bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Mucosal Inflammation on Oral Simian Immunodeficiency Virus Transmission
Authors: Giavedoni Luis D. , Chen Hui-Ling , Hodara Vida L. , Chu Lianrui , Parodi Laura M. , Smith Lisa M. , Sexton Valerie , Cappelli David , Sodora Donald L. 
Published: November 2012

ABSTRACT
Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus (HIV). There is epidemiological evidence that genital mucosal inflammation leads to enhanced HIV type 1 (HIV-1) transmission. The objective of this study was to assess the influence of periodontal inflammation on oral HIV transmission using a nonhuman primate model of teeth ligature-induced periodontitis. Simian immunodeficiency virus (SIV) was nontraumatically applied to the gingiva after moderate gingivitis was identified through clinical and immunologic analyses (presence of inflammatory cytokines). Overall oral SIV infection rates were similar in the gingivitis-induced and control groups (5 infections following 12 SIV administrations for each), although more macaques were infected with multiple viral variants in the gingivitis group. SIV infection also affected the levels of antiviral and inflammatory cytokines in the gingival crevicular fluid, and a synergistic effect was observed, with alpha interferon and interferon-inducible protein 10 undergoing significant elevations following SIV infection in macaques with gingivitis compared to controls. These increases in antiviral and inflammatory immune modulators in the SIV-infected gingivitis macaques could also be observed in blood plasma, although the effects at both compartments were generally restricted to the acute phase of the infection. In conclusion, while moderate gingivitis was not associated with increased susceptibility to oral SIV infection, it resulted in elevated levels of cytokines in the oral mucosa and plasma of the SIV-infected macaques. These findings suggest a synergy between mucosal inflammation and SIV infection, creating an immune milieu that impacts the early stages of the SIV infection with potential implications for long-term pathogenesis.
The Cellular Autophagy Pathway Modulates Human T-Cell Leukemia Virus Type 1 Replication
Authors: Tang Sai-Wen , Chen Chia-Yen , Klase Zachary , Zane Linda , Jeang Kuan-Teh 
Published: November 2012

ABSTRACT
Autophagy, a general homeostatic process for degradation of cytosolic proteins or organelles, has been reported to modulate the replication of many viruses. The role of autophagy in human T-cell leukemia virus type 1 (HTLV-1) replication has, however, been uncharacterized. Here, we report that HTLV-1 infection increases the accumulation of autophagosomes and that this accumulation increases HTLV-1 production. We found that the HTLV-1 Tax protein increases cellular autophagosome accumulation by acting to block the fusion of autophagosomes to lysosomes, preventing the degradation of the former by the latter. Interestingly, the inhibition of cellular autophagosome-lysosome fusion using bafilomycin A increased the stability of the Tax protein, suggesting that cellular degradation of Tax occurs in part through autophagy. Our current findings indicate that by interrupting the cell's autophagic process, Tax exerts a positive feedback on its own stability.
A Sendai Virus-Derived RNA Agonist of RIG-I as a Virus Vaccine Adjuvant
Authors: Martínez-Gil L. , Goff P. H. , Hai R. , García-Sastre A. , Shaw M. L. , Palese P. 
Published: November 2012

ABSTRACTThe innate immune system is responsible for recognizing invading pathogens and initiating a protective response. In particular, the retinoic acid-inducible gene 1 protein (RIG-I) participates in the recognition of single- and double-stranded RNA viruses. RIG-I activation leads to the production of an appropriate cytokine and chemokine cocktail that stimulates an antiviral state and drives the adaptive immune system toward an efficient and specific response against the ongoing infection. One of the best-characterized natural RIG-I agonists is the defective interfering (DI) RNA produced by Sendai virus strain Cantell. This 546-nucleotide RNA is a well-known activator of the innate immune system and an extremely potent inducer of type I interferon. We designed anin vitro-transcribed RNA that retains the type I interferon stimulatory properties, and the RIG-I affinity of the Sendai virus produced DI RNA bothin vitroandin vivo. Thisin vitro-synthesized RNA is capable of enhancing the production of anti-influenza virus hemagglutinin (HA)-specific IgG after intramuscular or intranasal coadministration with inactivated H1N1 2009 pandemic vaccine. Furthermore, our adjuvant is equally effective at increasing the efficiency of an influenza A/Puerto Rico/8/34 virus inactivated vaccine as a poly(I·C)- or a squalene-based adjuvant. Ourin vitro-transcribed DI RNA represents an excellent tool for the study of RIG-I agonists as vaccine adjuvants and a starting point in the development of such a vaccine.
Subcellular Localization and Function of an Epitope-Tagged p7 Viroporin in Hepatitis C Virus-Producing Cells
Authors: Vieyres Gabrielle , Brohm Christiane , Friesland Martina , Gentzsch Juliane , Wölk Benno , Roingeard Philippe , Steinmann Eike , Pietschmann Thomas 
Published: November 2012

