bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of Diffusion and Perfusion MRI in Evaluating Primary Central Nervous System Lymphomas of Different Locations
Authors: Xing Zhen , Kang Nannan , Lin Yu , Zhou Xiaofang , Xiao Zebin , Cao Dairong
Published: January 2020

BACKGROUND AND PURPOSE Diffusion and perfusion MRI can invasively define physical properties and angiogenic features of tumors, and guide the individual treatment. The purpose of this study was to investigate whether the diffusion and perfusion MRI parameters of primary central nervous system lymphomas (PCNSLs) are related to the tumor locations.MATERIALS AND METHODS We retrospectively reviewed the diffusion, perfusion, and conventional MRI of 68 patients with PCNSLs at different locations (group 1: cortical gray matter, group 2: white matter, group 3: deep gray matter). Relative maximum cerebral blood volume (rCBV max ) from perfusion MRI, minimum apparent diffusion coefficients (ADC min ) from DWI of each group were calculated and compared by one-way ANOVA test.RESULTS The rCBV max of PCNSLs yielded the lowest value in the white matter group, and the highest value in the cortical gray matter group ( P <0.001). However, the ADC min of each subgroup was not statistically different.CONCLUSIONS Our study confirms that rCBV max of PCNSLs are related to the tumor location, and provide simple but effective information for guiding clinical practice of PCNSLs.
An amyloid sensitive composite model to determine subtle cognitive differences in preclinical Alzheimer’s disease
Authors: Hahn Alice Min Jung , Kim Young Ju , Kim Hee Jin , Jang Hyemin , Na Duk L. , Chin Juhee , Seo Sang Won
Published: January 2020

Background: Recently, the focus of Alzheimer's disease (AD) research has shifted from the clinical and symptomatic stage to the preclinical and asymptomatic stage. However, studies on the distinctive neuropsychological features of preclinical AD with adjusted measurement errors are insufficient. The present study aimed to investigate the distinctive cognitive features of preclinical AD and develop a cognitive composite model that can sensitively distinguish between the amyloid positive (Aβ+) and amyloid negative (Aβ-) status in cognitively normal (CN) elderly participants.
Methods: A total of 423 CN elderly participants with amyloid positron emission tomography (PET) images were recruited. Using the multiple-indicator multiple-cause (MIMIC) model, sensitive cognitive domains to the Aβ+ group were found. Then, several cognitive tests were selected to create the cognitive composite model as a result of the multivariate analysis of covariance (MANCOVA).
Results: The MIMIC model revealed that the domains of episodic memory (verbal and visual) and executive functions were significantly different between Aβ- and Aβ+ ( p <0.05) participants. According to MANCOVA, the Seoul Verbal Learning Test-Elderly’s version (SVLT-E) and the Rey-Osterrieth Complex Figure Test (RCFT) both distinguished between the Aβ+ group and the Aβ- group on the delayed recall tests in terms of episodic memory ( p <0.1). Furthermore, on tests of executive functions, the Aβ+ group performed worse than the Aβ- group in color reading of the Korean-Color Word Stroop test (K-CWST) and the animal naming of the Controlled Oral Word Association Test (COWAT) ( p <0.1). Consequently, the Preclinical Amyloid Sensitive Composite (PASC) model was comprised of SVLT-E delayed recall, RCFT delayed recall, K-CWST color reading, COWAT-animal, and the Korean Mini-Mental State Examination (K-MMSE) according to the results from our study and previous studies.
Conclusions: In the present study, we developed our own composite PASC model with the distinctive cognitive profiles of Aβ+ CN individuals. Hence, this composite model can eventually contribute to not only early detection but also early interventions for AD.
Sociodemographic, health and fracture profiles of a 4-year cohort of 266,324 first incident upper extremity fractures in Ontario.
Authors: MacDermid Joy Christine , McClure J Andrew , Richard Lucie , Jaglal Susan , Faber Kenneth J.
Published: January 2020

