bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virotherapy with a Semliki Forest Virus–Based Vector Encoding IL12 Synergizes with PD-1/PD-L1 Blockade
Authors: Quetglas José I. , Labiano Sara , Aznar M. Ángela , Bolaños Elixabet , Azpilikueta Arantza , Rodriguez Inmaculada , Casales Erkuden , Sánchez-Paulete Alfonso R. , Segura Víctor , Smerdou Cristian , Melero Ignacio 
Published: February 2015

Abstract
Virotherapy and checkpoint inhibitors can be combined for the treatment of cancer with complementarity and potential for synergistic effects. We have developed a cytolytic but nonreplicative viral vector system based on Semliki Forest virus that encodes IL12 (SFV-IL12). Following direct intratumoral injection, infected cells release transgenic IL12, die, and elicit an inflammatory response triggered by both abundantly copied viral RNA and IL12. In difficult-to-treat mouse cancer models, such as those derived from MC38 and bilateral B16-OVA, SFV-IL12 synergized with an anti–PD-1 monoclonal antibody (mAb) to induce tumor regression and prolong survival. Similar synergistic effects were attained upon PD-L1 blockade. Combined SFV-IL12 + anti–PD-1 mAb treatment only marginally increased the elicited cytotoxic T-lymphocyte response over SFV-IL12 as a single agent, at least when measured by in vivo killing assays. In contrast, we observed that SFV-IL12 treatment induced expression of PD-L1 on tumor cells in an IFNγ-dependent fashion. PD-L1–mediated adaptive resistance thereby provides a mechanistic explanation of the observed synergistic effects achieved by the SFV-IL12 + anti–PD-1 mAb combination. Cancer Immunol Res; 3(5); 449–54. ©2015 AACR.
Committing Cytomegalovirus-Specific CD8 T Cells to Eliminate Tumor Cells by Bifunctional Major Histocompatibility Class I Antibody Fusion Molecules
Authors: Schmittnaegel Martina , Levitsky Victor , Hoffmann Eike , Georges Guy , Mundigl Olaf , Klein Christian , Knoetgen Hendrik 
Published: February 2015

Abstract
Tumor cells escape immune eradication through multiple mechanisms, including loss of antigenicity and local suppression of effector lymphocytes. To counteract these obstacles, we aimed to direct the unique cytomegalovirus (CMV)-specific immune surveillance against tumor cells. We developed a novel generation of fusion proteins composed of a tumor antigen–specific full immunoglobulin connected to a single major histocompatibility class I complex bearing a covalently linked virus-derived peptide (pMHCI–IgG). Here, we show that tumor antigen–expressing cancer cells, which are decorated with pMHCI–IgGs containing a HLA-A*0201 molecule associated with a CMV-derived peptide, are specifically eliminated through engagement of antigen-specific CD8+ T cells isolated from peripheral blood mononuclear cell preparations of CMV-infected humans. These CD8+ T cells act without additional expansion, preactivation, or provision of costimulatory signals. Elimination of tumor cells is induced at similar concentrations and with similar time kinetics as those seen with bispecific T-cell engagers (BiTE). However, while BiTE-like reagents indiscriminately activate T cells through binding to the T-cell receptor complex, pMHCI–IgGs selectively engage antigen-specific, constantly renewable, differentiated effector cytotoxic T lymphocytes to tumor cells, thereby representing a novel class of anticancer immunotherapeutics with potentially improved safety and efficacy profiles. Cancer Immunol Res; 3(7); 764–76. ©2015 AACR.
Temporal Trends in the Incidence and Prognosis of Aortic Stenosis
Authors: Martinsson Andreas , Li Xinjun , Andersson Charlotte , Nilsson Johan , Smith J. Gustav , Sundquist Kristina 
Published: February 2015

Background—
The aging of Western populations is expected to result in increasing occurrence of aortic stenosis (AS), but data are limited. Recent studies have reported declining incidence and mortality for other major heart diseases. We aimed to study temporal trends in the incidence and prognosis for AS in Sweden.

