bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Glucose and Caffeine Nasal Sprays Influence Exercise or Cognitive Performance?
Authors: De Pauw Kevin , Roelands Bart , Van Cutsem Jeroen , Decroix Lieselot , Valente Angelica , Taehee Kim , Lettan Robert B. , Carrillo Andres E. , Meeusen Romain 
Published: February 2017

Introduction:Nasal spray (NAS) containing caffeine (CAF) or glucose (GLUC) activates sensory(motor) cortices.
Purpose:To investigate the influence of CAF or GLUC NAS on exercise and cognitive performance.
Methods:Eleven male subjects (age 22 ± 2 y) performed a maximal cycle test and 2 familiarization and 3 experimental trials. Each trial included a 30-s Wingate test and a 30-min time-trial (TT) performance test interspersed by 15 min of rest. Before and after each exercise test a Stroop task was conducted. Placebo NAS with or without CAF or GLUC was provided before each exercise session and at each completed 25% of the TT. Exercise-performance, physiological, and cognitive measures were obtained. Magnitude-based inferences determined the likelihood that NAS solutions would be beneficial, trivial, or negative to exercise-performance measures based on the smallest worthwhile effect. Physiological and cognitive measures were analyzed using (non)parametric tests (P < .05).
Results:GLUC NAS substantially increased the average power output during the TT (very likely beneficial: 98%). No further worthwhile exercise-performance enhancements were found for both substances. In addition, no significant differences in physiological and cognitive measures were observed. In line with mouth rinsing, GLUC was shown to substantially enhance endurance performance, probably due to the activation of the olfactory pathway and/or extra-oral sweet-taste receptors.
Conclusion:GLUC NAS enhances endurance performance, which indicates a novel administration route. The higher activity in sensory brain cortices probably elicited the ergogenic effect. However, no further physiological and cognitive changes occurred, indicating that higher doses of substrates might be required.
Relationships of Functional Tests Following ACL Reconstruction: Exploratory Factor Analyses of the Lower Extremity Assessment Protocol
Authors: DiFabio Melissa , Slater Lindsay V. , Norte Grant , Goetschius John , Hart Joseph M. , Hertel Jay 
Published: February 2017

Context:After ACL reconstruction (ACLR), deficits are often assessed using a variety of functional tests, which can be time consuming. It is unknown whether these tests provide redundant or unique information.Objective:To explore relationships between components of a battery of functional tests, the Lower Extremity Assessment Protocol (LEAP) was created to aid in developing the most informative, concise battery of tests for evaluating ACLR patients.Design:Descriptive, cross-sectional.Setting:Laboratory.Participants:76 ACLR patients (6.86±3.07 months postoperative) and 54 healthy participants.Intervention:Isokinetic knee flexion and extension at 90 and 180 degrees/second, maximal voluntary isometric contraction for knee extension and flexion, single leg balance, 4 hopping tasks (single, triple, crossover, and 6-meter timed hop), and a bilateral drop vertical jump that was scored with the Landing Error Scoring System (LESS).Main Outcome Measures:Peak torque, average torque, average power, total work, fatigue indices, center of pressure area and velocity, hop distance and time, and LESS score. A series of factor analyses were conducted to assess grouping of functional tests on the LEAP for each limb in the ACLR and healthy groups and limb symmetry indices (LSI) for both groups. Correlations were run between measures that loaded on retained factors.Results:Isokinetic and isometric strength tests for knee flexion and extension, hopping, balance, and fatigue index were identified as unique factors for all limbs. The LESS score loaded with various factors across the different limbs. The healthy group LSI analysis produced more factors than the ACLR LSI analysis. Individual measures within each factor had moderate to strong correlations. Isokinetic and isometric strength, hopping, balance, and fatigue index provided unique information.Conclusions:Within each category of measures, not all tests may need to be included for a comprehensive functional assessment of ACLR patients due to the high amount of shared variance between them.
The Human Immune Response to Respiratory Syncytial Virus Infection
Authors: Russell Clark D. , Unger Stefan A. , Walton Marc , Schwarze Jürgen 
Published: February 2017

SUMMARYRespiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models andin vitrostudies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.
Diagnostic Accuracy of Cerebrospinal Fluid Procalcitonin in Bacterial Meningitis Patients with Empiric Antibiotic Pretreatment
Authors: Li Wen , Sun Xiaolong , Yuan Fang , Gao Qiong , Ma Yue , Jiang Yongli , Yang Xiai , Yang Fang , Ma Lei , Jiang Wen 
Published: February 2017

ABSTRACT

Accurate diagnosis of bacterial meningitis (BM) relies on cerebrospinal fluid (CSF) Gram staining and bacterial culture, which often present high false-negative rates because of antibiotic abuse. Thus, a novel and reliable diagnostic biomarker is required. Procalcitonin (PCT) has been well demonstrated to be specifically produced from peripheral tissues by bacterial infection, which makes it a potential diagnostic biomarker candidate. Here, we performed a prospective clinical study comprising a total of 143 patients to investigate the diagnostic value of CSF PCT, serum PCT, and other conventional biomarkers for BM. Patients were assigned to the BM (
n
= 49), tuberculous meningitis (TBM) (
n
= 25), viral meningitis/encephalitis (VM/E) (
n
= 34), autoimmune encephalitis (AIE) (
n
= 15), or noninflammatory nervous system diseases (NINSD) group (
n
= 20). Empirical antibiotic pretreatment was not an exclusion criterion. Our results show that the CSF PCT level was significantly (
P
< 0.01) higher in patients with BM (median, 0.22 ng/ml; range, 0.13 to 0.54 ng/ml) than in those with TBM (median, 0.12 ng/ml; range, 0.07 to 0.16 ng/ml), VM/E (median, 0.09 ng/ml; range, 0.07 to 0.11 ng/ml), AIE (median, 0.06 ng/ml; range, 0.05 to 0.10 ng/ml), or NINSD (median, 0.07 ng/ml; range, 0.06 to 0.08 ng/ml). Among the assessed biomarkers, CSF PCT exhibited the largest area under the receiver operating characteristic curve (0.881; 95% confidence interval, 0.810 to 0.932; cutoff value, 0.15 ng/ml; sensitivity, 69.39%; specificity, 91.49%). Our study sheds light upon the diagnostic dilemma of BM due to antibiotic abuse. (This study has been registered at ClinicalTrials.gov under registration no. NCT02278016.)
Online Databases for Taxonomy and Identification of Pathogenic Fungi and Proposal for a Cloud-Based Dynamic Data Network Platform
Authors: Prakash Peralam Yegneswaran , Irinyi Laszlo , Halliday Catriona , Chen Sharon , Robert Vincent , Meyer Wieland 
Published: February 2017

ABSTRACT
The increase in public online databases dedicated to fungal identification is noteworthy. This can be attributed to improved access to molecular approaches to characterize fungi, as well as to delineate species within specific fungal groups in the last 2 decades, leading to an ever-increasing complexity of taxonomic assortments and nomenclatural reassignments. Thus, well-curated fungal databases with substantial accurate sequence data play a pivotal role for further research and diagnostics in the field of mycology. This minireview aims to provide an overview of currently available online databases for the taxonomy and identification of human and animal-pathogenic fungi and calls for the establishment of a cloud-based dynamic data network platform.
Impaired STING Pathway in Human Osteosarcoma U2OS Cells Contributes to the Growth of ICP0-Null Mutant Herpes Simplex Virus
Authors: Deschamps Thibaut , Kalamvoki Maria 
Published: February 2017

ABSTRACT
Human herpes simplex virus 1 (HSV-1) is a widespread pathogen, with 80% of the population being latently infected. To successfully evade the host, the virus has evolved strategies to counteract antiviral responses, including the gene-silencing and innate immunity machineries. The immediately early protein of the virus, infected cell protein 0 (ICP0), plays a central role in these processes. ICP0 blocks innate immunity, and one mechanism is by degrading hostile factors with its intrinsic E3 ligase activity. ICP0 also functions as a promiscuous transactivator, and it blocks repressor complexes to enable viral gene transcription. For these reasons, the growth of a ΔICP0 virus is impaired in most cells, except cells of the human osteosarcoma cell line U2OS, and it is only partially impaired in cells of the human osteosarcoma cell line Saos-2. We found that the two human osteosarcoma cell lines that supported the growth of the ΔICP0 virus failed to activate innate immune responses upon treatment with 2′3′-cyclic GAMP (2′3′-cGAMP), the natural agonist of STING (i.e., stimulator of interferon genes) or after infection with the ΔICP0 mutant virus. Innate immune responses were restored in these cells by transient expression of the STING protein but not after overexpression of interferon-inducible protein 16 (IFI16). Restoration of STING expression resulted in suppression of ΔICP0 virus gene expression and a decrease in viral yields. Overexpression of IFI16 also suppressed ΔICP0 virus gene expression, albeit to a lesser extent than STING. These data suggest that the susceptibility of U2OS and Saos-2 cells to the ΔICP0 HSV-1 is in part due to an impaired STING pathway.

