bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluations of clinical-grade bone substitute-combined simvastatin carriers to enhance bone growth: In vitro and in vivo analyses
Authors: Lee Tien-Ching , Wang Yan-Hsiung , Huang Shih-Hao , Chen Chung-Hwan , Ho Mei-Ling , Fu Yin-Chih , Wang Chih-Kuang 
Published: July 2017

We demonstrated in a value-added study that the combination of calcium phosphate–based bone substitute (MaxiBone® bioceramics) and simvastatin/poly lactic- co-glycolic acid (SIMm) carriers which were fabricated by GMP pharmaceutical company and underwent our patterned double-emulsion technique can promote bone growth. The average size distribution of SIMm, the encapsulation efficacy, and the in vitro release profile of simvastatin in SIMm over 14 days were investigated in this study. Based on the results of Alizarin Red S staining and alkaline phosphatase activity, the released simvastatin of SIMm can effectively induce osteogenesis of bone marrow mesenchymal stem cells (D1 cells). In the non-union fracture model of animal study, the MaxiBone bioceramics group and MaxiBone bioceramics with SIMm group showed a significant increase in the percentages of new bone matrix compared with the control group and SIMm groups at the 8th and 10th weeks. Moreover, the MaxiBone bioceramics with SIMm group showed the strongest effect in new bone formation among these groups. We concluded that the calcium phosphate–based ceramics of MaxiBone combined with SIMm can accelerate osteogenic differentiation and bone growth in vitro and in vivo. Our results provide a proof of concept that SIMm can play as an osteoinductive material and the combination with bone substitutes with osteoconductive property effectively enhance bone growth, and this treatment is value added for clinical application, especially in the healing of large bone defects or non-union. Graphical abstract. The clinical-grade calcium phosphate–based bone substitute combined SIM/PLGA/HAp microspheres were fabricated by GMP pharmaceutical company to promote bone growth in bone defect model of mice.
A tissue factor-cascade-targeted nanoparticle forsite-directed inducing thrombosis
Authors: Jin Weiwei , Yin Yanxue , Zhang Bo , Mei Heng , Wang Huafang , Guo Tao , Shi Wei , Hu Yu 
Published: July 2017

Tissue factor is an upstream component of the cascade and a high-expressing factor under phathological conditions. In this study, a tissue factor cascade-targeted strategy for inducing local thrombosis was developed by combining ENP-HMME and photochemistry. In vitro study showed that protein EGFP-EGF1 conjugation to the nanoparticles could significantly contribute to the uptake of nanoparticles by tissue factor over-expressed brain capillary endothelial cells. Three-dimensional imaging and specklegram of brains in vivo showed that tissue factor cascade-targeted strategy successfully induced thrombosis of expected position. As shown by the in vivo multispectral fluorescent imaging, when ENP-HMME was combined with photochemistry, higher accumulation in the infarction hemisphere was observed, which might suggest that the photochemistry inducing tissue factor cascade recruited more ENP-HMME than HMME-loaded nanoparticles (NP-HMME). The data indicated the tissue factor cascade-targeted strategy has potential to induce local thrombosis, and might be applied in the treatment of a variety of hypervascular diseases.
Recipes for Structural Fairness in Games
Authors: Thavikulwat Precha 
Published: July 2017

Background. Although fairness is central to society and to games that are taken seriously, the structural aspect of fairness has not been addressed as a problem of games. Aim. To resolve the problem of structural fairness in multi-player, multi-episodic games, especially for business games that are transaction based, where sales result from individual transactions rather than from formulae that aggregate and allocate modeled-market demand. Method. Mathematics and examples are used to clarify positions, present proofs, and show application. Argument. Structural fairness is of three kinds: positional, order, and arrival. Finding. For fixed number of parties, positional rotation assures complete positional fairness, whereas order rotation assures both complete positional fairness and complete order fairness, but only when number-of-party and number-of-episode conditions are satisfied. For variable number of parties, arrival rotation assures fairness to parties added last. The classic Gold and Pray model can be modified to allow supply to affect demand by applying order rotation to stock outs. Application. The rotational procedures apply to business games with modeled and real markets, and may apply to all games with a scoring system that is taken seriously. Conclusion. Games can be structurally fair, but the game that is structurally fair must be a multi-episodic game that incorporates fairness into its design. For assuring structural fairness, proportional and random methods are generally inferior to rotation.
Real-world chart review study of adverse events management in patients taking tyrosine kinase inhibitors to treat metastatic renal cell carcinoma
Authors: Srinivas Sandy , Stein Dara , Teltsch Dana Y , Tao Sunning , Cisar Laura , Ramaswamy Krishnan 
Published: July 2017

