bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure Activity Relationship of 4-Amino-2-thiopyrimidine Derivatives as Platelet Aggregation Inhibitors
Authors: Cacciari Barbara , Crepaldi Pamela , Cheng Chun Yan , Bossi Elena , Spalluto Giampiero , Federico Stephanie , Jacobson Kenneth A. , Cattaneo Marco 
Published: February 2019

Background:
Platelet aggregation plays a pathogenic role in the development of arterial
thrombi, which are responsible for common diseases caused by thrombotic arterial occlusion, such
as myocardial infarction and stroke. Much efforts are directed toward developing platelet aggregation
inhibitors that act through several mechanisms: The main antiplatelet family of COXinhibitors,
phosphodiesterase inhibitors, and thrombin inhibitors. Recently, the important role in
the platelet aggregation of adenosine diphosphate (ADP)-activated P2Y12 and P2Y1 receptors, Gprotein
coupled receptors of the P2 purinergic family, has emerged, and their inhibitors are explored
as potential therapeutic antithrombotics. P2Y12 inhibitors, i.e. clopidogrel, prasugrel, ticagrelor,
and cangrelor, are already used clinically to reduce coronary artery thrombosis risk and
prevent acute coronary syndromes. The search for new P2Y12 inhibitors, with better risk-to-benefit
profiles is still ongoing.

Methods:
Several years ago, our group prepared a series of 6-amino-2-thio-3H-pyrimidin-4-one
derivatives that displayed an interesting platelet aggregation inhibiting activity. In order to probe
the structure-activity relationships and improve their inhibitory effects of these compounds, we
synthesized variously substituted 6-amino-2-thio-3H-pyrimidin-4-one derivatives and substituted
4-amino-2-thiopyrimidine-5-carboxylic acid analogues. All the synthesized compounds were
tested by light trasmission aggregometry (LTA) as inducers or inhibitors of platelet aggregation in
citrated platelet-rich plasma (PRP).

Results:
Among the 6-amino-2-thio-3H-pyrimidin-4-one derivatives, compounds 2c and 2h displayed
marked inhibitory activity, with a capability to inhibit the ADP(10-6M)-induced platelet aggregation
by 91% and 87% at 10-4M concentration, respectively. Selected 4-amino-2-
thiopyrimidine-5-carboxylic acid derivatives were tested as P2Y12 and P2Y1 antagonists and found
to display negligible activity.

Conclusion:
These negative findings demonstrated that this heterocyclic nucleus is not a useful
common pharmacophore for developing P2Y-dependent inhibitors of platelet aggregation. Nevertheless,
compounds 2c and 2h could represent a new chemotype to further develop inhibitors of
platelet aggregation.
Antibacterial and Cytotoxic Effects of the Cultivated Ruta chalepensis
Authors: Gali Lynda , Bedjou Fatiha 
Published: February 2019

Background:
Ruta chalepensis is a shrub from the Mediterranean basin widely used in the
traditional medicine. The plant presents an interesting composition containing alkaloids, coumarins and
volatile oil. The present work aims to study the antibacterial and the cytotoxic effects of the ethanol
extract, its fractions, and the alkaloid extract from the cultivated Ruta chalepensis.

Methods:
Extracts were tested against five bacterial strains using the agar well diffusion method and the
broth micro-dilution technique for the determination of the Minimum Inhibitory Concentration (MIC).
Brine shrimp assay was used to evaluate the cytotoxicity.

Results:
Chloroform fraction exhibited a strong antibacterial activity against S. aureus, and B. subtilis
with inhibition diameters of 25.5±0.7 and 18.5±2.12mm at 50mg/ml and 100mg/ml, respectively. Butanol
and aqueous fractions were found to be inactive against all the tested strains. Ethyl acetate was the
only active fraction against E. coli. Alkaloids showed a strong growth inhibition of B. subtilis and S.
aureus at low concentrations (22.5±0.71 and 18.00±0,00mm, respectively at 20mg/ml). The cytotoxicity
evaluation using the brine shrimp larvae indicated a high effect of alkaloids with an LC50 of 27.51μg/ml
supporting their antibacterial activity.

Conclusion:
These findings suggest a possible use of Ruta chalepensis as a source of antibacterial and
anti-proliferative agents.
Development and Validation of a Rapid and Efficient Method for Simultaneous Determination of Scopolin and Scopoletin in Convolvulus Species by Ultra- high-performance Liquid Chromatography-Tandem Mass Spectrometry
Authors: Al-Rifai Asma’a , Aqel Ahmad , Al-Saleem Muneera 
Published: February 2019

Background:
Convolvulus species are extensively used in traditional medicines for the
treatment of peptic ulcer diseases primarily associated with the presence of many bioactive compounds,
such as coumarins.

