bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward correcting drift in target position during radiotherapy via computer‐controlled couch adjustments on a programmable Linac
Authors: McNamara Joseph E. , Regmi Rajesh , Michael Lovelock D. , Yorke Ellen D. , Goodman Karyn A. , Rimner Andreas , Mostafavi Hassan , Mageras Gig S. 
Published: May 2013

Purpose:Real‐time tracking of respiratory target motion during radiation therapy is technically challenging, owing to rapid and possibly irregular breathing variations. The authors report on a method to predict and correct respiration‐averaged drift in target position by means of couch adjustments on an accelerator equipped with such capability.Methods:Dose delivery is broken up into a sequence of 10 s field segments, each followed by a couch adjustment based on analysis of breathing motion from an external monitor as a surrogate of internal target motion. Signal averaging over three respiratory cycles yields a baseline representing target drift. A Kalman filter predicts the baseline position 5 s in advance, for determination of the couch correction. The method's feasibility is tested with a motion phantom programmed according to previously recorded patient signals. Computed couch corrections are preprogrammed into a research mode of an accelerator capable of computer‐controlled couch translations synchronized with the motion phantom. The method's performance is evaluated with five cases recorded during hypofractionated treatment and five from respiration‐correlated CT simulation, using a root‐mean‐squared deviation (RMSD) of the baseline from the treatment planned position.Results:RMSD is reduced in all 10 cases, from a mean of 4.9 mm (range 2.7–9.4 mm) before correction to 1.7 mm (range 0.7–2.3 mm) after correction. Treatment time is increased ∼5% relative to that for no corrections.Conclusions:This work illustrates the potential for reduction in baseline respiratory drift with periodic adjustments in couch position during treatment. Future treatment machine capabilities will enable the use of “on‐the‐fly” couch adjustments during treatment.
Development of an Internally Controlled Real-Time Reverse Transcriptase PCR Assay for Pan-Dengue Virus Detection and Comparison of Four Molecular Dengue Virus Detection Assays
Authors: Waggoner Jesse J. , Abeynayake Janaki , Sahoo Malaya K. , Gresh Lionel , Tellez Yolanda , Gonzalez Karla , Ballesteros Gabriela , Balmaseda Angel , Karunaratne Kumudu , Harris Eva , Pinsky Benjamin A. 
Published: May 2013

ABSTRACT

A number of diagnostic tests are available for dengue virus (DENV) detection, including a variety of nucleic acid amplification tests (NAATs). However, reports describing a direct comparison of different NAATs have been limited. In this study, we report the design of an internally controlled real-time reverse transcriptase PCR (rRT-PCR) that detects all four DENV serotypes but does not distinguish between them (the pan-DENV assay). Two hundred clinical samples were then tested using four different DENV RT-PCR assays: the pan-DENV assay, a commercially produced, internally controlled DENV rRT-PCR (the Altona assay), a widely used heminested RT-PCR, and a serotype-specific multiplex rRT-PCR assay. The pan-DENV assay had a linear range extending from 1.0 to 7.0 log
10
cDNA equivalents/μl and a lower limit of 95% detection ranging from 1.7 to 7.6 cDNA equivalents/μl, depending on the serotype. When measured against a composite reference standard, the pan-DENV assay proved to be more clinically sensitive than either the Altona or heminested assays, with a sensitivity of 98.0% compared to 72.3% and 78.8%, respectively (
P
≤ 0.0001 for both comparisons). The pan-DENV assay detected DENV in significantly more samples collected on or after day 5 of illness and in a subgroup of patients with detectable anti-DENV IgM at presentation. No significant difference in sensitivity was observed between the pan-DENV assay and the multiplex rRT-PCR, despite the presence of an internal control in the former. The detection of DENV RNA late in the course of clinical illness should serve to lengthen the period during which a confirmed molecular diagnosis of DENV infection can be provided.
Development and Evaluation of a Next-Generation Digital PCR Diagnostic Assay for Ocular Chlamydia trachomatis Infections
Authors: Roberts Chrissy h. , Last Anna , Molina-Gonzalez Sandra , Cassama Eunice , Butcher Robert , Nabicassa Meno , McCarthy Elizabeth , Burr Sarah E. , Mabey David C. , Bailey Robin L. , Holland Martin J. 
Published: May 2013

