bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Cardiovascular Safety of Meglitinides
Authors: Philip Jim , Fernandez Cornelius James 
Published: October 2020

Abstract::
Meglitinides are a group of oral hypoglycemic medications currently approved for the
treatment of type 2 diabetes mellitus (T2DM). Two meglitinide molecules, Repaglinide and
Nateglinide, are presently in use. Repaglinide is preferred because of its superior glycemic efficacy.
They have modest efficacy with a mean decrement of glycosylated haemoglobin (HbA1c) ranging
between -0.2 to -1.50% with individual therapy. Additional HbA1c reduction can occur with
combination therapy with other oral hypoglycemics. This class of drugs is effective in controlling
postprandial hyperglycemia with minimal risk of hypoglycemia. It is also useful in patients with
variable meal timings, especially in the elderly, and in patients with renal failure. There are a
dearth of long-term studies on meglitinides to assess cardiovascular outcomes or mortality in
T2DM, although the Nateglinide and Valsartan in Impaired Glucose ToleranceOutcomes Research
(NAVIGATOR) study showed no difference between Nateglinide and placebo with regard to the
core composite cardiovascular outcomes. Based on a PubMed literature search using key words:
‘meglitinides’, ‘repaglinide’, ‘nateglinide’, ‘HbA1c’, ‘glycated haemoglobin’, ‘cardiovascular safety’,
‘cardiovascular events’, ‘cardiovascular outcome trials’, ‘type 2 diabetes mellitus’ and heart
failure, and combining the search terms using Boolean operators ‘AND’, ‘OR’ and ‘NOT’ as needed
we compiled current evidence for use of these oral hypoglycemic agents in clinical use. This article
is an attempt to review the efficacy and cardiovascular (CV) safety of Meglitinides to help clinicians
to use this class of oral hypoglycaemic agents prudently.
The Evaluation of Effect of Aurora Kinase Inhibitor CCT137690 in Melanoma and Melanoma Cancer Stem Cell
Authors: Sogutlu Fatma , Kayabasi Cagla , Yelken Besra O. , Asik Aycan , Gasimli Roya , Kipcak Sezgi , Susluer Sunde Y. , Avci Cigir B. , Gunduz Cumhur 
Published: October 2020

Background:
Dysregulation of the cell cycle is one of the main causes of melanomagenesis. Genomewide
studies showed that the expression of Aurora -A and -B significantly has been upregulated in melanoma.
However, there is no FDA approved drug targeting aurora kinases in the treatment of melanoma. In addition, the
development of resistance to chemotherapeutic agents in the treatment of melanoma and, as a result, the relapse
due to heterogeneous cell groups in patients is a second phenomenon that causes treatment failure. Therefore,
there is an urgent need for therapeutic alternatives targeting both melanoma and Melanoma Cancer Stem Cells
(MCSCs) in treatments. At this stage, cell cycle regulators become promising targets.

Objective:
In this study, we aimed to identify the effects of Aurora kinase inhibitor CCT137690 on the
cytotoxicity, apoptosis, cell cycle, migration, and colony formation and expression changes of genes related to
proliferation, cell death and cell cycle in melanoma and melanoma cancer stem cell. In addition, we investigated
the apoptotic and cytostatic effects of CCT137690 in normal fibroblast cells.

Methods:
We evaluated the cytotoxic effect of CCT137690 in MCSCs, NM2C5 referring as melanoma model
cells and WI-38 cells by using the WST-1 test. The effect of CCT137690 on apoptosis was detected via Annexin
V and JC-1 method; on cell cycle progression by cell cycle test; on gene expression by using RT-PCR, on
migration activity by wound healing assay and clonal growth by clonogenic assay in NM2C5 cells and MCSCs.
The effects of CCT137690 in WI-38, referring as healthy fibroblast cell, were assessed through Annexin V and
cell cycle method.

Results:
CCT137690 was determined to have a cytotoxic and apoptotic effect in MCSCs and melanoma. It
caused polyploidy and cell cycle arrest at the G2/M phase in MCSCs and melanoma cells. The significant
decrease in the expression of MMP2, MMP7, MMP10, CCNB1, IRAK1, PLK2 genes, and the increase in the
expression of PTEN, CASP7, p53 genes were detected.