ABSTRACT
The hepatitis C virus (HCV) viroporin p7 is crucial for production of infectious viral progeny. However, its role in the viral replication cycle remains incompletely understood, in part due to the poor availability of p7-specific antibodies. To circumvent this obstacle, we inserted two consecutive hemagglutinin (HA) epitope tags at its N terminus. HA-tagged p7 reduced peak virus titers ca. 10-fold and decreased kinetics of virus production compared to the wild-type virus. However, HA-tagged p7 rescued virus production of a mutant virus lacking p7, thus providing formal proof that the tag does not disrupt p7 function. In HCV-producing cells, p7 displayed a reticular staining pattern which colocalized with the HCV envelope glycoprotein 2 (E2) but also partially with viral nonstructural proteins 2, 3, and 5A. Using coimmunoprecipitation, we confirmed a specific interaction between p7 and NS2, whereas we did not detect a stable interaction with core, E2, or NS5A. Moreover, we did not observe p7 incorporation into affinity-purified virus particles. Consistently, there was no evidence supporting a role of p7 in viral entry, as an anti-HA antibody was not able to neutralize Jc1 virus produced from an HA-p7-tagged genome. Collectively, these findings highlight a stable interaction between p7 and NS2 which is likely crucial for production of infectious HCV particles. Use of this functional epitope-tagged p7 variant should facilitate the analysis of the final steps of the HCV replication cycle.
A randomised controlled trial of hospital-based case management to improve colorectal cancer patients’ health-related quality of life and evaluations of care
Authors: Wulff Christian Nielsen , Vedsted Peter , Søndergaard Jens 
Published: November 2012

ObjectiveTo analyse the effectiveness of hospital-based case management (CM) in terms of patient-reported outcomes.DesignRandomised controlled trial allocating participants 1 : 1 to either a CM intervention or a control group. Allocation status was evident to participants and case managers, but blinded to researchers.SettingPatients were recruited at a Danish surgical department where the case managers were situated.ParticipantsColorectal cancer patients who were to undergo further investigation or treatment. Exclusion criteria were participation in another study, poor Danish language skills or apparent cognitive impairment. 140 participants were randomised to each group. Recruitment period was 11 March 2009 to 29 December 2010.InterventionsControl group patients had usual care. Intervention group patients had usual care supplemented by hospital-based CM started at first visit to the out-patient clinic (before treatment start) and ended 4 weeks after completed cancer treatment. CM was conducted by nurse case managers who undertook care pathway supervision, information dissemination to health professionals and outreaching patient support.Outcome measuresPatient-reported global quality of life measured with the EORTC QLQ-C30 and eight ad hoc, piloted patient evaluation items assessed at eight, 30 and 52 weeks after randomisation.ResultsThe two groups were comparable as to questionnaire response rates and completed scales/items. There were no statistically significant group differences on any of the health-related quality of life subscales at eight, 30 or 52 weeks. In patient evaluations, all point estimates favoured CM at week 8 and 30; at week 52, 6 of 7 estimates favoured CM.ConclusionsWe found no evidence that CM influenced colorectal cancer patients’ health-related quality of life. Patients allocated to CM evaluated their care more positively than patients receiving usual care.Trial registrationClinicaltrials.gov identifier:NCT00845247.
Timing of gastrostomy insertion in children with a neurodisability: a cross-sectional study of early versus late intervention
Authors: Sharma Raman , Williams Andrew N , Zaw Win 
Published: November 2012

