bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and Functional Features of the Reovirus σ1 Tail
Authors: Dietrich Melanie H. , Ogden Kristen M. , Long Jacob M. , Ebenhoch Rebecca , Thor Alexandra , Dermody Terence S. , Stehle Thilo 
Published: April 2018

ABSTRACT
Mammalian orthoreovirus attachment to target cells is mediated by the outer capsid protein σ1, which projects from the virion surface. The σ1 protein is a homotrimer consisting of a filamentous tail, which is partly inserted into the virion; a body domain constructed from β-spiral repeats; and a globular head with receptor-binding properties. The σ1 tail is predicted to form an α-helical coiled coil. Although σ1 undergoes a conformational change during cell entry, the nature of this change and its contributions to viral replication are unknown. Electron micrographs of σ1 molecules released from virions identified three regions of flexibility, including one at the midpoint of the molecule, that may be involved in its structural rearrangement. To enable a detailed understanding of essential σ1 tail organization and properties, we determined high-resolution structures of the reovirus type 1 Lang (T1L) and type 3 Dearing (T3D) σ1 tail domains. Both molecules feature extended α-helical coiled coils, with T1L σ1 harboring central chloride ions. Each molecule displays a discontinuity (stutter) within the coiled coil and an unexpectedly seamless transition to the body domain. The transition region features conserved interdomain interactions and appears rigid rather than highly flexible. Functional analyses of reoviruses containing engineered σ1 mutations suggest that conserved residues predicted to stabilize the coiled-coil-to-body junction are essential for σ1 folding and encapsidation, whereas central chloride ion coordination and the stutter are dispensable for efficient replication. Together, these findings enable modeling of full-length reovirus σ1 and provide insight into the stabilization of a multidomain virus attachment protein.

IMPORTANCE
While it is established that different conformational states of attachment proteins of enveloped viruses mediate receptor binding and membrane fusion, less is understood about how such proteins mediate attachment and entry of nonenveloped viruses. The filamentous reovirus attachment protein σ1 binds cellular receptors; contains regions of predicted flexibility, including one at the fiber midpoint; and undergoes a conformational change during cell entry. Neither the nature of the structural change nor its contribution to viral infection is understood. We determined crystal structures of large σ1 fragments for two different reovirus serotypes. We observed an unexpectedly tight transition between two domains spanning the fiber midpoint, which allows for little flexibility. Studies of reoviruses with engineered changes near the σ1 midpoint suggest that the stabilization of this region is critical for function. Together with a previously determined structure, we now have a complete model of the full-length, elongated reovirus σ1 attachment protein.
Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions
Authors: Lee Hyun Jae , Georgiadou Athina , Otto Thomas D. , Levin Michael , Coin Lachlan J. , Conway David J. , Cunnington Aubrey J. 
Published: April 2018

SUMMARYTranscriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactionsin vitrounder tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling.
Hip and groin time-loss injuries decreased slightly but injury burden remained constant in men’s professional football: the 15-year prospective UEFA Elite Club Injury Study
Authors: Werner Jonas , Hägglund Martin , Ekstrand Jan , Waldén Markus 
Published: April 2018

