bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls
Authors: Verhagen Josanne H. , Höfle Ursula , van Amerongen Geert , van de Bildt Marco , Majoor Frank , Fouchier Ron A. M. , Kuiken Thijs 
Published: September 2015

ABSTRACT

Infections of domestic and wild birds with low-pathogenic avian influenza viruses (LPAIVs) have been associated with protective immunity to subsequent infection. However, the degree and duration of immunity in wild birds from previous LPAIV infection, by the same or a different subtype, are poorly understood. Therefore, we inoculated H13N2 (A/black-headed gull/Netherlands/7/2009) and H16N3 (A/black-headed gull/Netherlands/26/2009) LPAIVs into black-headed gulls (
Chroicocephalus ridibundus
), their natural host species, and measured the long-term immune response and protection against one or two reinfections over a period of >1 year. This is the typical interval between LPAIV epizootics in wild birds. Reinfection with the same virus resulted in progressively less virus excretion, with complete abrogation of virus excretion after two infections for H13 but not H16. However, reinfection with the other virus affected neither the level nor duration of virus excretion. Virus excretion by immunologically naive birds did not differ in total levels of excreted H13 or H16 virus between first- and second-year birds, but the duration of H13 excretion was shorter for second-year birds. Furthermore, serum antibody levels did not correlate with protection against LPAIV infection. LPAIV-infected gulls showed no clinical signs of disease. These results imply that the epidemiological cycles of H13 and H16 in black-headed gulls are relatively independent from each other and depend mainly on infection of first-year birds.

IMPORTANCE
Low-pathogenic avian influenza viruses (LPAIVs) circulate mainly in wild water birds but are occasionally transmitted to other species, including humans, where they cause subclinical to fatal disease. To date, the effect of LPAIV-specific immunity on the epidemiology of LPAIV in wild birds is poorly understood. In this study, we investigated the effect of H13 and H16 LPAIV infection in black-headed gulls on susceptibility and virus excretion of subsequent infection with the same or the other virus within the same breeding season and between breeding seasons. These are the only two LPAIV hemagglutinin subtypes predominating in this species. The findings suggest that H13 and H16 LPAIV cycles in black-headed gull populations are independent of each other, indicate the importance of first-year birds in LPAIV epidemiology, and emphasize the need for alternatives to avian influenza virus (AIV)-specific serum antibodies as evidence of past LPAIV infection and correlates of protection against LPAIV infection in wild birds.
Herpes Simplex Virus Capsid-Organelle Association in the Absence of the Large Tegument Protein UL36p
Authors: Kharkwal Himanshu , Furgiuele Sara Shanda , Smith Caitlin G. , Wilson Duncan W. 
Published: September 2015

ABSTRACT

UL36p (VP1/2) is the largest protein encoded by herpes simplex virus 1 (HSV-1) and resides in the innermost layer of the viral tegument, lying between the capsid and the envelope. UL36p performs multiple functions in the HSV life cycle, including an essential role in cytoplasmic envelopment. We earlier described the isolation of a virion-associated cytoplasmic membrane fraction from HSV-infected cells. Biochemical and ultrastructural analyses showed that the organelles in this buoyant fraction contain enveloped infectious HSV particles in their lumens and naked capsids docked to their cytoplasmic surfaces. These organelles can also recruit molecular motors and transport their cargo virions along microtubules
in vitro
. Here we examine the properties of these HSV-associated organelles in the absence of UL36p. We find that while capsid envelopment is clearly defective, a subpopulation of capsids nevertheless still associate with the cytoplasmic faces of these organelles. The existence of these capsid-membrane structures was confirmed by subcellular fractionation, immunocytochemistry, lipophilic dye fluorescence microscopy, thin-section electron microscopy, and correlative light and electron microscopy. We conclude that capsid-membrane binding can occur in the absence of UL36p and propose that this association may precede the events of UL36p-driven envelopment.