ObjectivesThe aim of the study was to assess whether gastrostomy placement before 18 months of age results in a greater increase in z-score for weight and to assess whether admission rates were reduced postgastrostomy in this age group.DesignRetrospective cross-sectional study.SettingSingle-centre secondary care District General Hospital.ParticipantsAll children with a neurodisability with a gastrostomy in situ in September 2011 were included. Those with primary neoplasia and undergoing chemo or radiotherapy or being palliated for an aggressive neurodegenerative disorder were excluded. Those with cystic fibrosis, primary congenital heart disease or Inflammatory bowel disease were also excluded. Forty-one children underwent final analysis. Twenty-four children underwent gastrostomy insertion less than 18 months and 17 children were older than 18 months.Primary and secondary outcome measuresPrimary outcome was z-scores for weight immediately pregastrostomy and 12 months postgastrostomy. Secondary outcomes were hospital admission rates pregastrostomy and postgastrostomy. Values were compared for those with gastrostomy insertion less than or equal to 18 months against those older than 18 months at insertion.ResultsZ-score for weight increased significantly in both age groups. There was significantly increased mean difference in the z-score for weight of +1.33 pregastrostomy and postgastrostomy in the less than 18 months age group as compared with an increased mean difference in the z-score for weight of +0.45 in the older age group (p=0.021). There was no significant difference in the admission rates postgastrostomy insertion in either age group.ConclusionsGastrostomy insertion before 18 months of age results in greater z-score for weight gain in children with a neurodisability. This conclusion is limited by the lack of height and skin-fold thickness measurements. Further long-term matched control studies are required to determine the neurodevelopmental and clinical benefit of early gastrostomy placement in such children.
Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens
Authors: Hacohen Yael , Wright Sukhvir , Waters Patrick , Agrawal Shakti , Carr Lucinda , Cross Helen , De Sousa Carlos , DeVile Catherine , Fallon Penny , Gupta Rajat , Hedderly Tammy , Hughes Elaine , Kerr Tim , Lascelles Karine , Lin Jean-Pierre , Philip Sunny , Pohl Keith , Prabahkar Prab , Smith Martin , Williams Ruth , Clarke Antonia , Hemingway Cheryl , Wassmer Evangeline , Vincent Angela , Lim Ming J 
Published: November 2012

ObjectiveTo report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens.MethodPatients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase.ResultsSeizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect.ConclusionsOur study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future.
Effects of high-intensity exercise training on body composition, abdominal fat loss, and cardiorespiratory fitness in middle-aged Korean females
Authors: Lee Man-Gyoon , Park Kyung-Shin , Kim Do-Ung , Choi Soon-Mi , Kim Hyoung-Jun 
Published: November 2012

The primary purpose of this study was to investigate the effects of high-intensity exercise training under relatively equal energy expenditure on whole body fat and abdominal fat loss, and cardiorespiratory fitness. Twenty-two untrained middle-aged Korean females were randomized into one of the following groups: control, low-intensity training group (LI), and high-intensity training group (HI). Subjects completed 14 weeks of training at 50% maximal oxygen consumption (LI) or 70% maximal oxygen consumption (HI) with the volume of exercise equated relative to kilograms of body weight. Weekly exercise volumes were 13.5 METs⋅h/week for the first 4 weeks, 18 METs⋅h/week for next 5 weeks, and 22.5 METs⋅h/week for the final 5 weeks. Data were analyzed using 2-way repeated measures ANOVA with post hoc test, using Bonferroni’s correction. HI showed significant reductions in fat mass (p < 0.05), total abdominal fat (p < 0.01), and subcutaneous abdominal fat (p < 0.01). LI reduced total abdominal fat (p < 0.05), but there were no other significant changes found in the control or LI groups. Maximal oxygen consumption was enhanced in both HI and LI with no significant group difference. High-density lipoprotein cholesterol increased significantly in HI (p < 0.05). IL-6, C-reactive protein, TNF-α, and other blood lipids were unaltered following training. Results indicate that high-intensity exercise training is more beneficial in whole body and abdominal fat loss; however, cardiorespiratory enhancement shows a dose–response relationship with weekly exercise volume. It is suggested that 14 weeks of aerobic exercise training at either high- or low-intensity is not sufficient enough to induce changes in levels of inflammatory proteins.
Changes in traditional chronic disease risk factors over time and their relationship with leisure-time physical activity in people living with spinal cord injury
Authors: Buchholz Andrea C. , Horrocks Julie , Martin Ginis Kathleen A. , Bray Steven R. , Craven B. Catharine , Hicks Audrey L. , Hayes Keith C. , Latimer Amy E. , McColl Mary Ann , Potter Patrick J. , Smith Karen , Wolfe Dalton L. 
Published: November 2012

