bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D localization of electrophysiology catheters from a single x‐ray cone‐beam projection
Authors: Robert Normand , Polack George G. , Sethi Benu , Rowlands John A. , Crystal Eugene 
Published: October 2015

Purpose:X‐ray images allow the visualization of percutaneous devices such as catheters in real time but inherently lack depth information. The provision of 3D localization of these devices from cone beam x‐ray projections would be advantageous for interventions such as electrophysiology (EP), whereby the operator needs to return a device to the same anatomical locations during the procedure. A method to achieve real‐time 3D single view localization (SVL) of an object of known geometry from a single x‐ray image is presented. svl exploits the change in the magnification of an object as its distance from the x‐ray source is varied. The x‐ray projection of an object of interest is compared to a synthetic x‐ray projection of a model of said object as its pose is varied.Methods:svl was tested with a 3 mm spherical marker and an electrophysiology catheter. The effect of x‐ray acquisition parameters on svl was investigated. An independent reference localization method was developed to compare results when imaging a catheter translated via a computer controlled three‐axes stage. svl was also performed on clinical fluoroscopy image sequences. A commercial navigation system was used in some clinical image sequences for comparison.Results:svl estimates exhibited little change as x‐ray acquisition parameters were varied. The reproducibility of catheter position estimates in phantoms denoted by the standard deviations, (σx, σy, σz) = (0.099 mm,  0.093 mm,  2.2 mm), where x and y are parallel to the detector plane and z is the distance from the x‐ray source. Position estimates (x, y, z) exhibited a 4% systematic error (underestimation) when compared to the reference method. The authors demonstrated that EP catheters can be tracked in clinical fluoroscopic images.Conclusions:It has been shown that EP catheters can be localized in real time in phantoms and clinical images at fluoroscopic exposure rates. Further work is required to characterize performance in clinical images as well as the sensitivity to clinical image quality.
Comparative Evaluation of Three Nucleic Acid-Based Assays for BK Virus Quantification
Authors: Descamps Veronique , Martin Elodie , Morel Virginie , François Catherine , Helle François , Duverlie Gilles , Castelain Sandrine , Brochot Etienne 
Published: October 2015

ABSTRACT

With the growing importance of BK virus (BKV), effective and efficient screening for BKV replication in plasma and urine samples is very important for monitoring renal transplant and hematopoietic stem cell transplant recipients, who are at increased risk of BKV-associated diseases. However, recent assays proposed by many manufacturers have not been tested, and the available tests have not been standardized. The aim of the present study was to evaluate and compare the performances of three commercially available kits, R-gene, GeneProof, and RealStar, on plasma and urine specimens from patients infected with various genotypes and to determine the correlations with the results from a reference laboratory. A qualitatively excellent global agreement (96.8%) was obtained. RealStar PCR tended to give a higher sensitivity, especially for subtype Ib1 samples. Comparison of 30 plasma samples and 53 urine samples showed a good agreement between the three assays, with Spearman's Rho correlation coefficient values falling between 0.92 and 0.98 (
P
< 0.001). Moreover, a perfect correlation was obtained for comparison of the assay performances with the AcroMetrix BKV panel (
P
< 0.001 for all comparisons). According to Bland-Altman analysis, more than 95% (240/249 comparisons) of sample comparisons were situated in the range of the mean ± 2 standard deviations (SD). The greatest variability between assays was observed for 10.2% of subtype Ib2 samples, with differences of >1 log
10
copies/ml. In conclusion, this study demonstrated the reliable and comparable performances of the R-gene, GeneProof, and RealStar real-time PCR systems for quantification of BKV in urine and plasma samples. All three real-time PCR assays are appropriate for screening of BKV replication in patients.
Characterization of Five Zoonotic Streptococcus suis Strains from Germany, Including One Isolate from a Recent Fatal Case of Streptococcal Toxic Shock-Like Syndrome in a Hunter
Authors: Eisenberg Tobias , Hudemann Christoph , Hossain Hamid M. , Hewer Angela , Tello Khodr , Bandorski Dirk , Rohde Manfred , Valentin-Weigand Peter , Baums Christoph Georg 
Published: October 2015

ABSTRACT

A
Streptococcus suis
isolate from a German hunter with streptococcal toxic shock-like syndrome (STSLS) and four additional zoonotic isolates were genotyped as
mrp
+
epf
* (variant 1890)
sly
+
cps2
+
. All five zoonotic German strains were characterized by high multiplication in human blood samples
ex vivo
, but induction of only low levels of proinflammatory cytokines compared to a Chinese STSLS strain.
MDA5 Is Critical to Host Defense during Infection with Murine Coronavirus
Authors: Zalinger Zachary B. , Elliott Ruth , Rose Kristine M. , Weiss Susan R. 
Published: October 2015