Purpose The purpose is to describe management of adverse events of special interest across tyrosine kinase inhibitors approved for metastatic renal cell carcinoma. Methods We conducted a retrospective chart review in metastatic renal cell carcinoma patients initiating tyrosine kinase inhibitor monotherapy between 15 November 2010 and 15 November 2013, and experiencing ≥ 1 adverse events of special interest (diarrhea, fatigue, hand-foot syndrome, hypertension, or stomatitis/mucositis) within 3 months of initiation. Demographics, medical history, treatment regimens, and adverse events of special interest management data for 3.5 months postonset were collected. Results In 220 charts from 27 centers, tyrosine kinase inhibitors prescribed included sunitinib (55%), pazopanib (27%), axitinib (9%), and sorafenib (8%). During the study period, patients experienced 376 adverse events of special interest (13% serious). Fatigue was most common (62% of patients), followed by hypertension (37%), diarrhea (30%), stomatitis/mucositis (29%), and hand-foot syndrome (12%). Over half (56%) the adverse events of special interest were resolved or resolving. Treatment discontinuation due to adverse events of special interest occurred in 15% of patients. Prophylaxis was rarely provided (8%), whereas 59% of patients received adverse events of special interest treatment (pharmacologic (55%) and/or nonpharmacologic (7%)), 27% received tyrosine kinase inhibitor dose management, 23% received both adverse events of special interest treatment and dose management, and 31% received neither. Hypertension was the most treated (72% of all events), and fatigue was the least treated (9%); only 4% of patients received pharmacologic treatment for fatigue. Conclusions Most adverse events of special interest were nonserious and more than half of the patients received pharmacologic and/or nonpharmacologic treatment. Fatigue was the most common yet least frequently treated adverse event of special interest, and few patients received prophylaxis or nonpharmacologic treatment. More emphasis on treatment and prophylaxis options for bothersome adverse events is warranted.
Assessment of the potential impact of dose rounding parenteral chemotherapy agents on cost savings and drug waste minimization
Authors: Chillari Kelly A , Southward Jessica , Harrigan Natasha 
Published: July 2017

Background Fiscally responsible utilization of anticancer treatments is necessary to combat their continually increasing cost. Dose rounding is one strategy that has been explored to minimize cost and waste without losing clinical effectiveness. Objectives To determine if dose rounding chemotherapy agents is a feasible cost-containment strategy at an institution with a small oncology clinic. Methods This study is a retrospective chart review of all body surface area dosed parenteral chemotherapy prescribed for an oncological diagnosis over a 12-month period (1 October 2015–30 September 2016). Chemotherapy doses were rounded down by 5%. Doses for patients with metastatic diagnoses were also rounded down by 10%. Rounded doses were evaluated for a potential decrease in vial size. Cost was represented as dollar/milligram of drug. Potential for drug waste minimization was also calculated. Results There were 877 total doses of chemotherapy administered to 70 unique patients throughout the 12-month duration of the study. When doses were rounded down by 5%, 140 doses qualified for a decrease in vial number. The potential for cost savings was $22,849 with 83,802 mg saved from wastage. A 10% decrease resulted in the reduction of vials for 248 doses, a potential savings of $30,911 with 129,011 milligrams saved. The targeted agents accounted for the majority of savings, $16,920 of the $22,849 with 5% rounding and $20,086 of the $30,911 with 10% rounding. Conclusion Dose rounding has the potential to be an effective cost-containment strategy in low volume oncology clinics.
Use of a complete autologous blood recovery system (the Sorin Xtra® Autotransfusion System) during mechanical thrombectomy of extensive cerebral venous sinus thrombosis
Authors: Castaño C , Cubells C , Remollo S , García-Sort MR , Terceño M 
Published: July 2017

