bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Studies of bis-2-Oxoindoline Succinohydrazides and their In Vitro Cytotoxicity
Authors: Jarapula Ravi , Badavath Vishnu N. , Rekulapally Shriram , Manda Sarangapani 
Published: January 2019

Background:
The discovery of clinically relevant EGFR inhibitors for cancer therapy has proven
to be a challenging task. To identify novel and potent EGFR inhibitors, the quantitative structure-activity
relationship (QSAR) and molecular docking approach became a very useful and largely widespread technique
for drug design.

Methods:
We performed the in vitro cytotoxic activity on HEPG-2 cell line and earlier on MCF-7 and A
549 by using MTT assay method. The development of 3D QSAR model of N1,N4-bis(2-oxoindolin-3-
ylidene) succinohydrazides using the stepwise-backward variable methods to generate Multiple Linear Regression
method elucidates the structural properties required for EGFR inhibitory activity and also perform
the Molecular Docking studies on EGFR (PDB ID:1M17). Further, we analysed for Lipinski’s rule of five
to evaluate the drug-likeness and established in silico ADMET properties.

Results:
The resulting cytotoxicity (IC50) values ranged from 9.34 to 100 μM and compared with cisplatin
as a standard. Among the series of compounds, 6j showed good cytotoxic activity on HEPG-2 cell line with
9.34 μM, IC50 value. Most of the evaluated compounds showed good antitumor activity on HEPG-2 than
MCF-7and A549. The developed 3D QSAR Multiple Linear Regression models are statistically significant
with non-cross-validated correlation coefficient r2 = 0.9977, cross-validated correlation coefficient q2 =
0.902 and predicted_r2 = 0.9205. Molecular docking studies on EGFR (PDB ID: 1M17) results, compounds
6d, 6j and 6l showed good dock/PLP scores i.e. -81.28, -73.98 and -75.37, respectively, by interacting with
Leu-694, Val-702 and Gly-772 amino acids via hydrophobic and hydrogen bonds with Asn818 and Met-
769. Further, we analysed drug-likeness and established in silico ADMET properties.

Conclusion:
The results of 3D QSAR studies suggest that the electrostatic and steric descriptors influence
the cytotoxic activity of succinohydrazides. From the molecular docking studies, it is evident that
hydrophobic, hydrogen and Van Der Waal’s interactions determine binding affinities. In addition to this, druglikeness
and ADMET properties were analysed. It is evident that there is a correlation between the QSAR and
docking results. Compound 6j was found to be too lipophilic due to its dihalo substitution on isatin nucleus,
and can act as a lead molecule for further and useful future development of new EGFR Inhibitors.
High-Affinity Detection of Metal-Mediated Nephrotoxicity by Aptamer Nanomaterial Complementation
Authors: Pan Huijuan , Lakshmipriya Thangavel , Gopinath Subash C.B. , Anbu Periasamy 
Published: January 2019

:
Nephrotoxicity, a chronic renal disease that results from the accumulation of endogenous
and exogenous toxins in the kidney, disturbs the excretion and detoxification function of the kidney.
Metal-mediated nephrotoxicity is induced by toxic metals/metalloids such as mercury, lead, arsenic,
chromate, uranium, and cadmium. These materials become concentrated in the kidneys and injure the
nephrons. Developing strategies to detect these metal ions will enable the earlier identification of
kidney damage. An aptamer, an artificial antibody generated against a wide range of targets
including metal ions, may be the right tool for the detection of metal ions associated with renal injury.
The use of a detection system consisting of an aptamer and metallic nanoparticles is a potential
way to overcome nephrotoxicity. Here, we discuss the detection of metal-mediated nephrotoxicity
caused by metals/metalloids using the aptamer and nanomaterial-conjugated system.
Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity
Authors: Elloumi-Mseddi Jihene , Msalbi Dhouha , Fakhfakh Raouia , Aifa Sami 
Published: January 2019

Background:Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates.Objective:In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).Methods:Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.Results:Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect.Conclusion:Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.
Detection of Hypoxia-Regulated MicroRNAs in Blood as Potential Biomarkers of HIF Stabilizer Molidustat
Authors: Marchand Alexandre , Roulland Ingrid , Semence Florian , Schröder Kaja , Domergue Valérie , Audran Michel 
Published: January 2019

Background:
The recent development of drugs that stabilize HIFalpha, called HIF stabilizers,
offers a new strategy for treating anemia. Although these drugs are still in clinical trials, misuse
for doping has already begun. Identifying the biomarkers of HIF stabilizers would therefore help
in detecting this drug misuse by athletes.

