bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replication of Human Norovirus RNA in Mammalian Cells Reveals Lack of Interferon Response
Authors: Qu Lin , Murakami Kosuke , Broughman James R. , Lay Margarita K. , Guix Susana , Tenge Victoria R. , Atmar Robert L. , Estes Mary K. 
Published: July 2016

ABSTRACT
Human noroviruses (HuNoVs), named after the prototype strain Norwalk virus (NV), are a leading cause of acute gastroenteritis outbreaks worldwide. Studies on the related murine norovirus (MNV) have demonstrated the importance of an interferon (IFN) response in host control of virus replication, but this remains unclear for HuNoVs. Despite the lack of an efficient cell culture infection system, transfection of stool-isolated NV RNA into mammalian cells leads to viral RNA replication and virus production. Using this system, we show here that NV RNA replication is sensitive to type I (α/β) and III (interleukin-29 [IL-29]) IFN treatment. However, in cells capable of a strong IFN response to Sendai virus (SeV) and poly(I·C), NV RNA replicates efficiently and generates double-stranded RNA without inducing a detectable IFN response. Replication of HuNoV genogroup GII.3 strain U201 RNA, generated from a reverse genetics system, also does not induce an IFN response. Consistent with a lack of IFN induction, NV RNA replication is enhanced neither by neutralization of type I/III IFNs through neutralizing antibodies or the soluble IFN decoy receptor B18R nor by short hairpin RNA (shRNA) knockdown of mitochondrial antiviral signaling protein (MAVS) or interferon regulatory factor 3 (IRF3) in the IFN induction pathways. In contrast to other positive-strand RNA viruses that block IFN induction by targeting MAVS for degradation, MAVS is not degraded in NV RNA-replicating cells, and an SeV-induced IFN response is not blocked. Together, these results indicate that HuNoV RNA replication in mammalian cells does not induce an IFN response, suggesting that the epithelial IFN response may play a limited role in host restriction of HuNoV replication.

IMPORTANCE
Human noroviruses (HuNoVs) are a leading cause of epidemic gastroenteritis worldwide. Due to lack of an efficient cell culture system and robust small-animal model, little is known about the innate host defense to these viruses. Studies on murine norovirus (MNV) have shown the importance of an interferon (IFN) response in host control of MNV replication, but this remains unclear for HuNoVs. Here, we investigated the IFN response to HuNoV RNA replication in mammalian cells using Norwalk virus stool RNA transfection, a reverse genetics system, IFN neutralization reagents, and shRNA knockdown methods. Our results show that HuNoV RNA replication in mammalian epithelial cells does not induce an IFN response, nor can it be enhanced by blocking the IFN response. These results suggest a limited role of the epithelial IFN response in host control of HuNoV RNA replication, providing important insights into our understanding of the host defense to HuNoVs that differs from that to MNV.
Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion
Authors: Coleman Christopher M. , Sisk Jeanne M. , Mingo Rebecca M. , Nelson Elizabeth A. , White Judith M. , Frieman Matthew B. 
Published: July 2016

ABSTRACT

The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV
in vitro
. Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication
in vitro
. These data demonstrate that specific approved drugs can be characterized
in vitro
for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses.

IMPORTANCE
Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.
The Cell Biology of Fission Yeast Septation
Authors: García Cortés Juan C. , Ramos Mariona , Osumi Masako , Pérez Pilar , Ribas Juan Carlos 
Published: July 2016

SUMMARY

In animal cells, cytokinesis requires the formation of a cleavage furrow that divides the cell into two daughter cells. Furrow formation is achieved by constriction of an actomyosin ring that invaginates the plasma membrane. However, fungal cells contain a rigid extracellular cell wall surrounding the plasma membrane; thus, fungal cytokinesis also requires the formation of a special septum wall structure between the dividing cells. The septum biosynthesis must be strictly coordinated with the deposition of new plasma membrane material and actomyosin ring closure and must occur in such a way that no breach in the cell wall occurs at any time. Because of the high turgor pressure in the fungal cell, even a minor local defect might lead to cell lysis and death. Here we review our knowledge of the septum structure in the fission yeast
Schizosaccharomyces pombe
and of the recent advances in our understanding of the relationship between septum biosynthesis and actomyosin ring constriction and how the two collaborate to build a cross-walled septum able to support the high turgor pressure of the cell. In addition, we discuss the importance of the septum biosynthesis for the steady ingression of the cleavage furrow.
Sex differences in the risk profile of hypertension: a cross-sectional study
Authors: Ghosh Saswata , Mukhopadhyay Simantini , Barik Anamitra 
Published: July 2016