Conclusion:
Aurora kinases inhibitor CCT137690 displays promising anticancer activity in melanoma and
especially melanoma cancer stem cells. The effect of CCT137690 on melanoma and MCSC may provide a new
approach to treatment protocols.
Different Effects of Fluoxetine and Paroxetine Combined with Vitamin D3 in Ovariectomized Rats Exposed to Unpredictable Stress
Authors: Fedotova Julia 
Published: October 2020

Background:
Vitamin D3 (VD3) is involved in the pathophysiological mechanisms of affective-related disorders and controls the functional activity of various hormonal systems. The complex interaction between estrogen and VD3 creates a neurobiological basis for their participation in similar behavioral disorders.

Objectives:
This study aimed to evaluate whether VD3 (5.0 mg/kg, s.c.) facilitates the antidepressant-like action of fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) by enhancing the antidepressant-like activity of these drugs in adult long-term Ovariectomized (OVX) rats subjected to Chronic Unpredictable Mild Stress (CUMS) protocol for 6 weeks.

Methods:
Sucrose Preference (SPT) and Forced Swim (FST) tests were performed to evaluate the anhedonia state and depressive symptoms, respectively. The Open-Field Test (OFT) was carried out to measure locomotor activity as well as grooming behavior produced by CUMS in long-term OVX rats. Corticosterone (CS)/estradiol (E2) in the serum was tested by rat ELISA kits. NF-kB, 5-HT/5-HIIA, and pro-inflammatory cytokine levels in the hippocampus were also examined by rat ELISA kits.

Results:
The results of this study suggest that combined treatment with fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) along with VD3 (5.0 mg/kg, s.c.) produces distinct effects on the depression-like behavior in long-term OVX/CUMS rats. Co-administration of fluoxetine (10.0 mg/kg, i.p.) with VD3 did not facilitate the antidepressant-like effects of fluoxetine in the long-term OVX rats with CUMS. On the other hand, co-treatment with paroxetine with VD3 resulted in faster and marked antianhedonic- and antidepressant-like effects in long-term OVX rats with CUMS as compared to treatment with paroxetine alone. The co-administration of paroxetine and VD3 attenuates stress-induced modifications of CS/E2 levels in the serum, as well as- proinflammatory cytokine/NF-kB/5-HT levels in the hippocampus of long-term OVX rats exposed to CUMS.

Conclusion:
Supplementation of VD3 (5.0 mg/kg, s.c.)to paroxetine (10.0 mg/kg, i.p.) facilitates antianhedonic- and antidepressant-like effects of paroxetine in adult long-term OVX rats exposed to CUMS.
Evaluation of In-vitro Antioxidant Potential, and Screening and Characterization of Phytochemicals Using hydroethanolic Leaf Extract of Caesalpinia Pulcherrima
Authors: Ilangovan Akila , Raghu Venkatesh , Venugopal Ramesh , Vijay Narayanan , Yellasamy Yellapa , Venkatramanan Akshaya 
Published: October 2020

Introduction:Novel Therapeutic Phytochemical studies are based on the use of plants in the production of drugs. The present study was carried out to perform the screening of phytochemicals and their quantitative analysis to assess in-vitro antioxidant activities of the hydroethanolic leaf extract of Caesalpinia Pulcherrima. FT-IR and GC-MS analyses of hydroethanolic leaf extract of Caesalpinia pulcherrima were also conducted.Methods:The investigation of qualitative and determination of quantitative phytochemical analysis were performed using standard procedures. The total alkaloid, flavonoid, phenols, and tannin content were determined spectrophotometrically. DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radical scavenging activity and ABTS (2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) free radical scavenging activity of hydroethanolic leaf extract of Caesalpinia pulcherrima were estimated by standard protocol. The identification of functional groups was made using plant leaf extracts by FTIR and GCMS.Results:The hydroethanolic leaf extract of Caesalpinia Pulcherrima gives positive results for alkaloids, flavonoids, phenols, carbohydrates, tannins, amino acids, and proteins. The content of total alkaloids, flavonoids, phenols, and tannins varies from 8.4 AE/g, 3.3 CE/g, 2.9, and 3.2 GAE/g, respectively. The antioxidant assay and IC50values were found to be DPPH (43.3μg/ml), ABTS (46.1 μg/ml), and ascorbic acid (41μg/ml), respectively and concentration ranging from 20 to 100 μg/ml. Functional groups were also identified using the extract by FTIR and GCMS.Conclusions:From this work, it can be concluded that the presence of phyto-component makes the plant useful in the treatment of various diseases. As such, it has been found that the hydroethanolic leaf extract of the plant contains more components and is beneficial for further research.
Research on an Enhanced Web Information Processing Technology based on AIS Text Mining
Authors: Li Canhui 
Published: October 2020

Background:
Background: To improve the information efficiency in web text mining, filtration is
utilized.