This study examined whether levels of chronic disease risk factors change over time, and whether leisure-time physical activity (LTPA) can explain any of the variation in those risk factors that change, in a sample of community-dwelling people living with spinal cord injury (SCI) in or near Hamilton, Ontario, Canada. LTPA was measured using the Physical Activity Recall Assessment for People with SCI at baseline (n = 76 adults with chronic (≥1 year) paraplegia or tetraplegia), at 6 months (n = 71) and at 18 months (n = 63). Body mass index, waist circumference at the lowest rib (WClowest rib) and iliac crest (WCiliac crest), fat mass, blood pressure, and biochemical data were collected at all 3 time points. Women’s BMI was higher at baseline (least square means (LSM) = 26.2 ± SE = 1.56 kg·m–2, p = 0.0004) and 6 months (25.9 ± 1.6, p = 0.0024) than at 18 months (22.1 ± 1.72). Men’s WClowest ribincreased from baseline (92.1 ± 1.87 cm) to 18 months (93.6 ± 1.87, p = 0.0253). Women who were active vs. inactive at baseline had a lower BMI at 6 months (23.1 ± 2.91 vs. 29.7 ± 2.52, p = 0.0957) and WCiliac crestat 6 months (82.8 ± 6.59 vs. 97.7 ± 5.10, p = 0.0818). Women who were active vs. inactive at 6 months had a lower WCiliac crestat 18 months (73.4 ± 14.3 vs. 102.5 ± 6.41, p = 0.0723). There was little change in traditional risk factors over 18 months. Future studies should extend beyond 18 months in a larger sample, and explore traditional vs. novel risk factors and onset of cardiovascular disease and diabetes in the SCI population.
Time to exhaustion at intermittent maximal lactate steady state is longer than continuous cycling exercise
Authors: Grossl Talita , de Lucas Ricardo Dantas , de Souza Kristopher Mendes , Guglielmo Luiz Guilherme Antonacci 
Published: November 2012

The maximal lactate steady state (MLSS) represents a submaximal intensity that may be important in prescribing both continuous and interval endurance training. This study compared time to exhaustion (TTE) at MLSS in continuous and intermittent (i.e., with pauses) exercise, investigating whether physiological variables differ between these exercise modes. Fourteen trained male cyclists volunteered for this investigation and performed an incremental test, several 30-min tests to determine two MLSS intensities (continuous and discontinuous protocol), and two randomized tests until exhaustion at MLSS intensities on a cycle ergometer. The intermittent or discontinuous protocol was performed using 5 min of cycling, with an interval of 1 min of passive rest. TTE at intermittent MLSS was 24% longer than TTE at continuous exercise (67.8 ± 14.3 min vs. 54.7 ± 10.9 min; p < 0.05; effect sizes = 1.04), even though the absolute power output of intermittent MLSS was higher than continuous (268 ± 29 W vs. 251 ± 29 W; p < 0.05). Additionally, the total mechanical work done was significantly lower at continuous exercise than at intermittent exercise. Likewise, regarding cardiorespiratory and metabolic variables, we observed greater responses during intermittent exercise than during continuous exercise at MLSS. Thus, for endurance training prescription, this is an important finding to apply in extensive interval sessions at MLSS. This result suggests that interval sessions at discontinuous MLSS should be used instead of continuous MLSS, as discontinuous MLSS allows for a larger amount of total work during the exhaustion trial.
Intermittent lower-limb occlusion enhances recovery after strenuous exercise
Authors: Beaven Christopher Martyn , Cook Christian John , Kilduff Liam , Drawer Scott , Gill Nicholas 
Published: November 2012

