bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib
Authors: Kim Jae-Joon , Ryu Min-Hee , Yoo Changhoon , Beck Mo Youl , Ma Jung Eun , Kang Yoon-Koo 
Published: April 2019

Abstract

Background
Regorafenib at the standard intermittent dosing schedule proved effective in the GRID trial for refractory gastrointestinal stromal tumors (GISTs). However, this dosing schedule requires frequent dose reduction, and the progression of GISTs or tumor-related symptoms during the off-treatment period has also been noted in some patients. Therefore, we conducted this phase II trial to evaluate the efficacy and safety of regorafenib at a lower dose on a continuous dosing schedule.

Methods
Patients with measurable, metastatic, or recurrent GISTs who failed to respond to both imatinib and sunitinib were eligible for this study. Regorafenib 100 mg p.o. daily was administered continuously. The primary endpoint was disease control rate (DCR: complete response plus partial response [PR] plus stable disease [SD]) lasting for at least 12 weeks using RECIST version 1.1.

Results
The best response was PR in 2 (8%), SD in 16 (64%), and progressive disease in 6 (24%) patients. DCR lasting for at least 12 weeks was 64% (16 of 25). The median progression-free survival was 7.3 months (95% confidence interval, 5.9–8.6), and the 1-year survival rate was 64.5%. Ten patients (40%) experienced grade 3–4 toxicities, including hand-foot skin reaction (n = 4, 16%) and elevation of alanine aminotransferase (n = 2, 8%). Only six patients (24%) needed dose modification with a relative dose intensity of 95.0% for eight cycles in all patients.

Conclusion
Regorafenib at a lower dose on a continuous schedule might be an alternative treatment in patients with GISTs after failure of imatinib and sunitinib. Clinical trial identification number. NCT02889328

Implications for Practice
Regorafenib at the standard intermittent dosing schedule proved effective in the GRID trial for refractory gastrointestinal stromal tumors (GISTs). However, this dosing schedule requires frequent dose reduction, and the progression of GISTs or tumor-related symptoms during the off-treatment period has been noted in some patients. This study was to evaluate the efficacy and safety of regorafenib at a lower dose on a continuous dosing schedule. With good efficacy and acceptable safety profiles, regorafenib at a lower, continuously administered dose might be an alternative treatment in patients with GISTs after imatinib and sunitinib. Rechallenge of regorafenib may slow the disease progression.
A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD
Authors: Sakaguchi Yusuke , Hamano Takayuki , Obi Yoshitsugu , Monden Chikako , Oka Tatsufumi , Yamaguchi Satoshi , Matsui Isao , Hashimoto Nobuhiro , Matsumoto Ayumi , Shimada Karin , Takabatake Yoshitsugu , Takahashi Atsushi , Kaimori Jun-Ya , Moriyama Toshiki , Yamamoto Ryohei , Horio Masaru , Yamamoto Koichi , Sugimoto Ken , Rakugi Hiromi , Isaka Yoshitaka 
Published: April 2019

Significance Statement
Developing strategies for managing coronary artery calcification (CAC) in patients with CKD remains a clinical challenge. Previous experimental studies showed that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it. In a 2-year, open-label, randomized, controlled trial with a two-by-two factorial design, the authors investigated whether oral magnesium oxide or the oral carbon adsorbent AST-120 affected CAC progression in patients with stage 3−4 CKD with risk factors for CAC. In an interim analysis with 125 enrolled patients (96 of whom completed the trial), patients taking magnesium oxide experienced a significantly smaller percentage change in CAC score compared with controls (11.3% versus 39.5%). AST-120 was not associated with a similar significant slowing of CAC. Larger-scale trials are warranted to confirm these findings.

Background
Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it.

Methods
To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3−4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score.

Results
We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group’s dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups.