IMPORTANCE
Membrane association and envelopment of the HSV capsid are essential for the assembly of an infectious virion. Envelopment involves the complex interplay of a large number of viral and cellular proteins; however, the function of most of them is unknown. One example of this is the viral protein UL36p, which is clearly essential for envelopment but plays a poorly understood role. Here we demonstrate that organelles utilized for HSV capsid envelopment still accumulate surface-bound capsids in the absence of UL36p. We propose that UL36p-independent binding of capsids to organelles occurs prior to the function of UL36p in capsid envelopment.
Immune Protection against Virus Challenge in Aging Mice Is Not Affected by Latent Herpesviral Infections
Authors: Marandu Thomas F. , Oduro Jennifer D. , Borkner Lisa , Dekhtiarenko Iryna , Uhrlaub Jennifer L. , Drabig Anja , Kröger Andrea , Nikolich-Zugich Janko , Cicin-Sain Luka 
Published: September 2015

ABSTRACT
Latent herpesvirus infections alter immune homeostasis. To understand if this results in aging-related loss of immune protection against emerging infections, we challenged old mice carrying latent mouse cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and/or murine gammaherpesvirus 68 (MHV-68) with influenza virus, West Nile virus (WNV), or vesicular stomatitis virus (VSV). We observed no increase in mortality or weight loss compared to results seen with herpesvirus-negative counterparts and a relative but not absolute reduction in CD8 responses to acute infections. Therefore, the presence of herpesviruses does not appear to increase susceptibility to emerging infections in aging patients.
Near misses and unsafe conditions reported in a Pediatric Emergency Research Network
Authors: Ruddy Richard M , Chamberlain James M , Mahajan Prashant V , Funai Tomohiko , O'Connell Karen J , Blumberg Stephen , Lichenstein Richard , Gramse Heather L , Shaw Kathy N ,   and the Pediatric Emergency Care Applied Research Network
Published: September 2015

ObjectivePatient safety may be enhanced by using reports from front-line staff of near misses and unsafe conditions to identify latent safety events. We describe paediatric emergency department (ED) near-miss events and unsafe conditions from hospital reporting systems in a 1-year observational study from hospitals participating in the Pediatric Emergency Care Applied Research Network (PECARN).DesignThis is a secondary analysis of 1 year of incident reports (IRs) from 18 EDs in 2007–2008. Using a prior taxonomy and established method, this analysis is of all reports classified as near-miss (events not reaching the patient) or unsafe condition. Classification included type, severity, contributing factors and personnel involved. In-depth review of 20% of IRs was performed.Results487 reports (16.8% of eligible IRs) are included. Most common were medication-related, followed by laboratory-related, radiology-related and process-related IRs. Human factors issues were related to 87% and equipment issues to 11%. Human factor issues related to non-compliance with procedures accounted for 66.4%, including 5.95% with no or incorrect ID. Handoff issues were important in 11.5%.ConclusionsMedication and process-related issues are important causes of near miss and unsafe conditions in the network. Human factors issues were highly reported and non-compliance with established procedures was very common, and calculation issues, communications (ie, handoffs) and clinical judgment were also important. This work should enable us to help improve systems within the environment of the ED to enhance patient safety in the future.
Mind the gap: Improving discharge communication between secondary and primary care
Authors: Cresswell Aynsley , Hart Matthew , Suchanek Ondrej , Young Tania , Leaver Laurence , Hibbs Stephen 
Published: September 2015

