bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moving metal artifact reduction in cone‐beam CT scans with implanted cylindrical gold markers
Authors: Toftegaard Jakob , Fledelius Walther , Seghers Dieter , Huber Michael , Brehm Marcus , Worm Esben S. , Elstrøm Ulrik V. , Poulsen Per R. 
Published: November 2014

Purpose:Implanted gold markers for image‐guided radiotherapy lead to streaking artifacts in cone‐beam CT (CBCT) scans. Several methods for metal artifact reduction (MAR) have been published, but they all fail in scans with large motion. Here the authors propose and investigate a method for automatic moving metal artifact reduction (MMAR) in CBCT scans with cylindrical gold markers.Methods:The MMAR CBCT reconstruction method has six steps. (1) Automatic segmentation of the cylindrical markers in the CBCT projections. (2) Removal of each marker in the projections by replacing the pixels within a masked area with interpolated values. (3) Reconstruction of a marker‐free CBCT volume from the manipulated CBCT projections. (4) Reconstruction of a standard CBCT volume with metal artifacts from the original CBCT projections. (5) Estimation of the three‐dimensional (3D) trajectory during CBCT acquisition for each marker based on the segmentation in Step 1, and identification of the smallest ellipsoidal volume that encompasses 95% of the visited 3D positions. (6) Generation of the final MMAR CBCT reconstruction from the marker‐free CBCT volume of Step 3 by replacing the voxels in the 95% ellipsoid with the corresponding voxels of the standard CBCT volume of Step 4. The MMAR reconstruction was performed retrospectively using a half‐fan CBCT scan for 29 consecutive stereotactic body radiation therapy patients with 2–3 gold markers implanted in the liver. The metal artifacts of the MMAR reconstructions were scored and compared with a standard MAR reconstruction by counting the streaks and by calculating the standard deviation of the Hounsfield units in a region around each marker.Results:The markers were found with the same autosegmentation settings in 27 CBCT scans, while two scans needed slightly changed settings to find all markers automatically in Step 1 of the MMAR method. MMAR resulted in 15 scans with no streaking artifacts, 11 scans with 1–4 streaks, and 3 scans with severe streaking artifacts. The corresponding numbers for MAR were 8 (no streaks), 1 (1–4 streaks), and 20 (severe streaking artifacts). The MMAR method was superior to MAR in scans with more than 8 mm 3D marker motion and comparable to MAR for scans with less than 8 mm motion. In addition, the MMAR method was tested on a 4D CBCT reconstruction for which it worked equally well as for the 3D case. The markers in the 4D case had very low motion blur.Conclusions:An automatic method for MMAR in CBCT scans was proposed and shown to effectively remove almost all streaking artifacts in a large set of clinical CBCT scans with implanted gold markers in the liver. Residual streaking artifacts observed in three CBCT scans may be removed with better marker segmentation.
DNA Microarray-Based PCR Ribotyping of Clostridium difficile
Authors: Schneeberg Alexander , Ehricht Ralf , Slickers Peter , Baier Vico , Neubauer Heinrich , Zimmermann Stefan , Rabold Denise , Lübke-Becker Antina , Seyboldt Christian 
Published: November 2014

ABSTRACT

This study presents a DNA microarray-based assay for fast and simple PCR ribotyping of
Clostridium difficile
strains. Hybridization probes were designed to query the modularly structured intergenic spacer region (ISR), which is also the template for conventional and PCR ribotyping with subsequent capillary gel electrophoresis (seq-PCR) ribotyping. The probes were derived from sequences available in GenBank as well as from theoretical ISR module combinations. A database of reference hybridization patterns was set up from a collection of 142 well-characterized
C. difficile
isolates representing 48 seq-PCR ribotypes. The reference hybridization patterns calculated by the arithmetic mean were compared using a similarity matrix analysis. The 48 investigated seq-PCR ribotypes revealed 27 array profiles that were clearly distinguishable. The most frequent human-pathogenic ribotypes 001, 014/020, 027, and 078/126 were discriminated by the microarray.
C. difficile
strains related to 078/126 (033, 045/FLI01, 078, 126, 126/FLI01, 413, 413/FLI01, 598, 620, 652, and 660) and 014/020 (014, 020, and 449) showed similar hybridization patterns, confirming their genetic relatedness, which was previously reported. A panel of 50
C. difficile
field isolates was tested by seq-PCR ribotyping and the DNA microarray-based assay in parallel. Taking into account that the current version of the microarray does not discriminate some closely related seq-PCR ribotypes, all isolates were typed correctly. Moreover, seq-PCR ribotypes without reference profiles available in the database (ribotype 009 and 5 new types) were correctly recognized as new ribotypes, confirming the performance and expansion potential of the microarray.
Validation of a Commercial Dry-Form Broth Microdilution Device (Sensititre) for Testing Tedizolid, a New Oxazolidinone
Authors: Jones Ronald N. , Holliday Nicole M. , Rhomberg Paul R. 
Published: November 2014

