bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation of a Novel Thioflavin S–Derived Compound That Inhibits BAG-1–Mediated Protein Interactions and Targets BRAF Inhibitor–Resistant Cell Lines
Authors: Enthammer Marion , Papadakis Emmanouil S. , Salomé Gachet Maria , Deutsch Martin , Schwaiger Stefan , Koziel Katarzyna , Ashraf Muhammad Imtiaz , Khalid Sana , Wolber Gerhard , Packham Graham , Cutress Ramsey I. , Stuppner Hermann , Troppmair Jakob 
Published: September 2013

Abstract
Protein–protein interactions mediated through the C-terminal Bcl-2–associated athanogene (BAG) domain of BAG-1 are critical for cell survival and proliferation. Thioflavin S (NSC71948)—a mixture of compounds resulting from the methylation and sulfonation of primulin base—has been shown to dose-dependently inhibit the interaction between BAG-1 and Hsc70 in vitro. In human breast cancer cell lines, with high BAG-1 expression levels, Thioflavin S reduces the binding of BAG-1 to Hsc70, Hsp70, or CRAF and decreases proliferation and viability. Here, we report the development of a protocol for the purification and isolation of biologically active constituents of Thioflavin S and the characterization of the novel compound Thio-2. Thio-2 blocked the growth of several transformed cell lines, but had much weaker effects on untransformed cells. Thio-2 also inhibited the proliferation of melanoma cell lines that had become resistant to treatment with PLX4032, an inhibitor of mutant BRAF. In transformed cells, Thio-2 interfered with intracellular signaling at the level of RAF, but had no effect on the activation of AKT. Thio-2 decreased binding of BAG-1 to Hsc70 and to a lesser extent BRAF in vitro and in vivo, suggesting a possible mechanism of action. Given that tumors frequently develop resistance to kinase inhibitors during treatment, Thio-2 and related compounds may offer promising alternative strategies to currently available therapies. Mol Cancer Ther; 12(11); 2400–14. ©2013 AACR.
“Me, This Wretched Sinner”: A Coptic Fragment from the Vision of Theophilus Concerning the Flight of the Holy Family to Egypt
Authors: Suciu Alin 
Published: September 2013

Abstract
The Vision of Theophilus is one of the important apocryphal narratives concerning the flight of the Holy Family to Egypt. Although the text is known to survive in Arabic, Ethiopic and Syriac, a lost Coptic original has long been accepted by scholars. The present paper introduces a hitherto unidentified fragment from the Coptic version of this text. The fragment came from the White Monastery in Upper Egypt and it is currently kept in the National Library in Paris. The fragment is edited in this article together with its Arabic and Ethiopic parallels.
A Closure for Updraft–Downdraft Representation of Subgrid-Scale Fluxes in Cloud-Resolving Models
Authors: Moeng Chin-Hoh 
Published: September 2013

Abstract
A closure relationship between subgrid-scale (SGS) updraft–downdraft differences and resolvable-scale (RS) variables is proposed and tested for cloud-resolving models (CRMs), based on a data analysis of a large-eddy simulation (LES) of deep convection. The LES flow field is partitioned into CRM-RS and CRM-SGS using a cutoff scale that corresponds to a typical CRM grid resolution. This study first demonstrates the capability of an updraft–downdraft model framework in representing the SGS fluxes of heat, moisture, and momentum over the entire deep convection layer. It then formulates a closure scheme to relate SGS updraft–downdraft differences to horizontal gradients of RS variables. The closure is based on the idea that largest SGS and smallest RS motions are spectrally linked and hence their horizontal fluctuations must be strongly communicated. This relation leads to an SGS scheme that expresses vertical SGS fluxes in terms of horizontal gradients of RS variables, which differs from conventional downgradient eddy diffusivity models. The new scheme is shown to better represent the forward and backscatter energy transfer between CRM-RS and CRM-SGS components than conventional eddy-viscosity models.
Physically routing robots in a multi-robot network: Flexibility through a three-dimensional matching graph
Authors: Liu Lantao , Shell Dylan A 
Published: September 2013

