bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Ingestion of Caffeinated Chewing Gum Improves Repeated Sprint Performance of Team Sport Athletes With Low Habitual Caffeine Consumption
Authors: Evans Mark , Tierney Peter , Gray Nicola , Hawe Greg , Macken Maria , Egan Brendan 
Published: November 2017

The effects of acute ingestion of caffeine on short-duration high-intensity performance are equivocal, while studies of novel modes of delivery and the efficacy of low doses of caffeine are warranted. The aims of the present study were to investigate the effect of acute ingestion of caffeinated chewing gum on repeated sprint performance (RSP) in team sport athletes, and whether habitual caffeine consumption alters the ergogenic effect, if any, on RSP. A total of 18 male team sport athletes undertook four RSP trials using a 40-m maximum shuttle run test, which incorporates 10 × 40-m sprints with 30 s between the start of each sprint. Each participant completed two familiarization sessions, followed by caffeine (CAF; caffeinated chewing gum; 200 mg caffeine) and placebo (PLA; noncaffeinated chewing gum) trials in a randomized, double-blind manner. RSP, assessed by sprint performance decrement (%), did not differ (p = .209; effect size = 0.16; N = 18) between CAF (5.00 ± 2.84%) and PLA (5.43 ± 2.68%). Secondary analysis revealed that low habitual caffeine consumers (<40 mg/day, n = 10) experienced an attenuation of sprint performance decrement during CAF relative to PLA (5.53 ± 3.12% vs. 6.53 ± 2.91%, respectively; p = .049; effect size =0.33); an effect not observed in moderate/high habitual caffeine consumers (>130 mg/day, n = 6; 3.98 ± 2.57% vs. 3.80 ± 1.79%, respectively; p = .684; effect size = 0.08). The data suggest that a low dose of caffeine in the form of caffeinated chewing gum attenuates the sprint performance decrement during RSP by team sport athletes with low, but not moderate-to-high, habitual consumption of caffeine.
The Effect of Mode of Transport on Intraindividual Variability in Glycemic and Insulinemic Response Testing
Authors: El-Chab Alaaddine , Clegg Miriam E. 
Published: November 2017

The effect of light- to moderate-intensity exercise, such as that used as a mode of transport, on glycemic response testing is unclear. The aim was to investigate the effect of acute exercise (walking and cycling), simulated to act as a mode of transport, prior to glycemic response testing on the intraindividual variability of blood glucose and insulin. A total of 11 male participants visited the laboratory four times. Initially, they undertook a maximum oxygen uptake and two submaximal exercise tests. For the other three visits, they either rested (25 min), cycled, or walked 5 km followed by a 2-hr glycemic response test after consuming a glucose drink (50 g of available carbohydrate). The mean coefficient of variation of each transport group was below the International Organization for Standardization cutoff of 30%. The highest mean coefficient of variation of glucose area under the curve (AUC) was between the rest and the walking trials (30%) followed by walking and cycling (26%). For insulin AUC, the highest mean coefficient of variation was between walking and cycling (28%) followed by rest and walking (24%). The lowest glucose AUC and insulin AUC were between rest and cycling (25% and 14%, respectively). This study did not find differences (p > .05) between the conditions for glucose AUC (at 120 min, rest: 134.5 ± 104.6 mmol/L; walking: 115.5 ± 71.7 mmol/L; and cycling: 142.5 ± 75 mmol/L) and insulin AUC (at 120 min, rest: 19.45 ± 9.12 μmol/ml; walking: 16.49 ± 8.42 μmol/ml; and cycling: 18.55 ± 9.23 μmol/ml). The results indicate no difference between the tests undertaken; however, further research should ensure the inclusion of two rest conditions.
Validity of the Online Athlete Management System to Assess Training Load
Authors: Menaspà Miranda J. , Menaspà Paolo , Clark Sally A. , Fanchini Maurizio 
Published: November 2017