AbstractFoundation year doctors (FYDs) write most hospital discharge communication, although they have minimal training in this skill. Poor quality discharge summaries increase the risk of adverse events and rehospitalisation. With a multidisciplinary team approach, we developed a list of "golden rules" for good discharge communication. Against these standards, we analysed the quality of electronic inpatient discharge documentation (eIDD) sent over two months from OUH Trust. We found one third of eIDDs were missing details of the discharging doctor. In 68%, changes to medications were not documented clearly and follow-up was not completed in 40%.To improve this suboptimal state, we implemented interactive teaching sessions for FYDs, designed an e-learning module, and suggested software changes to the current electronic discharge proforma. Early re-audit one month after the first teaching sessions did not demonstrate any significant improvement. However, re-auditing after twelve months is planned.Through data collection and discussion with key stakeholders, we have identified standards for discharge communication. We developed interventions to help the trust achieve these standards, aiming to enhance patient safety in the peri-discharge period. While discharge communication is delegated to less-experienced team members, they should receive clear guidance and training.
Improving efficiency management of radiopharmaceutical materials at a nuclear medicine department
Authors: Al Ahmed Ali , Al-Surimi Khaled 
Published: September 2015

AbstractThe cost of radiopharmaceutical materials is highly expensive compared with other resources employed in nuclear medicine department. Hence, inefficient utilization of these costly materials will lead to waste and more financial burden on the healthcare system, increasing the patient waiting list for important diagnostic procedures, especially in those with need urgent care on time. The available data for the previous 12 months about positron emission tomography / computed tomography (PET/CT) unit at nuclear medicine departments showed that over 16% of radiopharmaceutical materials were not utilized and being wasted due to increased number of cancelled or rescheduled oncology patients.The overall financial cost for the underutilized radiopharmaceutical materials due to cancelled and rescheduled procedures for 142 patient were about 39,760 US dollar. Most of these are the oncology patients with diabetes arriving at the nuclear medicine department with high blood glucose level and so are not fit for the procedure. This project aims to improve the oncology diabetic patients preparation for PET/CT procedure to avoid wasting the radiopharmaceutical materials. After implementing the PDSA cycles on 14 oncology patients we found that the quantity of not utilized radiopharmaceuticals were significantly reduced. On the other hand, majority of oncology diabetic patients became more aware about the importance of following the required preparation instruction.
Antigen Selection Shapes the T-cell Repertoire in Chronic Lymphocytic Leukemia
Authors: Vardi Anna , Agathangelidis Andreas , Stalika Evangelia , Karypidou Maria , Siorenta Alexandra , Anagnostopoulos Achilles , Rosenquist Richard , Hadzidimitriou Anastasia , Ghia Paolo , Sutton Lesley-Ann , Stamatopoulos Kostas 
Published: September 2015

AbstractPurpose: The role of antigen(s) in shaping the T-cell repertoire in chronic lymphocytic leukemia, although relevant for understanding malignant cell interactions with cognate T cells, is largely unexplored.Experimental Design: Here we profiled the T-cell receptor β chain gene repertoire in 58 chronic lymphocytic leukemia patients, focusing on cases assigned to well-characterized subsets with stereotyped clonotypic B-cell receptor immunoglobulins, therefore those cases most evidently selected by antigen (subsets #1, #2, and #4).Results: Remarkable repertoire skewing and oligoclonality were observed, and differences between subsets were noted regarding both T-cell receptor β chain gene usage and the extent of clonality, with subset #2 being the least oligoclonal. Longitudinal analysis of subset #4 cases revealed that although the repertoire may fluctuate over time, certain clonotypes persist, thus alluding to persistent antigenic stimulation. Shared (“stereotyped”) clonotypes were found between different patients, reflecting selection by common antigenic elements. Cross-comparison of our dataset with public databases showed that some T-cell clonotypes may have expanded secondary to common viral infections; however, the majority of clonotypes proved to be disease-specific.Conclusions: Overall, the T-cell receptor β chain repertoire in chronic lymphocytic leukemia is likely shaped by antigen selection and the implicated antigenic elements may concern epitopes that also select the malignant B-cell progenitors or, more intriguingly, chronic lymphocytic leukemia–derived epitopes. Clin Cancer Res; 22(1); 167–74. ©2015 AACR.
Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo
Authors: Lopez Salvatore , Cocco Emiliano , Black Jonathan , Bellone Stefania , Bonazzoli Elena , Predolini Federica , Ferrari Francesca , Schwab Carlton L. , English Diana P. , Ratner Elena , Silasi Dan-Arin , Azodi Masoud , Schwartz Peter E. , Terranova Corrado , Angioli Roberto , Santin Alessandro D. 
Published: September 2015

