bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice
Authors: Wohlbold Teddy John , Nachbagauer Raffael , Xu Haoming , Tan Gene S. , Hirsh Ariana , Brokstad Karl A. , Cox Rebecca J. , Palese Peter , Krammer Florian 
Published: March 2015

ABSTRACTIn an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection.IMPORTANCEDespite the existence of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to cause morbidity and mortality in the human population, emphasizing the continued need for research in the field. While the majority of influenza vaccine strategies target the viral hemagglutinin, the immunodominant antigen on the surface of the influenza virion, antibodies against the viral neuraminidase (NA) have been correlated with less severe disease and decreased viral shedding in humans. Nevertheless, the amount of NA is not standardized in current seasonal vaccines, and the exact breadth of NA-based protection is unknown. Greater insight into the cross-protective potential of influenza virus NA as a vaccine antigen may pave the way for the development of influenza vaccines of greater breadth and efficacy.
Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial ofS-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial)
Authors: Juel Jacob , Olesen Søren Schou , Olesen Anne Estrup , Poulsen Jakob Lykke , Dahan Albert , Wilder-Smith Oliver , Madzak Adnan , Frøkjær Jens Brøndum , Drewes Asbjørn Mohr 
Published: March 2015

IntroductionChronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of theN-methyl-d-aspartate receptor, which can be antagonised byS-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect ofS-ketamine in patients with CP.Methods and analysis40 patients with CP will be enrolled. Patients are randomised to receive 8 h of intravenousS-ketamine followed by oralS-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points include changes in patient-reported outcome measures, opioid consumption and rates of side effects. The end points are registered through the 4-week medication period and for an additional follow-up period of 8 weeks to investigate long-term effects. In addition, experimental pain measures also serves as secondary end points, and neurophysiological imaging parameters are collected. Furthermore, experimental baseline recordings are compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP.Ethics and disseminationThe protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberThe study is registered athttp://www.clinicaltrialsregister.eu(EudraCT number 2013-003357-17).
Mindfulness-based stress reduction in patients with interstitial lung diseases: a pilot, single-centre observational study on safety and efficacy
Authors: Sgalla Giacomo , Cerri Stefania , Ferrari Roberto , Ricchieri Maria Pia , Poletti Stefano , Ori Margherita , Garuti Martina , Montanari Gloria , Luppi Fabrizio , Petropulacos Kyriakoula , Richeldi Luca 
Published: March 2015

BackgroundChronic, progressive respiratory symptoms are associated with great psychological and emotional impact in patients suffering from interstitial lung disease (ILD). This single-centre pilot study evaluated for the first time the safety, feasibility and efficacy of a Mindfulness Based Stress Reduction Program (MBSR) in a group of patients with ILD.MethodsProspective observational study set in a university hospital ILD outpatient clinic. Nineteen patients with different ILDs were recruited 2 months prior to the start of the 8-week MBSR program and followed up for 12 months. Primary outcomes were program safety and feasibility, while secondary outcomes were changes in moods and stress (assessed by Profile Of Mood State (POMS) and Perceived Stress Scale (PSS) questionnaires), symptoms (Shortness Of Breath (SOB) and Cough And Sputum Assessment (CASA-Q) questionnaires), lung function and exercise tolerance at 12 months.ResultsTwo patients (10.5%) dropped out in the observational period before the start of the MBSR intervention because of non-respiratory causes. All 17 patients who entered the 8-week MBSR program managed to complete it with an adherence average of eight sessions of nine. No adverse events related to the mindfulness training were reported. Statistically significant improvements in the POMS total score and in several individual items of POMS and PSS were observed throughout the study. However, respiratory questionnaire scores, lung function and exercise tolerance did not show a significant difference over time.ConclusionsAn MBSR program appears to be safe and feasible in patients with ILD, and might affect perceived moods and stress producing a positive and lasting improvement in several stress-related negative domains. These findings pave the way to larger (possibly multicentre), randomised, controlled confirmatory trials.
Combination of tumour markers CEA and CA19-9 improves the prognostic prediction in patients with pancreatic cancer
Authors: Reitz Daniel , Gerger Armin , Seidel Julia , Kornprat Peter , Samonigg Hellmut , Stotz Michael , Szkandera Joanna , Pichler Martin 
Published: March 2015