Many multi-robot scenarios involve navigation of a set of networked robots through a constrained environment to achieve coverage, maintain a predefined shape, sense at predefined locations, or to satisfy some other distance-defined property. When new robots and tasks are added to a network of already deployed interchangeable robots, a trade-off arises in seeking to minimize cost to execute the tasks and the level of disruption to the system. This paper examines a navigation-oriented variant of this problem in which robots are physically routed through an existing network. We propose a parametrizable method to tune emphasis between minimizing global travel cost (or energy, or distance), minimizing interruption (i.e. obtaining the fewest number of robot reassignments), reducing travel distance per robot, and completing all operations as soon as possible. Since these are related optimization criteria, a single parameter provides sufficient flexibility to balance between them. Paths through the network are computed via a task-allocation formulation in which destination locations of newly deployed robots are added as tasks to an existing allocation. We adapt the graph matching variant of the Hungarian Algorithm—originally designed to solve the optimal assignment problem in complete bipartite graphs—to construct routing paths in sparse networks. We do this by constructing a three-dimensional graph that incorporates logical aspects of the Hungarian bipartite graph, and spatial elements of the Euclidean graph. The approach has several useful features including being particularly effective at generating multiple simultaneous, non-interfering paths. When new agent–task pairs are inserted, the assignment is globally reallocated in an incremental fashion so that it requires only linear time when the robots’ traversal options have bounded degree. The algorithm is studied systematically in simulation and also validated with physical robots.
Effect of Platelet-Rich Plasma and Porcine Dermal Collagen Graft Augmentation for Rotator Cuff Healing in a Rabbit Model
Authors: Chung Seok Won , Song Byung Wook , Kim Yeun Ho , Park Kyoung Un , Oh Joo Han 
Published: September 2013

Background: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. Purpose: To verify the effect of platelet-rich plasma (PRP) with and without porcine dermal collagen graft augmentation on tendon-to-bone healing, using the rabbit supraspinatus tendon. Study Design: Controlled laboratory study. Methods: A total of 80 rabbits were randomly allocated into 4 groups (20 rabbits per group: 12 for histological and 8 for mechanical testing): repair (R), repair + patch augmentation (RPa), repair + PRP (RPr), and repair + patch + PRP (RPaPr). The right shoulder was used for experimental interventions, and the left served as a control. Six weeks after the detachment of the supraspinatus, the torn tendon was repaired in a transosseous manner, simulating double-row repair in all groups. Platelet-rich plasma was prepared and applied onto the repair site in the RPr and RPaPr groups, and the patch was used to augment the repair in the RPa and RPaPr groups. The mechanical tensile strength test was performed at 8 weeks after repair and the histological evaluation at 4 and 8 weeks. Results: At 4 weeks, the collagen fibers were poorly organized, and fiber continuity was not established in all groups. However, vascularity and cellularity were higher with granulation tissue formation in the PRP-treated groups (RPr and RPaPr) than the nontreated groups (R and RPa). At 8 weeks, tendon-to-bone integration was much improved with more collagen fibers, and longitudinally oriented collagen fibers were visible in all groups. The PRP-treated groups showed better collagen fiber continuity and orientation than the nontreated groups; however, no distinctive difference was found between the patch-augmented groups (RPa and RPaPr) and nonaugmented groups (R and RPr). The mean load-to-failure results were 61.57 ± 29.99 N, 76.84 ± 16.08 N, 105.35 ± 33.82 N, and 117.93 ± 12.60 N for the R, RPa, RPr, and RPaPr groups, respectively, and they were significantly different between the R and RPr ( P = .018), R and RPaPr ( P = .002), and RPa and RPaPr ( P = .029) groups. Conclusion: This animal study showed the enhancement of tendon-to-bone healing after local administration of autologous PRP assessed by histological and biomechanical testing in a rabbit model of chronic rotator cuff tears. However, there was little additive effect of the patch graft. Clinical Relevance: The use of PRP might be a biological supplement to increase the rotator cuff healing rate, which still remains low even after successful cuff repair, but this result should be interpreted with caution regarding clinical applications.
The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort
Authors: Lee J , Peschken CA , Muangchan C , Silverman E , Pineau C , Smith CD , Arbillaga H , Zummer M , Clarke A , Bernatsky S , Hudson M , Hitchon C , Fortin PR , Pope JE 
Published: September 2013

Objectives Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Methods Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. Results Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6–8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1–4.7]), number of ACR SLE criteria (1.4 [1.1–1.7], baseline body mass index (BMI) (1.1 [1.0–1.1]), psychosis (3.4 [1.2–9.9]), aboriginal race (3.2 [1.5–6.7]), anti-Smith (2.6 [1.2–5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1–3.4]), proteinuria >0.5 g/d (4.2 [1.9–9.3], and SLAM-2 score (1.1 [1.0–1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. Conclusions The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.
Efficacy of Urokinase and Alteplase to Reopen Occluded Central Venous Catheters in Children
Authors: Bussières Jean-François , Therrien Roxane , David Michèle , Leclair Jean-Pierre , Harel François 
Published: September 2013

Objective: To compare the efficacy of alteplase with that of urokinase (UK) in restoring the patency of occluded central venous catheters in children. Study Design: Retrospective case–control study at Hôpital Ste-Justine, a pediatric teaching hospital. Results: 87 UK and 46 alteplase prescriptions were studied. Alteplase was effective in 93.2% of cases of occluded central venous catheters and UK in 54.5% of cases (p < 0.001). Conclusions: Alteplase was clearly superior to UK for restoring the patency of occluded central venous catheters in children. The study is limited by its retrospective design.
Pioglitazone Used for Reduction in Clozapine-Associated Hypertriglyceridemia
Authors: Lea Jessica Wehner , Stoner Steven C 
Published: September 2013

