bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous Nuclear Ribonucleoprotein M Facilitates Enterovirus Infection
Authors: Jagdeo Julienne M. , Dufour Antoine , Fung Gabriel , Luo Honglin , Kleifeld Oded , Overall Christopher M. , Jan Eric 
Published: April 2015

ABSTRACT

Picornavirus infection involves a dynamic interplay of host and viral protein interactions that modulates cellular processes to facilitate virus infection and evade host antiviral defenses. Here, using a proteomics-based approach known as TAILS to identify protease-generated neo-N-terminal peptides, we identify a novel target of the poliovirus 3C proteinase, the heterogeneous nuclear ribonucleoprotein M (hnRNP M), a nucleocytoplasmic shuttling RNA-binding protein that is primarily known for its role in pre-mRNA splicing. hnRNP M is cleaved
in vitro
by poliovirus and coxsackievirus B3 (CVB3) 3C proteinases and is targeted in poliovirus- and CVB3-infected HeLa cells and in the hearts of CVB3-infected mice. hnRNP M relocalizes from the nucleus to the cytoplasm during poliovirus infection. Finally, depletion of hnRNP M using small interfering RNA knockdown approaches decreases poliovirus and CVB3 infections in HeLa cells and does not affect poliovirus internal ribosome entry site translation and viral RNA stability. We propose that cleavage of and subverting the function of hnRNP M is a general strategy utilized by picornaviruses to facilitate viral infection.

IMPORTANCE
Enteroviruses, a member of the picornavirus family, are RNA viruses that cause a range of diseases, including respiratory ailments, dilated cardiomyopathy, and paralysis. Although enteroviruses have been studied for several decades, the molecular basis of infection and the pathogenic mechanisms leading to disease are still poorly understood. Here, we identify hnRNP M as a novel target of a viral proteinase. We demonstrate that the virus subverts the function of hnRNP M and redirects it to a step in the viral life cycle. We propose that cleavage of hnRNP M is a general strategy that picornaviruses use to facilitate infection.
Inefficient Codon Usage Impairs mRNA Accumulation: the Case of the v-FLIP Gene of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Bellare Priya , Dufresne Andrew , Ganem Don 
Published: April 2015

ABSTRACT
Latent Kaposi's sarcoma-associated herpesvirus (KSHV) genomes encode a homolog of cellular FLICE-inhibitory proteins (termed v-FLIP) that activates NF-κB and can trigger important proinflammatory and antiapoptotic changes in latently infected cells. The protein is present at very low levels in infection and has generally been difficult to efficiently express in recombinant vectors. Here we show that codon usage in the v-FLIP gene is strikingly suboptimal. Optimization of codon use in expression vectors, as expected, restores efficient protein expression. Surprisingly, however, it also dramatically increases the steady-state level of v-FLIP mRNA, at least in part by increasing mRNA stability. When codon-optimized v-FLIP sequences are reintroduced into intact KSHV genomes, the resulting virus expresses readily detectable monocistronic v-FLIP mRNAs that are undetectable in wild-type (WT) infection by blot hybridization, suggesting that such RNAs are in fact transcribed in WT infection but fail to accumulate. The overexpression of v-FLIP by codon-optimized latent genomes results in a 5- to 7-fold decrement in virus production following lytic induction, indicating that maximizing NF-κB signaling is deleterious to induction. These studies provide a clear explanation for the evolution of inefficient codon usage in this gene and point to a strong connection between translational efficiency and RNA accumulation in mammalian cells.

IMPORTANCE
This study reports that inefficient codon usage in a herpesviral gene is strikingly correlated with the inability of its mRNA to accumulate in cells; correction of efficient translatability restores RNA abundance. A similar correlation has been reported in yeast species, but the mechanisms operating in mammalian cells appear substantially different.
Intraoperative and Postoperative Anaesthetic and Analgesic Effect of Multipoint Transcutaneous Electrical Acupuncture Stimulation Combined with Sufentanil Anaesthesia in Patients Undergoing Supratentorial Craniotomy
Authors: Liu Xing , Li Shuqin , Wang Baoguo , An Lixin , Ren Xiujun , Wu Haifeng 
Published: April 2015