ObjectiveTo assess the socioeconomic and behavioural risk factors associated with hypertension among a sample male and female population in India.SettingCross-sectional survey data from a Health and Demographic Surveillance System (HDSS) of rural West Bengal, India was used.Participants27 589 adult individuals (13 994 males and 13 595 females), aged ≥18 years, were included in the study.Primary and secondary outcome measuresHypertension was defined as mean systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg, or if the subject was undergoing regular antihypertensive therapy. Prehypertension was defined as SBP 120–139 mm Hg and DBP 80–89 mm Hg. Individuals were categorised as non-normotensives, which includes both the prehypertensives and hypertensives. Generalised ordered logit model (GOLM) was deployed to fulfil the study objective.ResultsOver 39% of the men and 25% of the women were prehypertensives. Almost 12.5% of the men and 11.3% of the women were diagnosed as hypertensives. Women were less likely to be non-normotensive compared to males. Odds ratios estimated from GOLM indicate that women were less likely to be hypertensive or prehypertensive, and age (OR 1.04, 95% CI 1.03 to 1.05; and OR 1.08, 95% CI 1.07 to 1.09 for males and females, respectively) and body mass index (OR 1.64, 95% CI 1.38 to 1.97 for males; and OR 1.32, 95% CI 1.08 to 1.60 for females) are associated with hypertension.ConclusionsAn elevated level of hypertension exists among a select group of the rural Indian population. Focusing on men, an intervention could be designed for lifestyle modification to curb the prevalence of hypertension.
Hearing and vision screening tools for long-term care residents with dementia: protocol for a scoping review
Authors: McGilton Katherine S , Höbler Fiona , Campos Jennifer , Dupuis Kate , Labreche Tammy , Guthrie Dawn M , Jarry Jonathan , Singh Gurjit , Wittich Walter 
Published: July 2016

IntroductionHearing and vision loss among long-term care (LTC) residents with dementia frequently goes unnoticed and untreated. Despite negative consequences for these residents, there is little information available about their sensory abilities and care assessments and practices seldom take these abilities or accessibility needs into account. Without adequate knowledge regarding such sensory loss, it is difficult for LTC staff to determine the level of an individual's residual basic competence for communication and independent functioning. We will conduct a scoping review to identify the screening measures used in research and clinical contexts that test hearing and vision in adults aged over 65 years with dementia, aiming to: (1) provide an overview of hearing and vision screening in older adults with dementia; and (2) evaluate the sensibility of the screening tools.Methods and analysisThis scoping review will be conducted using the framework by Arksey and O'Malley and furthered by methodological enhancements from cited researchers. We will conduct electronic database searches in CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We will also carry out a ‘grey literature’ search for studies or materials not formally published, both online and through interview discussions with healthcare professionals and research clinicians working in the field. Our aim is to find new and existing hearing and vision screening measures used in research and by clinical professionals of optometry and audiology. Abstracts will be independently reviewed twice for acceptance by a multidisciplinary team of researchers and research clinicians.Ethics and disseminationThis review will inform health professionals working with this growing population. With the review findings, we aim to develop a toolkit and an algorithmic process to select the most appropriate hearing and vision screening assessments for LTC residents with dementia that will facilitate accurate testing and can inform care planning, thereby improving residents’ quality of life.
Improving the communication between teams managing boarded patients on a surgical specialty ward
Authors: Puvaneswaralingam Shobitha , Ross Daniella 
Published: July 2016