IMPORTANCE
The DNA sensor STING plays pivotal role in controlling HSV-1 infection both in cell culture and in mice. The HSV-1 genome encodes numerous proteins that are dedicated to combat host antiviral responses. The immediate early protein of the virus ICP0 plays major role in this process as it targets hostile host proteins for degradation with its E3 ligase activity, and it disrupts repressor complexes via protein-protein interaction to enable viral gene transcription. Therefore, the ΔICP0 HSV-1 virus is defective for growth in most cells, except the human osteosarcoma cell lines U2OS and Saos-2. We found that both cell lines that support ΔICP0 virus infection have defects in the STING DNA-sensing pathway, which partially accounts for the rescue of the ΔICP0 virus growth. Restoration of STING expression in these cells rescued innate immunity and suppressed ΔICP0 virus infection. This study underscores the importance of STING in the control of HSV-1.
Identification of Novel Functions for Hepatitis C Virus Envelope Glycoprotein E1 in Virus Entry and Assembly
Authors: Haddad Juliano G. , Rouillé Yves , Hanoulle Xavier , Descamps Véronique , Hamze Monzer , Dabboussi Fouad , Baumert Thomas F. , Duverlie Gilles , Lavie Muriel , Dubuisson Jean 
Published: February 2017

ABSTRACT
Hepatitis C virus (HCV) envelope glycoprotein complex is composed of E1 and E2 subunits. E2 is the receptor-binding protein as well as the major target of neutralizing antibodies, whereas the functions of E1 remain poorly defined. Here, we took advantage of the recently published structure of the N-terminal region of the E1 ectodomain to interrogate the functions of this glycoprotein by mutating residues within this 79-amino-acid region in the context of an infectious clone. The phenotypes of the mutants were characterized to determine the effects of the mutations on virus entry, replication, and assembly. Furthermore, biochemical approaches were also used to characterize the folding and assembly of E1E2 heterodimers. Thirteen out of 19 mutations led to viral attenuation or inactivation. Interestingly, two attenuated mutants, T213A and I262A, were less dependent on claudin-1 for cellular entry in Huh-7 cells. Instead, these viruses relied on claudin-6, indicating a shift in receptor dependence for these two mutants in the target cell line. An unexpected phenotype was also observed for mutant D263A which was no longer infectious but still showed a good level of core protein secretion. Furthermore, genomic RNA was absent from these noninfectious viral particles, indicating that the D263A mutation leads to the assembly and release of viral particles devoid of genomic RNA. Finally, a change in subcellular colocalization between HCV RNA and E1 was observed for the D263A mutant. This unique observation highlights for the first time cross talk between HCV glycoprotein E1 and the genomic RNA during HCV morphogenesis.

IMPORTANCE
Hepatitis C virus (HCV) infection is a major public health problem worldwide. It encodes two envelope proteins, E1 and E2, which play a major role in the life cycle of this virus. E2 has been extensively characterized, whereas E1 remains poorly understood. Here, we investigated E1 functions by using site-directed mutagenesis in the context of the viral life cycle. Our results identify unique phenotypes. Unexpectedly, two mutants clearly showed a shift in receptor dependence for cell entry, highlighting a role for E1 in modulating HCV particle interaction with a cellular receptor(s). More importantly, another mutant led to the assembly and release of viral particles devoid of genomic RNA. This unique phenotype was further characterized, and we observed a change in subcellular colocalization between HCV RNA and E1. This unique observation highlights for the first time cross talk between a viral envelope protein and genomic RNA during morphogenesis.
HIV-Specific Granzyme B-Secreting but Not Gamma Interferon-Secreting T Cells Are Associated with Reduced Viral Reservoirs in Early HIV Infection
Authors: Yue Feng Yun , Cohen Jared C. , Ho Mu , Rahman A. K. M. Nur-ur , Liu Jun , Mujib Shariq , Saiyed Aamir , Hundal Sabrina , Khozin Alexandra , Bonner Phil , Liu Daheng , Benko Erika , Kovacs Colin , Ostrowski Mario 
Published: February 2017

