bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
Authors: Shah Carl-Henrik , Pappot Helle , Agerbæk Mads , Holmsten Karin , Jäderling Fredrik , Yachnin Jeffrey , Grybäck Per , von der Maase Hans , Ullén Anders 
Published: December 2018

Abstract

Lessons Learned
First trial to report safety and activity of the microtubule inhibitor vinflunine plus the tyrosine kinase inhibitor sorafenib in post-platinum metastatic urothelial cancer (mUC) patients. A recommended phase II dose was identified for the treatment combination of vinflunine plus sorafenib, with main adverse events including fatigue, febrile neutropenia, neutropenia, hypertension, and hyponatremia. An overall response rate of 41% to second-line vinflunine plus sorafenib treatment in patients with platinum-resistant mUC was confirmed.

Background
Platinum-progressive metastatic urothelial carcinoma (mUC) is a clinical challenge. The tyrosine kinase inhibitor sorafenib has demonstrated varied activity in mUC. This trial was designed to examine safety and activity of vinflunine plus sorafenib in mUC.

Methods
In addition to standard dose of vinflunine (320 or 280 mg/m2), patients received sorafenib (400, 600, or 800 mg/day), in a 3 + 3 dose-escalation phase I design.

Results
Twenty-two patients (median age 62.5 years) were included. Five patients received vinflunine 320 mg/m2 and 17 received 280 mg/m2. The maximum tolerated dose (MTD) of sorafenib with vinflunine 280 mg/m2 was 600 mg, and with vinflunine 320 mg/m2 it was not determined, owing to toxicity. Adverse events (AEs) grades 3 + 4 consisted of neutropenia (6 patients), febrile neutropenia (5), and hyponatremia (5). The overall response rate (ORR) in the efficacy-evaluable patients was 41% (7 of 17), all partial responses evaluated by RECIST version 1.1. Median overall survival (OS) was 7.0 months (1.8–41.7).

Conclusion
The defined recommended phase II dose (RPTD) was vinflunine 280 mg/m2 plus sorafenib 400 mg. Sorafenib was too toxic in combination with vinflunine 320 mg/m2. The ORR of 41% to this second-line combination treatment of mUC is noteworthy and supports further trials.
Assessment of Hematological and Inflammatory Parameters in Patients Receiving Isotretinoin Therapy for Acne Vulgaris
Authors: YALDIZ Mahizer , ÇETİNKAYA Reyhan , SOLAK Berna 
Published: December 2018

Objectives:Isotretinoin (ISO) is a synthetic analog of vitamin A used at the doses of 0.5–2 mg/kg for four to five months in the treatment of moderate to severe acne vulgaris. In the present study, both hematological and inflammatory parameters were retrospectively assessed in patients receiving ISO therapy for acne vulgaris.Method: This study included 352 patients who were admitted to the Dermatology Clinic and received oral ISO for the treatment of acne vulgaris were included in the study. Each patient’s hematological and inflammatory parameters (hemoglobin, hematocrit, thrombocyte, mean platelet volume, leukocyte, erythrocyte, neutrophil, lymphocyte, monocyte, eosinophil, basophil, neutrophil/basophil, thrombocyte/lymphocyte, RDW, PCT and PDW) were evaluated before the treatment and retrospectively evaluated four months after the onset of treatment. Results: After treatment, a significant decrease was detected in the levels of leukocyte, neutrophil and neutrophil to lymphocyte ratio (NLR) (an indicator of inflammation), and a significant increase was detected in the levels of thrombocyte and procalcitonin (PCT).Conclusion: In our study, isotretinoin inhibited the anti-inflammatory effect of isotretinoin treatment of acne in patients with NLR decline after treatment with inflammatory markers. Patients with markedly elevated platelet counts or low leukocyte counts should be closely monitored.
PERBEDAAN PENGETAHUAN REMAJA TENTANG SADARI SEBELUM DAN SESUDAH PENYULUHAN KESEHATAN DI SMKN 5 SURABAYA
Authors: Yulinda Arif 
Published: December 2018

