bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized controlled trial studying efficacy and tolerance of a knee-ankle-foot orthosis used to prevent equinus in children with spastic cerebral palsy
Authors: Maas JC , Dallmeijer AJ , Huijing PA , Brunstrom-Hernandez JE , van Kampen PJ , Bolster EAM , Dunn C , Herndon K , Jaspers RT , Becher JG 
Published: August 2014

Objective: To examine whether using a knee-ankle-foot orthosis helps maintain ankle-foot dorsiflexion range of motion over time. Design: A multicentre randomized controlled trial. Setting: Two hospitals and one rehabilitation centre in the Netherlands and the USA. Subjects: Children (4-16 years old) with spastic cerebral palsy who were able to walk. Intervention: Use of a knee-ankle-foot orthosis, equipped with an Ultraflex® ankle power unit, for at least 6 hours every other night for one year. Main measures: Primary outcome measure: ankle-foot dorsiflexion range of motion. Secondary outcome measures: ankle-foot and knee angle in gait and gross motor function. Wearing time was also measured. Measurements were taken at baseline and at 3, 6, 9 and 12 months. Results: 28 children (experimental group: n=15, control group: n=13) participated in the study. 11 participants (experimental: n=4, control: n=7) did not complete all five measurements, as they needed additional treatment. No significant difference was found in the decrease of ankle-foot dorsiflexion range of motion between the experimental and control groups (difference: −1.05°, 95% confidence interval: −4.71° – 2.61°). In addition, secondary outcome measures did not show differences between groups. Despite good motivation, knee-ankle-foot orthosis wearing time was limited to a mean±SD of 3.2±1.9 hours per prescribed night due to discomfort. Conclusions: Knee-ankle-foot orthosis with dynamic ankle and fixed knee are poorly tolerated and are not beneficial in preventing a reduction in ankle-foot dorsiflexion range of motion in children with spastic cerebral palsy, at least with limited use.
Robot-assisted gait training is not superior to balance training for improving postural instability in patients with mild to moderate Parkinson’s disease: a single-blind randomized controlled trial
Authors: Picelli Alessandro , Melotti Camilla , Origano Francesca , Neri Roberta , Verzè Elisa , Gandolfi Marialuisa , Waldner Andreas , Smania Nicola 
Published: August 2014

Objective: The main aim was to compare robotic gait training vs. balance training for reducing postural instability in patients with Parkinson’s disease. The secondary aim was to compare their effects on the level of confidence during activities of daily living requiring balance, functional mobility and severity of disease. Design: Randomized controlled trial. Setting: University hospital. Subjects: A total of 66 patients with Parkinson’s disease at Hoehn and Yahr Stage 3. Intervention: After balanced randomization, all patients received 12, 45-minute treatment sessions, three days a week, for four consecutive weeks. A group underwent robot-assisted gait training with progressive gait speed increasing and body-weight support decreasing. The other group underwent balance training aimed at improving postural reactions (self and externally induced destabilization, coordination, locomotor dexterity exercises). Main measures: Patients were evaluated before, after and one month posttreatment. Main outcome measure: Berg Balance Scale. Secondary outcomes: Activities-Specific Balance Confidence Scale; Timed Up and Go Test; Unified Parkinson’s Disease Rating Scale. Results: No significant differences were found between the groups for the Berg Balance Scale either immediately after intervention (mean score in the robotic training group 51.58 ±3.94; mean score in the balance training group 51.15 ±3.46), or one-month follow-up (mean score in the robotic training group 51.03 ±4.63; mean score in the balance training group 50.97 ±4.28). Similar results were found for all the secondary outcome measures. Conclusions: Our findings indicate that robotic gait training is not superior to balance training for improving postural instability in patients with mild to moderate Parkinson’s disease.
Noninvasive ventilation with complex critical care ventilator in the treatment of acute exacerbation of chronic obstructive pulmonary disease
Authors: Zhang Jing , Wang Yan , Cao Jie , Chen Bao-yuan , Feng Jing 
Published: August 2014