ABSTRACT
Tedizolid, a novel oxazolidinone antibacterial with potent activity against a wide range of Gram-positive pathogens, was recently approved by regulatory authorities for the treatment of acute bacterial skin and skin structure infections. A commercial broth microdilution device (Sensititre; Thermo Fisher Scientific) was validated using 285 selected Gram-positive isolates, and the device was documented to have 100.0% essential and categorical agreement with reference MIC results and excellent MIC endpoint reproducibility.
Fruits of Virus Discovery: New Pathogens and New Experimental Models
Authors: Wang David 
Published: November 2014

ABSTRACT
The advent of high-throughput sequencing has led to a tremendous increase in the rate of discovery of viral sequences. In some instances, novel pathogens have been identified. What has been less well appreciated is that novel virus discoveries in distinct hosts have led to the establishment of unique experimental systems to define host-virus interactions. These new systems have opened new frontiers in the study of fundamental virology and infectious disease.
Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection
Authors: Punyadee Nuntaya , Mairiang Dumrong , Thiemmeca Somchai , Komoltri Chulaluk , Pan-ngum Wirichada , Chomanee Nusara , Charngkaew Komgrid , Tangthawornchaikul Nattaya , Limpitikul Wannee , Vasanawathana Sirijitt , Malasit Prida , Avirutnan Panisadee 
Published: November 2014

ABSTRACTShedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces.Ex vivoanalysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1–anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP sheddingin vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever.IMPORTANCEDengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care.
Andes Virus Nucleocapsid Protein Interrupts Protein Kinase R Dimerization To Counteract Host Interference in Viral Protein Synthesis
Authors: Wang Zekun , Mir Mohammad A. 
Published: November 2014

ABSTRACT
Pathogenic hantaviruses delay the type I interferon response during early stages of viral infection. However, the robust interferon response and induction of interferon-stimulated genes observed during later stages of hantavirus infection fail to combat the virus replication in infected cells. Protein kinase R (PKR), a classical interferon-stimulated gene product, phosphorylates the eukaryotic translation initiation factor eIF2α and causes translational shutdown to create roadblocks for the synthesis of viral proteins. The PKR-induced translational shutdown helps host cells to establish an antiviral state to interrupt virus replication. However, hantavirus-infected cells do not undergo translational shutdown and fail to establish an antiviral state during the course of viral infection. In this study, we showed for the first time that Andes virus infection induced PKR overexpression. However, the overexpressed PKR was not active due to a significant inhibition of autophosphorylation. Further studies revealed that Andes virus nucleocapsid protein inhibited PKR dimerization, a critical step required for PKR autophosphorylation to attain activity. The studies reported here establish a hantavirus nucleocapsid protein as a new PKR inhibitor. These studies provide mechanistic insights into hantavirus resistance to the host interferon response and solve the puzzle of the lack of translational shutdown observed in hantavirus-infected cells. The sensitivity of hantavirus replication to PKR has likely imposed a selective evolutionary pressure on hantaviruses to evade the PKR antiviral response for survival. We envision that evasion of the PKR antiviral response by NP has likely helped hantaviruses to exist during evolution and to survive in infected hosts with a multifaceted antiviral defense.

IMPORTANCE
Protein kinase R (PKR), a versatile antiviral host factor, shuts down the translation machinery upon activation in virus-infected cells to create hurdles for the manufacture of viral proteins. The studies reported here reveal that the hantavirus nucleocapsid protein counteracts the PKR antiviral response by inhibiting PKR dimerization, which is required for its activation. We report the discovery of a new PKR inhibitor whose expression in hantavirus-infected cells prevents the PKR-induced host translational shutdown to ensure the continuous synthesis of viral proteins required for efficient virus replication.
p38MAPK and MK2 Pathways Are Important for the Differentiation-Dependent Human Papillomavirus Life Cycle
Authors: Satsuka Ayano , Mehta Kavi , Laimins Laimonis 
Published: November 2014