AimsTumour markers including carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) are frequently determined at the time of diagnosis in patients with pancreatic cancer. Several studies indicate a prognostic relevance of these markers in pancreatic cancer, but space for improvement with regard to the predictive accuracy and ability is given. In this work, the main focus is on mathematical combinations of these two tumour markers in order to validate an improvement of prognostic test results in terms of sensitivity and specificity.MethodsThis retrospective study includes 393 patients with pancreatic cancer, who were treated between the years 2005 and 2012 at the Division of Oncology, Medical University of Graz, Austria. The goal of this study was to explore whether an appropriate combination of two tumour markers leads to a statistically significant improvement of the prognostic prediction.ResultsReceiver operating characteristic curves comparison analyses with the classification variable cancer-specific survival showed that the mathematical product of two tumour markers (TMproduct= (CEA×CA19-9); area under the curve (AUC)=0.727; 95% CI 0.680 to 0.770) is significantly better than CEA alone (AUC=0.644; 95% CI 0.594 to 0.691; p=0.003) but not significant compared with CA19-9 (AUC=0.710; 95% CI 0.662 to 0.754; p=0.1215). A linear combination of CEA and CA19-9 (TMlinear=(85×CEA+CA19-9); AUC=0.748; 95% CI 0.702 to 0.790) is significantly better than CEA (p<0.0001) as well as CA19-9 alone (p=0.0304).ConclusionsMathematical combinations of pretherapeutic tumour markers CEA and CA19-9 are feasible and can significantly improve the prognostic prediction in patients with pancreatic cancer.
Single-File System with Absorbing Boundary: Tracer Dynamics and First-Passage Properties
Authors: Ryabov Artem 
Published: March 2015

In this paper, we review the tagged particle dynamics in a semi-infinite system with an absorbing boundary. The emphasis is on an interplay between the hard-core interparticle interaction and the absorption process. The exact probability density function for the position of a tagged particle is derived by means of probabilistic arguments. First, the initially homogeneous system with constant density of particles is studied. In this setting, the dynamics of the tracer conditioned on nonabsorption becomes subdiffusive, the generalized diffusion coefficient being different from that reported for the system without absorbing boundary. Second, the case when the initial number of particles is finite is discussed. In this case, in the long time limit the tracer diffusion is normal and the hard-core interaction manifests itself through the renormalization of the tracer diffusion coefficient. The Gaussian distribution derived for infinite single-file systems is, in the present semi-infinite setting, replaced by the Rayleigh distribution. [Formula: see text]Special Issue Comments: This article presents results on the dynamics of a tagged particle in open systems, where the number of particles is not conserved in time. This article is related to the Special Issue articles about advanced statistical properties in single file dynamics,1 the calculation of correlations,2 files with force3 and the zig-zag patterns in files.4
Photovoltaic properties of silicon nanocrystals in silicon nitride prepared by ammonia sputtering
Authors: Chen Xiaobo 
Published: March 2015

In this work, we present an investigation of the photovoltaic properties of low-temperature (700°C annealing temperature) prepared P -doped Silicon nanocrystals ( Si NCs ) in silicon nitride by ammonia sputtering followed by rapid thermal annealing (RTA). We examined how the flow rate of NH3influenced the structural properties of the annealed films by using Raman scattering, grazing incidence X-ray diffraction (GI XRD) and transmission electron microscopy (TEM), it was found that the appropriate flow rate of NH3is 3 sccm. For the sample deposited at the flow rate of 3 sccm, TEM image showed that Si NCs were formed with a mean size about 3.7 nm and the density of ~ 2.1 × 1012cm-2; X-ray photoelectron spectroscopy (XPS) characterization showed the existence of Si – P bonds, indicating effective P doping; the average absorptance of higher than 65% and a significant amount of photocurrent makes it suitable for photoactive. Moreover, the experimental P -doped Si NCs : Si3N4/ p - Si heterojunction solar cell has been fabricated, and the device performance was studied. The photovoltaic device fabricated exhibits an open-circuit voltage (VOC) and a short-circuit current density (JSC) of 470 mV and 3.25 mA/cm2, respectively.
NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes
Authors: Johansson Åsa , Eriksson Niclas , Becker Richard C. , Storey Robert F. , Himmelmann Anders , Hagström Emil , Varenhorst Christoph , Axelsson Tomas , Barratt Bryan J. , James Stefan K. , Katus Hugo A. , Steg Philippe Gabriel , Syvänen Ann-Christine , Wallentin Lars , Siegbahn Agneta 
Published: March 2015

