bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased frequencies of the killer immunoglobulin‐like receptor genes KIR2DL2 and KIR2DS2 are associated with neuroblastoma
Authors: Keating S. E. , Ní Chorcora C. , Dring M. M. , Stallings R. L. , O'Meara A. , Gardiner C. M. 
Published: July 2015

AbstractNeuroblastoma is the most common extra‐cranial solid tumour in children. Natural killer (NK) cells are innate lymphocytes that are known to mediate the direct cytotoxicity of neuroblastoma tumour cells. Natural variation in the highly polymorphic killer immunoglobulin‐like receptors (KIR) and their cognate human leukocyte antigen (HLA) class I ligands results in considerable diversity in NK cell function. As the early onset of neuroblastoma suggests the contribution of genetic factors, we investigated if individual KIR genes, combined KIR gene haplotypes or compound KIR‐HLA ligand genotypes could influence susceptibility to neuroblastoma. Genotype analysis of the KIR genes as well as their three major HLA class I ligand groups, HLA‐C1, HLA‐C2 and HLA‐Bw4, was carried out in a cohort of 201 neuroblastoma patients compared with 240 healthy control subjects using polymerase chain reaction with sequence‐specific primers. We found a significant increase in the frequency of KIR2DL2 (P = 0.019) as well as KIR2DS2 (P = 0.008) in patients with neuroblastoma compared with the healthy control group. While the incidence of the least inhibitory compound KIR‐HLA‐C genotype, KIR2DL3 in the presence of HLA‐C1 was slightly reduced in neuroblastoma patients, this did not reach statistical significance (P = 0.069). In summary, while KIR‐HLA compound genotypes have previously been implicated in predicting treatment outcomes in neuroblastoma, here we show that the presence of the individual KIR genes, KIR2DL2 and KIR2DS2, irrespective of HLA‐C genotype is associated with the onset of this embryonal malignancy.
The Performance of Trading Firms in the Services Sectors – Comparable Evidence from Four EU Countries
Authors: Damijan Jože , Haller Stefanie A. , Kaitila Ville , Kostevc Črt , Maliranta Mika , Milet Emmanuel , Mirza Daniel , Rojec Matija 
Published: July 2015

AbstractWe examine trade complexity and the implications of adding additional dimensions of trade for firm performance among services producers. We use unique firm‐level data to compare these patterns across four EU countries. Overall, services firms are relatively less engaged in trade than manufacturing firms; they mostly trade goods and are more likely to import than to export. Trade in services is quite rare; services are more likely to be traded by firms already trading goods. Trading firms in the services sectors are significantly larger, more productive and pay higher wages than non‐traders. Two‐way traders outperform one‐way traders. Changes in trading status by either adding another dimension of trade (imports, exports) or another type of product (goods, services) are infrequent and are associated with significant preswitching premia. In contrast, learning effects from switching trading status are uncommon. This points to significant fixed cost of being engaged in trade and confirms some previous findings that trading services firms have similar traits as their manufacturing counterparts. Apart from greater trade participation in smaller countries, we do not observe systematic differences in terms of trade or switching premia between the four countries that might be attributable to differences in country characteristics.
Quantitative and Qualitative Comparison of Light Water and Advanced Small Modular Reactors
Authors: Aydogan Fatih , Black Geoffrey , Taylor Black Meredith A. , Solan David 
Published: July 2015

