bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUV39H1-Mediated DNMT1 is Involved in the Epigenetic Regulation of Smad3 in Cervical Cancer
Authors: Zhang Li , Tian Sijuan , Zhao Minyi , Yang Ting , Quan Shimin , Song Lihua , Yang Xiaofeng 
Published: July 2020

Background:
Smad3 is a pivotal intracellular mediator for participating in the activation of multiple immune
signal pathway.

Objective:
The epigenetic regulation mechanism of the positive immune factor Smad3 in cervical cancer remains
unknown. Therefore, the epigenetic regulation on Smad3 is investigated in this study.

Methods:
The methylation status of SMAD3 was detected by Methylation-specific PCR (MS-PCR) and Quantitative
Methylation-specific PCR (MS-qPCR) in cervical cancer tissues and cell lines. The underlying molecular mechanisms of
SUV39H1-DNMT1-Smad3 regulation was elucidated using cervical cancer cell lines containing siRNA or/and overexpression system. Confirmation of the regulation of DNMT1 by SUV39H1 used Chromatin immunoprecipitation-qPCR
(ChIP-qPCR). The statistical methods used for comparing samples between groups were paired t tests and one-way
ANOVAs.

Results:
H3K9me3 protein which regulated by SUV39H1 directly interacts with the DNMT1 promoter region to regulate
its expression in cervical cancer cells, resulting in the reduce expression of the downstream target gene DNMT1. In
addition, DNMT1 mediates the epigenetic modulation of the SMAD3 gene by directly binding to its promoter region. The
depletion of DNMT1 effectively restores the expression of Smad3 in vitro. Moreover, in an in vivo assay, the expression
profile of SUV39H1-DNMT1 was found to correlate with Smad3 expression in accordance with the expression at the
cellular level. Notably, the promoter region of SMAD3 was hypermethylated in cervical cancer tissues, and this
hypermethylation inhibits the subsequent gene expression.

Conclusion:
These results indicate that SUV39H1-DNMT1 is a crucial Smad3 regulatory axis in cervical cancer.
SUV39H1-DNMT1 axis may provide a potential therapeutic target for the treatment of cervical cancer.
New Approaches for the Synthesis of Heterocyclic Compounds Corporating Benzo[d]imidazole as Anticancer Agents, Tyrosine, Pim-1 Kinases Inhibitions and their PAINS Evaluations
Authors: Mohareb Rafat M. , Milad Yara R. , Mostafa Bahaa M. , El-Ansary Reem A. 
Published: July 2020

Background:
Benzo[d]imidazoles are highly biologically active, in addition, they are considered as a
class of heterocyclic compounds with many pharmaceutical applications.

Objective:
We are aiming in this work to synthesize target molecules that possess not only anti-tumor activities
but also kinase inhibitors. The target molecules were obtained starting from the benzo[d]imidazole derivatives
followed by their heterocyclization reactions to produce anticancer target molecules.

Methods:
The 1-(1H-benzo[d]imidazol-2-yl)propan-2-one (3) and the ethyl 2-(1H-benzo[d]imidazol-2-
yl)acetate (16) were used as the key starting material which reacted with salicylaldehyde to give the corresponding
benzo[4,5]imidazo[1,2-a]quinoline derivatives. On the other hand, both of them were reacted with different
reagents to give thiophene, pyran and benzo[4,5]imidazo[1,2-c]pyrimidine derivatives. The synthesized compounds
were evaluated against the six cancer cell lines A549, HT-29, MKN-45, U87MG, SMMC-7721, and
H460 together with inhibitions toward tyrosine kinases, c-Met kinase and prostate cancer cell line PC-3 using
the standard MTT assay in vitro, with foretinib as the positive control.

Results:
Most of the synthesized compounds exhibited high inhibitions toward the tested cancer cell lines. In
addition, tyrosine and Pim-1 kinases inhibitions were performed for the most active compounds where the variation
of substituent through the aryl ring and heterocyclic ring afforded compounds with high activities. Our
analysis showed that there is a strong correlation between the structure of the compound and the substituents of
target molecules.

