bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wheat streak mosaic virus Infects Systemically despite Extensive Coat Protein Deletions: Identification of Virion Assembly and Cell-to-Cell Movement Determinants
Authors: Tatineni Satyanarayana , Kovacs Frank , French Roy 
Published: November 2013

ABSTRACT

Viral coat proteins function in virion assembly and virus biology in a tightly coordinated manner with a role for virtually every amino acid. In this study, we demonstrated that the coat protein (CP) of
Wheat streak mosaic virus
(WSMV; genus
Tritimovirus
, family
Potyviridae
) is unusually tolerant of extensive deletions, with continued virion assembly and/or systemic infection found after extensive deletions are made. A series of deletion and point mutations was created in the CP cistron of wild-type and/or green fluorescent protein-tagged WSMV, and the effects of these mutations on cell-to-cell and systemic transport and virion assembly of WSMV were examined. Mutants with overlapping deletions comprising N-terminal amino acids 6 to 27, 36 to 84, 85 to 100, 48 to 100, and 36 to 100 or the C-terminal 14 or 17 amino acids systemically infected wheat with different efficiencies. However, mutation of conserved amino acids in the core domain, which may be involved in a salt bridge, abolished virion assembly and cell-to-cell movement. N-terminal amino acids 6 to 27 and 85 to 100 are required for efficient virion assembly and cell-to-cell movement, while the C-terminal 65 amino acids are dispensable for virion assembly but are required for cell-to-cell movement, suggesting that the C terminus of CP functions as a dedicated cell-to-cell movement determinant. In contrast, amino acids 36 to 84 are expendable, with their deletion causing no obvious effects on systemic infection or virion assembly. In total, 152 amino acids (amino acids 6 to 27 and 36 to 100 and the 65 amino acids at the C-terminal end) of 349 amino acids of CP are dispensable for systemic infection and/or virion assembly, which is rare for multifunctional viral CPs.
Differential Impact of Magnitude, Polyfunctional Capacity, and Specificity of HIV-Specific CD8
+
T Cell Responses on HIV Set Point
Authors: Riou Catherine , Burgers Wendy A. , Mlisana Koleka , Koup Richard A. , Roederer Mario , Abdool Karim Salim S. , Williamson Carolyn , Gray Clive M. 
Published: November 2013

ABSTRACT

Defining the characteristics of HIV-specific CD8
+
T cell responses that lead to viral control is crucial for vaccine development. We evaluated the differential impact of magnitude, polyfunctional capacity, and specificity of the CD8
+
response at approximately 6 months postinfection on the viral set point at 12 months in a cohort of HIV-infected individuals. High frequencies of Gag and Nef responses endowed with four functions were the best predictors of a low viral set point.
Novel Treatment with Neuroprotective and Antiviral Properties against a Neuroinvasive Human Respiratory Virus
Authors: Brison Elodie , Jacomy Hélène , Desforges Marc , Talbot Pierre J. 
Published: November 2013

ABSTRACT

Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an
N
-methyl-
d
-aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement.

IMPORTANCE
Mutations in the surface spike (S) protein of human respiratory coronavirus OC43 appear after persistent infection of human cells of the central nervous system, a possible viral adaptation to this environment. Furthermore, a single amino acid change in the viral S protein modulated virus-induced neuropathology in mice from an encephalitis to a neuropathology characterized by flaccid paralysis, which involves glutamate excitotoxicity. We now show that memantine, a drug that is used for alleviating symptoms associated with neuropathology, such as Alzheimer's disease, can partially restore the physiological state of infected mice by limiting both neurodegeneration and viral replication. This suggests that memantine could be used as an antiviral agent while improving neurological symptoms in various neurological diseases with a viral involvement.
Children's exposure to second-hand smoke at home in Bangladesh: a community survey
Authors: Zafar Ullah Abu Naser , Huque Rumana , Akter Salma , Nasreen Shammi , Akter Humaira , Thomson Heather , Cameron Ian , Newell James Nicholas , Siddiqi Kamran 
Published: November 2013