Kanker payudara merupakan kanker penyebab kematian tertinggi nomor 2 setelah kanker leher rahim. Saat ini, kanker payudara sudah mulai menyerang remaja. Namun remaja masih memiliki pengetahuan yang rendah mengenai kanker payudara dan deteksi dini kanker payudara. Tujuan dari penelitian ini adalah untuk menganalisis perbedaan pengetahuan sebelum dan sesudah penyuluhan kesehatan pada remaja putri di SMKN Negeri 5 Surabaya. Penelitian ini bersifat observational dengan desain cross-sectional dan analitik. Populasi penelitian adalah sebesar 100 orang. Besar sampel ditentukan dengan metode simple random sampling dan diperoleh 80 orang. Data didapatkan melalui penilaian pengetahuan sebelum dan sesudah penyuluhan kesehatan. Hasil penilaian menunjukkan terdapat peningkatan tingkat pengetahuan. Remaja putri dengan tingkat pengetahuan baik meningkat dari 64 orang (80%) menjadi 75 orang (83,75%). Dan tingkat pengetahuan cukup dari 16 orang (20%) menjadi 5 orang (6,25%). Hasil uji statistika dengan menggunakan Wilcoxon Signed Rank Test menunjukkan bahwa nilai p value (0,000) > α (0,05). Artinya bahwa terdapat perbedaan antara pengetahuanvsebelum dan sesudah penyuluhan kesehatan. Disarankan kepada remaja putri untuk melakukan SADARI secara rutin dan sekolah melakukan penyuluhan kesehatan siswanya. Kata kunci: kanker payudara, SADARI, pengetahuan, penyuluhan
Adenosine Deaminase Activity and HLA-DRB as Diagnostic Markers for Rheumatoid Arthritis
Authors: Valadbeigi Shirin , Saghiri Reza , Ebrahimi-Rad Mina , Khatami Shohreh , Akhbari Hadi 
Published: December 2018

Background:Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine Deaminase (ADA) isoenzymes could be useful and specific.Objective:The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases.Methods:Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive Protein (CRP), Rheumatoid Factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*01,*04 and *10 was detected using PCR-SSP.Results:ADA activity, particularly ADA2 level, was significantly higher among RA group (Pv <0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (Pv <0.05). The allele prevalence of DRB1*01 was significantly higher in RA patients (13.1%) compared with control group (5.5%, respectively) (P <0.05, Bonferroni adjustment P<0.003). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively.Conclusion:Increased tADA level and the frequency of DRB1*10 and *01 caused susceptibility to RA.
New Resensitizers for the Nicotinic Acetylcholine Receptor by Ligand-Based Pharmacophore Modeling
Authors: Wein Thomas , Wanner Klaus T. , Rappenglück Sebastian , Sichler Sonja , Niessen Karin V. , Seeger Thomas , Worek Franz , Thiermann Horst 
Published: December 2018

Introduction: Irreversible inhibition of the acetylcholinesterase upon intoxication with organophosphorus
compounds leads to an accumulation of acetylcholine in the synaptic cleft and a subsequent
desensitization of nicotinic acetylcholine receptors which may ultimately result in respiratory
failure. A direct intervention at the nicotinic acetylcholine receptor (nAChR) was proposed as an alternative
therapeutic approach to the treatment with atropine and oximes.
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Methods: The bispyridinium compound MB327 has been found to recover functional activity of
nAChR thus representing a promising starting point for the development of new drugs for the treatment
of organophosphate poisoning. Recent solid-supported membrane-based electrophysiological
experiments have identified symmetrically substituted bispyridinium compounds e.g. MB327, MB583,
and PTM0001 that are able to resensitize nAChR of Torpedo californica. In addition, six compounds
have been found not to show any resensitizing potential and were thus classified as inactive. This set
of active and inactive bispyridinium compounds was taken to develop a pharmacophore model and in
silico screening of a virtual database of bispyridinium compounds to identify new compounds that are
able to restore the functional activity of desensitized nAChR.

Results:
Screening of a virtual compound database of symmetrically substituted bispyridinium compounds
with the derived pharmacophore yielded several promising compounds which satisfy the pharmacophore
and ought to have the same or even better resensitizing effect on nAChR as the parent
compound MB327.
Interference of Gold Nanoparticles with In vitro Endotoxin Detection Assays
Authors: Vetten Melissa A. , Gulumian Mary 
Published: December 2018

Background:
Endotoxin-free engineered nanoparticle suspensions are imperative for their
successful applications in the field of nanomedicine as well as in the investigations in their toxicity.
Gold nanoparticles are known to interfere with various in vitro assays due to their optical properties
and potential for surface reactivity. In vitro endotoxin testing assays are known to be susceptible to
interference caused by the sample being tested.