Purpose: To validate the quantification of training load (session rating of perceived exertion [s-RPE]) in an Australian Olympic squad (women’s water polo), assessed with the use of a modified RPE scale collected via a newly developed online system (athlete management system). Methods: Sixteen elite women water polo players (age = 26 [3] y, height  = 1.78 [0.05] m, and body mass  = 75.5 [7.1] kg) participated in the study. Thirty training sessions were monitored for a total of 303 individual sessions. Heart rate was recorded during training sessions using continuous heart-rate telemetry. Participants were asked to rate the intensity of the training sessions on the athlete management system RPE scale, using an online application within 30 min of completion of the sessions. Individual relationships between s-RPE and both Banister training impulse (TRIMP) and Edwards’ method were analyzed. Results: Individual correlations with s-RPE ranged between r = .51 and .79 (Banister TRIMP) and r = .54 and .83 (Edwards’ method). The percentages of moderate and large correlation were 81% and 19% between s-RPE method and Banister TRIMP, and 56% and 44% between s-RPE and Edwards’ method. Conclusions: The online athlete management system for assessing s-RPE was shown to be a valid indicator of internal training load and can be used in elite sport.
Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation
Authors: Stakaitytė Gabrielė , Nwogu Nnenna , Dobson Samuel J. , Knight Laura M. , Wasson Christopher W. , Salguero Francisco J. , Blackbourn David J. , Blair G. Eric , Mankouri Jamel , Macdonald Andrew , Whitehouse Adrian 
Published: November 2017

ABSTRACT

Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β
1
integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC.

IMPORTANCE
Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds upon our previous observations, which demonstrated that the MCPyV ST antigen enhances cell motility, providing a potential link between MCPyV protein expression and the highly metastatic nature of MCC. Here, we show that MCPyV ST remodels the actin cytoskeleton, promoting the formation of filopodia, which is essential for MCPyV ST-induced cell motility, and we also implicate the activity of specific Rho family GTPases, Cdc42 and RhoA, in these processes. Moreover, we describe a novel mechanism for the activation of Rho-GTPases and the cell motility pathway due to the interaction between MCPyV ST and the cellular phosphatase catalytic subunit PP4C, which leads to the specific dephosphorylation of β1 integrin. These findings may therefore provide novel strategies for therapeutic intervention for disseminated MCC.
Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160
Authors: Polpitiya Arachchige Sachith , Henke Wyatt , Pramanik Ankita , Kalamvoki Maria , Stephens Edward B. 
Published: November 2017

ABSTRACT
Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways.

IMPORTANCE
HIV-1 infection of humans results in AIDS, characterized by the loss of CD4
+
T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell.
Aortic valve replacement associated with survival in severe regurgitation and low ejection fraction
Authors: Fiedler Amy G , Bhambhani Vijeta , Laikhter Elizabeth , Picard Michael H , Wasfy Meagan M , Tolis George , Melnitchouk Serguei , Sundt Thoralf M , Wasfy Jason H 
Published: November 2017

ObjectivesAlthough guidelines support aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular ejection fraction (LVEF) <50%, severe left ventricular dysfunction (LVEF <35%) is thought to confer high surgical risk. We sought to determine if a survival benefit exists with AVR compared with medical management in this high-risk, relatively rare population.MethodsA large institutional echocardiography database was queried to identify patients with severe AR and LVEF <35%. Manual chart review was performed. Due to small sample size and population heterogeneity, corrected group prognosis method was applied, which calculates the adjusted survival curve for each individual using fitted Cox proportional hazard model. Average survival adjusted for comorbidities and age was then calculated using the weighted average of the individual survival curves.ResultsInitially, 2 54 614 echocardiograms were considered, representing 1 45 785 unique patients, of which 40 patients met inclusion criteria. Of those, 18 (45.0%) underwent AVR and 22 (55.0%) were managed medically. Absolute mortality was 27.8% in the AVR group and 91.2% in the medical management group. After multivariate adjustment, end-stage renal disease (HR=17.633, p=0.0335) and peripheral arterial disease (HR=6.050, p=0.0180) were associated with higher mortality. AVR was associated with lower mortality (HR=0.143, p=0.0490). Mean follow-up time of the study cohort was 6.58 years, and mean survival for patients undergoing AVR was 6.31 years.ConclusionsEven after adjustment for clinical characteristics and patient age, AVR is associated with higher survival for patients with low LVEF and severe AR. Although treatment selection bias cannot be completely eliminated by this analysis, these results provide some evidence that surgery may be associated with prolonged survival in this high-risk patient group.
Aortic sinus diameter in middle age is associated with body size in young adulthood
Authors: Hernesniemi Jussi A , Heiskanen Jarkko , Ruohonen Saku , Kartiosuo Noora , Hutri-Kähönen Nina , Kähönen Mika , Jokinen Eero , Tossavainen Päivi , Kallio Merja , Laitinen Tomi , Lehtimäki Terho , Viikari Jorma S A , Juonala Markus , Raitakari Olli T 
Published: November 2017