ObjectivesIn Bangladesh, second-hand smoke (SHS) is recognised as a principal source of indoor air pollution and a major public health problem. However, we know little about the extent to which people are aware of the risks of second-hand smoking, or restrict smoking indoors or in the presence of children. We report findings of a community survey exploring these questions.Design and settingA total of 722 households were surveyed in urban and rural settings, using a multistage cluster random sampling approach and a semistructured questionnaire. In addition, we used qualitative methods to further explore the determinants of smoking-related behaviours inside homes.Findings55% of households in our sample had at least one regular smoker. Smoking indoors was common. In 30% of households, smoking occurred in the presence of children, exposing nearly 40% of children to SHS. Overall, we found a lack of awareness about the harms associated with second-hand smoking.ConclusionsOur study highlights that a sizeable proportion of children and non-smokers are exposed to SHS at homes in Bangladesh, posing a significant and grave public health problem. In the absence of any impetus to legislate against smoking in private places, an educational approach is recommended to change smoking practices at home. Such a shift toward voluntary smoking restrictions at home would require behaviour change among smokers and support from non-smoking family members.
Intention-to-treat analyses and missing data approaches in pharmacotherapy trials for alcohol use disorders
Authors: Del Re A C , Maisel Natalya C , Blodgett Janet C , Finney John W 
Published: November 2013

ObjectivesIntention to treat (ITT) is an analytic strategy for reducing potential bias in treatment effects arising from missing data in randomised controlled trials (RCTs). Currently, no universally accepted definition of ITT exists, although many researchers consider it to require either no attrition or a strategy to handle missing data. Using the reports of a large pool of RCTs, we examined discrepancies between the types of analyses that alcohol pharmacotherapy researchers stated they used versus those they actually used. We also examined the linkage between analytic strategy (ie, ITT or not) and how missing data on outcomes were handled (if at all), and whether data analytic and missing data strategies have changed over time.DesignDescriptive statistics were generated for reported and actual data analytic strategy and for missing data strategy. In addition, generalised linear models determined changes over time in the use of ITT analyses and missing data strategies.Participants165 RCTs of pharmacotherapy for alcohol use disorders.ResultsOf the 165 studies, 74 reported using an ITT strategy. However, less than 40% of the studies actually conducted ITT according to the rigorous definition above. Whereas no change in the use of ITT analyses over time was found, censored (last follow-up completed) and imputed missing data strategies have increased over time, while analyses of data only for the sample actually followed have decreased.ConclusionsDiscrepancies in reporting versus actually conducting ITT analyses were found in this body of RCTs. Lack of clarity regarding the missing data strategy used was common. Consensus on a definition of ITT is important for an adequate understanding of research findings. Clearer reporting standards for analyses and the handling of missing data in pharmacotherapy trials and other intervention studies are needed.
Development of an evaluation framework for African–European hospital patient safety partnerships
Authors: Rutter Paul , Syed Shamsuzzoha B , Storr Julie , Hightower Joyce D , Bagheri-Nejad Sepideh , Kelley Edward , Pittet Didier 
Published: November 2013

BackgroundPatient safety is recognised as a significant healthcare problem worldwide, and healthcare-associated infections are an important aspect. African Partnerships for Patient Safety is a WHO programme that pairs hospitals in Africa with hospitals in Europe with the objective to work together to improve patient safety.ObjectiveTo describe the development of an evaluation framework for hospital-to-hospital partnerships participating in the programme.MethodsThe framework was structured around the programme's three core objectives: facilitate strong interhospital partnerships, improve in-hospital patient safety and spread best practices nationally. Africa-based clinicians, their European partners and experts in patient safety were closely involved in developing the evaluation framework in an iterative process.ResultsThe process defined six domains of partnership strength, each with measurable subdomains. We developed a questionnaire to measure these subdomains. Participants selected six indicators of hospital patient safety improvement from a short-list of 22 based on their relevance, sensitivity to intervention and measurement feasibility. Participants proposed 20 measures of spread, which were refined into a two-part conceptual framework, and a data capture tool created.ConclusionTaking a highly participatory approach that closely involved its end users, we developed an evaluation framework and tools to measure partnership strength, patient safety improvements and the spread of best practice.
Mature Cytotoxic CD56bright/CD16+Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma
Authors: Messaoudene Meriem , Fregni Giulia , Fourmentraux-Neves Emmanuelle , Chanal Johan , Maubec Eve , Mazouz-Dorval Sarra , Couturaud Benoit , Girod Angelique , Sastre-Garau Xavier , Albert Sebastien , Guédon Charles , Deschamps Lydia , Mitilian Delphine , Cremer Isabelle , Jacquelot Nicolas , Rusakiewicz Sylvie , Zitvogel Laurence , Avril Marie-Francoise , Caignard Anne 
Published: November 2013

AbstractMelanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56bright NK cells among CD45+ hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56brightCD16+ NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN–derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node–positive melanoma. Cancer Res; 74(1); 81–92. ©2013 AACR.
Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism
Authors: Nendaz Mathieu , Spirk David , Aujesky Drahomir , Hayoz Daniel , Beer Jürg H. , Husmann Marc , Frauchiger Beat , Korte Wolfgang , Wuillemin Walter A. , Jäger Kurt , Righini Marc , Bounameaux Henri , Kucher Nils 
Published: November 2013

SummaryThere is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2–4.6%) in 962 high-risk vs 0.6% (95% CI 0.2–1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3–5.3%) in 714 high-risk vs 1.1% (95% CI 0.6–2.3%) in 764 lowrisk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10–0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28–0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.
Temporal Trend Analyses of Alpine Data Using North American Regional Reanalysis and In Situ Data: Temperature, Wind Speed, Precipitation, and Derived Blowing Snow
Authors: Hoover Jamie D. , Doesken Nolan , Elder Kelly , Laituri Melinda , Liston Glen E. 
Published: November 2013

AbstractAcross the globe, wind speed trends have shown a slight decline for in situ meteorological datasets. Yet few studies have assessed long-term wind speed trends for alpine regions or how such trends could influence snow transport and distribution. Alpine-region meteorological stations are sparsely distributed, and their records are short. To increase spatial and temporal coverage, use of modeled data is appealing, but the level of agreement between modeled and in situ data is unknown for alpine regions. Data agreement, temporal trends, and the potential effects on snow distribution were evaluated using two in situ sites in an alpine region [Niwot Ridge in Colorado and the Glacier Lakes Ecological Experiments Station (GLEES) in Wyoming] and the corresponding grid cells of the North American Regional Reanalysis (NARR). Temperature, precipitation, and wind speed variables were used to assess blowing-snow trends at annual, seasonal, and daily scales. The correlation between NARR and in situ datasets showed that temperature data were correlated but that wind speed and precipitation were not. NARR wind speed data were systematically lower when compared with in situ data, yet the frequency of wind events was captured. Overall, there were not many significant differences between NARR and in situ wind speed trends at annual, seasonal, and daily scales, aside from GLEES daily values. This finding held true even when trends presented opposite signatures and slopes, which was likely a result of low trend slopes. The lack of agreement between datasets prohibited the use of NARR to broaden analyses for blowing-snow dynamics in alpine regions.
Reply to “Comment on ‘Bias Correction, Quantile Mapping, and Downscaling: Revisiting the Inflation Issue’”
Authors: Maraun Douglas 
Published: November 2013

AbstractIn his comment, G. Bürger criticizes the conclusion that inflation of trends by quantile mapping is an adverse effect. He assumes that the argument would be “based on the belief that long-term trends and along with them future climate signals are to be large scale.” His line of argument reverts to the so-called inflated regression. Here it is shown, by referring to previous critiques of inflation and standard literature in statistical modeling as well as weather forecasting, that inflation is built upon a wrong understanding of explained versus unexplained variability and prediction versus simulation. It is argued that a sound regression-based downscaling can in principle introduce systematic local variability in long-term trends, but inflation systematically deteriorates the representation of trends. Furthermore, it is demonstrated that inflation by construction deteriorates weather forecasts and is not able to correctly simulate small-scale spatiotemporal structure.
Failure to Detect Critical Auditory Alerts in the Cockpit
Authors: Dehais Frédéric , Causse Mickaël , Vachon François , Régis Nicolas , Menant Eric , Tremblay Sébastien 
Published: November 2013