Background The endovascular therapy for cerebral venous sinus thrombosis (CVST) is currently accepted as a second-line treatment for patients who have failed or those in whom systemic anticoagulation is contraindicated or in a subgroup of patients presenting with rapid neurologic deterioration. A number of different mechanical and pharmacologic endovascular strategies have been reported, either as separate or combined approaches. These new catheters and aspiration systems have a high power and vacuum capacity, which carries a risk of anemization of the patient and hypovolemic shock, being necessitating the transfusion of the patient. Material and methods Because of the problems that donor blood transfusion can bring, we describe the use of a Sorin Xtra® Autotransfusion System (ATS). This complete autologous blood recovery system was designed for use in procedures where medium- to high-volume blood loss occurs, such as major surgeries. We have adapted it to recover all the blood aspirated during the mechanical thrombectomy procedures of the dural cerebral venous sinuses, since they are procedures that can cause a significant loss of blood. One advantage to this is the patient receives his or her own blood instead of donor blood, so there is no risk of contracting outside diseases or transfusion reactions. Conclusions This technical note describes a novel and previously unpublished technical approach to CVST that can be immediately applied to clinical practice. It also raises awareness among the interventional neuroradiologist and anesthesiologist communities about novel, potentially lifesaving endovascular treatments in patients with extensive CVST.
The Impact on Central Blood Pressure and Arterial Stiffness Post Renal Denervation in Patients With Stage 3 and 4 Chronic Kidney Disease: The Prairie Renal Denervation Study
Authors: Prasad Bhanu , St.Onge Jennifer Rose , McCarron Michelle C. E. , Goyal Kunal , Dehghani Payam 
Published: July 2017

Background: Central aortic blood pressures and arterial stiffness are better indicators of cardiovascular outcomes than brachial blood pressures. However, their response to renal denervation (RDN) in patients with stage 3 and stage 4 chronic kidney disease (CKD) has not yet been examined. Objective: To evaluate the impact of RDN on central blood pressures, brachial (office and ambulatory) blood pressures, arterial stiffness, glomerular filtration rate (GFR), 24-hour urine protein, and selective cardiac parameters observed on echocardiograms. Design: Single-center, single-arm with pre-RDN/post-RDN follow-up. Setting: Patients are being recruited from the multidisciplinary CKD clinic. Patients: Fifty consecutive patients with stage 3 or stage 4 CKD and resistant hypertension, with no radiological or laboratory evidence of secondary causes of hypertension. Measurements: The key measurements are central blood pressures, pulse wave velocity, ambulatory 24-hour blood pressure, office blood pressures on BP Tru, GFR, 24-hour urine protein and sodium, blood pressure medication, and doses. Methods: For our primary outcome, we will compare changes in central blood pressures from baseline to 6 months post RDN using a paired t test or Mann-Whitney U test. Secondary outcomes will examine changes in central blood pressures from baseline to 3, 12, 18, and 24 months post RDN as well as changes in office pressures, GFR, 24-hour urine protein and sodium, and medications at all time points using mixed-model analyses of variance or Friedman test. Multiple regression may be used to control for potential covariates. Limitations: Single-center study, with no sham arm. Conclusions: Aortic blood pressure, rather than brachial blood pressure, optimally reflects the load placed on the left ventricle. Aortic blood pressure is also better associated with cardiovascular outcomes. If our study shows a preferential decrease in central blood pressures and improvements in cardiac parameters on echocardiograms post RDN, this may influence the way in which blood pressures are managed in clinics and offices. Trial Registration: ClinicalTrials.gov (NCT01832233)
Local staging of sigmoid colon cancer using MRI
Authors: Dam Claus , Lindebjerg Jan , Jakobsen Anders , Jensen Lars Henrik , Rahr Hans , Rafaelsen Søren Rafael 
Published: July 2017