Background The purpose of this study was to describe 1st incident fractures of the upper extremity in terms of fracture characteristics, demographics, social deprivation and comorbid health profiles. Methods:Cases with a 1st adult upper extremity fracture from the years 2013 to 2017 were extracted from administrative data in Ontario, (population 14.3M). Fracture locations (ICD-10 codes) and associated characteristics (open/closed, associated hospitalization within 1-day, associated nerve or tendon injury) were described by fracture type, age category and sex. Fracture comorbidity characteristics were described in terms of the prevalence of diabetes, rheumatoid arthritis; and the Charlson Comorbidity Index. Social marginalization was expressed using the Ontario Marginalization Index (ON-Marg) for material deprivation, dependency, residential instability, ethnic concentration. ResultsFrom 266,324 first incident UE fractures occurring over 4 years, 51.5% were in women and 48.5% were in men. This masked large differences in age-sex profiles. Most commonly affected were the hand (93K), wrist/forearm(80K), shoulder (48K) or elbow (35K). The highest number of fractures: distal radius (DRF, 47.4K), metacarpal (30.4K), phalangeal (29.9K), distal phalangeal (24.4K), proximal humerus (PHF, 21.7K), clavicle (15.1K), radial head (13.9K), and scaphoid fractures (13.2K). The most prevalent multiple fractures included: multiple radius and ulna fractures (11.8K), fractures occurring in multiple regions of the upper extremity (8.7K), or multiple regions in the forearm (8.4K). Fractures most common in 18 – 40-year-old men included metacarpal and finger fractures. A large increase in fractures in women over the age of 50 occurred for: DRF, PHF and radial head. Tendon (0.6% overall; 8.2% in multiple finger fractures) or nerve injuries (0.3% overall, 1.5% in distal humerus) were rarely reported. Fractures were open in 4.7%, highest for distal phalanx (23%). Diabetes occurred in 15.3%, highest in PHF (29.7%). Rheumatoid arthritis occurred more commonly in women (2.8% vs 0.8% men). The Charlson Index indicated low comorbidity (mean=0.2; median=0: 2.4% 3+), highest in PHF (median=0; 6.6% 3+). Higher fracture burden was related to instability (excess of fractures in lower 2 quartiles 4.8%), although social indices varied by fracture type. ConclusionsFracture specific prevention strategies should consider fracture-specific age-sex interactions, health, behavioural and social risks
A Thing About Machines: Eça de Queirós's Technological Twilight Zone
Authors: Ilievska Ana
Published: January 2020

By reconstructing the acts and voices of technological artifacts in A cidade e as serras (1901), this paper outlines what I call Eça de Queirós’s technological “twilight zone,” where machines are granted literary citizenship, and human interlocutors are forced to reevaluate who and what counts as humanity and conversation. I argue that the unresponsiveness of technological artifacts to the human voice in A cidade e as serras reveals a process of destabilization of power hierarchies and vocal anthropocentrism. Eça neither demonizes nor glorifies machines; rather he elaborates ways in which productive coexistence and communication can remain a prime objective. In A cidade e as serras, Eça parses out anxieties about technology and modernity in subtle and balanced ways that can shed new light on enduring questions about humanmachine interactions in our era of technological dependence.
Groundwater Quality Assessment Using Geospatial Techniques and WQI in North East of Adama Town, Oromia Region, Ethiopia
Authors: Karuppannan Shankar , Serre Kawo Nafyad
Published: January 2020

Assessment of groundwater quality is vital for the sustainable use of the resources for domestic and agricultural purposes. In this study spatial variation of physicochemical parameters were analyzed for Northeast Adama Town. Water Quality Index (WQI) and irrigation indices were used to determine the suitability of groundwater for drinking and irrigation purposes, respectively. Further, the physical-chemical results were compared with the Ethiopian standards and the World Health Organization (WHO) standards for drinking and public health. Using GIS interpolation methods in Arc GIS 10.3.1, spatial distribution maps of pH, TDS, EC, Cl−, HCO32−, SO42−, Ca2+, Mg2+, Na+ and K+, RSC, SAR, Na% were prepared. Results indicated that except ASTU well 2, all samples are below the desirable limits of WHO. The WQI results indicated that 85% of samples and 15% of samples were in good and poor categories, respectively. Irrigation indices show that the most groundwater samples have excellent water classes, indicating that they are suitable for irrigation purposes.
ALIMENTAÇÃO SAUDÁVEL E ATIVIDADE FÍSICA NA ESCOLA ATRAVÉS DE UMA ABORDAGEM CONTEXTUALIZADA E INTERDISCIPLINAR
Authors: Dutra Raiane Da Rosa , Coutinho Renato Xavier
Published: January 2020