Objective To compare the clinical effect of noninvasive positive-pressure ventilation (NIPPV), delivered via critical care ventilator or miniventilator, in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Prospective comparison study. Patients with AECOPD underwent NIPPV via: miniventilator with BiLevel positive airway pressure (BiPAP; Group A); critical care ventilator with pressure support ventilation and positive end expiratory pressure (PSV + PEEP; Group B); critical care ventilator with pressure-synchronized intermittent mandatory ventilation (P-SIMV)+PSV + PEEP (Group C). Physiological parameters were recorded before, during and after ventilation. Results Patients in Group C ( n = 21) showed significantly better improvements in physiological parameters (compared with pretreatment values) than those in Group B ( n = 20) or Group A ( n = 22). Conclusion NIPPV delivered via critical care ventilator has a better treatment effect than miniventilator NIPPV in patients with AECOPD. The use of P-SIMV + PSV + PEEP mode provides a significantly better treatment effect than PSV + PEEP alone.
In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification
Authors: Wang Yu , Wu De-Pei , Liu Qi-Fa , Qin Ya-Zhen , Wang Jing-Bo , Xu Lan-Ping , Liu Yan-Rong , Zhu Hong-Hu , Chen Jia , Dai Min , Huang Xiao-Jun 
Published: August 2014

Key Points
RUNX1/RUNX1T1-based MRD status at 1, 2, and 3 months after HSCT could discriminate patients at high risk of post-HSCT relapse. Rather than c-KIT mutations, MRD monitoring allows further rapid identification of patients at high risk of relapse after allo-HSCT.
Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease
Authors: Kontsekova Eva , Zilka Norbert , Kovacech Branislav , Skrabana Rostislav , Novak Michal 
Published: August 2014

Abstract
Introduction
Pathologically modified tau protein is the main feature of Alzheimer’s disease (AD) and related tauopathies. Therefore, immunotherapies that target mis-disordered tau represent a promising avenue for the disease-modifying treatment of AD. In this report, we present our discovery of (1) a novel target for tau immunotherapy; (2) monoclonal antibody DC8E8, which neutralizes this target; and (3) the results of efficacy studies of DC8E8 in a murine model of tauopathy.

Methods
In vitro tau oligomerisation assays were used for the selection of antibodies. The therapeutic efficacy of DC8E8 was evaluated in transgenic mice. The structure of the DC8E8 epitope was determined by X-ray crystallography.

Results
Screening of a panel of monoclonal antibodies for their inhibitory activity in an in vitro pathological tau–tau interaction assay yielded DC8E8, which reduced the amount of oligomeric tau by 84%. DC8E8 recognised all developmental stages of tau pathology in AD human brains, including pretangles and intra- and extracellular tangles. Treatment with DC8E8 in a mouse AD model expressing mis-disordered human tau significantly reduced the amount of insoluble oligomerised tau and the number of early and mature neurofibrillary tangles in the transgenic mouse brains. By using a panel of tau-derived peptides in a competitive enzyme-linked immunosorbent assay, we identified the tau domain essential for pathological tau–tau interaction, which is targeted by DC8E8. The antibody was capable of binding to four highly homologous and yet independent binding regions on tau, each of which is a separate epitope. The X-ray structure of the DC8E8 Fab apo form, solved at 3.0 Å, suggested that the four DC8E8 epitopes form protruding structures on the tau molecule. Finally, by kinetic measurements with surface plasmon resonance, we determined that antibody DC8E8 is highly discriminatory between pathological and physiological tau.

Conclusions
We have discovered defined determinants on mis-disordered truncated tau protein which are responsible for tau oligomerisation leading to neurofibrillary degeneration. Antibody DC8E8 reactive with these determinants is able to inhibit tau–tau interaction in vitro and in vivo. DC8E8 is able to discriminate between the healthy and diseased tau proteome, making its epitopes suitable targets, and DC8E8 a suitable candidate molecule, for AD immunotherapy.
First-in-man tau vaccine targeting structural determinants essential for pathological tau–tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer’s disease model
Authors: Kontsekova Eva , Zilka Norbert , Kovacech Branislav , Novak Petr , Novak Michal 
Published: August 2014

Abstract
Introduction
We have identified structural determinants on tau protein that are essential for pathological tau–tau interaction in Alzheimer’s disease (AD). These regulatory domains, revealed by monoclonal antibody DC8E8, represent a novel target for tau-directed therapy. In order to validate this target, we have developed an active vaccine, AADvac1.