Methods:
A validation and improvement of a rapid, sensitive and simple technique for bioactive compounds
analysis of scopolin and scopoletin in Convolvulus pilosellifolius (CP) and Convolvulus
austroaegyptiacus (CA) plant extracts using UHPLC-MS/MS were performed. Both plants extracts
were subjected to high-resolution DART-ToF-MS technique for fast profiling of their constituents.

Results:
DART-ToF-MS spectra proved the presence of experimental mass at 193.05137 and
355.10371 m/z in the extract of CA plant and at 193.05084 and 355.10365 m/z in CP plant extract for
scopolin and scopoletin compounds, respectively. The total chromatographic analysis time was less
than 10 min with excellent resolution and negligible matrix effect. The validated parameter showed
good linearity (R2
≥0.998) over a wide concentration range of 0.05-10.0 μg mL-1 for both scopolin and
scopoletin, detection limits of scopolin and scopoletin were 0.03 and 0.01 μg mL-1, respectively. The
method also showed good intraday and interday precisions (RSD<4.33%). The recovery percentage
values were between 97.04 and 99.97% at three added concentration limits. The highest content of
scopolin (3.485 mg g-1) and scopoletin (0.795 mg g-1) was detected in CA ethanolic extract. The studied
plants were finally compared with all previous reports in terms of scopolin and scopoletin content.

Conclusion:
The results indicate that the suggested method can be used for regular analysis of active
compounds in medicinal plant extracts.
Comparison Study on the Contents of Eight Flavonoids in three Different Processed Products of Scutellariae Radix using Ultra-high Performance Liquid Chromatography Coupled With Triple-Quadrupole Mass Spectrometry
Authors: Yang Yuedong , Zhi Hao , Yan Baofei , Tian Yi , Shen Jianping , Zhu Xingyu , Li Zhipeng 
Published: February 2019

Background:
The simultaneous determination of multiple components in a sample is an important
factor in the quality control of traditional Chinese medicines and can give an indication of potential
clinical applications.

Introduction:
A rapid and sensitive method has been introduced for the simultaneous quantitative analysis
of eight bioactive flavonoid constituents from Scutellariae Radix using ultra-high performance
liquid chromatography coupled with triple quadrupole tandem mass spectrometry.

Methods:
The separation was performed on a Waters Acquity UPLC C18 column (2.1 mm×100 mm, 1.7
μm), under optimized mass spectrometry conditions, with a flow rate of 0.3 mL/min. The column temperature
was maintained at 35°C and the injection volume was 3 μL.

Results:
The method showed a good linear relationship of each component; all R2 values were above
0.9990 in the experiment. The RSDs of the precision test, repeatability test, stability test and recovery
test were all not more than 2.86 %. We found that the total percentage amounts of the eight flavonoids
were 22.19%, 18.63% and 10.86% in Raw Scutellariae Radix (RSR), Wine Scutellaria Radix (WSR)
and Scutellaria Radix Charcoal (SRC) respectively.

Conclusion:
The method was successfully applied to the simultaneous determination of the eight bioactive
flavonoids of Raw Scutellariae Radix, Wine Scutellaria Radix and Scutellaria Radix Charcoal.
The Hypolipidemic Effect of Active Components in the Decoction of Alisma Orientale and their Chemical Structures Characterized by LC-QTOF-MS/MS
Authors: Shi Qingxin , Zhang Qiongguang , Xiang Xingliang , Tian Ji , Xie Yun , Jin Shuna , Yuan En , Huang Rongzeng , Song Chengwu 
Published: February 2019

Background:
The decoction of Alisma orientale is used as a traditional medicine for the
treatment of hyperlipidemia in China with a long clinical history. The present study undertook a detailed
investigation to compare the hypolipidemic effect and chemical composition of two extracts of
Alisma orientale prepared by boiling water and organic reagent, respectively.

Methods:
The hyperlipidemic mice were induced by administration of a High-Fat Diet (HFD) for one
month. The body weight of mice and the serum Cholesterol (TC), high-density lipoprotein cholesterol
(HDL-C), Superoxide Dismutase (SOD), malondialdehyde (MDA), aspartate Aminotransferase (AST)
and alanine aminotransferase (ALT) levels were determined. Meanwhile, the chemical constituents of
the extracts were characterized using liquid chromatography-quadrupole time of flight mass spectrometry
(LC-QTOF-MS/MS).

