bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of anti‐CD40 antibody‐mediated costimulation blockade on non‐Gal antibody production and heterotopic cardiac xenograft survival in a GTKO.hCD46Tg pig‐to‐baboon model
Authors: Mohiuddin Muhammad M. , Singh Avneesh K. , Corcoran Philip C. , Hoyt Robert F. , Thomas Marvin L. , Lewis Billeta G. T. , Eckhaus Michael , Dabkowski Nicole L. , Belli Aaron J. , Reimann Keith A. , Ayares David , Horvath Keith A. 
Published: October 2013

AbstractBackgroundRecently, we have shown that an immunosuppression regimen including costimulation blockade via anti‐CD154 antibody significantly prolongs the cardiac xenograft survival in a GTKO.hCD46Tg pig‐to‐baboon heterotopic xenotransplantation model. Unfortunately, many coagulation disorders were observed with the use of anti‐CD154 antibody, and recipient survival was markedly reduced by these complications.Material and MethodsIn this experiment, we replaced anti‐CD154 antibody with a more clinically acceptable anti‐CD40 antibody while keeping the rest of the immunosuppressive regimen and the donor pig genetics the same. This was carried out to evaluate the antibody's role in xenograft survival and prevention of coagulopathies. Two available clones of anti‐CD40 antibody were tested. One mouse anti‐human CD40 antibody, (clone 3A8), activated B lymphocytes in vitro and only modestly suppressed antibody production in vivo. Whereas a recombinant mouse non‐human primate chimeric raised against macaque CD40, (clone 2C10R4), blocked B‐cell activation in vitro and completely blocked antibody production in vivo.ResultsThe thrombotic complications seen with anti‐CD154 antibody were effectively avoided but the graft survival, although extended, was not as prolonged as observed with anti‐CD154 antibody treatment. The longest survival for the 3A8 antibody group was 27 days, and the longest graft survival in the 2C10R4 antibody group was 146 days. All of the grafts except two rejected and were explanted. Only two recipient baboons had to be euthanized due to unrelated complications, and the rest of the baboons remained healthy throughout the graft survival period or after graft explantation. In contrast to our anti‐CD 154 antibody‐treated baboons, the non‐Gal antibody levels started to rise after B cells made their appearance around 8 weeks post‐transplantation.ConclusionsAnti‐CD40 antibody at the current dose does not induce any coagulopathies but while effective, had reduced efficacy to induce similar long‐term graft survival as with anti‐CD154 antibody perhaps due to ineffective control of B‐cell function and antibody production at the present dose. More experiments are required to determine antibody affinity and effective dose for inducing long‐term cardiac xenograft survival.
Exercise counteracts the effects of short‐term overfeeding and reduced physical activity independent of energy imbalance in healthy young men
Authors: Walhin Jean‐Philippe , Richardson Judith D. , Betts James A. , Thompson Dylan 
Published: October 2013

Key points
Physical exercise significantly improves health but to what extent these benefits depend on altered energy balance remains unclear.
In a human experimental model, we investigated whether daily exercise could counteract the effects of short‐term overfeeding and under‐activity independent of its impact on energy imbalance in healthy young men.
Short‐term positive energy balance from overfeeding and under‐activity resulted in impaired metabolic outcomes and alterations in the expression of several key genes within adipose tissue involved in nutritional balance, metabolism and insulin action.
These changes were mostly prevented by the addition of a daily vigorous‐intensity exercise bout even in the face of a standardised energy surplus.
Abstract  Physical activity can affect many aspects of metabolism but it is unclear to what extent this relies on manipulation of energy balance. Twenty‐six active men age 25 ± 7 years (mean ± SD) were randomly assigned either to consume 50% more energy than normal by over‐consuming their habitual diet for 7 days whilst simultaneously restricting their physical activity below 4000 steps day−1 to induce an energy surplus (SUR group; n= 14) or to the same regimen but with 45 min of daily treadmill running at 70% of maximum oxygen uptake (SUR+EX group; n= 12). Critically, the SUR+EX group received additional dietary energy intake to account for the energy expended by exercise, thus maintaining a matched energy surplus. At baseline and follow‐up, fasted blood samples and abdominal subcutaneous adipose tissue biopsies were obtained and oral glucose tolerance tests conducted. Insulinaemic responses to a standard glucose load increased 2‐fold from baseline to follow‐up in the SUR group (Δ17 ± 16 nmol (120 min) l−1; P= 0.002) whereas there was no change in the SUR+EX group (Δ1 ± 6 nmol (120 min) l−1). Seven of 17 genes within adipose tissue were differentially expressed in the SUR group; expression of SREBP‐1c, FAS and GLUT4 was significantly up‐regulated and expression of PDK4, IRS2, HSL and visfatin was significantly down‐regulated (P≤ 0.05). The pAMPK/AMPK protein ratio in adipose tissue was significantly down‐regulated in the SUR group (P= 0.005). Vigorous‐intensity exercise counteracted most of the effects of short‐term overfeeding and under‐activity at the whole‐body level and in adipose tissue, even in the face of a standardised energy surplus.
A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids
Authors: Egner Ingrid M. , Bruusgaard Jo C. , Eftestøl Einar , Gundersen Kristian 
Published: October 2013

