bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Epstein–Barr Virus Lytic Protein BZLF1 as a Candidate Target Antigen for Vaccine Development
Authors: Hartlage Alex S. , Liu Tom , Patton John T. , Garman Sabrina L. , Zhang Xiaoli , Kurt Habibe , Lozanski Gerard , Lustberg Mark E. , Caligiuri Michael A. , Baiocchi Robert A. 
Published: March 2015

AbstractThe Epstein–Barr virus (EBV) is an oncogenic, γ-herpesvirus associated with a broad spectrum of disease. Although most immune-competent individuals can effectivley develop efficient adaptive immune responses to EBV, immunocompromised individuals are at serious risk for developing life-threatening diseases, such as Hodgkin lymphoma and posttransplant lymphoproliferative disorder (PTLD). Given the significant morbidity associated with EBV infection in high-risk populations, there is a need to develop vaccine strategies that restore or enhance EBV-specific immune responses. Here, we identify the EBV immediate-early protein BZLF1 as a potential target antigen for vaccine development. Primary tumors from patients with PTLD and a chimeric human-murine model of EBV-driven lymphoproliferative disorder (EBV-LPD) express BZLF1 protein. Pulsing human dendritic cells (DC) with recombinant BZLF1 followed by incubation with autologous mononuclear cells led to expansion of BZLF1-specific CD8+ T cells in vitro and primed BZLF1-specific T-cell responses in vivo. In addition, vaccination of hu-PBL-SCID mice with BZLF1-transduced DCs induced specific cellular immunity and significantly prolonged survival from fatal EBV-LPD. These findings identify BZLF1 as a candidate target protein in the immunosurveillance of EBV and provide a rationale for considering BZLF1 in vaccine strategies to enhance primary and recall immune responses and potentially prevent EBV-associated diseases. Cancer Immunol Res; 3(7); 787–94. ©2015 AACR.
Analysis for Genetic Modifiers of Disease Severity in Patients With Long-QT Syndrome Type 2
Authors: Kolder Iris C.R.M. , Tanck Michael W.T. , Postema Pieter G. , Barc Julien , Sinner Moritz F. , Zumhagen Sven , Husemann Anja , Stallmeyer Birgit , Koopmann Tamara T. , Hofman Nynke , Pfeufer Arne , Lichtner Peter , Meitinger Thomas , Beckmann Britt M. , Myerburg Robert J. , Bishopric Nanette H. , Roden Dan M. , Kääb Stefan , Wilde Arthur A.M. , Schott Jean-Jacques , Schulze-Bahr Eric , Bezzina Connie R. 
Published: March 2015

Background—
Considerable interest exists in the identification of genetic modifiers of disease severity in the long-QT syndrome (LQTS) as their identification may contribute to refinement of risk stratification.

Methods and Results—

We searched for single-nucleotide polymorphisms (SNPs) that modulate the corrected QT (QTc)-interval and the occurrence of cardiac events in 639 patients harboring different mutations in
KCNH2
. We analyzed 1201 SNPs in and around 18 candidate genes, and in another approach investigated 22 independent SNPs previously identified as modulators of QTc-interval in genome-wide association studies in the general population. In an analysis for quantitative effects on the QTc-interval, 3 independent SNPs at
NOS1AP
(rs10494366,
P
=9.5×10
−8
; rs12143842,
P
=4.8×10
−7
; and rs2880058,
P
=8.6×10
−7
) were strongly associated with the QTc-interval with marked effects (>12 ms/allele). Analysis of patients versus general population controls uncovered enrichment of QTc-prolonging alleles in patients for 2 SNPs, located respectively at
NOS1AP
(rs12029454; odds ratio, 1.85; 95% confidence interval, 1.32–2.59;
P
=3×10
−4
) and
KCNQ1
(rs12576239; odds ratio, 1.84; 95% confidence interval, 1.31–2.60;
P
=5×10
−4
). An analysis of the cumulative effect of the 6
NOS1AP
SNPs by means of a multilocus genetic risk score (GRS

NOS1AP

) uncovered a strong linear relationship between GRS

NOS1AP

and the QTc-interval (
P
=4.2×10
−7
). Furthermore, patients with a GRS

NOS1AP

in the lowest quartile had a lower relative risk of cardiac events compared with patients in the other quartiles combined (
P
=0.039).

