bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of triptorelin pamoate 11.25 mg administered subcutaneously for achieving medical castration levels of testosterone in patients with locally advanced or metastatic prostate cancer
Authors: Lebret Thiery , Rouanne Mathieu , Hublarov Oleg , Jinga Viorel , Petkova Lidiya , Kotsev Rumen , Sinescu Ioanel , Dutailly Pascale 
Published: March 2015

Objectives: Gonadotropin-releasing hormone agonists are widely used as androgen deprivation therapy in many men with locally advanced or metastatic prostate cancer. Gonadotropin-releasing hormone agonists are delivered by intramuscular injection every 1, 3 or 6 months, but in some patients subcutaneous injection may be more appropriate. This study assessed the efficacy and safety profile of the gonadotropin-releasing hormone agonist, triptorelin pamoate, when administered by the subcutaneous route. Methods: In this multicentre, open-label, single-arm study, androgen deprivation therapy-naïve men with locally advanced or metastatic prostate cancer received the gonadotropin-releasing hormone agonist triptorelin pamoate 11.25 mg (3-month formulation) by the subcutaneous route twice (at baseline and 13 weeks later). The co-primary efficacy endpoints were the proportion of patients with a castration level of serum testosterone (<50 ng/dl) after 4 weeks, and of these, those still castrated after 26 weeks. Results: Of the 126 treated patients, 123 [97.6%; 95% confidence interval (CI): 93.2–99.5)] were castrated 4 weeks after the first subcutaneous injection, and 115/119 patients (96.6%; 95% CI: 91.6–99.1) castrated at 4 weeks maintained castration at 26 weeks. Median prostate-specific antigen levels were reduced by 64.2 and 96.0% at 4 and 26 weeks, respectively. The probability of maintaining a testosterone level <20 ng/dl up to 26 weeks was 90.0% (95% CI: 85.0–95.0). The most frequently occurring treatment-related adverse events were typical of gonadotropin-releasing hormone agonist treatment (hot flushes, increased weight, erectile dysfunction and hyperhidrosis). Conclusions: This study demonstrates that triptorelin pamoate 11.25 mg administered by the subcutaneous route every 3 months is as efficacious and well tolerated as administration via the intramuscular route in men with locally advanced or metastatic prostate cancer.
An evaluation of paediatric hand and upper limb assessment tools within the framework of the World Health Organisation International Classification of Disability, Functioning and Health
Authors: Aslam Riffat , van Bommel Annelotte , Southwood Taunton , Hackett Janine , Jester Andrea 
Published: March 2015

Introduction Evaluation of hand function has traditionally focused on objective measurements involving strength and range of movement measurements. The World Health Organisation International Classification of Disability, Functioning and Health (ICF) framework has introduced a more patient-orientated approach to assessment, incorporating four distinct areas of body structures, body functions, environment and activity limitation. These can be evaluated with both questionnaires and functional tests. Whereas there seems to be agreement over adult hand assessment, children’s hand assessment leaves involved therapists and clinician often wondering, which test to perform. The objective of this review was to evaluate the currently available childrens' hand and upper limb assessment tools within the framework of the ICF. Method A review of 19 of the most commonly used paediatric hand and upper limb assessment tools in the context of the components of the ICF. The International Classification of Disability, Functioning and Health linking rules composed by Cieza et al. were used in order to map each of the meaningful concepts in these assessment tools to the domains of the ICF. Results The activities domain of the ICF was found to be well represented in all assessment tools. Four out of 19 assessment tools had items that mapped to the environment domain. The highest number of different concepts mapped was found in musculoskeletal questionnaires. The lowest number of concepts was found in the pegboard tests. Conclusion Tests are often combined to attempt to cover as many aspects of the ICF yet our findings show that this may not always be achieved. Clinicians and therapists must be aware that in order to get a more complete overview of a child’s hand and upper limb functioning sometimes time- and resource-consuming tests have to be combined.
Acute Effects of Online Mind–Body Skills Training on Resilience, Mindfulness, and Empathy
Authors: Kemper Kathi J. , Khirallah Michael 
Published: March 2015