Objective:
Our aim was twofold: to determine whether hypoxamiRs, the microRNAs associated with
the cellular response to hypoxia, are potential biomarkers of HIF stabilizers in blood and whether the
response to treatment with an HIF stabilizer differs from the response to a hypoxic environment.

Method:
Rats were treated for 6 days with either a placebo or 2mg/kg of Molidustat, an HIF stabilizer,
or they were put under hypoxia (10% oxygen) for the same length of time. Plasma samples
were analyzed before, during and 48 hours after the treatments.

Results:
EPO concentration increased significantly in plasma during hypoxia and Molidustat treatment
and showed a negative retro-control 2 days after the end of the treatments. On the contrary, circulating
levels of VEGF were not modified. Among the hypoxamiRs tested, miR-130a and miR-21
were significantly increased during Molidustat treatment and miR-21 was still increased 48 hours after
treatment end.

Conclusion:
Although using these microRNAs as biomarkers seems unlikely due to other possible
factors of regulation, this study provides the first identification of a specific effect of HIF stabilizers
on microRNAs. Further investigations are needed to better understand the possible consequences of
such regulation.
Recent Patents in Additive Manufacturing of Continuous Fiber Reinforced Composites
Authors: Hu Chao , Sun Zeyu , Xiao Yi , Qin Qinghua 
Published: January 2019

Background:
Additive Manufacturing (AM) enables the accurate fabrication of designed
parts in a short time without the need for specific molds and tools. Although polymers are the most
widely used raw materials for AM, the products printed by them are inherently weak, unable to sustain
large tension or bending stresses. A need for the manufacturing of fiber reinforced composites, especially
continuous fiber as reinforcement, has attracted great attention in recent years.

Objective:
Identifying the progress of the AM of continuous carbon fiber reinforced composites over
time and therefore establishing a foundation on which current research can be based.

Methods:
Elaborating the most related patents regarding the AM techniques for fabricating continuous
fiber reinforced composites in the top three institutions, including Markforged company, Xi’an Jiaotong
University and President and Fellows of Harvard College.

Results:
The recent patents in AM of continuous fiber reinforced composites are classified into two
aspects: patents related to novel technique methods and patents related to novel structures. The current
issues and future development of AM-based composites are given.

Conclusion:
New structures and techniques have been introduced into conventional 3D printers to enable
the printing of continuous fiber reinforced composites. However, until now, Markforged is the only
company commercializing the fabrication of this kind of composites based on AM technique. Numerous
challenges and issues need to be solved so that AM of continuous fiber reinforced composites can
be a new manufacturing method.
Implementation of Quality by Design: A Review
Authors: Purohit Deepika , Saini Manisha , Pandey Parijat , Tripathy Swagat , Dureja Harish 
Published: January 2019

Background:
In pharmaceutical terms, quality means a product free from any contamination
and delivers the therapeutic benefit specified in the label at a reproducible rate which can
be assessed by carrying out in vivo or in vitro tests for evaluation of performance. Quality by Design
(QbD) is a necessary tool in pharmaceutical environment for having product/process/method
impregnated with quality. QbD is a move toward drug development that ensures the preplanned
product specifications by providing guidance for architecting the manufacturing processes and
formulation.

Methodology:
It has provided the solution to support both the regulatory bodies and industry to
shift towards added proactive and scientific approach. QbD is the greatest solution to construct
quality in all pharmaceutical products, while at the same time, making it a part of the system is
also a key challenge for the industry. By using QbD concept, regulators as well as industries are
making a move in geometric progress in bringing quality products. Regulatory bodies across the
world are showing significant attention to QbD.