Objective: The aim of this study was to test whether inattentional deafness to critical alarms would be observed in a simulated cockpit. Background: The inability of pilots to detect unexpected changes in their auditory environment (e.g., alarms) is a major safety problem in aeronautics. In aviation, the lack of response to alarms is usually not attributed to attentional limitations, but rather to pilots choosing to ignore such warnings due to decision biases, hearing issues, or conscious risk taking. Method: Twenty-eight general aviation pilots performed two landings in a flight simulator. In one scenario an auditory alert was triggered alone, whereas in the other the auditory alert occurred while the pilots dealt with a critical windshear. Results: In the windshear scenario, 11 pilots (39.3%) did not report or react appropriately to the alarm whereas all the pilots perceived the auditory warning in the no-windshear scenario. Also, of those pilots who were first exposed to the no-windshear scenario and detected the alarm, only three suffered from inattentional deafness in the subsequent windshear scenario. Conclusion: These findings establish inattentional deafness as a cognitive phenomenon that is critical for air safety. Pre-exposure to a critical event triggering an auditory alarm can enhance alarm detection when a similar event is encountered subsequently. Application: Case-based learning is a solution to mitigate auditory alarm misperception.
Cross-sectional and longitudinal evaluation of bone mass and quality in children and young adults with juvenile onset systemic lupus erythematosus (JSLE): role of bone mass determinants analyzed by DXA, PQCT and QUS
Authors: Stagi S , Cavalli L , Bertini F , Cerinic M Matucci , Brandi M Luisa , Falcini F 
Published: November 2013

Introduction Stefano Stagi and Loredana Cavalli contributed equally to the manuscript; Maria Luisa Brandi and Fernanda Falcini contributed equally to the manuscript. There are few prospective data on bone mass and quality in patients with juvenile onset systemic lupus erythematosus (JSLE). There are also few studies analyzing bone mass and quality determinants by using at the same time dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS). Objective The objective of this paper is to evaluate cross-sectionally and longitudinally bone mass and quality determinants in adolescents and young adults with JSLE, and to identify the main predictors of reduced bone mineral density (BMD) and bone quality using these techniques. Methods Fifty-six patients with JSLE (mean age 18.5 ± 5.7 years) entered the study. In all subjects DXA scan at the lumbar spine, radius pQCT and phalangeal QUS were performed the same day. Of these, 46 patients (mean age 23.1 ± 6.2 years) were revaluated with a second DXA, pQCT and QUS. The data obtained were compared with 72 and 80 age- and sex- matched healthy controls. Results At the first evaluation, JSLE patients had a reduced spine BMAD SDS ( p < 0.001), and significantly lower levels of TrabBMD ( p < 0.0001), SSIp ( p < 0.05), AD-SoS and QUS z-score ( p < 0.005) but not reduced muscleCSA and CBA values. CortBMD and FatCSA were significantly increased ( p < 0.0001). These data were confirmed at longitudinal evaluation regarding spine BMAD SDS ( p < 0.001), TrabBMD ( p < 0.0001), FatCSA ( p < 0.005), AD-SoS ( p < 0.001), and QUS z-score ( p < 0.005) but not muscle CSA ( p ≤ 0.05) and CBA ( p < 0.0001). SSIp and CortBMD longitudinal evaluation showed that JSLE patients did not present significant differences in comparison to controls. Conclusions Patients with JSLE have a low bone mass without catch-up growth over time, causing a reduction of peak bone mass with high risk of osteoporosis in early adulthood. To reduce the risk, close monitoring of BMD, better control of disease activity, physical activity and dietary intake of calcium and vitamin D are advocated to ameliorate the loss of bone mass. In patients with proved osteoporosis therapeutic approaches including bisphosphonates should be considered.