ObjectiveAortic sinus dilatation can lead to aortic valve regurgitation or even aortic dissection. Our objective was to examine the association between body surface area (BSA) measures from childhood to middle age and aortic sinus diameter in middle age. Understanding the relation of these two clarifies how aortic size is normally determined.MethodsCardiovascular Risk in Young Finns Study is a longitudinal study with follow-up of over 31 years (1980–2011). The study comprises information of body composition from multiple time points of 1950 subjects with cardiac ultrasound measurements made in 2011. The association between BSA in different ages and aortic sinus diameter in middle age was analysed by linear regression modelling adjusted with age, sex and diastolic blood pressure. Missing BSA values were derived for each life year (ages 3–33 years) from subject-specific curves for body weight and height estimated from longitudinal measurements using mixed model regression splines.ResultsBSA estimates in early 20s are most strongly associated with aortic sinus diameter in middle age. Top association was observed at age 23 years with one SD increase in estimated BSA corresponding to 1.04 mm (0.87–1.21 mm) increase in aortic diameter. Increase in body weight beyond early 20s does not associate with aortic sinus diameter, and the association between middle age BSA and aortic size is substantially weaker (0.74 mm increase (0.58–0.89 mm)). These results were confirmed in a subpopulation using only measured data.ConclusionThe association between aortic sinus diameter and BSA is stronger when considering BSA in young adulthood compared with BSA in middle age.
Using Coq to write fast and correct Haskell
Authors: Wiegley John , Delaware Benjamin 
Published: November 2017

Correctness and performance are often at odds in the field of systems engineering, either because correct programs are too costly to write or impractical to execute, or because well-performing code involves so many tricks of the trade that formal analysis is unable to isolate the main properties of the algorithm.
As a prime example of this tension, Coq is an established proof environment that allows writing correct, dependently-typed code, but it has been criticized for exorbitant development times, forcing the developer to choose between optimal code or tractable proofs. On the other side of the divide, Haskell has proven itself to be a capable, well-typed programming environment, yet easy-to-read, straightforward code must all too often be replaced by highly optimized variants that obscure the author's original intention.
This paper builds on the existing Fiat refinement framework to bridge this divide, demonstrating how to derive a correct-by-construction implementation that meets (or exceeds) the performance characteristics of highly optimized Haskell, starting from a high-level Coq specification. To achieve this goal, we extend Fiat with a stateful notion of refinement of abstract data types and add support for extracting stateful code via a free monad equipped with an algebra of heap-manipulating operations. As a case study, we reimplement a subset of the popular bytestring library, with little to no loss of performance, while retaining a high guarantee of program correctness.
Age- and speed-dependent modulation of gaits in DSCAM2Jmutant mice
Authors: Thiry Louise , Lemieux Maxime , Bretzner Frédéric 
Published: November 2017

Gaits depend on the interplay between distributed spinal neural networks, termed central pattern generators, generating rhythmic and coordinated movements, primary afferents, and descending supraspinal inputs. Recent studies demonstrated that the mouse displays a rich repertoire of gaits. Changes in gaits occur in mutant mice lacking particular neurons or molecular signaling pathways implicated in the normal establishment of these neural networks. Given the role of the Down syndrome cell adherence molecule (DSCAM) to the formation and maintenance of spinal interneuronal circuits and sensorimotor integration, we have investigated its functional contribution to gaits over a wide range of locomotor speeds using freely walking mice. We show in this study that the DSCAM2Jmutation, while not precluding any gait, impairs the age- and speed-dependent modulation of gaits. It impairs the ability of mice to maintain their locomotion at high treadmill speeds. DSCAM2Jmutation induces the dominance of lateral walk over trot and the emergence of aberrant gaits for mice, such as pace and diagonal walk. Gaits were also more labile in DSCAM2Jmutant mice, i.e., less stable, less attractive, and less predictable than in their wild-type littermates. Our results suggest that the DSCAM mutation affects the behavioral repertoire of gaits in an age- and speed-dependent manner.NEW & NOTEWORTHY Gaits evolve throughout development, up to adulthood, and according to the genetic background. Using mutant mice lacking DSCAM (a cell adherence molecule associated with Down syndrome), we show that the DSCAM2Jmutation alters the repertoire of gaits according to the mouse’s age and speed, and prevents fast gaits. Such an incapacity suggests a reorganization of spinal, propriospinal, and supraspinal neuronal circuits underlying locomotor control in DSCAM2Jmutant mice.
TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells
Authors: Li Taiwen , Fan Jingyu , Wang Binbin , Traugh Nicole , Chen Qianming , Liu Jun S. , Li Bo , Liu X. Shirley 
Published: November 2017