ABSTRACT

Droplet digital PCR (ddPCR) is an emulsion PCR process that performs absolute quantitation of nucleic acids. We developed a ddPCR assay for
Chlamydia trachomatis
infections and found it to be accurate and precise. Using PCR mixtures containing plasmids engineered to include the PCR target sequences, we were able to quantify with a dynamic range between 0.07 and 3,160 targets/μl (
r
2
= 0.9927) with >95% confidence. Using 1,509 clinical conjunctival swab samples from a population in which trachoma is endemic in Guinea Bissau, we evaluated the specificity and sensitivity of the quantitative ddPCR assay in diagnosing ocular
C. trachomatis
infections by comparing the performances of ddPCR and the Roche Amplicor CT/NG test. We defined ddPCR tests as positive when we had ≥95% confidence in a nonzero estimate of target load. The sensitivity of ddPCR against Amplicor was 73.3% (95% confidence interval [CI], 67.9 to 78.7%), and specificity was 99.1% (95% CI, 98.6 to 99.6%). Negative and positive predictive values were 94.6% (95% CI, 93.4 to 95.8%) and 94.5% (95% CI, 91.3 to 97.7%), respectively. Based on Amplicor CT/NG testing, the estimated population prevalence of
C. trachomatis
ocular infection was ∼17.5%. Receiver-operator curve analysis was used to select critical cutoff values for use in clinical settings in which a balance between higher sensitivity and specificity is required. We concluded that ddPCR is an effective diagnostic technology suitable for both research and clinical use in diagnosing ocular
C. trachomatis
infections.
Epidemiological and Clinical Complexity of Amoxicillin-Clavulanate-Resistant Escherichia coli
Authors: Rodríguez-Baño Jesús , Oteo Jesús , Ortega Adriana , Villar Macarena , Conejo M. Carmen , Bou Germán , Aranzamendi-Zaldumbide Maitane , Cercenado Emilia , Gurguí Mercè , Martínez-Martínez Luis , Merino María , Rivera Alba , Oliver Antonio , Weber Irene , Pascual Alvaro , Bartolomé Rosa M. , Gónzalez-López Juan José , Campos José 
Published: May 2013

ABSTRACT

Two hundred twelve patients with colonization/infection due to amoxicillin-clavulanate (AMC)-resistant
Escherichia coli
were studied. OXA-1- and inhibitor-resistant TEM (IRT)-producing strains were associated with urinary tract infections, while OXA-1 producers and chromosomal AmpC hyperproducers were associated with bacteremic infections. AMC resistance in
E. coli
is a complex phenomenon with heterogeneous clinical implications.
Interleukin-21 Is a Critical Cytokine for the Generation of Virus-Specific Long-Lived Plasma Cells
Authors: Rasheed Mohammed Ata Ur , Latner Donald R. , Aubert Rachael D. , Gourley Tania , Spolski Rosanne , Davis Carl W. , Langley William A. , Ha Sang-Jun , Ye Lilin , Sarkar Surojit , Kalia Vandana , Konieczny Bogumila T. , Leonard Warren J. , Ahmed Rafi 
Published: May 2013

ABSTRACTLong-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis of durable humoral immunity. The generation of these long-lived plasma cells depends upon a series of highly orchestrated interactions between antigen-specific CD4 T cells and B cells and the formation of germinal centers (GCs). In this study, we have examined the role of the cytokine interleukin-21 (IL-21) in regulating humoral immunity during acute viral infections. Using IL-21 receptor-deficient (IL-21R−/−) mice, we found that virus-specific CD4 T cells were generated after infection with lymphocytic choriomeningitis virus (LCMV) and that these CD4 T cells differentiated into T follicular helper (TFH)-like cells in the absence of IL-21 signaling. There was also no defect in the formation of GCs, although after day 15 these GCs disappeared faster in IL-21R−/−mice than in wild-type mice. Isotype switching and the initial LCMV-specific IgG response were normal in IL-21R−/−mice. However, these mice exhibited a profound defect in generating long-lived plasma cells and in sustaining antibody levels over time. Similar results were seen after infection of IL-21R−/−mice with vesicular stomatitis virus and influenza virus. Using chimeric mice containing wild-type or IL-21R−/−CD4 T cells and B cells, we showed that both B and CD4 T cells need IL-21 signaling for generating long-term humoral immunity. Taken together, our results highlight the importance of IL-21 in humoral immunity to viruses.
Immature and Mature Dengue Serotype 1 Virus Structures Provide Insight into the Maturation Process
Authors: Kostyuchenko Victor A. , Zhang Qian , Tan Joanne L. , Ng Thiam-Seng , Lok Shee-Mei 
Published: May 2013