Objective: To report a case of reduction of triglycerides and hemoglobin (Hb)A1C concentrations as a result of the use of the thiazolinedione pioglitazone in a psychiatric patient stabilized on clozapine therapy. Case Summary: A 49-year-old obese white man, who had uncontrolled diabetes and elevated triglycerides, was stabilized on an antipsychotic regimen using clozapine. After failing sulfonylurea therapy, metformin therapy, and fibric acid therapies, pioglitazone was used to reduce fasting blood glucose and HbA1c concentrations and reduce mean triglyceride concentrations. Discussion: Because of the necessity to keep this patient on his current antipsychotic medication and the possible association of exacerbation of diabetes and lipid abnormalities with clozapine, it was necessary to attempt to control the patient's blood glucose and triglycerides through therapeutic means. Numerous attempts to use other diabetic therapies failed. After the addition of pioglitazone to the patient's regimen, significant improvement was observed in the laboratory values, indicating an improvement in diabetes control. Conclusions: It appears that pioglitazone has played a role in reducing fasting plasma glucose concentrations and improving insulin sensitivity, while reducing triglycerides and increasing high-density lipoprotein concentrations in this patient. Expanded trials and further investigation are recommended to evaluate the clinical utility of pioglitazone in antipsychotic-associated diabetes and lipid abnormalities.
Various Dosing Weights and Correction to Serum Digoxin Assays in Hemodialysis Patients
Authors: Hirata Sumio , Uenishi Koji , Izumi Satoshi , Furukubo Taku , Ota Miyuki , Fujita Minori , Yamakawa Tomoyuki , Ohtani Hisakazu , Sawada Yasufumi 
Published: September 2013

Background: Digoxin is distributed in skeletal muscles in high concentrations. The most reliable parameter to measure the distribution of digoxin in patients undergoing hemodialysis is not known. Objective: To estimate which distribution parameter—estimated lean body mass (E-LBM) calculated by subtracting the fat mass from the dry weight, lean body mass, dry weight, and ideal body weight—is the most reliable predictor for assessing the accuracy of a digoxin dosing regimen in patients undergoing hemodialysis. Methods: A retrospective study was conducted to evaluate 21 patients undergoing hemodialysis who were administered digoxin. The patients were divided into 2 groups: digoxin 0.125 mg administered twice a week (low-dose group) or 3 times per week (high-dose group). The differences between E-LBM, lean body mass, dry weight, and ideal body weight for the low- and high-dose groups were determined. The relationships between serum digoxin concentrations and the weekly digoxin dose per E-LBM, lean body mass, dry weight, and ideal body weight were also determined. Results: E-LBM, lean body mass, dry weight, and ideal body weight in the high-dose group were significantly larger than those in the low-dose group (p = 0.021, 0.015, 0.024, and 0.0029, respectively), although no significant difference in serum digoxin concentrations was evident. Significant correlation was found between serum digoxin concentrations and the weekly digoxin dosage per E-LBM, dry weight, lean body mass, and ideal body weight (r = 0.746, p < 0.0001; r = 0.638, p = 0.0014; r = 0.645, p < 0.0011; r = 0.553, p = 0.0083, respectively). Conclusions: E-LBM appears to reflect the best parameter for predicting serum digoxin concentrations. The use of the dry weight parameter could be generally useful for adjusting the dosage of digoxin in patients undergoing hemodialysis.
Continuing Professional Development in Pharmacy
Authors: Rouse Michael J 
Published: September 2013

Objective: To summarize a resource document that explains the concept and components of continuing professional development (CPD) for pharmacists, describes some of the drivers behind the reevaluation of current systems of continuing pharmacy education (CE), defines relevant terms, and outlines some experiences with CPD in selected countries that have already adopted the model. Summary: CPD is an approach to lifelong learning being discussed as a potential model for pharmacists in the United States. CPD does not replace CE, but quality-assured CE is an essential component of CPD. Evidence is mounting, however, that traditional methods of CE do not adequately meet the lifelong learning and professional development needs of health care professionals (HCPs) and are not always successful in affecting practice behavior and improving patient outcomes. The Institute of Medicine has concluded that the education and training of HCPs are in need of major overhaul. CPD, which is based on sound principles and adopts educational strategies that have been shown to be effective, potentially offers a quality improvement to the current systems for pharmacist CE. Conclusion: Interest in and support for the concept of CPD is growing. Case studies of successful implementation in the United States and other countries now exist. Further discussion on the implications of widespread implementation for pharmacists in the United States is needed.
Long-Acting Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure: Does Multiple-Daily Dosing Provide Additional Benefit over Once-Daily Dosing?
Authors: Belgeri Myra T 
Published: September 2013

