bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically engineered T cells for the treatment of cancer
Authors: Essand M. , Loskog A. S. I. 
Published: April 2013

AbstractT‐cell immunotherapy is a promising approach to treat disseminated cancer. However, it has been limited by the ability to isolate and expand T cells restricted to tumour‐associated antigens. Using ex vivo gene transfer, T cells from patients can be genetically engineered to express a novel T cell receptor or chimeric antigen receptor to specifically recognize a tumour‐associated antigen and thereby selectively kill tumour cells. Indeed, genetically engineered T cells have recently been successfully used for cancer treatment in a small number of patients. Here we review the recent progress in the field, and summarize the challenges that lie ahead and the strategies being used to overcome them.
Manganese toxicity in the central nervous system: the glutamine/glutamate‐γ‐aminobutyric acid cycle
Authors: Sidoryk‐Wegrzynowicz M. , Aschner M. 
Published: April 2013

AbstractManganese (Mn) is an essential trace element that is required for maintaining proper function and regulation of numerous biochemical and cellular reactions. Despite its essentiality, at excessive levels Mn is toxic to the central nervous system (CNS). Increased accumulation of Mn in specific brain regions, such as the substantia nigra, globus pallidus and striatum, triggers neurotoxicity resulting in a neurological brain disorder, termed manganism. Mn has been also implicated in the pathophysiology of several other neurodegenerative diseases. Its toxicity is associated with disruption of the glutamine (Gln)/glutamate (Glu)‐γ‐aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons, thus leading to changes in Glu‐ergic and/or GABAergic transmission and Gln metabolism. Here we discuss the common mechanisms underlying Mn‐induced neurotoxicity and their relationship to CNS pathology and GGC impairment.
High levels of cystatin C predict the metabolic syndrome: the prospective Malmö Diet and Cancer Study
Authors: Magnusson M. , Hedblad B. , Engström G. , Persson M. , Nilsson P. , Melander O. 
Published: April 2013

AbstractObjectiveCystatin C is a novel marker of cardiovascular disease (CVD); however, the underlying mechanisms remain unclear. Here, we prospectively investigated whether plasma levels of cystatin C predict new‐onset metabolic syndrome (MetS) as well as long‐term progression and incidence of the different components of the MetS.MethodsCystatin C was measured in 1502 individuals included in the Malmö Diet and Cancer cardiovascular cohort (mean age 56 years, 59% women) who were free from the MetS at baseline and subsequently underwent a follow‐up examination after a median of 16 years. MetS was defined according to the NCEP‐ATP‐III guidelines. Logistic regression was used to adjust for covariates.Main outcome measuresMetabolic syndrome and long‐term progression as well as incidence of the different components of the MetS.ResultsDuring follow‐up, 428 subjects developed new‐onset MetS. In age‐ and sex‐adjusted analysis, compared with the lowest quartile of cystatin C, the odds ratios (95% confidence interval) for incident MetS in subjects with cystatin C levels in quartiles 2, 3 and 4 were 1.00 (0.71–1.40), 1.48 (1.06–2.07) and 1.91 (1.37–2.68), respectively (Ptrend < 0.001); this linear association remained significant even after full multivariate adjustment (Ptrend = 0.041). Interestingly, in this fully adjusted model, long‐term progression of abdominal obesity was the only component of the MetS significantly associated with increasing quartiles of baseline cystatin C levels (Ptrend = 0.008).ConclusionThese findings suggest that cystatin C may adversely affect metabolic factors, particularly abdominal obesity, thus contributing to development of the MetS. Our results may help to explain the link between cystatin C and development of CVD.
HCVclearance from saliva ofHIV–HCV‐coinfected patients on treatment with interferon plus ribavirin
Authors: Feijoo J , Eirea M , Limeres J , Abeleira M , Ramos I , Ocampo A , Diz P 
Published: April 2013