In recent years, several small modular reactor (SMR) designs have been developed. These nuclear power plants (NPPs) not only offer a small power size (less than 300 MWe), a reduced spatial footprint, and modularized compact designs fabricated in factories and transported to the intended sites, but also passive safety features. Some light water (LW)-SMRs have already been granted by Department of Energy: NuScale and mPower. New LW-SMRs are mainly inspired by the early LW-SMRs (such as process-inherent ultimate safety (PIUS), international reactor innovative and secure (IRIS), and safe integral reactor (SIR)). LW-SMRs employ significantly fewer components to decrease costs and increase simplicity of design. However, new physical challenges have appeared with these changes. At the same time, advanced SMR (ADV-SMR) designs (such as PBMR, MHR Antares, Prism, 4S, and Hyperion) are being developed that have improved passive safety and other features. This paper quantitatively and qualitatively compares most of the LW- and ADV-SMRs with respect to reactors, nuclear fuel, containment, reactor coolant systems, refueling, and emergency coolant systems. Economic and financing evaluations are also included in the paper. The detailed comparisons in this paper elucidate that one reactor is not superior to the others analyzed in this study, as each reactor is designed to meet different needs.
A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism
Authors: Fritz Georg , Dintner Sebastian , Treichel Nicole Simone , Radeck Jara , Gerland Ulrich , Mascher Thorsten , Gebhard Susanne 
Published: July 2015

ABSTRACT

Sensing of and responding to environmental changes are of vital importance for microbial cells. Consequently, bacteria have evolved a plethora of signaling systems that usually sense biochemical cues either via direct ligand binding, thereby acting as “concentration sensors,” or by responding to downstream effects on bacterial physiology, such as structural damage to the cell. Here, we describe a novel, alternative signaling mechanism that effectively implements a “flux sensor” to regulate antibiotic resistance. It relies on a sensory complex consisting of a histidine kinase and an ABC transporter, in which the transporter fulfills the dual role of both the sensor of the antibiotic and the mediator of resistance against it. Combining systems biological modeling with
in vivo
experimentation, we show that these systems in fact respond to changes in activity of individual resistance transporters rather than to changes in the antibiotic concentration. Our model shows that the cell thereby adjusts the rate of
de novo
transporter synthesis to precisely the level needed for protection. Such a flux-sensing mechanism may serve as a cost-efficient produce-to-demand strategy, controlling a widely conserved class of antibiotic resistance systems.

IMPORTANCE
Bacteria have to be able to accurately perceive their environment to allow adaptation to changing conditions. This is usually accomplished by sensing the concentrations of beneficial or harmful substances or by measuring the effect of the prevailing conditions on the cell. Here we show the existence of a new way of sensing the environment, where the bacteria monitor the activity of an antibiotic resistance transporter. Such a “flux-sensing” mechanism allows the cell to detect its current capacity to deal with the antibiotic challenge and thus precisely respond to the need for more transporters. We propose that this is a cost-efficient way of regulating antibiotic resistance on demand.
Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges
Authors: Khattar Sunil K. , Manoharan Vinoth , Bhattarai Bikash , LaBranche Celia C. , Montefiori David C. , Samal Siba K. 
Published: July 2015

ABSTRACT
Newcastle disease virus (NDV) avirulent strain LaSota was used to coexpress gp160 Env and p55 Gag from a single vector to enhance both Env-specific and Gag-specific immune responses. The optimal transcription position for both Env and Gag genes in the NDV genome was determined by generating recombinant NDV (rNDV)-Env-Gag (gp160 located between the P and M genes and Gag between the HN and L genes), rNDV-Gag-Env (Gag located between the P and M genes and gp160 between the HN and L genes), rNDV-Env/Gag (gp160 followed by Gag located between the P and M genes), and rNDV-Gag/Env (Gag followed by gp160 located between the P and M genes). All the recombinant viruses replicated at levels similar to those seen with parental NDV in embryonated chicken eggs and in chicken fibroblast cells. Both gp160 and Gag proteins were expressed at high levels in cell culture, with gp160 found to be incorporated into the envelope of NDV. The Gag and Env proteins expressed by all the recombinants except rNDV-Env-Gag self-assembled into human immunodeficiency virus type 1 (HIV-1) virus-like particles (VLPs). Immunization of guinea pigs by the intranasal route with these rNDVs produced long-lasting Env- and Gag-specific humoral immune responses. The Env-specific humoral and mucosal immune responses and Gag-specific humoral immune responses were higher in rNDV-Gag/Env and rNDV-Env/Gag than in the other recombinants. rNDV-Gag/Env and rNDV-Env/Gag were also more efficient in inducing cellular as well as protective immune responses to challenge with vaccinia viruses expressing HIV-1 Env and Gag in mice. These results suggest that vaccination with a single rNDV coexpressing Env and Gag represents a promising strategy to enhance immunogenicity and protective efficacy against HIV.