Background—
Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined.

Methods and Results—

Baseline plasma IL-18 levels were measured in 16 633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (
IL18, NLRC4
, and
MROH6
) were identified (
P
<3.15×10
−8
) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum
P
=6.99×10
–72
). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in
NLRC4
is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort.

Conclusions—

Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (
IL18
) or close to genes that are involved in procaspase-1 activation (
NLRC4
and
CARD16
,
CARD17
, and
CARD18
). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.
Seeing the Same Words Differently: The Time Course of Automaticity and Top–Down Intention in Reading
Authors: Strijkers Kristof , Bertrand Daisy , Grainger Jonathan 
Published: March 2015

Abstract
We investigated how linguistic intention affects the time course of visual word recognition by comparing the brain's electrophysiological response to a word's lexical frequency, a well-established psycholinguistic marker of lexical access, when participants actively retrieve the meaning of the written input (semantic categorization) versus a situation where no language processing is necessary (ink color categorization). In the semantic task, the ERPs elicited by high-frequency words started to diverge from those elicited by low-frequency words as early as 120 msec after stimulus onset. On the other hand, when categorizing the colored font of the very same words in the color task, word frequency did not modulate ERPs until some 100 msec later (220 msec poststimulus onset) and did so for a shorter period and with a smaller scalp distribution. The results demonstrate that, although written words indeed elicit automatic recognition processes in the brain, the speed and quality of lexical processing critically depends on the top–down intention to engage in a linguistic task.
Preconscious Prediction of a Driver's Decision Using Intracranial Recordings
Authors: Perez Omri , Mukamel Roy , Tankus Ariel , Rosenblatt Jonathan D. , Yeshurun Yehezkel , Fried Itzhak 
Published: March 2015

Abstract
While driving, we make numerous conscious decisions such as route and turn direction selection. Although drivers are held responsible, the neural processes that govern such decisions are not clear. We recorded intracranial EEG signals from six patients engaged in a computer-based driving simulator. Patients decided which way to turn (left/right) and subsequently reported the time of the decision. We show that power modulations of gamma band oscillations (30–100 Hz) preceding the reported time of decision (up to 5.5 sec) allow prediction of decision content with high accuracy (up to 82.4%) on a trial-by-trial basis, irrespective of subsequent motor output. Moreover, these modulations exhibited a spatiotemporal gradient, differentiating left/right decisions earliest in premotor cortices and later in more anterior and lateral regions. Our results suggest a preconscious role for the premotor cortices in early stages of decision-making, which permits foreseeing and perhaps modifying the content of real-life human choices before they are consciously made.
The Devil Is in the Detail: Brain Dynamics in Preparation for a Global–Local Task
Authors: Leaver Echo E. , Low Kathy A. , DiVacri Assunta , Merla Arcangelo , Fabiani Monica , Gratton Gabriele 
Published: March 2015