Methods:
A web content mining technology based on web text mining, augmented information
support (AIS), is proposed for improving the web text mining efficiency. Additionally, the AIS
technology is applied to the Xiangshan science conference website, and AIS4XSSC text mining
system is developed. The developed system is tested for its efficiency, and its main functions are
discussed.

Results:
192 documents are represented by 8352 vectors, and 192×8352 vectors are obtained; the
similarity between 192 vectors is calculated using the cosine of the included angle, 192×192
symmetric matrix is obtained, and 35 categories are formed by hierarchical clustering by using
similarity between texts.

Conclusion:
The results show that the AIS technology can effectively extract information from a
large number of web texts. The proposed system improves information retrieval efficiently and can
provide valuable information to users.
Data Object Exchange (DOEx) as a Method to Facilitate Intraorganizational Collaboration by Managed Data Sharing: Viewpoint
Authors: Hauser Ronald G , Bhargava Ankur , Talmage Ronald , Aslan Mihaela , Concato John 
Published: October 2020

Background
To help reduce expenses, shorten timelines, and improve the quality of final deliverables, the Veterans Health Administration (VA) and other health care systems promote sharing of expertise among informatics user groups. Traditional barriers to time-efficient sharing of expertise include difficulties in finding potential collaborators and availability of a mechanism to share expertise.

Objective
We aim to describe how the VA shares expertise among its informatics groups by describing a custom-built tool, the Data Object Exchange (DOEx), along with statistics on its usage.

Methods
A centrally managed web application was developed in the VA to share informatics expertise using database objects. Visitors to the site can view a catalog of objects published by other informatics user groups. Requests for subscription and publication made through the site are routed to database administrators, who then actualize the resource requests through modifications of database object permissions.

Results
As of April 2019, the DOEx enabled the publication of 707 database objects to 1202 VA subscribers from 758 workgroups. Overall, over 10,000 requests are made each year regarding permissions on these shared database objects, involving diverse information. Common “flavors” of shared data include disease-specific study populations (eg, patients with asthma), common data definitions (eg, hemoglobin laboratory results), and results of complex analyses (eg, models of anticipated resource utilization). Shared database objects also enable construction of community-built data pipelines.

Conclusions
To increase the efficiency of informatics user groups, a method was developed to facilitate intraorganizational collaboration by managed data sharing. The advantages of this system include (1) reduced duplication of work (thereby reducing expenses and shortening timelines) and (2) higher quality of work based on simplifying the adoption of specialized knowledge among groups.
Predictors of Walking Activity in Patients With Systolic Heart Failure Equipped With a Step Counter: Randomized Controlled Trial
Authors: Gade Josefine Dam , Spindler Helle , Hollingdal Malene , Refsgaard Jens , Dittmann Lars , Frost Lars , Mahboubi Kiomars , Dinesen Birthe 
Published: October 2020

Background
Physical activity has been shown to decrease cardiovascular mortality and morbidity. Walking, a simple physical activity which is an integral part of daily life, is a feasible and safe activity for patients with heart failure (HF). A step counter, measuring daily walking activity, might be a motivational factor for increased activity.

Objective
The aim of this study was to examine the association between walking activity and demographical and clinical data of patients with HF, and whether these associations could be used as predictors of walking activity.

Methods
A total of 65 patients with HF from the Future Patient Telerehabilitation (FPT) program were included in this study. The patients monitored their daily activity using a Fitbit step counter for 1 year. This monitoring allowed for continuous and safe data transmission of self-monitored activity data.

Results
A higher walking activity was associated with younger age, lower New York Heart Association (NYHA) classification, and higher ejection fraction (EF). There was a statistically significant correlation between the number of daily steps and NYHA classification at baseline (P=.01), between the increase in daily steps and EF at baseline (P<.001), and between the increase in daily steps and improvement in EF (P=.005). The patients’ demographic, clinical, and activity data could predict 81% of the variation in daily steps.

Conclusions
This study demonstrated an association between demographic, clinical, and activity data for patients with HF that could predict daily steps. A step counter can thus be a useful tool to help patients monitor their own physical activity.