Key points
Training studio folklore suggests that previous strength training, with or without the use of anabolic steroids facilitates re‐acquisition of muscle mass even after long intervening periods of inactivity. This ‘muscle memory’ has previously been attributed to motor learning, but our data suggest the existence of a cellular memory residing in the muscle fibres themselves.
Muscle fibres have multiple nuclei, and the number of nuclei increases when muscle mass increases.
When mice were briefly treated with steroids the muscle mass and number of nuclei increased. The drug was subsequently withdrawn for 3 months and the muscle mass returned to normal, but the excess cell nuclei persisted. When such muscles were subjected to overload they grew by 30% over 6 days while controls grew insignificantly.
Our data suggest that previous strength training might be beneficial later in life, and that a brief exposure to anabolic steroids might have long lasting performance‐enhancing effects.
Abstract  Previous strength training with or without the use of anabolic steroids facilitates subsequent re‐acquisition of muscle mass even after long intervening periods of inactivity. Based on in vivo and ex vivo microscopy we here propose a cellular memory mechanism residing in the muscle cells. Female mice were treated with testosterone propionate for 14 days, inducing a 66% increase in the number of myonuclei and a 77% increase in fibre cross‐sectional area. Three weeks after removing the drug, fibre size was decreased to the same level as in sham treated animals, but the number of nuclei remained elevated for at least 3 months (>10% of the mouse lifespan). At this time, when the myonuclei‐rich muscles were exposed to overload‐exercise for 6 days, the fibre cross‐sectional area increased by 31% while control muscles did not grow significantly. We suggest that the lasting, elevated number of myonuclei constitutes a cellular memory facilitating subsequent muscle overload hypertrophy. Our findings might have consequences for the exclusion time of doping offenders. Since the ability to generate new myonuclei is impaired in the elderly our data also invites speculation that it might be beneficial to perform strength training when young in order to benefit in senescence.
Multicenter Prospective Observational Study of the Comparative Efficacy and Safety of Vancomycin versus Teicoplanin in Patients with Health Care-Associated Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Yoon Young Kyung , Park Dae Won , Sohn Jang Wook , Kim Hyo Youl , Kim Yeon-Sook , Lee Chang-Seop , Lee Mi Suk , Ryu Seong-Yeol , Jang Hee-Chang , Choi Young Ju , Kang Cheol-In , Choi Hee Jung , Lee Seung Soon , Kim Shin Woo , Kim Sang Il , Kim Eu Suk , Kim Jeong Yeon , Yang Kyung Sook , Peck Kyong Ran , Kim Min Ja 
Published: October 2013

ABSTRACT

The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant
Staphylococcus aureus
(HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (
n
= 134) or teicoplanin (TEC) (
n
= 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 μg/ml (MIC
50
and MIC
90
, 1.5 μg/ml), and the TEC MIC ranged from 0.5 to 8 μg/ml (MIC
50
, 3 μg/ml; MIC
90
, 6 μg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.
Prevalence and Molecular Characterization of Fluoroquinolone-Resistant Mycobacterium tuberculosis Isolates in China
Authors: Zhang Zhijian , Lu Jie , Wang Yufeng , Pang Yu , Zhao Yanlin 
Published: October 2013

ABSTRACTChina is one of the countries with the highest burdens of multidrug-resistant (MDR) and fluoroquinolone (FQ)-resistant tuberculosis (TB) globally. Nevertheless, knowledge about the prevalence and molecular characterization of FQ-resistantMycobacterium tuberculosisisolates from this region remains scant. In this study, 138M. tuberculosisisolates determined by the agar proportion susceptibility method to be resistant to ofloxacin (OFX) were enrolled from a national drug resistance survey of China. All these strains were tested for susceptibility to ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, and sparfloxacin using liquid Middlebrook 7H9 medium. The entiregyrAandgyrBgenes conferring FQ resistance were sequenced, and spoligotyping was performed to distinguish different genotypes. Overall, the prevalence of resistance in China was highest for ofloxacin (3.76%), intermediate for levofloxacin (3.18%) and moxifloxacin (3.12%), and lowest for sparfloxacin (1.91%) and gatifloxacin (1.33%). Mutations in thegyrAgene were observed in 89 (64.5%) out of the 138 OFX-resistantM. tuberculosisstrains. Positions 94 and 90 were the most frequent sites of mutation conferring FQ resistance on these strains, accounting for high-level FQ resistance. Furthermore, the Beijing genotype showed no association with high-level FQ resistance or distribution in hot spots in the quinolone resistance-determining region (QRDR) ofgyrA. Our findings provide essential implications for the feasibility of genotypic tests relying on detection of mutations in the QRDR ofgyrAand the shorter first-line treatment regimens based on FQs in China.
Improving handovers across a North London Mental Health Trust
Authors: Perry Jennifer , Manghnani Reena , Sommerlad Andrew , Ikkos George 
Published: October 2013