ABSTRACT

A major barrier to a human immunodeficiency virus type 1 (HIV-1) infection cure is the establishment of a viral reservoir in spite of combined antiretroviral therapy (cART). It is unclear how HIV-specific cytotoxic T lymphocytes (CTLs) influence the size of the reservoir in early HIV infection. Twenty-eight subjects with early HIV infection were recruited to receive cART and followed for 48 weeks. HIV reservoirs in peripheral CD4
+
T cells measured by cell-associated proviral DNA and viral outgrowth cultures were determined at baseline and after 48 weeks of cART. At baseline, granzyme B and gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays were performed with peptides spanning the HIV proteome. All subjects had detectable HIV-specific granzyme B and IFN-γ responses at baseline. The quantity and specificity of granzyme B responses did not correlate with IFN-γ responses. For granzyme B, Tat/Rev was the most dominant whereas for IFN-γ, Gag predominated. HIV-specific granzyme B T cell responses negatively correlated with HIV proviral loads at baseline and at 48 weeks and with replication-competent viral infectious units per million (IUPM) CD4
+
T cells at baseline but not significantly at 48 weeks. Tat/Rev-, Env-, Gag-, and Vif-specific granzyme B responses correlated most strongly with reservoir control. There was no correlation of HIV-specific IFN-γ responses with reservoir size at baseline or at 48 weeks. The majority of granzyme B responses were contributed by CD8
+
T cells. Thus, our findings suggest that the induction of potent granzyme B-producing CTLs to Tat, Rev, Env, Gag, and Vif during early infection may be able to prevent the establishment of a large viral reservoir, thereby facilitating a reduced HIV burden.

IMPORTANCE
A major barrier to the cure of human immunodeficiency virus type 1 (HIV-1) infection is the establishment of a viral reservoir that must be significantly reduced or eradicated entirely to enable a cure. Combined antiretroviral therapy (cART) alone is unable to clear this viral reservoir. It has been shown that CD8
+
cytotoxic T lymphocytes (CTLs) are important in controlling early HIV infection by reducing plasma viremia. However, it is not known if these HIV-specific CTLs influence the establishment of the viral reservoir in early HIV infection. We show that HIV-specific granzyme B responses targeting HIV Tat/Rev, Env, Gag, and Vif, but not IFN-γ responses, are associated with reduced virus reservoirs at baseline and at 48 weeks of cART. These findings shed light on the nature of the effector CTL response that might limit reservoir size with implications for cure research and HIV vaccines.
Medial tibial stress syndrome can be diagnosed reliably using history and physical examination
Authors: Winters M , Bakker E W P , Moen M H , Barten C C , Teeuwen R , Weir A 
Published: February 2017

BackgroundThe majority of sporting injuries are clinically diagnosed using history and physical examination as the cornerstone. There are no studies supporting the reliability of making a clinical diagnosis of medial tibial stress syndrome (MTSS).AimOur aim was to assess if MTSS can be diagnosed reliably, using history and physical examination. We also investigated if clinicians were able to reliably identify concurrent lower leg injuries.MethodsA clinical reliability study was performed at multiple sports medicine sites in The Netherlands. Athletes with non-traumatic lower leg pain were assessed for having MTSS by two clinicians, who were blinded to each others’ diagnoses. We calculated the prevalence, percentage of agreement, observed percentage of positive agreement (Ppos), observed percentage of negative agreement (Pneg) and Kappa-statistic with 95%CI.ResultsForty-nine athletes participated in this study, of whom 46 completed both assessments. The prevalence of MTSS was 74%. The percentage of agreement was 96%, with Ppos and Pneg of 97% and 92%, respectively. The inter-rater reliability was almost perfect; k=0.89 (95% CI 0.74 to 1.00), p<0.000001. Of the 34 athletes with MTSS, 11 (32%) had a concurrent lower leg injury, which was reliably noted by our clinicians, k=0.73, 95% CI 0.48 to 0.98, p<0.0001.ConclusionOur findings show that MTSS can be reliably diagnosed clinically using history and physical examination, in clinical practice and research settings. We also found that concurrent lower leg injuries are common in athletes with MTSS.
The effects of the lower ignition propensity cigarettes standard in Estonia: time-series analysis
Authors: Saar Indrek 
Published: February 2017