Trial Registration
ClinicalTrials.gov NCT03388918; https://clinicaltrials.gov/ct2/show/NCT03388918

International Registered Report Identifier (IRRID)
RR2-10.2196/14517
REMOTION Blended Transdiagnostic Intervention for Symptom Reduction and Improvement of Emotion Regulation in an Outpatient Psychotherapeutic Setting: Protocol for a Pilot Randomized Controlled Trial
Authors: Bielinski Laura Luisa , Krieger Tobias , Moggi Franz , Trimpop Leonie , Willutzki Ulrike , Nissen Christoph , Berger Thomas 
Published: October 2020

Background
Emotion regulation has been identified as an important transdiagnostic factor relevant to the treatment of mental health disorders. Many empirically validated psychotherapeutic treatments incorporate elements targeting emotion regulation. Most of these treatment approaches are conceptualized as standard face-to-face treatments not as blended treatments, which include an internet-based intervention.

Objective
The aim of this study is to examine, for the first time, a new internet-based intervention—REMOTION—that will be provided transdiagnostically, as an add-on to psychotherapy, to provide a blended treatment format.

Methods
A total of 70 participants will be assigned (1:1 allocation ratio) to either the intervention group (REMOTION + psychotherapy) or the treatment-as-usual group that receives psychotherapy alone. To maximize external validity, a typical outpatient treatment sample of patients diagnosed with a range of disorders such as depression, anxiety disorders, and adjustment disorder will be recruited from a university outpatient clinic. Patients with bipolar disorder, psychotic disorders, or acute suicidality will be excluded from the study. The feasibility and potential effectiveness of the intervention will be examined by assessing data at baseline, 6 weeks (post), and 12 weeks (follow-up). The primary outcome is general symptom severity, assessed with the Brief Symptom Inventory. Secondary outcomes are emotion regulation, depressive symptoms, anxiety symptoms, health related quality of life, well-being, and a variety of feasibility parameters. Quantitative data will be analyzed on an intention-to-treat basis.

Results
Participant recruitment and data collection started in February 2020, and as of November 2020, are ongoing. Results for the study are expected in 2022.

Conclusions
This pilot randomized controlled trial will inform future studies using transdiagnostic blended treatment.

Trial Registration
ClinicalTrials.gov NCT04262726; http://clinicaltrials.gov/ct2/show/NCT04262726

International Registered Report Identifier (IRRID)
DERR1-10.2196/20936
Physical Activity Behavior Before, During, and After COVID-19 Restrictions: Longitudinal Smartphone-Tracking Study of Adults in the United Kingdom
Authors: McCarthy Hannah , Potts Henry W W , Fisher Abigail 
Published: October 2020

Background
The COVID-19 pandemic led to the implementation of worldwide restrictive measures to reduce social contact and viral spread. These measures have been reported to have a negative effect on physical activity (PA). Studies of PA during the pandemic have primarily used self-reported data. The single academic study that used tracked data did not report on demographics.

Objective
This study aimed to explore patterns of smartphone-tracked activity before, during, and immediately after lockdown in the United Kingdom, and examine differences by sociodemographic characteristics and prior levels of PA.

Methods
Tracked longitudinal weekly minutes of PA were captured using the BetterPoints smartphone app between January and June 2020. Data were plotted by week, demographics, and activity levels at baseline. Nonparametric tests of difference were used to assess mean and median weekly minutes of activity at significant points before and during the lockdown, and as the lockdown was eased. Changes over time by demographics (age, gender, Index of Multiple Deprivation, baseline activity levels) were examined using generalized estimating equations (GEEs).

Results
There were 5395 users with a mean age of 41 years (SD 12) and 61% (n=3274) were female. At baseline, 26% (n=1422) of users were inactive, 23% (n=1240) were fairly active, and 51% (n=2733) were active. There was a relatively even spread across deprivation deciles (31% [n=1693] in the least deprived deciles and 23% in the most [n=1261]). We found significant changes in PA from the week before the first case of COVID-19 was announced (baseline) to the week that social distancing restrictions were relaxed (Friedman test: χ22=2331, P<.001). By the first full week of lockdown, the median change in PA was 57 minutes less than baseline. This represents a 37% reduction in weekly minutes of PA. Overall, 63% of people decreased their level of activity between baseline and the first week of COVID-19 restrictions. Younger people showed more PA before lockdown but the least PA after lockdown. In contrast, those aged >65 years appeared to remain more active throughout and increased their activity levels as soon as lockdown was eased. Levels of PA among those classed as active at baseline showed a larger drop compared with those considered to be fairly active or inactive. Socioeconomic group and gender did not appear to be associated with changes in PA.