ABSTRACTInfection with the murine coronavirus mouse hepatitis virus (MHV) activates the pattern recognition receptors melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 7 (TLR7) to induce transcription of type I interferon. Type I interferon is crucial for control of viral replication and spread in the natural host, but the specific contributions of MDA5 signaling to this pathway as well as to pathogenesis and subsequent immune responses are largely unknown. In this study, we use MHV infection of the liver as a model to demonstrate that MDA5 signaling is critically important for controlling MHV-induced pathology and regulation of the immune response. Mice deficient in MDA5 expression (MDA5−/−mice) experienced more severe disease following MHV infection, with reduced survival, increased spread of virus to additional sites of infection, and more extensive liver damage than did wild-type mice. Although type I interferon transcription decreased in MDA5−/−mice, the interferon-stimulated gene response remained intact. Cytokine production by innate and adaptive immune cells was largely intact in MDA5−/−mice, but perforin induction by natural killer cells and levels of interferon gamma, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in serum were elevated. These data suggest that MDA5 signaling reduces the severity of MHV-induced disease, at least in part by reducing the intensity of the proinflammatory cytokine response.IMPORTANCEMulticellular organisms employ a wide range of sensors to detect viruses and other pathogens. One such sensor, MDA5, detects viral RNA and triggers induction of type I interferons, chemical messengers that induce inflammation and help regulate the immune responses. In this study, we sought to determine the role of MDA5 during infection with mouse hepatitis virus, a murine coronavirus used to model viral hepatitis as well as other human diseases. We found that mice lacking the MDA5 sensor were more susceptible to infection than were mice with MDA5 and experienced decreased survival. Viral replication in the liver was similar in mice with and without MDA5, but liver damage was increased in MDA5−/−mice, suggesting that the immune response is causing the damage. Production of several proinflammatory cytokines was elevated in MDA5−/−mice, suggesting that MDA5 may be responsible for keeping pathological inflammatory responses in check.
Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity
Authors: Olp Landon N. , Jeanniard Adrien , Marimo Clemence , West John T. , Wood Charles 
Published: October 2015

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries—where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment protocol followed by Illumina deep-sequencing, we generated and analyzed 16 unique Zambian, KS-derived, KSHV genomes. We enriched KSHV DNA over cellular DNA 1,851 to 18,235-fold. Enrichment provided coverage levels up to 24,740-fold; therefore, supporting highly confident polymorphism analysis. Multiple alignment of the 16 newly sequenced KSHV genomes showed low level variability across the entire central conserved region. This variability resulted in distinct phylogenetic clustering between Zambian KSHV genomic sequences and those derived from Western countries. Importantly, the phylogenetic segregation of Zambian from Western sequences occurred irrespective of inclusion of the highly variable genes K1 and K15. We also show that four genes within the more conserved region of the KSHV genome contained polymorphisms that partially, but not fully, contributed to the unique Zambian KSHV whole-genome phylogenetic structure. Taken together, our data suggest that the whole KSHV genome should be taken into consideration for accurate viral characterization.

IMPORTANCE
Our results represent the largest number of KSHV whole-genomic sequences published to date and the first time that multiple genomes have been sequenced from sub-Saharan Africa, a geographic area where KS is highly endemic. Based on our new sequence data, it is apparent that whole-genome KSHV diversity is greater than previously appreciated and differential phylogenetic clustering exists between viral genomes of Zambia and Western countries. Furthermore, individual genes may be insufficient for KSHV genetic characterization. Continued investigation of the KSHV genetic landscape is necessary in order to effectively understand the role of viral evolution and sequence diversity on KSHV gene functions and pathogenesis.
Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
Authors: Duque Velásquez Camilo , Kim Chiye , Herbst Allen , Daude Nathalie , Garza Maria Carmen , Wille Holger , Aiken Judd , McKenzie Debbie 
Published: October 2015