Background An accurate radiological staging of colon cancer is crucial to select patients who may benefit from neoadjuvant chemotherapy. Purpose To evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) in identifying locally advanced sigmoid colon cancer, poor prognostic factors, and the inter-observer variation of the tumor apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). Material and Methods Using 1.5 T MRI with high resolution T2-weighted (T2W) imaging, DWI, and no contrast enhancement, 35 patients with sigmoid colon cancer were assessed. T-stage, N-stage, extramural vascular invasion (EMVI), and ADC values of the tumors were assessed and blindly compared by two observers using postoperative histopathological examination as the gold standard. Early tumors were defined as T1 to T3ab, and advanced tumors as T3cd or T4. Results The accuracy of the two radiologists in staging early versus advanced tumors, N-stage, and identification of EMVI was 94%/89%, 60%/66%, and 77%/60% with an inter-observer agreement of к = 0.86 (95% confidence interval [CI] = 0.67–1.00), к = 0.64 (95% CI = 0.39–0.90), and к = 0.52 (95% CI = 0.23–0.80). All the measured mean ADC values were below 1.0 × 10−3 mm2/s with an intra-class correlation coefficient in T3cd–T4 tumors of 0.85. Conclusion Preoperative MRI can identify locally advanced sigmoid colon cancer and has potential as the imaging of choice to select patients for neoadjuvant chemotherapy. Initial experience with ADC measurement was achieved with an excellent inter-observer agreement in advanced tumors.
Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes
Authors: Blázquez-Moreno Alfonso , Pérez-Portilla Adriana , Agúndez-Llaca Miriam , Dukovska Daniela , Valés-Gómez Mar , Aydogmus Cigdem , Ikinciogullari Aydan , Regueiro José R. , Reyburn Hugh T. 
Published: July 2017

Key Points
The propensity of genes to mutate influences the probability of spontaneous reversion of genetic defects in PID.
Apples and pears? A comparison of two sources of national lung cancer audit data in England
Authors: Khakwani Aamir , Jack Ruth H. , Vernon Sally , Dickinson Rosie , Wood Natasha , Harden Susan , Beckett Paul , Woolhouse Ian , Hubbard Richard B. 
Published: July 2017

In 2014, the method of data collection from NHS trusts in England for the National Lung Cancer Audit (NLCA) was changed from a bespoke dataset called LUCADA (Lung Cancer Data). Under the new contract, data are submittedviathe Cancer Outcome and Service Dataset (COSD) system and linked additional cancer registry datasets. In 2014, trusts were given opportunity to submit LUCADA data as well as registry data. 132 NHS trusts submitted LUCADA data, and all 151 trusts submitted COSD data. This transitional year therefore provided the opportunity to compare both datasets for data completeness and reliability.We linked the two datasets at the patient level to assess the completeness of key patient and treatment variables. We also assessed the interdata agreement of these variables using Cohen's kappa statistic, κ.We identified 26 001 patients in both datasets. Overall, the recording of sex, age, performance status and stage had more than 90% agreement between datasets, but there were more patients with missing performance status in the registry dataset. Although levels of agreement for surgery, chemotherapy and external-beam radiotherapy were high between datasets, the new COSD system identified more instances of active treatment.There seems to be a high agreement of data between the datasets, and the findings suggest that the registry dataset coupled with COSD provides a richer dataset than LUCADA. However, it lagged behind LUCADA in performance status recording, which needs to improve over time.
TLR4 and C5aR crosstalk in dendritic cells induces a core regulatory network of RSK2, PI3Kβ, SGK1, and FOXO transcription factors
Authors: Zaal Anouk , Nota Benjamin , Moore Kat S , Dieker Miranda , van Ham S Marieke , ten Brinke Anja 
Published: July 2017