Abstract
Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor–immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor–immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108–10. ©2017 AACR.
Integrating DNA Methylation and Hydroxymethylation Data with the Mint Pipeline
Authors: Cavalcante Raymond G. , Patil Snehal , Park Yongseok , Rozek Laura S. , Sartor Maureen A. 
Published: November 2017

Abstract
DNA methylation (5mC) plays important roles in mammalian development, oncogenesis, treatment response, and responses to the environment. DNA hydroxymethylation (5hmC) is also an informative epigenetic mark with distinct roles in regulation and cancer. Gold-standard, widely used technologies (bisulfite conversion, followed by deep sequencing) cannot distinguish between 5mC and 5hmC. Therefore, additional experiments are required to differentiate the two marks, and in silico methods are needed to analyze, integrate, and interpret these data. We developed the Methylation INTegration (mint) pipeline to support the comprehensive analysis of bisulfite conversion and immunoprecipitation-based methylation and hydroxymethylation assays, with additional steps toward integration, visualization, and interpretation. The pipeline is available as both a command line and a Galaxy graphical user interface tool. Both implementations require minimal configuration while remaining flexible to experiment specific needs. Cancer Res; 77(21); e27–30. ©2017 AACR.
Variant Review with the Integrative Genomics Viewer
Authors: Robinson James T. , Thorvaldsdóttir Helga , Wenger Aaron M. , Zehir Ahmet , Mesirov Jill P. 
Published: November 2017

Abstract
Manual review of aligned reads for confirmation and interpretation of variant calls is an important step in many variant calling pipelines for next-generation sequencing (NGS) data. Visual inspection can greatly increase the confidence in calls, reduce the risk of false positives, and help characterize complex events. The Integrative Genomics Viewer (IGV) was one of the first tools to provide NGS data visualization, and it currently provides a rich set of tools for inspection, validation, and interpretation of NGS datasets, as well as other types of genomic data. Here, we present a short overview of IGV's variant review features for both single-nucleotide variants and structural variants, with examples from both cancer and germline datasets. IGV is freely available at https://www.igv.org. Cancer Res; 77(21); e31–34. ©2017 AACR.
DINC 2.0: A New Protein–Peptide Docking Webserver Using an Incremental Approach
Authors: Antunes Dinler A. , Moll Mark , Devaurs Didier , Jackson Kyle R. , Lizée Gregory , Kavraki Lydia E. 
Published: November 2017

Abstract
Molecular docking is a standard computational approach to predict binding modes of protein–ligand complexes by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accuracy and efficiency greatly decays for ligands with more than 10 flexible bonds. This prevents a broader use of these tools to dock larger ligands, such as peptides, which are molecules of growing interest in cancer research. To overcome this limitation, our group has previously proposed a meta-docking strategy, called DINC, to predict binding modes of large ligands. By incrementally docking overlapping fragments of a ligand, DINC allowed predicting binding modes of peptide-based inhibitors of transcription factors involved in cancer. Here, we describe DINC 2.0, a revamped version of the DINC webserver with enhanced capabilities and a more user-friendly interface. DINC 2.0 allows docking ligands that were previously too challenging for DINC, such as peptides with more than 25 flexible bonds. The webserver is freely accessible at http://dinc.kavrakilab.org, together with additional documentation and video tutorials. Our team will provide continuous support for this tool and is working on extending its applicability to other challenging fields, such as personalized immunotherapy against cancer. Cancer Res; 77(21); e55–57. ©2017 AACR.