ABSTRACT

Transmission of chronic wasting disease (CWD) between cervids is influenced by the primary structure of the host cellular prion protein (PrP
C
). In white-tailed deer,
PRNP
alleles encode the polymorphisms Q95 G96 (wild type [wt]), Q95 S96 (referred to as the S96 allele), and H95 G96 (referred to as the H95 allele), which differentially impact CWD progression. We hypothesize that the transmission of CWD prions between deer expressing different allotypes of PrP
C
modifies the contagious agent affecting disease spread. To evaluate the transmission properties of CWD prions derived experimentally from deer of four
PRNP
genotypes (wt/wt, S96/wt, H95/wt, or H95/S96), transgenic (tg) mice expressing the wt allele (tg33) or S96 allele (tg60) were challenged with these prion agents. Passage of deer CWD prions into tg33 mice resulted in 100% attack rates, with the CWD H95/S96 prions having significantly longer incubation periods. The disease signs and neuropathological and protease-resistant prion protein (PrP-res) profiles in infected tg33 mice were similar between groups, indicating that a prion strain (Wisc-1) common to all CWD inocula was amplified. In contrast, tg60 mice developed prion disease only when inoculated with the H95/wt and H95/S96 CWD allotypes. Serial passage in tg60 mice resulted in adaptation of a novel CWD strain (H95
+
) with distinct biological properties. Transmission of first-passage tg60CWD-H95
+
isolates into tg33 mice, however, elicited two prion disease presentations consistent with a mixture of strains associated with different PrP-res glycotypes. Our data indicate that H95-
PRNP
heterozygous deer accumulated two CWD strains whose emergence was dictated by the PrP
C
primary structure of the recipient host. These findings suggest that CWD transmission between cervids expressing distinct PrP
C
molecules results in the generation of novel CWD strains.

IMPORTANCE
CWD prions are contagious among wild and captive cervids in North America and in South Korea. We present data linking the amino acid variant Q95H in white-tailed deer cellular prion protein (PrP
C
) to the emergence of a novel CWD strain (H95
+
). We show that, upon infection, deer expressing H95-PrP
C
molecules accumulated a mixture of CWD strains that selectively propagated depending on the
PRNP
genotype of the host in which they were passaged. Our study also demonstrates that mice expressing the deer S96-
PRNP
allele, previously shown to be resistant to various cervid prions, are susceptible to H95
+
CWD prions. The potential for the generation of novel strains raises the possibility of an expanded host range for CWD.
Induction and Antagonism of Antiviral Responses in Respiratory Syncytial Virus-Infected Pediatric Airway Epithelium
Authors: Villenave Rémi , Broadbent Lindsay , Douglas Isobel , Lyons Jeremy D. , Coyle Peter V. , Teng Michael N. , Tripp Ralph A. , Heaney Liam G. , Shields Michael D. , Power Ultan F. 
Published: October 2015

ABSTRACT
Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well-differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda 1 (IFN-λ1)/interleukin-29 (IL-29). In contrast, type I IFNs were not detected following RSV infection of WD-PBECs. IFN responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV nonstructural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic.

IMPORTANCE
Most respiratory viruses target airway epithelium for infection and replication, which is central to causing disease. However, for most human viruses we have a poor understanding of their interactions with human airway epithelium. Respiratory syncytial virus (RSV) is the most important viral pathogen of young infants. To help understand RSV interactions with pediatric airway epithelium, we previously developed three-dimensional primary cell cultures from infant bronchial epithelium that reproduce several hallmarks of RSV infection in infants, indicating that they represent authentic surrogates of RSV infection in infants. We found that RSV induced a potent antiviral state in these cultures and that a type III interferon, interleukin IL-29 (IL-29), was involved. Indeed, our data suggest that IL-29 has potential to prevent RSV disease. However, we also demonstrated that RSV efficiently circumvents this antiviral immune response and identified mechanisms by which this may occur. Our study provides new insights into RSV interaction with pediatric airway epithelium.
Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women
Authors: Huebschmann A G , Kohrt W M , Herlache L , Wolfe P , Daugherty S , Reusch J EB , Bauer T A , Regensteiner J G 
Published: October 2015

ObjectiveType 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM.Research design and methodsWe enrolled overweight, sedentary women aged 50–75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration.ResultsVO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak).ConclusionsTaken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought.Trial numberNCT00785005.
Efficacy of advice from healthcare professionals to pregnant women on avoiding constrictive clothing around the trunk: a study protocol for a randomised controlled trial
Authors: Takehara Kenji , Kato Sachiko , Sasaki Aiko , Jwa Seung Chik , Kakee Naoko , Sago Haruhiko , Noguchi Yuko , Aoki Tomoko , Inoue Eisuke , Nitta Chieko , Ishii Yumiko 
Published: October 2015