AbstractThe GMC Survey June 2011 highlighted that trainees in Barnet, Enfield and Haringey Mental Health Trust (BEH-MHT) were dissatisfied with the Trust's handover process. At this time there were no Trust guidelines on handovers.A quality improvement project was developed to create a consistent out of hours handover process and to improve staff satisfaction thereafter. Handover guidelines were implemented throughout the Trust on 1/2/12. An audit was carried out to measure staff compliance with handovers. A questionnaire was sent out to staff before and after implementation of the guidelines to assess satisfaction with handovers.The audit results highlighted that handovers occurred relatively consistently across the Trust following implementation of the guidelines. The questionnaire results showed an improvement in staff satisfaction with the handover process.The clinical implication of this project is an improved process of out of hours handover across BEH-MHT.
Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing
Authors: Rughetti Aurelia , Rahimi Hassan , Belleudi Francesca , Napoletano Chiara , Battisti Federico , Zizzari Ilaria G. , Antonilli Morena , Bellati Filippo , Wandall Hans H. , Benedetti Panici Pierluigi , Burchell Joy M. , Torrisi Mara R. , Nuti Marianna 
Published: October 2013

Abstract
Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumor-associated glycoproteins. In cancer, MUC1 loses polarity and becomes overexpressed and hypoglycosylated. Changes in glycan moieties contribute to MUC1 immunogenicity and can modify the interactions of tumor cells with antigen-presenting cells such as dendritic cells that would affect the overall antitumor immune response. Here, we show that the form of the MUC1 antigen, i.e., soluble or as microvesicle cargo, influences MUC1 processing in dendritic cells. In fact, MUC1 carried by microvesicles translocates from the endolysosomal/HLA-II to the HLA-I compartment and is presented by dendritic cells to MUC1-specific CD8+ T cells stimulating IFN-γ responses, whereas the soluble MUC1 is retained in the endolysosomal/HLA-II compartment independently by the glycan moieties and by the modality of internalization (receptor-mediated or non–receptor mediated). MUC1 translocation to the HLA-I compartment is accompanied by deglycosylation that generates novel MUC1 glycoepitopes. Microvesicle-mediated transfer of tumor-associated glycoproteins to dendritic cells may be a relevant biologic mechanism in vivo contributing to define the type of immunogenicity elicited. Furthermore, these results have important implications for the design of glycoprotein-based immunogens for cancer immunotherapy. Cancer Immunol Res; 2(2); 177–86. ©2013 AACR.
Changes in Clinical and Microbiological Periodontal Profiles Relate to Progression of Carotid Intima‐Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study
Authors: Desvarieux Moïse , Demmer Ryan T. , Jacobs David R. , Papapanou Panos N. , Sacco Ralph L. , Rundek Tatjana 
Published: October 2013

Background
No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis.

Methods and Results

The Oral Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (
PD
) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by
DNA
‐
DNA
checkerboard hybridization. Common carotid artery intima‐medial thickness (
CCA
‐
IMT
) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%
PD
≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal
CCA
‐
IMT
progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (
SE
)
CCA
‐
IMT
increased during follow‐up by 0.139±0.008 mm. Longitudinal
IMT
progression attenuated with improvement in clinical or microbial periodontal status. Mean
CCA
‐
IMT
progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%
PD
≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (
P
for trend<0.0001). Likewise, mean
CCA
‐
IMT
increased by 0.20 (0.02), 0.18 (0.02), 0.15 (0.02), and 0.12 (0.02) mm (
P
<0.0001) across quartiles of longitudinal improvement in periodontal microbial status (Δetiologic dominance).