IMPORTANCE
A safe and effective vaccine that can induce both systemic and mucosal immune responses is needed to control HIV-1. In this study, we showed that coexpression of Env and Gag proteins of HIV-1 performed using a single Newcastle disease virus (NDV) vector led to the formation of HIV-1 virus-like particles (VLPs). Immunization of guinea pigs with recombinant NDVs (rNDVs) elicited potent long-lasting systemic and mucosal immune responses to HIV. Additionally, the rNDVs were efficient in inducing cellular immune responses to HIV and protective immunity to challenge with vaccinia viruses expressing HIV Env and Gag in mice. These results suggest that the use of a single NDV expressing Env and Gag proteins simultaneously is a novel strategy to develop a safe and effective vaccine against HIV.
CRISPR/Cas9-Induced Disruption of Paraflagellar Rod Protein 1 and 2 Genes in Trypanosoma cruzi Reveals Their Role in Flagellar Attachment
Authors: Lander Noelia , Li Zhu-Hong , Niyogi Sayantanee , Docampo Roberto 
Published: July 2015

ABSTRACT

Trypanosoma cruzi
is the etiologic agent of Chagas disease, and current methods for its genetic manipulation have been highly inefficient. We report here the use of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated gene 9) system for disrupting genes in the parasite by three different strategies. The utility of the method was established by silencing genes encoding the GP72 protein, which is required for flagellar attachment, and paraflagellar rod proteins 1 and 2 (PFR1, PFR2), key components of the parasite flagellum. We used either vectors containing single guide RNA (sgRNA) and Cas9, separately or together, or one vector containing sgRNA and Cas9 plus donor DNA for homologous recombination to rapidly generate mutant cell lines in which the
PFR1
,
PFR2
, and
GP72
genes have been disrupted. We demonstrate that genome editing of these endogenous genes in
T. cruzi
is successful without detectable toxicity of Cas9. Our results indicate that PFR1, PFR2, and GP72 contribute to flagellar attachment to the cell body and motility of the parasites. Therefore, CRISPR/Cas9 allows efficient gene disruption in an almost genetically intractable parasite and suggest that this method will improve the functional analyses of its genome.

IMPORTANCE
Trypanosoma cruzi
is the agent of Chagas disease, which affects millions of people worldwide. Vaccines to prevent this disease are not available, and drug treatments are not completely effective. The study of the biology of this parasite through genetic approaches will make possible the development of new preventive or treatment options. Previous attempts to use the CRISPR/Cas9 in
T. cruzi
found a detectable but low frequency of Cas9-facilitated homologous recombination and fluorescent marker swap between exogenous genes, while Cas9 was toxic to the cells. In this report, we describe new approaches that generate complete disruption of an endogenous gene without toxicity to the parasites and establish the relevance of several proteins for flagellar attachment and motility.
Efficacy of rehabilitation (lengthening) exercises, platelet-rich plasma injections, and other conservative interventions in acute hamstring injuries: an updated systematic review and meta-analysis
Authors: Pas Haiko IMFL , Reurink Gustaaf , Tol Johannes L , Weir Adam , Winters Marinus , Moen Maarten H 
Published: July 2015