Conclusion:
Our present research proved that the synthesized heterocyclic compounds with varieties of substituents
have a strong impact on the activity of compounds. The evaluations through different cell lines and
tyrosine kinases indicated that the compounds were the excellent candidates as anticancer agents. This could
encourage doing further research within this field for the building of compounds with high inhibitions.
Combination of Salinomycin and AZD3463 Reveals Synergistic Effect on Reducing the Viability of T98G Glioblastoma Cells
Authors: Asik Aycan , Ay Neslihan P.O. , Bagca Bakiye G. , Caglar Hasan O. , Gunduz Cumhur , Avci Cigir B. 
Published: July 2020

Background:
Salinomycin, an ionophore antibiotic, is known to be an effective agent in reducing the
viability of Glioblastoma (GBM) cells. The combination of salinomycin with other chemotherapeutic drugs
would help to overcome the drug resistance of GBM cells.

Objective:
This study aims to test the combinatorial effect of salinomycin and AZD3463 in T98G GBM cells.

Methods:
The cytotoxic effects of drugs on T98G GBM cells were determined by using WST-8 assay. Flow
cytometry was used to identify apoptosis and cell cycle profiles after treatments. Real-time PCR was used to
portray mRNA expression profiles of genes in the Wnt-signaling pathway after treatments.

Results:
IC50 concentrations of AZD3463 and salinomycin were 529nM and 7.3μM for 48h, respectively. The
combination concentrations of AZD3463 and salinomycin were 3.3μM and 333nM, respectively. The combination
treatment showed a synergistic effect on reducing the viability of GBM cells. AZD3463, salinomycin, and
their combination induced apoptosis in 1.2, 1.4, and 3.2 folds, respectively. AZD3463 and the combination
treatment induced the cell cycle arrest at the G1 phase. Salinomycin and AZD3463 treatments, either alone or in
combination, resulted in the downregulation or upregulation of mRNA expression levels of genes in the Wntsignaling
pathway.

Conclusion:
Salinomycin, AZD3463, and their combination may inhibit proliferation and induce apoptosis in
GBM cells due to a decrease in expression levels of genes acting in both the canonical and non-canonical Wnt
signaling pathways. The Wnt signaling pathway may be involved in salinomycin-AZD3463 drug interaction.
Pulsatilla saponin A Induces Apoptosis and Differentiation of Myeloma Cells
Authors: Ye Bibo , Zhou Yingying , Liu Yanli , Li Xuewei , Li Tianyu , Qi Xiaofei 
Published: July 2020

Objectives:
To investigate the performance of Pulsatilla saponin A (PsA) in Multiple Myeloma
(MM) cells.

Methods:
Proliferation, cell cycle analysis, apoptosis and TUNEL assays were conducted to detect the growth
and apoptosis in MM cells. Western blotting was used to identify the change in the protein.

Results:
In cell assays, PsA significantly inhibited the growth and apoptosis in MM cells. Cyclin B1, caspase-3,
cleaved-caspase-3, PARP, cleaved-PARP, p-ERK increased, while Bcl-2 decreased after PSA treatment. The
CD49e positive rate of U266 cells was increased after 96h PsA treatment. At the same time, immunoglobulin
and the Free Light Chain (FLC) ratio in the culture supernatant obviously increased. Also, the differentiation
induced by PsA was confirmed in the primary myeloma cells.

Conclusions:
Our findings reveal that PsA may exert its antitumor effect by causing G2 arrest and apoptosis in
myeloma cells. And low-dose PsA can induce the differentiation of myeloma cell lines and primary myeloma
cells, probably through the MEK/ERK signaling pathway in vitro.
Thieno[2,3-d]pyrimidin-4(3H)-one Derivatives of Benzimidazole as Potential Anti- Breast Cancer (MDA-MB-231, MCF-7) Agents
Authors: Dimov Stefan , Mavrova Anelia Ts. , Yancheva Denitsa , Nikolova Biliana , Tsoneva Iana 
Published: July 2020

Aims:
The purpose was the synthesis of some new thienopyrimidines derivative of 1,3-disubstituted
benzimidazoles and the evaluation of their cytotoxicity towards MDA-MB-231 and MCF-7 cell lines as well 3T3 cells.

Background:
An overexpression or mutational activation of TK receptors EGFR and HER2/neu are characteristic for
tumors. It has been found that some thieno[2,3-d]pyrimidines exhibit better inhibitory activity against epidermal growth
factor receptor (EGFR/ErbB-2) tyrosine kinase in comparison to aminoquinazolines. Breast cancer activity towards MDAMB-231 and MCF-7 cell lines by inhibiting EGFR was revealed by a novel 2-arylbenzimidazole. This motivated the
synthesis of new thienopyrimidines possessing benzimidazole fragment in order to evaluate their cytotoxicity to the above
mentioned cell lines.