Conclusion:
Therefore, an attempt has been made to highlight quality by designing generic drugs
and its implications to pharmaceutical industry including clinical trials, pharmaceutical validation
processes and in biologics and also to provide a brief description on the status of QbD in India and
as well as in Asia.
Experimental Optimization of Green Hydrogen Production from Phototrophic Bacteria Rhodobacter sphaeroides
Authors: Garimella Swetha , Vimal Archana , Merugu Ramchander , Kumar Awanish 
Published: January 2019

Background and Objective:
This study utilizes Rhodobacter sphaeroides bacteria
for the photoproduction of hydrogen under various cultural conditions. R. sphaeroides was
isolated from sewage water. We have examined different carbon and nitrogen sources for
hydrogen production and further established the conditions for optimum hydrogen production
by R. sphaeroides.

Methods:
The cumulative hydrogen produced by the bacteria at various intervals of time
was measured using a Gas Chromatograph. Initially, by classical one factor at a time
method, it was found that Benzoate and Glycine promote higher amounts of hydrogen production
under anaerobic light conditions after 96 h.

Results:
The production was also observed to be enhanced in the presence of growth factors
B12. Further, the Response Surface Methodology (RSM) was employed to optimize the hydrogen
production. The first level of optimization was done using Box-Behnken Design
(BBD) followed by Central Composite Design (CCD) method. The maximum production of
hydrogen achieved by BBD and CCD was 6.8 ml/30 ml and 8.12 ml/30 ml, respectively.
The significant model predicted is a quadratic model with R2 value 0.9459.

Conclusion:
Moreover, work presented here suggests an environment-friendly approach of
harvesting H2, which could meet energy demand as clean fuel via the green route.
Optimasi Formula dan Uji Aktivitas Secara In Vitro Lotion O/W Ekstrak Etanolik Rimpang Temu Mangga (Curcuma Mangga Val. dan van Zijp) sebagai Tabir Surya
Authors: Arizona Mercy , Zulkarnain A. Karim 
Published: January 2019

Ekstrak temu mangga (Curcuma mangga Val.) memiliki aktivitas sebagai tabir surya secara spektrofotometri. Penelitian ini bertujuan untuk mengetahui formula optimum lotion o/w, sifat dan stabilitas fisik formula optimum lotion o/w, serta aktivitas tabir surya formula optimum lotion o/w ekstrak temu mangga (Curcuma mangga Val.) secara spektrofotometri. Formula optimum diperoleh dengan metode Simplex Lattice Design (SLD). Respon yang digunakan untuk menentukan formula optimum adalah daya lekat dan viskositas. Stabilitas fisik lotion o/w pada suhu ruang meliputi uji daya sebar, daya lekat, dan viskositas, serta uji freeze thaw cycling. Aktivitas tabir surya lotion o/w ditentukan secara spektrofotometri untuk menentukan Sun Protecting Factor (SPF), % transmisi eritema, dan % transmisi pigmentasi. Data dianalisis dengan One Way ANOVA dan uji t. Hasil penelitian menunjukkan bahwa formula optimum lotion o/w pada kombinasi 5% trietanolamin (TEA)-stearat dan 5% setil alkohol. Lotion o/w ekstrak temu mangga memiliki memiliki daya sebar 63,21±2,69 cm2, daya lekat 2,32±0,15 detik, dan viskositas sebesar 133,5±8,05 dPas. Hasil analisis statistika menunjukkan bahwa lotion o/w smemiliki stabilitas yang baik. Lotion o/w mempunyai aktivitas sebagai tabir surya pada konsentrasi lotion o/w 12,5% yang ditunjukkan dengan nilai SPF sebesar 12,82±0,16 dan tidak efektif dalam perlindungan terhadap eritema dan pigmentasi.
Non-Alcoholic Fatty Liver Disease in Cardiac Patients with Overweight and Obesity
Authors: Logacheva I. V. , Ryazanova T. A. , Makarova V. R. , Surnina O. V. 
Published: January 2019