Objective: To determine if there is clinical evidence supporting the use of twice-daily long-acting angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). Data Sources: Articles were identified through searches of MEDLINE and PubMed (1966–June 2005). Search terms included angiotensin-converting enzyme inhibitors, congestive heart failure, dosing, dosing schedules, captopril, enalapril, fosinopril, lisinopril, quinapril, ramipril, and trandolapril. Only articles published in English were included. Additionally, bibliographies of articles cited were used to identify additional articles. Study Selection and Data Extraction: All available articles identified by the data sources were reviewed and those deemed relevant to the review were included. Data Synthesis: Data have suggested that long-acting ACE inhibitors are more effective than short-acting ACE inhibitors for the treatment of CHF. A few ACE inhibitors approved for the treatment of CHF have twice-daily dosing schedules; these same ACE inhibitors have once-daily dosing schedules when used in the treatment of hypertension. Recent data propose greater adrenergic blockage, and, thus, decreased stimulation of the renin–angiotensin–aldosterone system, with the twice-daily dosing schedule of the long-acting ACE inhibitors. This controversy has led some providers to prescribe all long-acting ACE inhibitors twice daily in the setting of CHF, which, when unnecessary, can lead to decreased compliance, increased morbidity, and decreased quality of life. Conclusions: The available clinical studies comparing dosing schedules of long-acting ACE inhibitors have many limitations. Until a well-designed, randomized, double-blind trial of appropriate duration evaluating clinical outcomes is conducted, multiple-daily dosing schedules do not provide additional benefit over once-daily dosing schedules of long-acting ACE inhibitors in the treatment of CHF.
Surveying Physicians' Attitudes about Herbal Supplements, Resources, and Pharmacy Consultations
Authors: Bouwmeester Carla J 
Published: September 2013

Objective: To investigate whether physicians discuss herbal supplement use with their patients and document this information in the medical record, to determine the perceived barriers to discussing herbal supplement use, and to assess all resources currently available to physicians in their office setting and additional resources needed to answer questions about herbal supplements. Methods: An electronic survey was conducted of physicians enrolled in a managed care electronic network as of November 2002; data were collected from December 2002 through March 2003. Results: Of the 203 physicians who responded to the survey, 18% always discussed herbal supplements with their patients, 57% sometimes carried on these discussions, 21% rarely did, and 4% never asked. These responses correlated roughly with how often herbal supplement use was documented in the medical chart (always 27%, sometimes 51%, rarely 20%, never 2%). The strongest barriers to discussing herbal supplements were lack of resources and lack of time. The largest number of physicians used Web sites or print resources for information on herbal supplements. The most preferred resources were Web sites, computer databases, and pharmacy consultations. Conclusions: Awareness of herbal supplement use is vital for the healthcare practitioner to deliver comprehensive health services. Physicians' attitudes regarding herbal supplements are influenced by the resources available and by personal bias. Pharmacists can play a pivotal role in providing consultation services, educational materials, and screening for drug–herb interactions.
Overview of Pharmacologic Treatment of Obesity: Past Experiences, Present Options, and Future Directions
Authors: Harrell T Kristopher , Ross Leigh Ann , King Deborah S 
Published: September 2013

Objective: To review the literature regarding the past, present, and future pharmacologic agents used in the treatment of obesity. Data Sources: Articles were identified by searching MEDLINE (1966–April 2005) and International Pharmaceutical Abstracts (1970–April 2005) using the key words obesity, antiobesity agents, sibutramine, orlistat, phentermine, and leptin. Additional resources were identified by examining the references of the articles cited. Searches were limited by human subject and English language, but were not limited by time of publication. Study Selection and Data Extraction: Large-scale clinical studies of pharmacologic agents used to treat obesity were selected for this review including agents that were previously available, currently available, and those currently undergoing clinical trials. Data Synthesis: Thyroid hormone was the first antiobesity agent used. Several other agents have been withdrawn from the market due to adverse effects. Current therapies indicated for obesity management include orlistat, sibutramine, and noradrenergic agents. Future therapies include both newer agents and existing agents that are principally used for other indications, mainly diabetes, depression, and seizure disorders. Conclusions: Obesity is a major epidemic in the US, affecting over half of the population. Past experiences with the pharmacologic treatment of obesity have been disappointing and, in some cases, harmful to patients. Current options are available that include noradrenergic agents, orlistat, and sibutramine. However, these agents still have only demonstrated limited efficacy for short-term use plus some undesirable adverse effects. Newer treatment options are being evaluated as new pathways are being identified and other related factors are being discovered.