BackgroundHip and groin injuries are common in men’s professional football, but the time-trend of these injuries is not known.AimTo investigate hip and groin injury rates, especially time-trends, in men’s professional football over 15 consecutive seasons.Study designProspective cohort study.SettingMen’s professional football.Methods47 European teams were followed prospectively for a varying number of seasons between 2001/2002 and 2015/2016, totalling 268 team seasons. Time-loss injuries and individual player exposure during training and matches were recorded. Injury rate was defined as the number ofinjuries/1000 hours and injury burden as the number oflay-off days/1000 hours. Time-trends for total hip and groin injuries and adductor-related injury rates were analysed using Poisson regression, and injury burden was analysed using a negative binomial regression model.ResultsHip and groin injuries contributed 1812 out of 12 736 injuries (14%), with adductor-related injury as the most common of hip and groin injuries (n=1139, 63%). The rates of hip and groin injury and adductor-related injury were 1.0/1000 hours and 0.6/1000 hours, and these rates decreased significantly with on average 2% (Exp(b)=0.98, 95% CI 0.97 to 0.99, P=0.003) and 3% (Exp(b)=0.97, 95% CI 0.95 to 0.99, P<0.001) per season (year on year), respectively. The seasonal trend of hip and groin injury burden did not improve (Exp(b)=0.99, 95% CI 0.97 to 1.01, P=0.40).ConclusionsHip and groin injuries constitute a considerable part of all time-loss injuries in men’s professional football. Although there was a promising slight decreasing trend in the rates of hip and groin injury (as a category) and adductor-related injury (as a specific diagnosis), the injury burden remained at a consistent level over the study period.
Role and prevalence of impaired awareness of hypoglycaemia in ambulance service attendances to people who have had a severe hypoglycaemic emergency: a mixed-methods study
Authors: Duncan Edward A S , Fitzpatrick David , Ikegwuonu Theresa , Evans Josie , Maxwell Margaret 
Published: April 2018

Objectives(1) To compare the experiences of people who are affected by diabetes-related hypoglycaemia and either do or do not require an emergency attendance and (2) to measure the prevalence of impaired awareness of hypoglycaemia in patients who are attended by an ambulance service due to a severe hypoglycaemic event.DesignA sequential mixed-methods study.SettingA qualitative interview study was undertaken with 31 people with diabetes (types 1 and 2) resident in the central belt of Scotland. A national prevalence survey of 590 Scottish Ambulance Service patients who had recently experienced a severe hypoglycaemic emergency requiring ambulance clinicians attendance. Impaired awareness of hypoglycaemia was measured using two standardised measures.ResultsConsiderable differences in impaired awareness of hypoglycaemia were found in the experiences of participants who did or did not require the ambulance service to treat their severe hypoglycaemic events. Those who required an ambulance reported fewer warning signs and symptoms. The prevalence of impaired awareness of hypoglycaemia in ambulance service call-outs as assessed by two standardised measures was 53% and 60%, respectively.ConclusionsThe prevalence of impaired awareness of hypoglycaemia among those who require an ambulance following a hypoglycaemic event is more than twice that found in the general population of people with diabetes. This may be because the experiences of impaired awareness in people who require an ambulance following a severe hypoglycaemic event differ to those who do not. This study provides important information to guide future prehospital clinical practice, and to develop and evaluate theoretically informed interventions. Improvements in prehospital care for this patient population could lead to global improvements in health outcomes and decreased service costs.
Static strength of molybdenum to 92 GPa under radial X-ray diffraction
Authors: Xiong L. , Tu P. , Li B. , Wu S. Y. , Hao J. B. , Bai L. G. , Li X. D. , Liu J. 
Published: April 2018

The high-pressure strength of molybdenum (Mo) to 92 GPa has been studied by radial X-ray diffraction (RXRD) technique. The ratio of t/G is found to decrease above [Formula: see text]24 GPa, showing the yield of Mo which is caused by plastic deformation at this pressure. Combined with high-pressure shear modulus, it was found that the differential stress corresponding to the yield of Mo at 24 GPa due to plastic deformation is 1.73 GPa. The second increase of t values occurs after [Formula: see text]66 GPa, suggesting the strength of Mo with a differential stress of [Formula: see text]1.93 GPa. In addition, the maximum difference stress of molybdenum at 87 GPa is 3.01 GPa.
Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group
Authors: Laetsch Theodore W. , Roy Angshumoy , Xu Lin , Black Jennifer O. , Coffin Cheryl M. , Chi Yueh-Yun , Tian Jing , Spunt Sheri L. , Hawkins Douglas S. , Bridge Julia A. , Parsons D. Williams , Skapek Stephen X. 
Published: April 2018