Conclusions
MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.
Türkçenin Eklemeli Yapısının İlkokul 1. Sınıf İlk Okuma Yazma Kitabında Kullanımı
Authors: ÇORA Hülya , SÖZER ÇAPAN Aylin 
Published: April 2019

İlkokul düzeyinde kazanılan okuma-yazma
becerisi, dil edinim sürecinin en önemli basamaklarındandır. Okuma-yazma
öğretilirken hangi yöntem kullanılırsa kullanılsın, her dilin kendi yapısal
özellikleri çerçevesinde hareket edilmesi gerekmektedir. Bu araştırmada
2017-2018 eğitim-öğretim yılında devlet okullarında okutulmaya başlanan İlkokul
1.Sınıf İlk Okuma Yazma Kitabı incelenmiş ve Türkçenin eklemeli dil olma
özelliğinden yararlanılarak kelime oluşturma durumu tespit edilmiştir.
Araştırmada, İlkokul 1.Sınıf İlk Okuma
Yazma Kitabı’nda 547 farklı sözcüğe rastlandığı, bu sözcüklerin 86’sının yapım
eki alarak oluşturulduğu, yapım eklerinin sistemli bir şekilde kullanılmadığı,
kullanılan yapım eklerinin ağırlıkla hece değeri taşımadığı, türetilen
sözcüklerin tekrarlanmadığı, kelime oluşturma sürecinde öğrencilerin üretici
kelime hazinesinin dikkate alınmadığı tespit edilmiştir.
B-lynch suture in the management of uterine atony during caesarean section section
Authors: C. Sudha H. , Pairu Jaganathan , . Kamalakshi 
Published: April 2019

Background: Third stage of labour is still the “sword of Damocle’s” hanging above an obstetrician , inspite of today’s advanced technologies and personal care .The importance in the management of this deadly stage lies in the anticipation of complications and being quick enough to treat them timely. Hence in such scenarios, B-lynch suture is most popular method in treatment of uterine atony during caesarean section. The objective is to study and evaluate the cases in which the B-Lynch suture was used to treat the uterine atony during caesarean section.Methods: A prospective randomized study consisting of 50 women with high risk factors for atonic pph during caesarean section were included as study group patients were subjected to B-Lynch suture application when conventional drugs failed to control PPH. Blood loss was measured using a measuring jar. The fall in Hb% and the need for blood transfusion, and the need for hysterectomy as a last resort to save the life was evaluated.Results: The average blood loss was 1490 ml and the majority of patients had reduction in Hb% from 1.1-1.5 gm% (52%), 36% of the patients did not receive any blood transfusion after B-Lynch suture, and in 80% of cases hysterectomy was avoided.Conclusions: Our study shows cases treated with B-Lynch procedure showed that it is an effective method of containing pph. It has the advantage of being applied easily and safely. It should be attempted when conservative management fails and before any radical surgery is considered.
Occurrence of hypothyroidism and its correlation with reproductive health problems: a cross sectional study
Authors: Kumar Selvi , Kotur Pushpa 
Published: April 2019

Background: Thyroid dysfunction is 10 times more common in women than in men. Hypothyroidism among women of reproductive age group is linked to menstrual irregularities, polycystic ovarian syndrome (PCOS), miscarriage and infertility. Several studies are available in the literature reporting regarding impact of hypothyroidism on one or the other isolated problems of reproductive health problems.Methods: This cross-sectional study is conducted including 290 participants having various reproductive health problems attending the gynaecology OPD of a rural based tertiary care hospital of Tamil Nadu during the year 2017-2018.These participants were investigated for thyroid dysfunction and its correlation of hypothyroidism with reproductive health problems viz. menstrual irregularities, Polycystic ovarian diseases (PCOS), infertility and pregnancy loss was studied.Results: It was observed that 80.6% of the 290 participants were euthyroid and 16.97% were hypothyroid, who presented with menstrual irregularities like menorrhagia (28.6%), oligomenorrhea (20.8%), amenorrhoea (21.3%), PCOS (28.6%), infertility (21.6%) and 23.8% hypothyroid women had pregnancy losses of varying number.Conclusions: In present study the occurrence of hypothyroidism was found to be 16.89%. Since hypothyroidism has close association with problems like menstrual irregularities, PCOS, miscarriages and infertility, thyroid function test should be routinely recommended for these women. Thyroid dysfunction can be corrected with simple, cost-effective treatment. This will help in improvement in pregnancy outcome and also avoid subjecting women for major surgeries for menorrhagia.
A study of the prevalence and severity of vitamin D deficiency in patient with diabetic foot and its association with vascular calcification and effect on healing
Authors: Kamble Ajonish , Swarnkar Manish 
Published: April 2019