Background. Some studies have begun to show benefits of brief in-person mind–body skills training. We evaluated the effects of 1-hour online elective mind–body skills training for health professionals on mindfulness, resilience, and empathy. Methods. Between May and November, 2014, we described enrollees for the most popular 1-hour modules in a new online mind–body skills training program; compared enrollees’ baseline stress and burnout to normative samples; and assessed acute changes in mindfulness, resilience, and empathy. Results. The 513 enrollees included dietitians, nurses, physicians, social workers, clinical trainees, and health researchers; about 1/4 were trainees. The most popular modules were the following: Introduction to Stress, Resilience, and the Relaxation Response (n = 261); Autogenic Training (n = 250); Guided Imagery and Hypnosis for Pain, Insomnia, and Changing Habits (n = 112); Introduction to Mindfulness (n = 112); and Mindfulness in Daily Life (n = 102). Initially, most enrollees met threshold criteria for burnout and reported moderate to high stress levels. Completing 1-hour modules was associated with significant acute improvements in stress ( P < .001), mindfulness ( P < .001), empathy ( P = .01), and resilience ( P < .01). Conclusion. Online mind–body skills training reaches diverse, stressed health professionals and is associated with acute improvements in stress, mindfulness, empathy, and resilience. Additional research is warranted to compare the long-term cost-effectiveness of different doses of online and in-person mind–body skills training for health professionals.
Neuromuscular Evaluation With Single-Leg Squat Test at 6 Months After Anterior Cruciate Ligament Reconstruction
Authors: Hall Michael P. , Paik Ronald S. , Ware Anthony J. , Mohr Karen J. , Limpisvasti Orr 
Published: March 2015

Background: Criteria for return to unrestricted activity after anterior cruciate ligament (ACL) reconstruction varies, with some using time after surgery as the sole criterion—most often at 6 months. Patients may have residual neuromuscular deficits, which may increase the risk of ACL injury. A single-leg squat test (SLST) can dynamically assess for many of these deficits prior to return to unrestricted activity. Hypothesis: A significant number of patients will continue to exhibit neuromuscular deficits with SLST at 6 months after ACL reconstruction. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients using a standardized accelerated rehabilitation protocol at their 6-month follow-up after primary ACL reconstruction were enrolled. Evaluation included bilateral SLST, single-leg hop distance, hip abduction strength, and the subjective International Knee Documentation Committee (IKDC) score. Results: Thirty-three patients were enrolled. Poor performance of the operative leg SLST was found in 15 of 33 patients (45%). Of those 15 patients, 7 (45%) had concomitant poor performance of the nonoperative leg compared with 2 of 18 patients (11%) in those who demonstrated good performance in the operative leg. The poor performers were significantly older (33.6 years) than the good performers (24.2 years) ( P = .007). Those with poor performance demonstrated decreased hip abduction strength (17.6 kg operative leg vs 20.5 kg nonoperative leg) ( P = .024), decreased single-leg hop distance (83.3 cm operative leg vs 112.3 cm nonoperative leg) ( P = .036), and lower IKDC scores (67.9 vs 82.3) ( P = .001). Conclusion: Nearly half of patients demonstrated persistent neuromuscular deficits on SLST at 6 months, which is when many patients return to unrestricted activity. Those with poor performance were of a significantly older age, decreased hip abduction strength, decreased single-leg hop distance, and lower IKDC subjective scores. Clinical Relevance: The SLST can be used to identify neuromuscular risk factors for ACL rupture. Many patients at 6 months have persistent neuromuscular deficits on SLST. Caution should be used when using time alone to determine when patients can return to unrestricted activity.
IP3 3-kinase B controls hematopoietic stem cell homeostasis and prevents lethal hematopoietic failure in mice
Authors: Siegemund Sabine , Rigaud Stephanie , Conche Claire , Broaten Blake , Schaffer Lana , Westernberg Luise , Head Steven Robert , Sauer Karsten 
Published: March 2015