ABSTRACTDengue virus is a major human pathogen that has four serotypes (DENV1 to -4). Here we report the cryoelectron microscopy (cryo-EM) structures of immature and mature DENV1 at 6- and 4.5-Å resolution, respectively. The subnanometer-resolution maps allow accurate placement of all of the surface proteins. Although the immature and mature viruses showed vastly different surface protein organizations, the envelope protein transmembrane (E-TM) regions remain in similar positions. The pivotal role of the E-TM regions leads to the identification of the start and end positions of all surface proteins during maturation.
The Cellular Interactome of the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein and Functional Implications for Virus Biology
Authors: Emmott Edward , Munday Diane , Bickerton Erica , Britton Paul , Rodgers Mark A. , Whitehouse Adrian , Zhou En-Min , Hiscox Julian A. 
Published: May 2013

ABSTRACT
The coronavirus nucleocapsid (N) protein plays a multifunctional role in the virus life cycle, from regulation of replication and transcription and genome packaging to modulation of host cell processes. These functions are likely to be facilitated by interactions with host cell proteins. The potential interactome of the infectious bronchitis virus (IBV) N protein was mapped using stable isotope labeling with amino acids in cell culture (SILAC) coupled to a green fluorescent protein-nanotrap pulldown methodology and liquid chromatography-tandem mass spectrometry. The addition of the SILAC label allowed discrimination of proteins that were likely to specifically bind to the N protein over background binding. Overall, 142 cellular proteins were selected as potentially binding to the N protein, many as part of larger possible complexes. These included ribosomal proteins, nucleolar proteins, translation initiation factors, helicases, and hnRNPs. The association of selected cellular proteins with IBV N protein was confirmed by immunoblotting, cosedimentation, and confocal microscopy. Further, the localization of selected proteins in IBV-infected cells as well as their activity during virus infection was assessed by small interfering RNA-mediated depletion, demonstrating the functional importance of cellular proteins in the biology of IBV. This interactome not only confirms previous observations made with other coronavirus and IBV N proteins with both overexpressed proteins and infectious virus but also provides novel data that can be exploited to understand the interaction between the virus and the host cell.
Intranasal Administration of Antibody-Bound Respiratory Syncytial Virus Particles Efficiently Primes Virus-Specific Immune Responses in Mice
Authors: Kruijsen Debby , Einarsdottir Helga K. , Schijf Marcel A. , Coenjaerts Frank E. , van der Schoot Ellen C. , Vidarsson Gestur , van Bleek Grada M. 
Published: May 2013

ABSTRACTInfants are protected from a severe respiratory syncytial virus (RSV) infection in the first months of life by maternal antibodies or by prophylactically administered neutralizing antibodies. Efforts are under way to produce RSV-specific antibodies with increased neutralizing capacity compared to the currently licensed palivizumab. While clearly beneficial during primary infections, preexisting antibodies might affect the onset of adaptive immune responses and the ability to resist subsequent RSV infections. Therefore, we addressed the question of how virus neutralizing antibodies influence the priming of subsequent adaptive immune responses. To test a possible role of the neonatal Fc receptor (FcRn) in this process, we compared the responses in C57BL/6 wild-type (WT) and FcRn−/−mice. We observed substantial virus-specific T-cell priming and B-cell responses in mice primed with RSV IgG immune complexes resulting in predominantly Th1-type CD4+T-cell and IgG2c antibody responses upon live-virus challenge. RSV-specific CD8+T cells were primed as well. Activation of these adaptive immune responses was independent of FcRn. Thus, neutralizing antibodies that localize to the airways and prevent infection-related routes of antigen processing can still facilitate antigen presentation of neutralized virus particles and initiate adaptive immune responses against RSV.
Antigenic Characterization of H3N2 Influenza A Viruses from Ohio Agricultural Fairs
Authors: Feng Zhixin , Gomez Janet , Bowman Andrew S. , Ye Jianqiang , Long Li-Ping , Nelson Sarah W. , Yang Jialiang , Martin Brigitte , Jia Kun , Nolting Jacqueline M. , Cunningham Fred , Cardona Carol , Zhang Jianqiang , Yoon Kyoung-Jin , Slemons Richard D. , Wan Xiu-Feng 
Published: May 2013