Conclusions—

We uncovered unexpectedly large effects of
NOS1AP
SNPs on the QTc-interval and a trend for effects on risk of cardiac events. For the first time, we linked common genetic variation at
KCNQ1
with risk of long-QT syndrome.
Population Risk Prediction Models for Incident Heart Failure
Authors: Echouffo-Tcheugui Justin B. , Greene Stephen J. , Papadimitriou Lampros , Zannad Faiez , Yancy Clyde W. , Gheorghiade Mihai , Butler Javed 
Published: March 2015

Background—
The prevalence of heart failure is expected to significantly rise unless high-risk patients are effectively screened and appropriate, cost-effective prevention interventions are implemented.

Methods and Results—
We performed a systematic review to evaluate the prediction characteristics of the published heart failure risk prediction models as of August 2014 using MEDLINE and EMBASE databases. Eligible studies reported the development, validation, or impact assessment of a model. Two investigators performed independent review to extract data on study design and characteristics, risk predictors, discrimination, calibration, and reclassification ability of models, as well as validation and impact analysis. We included 13 publications reporting on 28 heart failure risk prediction models. Models had acceptable-to-good discriminatory ability (c-statistics, >0.70) in the derivation sample. Calibration was less commonly assessed, but was acceptable when it was. Only 2 models were externally validated more than once, displaying modest-to-acceptable discrimination (c-statistics, 0.61–0.79). When assessed, novel blood and imaging markers modestly improved risk prediction. One model assessed the prediction properties in race-based subgroups, whereas 2 models evaluated sex-based subgroups. Impact analysis found none of the models recommended for use in any clinical practice guideline.

Conclusions—
Incident heart failure risk prediction remains at an early stage. The discrimination ability of current models is acceptable in derivation data sets but most models have not been externally validated. It remains unclear which models are cost-effective and best suit population screening needs. The effects of models on clinical and preventative care requires further study.
Consequence of Cerebral Embolism After Transcatheter Aortic Valve Implantation Compared With Contemporary Surgical Aortic Valve Replacement
Authors: Uddin Akhlaque , Fairbairn Timothy A. , Djoukhader Ibrahim K. , Igra Mark , Kidambi Ananth , Motwani Manish , Herzog Bernhard , Ripley David P. , Musa Tarique Al , Goddard Anthony J.P. , Blackman Daniel J. , Plein Sven , Greenwood John P. 
Published: March 2015

Background—
Incidence of cerebral microinfarcts is higher after transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR). It is unknown whether these lesions persist and what direct impact they have on health-related quality of life. The objective was to identify predictors of cerebral microinfarction and measure their effect on health-related quality of life during 6 months after TAVI when compared with SAVR.

Methods and Results—

Cerebral MRI was conducted at baseline, post procedure, and 6 months using diffusion-weighted imaging. Health-related quality of life was measured at baseline, 30 days, and 6 months with short form-12 health outcomes and EuroQol 5 dimensions questionnaires. One hundred eleven patients (TAVI, n=71; SAVR, n=40) were studied. The incidence (54 [77%] versus 17 [43%];
P
=0.001) and number (3.4±4.9 versus 1.2±1.8;
P
=0.001) of new microinfarcts were greater after TAVI than after SAVR. The total volume per microinfarct was smaller in TAVI than in SAVR (0.23±0.24 versus 0.76±1.8 mL;
P
=0.04). The strongest associations for microinfarction were: TAVI (arch atheroma grade:
r
=0.46;
P
=0.0001) and SAVR (concomitant coronary artery bypass grafting:
r
=−0.33;
P
=0.03). Physical component score in TAVI increased after 30 days (32.1±6.6 versus 38.9±7.0;
P
<0.0001) and 6 months (40.4±9.3;
P
<0.0001); the improvement occurred later in SAVR (baseline: 34.9±10.6; 30 days: 35.9±10.2; 6 months: 42.8±11.2;
P
<0.001). After TAVI, there were no differences in the short form-12 health outcome scores according to the presence or size of new cerebral infarction.