Objective:
The objectives of the study were to design and synthesize a novel series of thieno[2,3-d]pyrimidines
bearing biologically active moieties, such as 1,3-disubstituted-benzimidazole heterocycle, structurally similar to
diaryl ureas in order to evaluate their cytotoxicity against MDA-MB-231, and MCF-7 breast cancer cell lines.

Methods:
N,N-disubstituted benzimidazole-2-one carbonitriles were synthesized by Aza-Michael addition and
used as precursors to generate some of the new thieno[2,3-d]pyrimidines in acidic medium The interaction of
chloroethyl-2-thienopyrimidines, 2-amino-benzimidazole and benzimidazol-2-one nitriles under solid-liquid
transfer catalysis conditions led to new thienopyrimidines. MTT assay for cell survival was performed in order
to evaluate the cytotoxicity of the tested compounds. A fluorescence study was conducted to elucidate some
aspects of the mechanism of action.

Results:
The effects of nine synthesized compounds were investigated towards MDA-MB-231, MCF-7 and 3T3
cell lines. Thieno[2,3-d]pyirimidine-4-one 16 (IC50 - 0.058μM) and 21 (IC50 - 0.029μM) possess high cytotoxicity
against MDA-MB-231 cells after 24h. The most cytotoxic compounds against breast cancer MCF-7 cells was
compound 21 (IC50 - 0.074μM), revealing lower cytotoxicity against mouse fibroblast 3T3 cells with IC50 - 0.20μM.
SAR analysis was performed. Fluorescence study of the treatment of MDA-MB cells with compound 21 was
carried out in order to clarify some aspects of the mechanism of action.

Conclusion:
The relationship between cytotoxicity of compounds 14 and 20 against MCF-7 and 3T3 cells can suggest a
similar mechanism of action. The antitumor potential of the tested compounds proves the necessity for further
investigation to estimate the exact inhibition pathway in the cellular processes. The fluorescence study of the treatment of
MDA-MB cells with compound 21 showed a rapid process of apoptosis.
A Personalized Voice-Based Diet Assistant for Caregivers of Alzheimer Disease and Related Dementias: System Development and Validation
Authors: Li Juan , Maharjan Bikesh , Xie Bo , Tao Cui 
Published: July 2020

BackgroundThe world’s aging population is increasing, with an expected increase in the prevalence of Alzheimer disease and related dementias (ADRD). Proper nutrition and good eating behavior show promise for preventing and slowing the progression of ADRD and consequently improving patients with ADRD’s health status and quality of life. Most ADRD care is provided by informal caregivers, so assisting caregivers to manage patients with ADRD’s diet is important.ObjectiveThis study aims to design, develop, and test an artificial intelligence–powered voice assistant to help informal caregivers manage the daily diet of patients with ADRD and learn food and nutrition-related knowledge.MethodsThe voice assistant is being implemented in several steps: construction of a comprehensive knowledge base with ontologies that define ADRD diet care and user profiles, and is extended with external knowledge graphs; management of conversation between users and the voice assistant; personalized ADRD diet services provided through a semantics-based knowledge graph search and reasoning engine; and system evaluation in use cases with additional qualitative evaluations.ResultsA prototype voice assistant was evaluated in the lab using various use cases. Preliminary qualitative test results demonstrate reasonable rates of dialogue success and recommendation correctness.ConclusionsThe voice assistant provides a natural, interactive interface for users, and it does not require the user to have a technical background, which may facilitate senior caregivers’ use in their daily care tasks. This study suggests the feasibility of using the intelligent voice assistant to help caregivers manage patients with ADRD’s diet.
Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review
Authors: Quirch Miguel , Lee Jeannie , Rehman Shabnam 
Published: July 2020

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged medicine and health care on a global scale. Its impact and frightening mortality rate are in large part attributable to the fact that there is a lack of available treatments. It has been shown that in patients who are severely ill, SARS-CoV-2 can lead to an inflammatory response known as cytokine storm, which involves activation and release of inflammatory cytokines in a positive feedback loop of pathogen-triggered inflammation. Currently, cytokine storm is one of the leading causes of morbidity and mortality in SARS-CoV-2, but there is no proven treatment to combat this systemic response.

Objective
The aim of this paper is to study the cytokine storm response in SARS-CoV-2 and to explore the early treatment options for patients who are critically ill with the coronavirus disease (COVID-19) in the early stages of the pandemic by reviewing the literature.