Abstract
When analyzing visual scenes, it is sometimes important to determine the relevant “grain” size. Attention control mechanisms may help direct our processing to the intended grain size. Here we used the event-related optical signal, a method possessing high temporal and spatial resolution, to examine the involvement of brain structures within the dorsal attention network (DAN) and the visual processing network (VPN) in preparation for the appropriate level of analysis. Behavioral data indicate that the small features of a hierarchical stimulus (local condition) are more difficult to process than the large features (global condition). Consistent with this finding, cues predicting a local trial were associated with greater DAN activation. This activity was bilateral but more pronounced in the left hemisphere, where it showed a frontal-to-parietal progression over time. Furthermore, the amount of DAN activation, especially in the left hemisphere and in parietal regions, was predictive of subsequent performance. Although local cues elicited left-lateralized DAN activity, no preponderantly right activity was observed for global cues; however, the data indicated an interaction between level of analysis (local vs. global) and hemisphere in VPN. They further showed that local processing involves structures in the ventral VPN, whereas global processing involves structures in the dorsal VPN. These results indicate that in our study preparation for analyzing different size features is an asymmetric process, in which greater preparation is required to focus on small rather than large features, perhaps because of their lesser salience. This preparation involves the same DAN used for other attention control operations.
Effects of Eddy Vorticity Forcing on the Mean State of the Kuroshio Extension
Authors: Delman Andrew S. , McClean Julie L. , Sprintall Janet , Talley Lynne D. , Yulaeva Elena , Jayne Steven R. 
Published: March 2015

AbstractEddy–mean flow interactions along the Kuroshio Extension (KE) jet are investigated using a vorticity budget of a high-resolution ocean model simulation, averaged over a 13-yr period. The simulation explicitly resolves mesoscale eddies in the KE and is forced with air–sea fluxes representing the years 1995–2007. A mean-eddy decomposition in a jet-following coordinate system removes the variability of the jet path from the eddy components of velocity; thus, eddy kinetic energy in the jet reference frame is substantially lower than in geographic coordinates and exhibits a cross-jet asymmetry that is consistent with the baroclinic instability criterion of the long-term mean field. The vorticity budget is computed in both geographic (i.e., Eulerian) and jet reference frames; the jet frame budget reveals several patterns of eddy forcing that are largely attributed to varicose modes of variability. Eddies tend to diffuse the relative vorticity minima/maxima that flank the jet, removing momentum from the fast-moving jet core and reinforcing the quasi-permanent meridional meanders in the mean jet. A pattern associated with the vertical stretching of relative vorticity in eddies indicates a deceleration (acceleration) of the jet coincident with northward (southward) quasi-permanent meanders. Eddy relative vorticity advection outside of the eastward jet core is balanced mostly by vertical stretching of the mean flow, which through baroclinic adjustment helps to drive the flanking recirculation gyres. The jet frame vorticity budget presents a well-defined picture of eddy activity, illustrating along-jet variations in eddy–mean flow interaction that may have implications for the jet’s dynamics and cross-frontal tracer fluxes.
Current challenges in clinical development of “targeted therapies”: the case of acute myeloid leukemia
Authors: Estey Elihu , Levine Ross L. , Löwenberg Bob 
Published: March 2015

Abstract
A fundamental difficulty in testing “targeted therapies” in acute myeloid leukemia (AML) is the limitations of preclinical models in capturing inter- and intrapatient genomic heterogeneity. Clinical trials typically focus on single agents despite the routine emergence of resistant subclones and experience in blast-phase chronic myeloid leukemia and acute promyelocytic leukemia arguing against this strategy. Inclusion of only relapsed-refractory, or unfit newly diagnosed, patients risks falsely negative results. There is uncertainty as to whether eligibility should require demonstration of the putative target and regarding therapeutic end points. Although use of in vivo preclinical models employing primary leukemic cells is first choice, newer preclinical models including “organoids” and combinations of pharmacologic and genetic approaches may better align models with human AML. We advocate earlier inclusion of combinations ± chemotherapy and of newly diagnosed patients into clinical trials. When a drug plausibly targets a pathway uniquely related to a specific genetic aberration, eligibility should begin with this subset, including patients with other malignancies, with subsequent extension to other patients. In other cases, a more open-minded approach to initial eligibility would facilitate quicker identification of responsive subsets. Complete remission without minimal residual disease seems a particularly useful short-term end point. Genotypic and phenotypic studies should be prespecified and performed routinely to distinguish responders from nonresponders.