Conclusions—
Cerebral microinfarctions are more common after TAVI compared with SAVR but seem to have no negative effect on early (30 days) or medium term (6 months) health-related quality of life. Aortic atheroma (TAVI) and concomitant coronary artery bypass grafting (SAVR) are independent risk factors for cerebral microinfarction.
Moderate‐to‐Vigorous Physical Activity With Accelerometry is Associated With Visceral Adipose Tissue in Adults
Authors: Murabito Joanne M. , Pedley Alison , Massaro Joseph M. , Vasan Ramachandran S. , Esliger Dale , Blease Susan J. , Hoffman Udo , Fox Caroline S. 
Published: March 2015

Background

We examined the relation between objectively measured physical activity with accelerometry and subcutaneous adipose tissue (
SAT
) and visceral adipose tissue (
VAT
) in a community‐based sample.

Methods and Results

We evaluated 1249 participants of the Framingham Third Generation and Omni
II
cohorts (mean age 51.7 years, 47% women) who underwent assessment of moderate‐to‐vigorous physical activity (
MVPA
) with accelerometry over 5 to 7 days, and multi‐detector computed tomography for measurement of
SAT
and
VAT
volume; fat attenuation was estimated by
SAT
and
VAT
hounsfield units (
HU
). In women, higher levels of
MVPA
were associated with decreased
SAT
(
P
<0.0001) and
VAT
volume (
P
<0.0001). The average decrement in
VAT
per 30 minute/day increase in
MVPA
was −453 cm
3
(95%
CI
−574, −331). The association was attenuated but persisted upon adjustment for
BMI
(−122 cm
3
,
P
=0.002). Higher levels of
MVPA
were associated with higher
SAT HU
(all
P
≤0.01), a marker of fat quality, even after adjustment for
SAT
volume. Similar findings were observed in men but the magnitude of the association was less. Sedentary time was not associated with
SAT
or
VAT
volume or quality in men or women.

Conclusions

MVPA
was associated with less
VAT
and
SAT
and better fat quality.
Association of Short-Term Use of Nonsteroidal Anti-Inflammatory Drugs With Stroke in Patients With Hypertension
Authors: Chuang Shao-Yuan , Yu Yunxian , Huey-Herng Sheu Wayne , Tsai Yu-Ting , Liu Xin , Hsiung Chao A. , Tsai Hui-Ju 
Published: March 2015

Background and Purpose—
Limited studies have investigated the risk of cerebrovascular events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects at high risk. We examined the short-term (defined as 30-day period) effect of selective and nonselective NSAIDs use on the risk of ischemic and hemorrhagic stroke in patients with hypertension.

Methods—

We conducted a case-crossover study using the National Health Insurance Research Database in Taiwan. We identified 1653 hypertensive subjects with stroke (defined as
International Classification of Diseases-Ninth Revision
-CM-codes: 433.x, 434.x, and 436.x for ischemic stroke; 430 and 431 for hemorrhagic stroke) in 2010. We investigated the transient effect of NSAIDs use on stroke using conditional logistic regressions with the adjustment of potential confounders.

Results—
The results suggested that NSAIDs use during the 30 days before stroke was associated with a 1.57-fold increased risk of ischemic stroke, but not of hemorrhagic stroke (adjusted odds ratio, 1.57; 95% confidence interval, 1.26–1.97 for ischemic stroke; and adjusted odds ratio, 1.38; 95% confidence interval, 0.79–2.40 for hemorrhagic stroke). When classifying NSAIDs into selective and nonselective groups, nonselective NSAIDs use significantly increased the risk of ischemic stroke (adjusted odds ratio, 1.55; 95% confidence interval, 1.24–1.94), but not of hemorrhagic stroke (adjusted odds ratio, 1.56; 95% confidence interval, 0.90–2.73).

Conclusions—
The results demonstrate an increased risk of stroke, specifically ischemic stroke among hypertensive subjects with NSAIDs use. It would be important to closely monitor the transient effect of initial NSAIDs treatment, particularly in patients with hypertension.
Prosocial effects of MDMA: A measure of generosity
Authors: Kirkpatrick Matthew , Delton Andrew W , Robertson Theresa E , de Wit Harriet 
Published: March 2015