Results:
The better hypolipidemic effect was observed in mice administered with the decoction compared
to that of methanol extract. In addition, the liver protective effects were confirmed by the photographs
stained with oil red lipid stain. As for the chemical constituents in the extracts, twenty major
components were identified or characterized using LC-QTOF-MS/MS. Among them, eight oligopeptides
were characterized for the first time and proved to only exist in the decoction of Alisma orientale.

Conclusion:
It is reasonable to assume that the oligopeptides may partially contribute to the hypolipidemic
effect of Alisma orientale. The structural characterization procedures also provide a suitable
method to analyze oligopeptide analogues in plant samples.
Electrochemical Synthesis of Conducting Polymers Involving Deep Eutectic Solvents
Authors: Golgovici Florentina , Anicai Liana , Florea Andreea , Visan Teodor 
Published: February 2019

Background:Deep eutectic solvents (DESs) represent a new generation of ionic liquids which are widely promoted as “green solvents”. They are gaining widespread application in materials chemistry and electrochemistry. DESs are defined as eutectic mixtures of quaternary ammonium salt with a hydrogen bond donor in certain molar ratios. Their use as solvents for electrochemical synthesis of conducting polymers could influence the polymer properties and reduce their economic cost.Objective:This review presents the most recent results regarding the electropolymerization of common conductive polymers involving choline chloride based ionic liquids. New findings from our laboratory on the electrochemical growth of conductive polymers are also discussed.Methods:The electrochemical polymerization mechanisms during synthesis of polypyrrole (PPy), polyaniline (PANI) and poly(3,4-ethylenedioxythiophene) (PEDOT) using various formulations of DESs are reviewed, as well as their characteristics, mainly from surface morphology view point.Results:Some general information related to the preparation and characterization of DESs is also presented, followed by an overview of the recent advances in the field of electropolymerization using DESs.Conclusion:Electropolymerization of conducting polymers involving DESs represents an attractive route of synthesis due to their compositional flexibility which makes possible the preparation of unlimited formulations further influencing the polymer morphology and properties. The use of these inexpensive eutectic mixtures has a large potential to contribute to the development of more sustainable technological processes meeting many of the required features characteristic to the green chemistry.
Gold Nanoparticles-based Bio-Sensing Methods for Tumor-related Biomedical Applications in Bodily Fluids
Authors: Li Lingling , Han Bing , Wang Ying , Shi Hai , Zhao Jing , Li Genxi 
Published: February 2019

Background:
Cancer is one of most dangerous diseases that seriously threaten human
health, while tumor biomarkers provide important information for clinical diagnosis and treatment of
cancers. Given the low abundance of tumor biomarkers in the bodily fluids at the early stage of cancers,
it is particularly important to develop bio sensing methods for accurate measurement of tumor
biomarkers with high sensitivity.

Objective:
Nowadays, gold nanoparticles (AuNPs) that have remarkable physical and chemical properties
are extensively used in the design of biosensing strategies. In this context, we mainly review
the research progress of AuNPs-based biosensing methods for tumor-related biomedical applications
in bodily fluids in recent years.

Results:
Optical, electrochemical and mass spectrometric biosensing methods using AuNPs are
widely used for excellent performances in the assay of tumor biomarkers.

Conclusion:
The existing methods demonstrate high clinical value, while challenges and expectation
of biosensing method in tumor-related biomedical application are also discussed.
Effect of Solvents on Phytochemicals Content and Antioxidant Activity of Ganoderma lucidum
Authors: Uddin Pk Moyen , Talukder Rabiul I. , Sarkar Mohammad K. I. , Rahman Tasnia , Pervin Rumana , Rahman Matiar , Zenat Elina A. , Akther Lima 
Published: February 2019

Introduction:
The aim of this study was to assess the induction of solvents on the total phenol and flavonoid content and also the antioxidant activity of Ganoderma lucidum extracts.

Materials & Methods:
In this study, two concentrations (100% and 75%) of diethyl ether, ethanol, butanol, chloroform, and acetone were used as extractants of Ganoderma lucidum. Total phenol and flavonoid contents were measured by spectrophotometric methods and 1, 1-diphenyl-2-picrylhydrazyl (DPPH). Free radical scavenging assay was used for the investigation of antioxidant activity.