Methods and Results—
With the use of nationwide registers, all adult patients in the Swedish population with a first diagnosis of AS, heart failure, acute myocardial infarction, and aortic valve replacement for AS between 1989 and 2009 were identified and followed up until the end of 2010 for all-cause and cardiovascular-related mortality. The age-adjusted incidence of AS in Sweden declined from 15.0 to 11.4 in men and 9.8 to 7.1 in women per 100 000 between 1989 to 1991 and 2007 to 2009, and the median age at diagnosis increased by 4 years for both men and women. The age- and sex-adjusted relative risk of 1- and 3-year mortality in 2007 to 2009 was 0.58 (95% confidence interval, 0.53–0.63) and 0.60 (95% confidence interval, 0.56–0.65), respectively, compared with 1989 to 1991. Similar improvements were observed for heart failure and acute myocardial infarction. Findings were broadly consistent across subgroups. Postoperative mortality at 30 days declined despite increased median age at diagnosis.

Conclusions—
Incidence and mortality rates in AS in Sweden declined between 1989 and 2009 to an extent similar to that observed for heart failure and acute myocardial infarction. These findings could suggest that improved risk factor control and cardiovascular therapy, combined with increased use of aortic valve replacement in the elderly and reduced perioperative mortality in aortic valve replacement, have translated into favorable effects for AS.
Nucleotide-Binding Oligomerization Domain 2 Receptor Is Expressed in Platelets and Enhances Platelet Activation and Thrombosis
Authors: Zhang Si , Zhang Shenghui , Hu Liang , Zhai Lili , Xue Ruyi , Ye Jianqin , Chen Leilei , Cheng Guanjun , Mruk Jozef , Kunapuli Satya P. , Ding Zhongren 
Published: February 2015

Background—
Pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) is well investigated in immunity, but its expression and function in platelets has never been explored.

Method and Results—

Using reverse transcription polymerase chain reaction and Western blot, we show that both human and mouse platelets express NOD2, and its agonist muramyl dipeptide induced NOD2 activation as evidenced by receptor dimerization. NOD2 activation potentiates platelet aggregation and secretion induced by low concentrations of thrombin or collagen, and clot retraction, as well. These potentiating effects of muramyl dipeptide were not seen in platelets from NOD2-deficient mice. Plasma from septic patients also potentiates platelet aggregation induced by thrombin or collagen NOD2 dependently. Using intravital microscopy, we found that muramyl dipeptide administration accelerated in vivo thrombosis in a FeCl
3
-injured mesenteric arteriole thrombosis mouse model. Platelet depletion and transfusion experiments confirmed that NOD2 from platelets contributes to the in vivo thrombosis in mice. NOD2 activation also accelerates platelet-dependent hemostasis. We further found that platelets express receptor-interacting protein 2, and provided evidence suggesting that mitogen activated-protein kinase and nitric oxide/soluble guanylyl cyclase/cGMP/protein kinase G pathways downstream of receptor-interacting protein mediate the role of NOD2 in platelets. Finally, muramyl dipeptide stimulates proinflammatory cytokine interleukin-1β maturation and accumulation in human and mouse platelets NOD2 dependently.

Conclusions—
NOD2 is expressed in platelets and functions in platelet activation and arterial thrombosis, possibly during infection. To our knowledge, this is the first study on NOD-like receptors in platelets that link thrombotic events to inflammation.
Sex-Related Clustering of Intracranial Aneurysms Within Families
Authors: Sijtsma Laura C. , Rinkel Gabriel J.E. , Ruigrok Ynte M. 
Published: February 2015

Background and Purpose—
Family history is important risk factor for intracranial aneurysms (ICA), but the pattern of inheritance is unsettled. If ICA within families would cluster according to sex, this may have implications for risk prediction and screening advice within families. We assessed the relationship between the sex of probands and their affected first-degree relatives (FDRs) within families with ICA.

Methods—
We used data from our prospectively collected database of families with known familial ICA. We calculated relative risks for a female affected proband having a female affected FDR as compared with a male affected proband having female affected FDR with corresponding 95% confidence intervals.

Results—
We included 148 families with 376 affected FDR. For a female proband the relative risk for having a female affected FDR compared with a male proband having an affected female FDR was 1.2 (95% confidence interval, 1.0–1.6).