ObjectiveTo determine hepatitis C virus (HCV)RNAclearance from blood and saliva ofHIV–HCV‐coinfected patients undergoing combined therapy with pegylated interferon plus ribavirin (PEG‐IFN‐RIB).Subjects and MethodsStudy group was formed of 60HIV‐infected patients with chronic hepatitis C who were starting treatment withPEG‐IFN‐RIB. Blood and saliva samples were taken at baseline, at the end of treatment and 24 and 48 weeks later. A nestedRT‐PCRtechnique was used to detectHCV‐RNAin saliva.ResultsHCV‐RNAwas detected in saliva at baseline in 64.7% of patients. Thirty‐four patients completed follow‐up. The response rate (undetectableHCV‐RNA) in blood was 79.4% at the end of treatment; 55.8% at 24 weeks after the end of treatment and 50% at 48 weeks.HCVwas detected in saliva of 13 (38.2%) patients at the end of treatment and in 18 (52.9%) patients at 24 and 48 weeks later. Concordance ofHCVclearance from blood and saliva reached its maximum value at 48 weeks after the end of treatment (odds ratio, 112.51).ConclusionInHIV–HCV‐coinfected patients responders toPEG‐IFN‐RIB, the salivary glands do not appear to be a sanctuary site forHCV, although viral clearance from saliva may be slower than from blood.
The Interaction between Negative Emotionality and Effortful Control in Early Social‐emotional Development
Authors: Moran Lyndsey R. , Lengua Liliana J. , Zalewski Maureen 
Published: April 2013

AbstractInteractions between reactive and regulatory dimensions of temperament may be particularly relevant to children's adjustment but are examined infrequently. This study investigated these interactions by examining effortful control as a moderator of the relations of fear and frustration reactivity to children's social competence, internalizing, and externalizing problems. Participants included 306 three‐year‐old children and their mothers. Children's effortful control was measured using observational measures, and reactivity was assessed with both observational and mother‐reported measures. Mothers reported on children's adjustment. Significant interactions indicated that children with higher mother‐reported fear or higher observed frustration and lower executive control showed higher externalizing problems whereas children with higher observed fear and higher delay ability demonstrated lower externalizing problems. These results highlight effortful control as a moderator of the relation between reactivity and adjustment, and may inform the development of interventions geared toward the management of specific negative affects.
Comparison of the two fully automated anti‐HCMV IgG assays: Abbott Architect CMV IgG assay and Biotest anti‐HCMV recombinant IgG ELISA
Authors: Juhl D. , Vockel A. , Luhm J. , Ziemann M. , Hennig H. , Görg S. 
Published: April 2013

SUMMARYObjective and BackgroundTo assess the performance characteristics of two fully automated human cytomegalovirus (HCMV) antibody tests.Materials and MethodsSamples from negatively or not pre‐screened blood donors were tested by the Biotest anti‐HCMV recombinant IgG enzyme‐linked immunosorbent assay (ELISA) in comparison to the Abbott Architect CMV IgG assay [chemiluminescent microparticle immunoassay (CMIA)]. For clarification, samples with discordant results between both assays were subjected to supplemental testing for anti‐HCMV IgG, IgM and HCMV DNA in plasma.ResultsFrom 4938 samples tested, 362 delivered positive results in both assays (7·3%). 91 (1·8%) samples were discordant. Of 43 (two not further tested) samples positive only by ELISA, 41 were false positive, one true positive and one indeterminate. Of 45 (one not further tested) samples positive only by CMIA, 20 were false positive, 9 indeterminate and 16 true positive. Anti‐HCMV IgM and HCMV DNA testing from the plasma were negative in indeterminate samples. Considering the results of supplemental testing, the CMIA achieved altogether better results concerning resolved sensitivity, resolved specificity as well as negative predictive value. Both assays had an inferior positive predictive value, with a better result for CMIA.ConclusionOverall, the performance characteristics of the CMIA were better than those of the ELISA. Owing to the inferior positive predictive value, positive test results require confirmation if blood products from donors with remote HCMV infection should be administered.
Draft Genome Sequence of VIM-2-Producing Multidrug-Resistant Pseudomonas aeruginosa ST175, an Epidemic High-Risk Clone
Authors: Viedma Esther , Juan Carlos , Otero Joaquín R. , Oliver Antonio , Chaves Fernando 
Published: April 2013

ABSTRACT

The VIM-2-producing multidrug-resistant high-risk clone
Pseudomonas aeruginosa
sequence type (ST) 175 was isolated in the setting of a large outbreak in Hospital Universitario 12 de Octubre (Spain) from 2007 to 2010. This strain was resistant to all β-lactams, fluoroquinolones, and aminoglycosides, with the exception of amikacin, and has become an endemic clone in our institution.
Draft Genome Sequence of Dihydroxyacetone-Producing Gluconobacter thailandicus Strain NBRC 3255
Authors: Matsutani Minenosuke , Kawajiri Erika , Yakushi Toshiharu , Adachi Osao , Matsushita Kazunobu 
Published: April 2013