Background: With the increasing prevalence of diabetes mellitus (DM), vitamin D (vit D) deficiency and vascular calcification is frequently observed in DM and is an indicator of diabetic peripheral vascular disease with variable implications. Due to the current limited understanding, this research was initiated. Aims and objective was to critically assess the prevalence and severity of vitamin D deficiency in patients with diabetic foot infection, the association between vascular calcification and vitamin D deficiency and effect on healing in diabetic foot patient with and without vitamin D deficiency.Methods: This observational study was conducted on 50 patients with diabetes mellitus. A detailed clinical history was recorded. Infection was confirmed by culture positivity and Doppler was used to detect vascular calcification. A follow-up for 3 weeks was done after which wound healing rate was assessed by change in wound surface area. Data was analyzed by Chi-square test and multivariate regression analysis.Results: 58% patients were diagnosed with vitamin D deficiency. 40% of patients found to have VC associated with DM. 100 % association of VC was found in patients with severe vitamin D deficiency. Vitamin D deficiency significantly correlated with vascular calcification (p=0.0001). A significant difference was observed in wound healing between the patients with and without vitamin D deficiency i.e. 3.14±2.04mm.sq and 4.36±1.39mm.sq.Conclusions: This study opens up an issue of recognizing vitamin D deficiency as a possible risk factor for diabetic foot infections and suggests the need for vitamin D supplementation.
The effect of renewable energy resources on regional development at the Thrace Region in Turkey
Authors: Dursun Bahtiyar 
Published: April 2019

<p><span>Countries seek to increase their economic growth and development levels effectively by using their production factors. The living standards at the aforementioned regions to rise up to the desired level via regarded economic development. The main purpose of the local and regional development is to enhance underdeveloped and developing regions’ limited income level and increase the business opportunities when compared with the developed regions. One of the prominent actors in the local and regional development is undoubtedly energy. Especially, recently, the demand to the renewable energy sources usage has been increasing.<span> </span>Renewable energy sources are evaluated according to their potentials. When a region has a renewable energy potential, establishing and running renewable energy sources based power plants will have positive effects on regional development. In this study, energy concept, which is one of the most important inputs of regional development, is discussed. Current usage potential of the Thrace Region’s current energy sources are presented and the effects of renewable energy sources on regional development are studied when they are used. </span></p>
CONFORMITY VERSUS INFORMALITY: ON RELATIONSHIP BETWEEN THE SOCIALISTS AND BUREAUCRATIC ELITE IN TURKEY
Authors: KAYNAR Mete Kaan 
Published: April 2019

Might the history of socialism in Turkey be
read as the history of “ostracism” and “proscription”
of the socialists from the political
system? On the other hand, might the socialists in Turkey be considered as a (one of the) outsider(s) or political (one of
the) enemy/enemies? This article wants to answer these questions and focus on
the problem of how Turkish socialists affect the political system, while they
are in mainly the outside of the system. The main argument of this article is
that the socialists can be considered as an outsider/public enemy of Turkish
political system by the bureaucratic elite,
but social relations occurred in the non-political institutions of Turkish
society have given opportunities to the socialists for affecting the political
system. In other words, nonpolitical
social institutions and daily social relations occurred in these institutions
have been the only space for the socialists to be politically active and to
illegally and informally affect the inside (formal institutions) of the political system. This is also one of the main
reason for the endemic informality and/or
illegality tradition in the Turkish left. The main aim of this study is to
explore the relationship, interactions, and
dilemmas regarding conformity versus illegality in line with the contradictive
evolvement of relations between the socialists and bureaucratic elite in the
Turkish political life.&nbsp;&nbsp;
ANALISIS PERMINTAAN KEDELAI DI INDONESIA
Authors: Pusposari Luthfiya Fathi 
Published: April 2019