Objective:
This study aimed to identify a preferred assay for the testing of endotoxin contamination
in gold nanoparticle suspensions.

Methods:
The interference by gold nanoparticles on three assays namely, the commonly used
limulus amebocyte lysate chromogenic assay, the limulus amebocyte lysate gel-clot method, and the
less common recombinant Factor C (rFC) assay, was tested.

Results:
Possible interference could be observed with all three assays. The interference with the absorbance-
based chromogenic assay could not be overcome by dilution; whilst the qualitative nature
of the gel-clot assay excluded the possibility of distinguishing between a false positive result due to
enhancement of the sensitivity of the assay, and genuine endotoxin contamination. However, interference
with the rFC assay was easily overcome through dilution.

Conclusion:
The rFC assay is recommended as an option for endotoxin contamination detection in
gold nanoparticle suspensions.
Precision Displacement Control of a Diamond-shaped Amplifying Mechanism Driven by Piezoelectric Actuator Based on Fuzzy Fractionalorder PIλDμ Controller
Authors: Lu Shizhou , Liu Wei , Zhu Chenyu , Zhai Qiang , Cao Renshui 
Published: December 2018

Background:As a high-performance functional material, stacked piezoelectric actuator can produce a displacement under the effect of changing voltage. Its advantages of fast response and easy operation make it to be widely applied in the precision structure field. However, its small displacement stroke and hysteresis nonlinearity affect the accuracy of the output.:In the next step, some experiments were undertaken based on the constructed platform.Methods:In order to enlarge the displacement of piezoelectric actuator and reduce the influence of hysteresis, this study designs a diamond-shaped amplifying mechanism to amplify the output of the piezoelectric actuator, and then develops a self-tuning fuzzy fractional-order PIλDμ controller for the high precision displacement control of the proposed amplifying mechanism. After analyzing the working principle and modeling the amplifying mechanism, the fractional-order PIλDμ control model of the proposed mechanism was built and discretized according to the theoretical base of the fractional calculus in the time domain. Moreover, the fuzzy control algorithm was also introduced to achieve self-turning of parameters. Besides, the amplifying mechanism was also adopted for a microdroplet jetting dispenser to verify the practicability of the mechanism and control strategy. In the next step, some experiments were undertaken based on the constructed platform.Results:Experiments show that the displacement overshoots, the times of reaching a steady state of the traditional integer-order controller and the fractional-order controller are 5.08%, 1.17% and 17.25 s, 12.00 s, respectively. However, the fuzzy PIλDμ controller lowers the overshoot and the time of reaching a steady state to 0.95% and 9.00 s, respectively. The control algorithm can not only improve the follow-ability of the output displacement of the proposed mechanism, but also maintain the deviation within the range of 0.4% after the displacement stroke is stable and reduce the entering time of the mechanism up to 47.8%. In actual application, the droplet volume of micro-droplet jetting dispenser under fuzzy fractional-order PID control method is more stable, and its repeatability accuracy can reach up to 1.6475%.Conclusion:Experimental results indicate that the self-tuning fuzzy fractional-order PIλDμ controller can significantly improve the tracking performances of the PID and the integer-order PID with regard to the amplifying mechanism with the advantages of good dynamic character and regulation precision. Furthermore, the diamond-shaped amplification mechanism and control strategy can be applied for some micro-droplet jetting dispensers used in microelectronic packaging, life science and 3D printing fields.
Recurrent Peripheral Giant Cell Granuloma: A Case Report
Authors: Barros de Alencar Catarina Ribeiro , Porto Damião Edgleys , Cavalcanti Alidianne Fábia Cabral , Cavalcanti Alessandro Leite 
Published: December 2018