Aim.In this research, we set out to study organic changes in the heart and blood vessels of obese men suffering from non-alcoholic fatty liver disease (NAFLD) combined with cardiac pathology in the metabolically unhealthy phenotype (MUHP). Another objective consisted in establishing a relationship between liver damage and the pathology of the heart and blood vessels.Materials and methods.A group of 112 men (male)aged 61.2±1.7 diagnosed with the ischemic heart disease (IHD) and stage 1–3 arterial hypertension (AH) were examined during the stationary treatment in the Republican Clinical Diagnostic Centre (Izhevsk, Russia). The patients were divided into 3 groups according to their body mass index (BMI): 29 men with a BMI under 25 kg/m2(I group); 43 overweight men a BMI over 25 of kg/m2(II group); 40 men with obesity and a BMI above 30 of kg/m2(III group). Laboratory and non-invasive instrumental examinations required for the diagnostics of NAFLD and IHD were carried out, including liver ultrasound and FibroScan elastometry. Other examinations included the measurement of the intra-abdominal adipose tissue (IAT) and epicardial adipose tissue (EAT) thickness, the calculation of the visceral adiposity index (VAI), the estimation of endothelial dysfunction indicators, as well as the assessment of the structural and functional parameters of the heart and blood vessels.Results.In obese patients with pronounced NAFLD signs, IAT, EAT and VAI indicators are shown to increase in direct correlation with the parameters of liver steatosis. A relationship is established between the most significant structural and functional indicators of the heart (myocardial mass index, volume of the left atrium), blood vessels (endotheliumdependent vasodilation, the size of the intima-media complex of the common carotid artery) and NAFLD. It is demonstrated that the correlation coefficients grow with the progression of fatty infiltration and liver fibrosis signs.Conclusions.The results of the study have revealeda connection between the NAFLD presence and the main markers of visceral fat depots (IAT, EAT, VAI), which is shown to increase the risk of cardio-vascular complications in such patients. NAFLD is accompanied by endothelial dysfunction and a change in the most significant parameters of cardiac and vascular remodelling. These parameters manifest the progression of pathological changes in the liver parenchyma, which increases the cardio-metabolic risk in patients with MUHP.
Formação de professores com dimensões colaborativas: as estruturas multiplicativas em foco
Authors: De Souza Santos Jaqueline Santana 
Published: January 2019

Esta pesquisa tem por objetivo identificar as possíveis contribuições para a prática docente que uma formação continuada, com dimensões colaborativas, pode proporcionar aos professores dos anos iniciais no que concerne ao Campo Conceitual Multiplicativo no âmbito da relação ternária. Para tanto, o referencial teórico teve como base a Teoria dos Campos Conceituais de Vergnaud, atrelado às ideias do profissional reflexivo descrito por Schön. A abordagem metodológica foi qualitativa, realizada em uma escola da rede pública do sul da Bahia dos anos iniciais do Ensino Fundamental, com um grupo constituído de 14 professores e 3 professores formadores. Dentre esse grupo de professores, foram escolhidos os três sujeitos de pesquisa: Ana, Cida e João. Os critérios dessa escolha foram: participação efetiva em todo processo dialético da estratégia formativa proposta; elaboração e aplicação das situações elaboradas; ser bolsista do projeto PEM. A estratégia formativa utilizada foi a espiral de fluxo RePARe: Reflexão-planejamento-ação-reflexão de Magina, atrelada à formação com dimensões colaborativas. A pesquisa se desenvolveu em três etapas: diagnóstica, formativa e avaliação do processo formativo. A primeira etapa buscou identificar quais as concepções dos professores participantes acerca do CCM. A segunda, por meio de uma observação participante durante 11 encontros, procurou identificar as contribuições de um processo formativo, com dimensões colaborativas, para a prática docente desse professor. Por fim, avaliar o processo formativo na voz dos sujeitos da pesquisa, bem como fazer uma análise comparativa, identificando as possíveis contribuições da formação. Os instrumentos de coleta de dados foram: áudio gravação, diário de bordo, entrevista semiestruturada e registros escritos. Ao analisar os dados foi possível identificar as seguintes contribuições, em relação às dimensões colaborativas: a presença da colaboração, o trabalho em conjunto com seus pares compartilhando suas práticas; a afetividade; o companheirismo. Quanto a espiral RePARe: uma reflexão crítica sobre a própria prática docente; indicativos de mudança da prática pedagógica; maior interesse e percepção na estratégia dos alunos; reflexões individuais e em grupo, com o intuito de intervir na prática docente. No que concerne a teoria: expansão do CCM; utilização desse campo conceitual na prática docente; compreensão de que é preciso apresentar uma diversidade de situações. Dessa maneira, foi possível perceber que: os professores ressignificaram a sua prática docente; a formação contribuiu para uma mudança da perspectiva dos professores com relação à Matemática; ampliaram o conhecimento dos conceitos básicos da estrutura multiplicativa para utilizar na prática; passaram a compreender o erro como uma oportunidade de aprendizagem.
As estratégias de resolução dos estudantes de 1º ano em situações de proporção simples
Authors: Merlini Vera Lucia , Nascimento Teixeira Antonio César 
Published: January 2019