O presente estudo teve como objetivo analisar uma intervenção pedagógica realizada em uma escola pública do RS, visando promover saúde através do tema alimentação/prática de atividade física, buscando uma abordagem contextualizada e interdisciplinar, bem como analisar a concepção dos partícipes sobre esta prática. Utilizou-se metodologia qualitativa, através da dinâmica dos Três Momentos Pedagógicos; participaram 194 alunos – 11 a 17 anos – e 5 professores. No decorrer dos Três Momentos, identificou-se que os alunos compreendem o que são hábitos saudáveis, bem como sua importância para a saúde, porém não adotam na prática; o ensino com ênfase na pesquisa foi válido para a elaboração das atividades, onde os alunos foram os protagonistas na construção do conhecimento; e além de compreenderem a proposta, colaboraram ativamente durante as mesmas. Deste modo, partindo das concepções dos alunos sobre esta prática, infere-se que a promoção de saúde foi efetiva, bem como, conforme relatos dos professores foi importante no que concerne o assunto abordado e o método utilizado para o processo de ensino-aprendizagem. Desta maneira, conclui-se que atividades como esta são significativas no que tange a um entendimento mais amplo a respeito do assunto, fazendo com que o mesmo possa ser associado e utilizado em situações cotidianas.
O SISTEMA SENSORIAL EM AULAS DE CIÊNCIAS POR INVESTIGAÇÃO: EFEITOS DE SENTIDO EM ANÁLISE
Authors: Bavaresco Julia , Palcha Leandro Siqueira
Published: January 2020

A pesquisa foi orientada por autores que reivindicam a emergência de práticas menos expositivas para o Ensino de Ciências e buscam problematizar as questões de aprendizagem visando à alfabetização científica na escola. Com base na abordagem do Ensino por Investigação pretende-se estudar uma sequência de ensino envolvendo o bloco temático do sistema sensorial a partir de questões-problemas envolvendo um conjunto de plantas medicinas. O objetivo da pesquisa é analisar os efeitos de sentido sobre o sistema sensorial em aulas de ciências por investigação e visando mobilizar aspectos da alfabetização científica. A pesquisa guiou-se pelo referencial da Análise de Discurso, sendo que para a apresentação e discussão do corpus de análise foram destacados efeitos de sentidos que emergiram da escrita dos alunos, do ensino fundamental, de uma escola pública. Os instrumentos de pesquisa constituem-se por um roteiro de aula e um questionário. Os resultados apontam que a sequência dotou os alunos de autonomia e criatividade, assim como manifestou efeitos de sentidos que podem ser trabalhados em aulas. Por fim, defende-se um trabalho coletivo a favor da educação em que universidade, escola e comunidade devem colocar em prática os pressupostos de alfabetização científica.
O Programa Nacional de Fortalecimento da Agricultura Familiar no Brasil: análise da evolução e distribuição entre 1999 e 2017
Authors: Troian Alessandra , Machado Edenilson Tafernaberry Lencina
Published: January 2020

O Estado brasileiro legitimou tardiamente a agricultura familiar como categoria social, simultaneamente com a constituição do Programa Nacional de Fortalecimento da Agricultura Familiar (PRONAF), em meados da década de 1990. Desde sua criação, o PRONAF vem passando por transformações visando ampliar as linhas de crédito e o público-alvo. Neste sentido, o presente estudo objetiva analisar a evolução e a distribuição dos recursos do Programa Nacional de Fortalecimento da Agricultura Familiar entre as regiões brasileiras no período de 1999 a 2017. Especificamente, buscou-se: a) apresentar o programa; b) identificar o valor de recursos distribuídos entre as regiões brasileiras; e c) elencar os principais entraves e desafios do programa. Metodologicamente a pesquisa classifica-se como qualitativa, a partir do método dedutivo. Buscaram-se dados secundários junto ao Banco Central do Brasil (BCB). Também foi utilizada a pesquisa bibliográfica. Como principais resultados destaca-se a desigualdade e concentração na distribuição do crédito, o qual se agrupou na Região Sul entre os anos 1999 a 2002. Entre 2003 a 2006 os recursos foram melhor distribuídos e a Região Sul diminuiu sua participação com aumento da participação das regiões Nordeste, Sudeste e Norte. A partir de 2007 ocorreu reconcentração dos recursos na Região Sul, o programa voltou a promover a agricultura moderna, sendo acessado basicamente por produtores de commodities em regiões capitalizadas. Como limitações do PRONAF, destaca-se a seletividade em favor de agricultores capitalizados, produtores de commodities, a concentração regional de crédito e o baixo acesso de unidades familiares mais empobrecidas.
Relação entre Emissões de CO2, Crescimento Econômico e Energia Renovável
Authors: Ceretta Paulo Sergio , Sari Jorge Fernando , Ceretta Franciane Cougo da Cruz
Published: January 2020