Conclusion

Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery
IMT
progression at 3‐year average follow‐up.
How We Learn to Make Decisions: Rapid Propagation of Reinforcement Learning Prediction Errors in Humans
Authors: Krigolson Olav E. , Hassall Cameron D. , Handy Todd C. 
Published: October 2013

Abstract
Our ability to make decisions is predicated upon our knowledge of the outcomes of the actions available to us. Reinforcement learning theory posits that actions followed by a reward or punishment acquire value through the computation of prediction errors—discrepancies between the predicted and the actual reward. A multitude of neuroimaging studies have demonstrated that rewards and punishments evoke neural responses that appear to reflect reinforcement learning prediction errors [e.g., Krigolson, O. E., Pierce, L. J., Holroyd, C. B., & Tanaka, J. W. Learning to become an expert: Reinforcement learning and the acquisition of perceptual expertise. Journal of Cognitive Neuroscience, 21, 1833–1840, 2009; Bayer, H. M., & Glimcher, P. W. Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron, 47, 129–141, 2005; O'Doherty, J. P. Reward representations and reward-related learning in the human brain: Insights from neuroimaging. Current Opinion in Neurobiology, 14, 769–776, 2004; Holroyd, C. B., & Coles, M. G. H. The neural basis of human error processing: Reinforcement learning, dopamine, and the error-related negativity. Psychological Review, 109, 679–709, 2002]. Here, we used the brain ERP technique to demonstrate that not only do rewards elicit a neural response akin to a prediction error but also that this signal rapidly diminished and propagated to the time of choice presentation with learning. Specifically, in a simple, learnable gambling task, we show that novel rewards elicited a feedback error-related negativity that rapidly decreased in amplitude with learning. Furthermore, we demonstrate the existence of a reward positivity at choice presentation, a previously unreported ERP component that has a similar timing and topography as the feedback error-related negativity that increased in amplitude with learning. The pattern of results we observed mirrored the output of a computational model that we implemented to compute reward prediction errors and the changes in amplitude of these prediction errors at the time of choice presentation and reward delivery. Our results provide further support that the computations that underlie human learning and decision-making follow reinforcement learning principles.
Multiple Aspects of Neural Activity during Reaching Preparation in the Medial Posterior Parietal Area V6A
Authors: Breveglieri Rossella , Galletti Claudio , Dal Bò Giulia , Hadjidimitrakis Kostas , Fattori Patrizia 
Published: October 2013

Abstract
The posterior parietal cortex is involved in the visuomotor transformations occurring during arm-reaching movements. The medial posterior parietal area V6A has been shown to be implicated in reaching execution, but its role in reaching preparation has not been sufficiently investigated. Here, we addressed this issue exploring the neural correlates of reaching preparation in V6A. Neural activity of single cells during the instructed delay period of a foveated Reaching task was compared with the activity in the same delay period during a Detection task. In this latter task, animals fixated the target but, instead of performing an arm reaching movement, they responded with a button release to the go signal. Targets were allocated in different positions in 3-D space. We found three types of neurons: cells where delay activity was equally spatially tuned in the two tasks (Gaze cells), cells spatially tuned only during reaching preparation (Set cells), and cells influenced by both gaze and reaching preparation signals (Gaze/Set cells). In cells influenced by reaching preparation, the delay activity in the Reaching task could be higher or lower compared with the Detection task. All the Set cells and a minority of Gaze/Set cells were more active during reaching preparation. Most cells modulated by movement preparation were also modulated with a congruent spatial tuning during movement execution. Present results highlight the convergence of visuospatial information, reach planning and reach execution signals on V6A, and indicate that visuospatial processing and movement execution have a larger influence on V6A activity than the encoding of reach plans.
Evaluation of Global Monsoon Precipitation Changes based on Five Reanalysis Datasets
Authors: Lin Renping , Zhou Tianjun , Qian Yun 
Published: October 2013

Abstract
With the motivation to identify whether a reasonably simulated atmospheric circulation would necessarily lead to a successful reproduction of monsoon precipitation, the performances of five sets of reanalysis data [NCEP–U.S. Department of Energy (DOE) Atmospheric Model Intercomparison Project II (AMIP-II) reanalysis (NCEP-2), 40-yr ECMWF Re-Analysis (ERA-40), Japanese 25-yr Reanalysis Project (JRA-25), Interim ECMWF Re-Analysis (ERA-Interim), and Modern-Era Retrospective Analysis for Research and Applications (MERRA)] in reproducing the climatology, interannual variation, and long-term trend of global monsoon (GM) precipitation are comprehensively evaluated. To better understand the variability and long-term trend of GM precipitation, the authors also examined the major components of water budget, including evaporation, water vapor convergence, and the change in local column water vapor, based on the five reanalysis datasets. Results show that all five reanalysis datasets reasonably reproduce the climatology of GM precipitation. ERA-Interim (NCEP-2) shows the highest (lowest) skill among the five datasets. The observed GM precipitation shows an increasing tendency during 1979–2011 along with a strong interannual variability, which is reasonably reproduced by five reanalysis datasets. The observed increasing trend of GM precipitation is dominated by contributions from the Asian, North American, Southern African, and Australian monsoons. All five datasets fail in reproducing the increasing tendency of the North African monsoon precipitation. The wind convergence term in the water budget equation dominates the GM precipitation variation, indicating a consistency between the GM precipitation and the seasonal change of prevailing wind.