O objetivo deste artigo é objetivo analisar o desempenho dos estudantes do 1º ano da Bahia e categorizamos as estratégias de resolução adotadas pelos estudantes que levaram ao acerto do núcleo da Universidade Estadual de Santa Cruz-UESC, ao resolverem uma situação de proporção simples, da classe um para muitos, cuja operação mais indicada é a multiplicação. Esse estudo é um recorte de dois projetos que se complementam, são eles: Um estudo sobre o domínio das estruturas multiplicativas no Ensino Fundamental” (E-Mult)[1] e As Estruturas Multiplicativas e a formação de professores que ensinam Matemática na Bahia (PEM)[2]. Os dados foram coletados em escolas públicas de cinco regiões distintas do estado da Bahia, totalizando 162 estudantes do 1º ano de. A situação de proporção simples analisada consta em um teste diagnóstico que continha ao todo 14 situações relativas à Estrutura Multiplicativa, fundamentadas na Teoria do Campo Conceitual Multiplicativo de Vergnaud. Para efeito desse artigo serão analisados o desempenho dos estudantes das cinco regiões da Bahia e as estratégias de resolução dessa situação dos estudantes de uma região. Concluímos que mesmo estudantes do 1º ano do Ensino Fundamental que ainda não tiveram contato formalmente com situações da estrutura multiplicativa, demonstraram possuir noções matemáticas, pois ao utilizar a representação icônica como estratégia de resolução, eles conseguiram solucionar situações das estruturas multiplicativas.

[1] Projeto de número 15.727 do Programa Observatório da Educação (OBEDUC) financiado pela CAPES
[2] Projeto de número PES0019/2013 financiado pela FAPESB
O desempenho de estudantes do 5º e 9º anos frente a situações de proporção simples: uma análise comparativa
Authors: Teixeira Antonio César Nascimento , Silva Filho Deusdete Luiz da , Merlini Vera Lucia 
Published: January 2019

O objetivo deste artigo é analisar comparativamente o desempenho dos estudantes do 5º e 9º anos do Ensino Fundamental ao resolver três situações de proporção simples, da classe de muitos para muitos. Esse estudo é um recorte de dois projetos interligados: Um estudo sobre o domínio das estruturas multiplicativas no Ensino Fundamental (E-Mult)[1] e As Estruturas Multiplicativas e a formação de professores que ensinam Matemática na Bahia (PEM)[2]. Os dados foram coletados de estudantes de quatro escolas públicas do sul da Bahia parceiras dos projetos, sendo 235 estudantes do 5º ano e 88 do 9º ano, que responderam um teste diagnóstico contendo 14 situações relativas à Estrutura Multiplicativa. A análise dessas três situações foi quantitativa e comparativa, relacionada ao desempenho e contou com testes estatísticos. Os resultados obtidos revelam que os estudantes dos dois anos escolares foram pífios, sendo que 5º ano não atingiu 10%, o que é razoável supor que esses estudantes não tiveram contato com situações desse tipo. Apesar do 9º ano ter alcançado melhor resultado em relação ao 5º ano, esse não passou dos 42% de acerto, apontando fragilidades no domínio do conteúdo de proporcionalidade. Esses resultados revelam um sinal de alerta e apontam que é preciso trabalhar com uma variedade de situações de proporção simples, em especial da classe de muitos para muitos, permitindo que os estudantes possam aprimorar e expandir o Campo Conceitual Multiplicativo.

[1] Projeto de número 15.727 do Programa Observatório da Educação (OBEDUC) financiado pela CAPES
[2] Projeto de número PES0019/2013 financiado pela FAPESB