O objetivo deste estudo é investigar a relação entre emissão de CO2, crescimento econômico, energia fóssil e energia renovável. A amostra utilizada na pesquisa é composta por 37 países e os dados são do período de 1996 até 2013. Foi utilizada a abordagem de dados em painel com threshold, incluindo as variáveis emissão de dióxido de carbono; consumo de combustíveis fósseis; consumo de energia renovável e Produto Interno Bruto per capita baseado na paridade de poder de compra como indicador de crescimento econômico dos países. Relativo a utilização de combustíveis fósseis, constatou-se que a variável tem um relacionamento direto com a emissão de CO2. Porém, a magnitude do impacto é bem mais forte nos países classificados no regime 1 (baixa renda per capita). Relativo ao crescimento econômico foram encontrados impactos positivos e estatisticamente significativos para todos os grupos de países, sendo a influência na emissão de CO2 mais forte nos países do regime 2. Quanto ao uso de energia renovável foi encontrada uma relação significante e negativa para todos os grupos, sendo que para os países menos geradores de riqueza o uso de energia renovável tem um trade off mais forte do que para os países mais geradores de riqueza.
Reducing river export of nutrients and eutrophication in Lake Dianchi in the future
Authors: Ma Chuan , Strokal Maryna , Kroeze Carolien , Wang Mengru , Li Xiaolin , Hofstra Nynke , Ma Lin
Published: January 2020

Lake Dianchi is severely polluted with nitrogen (N) and phosphorus (P). The effects of implementing environmental policies and technologies on future lake quality are not well understood. We analyse effects of environmental policies and technologies on future river export of nutrients into Lake Dianchi. We develop scenarios for 2050 and analyse these with the existing MARINA-Lakes model (Model to Assess River Inputs of Nutrient to lAkes). The scenarios differ in assumptions about future nutrient management in agriculture, sewage systems and mining. In the SSP3 (Shared Socio-economic Pathway 3) scenario, river export of nutrients to Lake Dianchi is projected to increase 1.4–4.4 times between 2012 and 2050. In the Current Policies scenario, rivers may export fewer nutrients than in SSP3, but this may not avoid eutrophication. Effects of improved nutrient management on river export of nutrients differ among nutrient forms, sub-basins and sources (e.g., urbanization in the north, agriculture in the middle and south). Pollution levels can be reduced below the 2012 level in an Optimistic scenario assuming advanced wastewater treatment, improved nutrient management in agriculture and no mining. However, even this may not completely prevent eutrophication. Preventing eutrophication requires even more efforts, for example, in implementing circular-oriented management options.
One-step synthesis of zerovalent-iron–biochar composites to activate persulfate for phenol degradation
Authors: Yao Shu-hua , Chen Xue-jing , Gomez Mario Alberto , Ma Xi-chun , Wang Hai-bo , Zang Shu-yan
Published: January 2020

A novel zerovalen-iron–biochar composite (nZVI/SBC) was synthesized by using FeCl3-laden sorghum straw biomass as the raw material via a facile one-step pyrolysis method without additional chemical reactions (e.g., by NaBH4 reduction or thermochemical reduction). The nZVI/SBC was successfully employed as an activator in phenol degradation by activated persulfate. XRD, SEM, N2 adsorption–desorption and atomic absorption spectrophotometry analysis showed that the nanosized Fe0 was the main component of the 4ZVI/SBC activator, which was a mesopore material with an optimal FeCl3·6H2O/biomass impregnation mass ratio of 2.7 g/g. The 4ZVI/SBC activator showed an efficient degradation of phenol (95.65% for 30 min at 25 °C) with a large specific surface area of 78.669 m2·g−1. The recovery of 4ZVI/SBC activator after the degradation reaction of phenol can be realized with the small amount of dissolved iron in the water. The 4ZVI/SBC activator facilitated the activation of persulfate to degrade phenol into non-toxic CO2 and H2O. The trend of Cl−, SO42− and NO3− affected the removal efficiency of phenol by using the 4ZVI/SBC activator in the following order: NO3− > SO42− > Cl−. The one-step synthesis of the nanosized zerovalent-iron–biochar composite was feasible and may be applied as an effective strategy for controlling organic waste (e.g. phenol) by waste biomass.
Recent Advances in Multi-target Drugs Targeting Protein Kinases and Histone Deacetylases in Cancer Therapy
Authors: Ling Yong , Liu Ji , Qian Jianqiang , Meng Chi , Guo Jing , Gao Weijie , Xiong Biao , Ling Changchun , Zhang Yanan
Published: January 2020