Abstract
HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu–amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0–G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent–treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor–resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. Mol Cancer Ther; 14(11); 2519–26. ©2015 AACR.
Therapy with activated prothrombin complex concentrate is effective in reducing dabigatran-associated blood loss in a porcine polytrauma model
Authors: Honickel Markus , Maron Benjamin , Ryn Joanne van , Braunschweig Till , Cate Hugo ten , Spronk Henri M. H. , Rossaint Rolf , Grottke Oliver 
Published: September 2015

SummaryClinical use of non-vitamin K antagonist oral anticoagulants is increasingly well established. However, specific agents for reversal of these drugs are not currently available. It was to objective of this study to investigate the impact of activated prothrombin complex concentrate (aPCC) on the anticoagulant effects of dabigatran in a randomised, controlled, porcine trauma model. Twenty-one pigs received oral and intravenous dabigatran, resulting in supratherapeutic plasma concentrations. Twelve minutes after injury (standardised bilateral femur fractures and blunt liver injury), animals (n=7/group) received 25 or 50 U/kg aPCC (aPCC25 and aPCC50) or placebo (control) and were followed for 5 hours. The primary endpoint was total volume of blood loss (BL). Haemodynamic and coagulation variables (prothrombin time [PT], activated partial thromboplastin time, diluted thrombin time, thrombin–antithrombin complexes, thromboelastometry, thrombin generation and D-dimers) were measured. Twelve minutes post-injury, BL was similar between groups. Compared with control (total BL: 3807 ± 570 ml) and aPCC25 (3690 ± 454 ml; p=0.77 vs control), a significant reduction in total BL (1639 ± 276 ml; p< 0.0001) and improved survival (p< 0.05) was observed with aPCC50. Dabigatran’s anticoagulant effects were effectively treated in the aPCC50 group, as measured by several parameters including EXTEM clotting time (CT) and PT. In contrast, with aPCC25, laboratory values were initially corrected but subsequently deteriorated due to ongoing blood loss. Thromboembolic or bleeding effects were not detected. In conclusion, blood loss following trauma in dabigatran-anticoagulated pigs was successfully reduced by 50 U/kg aPCC. Optimal methodology for measuring amelioration of dabigatran anticoagulation by aPCC is yet to be determined.
Risk of venous thromboembolism in patients with splenic injury and splenectomy
Authors: Lin Jiun-Nong , Chen Hsuan-Ju , Lin Ming-Chia , Lai Chung-Hsu , Lin Hsi-Hsun , Yang Chih-Hui , Kao Chia-Hung 
Published: September 2015

SummaryThe spleen is a crucial organ in humans. However, little is known about the association of venous thromboembolism (VTE) with splenic injury and splenectomy in trauma patients. The aim of this study was to determine the subsequent risk of VTE following splenic injury and splenectomy. A nationwide retrospective cohort study was conducted by analysing data from the National Health Insurance Research Database in Taiwan. We included 6,162 splenic injury patients (3,033 splenectomised and 3,129 nonsplenectomised patients) and 24,648 comparison patients who were selected by frequency match based on sex, age, and the index year during 2000–2006. All patients were followed until the occurrence of VTE, 31 December, 2011, death, or withdrawal from the insurance program. The age of patients with splenic injury was 41.93 ± 16.44 years. The incidence rates of VTE were 11.81, 8.46, and 5.21 per 10,000 person-years in the splenic injury patients with splen -ectomy, splenic injury patients without splenectomy, and comparison patients, respectively. Compared with the comparison cohort, splenic injury patients with splenectomy exhibited a 2.21-fold risk of VTE (95 % confidence interval [CI], 1.43–3.43), whereas those without splenectomy exhibited a 1.71-fold risk of VTE (95 % CI, 1.05–2.80). The overall incidence rate of VTE was 1.97-fold higher in the splenic injury cohort than the comparison cohort (95 % CI, 1.38–2.81). Although splenectomy increased the risk of VTE 1.35-fold compared with no splenectomy, the difference was not statistically significant (95 % CI, 0.74–2.45). These results may alert physicians and patients to the complications of splenic injury and splenectomy.
Prevention of cardiovascular events with antiplatelet treatment: does time of intake matter for aspirin and ADP receptor blockers?
Authors: Aradi Dániel , Sibbing Dirk , Gross Lisa 
Published: September 2015