Background: 3,4-methylenedioxymethamphetamine (MDMA) produces “prosocial” effects that contribute to its recreational use. Few studies have examined the cognitive and behavioral mechanisms by which MDMA produces these effects. Here we examined the effect of MDMA on a specific prosocial effect, i.e. generosity, using a task in which participants make decisions about whether they or another person will receive money (Welfare Trade-Off Task; WTT). Methods: The project included one study without drug administration and one with MDMA. In Study 1, we administered the WTT to healthy adults ( N = 361) and examined their performance in relation to measures of personality and socioeconomic status. In Study 2, healthy volunteers with MDMA experience ( N = 32) completed the WTT after MDMA administration (0, 0.5, or 1.0 mg/kg). Results: As expected, in both studies participants were more generous with a close friend than an acquaintance or stranger. In Study 1, WTT generosity was related to household income and trait Agreeableness. In Study 2, MDMA (1.0 mg/kg) increased generosity toward a friend but not a stranger, whereas MDMA (0.5 mg/kg) slightly increased generosity toward a stranger, especially among female participants. Conclusions: These data indicate that the WTT is a valuable, novel tool to assess a component of prosocial behavior, i.e. generosity to others. The findings support growing evidence that MDMA produces prosocial effects, but, as with oxytocin, these appear to depend on the social proximity of the relationships. The brain mechanisms underlying the construct of generosity, or the effects of MDMA on this measure, remain to be determined.
Functional Neuroanatomical Correlates of The Frontal Assessment Battery Performance in Alzheimer Disease
Authors: Lee Jun Ho , Byun Min Soo , Sohn Bo Kyung , Choe Young Min , Yi Dahyun , Han Ji Young , Choi Hyo Jung , Baek Hyewon , Woo Jong Inn , Lee Dong Young 
Published: March 2015

Background/Objectives: We aimed to elucidate the functional neuroanatomical correlates of Frontal Assessment Battery (FAB) performances by applying [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) to a large population of patients with Alzheimer disease (AD). Methods: The FAB was administered to 177 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by FDG-PET scan. Correlations between FAB scores and rCMglc were explored using both region-of-interest-based (ROI-based) and voxel-based approaches. Results: The ROI-based analysis showed that FAB scores correlated with the rCMglc of the dorsolateral prefrontal cortices. Voxel-based approach revealed significant positive correlations between FAB scores and rCMglc which were in various cortical regions including the temporal and parietal cortices as well as frontal regions, independent of age, gender, and education. After controlling the effect of global disease severity with Mini-Mental State Examination score, significant positive correlation was found only in the bilateral prefrontal regions. Conclusions: Although FAB scores are influenced by temporoparietal dysfunction due to the overall progression of AD, it likely reflects prefrontal dysfunction specifically regardless of global cognitive state or disease severity in patients with AD.
Clarifying perspectives
Authors: Bartholdson Cecilia , Lützén Kim , Blomgren Klas , Pergert Pernilla 
Published: March 2015

Background: Childhood cancer care involves many ethical concerns. Deciding on treatment levels and providing care that infringes on the child’s growing autonomy are known ethical concerns that involve the whole professional team around the child’s care. Objectives: The purpose of this study was to explore healthcare professionals’ experiences of participating in ethics case reflection sessions in childhood cancer care. Research design: Data collection by observations, individual interviews, and individual encounters. Data analysis were conducted following grounded theory methodology. Participants and research context: Healthcare professionals working at a publicly funded children’s hospital in Sweden participated in ethics case reflection sessions in which ethical issues concerning clinical cases were reflected on. Ethical considerations: The children’s and their parents’ integrity was preserved through measures taken to protect patient identity during ethics case reflection sessions. The study was approved by a regional ethical review board. Findings: Consolidating care by clarifying perspectives emerged. Consolidating care entails striving for common care goals and creating a shared view of care and the ethical concern in the specific case. The inter-professional perspectives on the ethical aspects of care are clarified by the participants’ articulated views on the case. Different approaches for deliberating ethics are used during the sessions including raising values and making sense, leading to unifying interactions. Discussion: The findings indicate that ethical concerns could be eased by implementing ethics case reflection sessions. Conflicting perspectives can be turned into unifying interactions in the healthcare professional team with the common aim to achieve good pediatric care. Conclusion: Ethics case reflection sessions is valuable as it permits the discussion of values in healthcare-related issues in childhood cancer care. Clarifying perspectives, on the ethical concerns, enables healthcare professionals to reflect on the most reasonable and ethically defensible care for the child. A consolidated care approach would be valuable for both the child and the healthcare professionals because of the common care goals.
Remodeling of the Proximal Tibia Subsequent to Bone Graft Harvest
Authors: Vanryckeghem Vincent , Vandeputte Geoffroy , Heylen Steven , Somville Johan 
Published: March 2015