BackgroundOur 2012 review on therapeutic interventions for acute hamstring injuries found a lack of high-quality studies. The publication of new studies warranted an update.ObjectivesTo update and reanalyse the efficacy of conservative treatments for hamstring injury.Data sourcesPubMed, EMBASE, Web of Science, Cochrane library, CINAHL and SPORTDiscus were searched till mid-February 2015.Study eligibility criteriaRandomised controlled trials (RCTs) on the effect of conservative interventions versus a control group or other intervention for hamstring injuries (HI) were included.Data analysisThe search results were screened independently by two authors. Risk of bias assessment was performed using a modified Downs and Black scale with a maximum score of 28. Meta-analysis was performed, where possible.Main results10 RCTs (526 participants), including 6 new RCTs, were identified. Two RCTs were of good/excellent quality, the rest were fair or poor (median Downs and Black score 16 (IQR 9)). Meta-analysis of two studies on rehabilitation (lengthening) exercises showed a significantly reduced time to return to play (HR 3.22 (95% CI 2.17 to 4.77), p<0.0001) but no difference in risk of re-injury. Meta-analysis of three studies investigating platelet-rich plasma (PRP) showed no effect when compared to control (HR 1.03 (95% CI 0.87 to 1.22), p=0.73). Limited evidence was found that progressive agility and trunk stability training may reduce re-injury rates.ConclusionsMeta-analysis showed superior efficacy for rehabilitation exercises. PRP injection had no effect on acute hamstring injury. Limited evidence was found that agility and trunk stabilisation may reduce re-injury rates. The limitations identified in the majority of RCTs should improve the design of new hamstring RCTs.
Is the introduction of violence and injury observatories associated with a reduction of violence in adult populations? Rationale and protocol for a systematic review
Authors: Jabar Ardil , Barth Dylan , Matzopoulos Richard , Engel Mark Emmanuel 
Published: July 2015

IntroductionThe violence and injury observatories developed in Colombia and found throughout the Americas and Western Europe aim to maximise inter-institutional cooperation, information-sharing, analysis and security policy development initiatives to enhance governance. The purpose of the violence and injury observatories is directed towards preventing crime and violence at the local and regional levels. To date, there has been no systematic review of the literature to present a succinct review of the evidence. We therefore sought to summarise the evidence from existing studies on the contribution of violence and injury observatories towards violence prevention.Methods and analysisA number of databases will be searched, supplemented by the same keyword searches in the grey literature. Search terms will include studies published from 1 January 1990 to 30 October 2014. Study quality will be assessed using a validated quality assessment tool. Two researchers will independently assess articles for study eligibility to reduce bias, minimise errors and enhance the reliability of findings. Disagreements will be resolved by consensus among three authors. This review protocol has been published in the PROSPERO International Prospective Register of systematic reviews, registration number 2014:CRD42014009818.DisseminationThere is a paucity of evidence for the effectiveness of violence and injury observatories and their influence on violence in an adult population. We plan to address this gap in knowledge by way of a systematic review and meta-analysis outlined in this abstract. We anticipate that the results could be used by researchers and policymakers to help inform them of the efficacy of violence and injury observatories and their broader role in contributing to violence prevention.Trial registration numberCRD42014009818.
Safety in numbers: more walkers and bicyclists, safer walking and bicycling
Authors: Jacobsen P L 
Published: July 2015

ObjectiveTo examine the relationship between the numbers of people walking or bicycling and the frequency of collisions between motorists and walkers or bicyclists. The common wisdom holds that the number of collisions varies directly with the amount of walking and bicycling. However, three published analyses of collision rates at specific intersections found a non-linear relationship, such that collisions rates declined with increases in the numbers of people walking or bicycling.DataThis paper uses five additional data sets (three population level and two time series) to compare the amount of walking or bicycling and the injuries incurring in collisions with motor vehicles.ResultsThe likelihood that a given person walking or bicycling will be struck by a motorist varies inversely with the amount of walking or bicycling. This pattern is consistent across communities of varying size, from specific intersections to cities and countries, and across time periods.DiscussionThis result is unexpected. Since it is unlikely that the people walking and bicycling become more cautious if their numbers are larger, it indicates that the behavior of motorists controls the likelihood of collisions with people walking and bicycling. It appears that motorists adjust their behavior in the presence of people walking and bicycling. There is an urgent need for further exploration of the human factors controlling motorist behavior in the presence of people walking and bicycling.ConclusionA motorist is less likely to collide with a person walking and bicycling if more people walk or bicycle. Policies that increase the numbers of people walking and bicycling appear to be an effective route to improving the safety of people walking and bicycling.
Clinical reasoning in canine spinal disease: what combination of clinical information is useful?
Authors: Cardy T. J. A. , De Decker S. , Kenny P. J. , Volk H. A. 
Published: July 2015