Abstract
Purpose: A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy-number alterations and fusion status in patients with UDS prospectively treated on Children's Oncology Group protocol ARST0332.
Experimental Design: Copy-number alterations were assessed by OncoScan FFPE Express on 32 UDS. Whole-exome and transcriptome libraries from eight tumors with sufficient archived material were sequenced on HiSeq (2 × 100 bp). Targeted RNA-sequencing using Archer chemistry was performed on two additional cases.
Results: Five-year overall survival for patients with UDS was 83% (95% CI, 69%–97%) with risk-adapted therapy (surgery, chemotherapy, and radiotherapy). Both focal and arm-level copy-number alterations were common including gain of 1q (8/32, 25%) and loss of 1p (7/32, 22%), both of which occurred more often in clinically defined high-risk tumors. Tumors with both loss of 1p and gain of 1q carried an especially poor prognosis with a 5-year event-free survival of 20%. GISTIC analysis identified recurrent amplification of FGF1 on 5q31.3 (q = 0.03) and loss of CDKN2A and CDKN2B on 9p21.3 (q = 0.07). Known oncogenic fusions were identified in eight of 10 cases analyzed by next-generation sequencing.
Conclusions: Pediatric UDS generally has a good outcome with risk-adapted therapy. A high-risk subset of patients whose tumors have copy-number loss of 1p and gain of 1q was identified with only 20% survival. Oncogenic fusions are common in UDS, and next-generation sequencing should be considered for children with UDS to refine the diagnosis and identify potentially targetable drivers. Clin Cancer Res; 24(16); 3888–97. ©2018 AACR.
Evaluation of Biodistribution of Sulforaphane after Administration of Oral Broccoli Sprout Extract in Melanoma Patients with Multiple Atypical Nevi
Authors: Tahata Shawn , Singh Shivendra V. , Lin Yan , Hahm Eun-Ryeong , Beumer Jan H. , Christner Susan M. , Rao Uma N. , Sander Cindy , Tarhini Ahmad A. , Tawbi Hussein , Ferris Laura K. , Wilson Melissa , Rose Amy , Dietz Catherine M. , Hughes Ellen , Fahey Jed W. , Leachman Sancy A. , Cassidy Pamela B. , Butterfield Lisa H. , Zarour Hassane M. , Kirkwood John M. 
Published: April 2018

Abstract
Broccoli sprout extract containing sulforaphane (BSE-SFN) has been shown to inhibit ultraviolet radiation–induced damage and tumor progression in skin. This study evaluated the toxicity and potential effects of oral BSE-SFN at three dosages. Seventeen patients who each had at least 2 atypical nevi and a prior history of melanoma were randomly allocated to 50, 100, or 200 μmol oral BSE-SFN daily for 28 days. Atypical nevi were photographed on days 1 and 28, and plasma and nevus samples were taken on days 1, 2, and 28. Endpoints assessed were safety, plasma and skin sulforaphane levels, gross and histologic changes, IHC for phospho-STAT3(Y705), Ki-67, Bcl-2, HMOX1, and TUNEL, plasma cytokine levels, and tissue proteomics. All 17 patients completed 28 days with no dose-limiting toxicities. Plasma sulforaphane levels pooled for days 1, 2, and 28 showed median postadministration increases of 120 ng/mL for 50 μmol, 206 ng/mL for 100 μmol, and 655 ng/mL for 200 μmol. Median skin sulforaphane levels on day 28 were 0.0, 3.1, and 34.1 ng/g for 50, 100, and 200 μmol, respectively. Plasma levels of proinflammatory cytokines decreased from day 1 to 28. The tumor suppressor decorin was increased from day 1 to 28. Oral BSE-SFN is well tolerated at daily doses up to 200 μmol and achieves dose-dependent levels in plasma and skin. A larger efficacy evaluation of 200 μmol daily for longer intervals is now reasonable to better characterize clinical and biological effects of BSE-SFN as chemoprevention for melanoma. Cancer Prev Res; 11(7); 429–38. ©2018 AACR.
Predicted Land Carbon Dynamics Are Strongly Dependent on the Numerical Coupling of Nitrogen Mobilizing and Immobilizing Processes: A Demonstration with the E3SM Land Model
Authors: Tang Jinyun , Riley William J. 
Published: April 2018