Background: Proximal tibia bone autograft (PTBG) is regularly used in reconstructive foot, ankle, and maxillofacial surgery. Although many surgeons prefer PTBG rather than the conventional iliac crest, little is known about the remodeling capacity of the proximal tibia after harvesting cancellous bone. Methods: Via bilateral postoperative computed tomography of 17 harvesting sites, comparing the defect side with the healthy side, we measured the repair capacity of the proximal tibia in response to bone defect created by the harvest at medium-term follow-up (mean 29 months; range, 7-55 months). Results: 16 of 17 (94%) cortical defects showed complete consolidation. Cancellous remodeling was graded 0 to 3, with 2 defects showing complete remodeling (grade 3), 4 defects partial remodeling (more than 50%), 8 defects partial remodeling (less than 50%) and 3 defects no remodeling at all (grade 0). Conclusion: The proximal tibia has the potential to form new cancellous bone after cancellous bone graft harvesting. More data are required to identify possible variables influencing this remodeling capacity. When performing knee surgery, knee surgeons should take into account the relatively small defect size and the consolidation of the cortical window after proximal tibia bone harvesting. Level of Evidence: Level IV, case series.
Detection of feline coronavirus in cerebrospinal fluid for diagnosis of feline infectious peritonitis in cats with and without neurological signs
Authors: Doenges Stephanie J , Weber Karin , Dorsch Roswitha , Fux Robert , Fischer Andrea , Matiasek Lara A , Matiasek Kaspar , Hartmann Katrin 
Published: March 2015

Objectives The objective of this study was to evaluate the sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) detecting feline coronavirus (FCoV) RNA in cerebrospinal fluid (CSF) of cats with and without neurological and/or ocular signs for the diagnosis of feline infectious peritonitis (FIP). Methods This prospective case-control study included 34 cats. Nineteen cats had a definitive histopathological diagnosis of FIP (seven of these with neurological and/or ocular signs), and 15 cats had other diseases but similar clinical signs (three of these with neurological and/or ocular signs). Real-time RT-PCR was performed on the CSF of all cats, and sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were calculated. Results Real-time RT-PCR of CSF showed a specificity of 100% in diagnosing FIP, a sensitivity of 42.1%, a PPV of 100% and an NPV of 57.7%. The sensitivity of the real-time RT-PCR of CSF in cats with neurological and/or ocular signs was 85.7%. Conclusions and relevance Although it is known that RT-PCR can give false positive results, especially if performed using serum or plasma, this real-time RT-PCR detecting FCoV RNA in CSF can be considered a reliable specific tool for the diagnosis of FIP. If only cats with neurological involvement are evaluated, the sensitivity of this real-time RT-PCR in CSF is also high.
Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow's milk: Pilot study
Authors: Nucera Eleonora , Pecora Valentina , Buonomo Alessandro , Rizzi Angela , Aruanno Arianna , Pascolini Lucilla , Ricci Anna G , Di Rienzo Alessia , Mezzacappa Simona , Ferraironi Manuela , Patriarca Giampiero , Gasbarrini Giovanni , Schiavino Domenico 
Published: March 2015

ObjectiveThe quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate‐type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen‐induced CD63 up‐regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic.Materials and methodsThree male patients affected by cow's milk allergy underwent successful oral desensitization to cow's milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol.ResultsUsing a fluorescent enzyme immunoassay, the comparison of specific cow's milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow's milk proteins (α‐lactoalbumin, β‐lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases.ConclusionsUsing flow cytometry, food allergen‐specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.
Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML
Authors: Rijal Sewa , Fleming Shaun , Cummings Nik , Rynkiewicz Natalie K. , Ooms Lisa M. , Nguyen Nhu-Y. N. , Teh Tse-Chieh , Avery Sharon , McManus Julie F. , Papenfuss Anthony T. , McLean Catriona , Guthridge Mark A. , Mitchell Christina A. , Wei Andrew H. 
Published: March 2015

Key PointsINPP4B promotes chemoresistance in AML independent of phosphoinositide phosphatase function.