<p>Indonesian population growth from year to year has increased, the population of Indonesia has incense for about 20 million people from the previous census data. Soybean is one of commodity most consumed by society census. Demand of soybean in this country 2,4 million tons per year, as much as 70% comes from imported soybean. Based on demand theory there are many factors that influence demand of goods, among others, the price of the goods themselves, the price of other goods, population, etc. Purpose of this research is to understand the elasticity of soybean’s demand in East Java and what variable which have the highest elasticity. The result of this research shows that variable of soybean's price is in elastic towards demand of soybean while variable of corn's price, income per capita and population is elastic. Variable which has sensitivity or the highest elasticity is variable of population</p><p>Keyword: Demand, Elasticity, Soybean</p>
Şanlıurfa’da çalışan aile sağlığı elemanlarının iş doyum düzeyleri ve etkileyen faktörler
Authors: GÖKLER Mehmet Enes , DURMUŞ Hasan 
Published: April 2019

Amaç: Çalışmada, Şanlıurfa ilinde hizmet veren aile
sağlığı elemanlarının demografik özellikleri, hizmet sundukları nüfusun
özellikleri, meslekleriyle ilgili düşünceleri, iş doyumları ve iş doyumu
üzerine etkili olabilecek değişkenlerin tespiti amaçlanmıştır. Yöntem: Çalışma,
Şanlıurfa’da görev yapan aile sağlığı elemanları üzerinde yapılan kesitsel
tipte bir araştırmadır. Hesaplanan örneklem hacmine göre ilçe dağılımı ve
kır-kent hizmet sunumu durumu göz önünde bulundurularak rasgele seçilen 150
aile sağlığı elemanına ulaşılması hedeflendi. Hazırlanan anket formu, aile
sağlığı elemanlarının sosyo-demografik ve mesleki özelliklerini ve Minnesota iş
doyum ölçeğini içermekteydi. Bulgular: Toplam 125 (%83.3) aile sağlığı elemanına
ulaşıldı. Çalışmaya katılan aile sağlığı elemanlarının %87.2’si kadın, %28.8’i
kırsalda hizmet vermekteydi. Çalışma grubunun genel, içsel ve dışsal iş doyum
puan ortalamaları sırasıyla 3.05±0.74, 2.79±0.79 ve 3.23±0.79 olarak bulundu.
Aile sağlığı elemanlarının %26.4’ünün iş doyumu yüksektir. Aile sağlığı
merkezinde kalıcı olarak çalışmayı düşünme [OR: 3.25 (1.18-8.96)] ve genel olarak işinden
memnun olma [OR: 4.46
(1.17-16.93)] iş doyumunun yüksek olmasında ilişkili faktörlerdir. Sonuç: Aile
sağlığı elemanlarının iş doyumu düzeyleri düşüktür. Aile sağlığı elemanları
birinci basamak sağlık hizmeti sunumun da önemli bir yere sahiptirler. İş
doyumlarını arttıracak düzenlemelerin yapılması hizmetin kalitesini
arttıracaktır.
KEEFEKTIFAN KONSELING KELOMPOK COGNITIVE BEHAVIOR UNTUK MENINGKATKAN REGULASI DIRI SISWA SMP
Authors: Habsy Bakhrudin All 
Published: April 2019

Self regulation is a process of self-regulation to set a mind and feeling to achieve a goal to be achieved. Self regulation determines student success, because students who have self-regulation can plan, evaluate, and control themselves. This study aims to determine the effectiveness of cognitive behavior group counseling can improve self-regulation of junior high school students. This study, using an experimental design with the Nonequivalent Control Group Design design. The data normality test results show that the control group is not normally distributed where the Sig.Asymp is smaller than 0.05. Whereas for the experimental group is normally distributed, where Sig.Asymp is greater than 0.05. Then it is obtained a hypothesis test that is appropriate for the control group using Wilcoxon test and for the experimental group using paired samples t test. Wilcoxon test results showed Sig.Asymp (2-tailed) of 0.080> 0.05, meaning that without giving counseling the Cognitive behavior group in the control group was not effective in improving student self-regulation, while for the paired samples t test test results showed Sig.Asymp ( 2-tailed) of 0.003 <0.05 means that the counseling behavior of Cognitive behavior groups in the experimental group is effective in enhancing student self-regulation. The research was carried out starting from April 2018 to January 2019, which took place at SMP Islam Mbah Bolong Jombang. Based on the results of the research, researcher gives suggestions for: 1) Teachers of Counseling Guidance, can be used as a reference that Cognitive behavior group counseling services can improve student self-regulation, 2) For further research: can apply Cognitive behavior counseling and can use different techniques in group counseling services so that they will gain a broader insight
Kinetic Modeling of pH‐Dependent Molybdenum(VI) Adsorption and Desorption on Iron Oxide‐Coated Sand
Authors: Sun Wenguang , Selim H. Magdi 
Published: April 2019