Objective:This article describes a case of a Peripheral Giant Cell Granuloma (PGCG) in a girl.Introduction:PGCG is a relatively infrequent benign reactive lesion of the gingiva or alveolar ridge that develops in response to local irritation. Clinical appearance consists of a firm or soft smooth surface nodule in dissimilar colors of varying size with sessile or pedunculated implantation base. Radiographic features are generally nonspecific, thereby definitive diagnosis depends on microscopic examination to confirm the entity of PGCG.Case Report:A 6-year-old female patient was referred to the outpatient clinic of an Oral & Maxillofacial Surgery Department with the chief complaint of an intraoral swelling. The intraoral examination showed a painless sessile mass with exophytic growth similar to a tumorous lesion located on the mandibular alveolar ridge extending from distal aspect of right mandibular primary canine to mesial aspect of first permanent molar of the same side.Conclusion:Peripheral giant cell granuloma is a relatively uncommon lesion in children and potential for collaboration with the treatment in young patients should be considered for a successful therapeutic approach.
Global Stability and Optimal Control Analysis of Malaria Dynamics in the Presence of Human Travelers
Authors: Olaniyi Samson , Okosun Kazeem O. , Adesanya Samuel O. , Areo Emmanuel A. 
Published: December 2018

Introduction:
The impact of unguarded human movement on the spread of infectious disease like malaria cannot be underestimated. Therefore, this study examines the significance of short term human travelers on malaria transmission dynamics.

Methods:
A non-autonomous system of ordinary differential equations incorporating four control strategies, namely personal protection, chemo-prophylaxis, chemotherapy and mosquito-reduction effort is presented to describe the dynamics of malaria transmission between two interacting populations. Suitable Lyapunov functions are constructed to analyze the global dynamics of the autonomous version. Moreover, the model which incorporates time-dependent vigilant controls is qualitatively analyzed with the overall goal of minimizing the spread of malaria and the associated costs of control implementation using the optimal control theory. An iterative method of forward-backward Runge-Kutta fourth order scheme is used to simulate the optimality system in order to investigate the effects of the control strategies on the magnitude of infected individuals in the population.

Results:
Analysis of the autonomous system shows that the disease-free equilibrium is globally asymptotically stable whenever the basic reproduction is less than unity and a uniquely determined endemic equilibrium is shown to be globally asymptotically stable whenever the associated basic reproduction number exceeds unity. In the case of non-autonomous system, necessary conditions for the optimal control of malaria are derived. It is shown that adherence to the combination of the control strategies by short term human travelers helps in curtailing the spread of malaria in the population.
Capturing Day-to-day Diurnal Variations in Stability in the Convective Atmospheric Boundary Layer Using Large Eddy Simulation
Authors: Nielson Jordan , Bhaganagar Kiran 
Published: December 2018

Introduction:Large Eddy Simulation (LES) modelers must begin to answer the question of how to better incorporate large datasets into simulations. This question is important because, at a given location, the diurnal, seasonal, and day-to-day variations of atmospheric stability have significant consequences for the power generated by wind turbines. The following study provides a methodology to obtain discrete values of surface flux, inversion height and geostrophic wind for LES using field data over multiple diurnal cycles (averaged over a month) at 12 Local Time (LT) (during the convective ABL). The methodology will allow the discrete LES to quantify the day-to-day variations over multiple diurnal cycles.Methods:The study tests the hypothesis that LES can capture the mean velocity and TKE profiles from the averaged variations in surface heat flux at 12 LT measured in the field (mean, +1 standard deviation, and -1 standard deviation). The discrete LES from the mean, +1 standard deviation, and -1 standard deviation surface heat flux represent the variations in the ABL due to the day-to-day variations in surface heat flux. The method calculates the surface heat flux for the NREL NWTC M5 dataset. The field data were used to generate Probability Density Functions (PDFs) of surface heat flux for the January and July 12 LT. The PDFs are used to select the surface heat fluxes as inputs into the discrete LES.Results / Conclusion:A correlation function between the surface heat flux and the boundary layer height was determined to select the initial inversion height, and the geostrophic departure function was used to determine the geostrophic wind for each surface heat flux. The LES profiles matched the averaged velocity profiles from the field data to 4% and the averaged TKE profiles to 6% and, therefore, validated the methodology. The method allows for further quantification of day-to-day stability variations using LES.
Synthesis, α-Amylase Inhibitory Activity and Molecular Docking Studies of 2,4-Thiazolidinedione Derivatives
Authors: Naeem Fawad , Nadeem Humaira , Muhammad Aun , Zahid Muhammad Ammar , Saeed Adil 
Published: December 2018