Protein Kinase Inhibitors (PKIs) and Histone Deacetylase Inhibitors (HDACIs) are two important classes
of anticancer agents and have provided a variety of small molecule drugs for the treatment of various types of
human cancers. However, malignant tumors are of a multifactorial nature that can hardly be “cured” by targeting a
single target, and treatment of cancers hence requires modulation of multiple biological targets to restore the physiological
balance and generate sufficient therapeutic efficacy. Multi-target drugs have attracted great interest because
of their advantages in the treatment of complex cancers by simultaneously targeting multiple signaling
pathways and possibly leading to synergistic effects. Synergistic effects have been observed in the combination of
kinase inhibitors, such as imatinib, dasatinib, or sorafenib, with an array of HDACIs including vorinostat, romidepsin,
or panobinostat. A considerable number of multi-target agents based on PKIs and HDACIs have been
developed. In this review, we summarize the recent literature on the development of multi-target kinase-HDAC
inhibitors and provide our view on the challenges and future directions on this topic.
A Computational Study of Natural Compounds from Bacopa monnieri in the Treatment of Alzheimer's Disease
Authors: Jamal Qazi M.S. , Siddiqui Mughees U. , Alharbi Ali H. , Albejaidi Fahad , Akhtar Salman , Alzohairy Mohammad A. , Kamal Mohammad A. , Kesari Kavindra K.
Published: January 2020

:

Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence
and progression indicate the needs for best treatment options. The present bioinformatics study explores the
binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase
(BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds
as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The
analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a
significant role in finding out the interacting position at the active site. However, after analyzing the binding
energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol
could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that
the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of
inhibitors.
Green-Synthesized FeSO4 Nanoparticles Exhibit Antibacterial and Cytotoxic Activity by DNA Degradation
Authors: Bharath B. , Sasidharan Santanu , Bhamidipati Sai K. , Saudagar Prakash
Published: January 2020

Objective:

The current study reports a green, rapid and one-pot synthesis of FeSO4 nanoparticles
using Hibiscus rosasinensis floral extract as a reducing and capping agent. 0.5M of FeSO4 was
stirred with the floral extract of H. rosasinensis for around 20 minutes at 37ºC and pH 7.

Methods:

The development of pink color was considered as the endpoint of reduction and the nanoparticles
were characterized by UV-Vis spectrum, EDAX, DLS, FTIR, FESEM, and XRD. UV-Vis spectral
analysis indicated a peak at 530 nm and EDAX measurement revealed the presence of Fe, S, O and
C elements in the nanoparticle sample. The FTIR analysis showed amines, alcohol and alkene groups
that act as capping agents for the produced nanoparticles. FESEM and XRD determination presented
FeSO4 nanoparticles of 40-60 nm in size. The synthesized nanoparticles were found to have antibacterial
activity against 6 pathogenic bacteria with MIC and MBC of 40 mg/mL.

Results:

To determine the toxicity at the eukaryotic level, brine shrimp toxicity assay was conducted
and 100% mortality was found at concentrations >0.06 mg/mL. Gel shift assay suggested the mechanism
of toxicity of FeSO4 NPs by binding and degradation of DNA molecules.

Conclusion:

From the results, the authors demonstrate the ease of green synthesis of FeSO4 nanoparticles
and its bioactivity that may have potential applications as drugs and drug delivery systems against
various diseases.
Peptide Nanomaterials for Drug Delivery Applications
Authors: Pentlavalli Sreekanth , Coulter Sophie , Laverty Garry
Published: January 2020

Self-assembled peptides have been shown to form well-defined nanostructures which display
outstanding characteristics for many biomedical applications and especially in controlled drug
delivery. Such biomaterials are becoming increasingly popular due to routine, standardized methods of
synthesis, high biocompatibility, biodegradability and ease of upscale. Moreover, one can modify the
structure at the molecular level to form various nanostructures with a wide range of applications in the
field of medicine. Through environmental modifications such as changes in pH and ionic strength and
the introduction of enzymes or light, it is possible to trigger self-assembly and design a host of different
self-assembled nanostructures. The resulting nanostructures include nanotubes, nanofibers, hydrogels
and nanovesicles which all display a diverse range of physico-chemical and mechanical properties.
Depending on their design, peptide self-assembling nanostructures can be manufactured with improved
biocompatibility and in vivo stability and the ability to encapsulate drugs with the capacity for
sustained drug delivery. These molecules can act as carriers for drug molecules to ferry cargo intracellularly
and respond to stimuli changes for both hydrophilic and hydrophobic drugs. This review explores
the types of self-assembling nanostructures, the effects of external stimuli on and the mechanisms
behind the assembly process, and applications for such technology in drug delivery.
Effect of Different Aβ Aggregates as Antigen on the Measure of Naturally Occurring Autoantibodies against Amyloid-β40/42 in IVIG
Authors: Cao Haijun , Du Xi , Zeng Renyong , Lv Zhaoji , Ye Shengliang , Jiang Peng , Wang Zongkui , Ma Li , Huang Yun , Li Changqing , Zhang Rong , Liu Fengjuan
Published: January 2020

Background:

The specific Intravenous Immunoglobulin (IVIG) for Alzheimer’s Disease
(AD) is developing, which contains a high level of naturally occurring autoantibodies against amyloid-β
(nAbs-Aβ), and the measure of nAbs-Aβ content is greatly essential. Though Enzyme-Linked Immunosorbent
Assay (ELISA) has been widely used in detecting the nAbs-Aβ content, the impact of Aβ aggregates
species chosen as antigen in ELISA on this measure has not been evaluated.