ABSTRACT

Here, we report the draft genome sequence of the acetic acid bacterium
Glucnobacter thailandicus
strain NBRC 3255. The draft genome sequence is composed of 109 contigs in 3,305,227 bp and contains 3,225 protein-coding genes. Two paralogous sets of
sldAB
operons, which are responsible for dihydroxyacetone production from glycerol, were identified.
Juvenile Huntington's disease: a population-based study using the General Practice Research Database
Authors: Douglas Ian , Evans Stephen , Rawlins Michael D , Smeeth Liam , Tabrizi Sarah J , Wexler Nancy S 
Published: April 2013

BackgroundThe juvenile form of Huntington's disease (HD) is a rare disorder. There are no population-based estimates of either its incidence or prevalence in any population in the world. The present study was undertaken to estimate the frequency of juvenile HD in the UK and to examine the range of pharmacological treatments used in its management.MethodThe records of individuals under the age of 21 who had recorded diagnoses of HD were retrieved from the General Practice Research Database from 1990 through 2010. From these data estimates of incidence and prevalence were made as well as the specific treatments used in the treatment of its physical and psychological manifestations.Results12 incident and 21 prevalent patients with juvenile HD were identified. The 21 prevalent cases included the 12 incident cases. The minimum population-based estimate of incidence is 0.70 (95% CI 0.36 to 1.22) per million patient-years. The minimum estimate of prevalence is 6.77/million (95% CI 5.60 to 8.12) per million patient-years. Patients were most frequently prescribed antidepressants, hypnotics, antipsychotics and treatments for motor abnormalities.ConclusionsIn the UK, juvenile HD is an extremely rare and complex disorder. The prescribing data demonstrate that the clinical management of juvenile HD is undertaken with no formal evidence base for the efficacy or safety of the treatments used. Research into the safety and efficacy of appropriate therapies is urgently required to offset the haphazard nature of prescribing. Multinational collaboration will be necessary to enrol sufficient numbers. Exploratory studies, though, should begin now.
A qualitative study of GP, NP and patient views about the use of rapid streptococcal antigen detection tests (RADTs) in primary care: ‘swamped with sore throats?’
Authors: Leydon Gerry M , McDermott Lisa , Moore Mike , Williamson Ian , Hobbs F D Richard , Lambton Tessa , Cooper Rebecca , Henderson Hugo , Little Paul 
Published: April 2013

ObjectiveTo explore patient and healthcare professionals’ (HCP) views of clinical scores and rapid streptococcal antigen detection tests (RADTs) for acute sore throat.DesignQualitative semistructured interview study.SettingUK primary care.ParticipantsGeneral practitioners (GPs), nurse practitioners (NPs) and patients from general practices across Hampshire, Oxfordshire and the West Midlands who were participating in the Primary Care Streptococcal Management (PRISM) study.MethodSemistructured, face-to-face and phone interviews were conducted with GPs, NPs and patients from general practices across Hampshire, Oxfordshire and the West Midlands.Results51 participants took part in the study. Of these, 42 were HCPs (29 GPs and 13 NPs) and 9 were patients. HCPs could see a positive role for RADTs in terms of reassurance, as an educational tool for patients, and for aiding inexperienced practitioners, but also had major concerns about RADT use in clinical practice. Particular concerns included the validity of the tests (the role of other bacteria, and carrier states), the tension and possible disconnect with clinical assessment and intuition, the issues of time and resource use and the potential for medicalisation of self-limiting illness. In contrast, however, experience of using RADTs over time seemed to make some participants more positive about using the tests. Moreover, patients were much more positive about the place of RADTs in providing reassurance and in limiting their antibiotic use.ConclusionsIt is unlikely that RADTs will have a (comfortable) place in clinical practice in the near future until health professionals’ concerns are met, and they have direct experience of using them. The routine use of clinical scoring systems for acute upper respiratory illness also face important barriers related to clinicians’ perceptions of their utility in the face of clinician experience and intuition.
THERMAL EQUILIBRIUM STATES OF A LINEAR SCALAR QUANTUM FIELD IN STATIONARY SPACE–TIMES
Authors: SANDERS KO 
Published: April 2013