Methods
A literature review was performed from December 1, 2000, to April 4, 2020, to explore and compare therapies that target cytokine storm among SARS-CoV-2 and prior coronavirus cases.

Results
A total of 38 eligible studies including 24 systematic reviews, 5 meta-analyses, 5 experimental model studies, 7 cohort studies, and 4 case reports matched the criteria.

Conclusions
The severity of the cytokine storm, measured by elevated levels of interleukin-1B, interferon-γ, interferon-inducible protein 10, and monocyte chemoattractant protein 1, was associated with COVID-19 disease severity. Many treatment options with different targets have been proposed during the early stages of the COVID-19 pandemic, ranging from targeting the virus itself to managing the systemic inflammation caused by the virus and the excessive cytokine response. Among the different agents to manage cytokine storm in patients with COVID-19, there is developing support for convalescent plasma therapy particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. Treatment options that were proposed in the beginning phases of the pandemic were multidimensional, and further research is needed to develop a more established treatment guideline.
How Data Analytics and Big Data Can Help Scientists in Managing COVID-19 Diffusion: Modeling Study to Predict the COVID-19 Diffusion in Italy and the Lombardy Region
Authors: Tosi Davide , Campi Alessandro 
Published: July 2020

Background
COVID-19 is the most widely discussed topic worldwide in 2020, and at the beginning of the Italian epidemic, scientists tried to understand the virus diffusion and the epidemic curve of positive cases with controversial findings and numbers.

Objective
In this paper, a data analytics study on the diffusion of COVID-19 in Italy and the Lombardy Region is developed to define a predictive model tailored to forecast the evolution of the diffusion over time.

Methods
Starting with all available official data collected worldwide about the diffusion of COVID-19, we defined a predictive model at the beginning of March 2020 for the Italian country.

Results
This paper aims at showing how this predictive model was able to forecast the behavior of the COVID-19 diffusion and how it predicted the total number of positive cases in Italy over time. The predictive model forecasted, for the Italian country, the end of the COVID-19 first wave by the beginning of June.

Conclusions
This paper shows that big data and data analytics can help medical experts and epidemiologists in promptly designing accurate and generalized models to predict the different COVID-19 evolutionary phases in other countries and regions, and for second and third possible epidemic waves.
Out of the Jar into the World! A Case Study on Storing and Sharing Vertebrate Data
Authors: Borda Susan 
Published: July 2020

In 2018, the Deep Blue Repositories and Research Data Services (DBRRDS) team at the University of Michigan Library began working with the University of Michigan Museum of Zoology (UMMZ) to provide a persistent and sustainable (i.e., non-grant funded, institutionally supported) solution for their part of the National Science Foundation’s (NSF) openVertebrate (oVert) initiative. The objective of oVert is to the digitize scientific collections of thousands of vertebrate specimens stored in jars on museum shelves and make the data freely accessible to researchers, students, classrooms, and the general public anywhere in the world. The University of Michigan (U-M) is one of five scanning centers working on oVert and will contribute scans of more than 3,500 specimens from the UMMZ collections (Erickson 2017).
In addition to ingesting scans, the project involved developing methods to work around several significant system constraints: Deep Blue Data’s file structure (flat files only, no folders) and the closed use of Specify, UMMZ’s specimen database, for specimen metadata. DBRRDS had to create a completely new workflow for handling batch deposits at regular intervals, develop scripts to reorganize the data (according to a third-party data model) and augment the metadata using a third-party resource, Global Biodiversity Information Facility (GBIF).
This paper will describe the following aspects of the UMMZ CT Scanning Project partnership in greater detail: data generation, metadata requirements, workflows, code development, lessons learned, and next steps.
Finding a Repository with the Help of Machine-Actionable DMPs: Opportunities and Challenges
Authors: Oblasser Simon , Miksa Tomasz , Kitamoto Asanobu 
Published: July 2020