BackgroundIn 2011, the lower ignition propensity (LIP) standard for cigarettes was implemented in the European Union. Evidence about the impact of that safety measure is scarce.ObjectiveThe aim of this paper is to examine the effects of the LIP standard on fire safety in Estonia.MethodsThe absolute level of smoking-related fire incidents and related deaths was modelled using dynamic time-series regression analysis. The data about house fire incidents for the 2007–2013 period were obtained from the Estonian Rescue Board.ResultsImplementation of the LIP standard has reduced the monthly level of smoking-related fires by 6.2 (p<0.01, SE=1.95) incidents and by 26% (p<0.01, SE=9%) when estimated on the log scale. Slightly weaker evidence was found about the fatality reduction effects of the LIP regulation. All results were confirmed through counterfactual models for non-smoking-related fire incidents and deaths.ConclusionsThis paper indicates that implementation of the LIP cigarettes standard has improved fire safety in Estonia.
Association between large artery atherosclerosis and cerebral microbleeds: a systematic review and meta-analysis
Authors: Ding Lingling , Hong Yuehui , Peng Bin 
Published: February 2017

ObjectiveThe aim of this systematic review and meta-analysis was to provide evidence that biomarkers of large artery atherosclerosis, including arterial stenosis and greater carotid intima-media thickness (cIMT), may serve as clinical markers of subclinical haemorrhage-prone cerebral small vessel disease, reflected by cerebral microbleeds (CMBs).MethodsWe searched PubMed, MEDLINE, Web of Science, EMBASE and the Cochrane Library to identify relevant studies published before 1 July 2016. The association between arterial stenosis and CMBs was estimated by the OR and 95% CI. The association of cIMT and CMBs was calculated using the standardised mean difference (SMD). Heterogeneity and publication bias were explored.Results8 studies including a total of 7160 participants were pooled in the meta-analysis. 6 of the included studies were cross-sectional, except that 2 were prospective. We found a significant association between arterial stenosis >50% and the presence of CMBs (OR 1.95, 95% CI 1.13 to 3.36, I2=56.1%). A fixed-effects model suggested that patients with CMBs were more likely to have a greater cIMT (SMD 0.20, 95% CI 0.11 to 0.28, I2=24.7%).ConclusionsThis systematic review and meta-analysis found that there is a relationship between large artery atherosclerosis and CMBs. Future studies are needed to confirm the impact of atherosclerosis on the CMBs, which may have potential therapeutic implications.
Clues on the Majorana scale from scalar resonances at the LHC
Authors: Fischer Oliver 
Published: February 2017

In order to address the observation of the neutrino oscillations and the metastability of the Standard Model (SM), we extend the fermion sector with two right-handed (i.e. sterile) neutrinos, and the scalar sector of the SM with a real scalar, the Hill field. The latter takes the role of a Majoron and generates the Majorana masses for the neutrino sector, such that the particle spectrum features two CP-even scalars h1and h2, and also two heavy, mass degenerate neutrinos. When the h1is identified with the scalar resonance at [Formula: see text] 125 GeV and the condition is imposed that the h1self-coupling and its running vanish at the Planck scale, the scalar mixing and the vacuum expectation value of the Hill field are fixed by the h2mass.The h2can be searched for at the LHC, and it has prospects of being discovered for the target integrated luminosities of the HL-LHC and the Future Circular hadron Collider (FCC-hh) when its mass is on the weak scale. The knowledge of the h2mass and its decay properties can yield an insight into its coupling to the heavy neutrinos, and thus also on the heavy neutrino mass scale. This yields an interesting connection between potentially detectable heavy scalars in high-energy proton collisions and the mass scale of the heavy neutrinos that is testable at the LHC and at future colliders.