Objective:

To clarify the influence of different Aβ40/42 aggregates as antigen during ELISA on the content
of nAbs-Aβ40/42 measured in IVIG.

Method:

Preparation of various Aβ40/42 aggregates was performed by different aggregation solutions and
various lengths of time, and analyzed by western blot. Different Aβ40/42 aggregates as antigen were
adopted to measure the nAbs-Aβ40/42 content in IVIG by ELISA, and the control was carried out to reduce
interference of nonspecific binding. The Bonferroni and Dunnett’s T3 were used
for statistical analysis.

Results:

The duration for the formation of Aβ40/42 aggregates had more effect on detecting nAbs-Aβ40/42
content in IVIG than the aggregation solution. Higher content of nAbs-Aβ40/42 in the same IVIG was
displayed when measured with Aβ40/42 aggregates at day 3, instead of at day 0.5 and day 7.0. The nAbs-
Aβ40/42 contents in the same IVIG measured with Aβ40/42 aggregates prepared in different solutions were
obviously different, but there was no significant regularity among them.

Conclusion:

The nAbs-Aβ40/42 content in the same IVIG is significantly different when measured with
Aβ40/42 aggregated under different conditions. The nAbs-Aβ40/42 content in IVIG by antigen-dependent
measures, like ELISA, is uncertain.
Design, Synthesis and Biological Evaluation of Novel 4-phenoxypyridine Derivatives Containing Semicarbazones Moiety as Potential c-Met Kinase Inhibitors
Authors: Li Jun , Li Jie , Zhang Jiaojiao , Shi Jiantao , Ding Shi , Liu Yajing , Chen Ye , Liu Ju
Published: January 2020

Background:

The Hepatocyte Growth Factor Receptor (HGFR) c-Met is over-expressed and/or
mutated in various human tumor types. Dysregulation of c-Met/HGF signaling pathway affects cell proliferation,
survival and motility, leading to tumor growth, angiogenesis, and metastasis. Therefore, c-Met has become
an attractive target for cancer therapy.

Objective:

This study is aimed to evaluate a new series of 4-phenoxypyridine derivatives containing semicarbazones
moiety for its cytotoxicity.

Methods:

A series of novel 4-phenoxypyridines containing semicarbazone moieties were synthesized and
evaluated for their in vitro cytotoxic activities against MKN45 and A549 cancer cell lines and some selected
compounds were further examined for their inhibitory activity against c-Met kinase. In order to evaluate the
mechanism of cytotoxic activity of compound 24, cell cycle analysis, Annexin V/PI staining assay, AO/EB
assay, wound-healing assay and docking analysis with c-Met were performed.

Results:

The results indicated that most of the compounds showed moderate to good antitumor activity. The
compound 28 showed well cytotoxic activity against MKN45 and A549 cell lines with IC50 values of 0.25μM
and 0.67μM, respectively. Compound 24 showed good activity on c-Met and its IC50 value was 0.093μM.

Conclusion:

Their preliminary Structure-Activity Relationships (SARs) studies indicated that electronwithdrawing
groups on the terminal phenyl rings are beneficial for improving the antitumor activity. Treatments
of MKN45 cells with compound 24 resulted in cell cycle arrest in G2/M phase and induced apoptosis in a
dose-dependent manner. In addition, AO/EB assays indicated 24 induced dose-dependent apoptosis of A549
and MKN45 cells. Wound-healing assay results indicated that compound 24 strongly inhibited A549 cell
motility.
The Effect of a Newly Synthesized Ferrocene Derivative against MCF-7 Breast Cancer Cells and Spheroid Stem Cells through ROS Production and Inhibition of JAK2/STAT3 Signaling Pathway
Authors: Nourbakhsh Mitra , Farzaneh Shabnam , Taghikhani Adeleh , Zarghi Afshin , Noori Shokoofe
Published: January 2020

Background:

Breast Cancer Stem Cells (BCSCs) possess the ability of self-renewal and cellular
heterogeneity, and therefore, play a key role in the initiation, propagation and clinical outcome of breast cancer.
It has been shown that ferrocene complexes have remarkable potential as anticancer drugs.

Objective:

The present study was conducted to investigate the effects of a novel ferrocene complex, 1-
ferrocenyl-3-(4-methylsulfonylphenyl)propen-1-one (FMSP) on MCF-7 breast cancer cell line and its derived
mammospheres with cancer stem cell properties.