ABSTRACT
The demonstrated link between the emergence of H3N2 variant (H3N2v) influenza A viruses (IAVs) and swine exposure at agricultural fairs has raised concerns about the human health risk posed by IAV-infected swine. Understanding the antigenic profiles of IAVs circulating in pigs at agricultural fairs is critical to developing effective prevention and control strategies. Here, 68 H3N2 IAV isolates recovered from pigs at Ohio fairs (2009 to 2011) were antigenically characterized. These isolates were compared with other H3 IAVs recovered from commercial swine, wild birds, and canines, along with human seasonal and variant H3N2 IAVs. Antigenic cartography demonstrated that H3N2 IAV isolates from Ohio fairs could be divided into two antigenic groups: (i) the 2009 fair isolates and (ii) the 2010 and 2011 fair isolates. These same two antigenic clusters have also been observed in commercial swine populations in recent years. Human H3N2v isolates from 2010 and 2011 are antigenically clustered with swine-origin IAVs from the same time period. The isolates recovered from pigs at fairs did not cross-react with ferret antisera produced against the human seasonal H3N2 IAVs circulating during the past decade, raising the question of the degree of immunity that the human population has to swine-origin H3N2 IAVs. Our results demonstrate that H3N2 IAVs infecting pigs at fairs and H3N2v isolates were antigenically similar to the IAVs circulating in commercial swine, demonstrating that exhibition swine can function as a bridge between commercial swine and the human population.
Human Cytomegalovirus-Induced NKG2ChiCD57hiNatural Killer Cells Are Effectors Dependent on Humoral Antiviral Immunity
Authors: Wu Zeguang , Sinzger Christian , Frascaroli Giada , Reichel Johanna , Bayer Carina , Wang Li , Schirmbeck Reinhold , Mertens Thomas 
Published: May 2013

ABSTRACTRecent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2ChiCD57hiNK cells gated on CD3negCD56dimcells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2ChiCD57hiNK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2ChiCD57hiNK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2ChiCD57hiNK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.
Structures of the Procapsid and Mature Virion of Enterovirus 71 Strain 1095
Authors: Cifuente Javier O. , Lee Hyunwook , Yoder Joshua D. , Shingler Kristin L. , Carnegie Michael S. , Yoder Jennifer L. , Ashley Robert E. , Makhov Alexander M. , Conway James F. , Hafenstein Susan 
Published: May 2013

ABSTRACTEnterovirus 71 (EV71) is an important emerging human pathogen with a global distribution and presents a disease pattern resembling poliomyelitis with seasonal epidemics that include cases of severe neurological complications, such as acute flaccid paralysis. EV71 is a member of thePicornaviridaefamily, which consists of icosahedral, nonenveloped, single-stranded RNA viruses. Here we report structures derived from X-ray crystallography and cryoelectron microscopy (cryo-EM) for the 1095 strain of EV71, including a putative precursor in virus assembly, the procapsid, and the mature virus capsid. The cryo-EM map of the procapsid provides new structural information on portions of the capsid proteins VP0 and VP1 that are disordered in the higher-resolution crystal structures. Our structures solved from virus particles in solution are largely in agreement with those from prior X-ray crystallographic studies; however, we observe small but significant structural differences for the 1095 procapsid compared to a structure solved in a previous study (X. Wang, W. Peng, J. Ren, Z. Hu, J. Xu, Z. Lou, X. Li, W. Yin, X. Shen, C. Porta, T. S. Walter, G. Evans, D. Axford, R. Owen, D. J. Rowlands, J. Wang, D. I. Stuart, E. E. Fry, and Z. Rao, Nat. Struct. Mol. Biol. 19:424–429, 2012) for a different strain of EV71. For both EV71 strains, the procapsid is significantly larger in diameter than the mature capsid, unlike in any other picornavirus. Nonetheless, our results demonstrate that picornavirus capsid expansion is possible without RNA encapsidation and that picornavirus assembly may involve an inward radial collapse of the procapsid to yield the native virion.
Citations of scientific results and conflicts of interest: the case of mammography screening
Authors: Rasmussen Kristine , Jørgensen Karsten Juhl , Gøtzsche Peter C 
Published: May 2013