Objectives To investigate the anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation (TEAS) during supratentorial tumour resection for postoperative recovery and side effects. Methods In a blinded clinical trial, 92 patients scheduled for supratentorial craniotomy under general anaesthesia were randomly allocated into either a multipoint TEAS (n=46) or a sham TEAS group (n=46). All patients received total intravenous anaesthesia (TIVA) with propofol and sufentanil. The target concentration of sufentanil was adjusted and recorded according to mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). Patients in the TEAS group received TEAS 30 min before anaesthesia induction and this was maintained throughout the operation at four pairs of acupuncture points. Postoperative pain, recovery and side effects were evaluated. Results Eighty-eight patients completed the study. Continuous monitoring of MAP, HR and BIS showed stable values with no significant differences between the two groups (p>0.05). Sufentanil target plasma concentration in TEAS patients was significantly lower at some time points during supratentorial craniotomy, and total sufentanil consumption was significantly higher in the sham group (p<0.05). Postoperative recovery and pain were significantly improved by TEAS (p<0.001), without the postoperative side effects. Conclusions Multipoint TEAS at both proximal and distal points combined with TIVA can significantly decrease intraoperative sufentanil requirements, increase pain relief on postoperative day 1 and improve postoperative recovery of patients during supratentorial tumour resection, with no significant increase of side effects. These findings suggest that multipoint TEAS may be clinically effective as an adjunct to analgesia in intraoperative anaesthesia and postoperative pain treatment and may speed recovery. Trial Registration Number Chinese Clinical Trial Registry (registration number ChiCTR-TRC-10001078).
Survival in patients with breast cancer with bone metastasis: a Danish population-based cohort study on the prognostic impact of initial stage of disease at breast cancer diagnosis and length of the bone metastasis-free interval
Authors: Cetin Karynsa , Christiansen Christian Fynbo , Sværke Claus , Jacobsen Jacob Bonde , Sørensen Henrik Toft 
Published: April 2015

ObjectivesSince population-based data on prognostic factors affecting survival in patients with breast cancer with bone metastasis (BM) are currently limited, we conducted this nationwide retrospective cohort study to examine the prognostic role of disease stage at breast cancer diagnosis and length of BM-free interval (BMFI).SettingDenmark.Participants2427 women with a breast cancer diagnosis between 1997 and 2011 in the Danish Cancer Registry and a concurrent or subsequent BM diagnosis in the Danish National Registry of Patients.Primary and secondary outcome measuresSurvival (crude) based on Kaplan-Meier method and mortality risk (crude and adjusted for age, year of diagnosis, estrogen receptor status and comorbidity) based on Cox proportional hazards regression analyses by stage of disease at breast cancer diagnosis and by length of BMFI (time from breast cancer to BM diagnosis), following patients from BM diagnosis until death, emigration or until 31 December 2012, whichever came first.ResultsSurvival decreased with more advanced stage of disease at the time of breast cancer diagnosis; risk of mortality during the first year following a BM diagnosis was over two times higher for those presenting with metastatic versus localised disease (adjusted HR=2.12 (95% CI 1.71 to 2.62)). With respect to length of BMFI, survival was highest in women with a BMFI <1 year (ie, in those who presented with BM at the time of breast cancer diagnosis or were diagnosed within 1 year). However, among patients with a BMFI ≥1 year, survival increased with longer BMFI (1-year survival: 39.9% (95% CI 36.3% to 43.6%) for BMFI 1 to <3 years and 52.6% (95% CI 47.4% to 57.6%) for BMFI ≥5 years). This pattern was also observed in multivariate analyses.ConclusionsStage of disease at breast cancer diagnosis and length of BMFI appear to be important prognostic factors for survival following BM.
A minimally invasive technique for decompression of Chiari malformation type I (DECMI study): study protocol for a randomised controlled trial
Authors: Hu Yu , Liu Jiagang , Chen Haifeng , Jiang Shu , Li Qiang , Fang Yuan , Gong Shuhui , Wang Yuelong , Huang Siqing 
Published: April 2015

IntroductionChiari malformation type I (CM-I) is a congenital hindbrain anomaly that requires surgical decompression in symptomatic patients. Posterior fossa decompression with duraplasty (PFDD) has been widely practiced in Chiari decompression, but dural opening carries a high risk of surgical complications. A minimally invasive technique, dural splitting decompression (DSD), preserves the inner layer of the dura without dural opening and duraplasty, potentially reducing surgical complications, length of operative time and hospital stay, and cost. If DSD is non-inferior to PFDD in terms of clinical improvement, DSD could be an alternative treatment modality for CM-I. So far, no randomised study of surgical treatment of CM-I has been reported. This study aims to evaluate if DSD is an effective, safe and cost-saving treatment modality for adult CM-I patients, and may provide evidence for using the minimally invasive procedure extensively.Methods and analysisDECMI is a randomised controlled, single-masked, non-inferiority, single centre clinical trial. Participants meeting the criteria will be randomised to the DSD group and the PFDD group in a 1:1 ratio. The primary outcome is the rate of clinical improvement, which is defined as the complete resolution or partial improvement of the presenting symptoms/signs. The secondary outcomes consist of the incidence of syrinx reduction, postoperative morbidity rates, reoperation rate, quality of life (QoL) and healthcare resource utilisation. A total of 160 patients will be included and followed up at 3 and 12 months postoperatively.Ethics and disseminationThe study protocol was approved by the Biological and Medical Ethics Committee of West China Hospital. The findings of this trial will be published in a peer-reviewed scientific journal and presented at scientific conferences.Trial registration numberChiCTR-TRC-14004099.
Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma
Authors: Hirbe Angela C. , Dahiya Sonika , Miller Christopher A. , Li Tiandao , Fulton Robert S. , Zhang Xiaochun , McDonald Sandra , DeSchryver Katherine , Duncavage Eric J. , Walrath Jessica , Reilly Karlyne M. , Abel Haley J. , Pekmezci Melike , Perry Arie , Ley Timothy J. , Gutmann David H. 
Published: April 2015