Methods:

Mammospheres were developed from MCF-7 cells and validated by the evaluation of CD44 and
CD24 cell surface markers by flow cytometry as well as of the expression of genes that are associated with stem
cell properties by real-time PCR. Cells viability was assessed by a soluble tetrazolium salt (MTS) after the
treatment of cells with various concentrations of FMSP. Apoptosis was evaluated by flow cytometry analysis of
annexin V and PI labeling of cells. Reactive Oxygen Species (ROS) production was measured using a cellpermeable,
oxidant-sensitive fluorescence probe (carboxy-H2DCFDA). The involvement of the JAK2/STAT3
pathway was also investigated by western blotting.

Results:

FMSP could successfully prevent mammosphere formation from differentiated MCF-7 cells and significantly
down-regulated the expression of genes involved in the production of the stem cell properties including
Wnt1, Notch1, β -catenin, SOX2, CXCR4 and ALDH1A1. FMSP decreased cell viability in both MCF-7
cells and spheroid cells, although MCF-10A cells were unaffected by this compound. Apoptosis was also dramatically
induced by FMSP, via ROS production but independent of CD95 activation. Phosphorylation levels of
JAK2 and STAT3 were also found to be significantly attenuated even in the presence of IL-6, the putative activator
of the JAK/STAT pathway.

Conclusion:

FMSP can effectively target BCSCs via ROS production and modulation of major signaling pathways
that contribute to the stemness of breast cancer cells, and therefore, might be considered a promising anticancer
agent after in vivo studies.
Analysis of Bending Ability of Soft Pneu-nets Actuators for Soft Robotics
Authors: Wang Yazhou
Published: January 2020

Background:

There has been an increasing interest in the soft pneumatic networks (also
referred to as pneu-nets) actuators for soft robotics due to their innate softness, ease of fabrication
and high customizability. More and more structures of the soft pneu-nets actuators are reported in
various relevant patents and papers. The bending ability of soft pneu-nets actuator is one of the key
characterizing performances. It is characterized as a function of input air pressure as well as geometrical
and material parameters, and influenced by the air pressures and design angle.

Objective:

In this paper, a new structure soft pneu-nets actuators (with different chambers morphology)
was developed. The goal of this paper is to analyze the influence of the air pressures and design
angle on the bending ability of the soft pneu-nets actuators with a new structure.

Method:

Firstly, a new structure of soft pneu-nets (adjusting chamber’s shape), based on the soft
pneu-nets architecture described previously was developed. Then, the soft pneu-nets actuators were
treated with a standard Finite Element Method (FEM) using the Abaqus 6.14 Computer-Aided Engineering
(CAE) package. Several soft pneu-nets actuators with various design angles were analyzed
to investigate the influence of the design angle on the bending ability. In order to investigate
the effect of these parameters, the relationship between the angle of bending and these parameters
was conducted. Thirdly, the influence of chambers morphology on the bending ability of soft pneunets
actuators could be assessed.

Results:

When the air pressure P is under 13.5 kPa, with increase the air pressure, the difference of
angle of bending under same design angle is less evident, but when the air pressure P is over 13.5
kPa, the difference of angle of bending at same design angle increase; At the same air pressure P,
when the air pressure P is under 13.5 kPa, the difference of the angle of the bending between different
design angle is less, The effect of gravity is greater than that of the air pressures P. When the air
pressure P is over 13.5 kPa, the design angle shows more influential on the angle of the bending.

Conclusion:

The angle of bending increases with the increase of the air pressures P; the chambers
with a bigger design angle (thinner inside walls) enabled greater bending at given air pressures P.
Microwave Breast Imaging Using Rotational Bistatic Impulse Radar for the Detection of Breast Cancer: Protocol for a Prospective Diagnostic Study (Preprint)
Authors: Sasada Shinsuke , Masumoto Norio , Song Hang , Emi Akiko , Kadoya Takayuki , Arihiro Koji , Kikkawa Takamaro , Okada Morihito
Published: January 2020

BACKGROUND

Mammography is the standard examination for breast cancer screening; however, it is associated with pain and exposure to ionizing radiation. Microwave breast imaging is a less invasive method for breast cancer surveillance. A bistatic impulse radar–based breast cancer detector has recently been developed.

OBJECTIVE

This study aims to present a protocol for evaluating the diagnostic accuracy of the novel microwave breast imaging device.