IntroductionAs a component of midwife care, eliminating clothing that constricts the trunk has been shown to markedly elevate the uterine fundus, soften the uterus and abdomen, and reduce the abdominal wall tension in women admitted to hospital due to the risk of miscarriage or premature delivery. However, no prospective study has conclusively verified the efficacy of avoiding constrictive clothes around the trunk in pregnant women. We aim to verify the efficacy of instructing pregnant women to wear loose clothing that does not constrict the trunk to reduce the risk of premature birth and improve quality of life (QoL) during pregnancy.Methods and analysisWe will conduct a randomised controlled trial of pregnant women scheduled to deliver at the National Center for Child Health and Development in Tokyo, Japan. A total of 616 pregnant women, from whom written informed consent will be obtained, will be allocated randomly to an intervention group or a control group. Women in the control group will be provided with anaemia prevention leaflets at 20 weeks’ gestation and skin-care leaflets at 30 weeks’ gestation. Women in the intervention group will be provided with the same leaflets and will also receive health advice from health professionals to avoid constrictive clothing around the trunk. The primary outcome will be a difference between these groups in the frequency of any one of the following category variables: (1) cervical length <30 mm up to 28 weeks’ gestation, (2) hospital admission for threatened premature delivery, or (3) premature delivery. Secondary outcomes will include QoL during pregnancy, maternal state of health, and status of fetal development.Ethics and disseminationThe Institutional Review Board and Ethics Committee at the National Center for Child Health and Development, Japan, has approved this study. Our findings will be widely disseminated through conference presentations and peer-reviewed publications.Trial registration numberUMIN000016853.
Are we meeting current standards in medicines reconciliation? A study in a District General Hospital.
Authors: Iddles Emma , Williamson Andrew , Bradley Alison , Khan Khurram 
Published: October 2015

AbstractIntroduction: Inadequate medicines reconciliation on admission is often identified as a major cause of patient morbidity, with poor access to patient's regular medications often cited as a barrier to care. In the surgical admission unit of our district general hospital, drug charts are completed by junior doctors who do not have access to the Emergency Care Summary (ECS) thus making it difficult to accurately complete admission drug charts.Methods: Our initial measurement of all acute surgical admissions revealed that 49% of patients had an accurate medicines reconciliation upon admission, increasing to 75% within 24 hours of admission. It was clear from this data that our current practice needed improvement in order to ensure patient safety. Resultantly the junior medical staff were provided with ECS accounts and teaching to aid the process of medicines reconciliation.Results: Following the introduction of access to ECS and junior doctor education, a further two data cycles were completed. On the first cycle, the number of accurately completed drug charts increased to 62% on admission and 86% at 24 hours. After the second cycle 57% were complete on admission increasing to 84% at 24 hours.Conclusion: Our project has shown that by providing junior doctors with medicines reconciliation education and access to patients’ pre-admission medications through a nationwide electronic system resulted in a considerable increase in the completion of medicine reconciliation.
Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6
Authors: Draper Lindsey M. , Kwong Mei Li M. , Gros Alena , Stevanović Sanja , Tran Eric , Kerkar Sid , Raffeld Mark , Rosenberg Steven A. , Hinrichs Christian S. 
Published: October 2015

Abstract
Purpose: The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in principle ideal immunotherapeutic targets, but evidence that T cells specific for these antigens can recognize and kill HPV+ tumor cells is limited. We sought to determine whether TCR gene engineered T cells directed against an HPV oncoprotein can successfully target HPV+ tumor cells.
Experimental Design: T-cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22-month disease-free interval after her second resection of distant metastatic anal cancer. T cells genetically engineered to express an oncoprotein-specific TCR from this patient's tumor-infiltrating T cells were tested for specific reactivity against HPV+ epithelial tumor cells.
Results: We identified, from an excised metastatic anal cancer tumor, T cells that recognized an HLA-A*02:01–restricted epitope of HPV-16 E6. The frequency of the dominant T-cell clonotype from these cells was approximately 400-fold greater in the patient's tumor than in her peripheral blood. T cells genetically engineered to express the TCR from this clonotype displayed high avidity for an HLA-A*02:01–restricted epitope of HPV-16, and they showed specific recognition and killing of HPV-16+ cervical, and head and neck cancer cell lines.
Conclusions: These findings demonstrate that HPV-16+ tumors can be targeted by E6-specific TCR gene engineered T cells, and they provide the foundation for a novel cellular therapy directed against HPV-16+ malignancies, including cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. Clin Cancer Res; 21(19); 4431–9. ©2015 AACR.