Results & Discussion:
Extractants significantly affected the % yield of extract, the quantity of phenol and flavonoids and antioxidant activity of Ganoderma lucidum mushroom. The highest extraction yield, around 38%, was achieved by 75% acetone, followed by 100% acetone (about 36%) and 75% chloroform (approximate 21%). Hydro-acetone extract exhibited the most significant antioxidative properties (EC50 value; 645.55 µg/mL) comprised of a higher total of phenol content. In conclusion, the total phenol content encouraged the antioxidative potential of Ganoderma lucidum mushroom.

Conclusion:
These findings indicate that the selective extraction of Ganoderma lucidum shows significant biological activities.
Evaluation of Skin Permeability of Resveratrol Loaded Liposomes and Nanostructured Lipid Carriers using a Skin Mimic Artificial Membrane (skin-PAMPA)
Authors: Casamonti Marta , Piazzini Vieri , Bilia Anna Rita , Bergonzi Maria Camilla 
Published: February 2019

Background:The skin-PAMPA test is a quick and relatively deep tool in the early stages of drug discovery and formulation of dermal and transdermal delivery systems.Objective:This study focused on the application of the skin-PAMPA test to evaluate the permeation of Resveratrol (RSV) and also of two formulations, Liposomes (LP) and Nanostructured Lipid Carriers (NLC), prepared to improve RSV topical delivery.Methods:LP and NLC were physically and chemically characterized. Stability and in vitro release studies were also assessed in different pH media. The release results were applied to define the kinetic and mechanism of RSV release from the LP and NLC formulations. In vitro permeability was estimated through the skin-PAMPA and the antioxidant capacity was evaluated by DPPH test.Results:Nanoparticles have a spherical shape, dimensions suitable for skin application, and narrow size distribution. Encapsulation efficiency was 96.5% ± 2.1 for LP and 86.0% ± 2.4 for NLC. The formulations increased RSV solubility. Nanoparticles showed excellent physical and chemical stability during storage at 4°C for two months. In vitro release studies were performed at pH 5.5 and 7.4. The nanoparticles achieved a prolonged release of RSV. Skin-PAMPA proved an increased cutaneous permeability of RSV when loaded into LP or NLC. Both formulations maintained the antioxidant capacity of RSV, as evidenced by DPPH test.Conclusion:LP and NLC could be applied as drug delivery systems suitable for the topical delivery of the RSV. Skin-PAMPA has proved to be an effective tool for studying the permeability not only of the RSV but also of its formulations.
In silico Defining the Repeat-containing Proteins in the Acinetobacter baumannii Proteome, a Great Reservoir of Templates for Synthetic Biology
Authors: Rahbar Mohammad Reza , Zarei Mahboubeh , Nezafat Navid , Negahdaripour Manica , Ghasemi Younes 
Published: February 2019

Background:
Acinetobacter baumannii is an important nosocomial pathogen with
great ability to resist antibiotics. Tandem repeat proteins, abundant in prokaryotic proteomes,
attract attention due to their role in virulence and various biological processes. Defining repeat-
containing proteins may pave the way to find novel therapeutic targets as well as vaccine
candidate and give pieces of evidence of mechanisms of evolution and adaptation of organisms
to various environmental conditions.

Objective:
In the present study, we employed bioinformatics tools to define repeatcontaining
proteins within A. baumannii proteome for emphasizing the existence of natural
sources for synthesizing novel therapeutic and diagnosis material.

Results:
We defined various kinds of repeat modules in a number of proteins and compared
the abundance of these proteins in some closely related species. No significant difference
was observed in the count of repeat-containing proteins in different species. But the existence
of some important virulence factors is mentionable in our screening.

Conclusion:
Repeat containing proteins are important biological determinants of A. baumannii
and are well worth researching for finding drug targets and vaccine candidates. These
proteins can be served as a template for designing and synthesizing peptides for therapeutic
and diagnostic approaches.
Analysis and Synthesis of A Human Prakriti Identification System Based on Soft Computing Techniques
Authors: Madaan Vishu , Goyal Anjali 
Published: February 2019

Background:
The research done on the side effects of modern medicines motivates us to bring Ayurveda
back in our modern lifestyle. All allopathic medicines are artificially created and the chemicals used are
designed in such a way that they only cure the problem on the surface. This paper will discuss the how can
we retain our health for longer time.