Key Points
Itpkb produces the soluble messenger IP4, which limits cytokine-induced Akt/mTORC1 activation in HSC. Itpkb loss in mice activates HSC and impairs their longevity and function, resulting in lethal hematopoietic failure and anemia.
Real-world research and its importance in respiratory medicine
Authors: Price David , Brusselle Guy , Roche Nicolas , Freeman Daryl , Chisholm Alison 
Published: March 2015

Educational AimsTo improve understanding of:The relative benefits and limitations of evidence derived from different study designs and the role that real-life asthma studies can play in addressing limitations in the classical randomised controlled trial (cRCT) evidence base.The importance of guideline recommendations being modified to fit the populations studied and the model of care provided in their reference studies.Key pointsClassical randomised controlled trials (cRCTs) show results from a narrow patient group with a constrained ecology of care.Patients with “real-life” co-morbidities and lifestyle factors receiving usual care often have different responses to medication which will not be captured by cRCTs if they are excluded by strict selection criteria.Meta-analyses, used to direct guidelines, contain an inherent meta-bias based on patient selection and artificial patient care.Guideline recommendations should clarify where they related to cRCT ideals (in terms of patient populations, medical resources and care received) and could be enhanced through inclusion of evidence from studies designed to better model the populations and care approaches present in routine care.SummaryClinical practice requires a complex interplay between experience and training, research, guidelines and judgement, and must not only draw on data from traditional or classical randomised controlled trials (cRCTs), but also from pragmatically designed studies that better reflect real-life clinical practice. To minimise extraneous variables and to optimise their internal validity, cRCTs exclude patients, clinical characteristics and variations in care that could potentially confound outcomes. The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes.Evidence from real-life studies (e.g.naturalistic or pragmatic clinical trials and observational studies encompassing healthcare database studies and cohort studies) can be combined with cRCT evidence to provide a fuller picture of intervention effectiveness and realistic treatment outcomes, and can provide useful insights into alternative management approaches in more challenging asthma patients. The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence. A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.
Optimising inhaled mannitol for cystic fibrosis in an adult population
Authors: Flume Patrick A. , Aitken Moira L. , Bilton Diana , Agent Penny , Charlton Brett , Forster Emma , Fox Howard G. , Hebestreit Helge , Kolbe John , Zuckerman Jonathan B , Button Brenda M. 
Published: March 2015

AbstractThere has been remarkable progress in the treatment of cystic fibrosis (CF) patients over the past 20 years. However, limitations of standard therapies have highlighted the need for a convenient alternative treatment to effectively target the pathophysiologic basis of CF-related disease by improving mucociliary clearance of airway secretions and consequently improve lung function and reduce respiratory exacerbations. Mannitol is an osmotic agent available as a dry powder, dispensed in a convenient disposable inhaler device for the treatment of adult patients with CF. Inhalation of mannitol as a dry powder is thought to change the viscoelastic properties of airway secretions, increase the hydration of the airway surface liquid and contribute to increased mucociliary and cough clearance of retained secretions. In two large phase 3 studies [1, 2], long-term use of inhaled mannitol resulted in a significant and clinically meaningful improvement in lung function relative to control in adult CF subjects and had an acceptable safety profile. Clinical experience with inhaled mannitol confirms that it is safe and effective. A minority of patients are unable to tolerate the medication. However, through training in proper inhaler technique and setting clear expectations regarding therapeutic effects, both the tolerance and adherence necessary for long term efficacy can be positively influenced.Educational aimsTo discuss the importance of airway clearance treatments in the management of cystic fibrosis.To describe the clinical data that supports the use of mannitol in adult patients with cystic fibrosis.To highlight the role of mannitol tolerance testing in screening for hyperresponsiveness.To provide practical considerations for patient education in use of mannitol inhaler.Key pointsInhaled mannitol is a safe and effective option in adult patients with cystic fibrosis.Mannitol tolerance testing effectively screens for hyperresponsiveness prior to initiation of therapy.Physiotherapists and respiratory therapists play an integral role in the introduction and maintenance of dry powder inhalation therapy.Patient training and follow-up is important for optimising longer term adherence.
Excellent resistive switching properties of atomic layer-deposited Al2O3/HfO2/Al2O3 trilayer structures for non-volatile memory applications
Authors: Wang Lai-Guo , Qian Xu , Cao Yan-Qiang , Cao Zheng-Yi , Fang Guo-Yong , Li Ai-Dong , Wu Di 
Published: March 2015