IntroductionIn 2001, a Cochrane review of mammography screening questioned whether screening reduces breast cancer mortality, and a more comprehensive review inLancet, also in 2001, reported considerable overdiagnosis and overtreatment. This led to a heated debate and a recent review of the evidence by UK experts intended to be independent.ObjectiveTo explore if general medical and specialty journals differed in accepting the results and methods of three Cochrane reviews on mammography screening.MethodsWe identified articles citing theLancetreview from 2001 or updated versions of the Cochrane review (last search 20 April 2012). We explored which results were quoted, whether the methods and results were accepted (explicit agreement or quoted without caveats), differences between general and specialty journals, and change over time.ResultsWe included 171 articles. The results for overdiagnosis were not quoted in 87% (148/171) of included articles and the results for breast cancer mortality were not quoted in 53% (91/171) of articles. 11% (7/63) of articles in general medical journals accepted the results for overdiagnosis compared with 3% (3/108) in specialty journals (p=0.05). 14% (9/63) of articles in general medical journals accepted the methods of the review compared with 1% (1/108) in specialty journals (p=0.001). Specialty journals were more likely to explicitly reject the estimated effect on breast cancer mortality 26% (28/108), compared with 8% (5/63) in general medical journals, p=0.02.ConclusionsArticles in specialty journals were more likely to explicitly reject results from the Cochrane reviews, and less likely to accept the results and methods, than articles in general medical journals. Several specialty journals are published by interest groups and some authors have vested interests in mammography screening.
New Paradigms in Microtubule-Mediated Endocrine Signaling in Prostate Cancer
Authors: Mistry Sucharita J. , Oh William K. 
Published: May 2013

Abstract
Metastatic prostate cancer has limited therapeutic options and has remained a major clinical challenge. Historically, prostate cancer has been widely recognized as a chemotherapy-resistant disease. However, clinical studies with anti-microtubule agents over the past decade have shown important efficacy in improving survival in patients with advanced disease. The favorable outcomes with microtubule-targeted agents have thus rekindled interest in such therapies for the clinical management of prostate cancer. Microtubules are dynamic polymers of tubulin molecules that play diverse roles within the cell. The dynamic property of microtubules is responsible for forming the bipolar mitotic apparatus, the mitotic spindle, that functions to precisely segregate the chromosomes during cell division. Thus, owing to the pivotal role that they play in the orchestration of mitotic events, microtubules provide excellent targets for anti-cancer therapy. Recent evidence also suggests that microtubules play a crucial role in the regulation of endocrine signaling pathways. Interestingly, microtubule-targeted agents such as taxanes not only inhibit cell division but also impair endocrine receptor signaling in prostate cancer. Herein, we provide an overview of the current status of microtubule-targeted therapies that are used in the treatment of prostate cancer and discuss novel mechanisms by which such therapies modulate endocrine signaling in prostate cancer. We also address the emerging roles of microtubule regulatory proteins in prostate carcinogenesis that could serve as attractive targets for prostate cancer therapy and might also serve as predictive biomarkers to identify patients who may benefit from endocrine and/or chemotherapy. This may have important implications in designing mechanism-based and targeted-therapeutic strategies for prostate cancer. Mol Cancer Ther; 12(5); 555–66. ©2013 AACR.
Transcription Factor Interactions Mediate EGF-Dependent COX-2 Expression
Authors: Xu Kaiming , Shu Hui-Kuo G. 
Published: May 2013

Abstract
Cyclooxygenase-2 (COX-2) is linked to poor prognosis in patients with malignant gliomas. Amplification/overexpression of epidermal growth factor receptor (EGFR) is commonly seen in these tumors. EGFR signaling, through activation of the p38-MAPK/PKC-δ/Sp1 cascade, plays an essential role in the regulation of COX-2 expression in glioma cells. Here, we report that Src kinase contributes upstream to this signaling cascade. In addition, more detailed analysis revealed the involvement of FOXM1, a member of the forkhead box family of transcriptional activators, in EGF-dependent COX-2 induction. FOXM1 protein increased after stimulation with EGF, although its role in modulating COX-2 expression does not depend on this increase. While a conventional FOXM1 responsive element resides in a distal region (−2872/−2539 relative to the transcriptional start site) of the COX-2 promoter, this is not required for EGF-dependent induction of COX-2. Instead, FOXM1 forms a cooperative interaction with Sp1 at the Sp1-binding site (-245/-240 relative to the start site) of the COX-2 promoter to mediate EGF-induced COX-2 expression. Definition of this novel interaction provides a clearer understanding of the mechanistic basis for EGF induction of COX-2.
Implications: These data provide a guide for the evaluation of potential newer therapeutic targets that have relevance in this disease. Mol Cancer Res; 11(8); 875–86. ©2013 AACR.