Abstract
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation. Analysis of functional relationships among these genes uncovered induction of a central immune regulatory network upon C5aR and TLR4 crosstalk, involving the transcription factors forkhead box (FOX)O1 and FOXO3 and the signaling molecules serum- and glucocorticoid-inducible kinase (SGK1), ribosomal S6 kinase 2 (RSK2), and PI3Kβ. C5aR and TLR crosstalk, furthermore, yielded down-regulation of mainly proinflammatory network branches, including IL-12B, IL-2Rα (IL-2RA), and jagged 1 (JAG1) and cooperative induction of predominantly anti-inflammatory network branches, including sphingosine kinase 1 (SPHK1), β2 adrenergic receptor (ADRB2), gastric inhibitory polypeptide receptor (GIPR), and four-and-a-half Lin11, Isl-1, and Mec-3 domains protein 2 (FHL2). Together, these data point toward induction of generalized immune regulation of DC function. Motif enrichment analysis indicate a prominent role for basic leucine zipper (bZIP) and IFN regulatory factor 4 (IRF4) transcription factors upon C5aR and TLR4 crosstalk. Additionally, differences were observed in the modulating capacity of C5a on DCs in the absence or presence of a pathogen (TLR stimulus). Our findings shed new light on the depth and complexity of C5aR and TLR4 crosstalk and provide new foci of research for future studies.
Investigation of magnetic inversion methods in highly magnetic environments under strong self-demagnetization effect
Authors: Krahenbuhl Richard A. , Li Yaoguo 
Published: July 2017

We investigate self-demagnetization effects on magnetic data and develop a comparison of two existing inversion methods as they apply to quantitative interpretation of such data in highly magnetic environments. We begin by evaluating the effect on magnetization direction when susceptibility is a scalar and increases from low values into the realm of self-demagnetization. We show through numerical experiments that susceptibility values of greater than 0.1 SI lead to significant self-demagnetization effects. Second, we show that conventional inversion can perform well for interpretation of self-demagnetization problems with simple source geometries. However, as the geometry becomes more complex in realistically complex problems, this approach can produce poor results and a more robust technique is required. Our numerical experiments indicate that directly inverting amplitude data, which can be derived from total-field magnetic anomaly data and are weakly dependent on magnetization direction, produces superior results when interpreting data from areas with complex geology and high magnetic susceptibilities. We conclude by evaluating the application of our preferred approach on a large field data set exhibiting strong self-demagnetization, multiple source bodies, and complex structures.
Differential source-to-sink system analysis for three types of stepped terrains in China
Authors: Cheng Yuan , Zhu Hongtao , Zeng Hongliu , Liu Qianghu , Zhu Xiu 
Published: July 2017

The terrains of China, showing a trend of being high in the west and low in the east, can be categorized largely into three types of stepped terrains that consist of different geomorphic units — namely, glaciers and mountains (the first [highest] step), basins and plateaus (the second [less high] step), and plains (the third [lowest] step). The source-to-sink systems in the first and second steps are closed systems from land to lake, whereas those of the third step are mainly open systems from land to ocean. We have based our analytical methods mainly on the parameters of the source-to-sink systems for the three types of stepped terrains using the Google Earth database. We acquired data for the catchment area in the source unit, the longest channel and coefficient of river-network development in the conduit unit, the fan area and fan length: width ratio in the sink unit, and the gradient of the entire system. On the basis of our comparison of these parameters in the three types of stepped terrains, results indicate differential source-to-sink system parameters (catchment area, longest channel, coefficient of river-network development, fan area, fan length:width ratio, and gradient) and a transition among these parameters from the first step to the third. The gradient varies in different geomorphic units, being relatively small on the plains (third step) and relatively large in the basins and on plateaus (the first or second step). The other five parameters become higher from the first step to the third. By analyzing the correlations of these parameters, we found out that (1) the coefficient of river-network development declines with the gradient increasing, (2) the catchment area and the coefficient of river-network development show a positive correlation, (3) the fan area increases with the catchment area increasing, and (4) the fan area and gradient show a negative correlation. From the perspective of controlling factors, we focused on the formation of the geomorphic units, tectonic conditions, and the climate resulting from the obvious differences between the three types of stepped terrains. A new approach to compare the parameters of each step and analyze the correlations between parameters has been used in this study with the goal of predicting the correlations between parameters of different units.