigarettes (5.8%) than tobacco (1.6%). Ever use of e-cigarettes remained more prevalent than ever use of tobacco until age 14–15. Overall, 12.3% of secondary-school students (aged 11–16) reported ever using e-cigarettes, with no differences according to gender, ethnicity or family affluence. The percentage of ‘never smokers’ reporting having used e-cigarettes was 5.3% at age 10–11 to 8.0% at age 15–16. The proportion of children who had ever used an e-cigarette and reported currently smoking increased from 6.9% among 10–11 year olds to 39.2% in 15–16 year olds. Only 1.5% (n=125) of 11–16 year-olds, including 0.3% of never smokers, reported regular e-cigarette use (use at least once a month). Current weekly smokers were 100 times more likely than non-smokers to report regular e-cigarette use (relative risk ratio (RRR=121.15; 95% CI 57.56 to 254.97). Regular e-cigarette use was also more likely among those who had smoked cannabis (RRR 53.03; 95% CI 38.87 to 80.65).ConclusionsMany young people (including never-smokers) have tried e-cigarettes. However, regular use is less common, and is associated with tobacco cigarette use. Longitudinal research is needed to understand age-related trajectories of e-cigarette use and to understand the temporal nature of relationships between e-cigarette and tobacco use.
Introducing consultant outpatient clinics to community settings to improve access to paediatrics: an observational impact study
Authors: McLeod Hugh , Heath Gemma , Cameron Elaine , Debelle Geoff , Cummins Carole 
Published: April 2015

ObjectivesIn line with a national policy to move care ‘closer to home’, a specialist children's hospital in the National Health Service in England introduced consultant-led ‘satellite’ clinics to two community settings for general paediatric outpatient services. Objectives were to reduce non-attendance at appointments by providing care in more accessible locations and to create new physical clinic capacity. This study evaluated these satellite clinics to inform further development and identify lessons for stakeholders.MethodsImpact of the satellite clinics was assessed by comparing community versus hospital-based clinics across the following measures: (1) non-attendance rates and associated factors (including patient characteristics and travel distance) using a logistic regression model; (2) percentage of appointments booked within local catchment area; (3) contribution to total clinic capacity; (4) time allocated to clinics and appointments; and (5) clinic efficiency, defined as the ratio of income to staff-related costs.ResultsSatellite clinics did not increase attendance beyond their contribution to shorter travel distance, which was associated with higher attendance. Children living in the most-deprived areas were 1.8 times more likely to miss appointments compared with those from least-deprived areas. The satellite clinics’ contribution to activity in catchment areas and to total capacity was small. However, one of the two satellite clinics was efficient compared with most hospital-based clinics.ConclusionsOutpatient clinics were relocated in pragmatically chosen community settings using a ‘drag and drop’ service model. Such clinics have potential to improve access to specialist paediatric healthcare, but do not provide a panacea. Work is required to improve attendance as part of wider efforts to support vulnerable families. Satellite clinics highlight how improved management could contribute to better use of existing capacity.
Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: a single-center series with special emphasis on covered cortical branches and perforating arteries
Authors: Gawlitza Matthias , Januel Anne-Christine , Tall Philippe , Bonneville Fabrice , Cognard Christophe 
Published: April 2015