Methods
A tau peptide encompassing the epitope revealed by DC8E8 was selected for the development of an active vaccine targeting structural determinants on mis-disordered tau protein that are essential for pathological tau–tau interaction. The efficacy of the vaccine was tested in a transgenic rat model of human tauopathies. Toxicology and safety pharmacology studies were conducted under good laboratory practice conditions in multiple rodent and nonrodent species.

Results
We have administered the tau peptide vaccine to a rat model of AD to investigate whether the vaccine can improve its clinical, histopathological and biochemical AD phenotype. Our results show that vaccination induced a robust protective humoral immune response, with antibodies discriminating between pathological and physiological tau. Active immunotherapy reduced the levels of tau oligomers and the extent of neurofibrillary pathology in the brains of transgenic rats. Strikingly, immunotherapy has reduced AD-type hyperphosphorylation of tau by approximately 95%. Also, the tau peptide vaccine improved the clinical phenotype of transgenic animals. Toxicology and safety pharmacology studies showed an excellent safety and tolerability profile of the AADvac1 vaccine.

Conclusions
Active immunisation targeting crucial domains of Alzheimer tau eliminated tau aggregation and neurofibrillary pathology. Most importantly, the AD type of tau hyperphosphorylation was abolished by vaccination across a wide range of AD phospho-epitopes. Our results demonstrate that active immunisation led to elimination of all major hallmarks of neurofibrillary pathology, which was reflected by a profound improvement in the clinical presentation of transgenic rats. This makes the investigated tau peptide vaccine a highly promising candidate therapeutic for the disease-modifying treatment of AD. The tested vaccine displayed a highly favourable safety profile in preclinical toxicity studies, which opens up the possibility of using it for AD prophylaxis in the future. The vaccine has already entered phase I clinical trial under the name AADvac1.

Trial registration
Current Controlled Trials NCT01850238. Registered 7 May 2013.
Myogenic differentiation and reparative activity of stromal cells derived from pericardial adipose in comparison to subcutaneous origin
Authors: Wang Xiaoming , Zhang Hui , Nie Liangming , Xu Linhai , Chen Min , Ding Zhaoping 
Published: August 2014

Abstract
Introduction
Adipose tissue-derived stromal cells (ADSCs) are abundant and easy to obtain, but the diversity of differentiation potential from different locations may vary with the developmental origin of their mesenchymal compartment. We therefore aim to compare the myogenic differentiation and reparative activity of ADSCs derived from the pericardial tissue to ADSCs of subcutaneous origin.

Methods
Pericardial and inguinal adipose tissues from Wistar rats were surgically obtained, and the stromal fraction was isolated after enzymatic digestion. The phenotypic epitopes of the resultant two types of ADSCs were analyzed with flow cytometry, and the expression of transcriptional factors was analyzed with immunostaining. Furthermore, their potential toward adipogenic, osteogenic, and myogenic differentiation also was compared. Finally, the reparative activity and the resultant functional benefits were examined by allograft transplantation into an infarcted model in rats.

Results
ADSCs from two adipose sources showed identical morphology and growth curve at the initial stage, but inguinal ADSCs (ingADSCs) sustained significantly vigorous growth after 25 days of cultivation. Although both ADSCs shared similar immunophenotypes, the pericardial ADSCs (periADSC) intrinsically exhibited partial expression of transcription factors for cardiogenesis (such as GATA-4, Isl-1, Nkx 2.5, and MEF-2c) and more-efficient myogenic differentiation, but less competent for adipogenic and osteogenic differentiation. After in vivo transplantation, periADSCs exhibited significantly vigorous reparative activity evidenced by thickening of ventricular wall and pronounced vasculogenesis and myogenesis, although the majority of prelabeled cells disappeared 28 days after transplantation. The structural repair also translated into functional benefits of hearts after infarction.