Introduction:2,4-Thiazolidinedione and its derivatives exhibit a variety of pharmacological activities including antidiabetic, antiviral, antifungal, anti-inflammatory, anti-cancer and aldose reductase inhibitory activities. Keeping in mind the pharmacological potential of 2,4-Thiazolidinedione derivatives as antidiabetic agents, seven arylidene derivatives of 2,4-thiazolidinedione1(a-g)and four corresponding acetic acid derivatives 2(a-d)have been synthesized by a three-step procedure.Methods:All the synthesized compounds were characterized by elemental analysis, FTIR,1HNMR, and13CNMR and further screened for their α-amylase inhibitory potential.Results:All the compounds1(a-g)and2(a-d)showed varying degree of α-amylase inhibition, especially compound1c(IC50= 6.59μg/ml),1d(IC50=2.03μg/ml) and1g(IC50= 3.14μg/ml) displayed significantly potent α-amylase inhibition as compared to the standard acarbose (IC50= 8.26μg/ml). None of the acetic acid derivatives of 5-arylidene-2,4-thiazolidinedione showed prominent inhibitory activity. Docking results indicated that the best binding conformation was found inside the active site cleft of enzyme responsible for hydrolysis of carbohydrates.Conclusion:Therefore, it can be concluded that 2,4-thiazolidinedione derivatives can be used as effective lead molecules for the development of α-amylase inhibitors for the management of diabetes.
Effect of Cash Transfer on School Dropout Rates using Longitudinal Data Modelling: A Randomized Trial of Research Initiative to Support the Empowerment of girls (RISE) in Zambia
Authors: Sampa Mutale , Jacobs Choolwe , Musonda Patrick 
Published: December 2018

Background:
School dropout rates, as well as early marriages and pregnancies, are high among adolescent girls in rural Zambia. In the quest to fight this, the Research Initiative to Support the Empowerment of girls (RISE) trial has been providing cash transfers and community dialogues to adolescent girls in rural Zambia. The overall goal of the study was to establish the effects of cash transfers on adolescent girls’ school dropout rates in selected provinces of Zambia.

Methods:
The study was nested in the RISE trial which is a cluster randomized trial conducted in Central and Southern provinces of Zambia. A total of 3500 adolescent girls were included in the study. Random intercepts model was used to model the individual effects estimates, taking account of the dependency that was likely to occur due to the repeated measurements and clustering in the study.

Results:
Girls who were married or cohabiting and girls who had given birth, were significantly less likely to be in school (OR=0.004, 95% CI {0.001-0.02}, p-value=<0.0001) and (OR=0.003, 95% CI {0.02-0.04}, p-value=<0.0001) respectively. Consistently receiving cash transfers increased the chance of a girl being in school (OR=8.51, 95% CI {4.50-16.08}, p-value=<0.0001). There was an indication that the combined intervention arm had a reduced chance of girls being in school, however, we could not rule out chance finding (OR=0.89, 95% CI {0.59-1.36}, p=0.606).

Conclusion:
The study found that marriage or cohabiting and giving birth whilst in school reduce the chances of the girl continuing schooling. No significant association could be attributed to the type of intervention, However, consistent receipt of cash transfers was shown to be a protective factor of school dropout rates in the study.
Effects of Various Agroindustrial Wastes on Nutrition Yield and Quality of Canola (Brassica napus L.)
Authors: Seçer Müzeyyen , Ömer Lütfü Elmaci , Ceylan Şafak 
Published: December 2018

Introduction:Canola is an important agricultural crop generally grown for oil and biofuel generation.Materials and Methods:The agroindustrial solid wastes of oregano and cumin wastes were used in a vegetation experiment to determine their effect on the nutrition, yield and quality of the canola plant (Brassica napusL.) The experiment was performed on 12 plots of 6 m2and was conducted with four treatments of composted oregano and cumin wastes, mineral fertilization and control in three replications. Physical and chemical properties and macro-micro nutrients were determined in the soils at the beginning and the end of the experiment.Results and Discussion:The leaves showed sufficient levels of N, P, K, Ca, Mg and low sufficient levels of Na, Fe, Cu, Zn and Mn. The boron content of the leaves was insufficient. Manganese and B were affected significantly by the applications. The applications did not affect plant height, shoot and carob number per plant, and seed numbers per carob significantly. Statistically, the highest number of plants per m2was observed in the plots to which cumin wastes were applied, and these plots also showed the maximum yield.Conclusion:Seed yield, protein and oil percentages were not affected significantly by the applications.