Objective:
Building a trained and intelligent decision making system that can categorize any health or unhealthy
human being into a suitable category of human prakriti dosha.

Methods:
Proposed adaptive neuro-fuzzy inference system is trained using hybrid learning technique. Grid
Partitioning method is used for membership functions. Total 28 parameters that identify human prakriti are
reduced to 7 effective components to get maximum accuracy of results. System is trained with data of 346
healthy individuals to avoid biasing in the result.

Results:
The resulting system can answer to any individual about his prakriti dosha, based on its output one
can make changes in his lifestyle to avoid the effect of diseases in future. System is obtained with 94.23%
accuracy for identifying prakriti dosha.

Conclusion:
Building an ANFIS system trained with 346 individuals has shown the improved performance.
Consideration of 28 input parameters have actually enhanced the robustness of the system aimed to
identify human prakriti dosha.
Using Augmented Reality to Motivate Oral Hygiene Practice in Children: Protocol for the Development of a Serious Game
Authors: Amantini Susy Nazaré Silva Ribeiro , Montilha Alexandre Alberto Pascotto , Antonelli Bianca Caseiro , Leite Kim Tanabe Moura , Rios Daniela , Cruvinel Thiago , Lourenço Neto Natalino , Oliveira Thais Marchini , Machado Maria Aparecida Andrade Moreira 
Published: February 2019

Background
New technologies create possible new ways of action, interaction, and learning which is extremely relevant in the field of oral health education. There is a lack of protocol in using an immersive interactive ludic-educational interface to motivate oral hygiene practice in children by means of augmented reality.

Objective
This study aims to present a protocol on the development of a serious game to motivate oral hygiene practice in children.

Methods
A serious game will be designed by augmented reality techniques to improve toothbrushing effectiveness of children aged 6 to 10 years. The functional structure of this interface is activated by means of movements recognized by Kinect (Microsoft Corp). The toothbrushing technique will be available in the game, enabling the children to execute the movement in the virtual environment. By identifying errors, this game will be tailored to improve the oral health of children by correcting the technique and teaching the user the adequate toothbrushing method. A template analysis will be performed to identify barriers and facilitators in each scenario.

Results
After the implementation of the virtual interactive and immersive panels, enrollment will begin and evaluations will be made by means of questionnaires distributed to participants who interact with the game. Thus, an analysis of the product efficacy will be conducted. The expected outcome will be to obtain a digital instrument to motivate oral hygiene practice and enhance health awareness in children.

Conclusions
The serious game will support the prevention of oral diseases by sharing scientific research in the school environment and community.

International Registered Report Identifier (IRRID)
PRR1-10.2196/10987
Discontinuation and primary care visits in nonvalvular atrial fibrillation patients treated with apixaban or warfarin
Authors: Ramagopalan Sreeram V , Graham Sophie , Carroll Robert , Raluy-Callado Mireia , Nordstrom Beth L , Donaldson Robert , Colby Chris , Mehmud Faisal , Alikhan Raza 
Published: February 2019

Aim:
Nonvalvular atrial fibrillation (NVAF) requires long-term anticoagulation treatment, which may necessitate frequent primary care visits.
Materials & methods:
NVAF patients initiating warfarin or apixaban in 2012–2017 were identified from linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. A propensity score matched Cox regression model compared discontinuation risk. Primary care visits were compared via negative binomial regression.
Results:
A total of 2695 apixaban users were matched to warfarin patients. Discontinuation risk was lower with apixaban than warfarin (hazard ratio: 0.40; 95% CI: 0.35–0.46). Apixaban patients averaged 12.2 annual primary care visits, versus 17.1 for warfarin users (p < 0.001).
Conclusion:
Apixaban was associated with reduced rates of discontinuation and primary care visits compared with warfarin.
Coaching as a Knowledge Mobilization Strategy: Coaches' Centrality in a Provincial Research Brokering Network
Authors: Rodway Joelle 
Published: February 2019

Ontario’s Child and Youth Mental Health (CYMH) program is a provinciallysponsored initiative that aims to build school district capacity for developing research-informed school mental health policies. This article reports findings from a mixed-methods study that employs social network theory and analysis tools to explore the centrality of CYMH coaches within this research brokering network. Overall, CYMH coaches are central within these social networks, although the patterns of interaction differ from the program’s original design, with some coaches being more central than others. While formal CYMH professional development events appear to be the most direct approach to connecting research, policy, and practice, informal social networks provide the support necessary to make sense of research-based materials for use in local policymaking.