AbstractWhile coupling carbon and nitrogen processes is critical for Earth system models to accurately predict future climate and land biogeochemistry feedbacks, it has not yet been analyzed how numerical methods that land biogeochemical models apply to couple soil mineral nitrogen mobilizing and immobilizing processes affect predicted ecosystem carbon and nitrogen cycling. These effects were investigated here by using the E3SM land model and an evaluation of three plausible and widely used numerical couplings: 1) the mineral nitrogen–based limitation scheme, 2) the net uptake–based limitation scheme, and 3) the proportional nitrogen flux–based limitation scheme. It was found that these three schemes resulted in large differences (with a range of 316 PgC) in predicted cumulative land–atmosphere carbon exchanges under the RCP4.5 atmospheric CO2 simulations. This large uncertainty is without accounting for the different representations of the many land biogeochemical processes, but is about 73% of the range (434 PgC) reported for CMIP5 RCP4.5 simulations. These results help explain the large uncertainty found in various model intercomparison experiments and suggest that more robust numerical implementations are needed to improve carbon–nutrient cycle coupling in terrestrial ecosystem models.
A Water Balance–Based, Spatiotemporal Evaluation of Terrestrial Evapotranspiration Products across the Contiguous United States
Authors: Carter Elizabeth , Hain Christopher , Anderson Martha , Steinschneider Scott 
Published: April 2018

AbstractAccurate gridded estimates of evapotranspiration (ET) are essential to the analysis of terrestrial water budgets. In this study, ET estimates from three gridded energy balance–based products (ETEB) with independent model formations and data forcings are evaluated for their ability to capture long-term climatology and interannual variability in ET derived from a terrestrial water budget (ETWB) for 671 gauged basins across the contiguous United States. All three ETEB products have low spatial bias and accurately capture interannual variability of ETWB in the central United States, where ETEB and ancillary estimates of change in total surface water storage (ΔTWS) from the GRACE satellite project appear to close terrestrial water budgets. In humid regions, ETEB products exhibit higher long-term bias, and the covariability of ETEB and ETWB decreases significantly. Several factors related to either failure of ETWB, such as errors in ΔTWS and precipitation, or failure of ETEB, such as treatment of snowfall and horizontal heat advection, explain some of these discrepancies. These results mirror and build on conclusions from other studies: on interannual time scales, ΔTWS and error in precipitation estimates are nonnegligible uncertainties in ET estimates based on a terrestrial water budget, and this confounds their comparison to energy balance ET models. However, there is also evidence that in at least some regions, climate and landscape features may also influence the accuracy and long-term bias of ET estimates from energy balance models, and these potential errors should be considered when using these gridded products in hydrologic applications.
Calibration and Validation of Reprocessed HY-2A Altimeter Wave Height Measurements Using Data from Buoys, Jason-2, Cryosat-2, and SARAL/AltiKa
Authors: Jiang Maofei , Xu Ke , Liu Yalong 
Published: April 2018