The linear scalar quantum field, propagating in a globally hyperbolic space–time, is a relatively simple physical model that allows us to study many aspects in explicit detail. In this review, we focus on the thermal equilibrium (KMS) states of such a field in a stationary space–time. Our presentation draws on several existing sources and aims to give a unified exposition, while weakening certain technical assumptions. In particular we drop all assumptions on the behavior of the time-like Killing field, which is important for physical applications to the exterior region of a stationary black hole.Our review includes results on the existence and uniqueness of ground and KMS states, as well as an evaluation of the evidence supporting the KMS-condition as a characterization of thermal equilibrium. We draw attention to the poorly understood behavior of the temperature of the quantum field with respect to locality.If the space–time is standard static, the analysis can be done more explicitly. For compact Cauchy surfaces we consider Gibbs states and their properties. For general Cauchy surfaces we give a detailed justification of the Wick rotation, including the explicit determination of the Killing time dependence of the quasi-free KMS states.
Diesel Exhaust Induces Systemic Lipid Peroxidation and Development of Dysfunctional Pro-Oxidant and Pro-Inflammatory High-Density Lipoprotein
Authors: Yin Fen , Lawal Akeem , Ricks Jerry , Fox Julie R. , Larson Tim , Navab Mohamad , Fogelman Alan M. , Rosenfeld Michael E. , Araujo Jesus A. 
Published: April 2013

Objective—
To evaluate whether exposure to air pollutants induces oxidative modifications of plasma lipoproteins, resulting in alteration of the protective capacities of high-density lipoproteins (HDLs).

Approach and Results—

We exposed apolipoprotein E–deficient mice to diesel exhaust (DE) at ≈250 µg/m
3
for 2 weeks, filtered air (FA) for 2 weeks, or DE for 2 weeks, followed by FA for 1 week (DE+FA). DE led to enhanced lipid peroxidation in the brochoalveolar lavage fluid that was accompanied by effects on HDL functionality. HDL antioxidant capacity was assessed by an assay that evaluated the ability of HDL to inhibit low-density lipoprotein oxidation estimated by 2′,7′-dichlorofluorescein fluorescence. HDL from DE-exposed mice exhibited 23 053±2844 relative fluorescence units, higher than FA-exposed mice (10 282±1135 relative fluorescence units,
P
<0.001) but similar to the HDL from DE+FA-exposed mice (22 448±3115 relative fluorescence units). DE effects on HDL antioxidant capacity were negatively correlated with paraoxonase enzymatic activity, but positively correlated with levels of plasma 8-isoprostanes, 12-hydroxyeicosatetraenoic acid, 13-hydroxyoctadecadienoic acid, liver malondialdehyde, and accompanied by perturbed HDL anti-inflammatory capacity and activation of the 5-lipoxygenase pathway in the liver.

Conclusions—
DE emissions induced systemic pro-oxidant effects that led to the development of dysfunctional HDL. This may be one of the mechanisms by which air pollution contributes to enhanced atherosclerosis.
Dietary Carnosine Prevents Early Atherosclerotic Lesion Formation in Apolipoprotein E–Null Mice
Authors: Barski Oleg A. , Xie Zhengzhi , Baba Shahid P. , Sithu Srinivas D. , Agarwal Abhinav , Cai Jian , Bhatnagar Aruni , Srivastava Sanjay 
Published: April 2013

Objective—
Atherosclerotic lesions are associated with the accumulation of reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde metabolism has been shown to exacerbate atherosclerosis and enhance the accumulation of aldehyde-modified proteins in atherosclerotic plaques, no therapeutic interventions have been devised to prevent aldehyde accumulation in atherosclerotic lesions.

Approach and Results—

We examined the efficacy of carnosine, a naturally occurring β-alanyl-histidine dipeptide, in preventing aldehyde toxicity and atherogenesis in apolipoprotein E–null mice. In vitro, carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes. Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the formation of free aldehydes 4-hydroxynonenal and malonaldialdehyde in Cu
2+
-oxidized low-density lipoprotein. Preloading bone marrow–derived macrophages with cell-permeable carnosine analogs reduced 4-hydroxynonenal–induced apoptosis. Oral supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation in aortic valves of apolipoprotein E–null mice and attenuated the accumulation of protein-acrolein, protein-4-hydroxyhexenal, and protein-4-hydroxynonenal adducts in atherosclerotic lesions, whereas urinary excretion of aldehydes as carnosine conjugates was increased.