Abstract
Purpose: Malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have used a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma.
Experimental Design: Whole-exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n = 3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was used for functional analysis.
Results: There was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with nonsynonymous somatic mutations (βIII-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Finally, increased βIII-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo.
Conclusions: Collectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study. Clin Cancer Res; 21(18); 4201–11. ©2015 AACR.
Improved Simulation of Regional Climate by Global Models with Higher Resolution: Skill Scores Correlated with Grid Length*
Authors: Watterson I. G. 
Published: April 2015

Abstract
The current generation of climate models, as represented by phase 5 of the Coupled Model Intercomparison Project (CMIP5), has previously been assessed as having more skill in simulating the observed climate than the previous ensemble from phase 3 of CMIP (CMIP3). Furthermore, the skill of models in reproducing seasonal means of precipitation, temperature, and pressure from two observational datasets, quantified by the nondimensional Arcsin–Mielke skill score, appeared to be influenced by model resolution. The analysis is extended to 42 CMIP5 and 24 CMIP3 models. For the combined skill scores for six continents, averaged over the three variables and four seasons, the correlation with model grid length in the 66-model ensemble is −0.73. Focusing on the comparison with ERA-Interim data at higher resolution and with greater regional detail, correlations are nearly as strong for scores over the ocean domain as for land. For the global domain (excluding the Antarctic cap), the correlation of the overall skill score with grid length is −0.61, and it is nearly as strong for each variable. For most tests the improved averaged score of CMIP5 models relative to those from CMIP3 is largely consistent with their increased resolution. However, the improvement for precipitation and the correlations with length are both smaller if rmse is used as a metric. They are smaller again using the GPCP observational data, as the regional detail from a high-resolution model can lead to larger differences when compared to relatively smooth observational fields.
Arctic Radiative Fluxes: Present-Day Biases and Future Projections in CMIP5 Models
Authors: English Jason M. , Gettelman Andrew , Henderson Gina R. 
Published: April 2015

Abstract
Radiative fluxes are critical for understanding the energy budget of the Arctic region, where the climate has been changing rapidly and is projected to continue to change. This work investigates causes of present-day biases and future projections of top-of-atmosphere (TOA) Arctic radiative fluxes in phase 5 of the Coupled Model Intercomparison Project (CMIP5). Compared to Clouds and the Earth’s Radiant Energy System Energy Balanced and Filled (CERES-EBAF), CMIP5 net TOA downward shortwave (SW) flux biases are larger than outgoing longwave radiation (OLR) biases. The primary contributions to modeled TOA SW flux biases are biases in cloud amount and snow cover extent compared to the GCM-Oriented CALIPSO Cloud Product (CALIPSO-GOCCP) and the newly developed Making Earth System Data Records for Use in Research Environments (MEaSUREs) dataset, respectively (with most models predicting insufficient cloud amount and snow cover in the Arctic), and biases with sea ice albedo. Future projections (2081–90) with representative concentration pathway 8.5 (RCP8.5) simulations suggest increasing net TOA downward SW fluxes (+8 W m−2) over the Arctic basin due to a decrease of surface albedo from melting snow and ice, and increasing OLR (+6 W m−2) due to an increase in surface temperatures. The largest contribution to future Arctic net TOA downward SW flux increases is declining sea ice area, followed by declining snow cover area on land, reductions to sea ice albedo, and reductions to snow albedo on land. Cloud amount is not projected to change significantly. These results suggest the importance of accurately representing both the surface area and albedos of sea ice and snow cover as well as cloud amount in order to accurately represent TOA radiative fluxes for the present-day climate and future projections.
Alcohol use amongst older adults: Knowledge and beliefs of occupational therapists working in physical health care settings
Authors: Maclean Fiona , Gill Jan , O’May Fiona , Breckenridge Jenna 
Published: April 2015