Conclusions
Although two sources of ADSCs are phenotypically identical, pericADSCs constituted intrinsic properties toward myogenesis and vasculogenesis, and thus provided more potent reparative effects after transplantation; therefore, they represent an attractive candidate cell donor for cardiac therapy.
Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis
Authors: Penttilä Matti , Jääskeläinen Erika , Hirvonen Noora , Isohanni Matti , Miettunen Jouko 
Published: August 2014

BackgroundDuration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcomes of schizophrenia. Long DUP as a predictor of poor short-term outcome has been addressed in previous meta-analyses, but the long-term effects of DUP remain unclear.AimsTo analyse the associations between DUP and long-term outcomes of schizophrenia.MethodA systematic literature search was performed using seven electronic databases and manual searches. Random effects weighted meta-analysis with correlation coefficients was used to pool the results.ResultsWe identified 3493 unique publications, from which 33 samples met our predefined selection criteria. Long DUP correlated statistically significantly with poor general symptomatic outcome, more severe positive and negative symptoms, lesser likelihood of remission and poor social functioning and global outcome (correlations 0.13–0.18). Long DUP was not associated with employment, quality of life or hospital treatment.ConclusionsThe small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness.
School-based interventions targeting stigma of mental illness: systematic review
Authors: Mellor Catriona 
Published: August 2014

Aims and methodTo systematically review the published literature on the effectiveness of classroom-based interventions to tackle the stigma of mental illness in young people, and to identify any consistent elements within successful programmes.ResultsSeventeen studies were included in the analysis. A minority of studies reported a positive impact on stigma or knowledge outcomes at follow-up and there were considerable methodological shortcomings in the studies reviewed. These interventions varied substanitally in content and delivery. It was not possible to use this data to draw out what aspects make a successful intervention. There is currently no strong evidence to support previous conclusions that these types of intervention work for children and adolescents.Clinical implicationsWhen anti-stigma interventions for young people are rolled out in the future, it is important that the programme design and method of delivery have evidence to prove their effectiveness, and that the audience and setting are the most appropriate to target. There is a current lack of strong evidence to inform this.
Pre-operative function, motivation and duration of symptoms predict sporting participation after total hip replacement
Authors: Ollivier M. , Frey S. , Parratte S. , Flecher X. , Argenson J. N. 
Published: August 2014

There is little in the literature on the level of participation in sports which patients undertake after total hip replacement (THR). Our aims in this study were to determine first, the level of sporting activity, second, the predictive factors for returning to sporting activity, and third, the correlation between participation in sports and satisfaction after THR. We retrospectively identified 815 patients who had undergone THR between 1995 and 2005. All were asked to complete a self-administered questionnaire regarding their sporting activity. A total of 571 patients (71%) met the inclusion criteria and completed the evaluation. At a mean follow-up of 9.8 years (sd 2.9), 366 patients (64%) returned to sporting activity as defined by a University of California at Los Angeles (UCLA) score of > 5. The main reasons that patients had for refraining from sports were fear of dislocation (65; 31.6%), avoiding wear (52; 25.4%), and the recommendation of the surgeon (34; 16.6%). There was a significant relationship between higher post-operative participation in sport in those patients with a higher pre-operative Harris hip score (HHS) (p = 0.0074), motivation to participate in sporting activities (p = 0.00022) and a shorter duration of symptoms (p = 0.0034). Finally, there was a correlation between age (p = 0.00013), UCLA score (p = 0.012) and pre-operative HHS (p = 0.00091) and satisfaction. In conclusion, we found that most patients participate in sporting activity after THR, regardless of the advice of their surgeon, and that there is a correlation between the level of participation and pre-operative function, motivation, duration of symptoms and post-operative satisfaction. Cite this article: Bone Joint J 2014;96-B:1041–6
Implementation of Polymerase Chain Reaction to Rule Out Clostridium difficile Infection is Associated with Reduced Empiric Antibiotic Duration of Therapy
Authors: Peppard William J. , Ledeboer Nathan A. 
Published: August 2014