Conclusions—
The clustering of ICA within families is greater in women than in men, with an excess of affected female FDR in female probands. However, because this excess is modest, our findings indicate that sex is not a relevant factor in risk prediction or screening advice in families with ICA.
On the Conditional Frazil Ice Instability in Seawater
Authors: Jordan James R. , Kimura Satoshi , Holland Paul R. , Jenkins Adrian , Piggott Matthew D. 
Published: February 2015

AbstractIt has been suggested that the presence of frazil ice can lead to a conditional instability in seawater. Any frazil forming in the water column reduces the bulk density of a parcel of frazil–seawater mixture, causing it to rise. As a result of the pressure decrease in the freezing point, this causes more frazil to form, causing the parcel to accelerate, and so on. This study uses linear stability analysis and a nonhydrostatic ocean model to study this instability. The authors find that frazil ice growth caused by the rising of supercooled water is indeed able to generate a buoyancy-driven instability. Even in a gravitationally stable water column, the frazil ice mechanism can still generate convection. The instability does not operate in the presence of strong density stratification, high thermal driving (warm water), a small initial perturbation, high background mixing, or the prevalence of large frazil ice crystals. In an unstable water column, the instability is not necessarily expressed in frazil ice at all times; an initial frazil perturbation may melt and refreeze. Given a large enough initial perturbation, this instability can allow significant ice growth. A model shows frazil ice growth in an Ice Shelf Water plume several kilometers from an ice shelf, under similar conditions to observations of frazil ice growth under sea ice. The presence of this instability could be a factor affecting the growth of sea ice near ice shelves, with implications for Antarctic Bottom Water formation.
The Modulation of Equatorial Turbulence by Tropical Instability Waves in a Regional Ocean Model
Authors: Holmes R. M. , Thomas L. N. 
Published: February 2015

AbstractSmall-scale turbulent mixing in the upper Equatorial Undercurrent (EUC) of the eastern Pacific cold tongue is a critical component of the SST budget that drives variations in SST on a range of time scales. Recent observations have shown that turbulent mixing within the EUC is modulated by tropical instability waves (TIWs). A regional ocean model is used to investigate the mechanisms through which large-scale TIW circulation modulates the small-scale shear, stratification, and shear-driven turbulence in the EUC. Eulerian analyses of time series taken from both the model and the Tropical Atmosphere Ocean (TAO) array suggest that increases in the zonal shear of the EUC drive increased mixing on the leading edge of the TIW warm phase. A Lagrangian vorticity analysis attributes this increased zonal shear to horizontal vortex stretching driven by the strain in the TIW horizontal velocity field acting on the existing EUC shear. To investigate the impact of horizontal vortex stretching on the turbulent heat flux averaged over a TIW period the effects of periodic TIW strain are included as forcing in a simple 1D mixing model of the EUC. Model runs with TIW forcing show turbulent heat fluxes up to 30% larger than runs without TIW forcing, with the magnitude of the increase being sensitive to the vertical mixing scheme used in the model. These results emphasize the importance of coupling between the large-scale circulation and small-scale turbulence in the equatorial regions, with implications for the SST budget of the equatorial Pacific.
Evaluating Two Array Autocalibration Methods with Multifrequency HF Radar Current Measurements
Authors: Zhao Chen , Chen Zezong , Zeng Gengfei , Zhang Longgang 
Published: February 2015

AbstractOne pivotal factor affecting the accuracy of HF radar current measurements is the direction of arrival (DOA) estimation performance of the current signal. The beamforming technology or superresolution algorithm cannot always perform best in practical applications because of the phase errors existing in array channels. These phase errors, which cause uncertain estimation of DOA, lead to confused values in radial current maps. To solve this problem, this paper is focused on discussing the performances of two autocalibration methods using sea echoes for multifrequency high-frequency (MHF) radar current measurements. These two array calibration methods, based on maximum likelihood (ML) and multiple signal classification (MU), first seek single-DOA sea echoes and then gather them for array calibration using different cost functions. The ML and MU methods provide approximate mean phases, while the standard phase errors of the MU method are smaller. After array calibration using these two methods, the results show significant improvements in current retrievals. Comparisons between the MHF radar and ADCPs reveal that array calibration using the ML and MU methods also improves the estimation of radial currents clearly, with correlation coefficients over 0.93 and rms differences of 0.09–0.18 m s−1 at different operating frequencies and sampling locations. The performance of the bearing offset is also improved. Only small bearing offsets less than 10° exist in radial current measurements. Therefore, this paper demonstrates that array calibration is a crucial part for current measurements, especially for direction-finding HF radar.
The Predictability of DOJ Cartel Fines
Authors: Connor John M. , Miller Douglas J. 
Published: February 2015