Introduction There is little discussion in the United Kingdom occupational therapy literature surrounding the topic of older people and alcohol, despite the growing prevalence of alcohol-related health problems in older adults resulting from an ageing population and changing patterns of consumption. Occupational therapists in physical health care settings are likely to work with older people whose drinking pattern may not be alcohol dependent, but may put their physical or psychological health at risk. Method A survey methodology was employed using open and closed questions, recruiting occupational therapists (band 5 to 9) ( n = 122) working with older people (65+ years) in physical health care settings across all, except one, National Health Service Regional Health Boards in Scotland. Results Responses highlight gaps in occupational therapists’ knowledge around alternative ‘safe limits’ of alcohol intake for older people. Belief in professional role was evident, but the perception was that this was not supported by undergraduate education. Occupation focused theory and assessment were not prioritized when considering alcohol in the older adult. Conclusion This study has highlighted a need to develop pre- and post-qualification education for occupational therapists, to enhance understanding of theory, assessment and knowledge of alcohol with older adults in physical health care settings.
Association of Equipment Worn and Concussion Injury Rates in National Collegiate Athletic Association Football Practices
Authors: Kerr Zachary Y. , Hayden Ross , Dompier Thomas P. , Cohen Randy 
Published: April 2015

Background: The epidemiology of football-related concussions has been extensively examined. However, although football players experience more at-risk exposure time during practices than competitions, there is a dearth of literature examining the nature of the activities or equipment worn during practice. In particular, varying levels of equipment worn during practices may place players at varying levels of risk for concussion. Purpose: To describe the epidemiology of NCAA men’s football concussions that occurred during practices from the 2004-2005 to 2008-2009 academic years by amount of equipment worn. Study Design: Descriptive epidemiology study. Methods: Men’s collegiate football data from the National Collegiate Athletic Association Injury Surveillance System (NCAA ISS) during the 5-year study period were analyzed. Injury rates and injury rate ratios (RRs) were reported with 95% confidence intervals. Results: During the study period, 795 concussions were reported during practices, resulting in an injury rate of 0.39 per 1000 athlete-exposures (AEs) (95% CI, 0.36-0.42). Among NCAA divisions, Division III had the highest concussion rate (0.54/1000 AEs), followed by Division I (0.34/1000 AEs) and Division II (0.24/1000 AEs) (all P values for RRs comparing divisions <.001). Most concussions in practice occurred when players were fully padded (69.9%), followed by wearing shells (23.5%) and helmets only (1.9%). The practice concussion rate was higher in fully padded practices (0.66/1000 AEs) compared with practices when shells were worn (0.33/1000 AEs; RR = 1.99 [95% CI, 1.69-2.35]; P < .001) and practices when only helmets were worn (0.03/1000 AEs; RR = 22.39 [95% CI, 13.41-37.39]; P < .001). The practice concussion rate of the preseason (0.76/1000 AEs) was higher than that of the regular season (0.18/1000 AEs; RR = 4.14 [95% CI, 3.55-4.83]; P < .001) and that of postseason (0.25/1000 AEs; RR = 3.02 [95% CI, 1.95-4.67]; P < .001). The types of practice with the highest concussion rate were scrimmages (1.55/1000 AEs). Although only 3 concussions were sustained during scrimmage practices in which players wore shells, the concussion rate (2.84/1000 AEs) was higher than all other reported rates. Conclusion: Practice concussion rates are highest during fully padded practices, preseason practices, and scrimmages, suggesting that the nature, focus, and intensity of football practices affect concussion risk. In addition, coaching staff should continue to closely monitor player safety during scrimmages. Meanwhile, future surveillance should examine whether removing scrimmages, particularly those that are not fully padded, will meaningfully reduce the incidence and rate of concussions.
Individual variations in ankle brachial index measurement among Turkish adults
Authors: Demir Orhan , Tasci Ilker , Acikel Cengizhan , Saglam Kenan , Gezer Mustafa , Acar Ramazan , Yildiz Birol , Bulucu Fatih , Kabul Hasan Kutsi , Dogan Mustafa Inanc , Koc Bayram 
Published: April 2015

Purpose Variability of ankle brachial index (ABI) measured by the same observer in the same individual on three different occasions was examined. Basic methods A single morning ABI was initially determined (measurement 1) with handheld Doppler device. One to four weeks apart, another morning (measurement 2) and afternoon (measurement 3) ABI was measured on the same day. Principal findings A total of 161 adults were enrolled. Mean ABI was similar among the three measurements. ABI differed more than ≥0.15 in 15 individuals between measurement 1 and 3, in 10 subjects between measurement 1 and 2, and in 12 individuals between measurement 2 and 3. Intra-group correlation coefficients of reproducibility of ABI were 0.808 for single measurements (coefficient of the values lacking association with each other), and 0.927 for average measurements (coefficient of the values that were associated with each other). Conclusions Although reproducibility of ABI values was found satisfactory, up to 12% of participants displayed more than 0.15 alternations between measurements, either on the same day or more than a week apart.