Repeated cycles of vascular occlusion followed by reperfusion initiate a protective mechanism that acts to mitigate future cell injury. Such ischemic episodes are known to improve vasodilation, oxygen utilization, muscle function, and have been demonstrated to enhance exercise performance. Thus, the use of occlusion cuffs represents a novel intervention that may improve subsequent exercise performance. Fourteen participants performed an exercise protocol that involved lower-body strength and power tests followed by repeated sprints. Occlusion cuffs were then applied unilaterally (2 × 3-min per leg) with a pressure of either 220 (intervention) or 15 mm Hg (control). Participants immediately repeated the exercise protocol, and then again 24 h later. The intervention elicited delayed beneficial effects (24 h post-intervention) in the countermovement jump test with concentric (effect size (ES) = 0.36) and eccentric (ES = 0.26) velocity recovering more rapidly compared with the control. There were also small beneficial effects on 10- and 40-m sprint times. In the squat jump test there were delayed beneficial effects of occlusion on eccentric power (ES = 1.38), acceleration (ES = 1.24), and an immediate positive effect on jump height (ES = 0.61). Thus, specific beneficial effects on recovery of power production and sprint performance were observed both immediately and 24 h after intermittent unilateral occlusion was applied to each leg.
Energy expenditure during the LANY Footrace 2011 – a case study
Authors: Ardigò Luca Paolo , Capelli Carlo 
Published: November 2012

We reported results obtained in estimating the energy expenditure (EE) of an active adult subject participating in LANY Footrace 2011 (5129 km, 70 consecutive days). At each stage EE was calculated from literature metabolic cost equations and GPS-measured speeds–inclines. The subject’s average speed was 7.41 ± 0.51 km·h–1. Race expenditure amounted to 87% of EE (31.3 MJ·day–1) (47.8%–37.1% of measured maximal oxygen uptake). These results provide data about EE for future stage-type ultra-endurance competitors.
Tumor Burden Modeling Versus Progression-Free Survival for Phase II Decision Making
Authors: Kaiser Lee D. 
Published: November 2012

Abstract
Randomized Phase II oncology trial endpoints for decision making include both progression-free survival (PFS) and change in tumor burden as measured by the sum of longest diameters (SLD) of the target lesions. In addition to observed SLD changes, tumor shrinkage and growth parameters can be estimated from the patient-specific SLD profile over time. The ability of these SLD analyses to identify an active drug is contrasted with that of a PFS analysis through the simulation of Phase II trials via resampling from each of 6 large, Phase II and III trials, 5 of which were positive and one negative. From each simulated Phase II trial, a P value was obtained from 4 analyses—a log-rank test on PFS, a Wilcoxon rank-sum test on the minimum observed percentage change from baseline in SLD, and 2 nonlinear, mixed-effects model analyses of the SLD profiles. All 4 analyses led to approximately uniformly distributed P values in the negative trial. The PFS analysis was the best or nearly the best analysis in the other 5 trials. In only one of the positive studies did the modeling analysis outperform the analysis of the minimum SLD. In conclusion, for the decision to start a Phase III trial based on the results of a randomized Phase II trial of an oncology drug, PFS appears to be a better endpoint than does SLD, whether analyzed through simple SLD endpoints, such as the minimum percentage change from baseline, or through the modeling of the SLD time course to estimate tumor dynamics. Clin Cancer Res; 19(2); 314–9. ©2012 AACR.
Breast Cancer Treatment with Imiquimod: Applying an Old Lotion to a New Disease
Authors: Kohrt Holbrook 
Published: November 2012

AbstractOver the prior two decades, imiquimod, a toll-like receptor 7 agonist, has been applied to nearly 50 clinical settings. Because of its immunomodulatory role, the topical cream today, for the first time, is being applied to cutaneous breast cancer in preclinical models and in a phase II clinical trial. Clin Cancer Res; 18(24); 6571–3. ©2012 AACR.