ABSTRACT
Amplification of human papillomaviruses (HPV) is dependent on the ATM DNA damage pathway. In cells with impaired p53 activity, DNA damage repair requires the activation of p38MAPK along with MAPKAP kinase 2 (MK2). In HPV-positive cells, phosphorylation of p38 and MK2 proteins was induced along with relocalization to the cytoplasm. Treatment with MK2 or p38 inhibitors blocked HPV genome amplification, identifying the p38/MK2 pathway as a key regulator of the HPV life cycle.
Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors
Authors: Abbink Peter , Maxfield Lori F. , Ng'ang'a David , Borducchi Erica N. , Iampietro M. Justin , Bricault Christine A. , Teigler Jeffrey E. , Blackmore Stephen , Parenteau Lily , Wagh Kshitij , Handley Scott A. , Zhao Guoyan , Virgin Herbert W. , Korber Bette , Barouch Dan H. 
Published: November 2014

ABSTRACT
Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.

IMPORTANCE
Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens.
Early Activation of Teleost B Cells in Response to Rhabdovirus Infection
Authors: Abós Beatriz , Castro Rosario , González Granja Aitor , Havixbeck Jeffrey J. , Barreda Daniel R. , Tafalla Carolina 
Published: November 2014

ABSTRACTTo date, the response of teleost B cells to specific pathogens has been only scarcely addressed. In this work, we have demonstrated that viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, has the capacity to infect rainbow trout spleen IgM-positive (IgM+) cells, although the infection is not productive. Consequently, we have studied the effects of VHSV on IgM+cell functionality, comparing these effects to those elicited by a Toll-like receptor 3 (TLR3) ligand, poly(I·C). We found that poly(I·C) and VHSV significantly upregulated TLR3 and type I interferon (IFN) transcription in spleen and blood IgM+cells. Further effects included the upregulated transcription of the CK5B chemokine. The significant inhibition of some of these effects in the presence of bafilomycin A1 (BAF), an inhibitor of endosomal acidification, suggests the involvement of an intracellular TLR in these responses. In the case of VHSV, these transcriptional effects were dependent on viral entry into B cells and the initiation of viral transcription. VHSV also provoked the activation of NF-κB and the upregulation of major histocompatibility complex class II (MHC-II) cell surface expression on IgM+cells, which, along with the increased transcription of the costimulatory molecules CD80/86 and CD83, pointed to VHSV-induced IgM+cell activation toward an antigen-presenting profile. Finally, despite the moderate effects of VHSV on IgM+cell proliferation, a consistent effect on IgM+cell survival was detected.IMPORTANCEInnate immune responses to pathogens established through their recognition by pattern recognition receptors (PRRs) have been traditionally ascribed to innate cells. However, recent evidence in mammals has revealed that innate pathogen recognition by B lymphocytes is a crucial factor in shaping the type of immune response that is mounted. In teleosts, these immediate effects of viral encounter on B lymphocytes have not been addressed to date. In our study, we have demonstrated that VHSV infection provoked immediate transcriptional effects on B cells, at least partially mediated by intracellular PRR signaling. VHSV also activated NF-κB and increased IgM+cell survival. Interestingly, VHSV activated B lymphocytes toward an antigen-presenting profile, suggesting an important role of IgM+cells in VHSV presentation. Our results provide a first description of the effects provoked by fish rhabdoviruses through their early interaction with teleost B cells.
Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation
Authors: Mesher David , Cuschieri Kate , Hibbitts Sam , Jamison Jackie , Sargent Alex , Pollock Kevin G , Powell Ned , Wilson Robbie , McCall Fiona , Fiander Alison , Soldan Kate 
Published: November 2014

AimsTo establish the human papillomavirus (HPV) type-specific prevalence in cervical cancer and high-grade cervical lesions in the UK prior to the introduction of national HPV vaccination.MethodsSpecimens of cervical cancer (n=1235) and cervical intraepithelial neoplasia (CIN)3 (n=2268) were tested for HPV genotypes in England, Scotland, Wales and Northern Ireland. Data were pooled and weighted estimates presented.ResultsAmong cervical cancer cases, 95.8% were positive for at least one high-risk (HR) HPV type. Restricting to those with HR HPV, the proportion positive for HPV16 and/or HPV18 was similar across countries (weighted overall prevalence 83.0%). This proportion decreased with increasing age at diagnosis (p=0.0005). HPV31, HPV33, HPV45, HPV52 and/or HPV58 were detected in 16.1% of HR HPV-positive cervical cancers and there was no significant association with age for these types. For HR HPV-positive CIN3 cases, there was a similar age-specific pattern with the highest positivity of HPV16 and/or HPV18 in the youngest age group (77.2%). The proportion of HR HPV CIN3 cases positive for HPV31, HPV33, HPV45, HPV52 and/or HPV58 was 36.3% in those aged <30 years at diagnosis.ConclusionsThe prevalence of HPV 16 and/or 18 was high in all UK countries and highest in those diagnosed at a younger age. The UK is well placed to monitor the impact of HPV vaccination on type-specific HPV prevalence in cervical disease.
Plasma levels of galectin-3-binding protein reflect type I interferon activity and are increased in patients with systemic lupus erythematosus
Authors: Nielsen Christoffer T , Lood Christian , Østergaard Ole , Iversen Line V , Voss Anne , Bengtsson Anders , Jacobsen Søren , Heegaard Niels H H 
Published: November 2014