Core Ideas
Molybdenum(VI) sorption and kinetic rate are significantly reduced by increasing pH.
A Diffuse Layer Model simulated protonated monodentate complex was dominant at low pH.
A kinetic two‐site model successfully described Mo(VI) adsorption–desorption behavior.
Quantitative understanding of retention kinetics controlling molybdenum [Mo(VI)] on soil constituents such as iron oxide binding sites is crucial for accurately evaluating environmental risk of ground and surface water contamination. In this study, kinetic batch experiments were performed to investigate Mo(VI) adsorption–desorption behavior on iron oxide‐coated sand (IOCS) at different reaction conditions and time scale. Batch results indicated that adsorption of Mo(VI) on IOCS was highly nonlinear and kinetic, where both sorption and the extent of kinetics decreased with increasing solution pH. A two‐site model based on the heterogeneity of binding sites and variations of solution chemistry was developed to describe Mo(VI) adsorption and desorption on IOCS. The approach integrates kinetic nonlinear sorption into the surface complexation Diffuse Layer Model (DLM). Our results indicated that kinetic rate of non‐protonated monodentate complexes was much higher than that of protonated monodentate complexes. The kinetic model was capable of describing the experimental data with limited number model fitting parameters.
Design, Synthesis, Pharmacological Evaluation and Vascular Effects of Delphinidin Analogues
Authors: Legeay Samuel , Trân Kien , Abatuci Yannick , Justiniano Hélène , Lugnier Claire , Duval Olivier , Helesbeux Jean-Jacques , Faure Sébastien 
Published: April 2019

Background:
Among polyphenolic compounds suggested to prevent cardiovascular diseases (CVDs)
and to explain the “French paradox”, the anthocyanidin delphinidin (Dp) has been reported to support at least
partly the vascular beneficial effects of dietary polyphenolic compounds including those from fruits and related
products as red wine. It has also been highlighted that Dp interacts directly with the active site of estrogen receptor
α (ERα), leading to activation of endothelial NO synthase (eNOS) pathway thus contributing to the prevention
of endothelial dysfunction in mice aorta. However, anthocyanidins have very low bioavailability and despite a
well described in vitro efficacy, the very high hydrophilicity and physicochemical instability of Dp might explain
the lack of in vivo reported effects.

Objective:
The aim of this study was to identify new Dp analogues with increased lipophilicity and vasorelaxation
potential by a chemical modulation of its structure and to characterize the signaling pathway notably in relation
with ERα signaling and nitric oxide (NO) production.

Method:
OCH3-substituted delphinidin analogues were obtained through the coupling of the corresponding acetophenones
with substituted benzaldehydes. Prediction of resorption of the flavylium derivatives was performed
with the calculated logP and induction of vasorelaxation was performed by myography on WT and ERαKO mice
thoracic aorta rings and compared to Dp. NO production was evaluated in vitro on human primary endothelial
cells.

Results:
Eight Dp analogues were synthesized including four new flavylium derivatives. Two compounds (9 and
11) showed a strong increase of vasorelaxation potential and a theoretically increased bioavailability compared to
Dp. Interestingly, 9 and 11 induced increased O2
- or NO endothelial production respectively and revealed a novel
NO-dependent ERα-independent relaxation compared to Dp. We suggested that this mechanism may be at least in
part supported by the inhibition of vascular cyclic nucleotide phosphodiesterase (PDEs).

Conclusion:
The current study demonstrated that pharmacomodulation of the Dp backbone by replacement of
OH groups by OCH3 groups of the A and B rings led to the identification and characterization of two compounds
(9 and 11) with enhanced physio-chemical properties that could be associated to higher permeability capability
and pharmacological activity for the prevention of CVDs compared to Dp.