Purpose The polymerase chain reaction (PCR) test has higher sensitivity and a faster turnaround time than the enzyme immunoassay (EIA) for identification of Clostridium difficile, although the clinical implications of these variables are not well described. Methods Inpatients with a negative EIA ( n = 79) or PCR ( n = 87) test were retrospectively evaluated. Patients were excluded if they had a positive EIA or PCR test during the same hospitalization or if they were currently receiving treatment for C. difficile infection (CDI) prior to admission. The primary outcome was empiric CDI antibiotic duration of therapy associated with each test method. Results Empiric CDI antibiotic duration of therapy was 2.31 (95% confidence interval [CI], 1.48–3.15) days for the EIA group and 0.88 (0.45–1.33) days for the PCR group ( P = .007). Number of diagnostic laboratory tests performed per patient were 2.73 (2.64–2.83) and 1.16 (1.04–1.28) tests, respectively ( P < .001). Conclusion Use of the PCR test to rule out CDI was associated with reduced duration of empiric CDI antibiotic therapy and fewer diagnostic laboratory tests performed per patient. When combined with fewer diagnostic laboratory tests performed per patient and shorter duration of contact isolation, the higher acquisition cost of the PCR test was offset, resulting in cost neutrality. These findings provide additional data to support the routine use of the PCR test.
Optimal Application Conditions of Solvent Injection Into Oil Sands To Minimize the Effect of Asphaltene Deposition: An Experimental Investigation
Authors: Moreno-Arciniegas L.. , Babadagli T.. 
Published: August 2014

Summary
Solvent injection into heavy-oil reservoirs is quite complex because of the asphaltene destabilization that occurs because of the changes in temperature, pressure, and solvent type dissolved in oil. As a result of this destabilization, the asphaltene flocculates, agglomerates, and eventually plugs the pores in the reservoir because of the formation of asphaltene clusters. In solvent applications, light-molecular-weight hydrocarbon solvents are preferred because of their high diffusion coefficient; however, as the carbon number of n-alkane solvents decreases, asphaltene precipitation increases. Therefore, the selection of the solvent and application condition is highly critical in cold and thermally aided solvent applications.
In this research, low-carbon-number n-alkane (propane, n-hexane, and n-decane) and a distillate-hydrocarbon (obtained from a heavy-oil-upgrading facility) injection into glass-bead-pack systems saturated with heavy oil (87,651 and 20,918 cp at 25°C) were evaluated at different pressure conditions that are applicable to typical Canadian oil-sand reservoirs (698–2068 kPa) and temperatures (25–120°C). First, the asphaltene behavior of different solvents at different pressures and temperatures was studied through deasphalting work in a pressure/volume/temperature (PVT) cell in previous work [Moreno and Babadagli (2013)]. By use of quantitative (amount of asphaltene precipitated) and qualitative (microscopic images of asphaltene clusters) observations, asphaltenes were classified in terms of their shape, size, and quantity for different oil/solvent types, pressure, and temperature.
Continually, the same n-alkane, distillate-hydrocarbon solvents, and heavy oil were used in gravity-stable-displacement glass-bead-pack experiments. 3-D (cylindrical) glass-bead-pack experiments were carried out at the same temperature and pressure conditions used for the PVT experiments. The operational conditions, oil composition, and solvent type showed significant effects on oil-recovery factor. Asphaltene deposition and residual oil saturation (ROS) in the glass-bead pack and the amount of asphaltene in the produced oil were measured, and the standard saturate, aromatic, resin, and asphaltene (SARA) analysis was applied to determine the optimal operating conditions yielding the highest recoveries with minimal pore plugging. Moreover, the pore-plugging process was analyzed through a visual scanning electron microscope (SEM) and optical microscope to find the different organic deposition formation and agglomeration. Oil production was evaluated by use of microscope visualization, viscosity reduction, and refractive-index values. Eventually, optimal application conditions for solvent and thermally aided solvent injection were listed for a wide range of heavy-oil and solvent types.