Abstract
We have demonstrated a flexible resistive random access memory unit with trilayer structure by atomic layer deposition (ALD). The device unit is composed of Al2O3/HfO2/Al2O3-based functional stacks on TiN-coated Si substrate. The cross-sectional HRTEM image and XPS depth profile of Al2O3/HfO2/Al2O3 on TiN-coated Si confirm the existence of interfacial layers between trilayer structures of Al2O3/HfO2/Al2O3 after 600°C post-annealing. The memory units of Pt/Al2O3/HfO2/Al2O3/TiN/Si exhibit a typical bipolar, reliable, and reproducible resistive switching behavior, such as stable resistance ratio (>10) of OFF/ON states, sharp distribution of set and reset voltages, better switching endurance up to 103 cycles, and longer data retention at 85°C over 10 years. The possible switching mechanism of trilayer structure of Al2O3/HfO2/Al2O3 has been proposed. The trilayer structure device units of Al2O3/HfO2/Al2O3 on TiN-coated Si prepared by ALD may be a potential candidate for oxide-based resistive random access memory.
Characterization of the major histocompatibility complex locus association with Behçet’s disease in Iran
Authors: Xavier Joana M , Davatchi Fereydoun , Abade Olga , Shahram Farhad , Francisco Vânia , Abdollahi Bahar Sadeghi , Trindade Hélder , Nadji Abdolhadi , Shafiee Niloofar Mojarad , Ghaderibarmi Fahmida , Ligeiro Dário , Oliveira Sofia A 
Published: March 2015

Abstract
Introduction
The aim of this study was to characterize the association of human leukocyte antigen (HLA) B alleles and major histocompatibility complex (MHC) single nucleotide polymorphisms (SNPs) with Behçet’s disease (BD) in an Iranian dataset.

Methods
The association of three SNPs in the MHC region previously identified as the most associated in high-density genotyping studies was tested in a case–control study on 973 BD patients and 825 controls from Iran, and the association of HLA-B alleles was tested in a subset of 681 patients and 414 controls.

Results
We found that HLA-B*51 (P = 4.11 × 10−41, OR [95% CI] = 4.63[3.66-5.85]) and B*15 confer risk for BD (P = 2.83 × 10−2, OR [95% CI] = 1.75[1.08-2.84]) in Iranian, and in B*51 negative individuals, only the B*15 allele is significantly associated with BD (P = 2.51 × 10−3, OR [95% CI] = 2.40[1.37-4.20]). rs76546355, formerly known as rs116799036, located between HLA-B and MICA (MHC class I polypeptide-related sequence A), demonstrated the same level of association with BD as HLA-B*51 (Padj = 1.78 × 10−46, OR [95% CI] = 5.46[4.21-7.09], and Padj = 8.34 × 10−48, OR [95% CI] = 5.44[4.20-7.05], respectively) in the HLA-B allelotyped subset, while rs2848713 was less associated (Padj = 7.14 × 10−35, OR [95% CI] = 3.73[2.97-4.69]) and rs9260997 was not associated (Padj = 1.00 × 10−1). Additionally, we found that B*51 genotype-phenotype correlations do not survive Bonferroni correction, while carriers of the rs76546355 risk allele predominate in BD cases with genital ulcers, positive pathergy test and positive BD family history (2.31 × 10−4 ≤ P ≤ 1.59 × 10−3).