For criminal violations of the Sherman Act, although guided by federal sentencing guidelines, the U.S. Department of Justice has great latitude in recommending corporate cartel fines to the federal courts, and its recommendations are nearly always determinative. In this article, we analyze the determinants of variation in size of criminal fines imposed by the Antitrust Division of the Department of Justice on 124 corporate participants in hard core global cartels. Our behavioral model provides the first direct test of the optimal deterrence theory of antitrust crimes. Regressions are fitted to a sample of the corporations that participated in international cartels and that were fined between 1996 and March 2010. The predictive power of the optimal-deterrence model is quite good. We find that U.S. corporate cartel fines are strongly directly related to economic injuries from collusion. However, U.S. fines do not conform to the theory's predictions about the probability of detection and conviction of clandestine cartels. We also find that fines complement other antitrust penalties, such as the number of months that a corporate defendant's managers are sentenced to prison and private damages paid.
The “Triangle That Moves the Mountain” and Thai Alcohol Policy Development: Four Case Studies
Authors: Thamarangsi Thaksaphon 
Published: February 2015

The “Triangle that Moves the Mountain” is a conceptualized strategy initiated as a social tool for solving difficult social problems, by simultaneously strengthening capacity in three interrelated sectors: (1) creation of knowledge; (2) social movement; and (3) political involvement. The concept has been claimed as the basis of many successes in various Thai policy arenas. This article describes the strategy implications of four alcohol policy development case studies. The first case is the establishment process for the Thai Health Promotion Foundation and its contribution to the alcohol policy area. The second and third cases are two phases in the development of alcohol promotion regulation. The last case reviews the movement against the approval of an alcohol company listing on the Stock Exchange of Thailand. The case studies show that capacity strengthening in three sectors, based on this concept, benefited Thai alcohol policy development.
Developing a Data Resource to Support State Substance Abuse Prevention Planning: Approaches Used in Implementing CSAP's Strategic Prevention Framework
Authors: Flewelling Robert L. , Birckmayer Johanna , Boothroyd Renee 
Published: February 2015

A number of data collection systems designed to monitor selected substance abuse behaviors and consequences are in place in the United States. Some of these systems provide only national-level data, while others provide data disaggregated by state and in some cases by sub-state units such as counties or communities. Less progress has been made in identifying a key set of epidemiologic indicators across the three major substance categories (i.e., alcohol, tobacco, and illicit drugs), and assembling them in a manner designed to effectively support substance abuse prevention planning at the state and local levels. A recent federal initiative funded by the U.S. Center for Substance Abuse Prevention (CSAP) seeks to accelerate progress in this area through its Strategic Prevention Framework (SPF). The framework is intended to stimulate the prudent use of available data, and the development of additional data resources, for: 1) identifying statewide priorities for substance abuse prevention, 2) informing resource allocation decisions, 3) monitoring state and local trends in substance abuse and related consequences, and 4) evaluating state and local prevention efforts. This article describes the underlying rationale and issues considered in developing the database, some of the challenges and limitations in applying the data to prevention planning processes, and current strategies employed by CSAP to guide states and communities in effectively using the data in their substance abuse prevention planning and monitoring efforts.
“Yes, I Do but Not with You”: Qualitative Analyses of Sexual/romantic Overture-Related Aggression in Bars and Clubs
Authors: Graham Kathryn , Wells Samantha , Bernards Sharon , Dennison Susan 
Published: February 2015