Transferring patients from the ward of their specialty or consultant is described as boarding. 1 Boarding patients is becoming increasingly prevalent due to greater pressure on hospital capacity. This practice compromises patient safety through delayed investigations, prolonged hospital stays, and increased risk of hospital-acquired infections. 1 2 We evaluated how regularly boarded patients were reviewed, and how effectively information regarding their management was communicated from their primary specialty to ward staff. We aimed to improve the frequency of patient reviews by ensuring that each patient was reviewed every weekday and increase communication between primary specialty, and medical and nursing teams by 20% from baseline during the data collection period.The project was based in the Otolaryngology ward in Ninewells Hospital, Dundee, where there was a high prevalence of boarded patients. Baseline data showed a clear deficit in communication between the primary specialty and ward staff with only 31% of patient reviews being communicated to ward doctors. We designed and implemented a communication tool, in the form of a sticker, to be inserted into patients' medical notes for use by the primary specialty.Implementation of the sticker improved communication between teams as stickers were completed in 93% of instances. In 88% of patient reviews, the junior doctor was informed of the management plan, showing a large increase from baseline. Through PDSA cycles, we aimed to increase the sustainability and reliability of the sticker; however, we faced challenges with sustainability of sticker insertion. We aim to engage more stakeholders to raise awareness of the problem, brainstorm solutions together, and review the production and implementation of stickers with senior hospital management to discuss the potential use of this tool within practice. There is potentially a large scope for utilisation of this communication tool on a local level, which we hope will significantly improve patient safety.
Immune pathogenesis of heparin-induced thrombocytopenia
Authors: Khandelwal Sanjay , Arepally Gowthami M. 
Published: July 2016

SummaryThe immune response to heparin is one of the most common drug-induced allergies, and yet, atypical for a drug hypersensitivity reaction. Whereas most drug-induced allergies are rare, idiosyncratic and lifelong, the allergic response to heparin is common, predictable in certain clinical settings and transient. Advances in the last decade with regards to structural characterisation of the PF4/heparin antigenic complex, contributions of innate immunity and development of animal models have provided insights into the distinctive features of the HIT immune response. Recent descriptions of the crystal structure of the PF4/heparin complex, alongside other biophysical studies, have clarified the structural requirements for immunogenicity and heparin-dependency of antibody formation. Studies of interactions of PF4 with bacterial cell walls as well as epidemiologic associations of anti-PF4/heparin antibody formation and infection suggest a role for immune priming and explain the rapid evolution of an isotype-switched immune response in sensitised patients. Murine models have greatly facilitated investigations of cellular basis of the HIT response and identified a major role for T-cells and marginal zone B-cells, but key findings have yet to be validated in human disease. This chapter will summarise recent investigations of the HIT immune response in the context of major pathways of immune activation and identify areas of uncertainty.
Current incidence of venous thromboembolism and comparison with 1998: a community-based study in Western France
Authors: Delluc Aurélien , Tromeur Cécile , Le Ven Florent , Gouillou Maelenn , Paleiron Nicolas , Bressollette Luc , Nonent Michel , Salaun Pierre-Yves , Lacut Karine , Leroyer Christophe , Le Gal Grégoire , Couturaud Francis , Mottier Dominique ,   for the EPIGETBO study group
Published: July 2016

SummaryIn 1998 we estimated the incidence of venous thromboembolism (VTE) to be 1.8/1,000 per year. The aim of this study was to compare current VTE incidence to that observed in 1998. We prospectively recorded all cases of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) of the lower limbs diagnosed between March 1, 2013 and February 28, 2014 in hospitals and in the community, using the same method and geographic area than in 1998. The 2013 incidence rates of VTE were computed and compared with those of 1998 using age- and sex-specific standardised incidence ratios (SIRs). In 2013, we recorded 576 VTE cases (279 isolated DVT and 297 PE ± DVT). Among 367,911 inhabitants, the overall incidence of VTE was 1.57/1,000 (95 % CI 1.44–1.69). The overall VTE incidence was significantly lower in 2013 as compared with 1998: SIR 0.72 (95 % CI 0.67–0.79) as well as the incidence of isolated DVT: SIR 0.53 (95 % CI 0.47–0.60); conversely, the overall incidence of PE was unchanged: SIR 1.10 (95 % CI, 0.98–1.23) despite an increase in the incidence of isolated PE: SIR 1.29 (95 % CI, 1.10–1.52). In 1998, 4.4 % of PE cases were diagnosed using CTPA as compared with 73.7 % in 2013 (p < 0.001). In conclusion, between 1998 and 2013, the incidence of symptomatic DVT decreased. Conversely, we found no similar reduction in the incidence of symptomatic PE; whether this is due to changes in diagnostic tests and algorithms in the management of suspected PE requires further investigations.Supplementary Material to this paper is available online at www.thrombosis-online.com.
Theatre and War
Authors: Dinesh Nandita 
Published: July 2016