BackgroundData regarding anatomic and clinical results of flow diversion treatment in complex bifurcation aneurysms of the anterior circulation are scarce.ObjectiveTo present our results of treatment of these lesions with special emphasis on the fate of ‘jailed’ cortical branches and perforating arteries.MethodsSeventeen patients were treated with flow diverters (FDs) for 18 aneurysms of the middle cerebral artery bifurcation (n=13) and the anterior communicating artery complex (n=5). Nineteen cortical branches were covered. A single FD was used in all patients.ResultsAt latest follow-up (mean 7.9 months; range 3–36; median 4.0) 2/19 (10.5%) of the covered branches were occluded, 9/19 (47.4%) showed a decreased caliber and the remaining branches were unchanged. All branch modifications were clinically asymptomatic. Mortality and permanent morbidity were 0%. Symptomatic ischemic events in perforator territories occurred in three patients (17.6%), which were reversible in all of them within 24 h. Follow-up MRI disclosed asymptomatic lacunar defects corresponding to covered perforating artery territories in five patients (29.4%). Altogether, perforator lesions—symptomatic and asymptomatic—occurred in 7/17 patients (41.2%). 33.3% of the aneurysms were occluded at latest follow-up; decreased diameters were seen in the other 66.7%.ConclusionsFlow diversion of bifurcation aneurysms is feasible with low rates of permanent morbidity and mortality. Caliber reduction and asymptomatic occlusion of covered cortical branches seems to be common, yet ischemic complications are rather linked to perforator occlusions. Our results on aneurysm occlusion rates are preliminary and longer follow-up periods are warranted.
The influence of system delay on 30-day and on long-term mortality in patients with anterior versus non-anterior ST-segment elevation myocardial infarction: a cohort study
Authors: Postma Sonja , Dambrink Jan-Henk E , Gosselink A T Marcel , Ottervanger Jan Paul , Kolkman Evelien , ten Berg Jurrien M , Suryapranata Harry , van ‘t Hof Arnoud W J 
Published: April 2015

AimTo evaluate the relationship between system delay and 30-day and long-term mortality in patients with anterior versus non-anterior ST-elevation myocardial infarction (STEMI).MethodsWe conducted a prospective observational cohort study. Patients with STEMI who were transported to the Isala Hospital, Zwolle, and underwent primary percutaneous coronary intervention (pPCI) from 2005 until 2010 were included. These patients were divided into quartiles of system delay (time from first medical contact until reperfusion therapy): Q1–Q4.ResultsIn total, 3041 patients were included in our study. 41% (n=1253) of the patients had an anterior myocardial infarction (MI) and 59% of the patients (n=1788) had a non-anterior MI. Only in patients with an anterior MI, prolonged system delay was associated with a higher mortality (30-day Q1: 2.6%, Q2: 3.1%, Q3: 6.8%, Q4: 7.4%, p=0.001; long-term Q1: 12.8%, Q2: 13.7%, Q3: 24.1%, Q4: 22.6%, p<0.001). After multivariable adjustment, prolonged system delay was associated with a higher 30-day and long-term mortality in patients with an anterior MI (30 day Q2: HR 1.18, 95% CI (0.46 to 3.00), Q3: HR 2.45, 95% CI (1.07 to 5.63), Q4: HR 2.25, 95% CI (0.97 to 5.25)); long-term Q2: HR 1.09, 95% CI (0.71 to 1.68), Q3: HR 1.68, 95% CI (1.13 to 2.49), Q4: HR 1.55, 95% CI (1.03 to 2.33)), but not in patients with a non-anterior MI.ConclusionsProlonged system delay significantly increased short-term as well as long-term mortality in patients with an anterior MI. This effect was not demonstrated in patients with a non-anterior MI. Therefore, it is of the greatest importance to minimise system delay in patients who present with an anterior MI.
Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures
Authors: Stone Jennifer , Thompson Deborah J. , dos Santos Silva Isabel , Scott Christopher , Tamimi Rulla M. , Lindstrom Sara , Kraft Peter , Hazra Aditi , Li Jingmei , Eriksson Louise , Czene Kamila , Hall Per , Jensen Matt , Cunningham Julie , Olson Janet E. , Purrington Kristen , Couch Fergus J. , Brown Judith , Leyland Jean , Warren Ruth M.L. , Luben Robert N. , Khaw Kay-Tee , Smith Paula , Wareham Nicholas J. , Jud Sebastian M. , Heusinger Katharina , Beckmann Matthias W. , Douglas Julie A. , Shah Kaanan P. , Chan Heang-Ping , Helvie Mark A. , Le Marchand Loic , Kolonel Laurence N. , Woolcott Christy , Maskarinec Gertraud , Haiman Christopher , Giles Graham G. , Baglietto Laura , Krishnan Kavitha , Southey Melissa C. , Apicella Carmel , Andrulis Irene L. , Knight Julia A. , Ursin Giske , Alnaes Grethe I. Grenaker , Kristensen Vessela N. , Borresen-Dale Anne-Lise , Gram Inger Torhild , Bolla Manjeet K. , Wang Qin , Michailidou Kyriaki , Dennis Joe , Simard Jacques , Pharoah Paul , Dunning Alison M. , Easton Douglas F. , Fasching Peter A. , Pankratz V. Shane , Hopper John L. , Vachon Celine M. 
Published: April 2015

AbstractMammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P &lt; 10−5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk. Cancer Res; 75(12); 2457–67. ©2015 AACR.
XPO1/CRM1 Inhibition Causes Antitumor Effects by Mitochondrial Accumulation of eIF5A
Authors: Miyake Takahito , Pradeep Sunila , Wu Sherry Y. , Rupaimoole Rajesha , Zand Behrouz , Wen Yunfei , Gharpure Kshipra M. , Nagaraja Archana S. , Hu Wei , Cho Min Soon , Dalton Heather J. , Previs Rebecca A. , Taylor Morgan L. , Hisamatsu Takeshi , Kang Yu , Liu Tao , Shacham Sharon , McCauley Dilara , Hawke David H. , Wiktorowicz John E. , Coleman Robert L. , Sood Anil K. 
Published: April 2015

AbstractPurpose: XPO1 inhibitors have shown promise for cancer treatment, and yet the underlying mechanisms for the antitumor effects are not well understood. In this study, we explored the usefulness of selective inhibitors of nuclear export (SINE) compounds that are specific inhibitors of XPO1.Experimental Design: We used proteomic analysis in XPO1 inhibitor–treated ovarian cancer cell lines and examined antitumor effects in ovarian and breast cancer mouse models. We also studied the effects of XPO1 inhibitor in combination with chemotherapeutic agents.Results: XPO1 inhibitor treatment substantially increased the percentage of apoptotic cells (60%) after 72 hours of incubation. XPO1 inhibitor promoted the accumulation of eIF5A in mitochondria, leading to cancer cell death. Topotecan showed the greatest synergistic effect with XPO1 inhibitor. XPO1 inhibitors prevented the translocation of IGF2BP1 from the nucleus to the cytoplasm, thereby permitting the localization of eIF5A in the mitochondria. This process was p53, RB, and FOXO independent. Significant antitumor effects were observed with XPO1 inhibitor monotherapy in orthotopic ovarian (P &lt; 0.001) and breast (P &lt; 0.001) cancer mouse models, with a further decrease in tumor burden observed in combination with topotecan or paclitaxel (P &lt; 0.05). This mitochondrial accumulation of eIF5A was highly dependent on the cytoplasmic IGF2BP1 levels.Conclusions: We have unveiled a new understanding of the role of eIF5A and IGF2BP1 in XPO1 inhibitor–mediated cell death and support their clinical development for the treatment of ovarian and other cancers. Our data also ascertain the combinations of XPO1 inhibitors with specific chemotherapy drugs for therapeutic trials. Clin Cancer Res; 21(14); 3286–97. ©2015 AACR.
CD38-Targeted Immunochemotherapy in Refractory Multiple Myeloma: A New Horizon
Authors: Laubach Jacob P. , Richardson Paul G. 
Published: April 2015

Abstract
CD38 is a type II transmembrane glycoprotein that is highly expressed in multiple myeloma and is a promising target for immunotherapy. Daratumumab is a human monoclonal antibody that has potent anti-multiple myeloma activity both as monotherapy and in combination with other multiple myeloma treatments, and has breakthrough designation on this basis. Clin Cancer Res; 21(12); 2660–2. ©2015 AACR.
See related article by Nijhof et al., p. 2802