Assaultive and aggressive behaviors related to sexual overtures are common in commercial drinking establishments (bars, pubs, and clubs). In this article, we examined the thematic content of 251 incidents of verbal and physical aggression related to sexual/romantic overtures documented by researcher-observers in a study of Toronto bars and clubs. Aggression was examined as it emerged in the following stages of the social interaction process: (a) sexual/romantic overtures that began aggressively; (b) initiators of sexual/romantic overtures who became aggressive later in the social interaction process; (c) aggression by targets of overtures; and (d) aggression by third parties. From these thematic analyses we identify the distinctions between predatory and genuine overtures and explore the potential role of the effects of alcohol. In these social overtures aggression occurred as part of the initial overture, during the interaction following the overture (i.e., aggression by the person who made the initial overture, by the target or third parties), and in response to rejection by the target. Targets of overtures responded aggressively to perceived inappropriate overtures; third parties played important aggressive and nonaggressive roles; and alcohol intoxication was identified as contributing to aggression in a number of ways. The theoretical significance and practical implications for prevention of the findings are discussed.
Effectiveness of resistance training on muscle strength and physical function in people with Parkinson’s disease: a systematic review and meta-analysis
Authors: Chung Chloe Lau Ha , Thilarajah Shamala , Tan Dawn 
Published: February 2015

Objectives: To systematically review the evidence investigating the effectiveness of resistance training on strength and physical function in people with Parkinson’s disease. Data sources: Seven electronic databases (COCHRANE, CINAHL, Medline ISI, Psycinfo, Scopus, Web of Science ISI and Embase) were systematically searched for full-text articles published in English between 1946 and November 2014 using relevant search terms. Review methods: Only randomized controlled trials investigating the effects of resistance training on muscle strength and physical function in people with Parkinson’s disease were considered. The PEDro scale was used to assess study quality. Studies with similar outcomes were pooled by calculating standardized mean differences (SMD) using fixed or random effects model, depending on study heterogeneity. Results: Seven studies, comprising of 401 participants with early to advanced disease (Hoehn & Yahr stage 1 to 4), were included. The median quality score was 6/10. The meta-analyses demonstrated significant SMD in favour of resistance training compared to non-resistance training or no intervention controls for muscle strength (0.61; 95% CI, 0.35 to 0.87; P <0.001), balance (0.36; 95% CI, 0.08 to 0.64; P = 0.01) and parkinsonian motor symptoms (0.48; 95% CI, 0.21 to 0.75; P < 0.001) but not for gait, balance confidence and quality of life. Conclusion: This review demonstrates that moderate intensity progressive resistance training, 2-3 times per week over 8-10 weeks can result in significant strength, balance and motor symptoms gains in people with early to moderate Parkinson’s disease.
Headache neuroimaging: Routine testing when guidelines recommend against them
Authors: Callaghan Brian C , Kerber Kevin A , Pace Robert J , Skolarus Lesli , Cooper Wade , Burke James F 
Published: February 2015

Aims The aim of this article is to determine the patient-level factors associated with headache neuroimaging in outpatient practice. Methods Using data from the 2007–2010 National Ambulatory Medical Care Surveys (NAMCS), we estimated headache neuroimaging utilization (cross-sectional). Multivariable logistic regression was used to explore associations between patient-level factors and neuroimaging utilization. A Markov model with Monte Carlo simulation was used to estimate neuroimaging utilization over time at the individual patient level. Results Migraine diagnoses (OR = 0.6, 95% CI 0.4–0.9) and chronic headaches (routine, chronic OR = 0.3, 95% CI 0.2–0.6; flare-up, chronic OR = 0.5, 95% CI 0.3–0.96) were associated with lower utilization, but even in these populations neuroimaging was ordered frequently. Red flags for intracranial pathology did not increase use of neuroimaging studies (OR = 1.4, 95% CI 0.95–2.2). Neurologist visits (OR = 1.7, 95% CI 0.99–2.9) and first visits to a practice (OR = 3.2, 95% CI 1.4–7.4) were associated with increased imaging. A patient with new migraine headaches has a 39% (95% CI 24–54%) chance of receiving a neuroimaging study after five years and a patient with a flare-up of chronic headaches has a 51% (32–68%) chance. Conclusions Neuroimaging is routinely ordered in outpatient headache patients including populations where guidelines specifically recommend against their use (migraines, chronic headaches, no red flags).