AbstractThe Haiyang-2A (HY-2A) satellite is China’s first ocean dynamic environment satellite, and the radar altimeter is one of its main payloads. In this study the HY-2A altimeter sensor interim geophysical dataset records (SIGDR) data are reprocessed to obtain better significant wave height (Hs) measurements over a period of more than four years (from 1 October 2011 to 15 March 2016). The reprocessed HY-2A Hs measurements are calibrated and validated using National Data Buoy Center (NDBC) buoys and several operating altimeters: Joint Altimetry Satellite Oceanography Network-2 (Jason-2), CryoSat-2, and Satellite with Argos Data Collection System and Ka-Band Altimeter (SARAL/ALtiKa) The final results of buoys and cross-altimeter comparisons show that the accuracy of the reprocessed HY-2A Hs measurements is significantly improved with respect to the Hs measurements in the operational HY-2A interim geophysical data record (IGDR) publicly distributed by the National Satellite Ocean Application Service (NSOAS), State Oceanic Administration (SOA) of China. Compared with the NDBC Hs measurements, the reprocessed HY-2A Hs measurements show a root-mean-square error (RMSE) of 0.215 m with a positive bias of 0.117 m. After calibrating with the two-branched corrections, the RMSE for the reprocessed HY-2A Hs measurements is reduced to 0.173 m, which is lower than those for the calibrated HY-2A IGDR, Jason-2, Cryosat-2, and SARAL measurements with an RMSE of 0.278, 0.233, 0.239, and 0.184 m, respectively. Long-term validation of the altimeter Hs measurements shows that the reprocessed HY-2A Hs measurements after calibration are stable with respect to the buoys and three other altimeters over the entire period. The reprocessed HY-2A Hs measurements are expected to improve the practical applicability of HY-2A Hs measurements significantly.
Priorities in Swedish Alcohol and Drug Treatment: Policies, Staff Views, and Competing Logics
Authors: Palm Jessica 
Published: April 2018

The aim of the article is to report how treatment staff think priorities for access to alcohol and drug treatment are and should be set and to describe the extent to which different client groups are seen as receiving the treatment they need. Questionnaires were sent to staff in the social and health care systems in Stockholm County. The empirical data is contrasted against official priorities and different ways of ethical reasoning. Official priorities are mainly based on an egalitarian way of reasoning. Data collected from staff indicates that “misusers with children,” “new misusers” and “youth” are seen as groups that should be prioritized, whereas few think that “persons who have been misusing for a long time” and “heavy misusers” should be prioritized. Staff also favored prioritizing a larger number of groups than are seen as receiving emphasis now. The reasoning of staff seems to be based on clients’ past actions, and to a lesser extent on utilitarian and egalitarian concerns.
Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival
Authors: Morse Elliot , Fujiwara Rance J. T. , Husain Zain , Judson Benjamin , Mehra Saral 
Published: April 2018

ObjectiveTo characterize the epidemiology of pediatric salivary cancer and associate patient, tumor, and treatment factors with treatment modality and survival.Study DesignCross‐sectional analysis.SettingUS national database.Subjects and MethodsWe identified 588 patients 19 years or younger diagnosed with salivary cancer in the National Cancer Database 2004‐2013. We characterized patient, tumor, and treatment factors as proportions and associated these factors with treatment modality and overall survival via multivariable logistic regression and multivariable Cox proportional hazards regression, respectively.ResultsIn total, 588 patients were included. Mucoepidermoid carcinoma was identified in 234 of 588 patients (40%) and acinar cell carcinoma in 215 of 588 (37%). Parotid tumors were seen in 504 (86%) of patients. Surgery alone was used to treat 351 (60%) of patients; surgery plus adjuvant radiation was used to treat 145 (25%). Overall 5‐year survival was 93%. Controlling for patient and tumor characteristics, treatment with surgery and radiation vs surgery alone was associated with improved overall survival (hazard ratio [HR] = 0.15; 95% confidence interval [CI], 0.02‐0.92; P =. 041). High tumor grade was associated with decreased overall survival (HR = 33.17; 95% CI, 5.89‐186.8; P <. 001). Treatment with surgery plus radiation remained associated with improved overall survival in the subset of patients with high tumor grade (HR = 0.12; 95% CI, 0.02‐0.64; P =. 014).ConclusionTumor grade is an important predictor of survival in pediatric patients with salivary gland cancer. Surgery plus adjuvant radiation vs surgery alone is associated with improved overall survival and may be considered for high‐risk patients, particularly those with high‐grade tumors.