SummaryLong-term evidence supports a clustering of cardiovascular events in the early morning. Several studies have shown that platelet hyper-reactivity to various stimuli is also present at this period of the day. However, the idea of treatment strategies reflecting the circadian variation in platelet reactivity has been largely neglected so far, and this is true despite the huge number of patients being treated with these drugs. Some pharmacodynamic data suggest that early-morning platelet hyper-reactivity may be overcome by shifting aspirin intake to the bedtime. However, there is lack of evidence whether shifting the time of intake or splitting the daily dose of P2Y12-inhibitors with a regular QD dosing (clopidogrel or prasugrel) to the evening would be effective to overcome platelet hyper-reactivity or to suppress the excess of cardiovascular events observed during morning hours. Further research is warranted to clarify whether such a simple and costless effort like dose shifting or splitting may be beneficial to prevent cardiovascular events.
In Other Words: The Ethics of the Translator in 17th-century al-Andalus. The Perspective of Aḥmad Ibn Qāsim al-Ḥaǧarī al-Andalusī
Authors: Sciortino Maria Grazia 
Published: September 2015

This study focuses on a particular aspect of the Translation Studies orDirāsāt al-tarǧamah, i.e. the ethics of the translator.Starting from the analysis of concepts like “cultural otherness” or “linguistic hospitality”, theorized by Antoine Berman, Lawrence Venuti and Paul Ricoeur, and concerning the translator’s process of mediating between languages and between cultures, it will be taken into account the specific case of a muslim traveller and interpreter, Aḥmad ibn Qāsim al-Ḥaǧarī al-Andalusī (d. 1051/1641), author of theKitāb Nāṣir al-dīn ʿalà l-qawm al-kāfirīn, who was asked, by a Christian authority (the Archbishop of Granada), to translate some Arabic manuscripts.In such a context, the act of translating highlights not only the problem of hermeneutics and inter-religious dialogue, as interpretation of a different text and a different faith’s language, but also the problem of ethic relationships inherent in encounteringthe Other.
Application of Bayesian Model Averaging in the Reconstruction of Past Climate Change Using PMIP3/CMIP5 Multimodel Ensemble Simulations
Authors: Fang M. , Li X. 
Published: September 2015

Abstract
Climate change simulations based on climate models are inevitably uncertain. This uncertainty typically stems from parametric and structural uncertainties in climate models as well as climate forcings. However, combining model simulations with instrumental observations using appropriate statistical methods is an effective approach for describing this uncertainty. In this study, the authors applied Bayesian model averaging (BMA), a statistical postprocessing method, to an ensemble of climate model simulations from the Paleoclimate Modelling Intercomparison Project phase 3 (PMIP3) and phase 5 of the Coupled Model Intercomparison Project (CMIP5). Uncertainties, weights, and variances of individual model simulations were estimated from a training period using the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis dataset. The results presented here demonstrate that the BMA method is successful and attains a positive performance in this study. These results show that the selected proxy-based reconstructions and simulations are consistent with BMA estimates regarding climate variability in the past 1000 years, though differences can be found for some periods. The authors conclude that BMA is an effective tool for describing uncertainties associated with individual model simulations, as it accounts for the diverse capabilities of different models and generates a more credible range of past climate change over a relatively long-term period based on multimodel ensemble simulations and training data.