Finding a suitable repository to deposit research data is a difficult task for researchers since the landscape consists of thousands of repositories and automated tool support is limited. Machine-actionable DMPs can improve the situation since they contain relevant context information in a structured and machine-friendly way and therefore enable automated support in repository recommendation.
This work describes the current practice of repository selection and the available support today. We outline the opportunities and challenges of using machine-actionable DMPs to improve repository recommendation. By linking the use case of repository recommendation to the ten principles for machine-actionable DMPs, we show how this vision can be realized. A filterable and searchable repository registry that provides rich metadata for each indexed repository record is a key element in the architecture described. At the example of repository registries we show that by mapping machine-actionable DMP content and data policy elements to their filter criteria and querying their APIs a ranked list of repositories can be suggested.
THE COMPARISON STUDY ON TWO-TYPES OF STUDENTS` PERSONALITY: SANGUINE AND PHLEGMATIC TOWARD THEIR ENGLISH SPEAKING ABILITY
Authors: Rakhmanina Lisa , Martina Feny , Jayadi Nevan 
Published: July 2020

The study is an attempt to find out the difference between Sanguine and Phlegmatic personality toward their speaking ability. The design in this study was comparative analysis design. The samples of this study were 44 students from Faculty of Law. Personality test was carried out to decide whether the students were categorized to the group of Sanguine or Phlegmatic. Furthermore, the researcher used personal description for monologue speaking technique for testing the students speaking skills. The data were analyzed by using t-test formula to investigate whether there was significant difference result between the Sanguine and the Phlegmatic students in their speaking skill. From the result of the study, it could be concluded that there was no significant different result between the Sanguine and the Phlegmatic students toward their speaking skill. It means, there were not any better students in speaking between both Sanguine and Phlegmatic students. Those two personalities, the Sanguine and the Phlegmatic students could perform better English speaking skill through their own personal way.Keywords: Comparison Study, Sanguine, Phlegmatic, Speaking Ability
AN ANALYSIS OF DEIXIS IN PAMUNGKAS'S "ONE ONLY" SONG LYRICS
Authors: Kusumadewi Siti , Anggraeni Anita 
Published: July 2020

The aims of this research are to analyze the kinds of deixis that are used in One Only song lyrics and to find out the types of deixis that are major used in in the song lyrics. The researcher choose this song because this song is easy to listen to and got a good response from the listener. This research used qualitative research. The result of this research showed that in the One Only song lyrics there are four kinds of deixis, there are personal deixis, spatial deixis, temporal deixis and social deixis. Based on the discussion, personal deixis came as the most often appears deixis with 50 deictic words found or 92.6 %, the second is Spatial deixis (2 deictic words or 3.7 %), followed by temporal deixis and social deixis with the percentage of 1.85 % each. Keywords: Deixis, Song Lyrics, Pamungkas
THE ANALYSIS OF ENDHOPORIC REFERENCE IN OPRAH’S INSPIRATIONAL GOLDEN GLOBAL SPEECH
Authors: Andriani Renny , Supartini Nai 
Published: July 2020

The aims of the research is to know endhoporic reference in Oprah’s speech. This research use descriptive qualitative method. The writer choose a transcript about Oprah’s speech from the website Endophoric is diveded in two types, there are anaphoric and cataphoric. The result shows that endhoporic references can be found in each paragraph in Oprah’s speech. This research found that anaphoric predominate in Oprah’s speech because she refers to something that has mentioned at before. In this study there were six sentences that referred to anaphoric reference and only one sentence referred to the cathaporic reference. Anaphoric is the only reference related to cohesion.
Sistemas Modernos de Contabilidad
Authors: Juárez Fonseca Verónica , Pérez Paredes Alfredo , Garcia Vásquez Jorge Manuel 
Published: July 2020

El libro trata de temas relevantes y actuales acerca de los sistemas, métodos y registros contables a partir de la segunda década del siglo XX. Los primeros conocimientos vinculados a la función de la contaduría se ven reflejados en la aportación univoca que el autor consuma con la expresión al castellano, con un estilo particular elocuente y sutil, sin apartarse de los tecnicismos científicos provenientes de otro continente. Este es el primer libro de contabilidad en México, que traduce conceptos y tecnicismos del inglés (Inglaterra y Estados unidos de Norte América) al español sin descuidar las funciones y necesidades empresariales mexicanas.
Esta primera aportación, centra su objetivo en proporcionar los conocimientos al argot contable y la convergencia hacia estudios de casos de empresas reales que iniciaban sus operaciones en México, como intento de resarcir la economía debilitada por las secuelas de la revolución mexicana. Asimismo, el libro separa la sistematización, de la practicidad hasta llegar a los resultados empresariales para la toma de decisiones de los futuros y actuales contadores de aquella época, a través estados financieros hasta hoy vigentes. Este legado permanece vigente a reserva de los cambios tecnológicos globales.