Conclusions
We found that the HLA-B*51 allele and the rs76546355/rs116799036 MHC SNP are independent genetic risk factors for BD in Iranian, and that positivity for the rs76546355/rs116799036 risk allele, but not for B*51, does correlate with specific demographic characteristics or clinical manifestations in BD patients.
Pullulan: a new cytoadhesive for cell-mediated cartilage repair
Authors: Bulman Sarah E , Coleman Cynthia M , Murphy J Mary , Medcalf Nicholas , Ryan Aideen E , Barry Frank 
Published: March 2015

Abstract
Introduction
Local delivery of mesenchymal stem cells (MSCs) to the acutely injured or osteoarthritic joint retards cartilage destruction. However, in the absence of assistive materials the efficiency of engraftment of MSCs to either intact or fibrillated cartilage is low and localization is further reduced by natural movement of the joint surfaces. It is hypothesised that enhanced engraftment of the delivered MSCs at the cartilage surface will increase their reparative effect and that the application of a bioadhesive to the degraded cartilage surface will provide improved cell retention. Pullulan is a structurally flexible, non-immunogenic exopolysaccharide with wet-stick adhesive properties and has previously been used for drug delivery via the wet surfaces of the buccal cavity. In this study, the adhesive character of pullulan was exploited to enhance MSC retention on the damaged cartilage surface.

Methods
MSCs labeled with PKH26 were applied to pullulan-coated osteoarthritic cartilage explants to measure cell retention. Cytocompatability was assessed by measuring the effects of prolonged exposure to the bioadhesive on MSC viability and proliferation. The surface phenotype of the cells was assessed by flow cytometry and their multipotent nature by measuring osteogenic, adipogenic and chrondrogenic differentiation. Experiments were also carried out to determine expression of the C-type lectin Dectin-2 receptor.

Results
MSCs maintained a stable phenotype following exposure to pullulan in terms of metabolic activity, proliferation, differentiation and surface antigen expression. An increase in osteogenic activity and Dectin-2 receptor expression was seen in MSCs treated with pullulan. Markedly enhanced retention of MSCs was observed in explant culture of osteoarthritic cartilage.

Conclusions
Pullulan is a biocompatible and effective cytoadhesive material for tissue engraftment of MSCs. Prolonged exposure to pullulan has no negative impact on the phenotype, viability and differentiation potential of the cells. Pullulan dramatically improves the retention of MSCs at the fibrillated surface of osteoarthritic articular cartilage. Pullulan causes an upregulation in expression of the Dectin-2 C-type lectin transmembrane complex.
[18F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections
Authors: Mills Bethany , Awais Ramla O , Luckett Jeni , Turton Dave , Williams Paul , Perkins Alan C , Hill Philip J 
Published: March 2015

Abstract

Background
Management of infection is a major clinical problem. Staphylococcus aureus is a Gram-positive bacterium which colonises approximately one third of the adult human population. Staphylococcal infections can be life-threatening and are frequently complicated by multi-antibiotic resistant strains including methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([18F]FDG) imaging has been used to identify infection sites; however, it is unable to distinguish between sterile inflammation and bacterial load. We have modified [18F]FDG by phosphorylation, producing [18F]FDG-6-P to facilitate specific uptake and accumulation by S. aureus through hexose phosphate transporters, which are not present in mammalian cell membranes. This approach leads to the specific uptake of the radiopharmaceutical into the bacteria and not the sites of sterile inflammation.

Methods
[18F]FDG-6-P was synthesised from [18F]FDG. Yield, purity and stability were confirmed by RP-HPLC and iTLC. The specificity of [18F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT) was confirmed with S. aureus and mammalian cell assays in vitro. Whole body biodistribution and accumulation of [18F]FDG-6-P at the sites of bioluminescent staphylococcal infection were established in a murine foreign body infection model.

Results

In vitro validation assays demonstrated that [18F]FDG-6-P was stable and specifically transported into S. aureus but not mammalian cells. [18F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared to uninfected controls; however, the increase in signal was not significant and unexpectedly, the whole-body biodistribution of [18F]FDG-6-P was similar to that of [18F]FDG.

Conclusions
Despite conclusive in vitro validation, [18F]FDG-6-P did not behave as predicted in vivo. However at the site of known infection, [18F]FDG-6-P levels were elevated compared with uninfected controls, providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose phosphates other than glucose, and therefore alternative sugars may show differential biodistribution and provide a means for specific bacterial detection.