Conclusions
Our tracked PA data suggests a significant drop in PA during the United Kingdom’s COVID-19 lockdown. Significant differences by age group and prior PA levels suggests that the government’s response to COVID-19 needs to be sensitive to these individual differences and the government should react accordingly. Specifically, it should consider the impact on younger age groups, encourage everyone to increase their PA, and not assume that people will recover prior levels of PA on their own.
Feasibility and Effect of the Exergame BOOSTH Introduced to Improve Physical Activity and Health in Children: Protocol for a Randomized Controlled Trial
Authors: ten Velde Gabrielle , Plasqui Guy , Willeboordse Maartje , Winkens Bjorn , Vreugdenhil Anita 
Published: October 2020

Background
Despite the well-known beneficial health effects of physical activity (PA), the majority of Dutch primary school children do not meet the recommended PA guidelines. Although there is growing evidence on the effectiveness of exergames for PA in children, there is limited evidence on their effect on health outcomes, such as cardiovascular health and health-related quality of life (HRQOL), and on factors influencing their effectiveness and feasibility. The exergame BOOSTH uses a wrist-worn activity tracker to measure steps per day. As a reward for the performed PA, children can unlock levels in the online BOOSTH game. In addition, “BOOSTH battle” enables competition between groups.

Objective
This protocol describes a cluster randomized controlled trial in 16 primary schools in the Netherlands investigating the effect of BOOSTH on moderate-to-vigorous PA (MVPA) using accelerometry. Secondary aims are to investigate the feasibility of BOOSTH (mixed methods: questionnaires and focus group interviews) and its effect on cardiovascular risk factors (anthropometrics, blood pressure, and retinal microvasculature) and HRQOL.

Methods
Stratification variables and relevant variables related to outcomes (such as BMI [z-score], sex, age, and parenting style) and/or missingness will be taken into account. Measurements will be performed at baseline and after 3, 6, and 12 months.

Results
The study has received funding from Province Limburg (SAS-2015-04956) and received ethical approval from the Medical Ethics Committee of Maastricht University Medical Centre (METC172043/NL64324.068.17). The results of the analyses are expected to be published in 2021.

Conclusions
With this study, the ability of the exergame BOOSTH to increase PA and improve health in children of primary school age will be investigated. The insights into effectiveness and feasibility will result in scientific and societal recommendations, which could potentially contribute to widespread implementation of exergames for children.

Trial Registration
ClinicalTrials.gov NCT03440580; https://clinicaltrials.gov/ct2/show/NCT03440580.

International Registered Report Identifier (IRRID)
DERR1-10.2196/24035
Peran Perceived Organizational Support terhadap Work Engagement Karyawan
Authors: Mufarrikhah Jufi Lailatul , Yuniardi Muhammad Salis , Syakarofath Nandy Agustin 
Published: October 2020

Work engagement adalah sikap yang menggambarkan individu secara penuh terlibat dengan pekerjaannya, baik secara emosi maupun fisik dengan menunjukkan perilaku yang penuh semangat, penuh dedikasi, dan penghayatan dalam menunaikan pekerjaan. Salah satu faktor yang dapat berperan dalam meningkatkan work engagement adalah perceived organizational support, yaitu persepsi karyawan mengenai dukungan, kepedulian dan kontribusi organisasi terhadap kesejahteraan karyawannya. Tujuan penelitian ini adalah untuk menguji peran perceived organizational support terhadap work engagement karyawan. Subjek penelitian ini sejumlah 300 karyawan di bidang jasa dan produksi yang diperoleh menggunakan teknik quota sampling. Instrumen penelitian menggunakan SPOS (Survey Perceived Organizational Support) sebanyak 13 aitem dan UWES-17 (Utrecht Work Engagement Scale-17) sebanyak 17 aitem. Analisis data menggunakan teknik regresi linier sederhana dengan hasil perceived organizational support berperan positif terhadap work engagement karyawan (Nilai F = 152,442; p = <0,005). Adapun, sumbangan efektif yang diberikan oleh perceived organizational support dapat memprediksi work engagement sebesar 33,8%. Artinya, perceived organizational support terbukti memiliki peran terhadap tinggi rendahnya work engagement karyawan.