ObjectiveSimple measures of type I interferon (IFN) activity constitute highly attractive biomarkers in systemic lupus erythematosus (SLE). We explore galectin-3-binding protein (G3BP) as a novel measure of type I IFN activity and serum/plasma biomarker in large independent cohorts of patients with SLE and controls.MethodsSerum and plasma G3BP concentrations were quantified using ELISA. Type I IFN activity was assessed by Mx1 reporter gene expression assays and correlated to serum G3BP concentrations (SLE-IFN-α, n=26 and healthy controls (HCs), n=10). Plasma G3BP concentrations in the SLE-Denmark (DK) (n=70) and SLE-Sweden (SE) (n=68) cohorts were compared with the HC-DK (n=47) and HC-SE (n=50) cohorts and patients with systemic sclerosis (n=111). In 15 patients with SLE, serum G3BP in consecutive samples was correlated to disease activity. Correlation analysis between G3BP, clinical parameters including disease activity in the four SLE cohorts was performed.ResultsG3BP concentrations correlated significantly with the IFN-α reporter gene assay (r=0.56, p=0.0005) and with IFN-α gene expression scores (r=0.54, p=0.0002). Plasma concentrations were significantly increased in the SLE-DK and SLE-SE cohorts compared with HCs and patients with systemic sclerosis (p<0.0001 and p=0.0009). G3BP concentrations correlated with disease activity measures in the SLE-DK- and SLE-IFN-α cohorts (p=0.0004 and p=0.05) but not in the SLE-SE cohort (p=0.98). Markedly temporal variation was observed in G3BP levels in the consecutive SLE-samples and was significantly associated with changes in disease activity (r=0.44, p=0.014).ConclusionsG3BP plasma levels reflect type I IFN activity and are increased in SLE. Associations with disease activity or clinical manifestations are uncertain. This study highlights G3BP as a convenient measure of type I IFN-dependent gene activation.
Comparison of Solitaire thrombectomy and Penumbra suction thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion
Authors: Son Seungnam , Choi Dae Seob , Oh Min Kyun , Hong Jiho , Kim Soo-Kyoung , Kang Heeyoung , Park Ki-Jong , Choi Nack-Cheon , Kwon Oh-Young , Lim Byeong Hoon 
Published: November 2014

Background and purposeAcute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) is a very severe neurological disease with a high mortality rate and poor clinical outcomes. In this study, we compared our experience of mechanical thrombectomy using the Solitaire stent (Solitaire thrombectomy) and manual aspiration thrombectomy using the Penumbra reperfusion catheter (Penumbra suction thrombectomy) in patients with AIS caused by BAO.Materials and methodsBetween March 2011 and December 2011, 13 patients received Solitaire thrombectomy. In January 2012, the Korean Food and Drug Administration banned the use of the Solitaire stent as a thrombectomy device, and a further 18 patients received Penumbra suction thrombectomy until December 2013. We compared parameters between patients treated with each device.ResultsSuccessful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b: 84.6% vs 100%, p=0.168) and clinical outcomes (judged by the modified Rankin Scale scores recorded at 3 months: 3.6±2.6 vs 3.2±2.6, p=0.726) were not significantly different between the two groups. However, complete recanalization rates (TICI score of 3: 23.1% vs 72.2%, p=0.015) and total procedure times (101.9±41.4 vs 62.3±34.8 min, p=0.044) were significantly higher, and shorter, respectively, in patients treated by Penumbra suction thrombectomy.ConclusionsThe two thrombectomy devices were associated with similar recanalization rates and clinical outcomes in patients with AIS caused by BAO. However, Penumbra suction thrombectomy seemed to allow more rapid and complete recanalization than Solitaire thrombectomy.