Nandita Dinesh places Kipling’s "six honest serving-men" (who, what, when, where, why, how) in productive conversation with her own experiences in conflict zones across the world to offer a theoretical and practical reflection on making theatre in times of war. This timely and important book weaves together Dinesh’s personal narrative with the public story of modern conflict, illustrating as it does, the importance of theatre as a force for ethical deliberation and social justice. In it Dinesh asks how theatre might intervene in times and places of conflict and how we might reflect on such interventions. In pursuit of answers, Theatre and War adopts the methods of auto-ethnography, positioning the theatrical practitioner at the heart of conflict zones in northern Uganda, Guatemala, Northern Ireland, Mexico, Rwanda, Kenya, Nagaland, and Kashmir. No longer a detached observer, the researcher and practitioner has to be able to meld theory with practice; to speak to ‘doing’, without undervaluing the importance of ‘thinking about doing’.
Each chapter approaches the need for a synthesis of theory and practice by way of a term of inquiry―Why, Where, Who, What, When―and each is equipped with a set of unflinchingly honest field notes that are designed to reveal some of the ‘hows’ from the author’s own repertoire: questions and issues that were encountered during her own theatrical undertakings, along with first hand reflection on the complexities, potential, and challenges that attended her global work in community theatre. Within these notes are strategies that give the reader a practical insight into how the discussion might find its footing on the ground of war.
The range and scope of this book make it required reading for those interested in theatre―practitioners, researchers, and students alike—as well as those seeking to understand the applications of the arts for ethics, politics, and education.
February Drying in Southeastern Brazil and the Australian Monsoon: Global Mechanism for a Regional Rainfall Feature
Authors: Kelly Patrick , Mapes Brian 
Published: July 2016

Abstract
A dry February rainfall signal in southeastern Brazil is shown to be a robust, repeatable feature of climatology. This February depression or minimum in climatological rain curves has an amplitude of about 30% of the seasonal mean and coincides with a poleward excursion of tropical barotropic easterlies to about 25°S in austral midsummer. Momentum budget decomposition indicates that stationary eddy momentum flux [u*υ*] near 150 hPa in Australian longitudes is a main sink in that latitude belt’s zonal momentum budget. A physical linkage among these phenomena is suggested by statistically significant interannual correlations among February anomalies of southeastern Brazil rainfall, zonal-mean zonal wind, and indices of the Australian monsoon. To test a causality hypothesis that the sharply peaked Australian region monsoon drives the sharp climatological dry signal over Brazil, an observation-inspired tropospheric heating signal near Australia is added to the temperature equation of the full-physics Community Atmosphere Model. Results indicate the near linearity of the global subtropical responses for the modest (roughly 1 and 2 K day−1) magnitudes and scales of imposed heating. Consistent with the hypothesis, this imposed heating robustly causes easterly changes to subtropical, barotropic, zonal-mean momentum, a westward displacement of the mean synoptic-scale pattern in the western Atlantic (the western edge of the subtropical high), and reduced rainfall in southeastern Brazil. These results are closely analogous to the previous findings on a related boreal summer subtropical signal.
Reforming the French health-care system: the quest for accountability
Authors: Simonet Daniel 
Published: July 2016

The resurgence of New Right politics in the late 1970s and 1980s (e.g. ‘Reaganomics’ and ‘Thatcherism’), which were pro-market and pro-private sector ( Lorenz, 2012 ), has increased the reliance on the private sector for the provision of public services. In France, the support for the private sector is no longer a partisan or ideological issue, but rather a pragmatic and increasingly routine approach to the delivery of public services. Whether this will improve the efficiency of the health-care system is still open to question. The article: investigates the use of the New Public Management toolbox ( Goldfinch and Wallis, 2009 : 151) in the French health-care system; examines its selective adoption; and assesses its impact on the accountability and transparency of the medical profession. The French government eventually opted for a re-centralization of the health-care system for monitoring purposes. The reforms antagonized the medical profession and strengthened private care providers. Point for practitioners Despite reiterated calls for devolution, the implementation of New Public Management in the French health-care system led to a greater re-centralization and rising regulations for efficiency purposes. It also allowed the French administrative elite to regain its prerogatives and regional health agencies to reform more rapidly than a multitude of local public organizations. The quest for greater accountability remains an ongoing process.