Spinal disease in dogs is commonly encountered in veterinary practice. Numerous diseases may cause similar clinical signs and presenting histories. The study objective was to use statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination that could suggest the most likely diagnoses with statistical significance. A retrospective study of 500 dogs referred to the Queen Mother Hospital for Animals before June 2012 for the investigation of spinal disease was performed. Details regarding signalment, history, physical and neurological examinations, neuroanatomical localisation and imaging data were obtained. Univariate analyses of variables (breed, age, weight, onset, deterioration, pain, asymmetry, neuroanatomical localisation) were performed, and variables were retained in a multivariate logistic regression model if P<0.05. Leading diagnoses were intervertebral disc extrusion (IVDE, n=149), intervertebral disc protrusion (n=149), ischaemic myelopathy (IM, n=48) and neoplasms (n=44). Multivariate logistic regression characterised IM and acute non‐compressive nucleus pulposus extrusions as the only peracute onset, non‐progressive, non‐painful and asymmetrical T3‐L3 myelopathies. IVDE was most commonly characterised as acute onset, often deteriorating, painful and largely symmetrical T3‐L3 myelopathy. This study suggests that most spinal diseases cause distinctive combinations of presenting clinical parameters (signalment, onset, deterioration, pain, asymmetry, neuroanatomical localisation). Taking particular account of these parameters may aid decision making in a clinical setting.
Racial and Ethnic Disparity in Symptomatic Breast Cancer Awareness despite a Recent Screen: The Role of Tumor Biology and Mammography Facility Characteristics
Authors: Mortel Mylove , Rauscher Garth H. , Murphy Anne Marie , Hoskins Kent , Warnecke Richard B. 
Published: July 2015

Abstract
Background: In a racially and ethnically diverse sample of recently diagnosed urban patients with breast cancer, we examined associations of patient, tumor biology, and mammography facility characteristics on the probability of symptomatic discovery of their breast cancer despite a recent prior screening mammogram.
Methods: In the Breast Cancer Care in Chicago study, self-reports at interview were used to define patients as having a screen-detected breast cancer or having symptomatic awareness despite a recent screening mammogram (SADRS), in the past 1 or 2 years. Patients with symptomatic breast cancer who did not report a recent prior screen were excluded from these analyses. Characteristics associated with more aggressive disease [estrogen receptor (ER)– and progesterone receptor (PR)–negative status and higher tumor grade] were abstracted from medical records. Mammogram facility characteristics that might indicate aspects of screening quality were defined and controlled for in some analyses.
Results: SADRS was more common among non-Hispanic black and Hispanic than among non-Hispanic white patients (36% and 42% vs. 25%, respectively, P = 0.0004). SADRS was associated with ER/PR-negative and higher-grade disease. Patients screened at sites that relied on dedicated radiologists and sites that were breast imaging centers of excellence were less likely to report SADRS. Tumor and facility factors together accounted for two thirds of the disparity in SADRS (proportion mediated = 70%, P = 0.02).
Conclusion: Facility resources and tumor aggressiveness explain much of the racial/ethnic disparity in symptomatic breast cancer among recently screened patients.
Impact: A more equitable distribution of high-quality screening would ameliorate but not eliminate this disparity. Cancer Epidemiol Biomarkers Prev; 24(10); 1599–606. ©2015 AACR.