Conclusions—
The results of this study suggest that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Endogenous levels of carnosine may be important determinants of atherosclerotic lesion formation, and treatment with carnosine or related peptides could be a useful therapy for the prevention or the treatment of atherosclerosis.
Pulmonary Vein Isolation Using a Visually Guided Laser Balloon Catheter
Authors: Dukkipati Srinivas R. , Kuck Karl-Heinz , Neuzil Petr , Woollett Ian , Kautzner Josef , McElderry H. Thomas , Schmidt Boris , Gerstenfeld Edward P. , Doshi Shephal K. , Horton Rodney , Metzner Andreas , d’Avila Andre , Ruskin Jeremy N. , Natale Andrea , Reddy Vivek Y. 
Published: April 2013

Background—
Because of the technical difficulty with achieving pulmonary vein (PV) isolation in the treatment of patients with paroxysmal atrial fibrillation, novel catheter designs to facilitate the procedure are in development. A visually guided laser ablation (VGLA) catheter was designed to allow the operator to directly visualize target tissue for ablation and then deliver laser energy to perform point-to-point circumferential ablation. Single-center studies have demonstrated favorable safety and efficacy. We sought to determine the multicenter feasibility, efficacy, and safety of performing PV isolation using the VGLA catheter.

Methods and Results—
This study includes the first 200 paroxysmal atrial fibrillation patients treated with the VGLA catheter (33 operators, 15 centers). After transseptal puncture, the VGLA catheter was used to perform PV isolation. Electric isolation was assessed using a circular mapping catheter. Using the VGLA catheter, 98.8% (95% confidence interval, 97.8%–99.5%) of targeted PVs were isolated using a mean of 1.07 catheters per patient. Fluoroscopy and procedure times were 31±21 (mean±SD) and 200±54 minutes, respectively, and improved with operator experience. There were no instances of stroke, transient ischemic attack, atrioesophageal fistulas, or significant PV stenosis. There was a 2% incidence of cardiac tamponade and a 2.5% incidence of phrenic nerve palsy. At 12 months, the drug-free rate of freedom from atrial arrhythmias after 1 or 2 procedures was 60.2% (95% confidence interval, 52.7%–67.4%).

Conclusions—
In this multicenter experience of the first 200 patients treated with the VGLA catheter, PV isolation can be achieved in virtually all patients using a single VGLA catheter with an efficacy similar to radiofrequency ablation.
Chronic Pain Syndromes After Ischemic Stroke
Authors: O’Donnell Martin J. , Diener Hans-Christoph , Sacco Ralph L. , Panju Akbar A. , Vinisko Richard , Yusuf Salim 
Published: April 2013

Background and Purpose—
Chronic pain syndromes are reported to be common after stroke, but most previous epidemiological studies have generally included small cohorts of patients with relatively short-term follow-up. In a large cohort with ischemic stroke (Prevention Regimen for Effectively avoiding Second Stroke [PRoFESS] trial), we determined the prevalence, risk factors, and clinical consequence of new poststroke pain syndromes.

Methods—
Within the PRoFESS trial (mean follow-up 2.5 years), a standardized chronic pain questionnaire was administered (at the penultimate follow-up visit) to all participants who reported chronic pain since their stroke and did not have a history of chronic pain before their index stroke. Multivariable logistic regression analyses were used to determine risk factors for poststroke pain (and pain subtypes), and the association between poststroke pain and cognitive (≥3 reduction in Mini-Mental State Examination score) and functional decline (≥1 increase in m-Rankin).

Results—
In total, 15 754 participants were included; of which 1665 participants (10.6%) reported new chronic poststroke pain, and included 431 participants (2.7%) with central poststroke pain, 238 (1.5%) with peripheral neuropathic pain, 208 (1.3%) with pain from spasticity, and 136 participants (0.9%) with pain from shoulder subluxation. More than 1 pain subtype was reported in 86 participants (0.6%). Predictors of poststroke pain included increased stroke severity, female sex, alcohol intake, statin use, depressive symptoms, diabetes mellitus, antithrombotic regimen, and peripheral vascular disease. A new chronic pain syndrome was associated with greater dependence (odds ratio, 2.16; 95% confidence interval, 1.82–2.56). Peripheral neuropathy and pain from spasticity/shoulder subluxation were associated with cognitive decline.

Conclusions—
Chronic pain syndromes are common after ischemic stroke and are associated with increased functional dependence and cognitive decline.