METHODS

This is a prospective diagnostic study. A total of 120 participants were recruited before treatment administration and divided into 2 cohorts: 100 patients diagnosed with breast cancer and 20 participants with benign breast tumors. The detector will be directly placed on each breast, while the participant is in supine position, without a coupling medium. Confocal images will be created based on the analyzed data, and the presence of breast tumors will be assessed. The primary endpoint will be the diagnostic accuracy, sensitivity, and specificity of the detector for breast cancer and benign tumors. The secondary endpoint will be the safety and detectability of each molecular subtype of breast cancer. For an exploratory endpoint, the influence of breast density and tumor size on tumor detection will be investigated.

RESULTS

Recruitment began in November 2018 and was completed by March 2020. We anticipate the preliminary results to be available by summer 2021.

CONCLUSIONS

This study will provide insights on the diagnostic accuracy of microwave breast imaging using a rotational bistatic impulse radar. The collected data will improve the diagnostic algorithm of microwave imaging and lead to enhanced device performance.

CLINICALTRIAL

Japan Registry of Clinical Trials jRCTs062180005; https://jrct.niph.go.jp/en-latest-detail/jRCTs062180005

INTERNATIONAL REGISTERED REPORT

DERR1-10.2196/17524
The impact of algorithmic decision-making processes on young people’s well-being (Preprint)
Authors: Perez Vallejos Elvira , Dowthwaite Liz , Creswich Helen , Portillo Virginia , Koene Ansgar , Jirotka Marina , McCarthy Amy , McAuley Derek
Published: January 2020

BACKGROUND

Algorithms rule the online environments and are essential for performing data processing, filtering, personalisation and other tasks. Research has shown that children and young people make up a significant proportion of Internet users, however little attention has been given to their experiences of algorithmically-mediated online platforms, or the impact of them on their mental health and well-being. The algorithms that govern online platforms are often obfuscated by a lack of transparency in their online Terms and Conditions and user agreements. This lack of transparency speaks to the need for protecting the most vulnerable users from potential online harms.

OBJECTIVE

To capture young people's experiences when being online and perceived impact on their well-being.

METHODS

In this paper, we draw on qualitative and quantitative data from a total of 260 children and young people who took part in a ‘Youth Jury’ to bring their opinions to the forefront, elicit discussion of their experiences of using online platforms, and perceived psychosocial impact on users.

RESULTS

The results of the study revealed the young people’s positive as well as negative experiences of using online platforms. Benefits such as being convenient and providing entertainment and personalised search results were identified. However, the data also reveals participants’ concerns for their privacy, safety and trust when online, which can have a significant impact on their well-being.

CONCLUSIONS

We conclude by making recommendations that online platforms acknowledge and enact on their responsibility to protect the privacy of their young users, recognising the significant developmental milestones that this group experience during these early years, and the impact that technology may have on them. We argue that governments need to incorporate policies that require technologists and others to embed the safeguarding of users’ well-being within the core of the design of Internet products and services to improve the user experiences and psychological well-being of all, but especially those of children and young people.

CLINICALTRIAL

N/A
EFFECTS OF EXTRA VIRGIN OLIVE OIL VERSUS RICE BRAN OIL ON GLYCEMIC CONTROL IN PATIENTS WITH TYPE-2 DIABETES MELLITUS
Authors: WIJAYANTHIE NADIYAH , GUNARTI DWIRINI RETNO , MANIKAM NURUL RATNA , YULHASRI
Published: January 2020

Objective: The purpose of this study was to determine the effect of extra virgin olive oil (EVOO) and rice bran oil (RBO) on glycemic control and lipid profiles in patients with type-2 diabetes mellitus (T2DM).

Methods: Ten patients with T2DM received 15 ml/day of EVOO or RBO. Levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TGs) were measured. RBO or EVOO was administered for 4 consecutive weeks. During a 2-week interval, the treatment was not administered. After this washout period, a crossover design was implemented by exchanging EVOO supplementation with RBO supplementation and vice versa for 4 consecutive weeks.

Results: Changes in levels of FBG, PBG, TC, LDL-C, and TGs were not significantly different in the two groups. However, significantly decreased the levels of HDL-C were observed in both groups.

Conclusion: RBO and EVOO had no significant influence on levels of FBG or PBG.
THE ROLE OF TREATMENT WITH HIGH-DOSE CORTICOSTEROIDS IN SEVERE LEPTOSPIROSIS WITH PULMONARY COMPLICATIONS
Authors: PARAMITHA MARIA SATYA , SUTRISUNA  , PUSPITASARI MYRA
Published: January 2020

Objective: To investigate the effectiveness of high-dose corticosteroids in patients with severe leptospirosis, especially in reducing morbidity and mortality rates.

Methods: Literature searches were conducted using PubMed® and SCOPUS®. One systematic review and one systematic review with meta-analysis were selected from three chosen studies.

Results: The systematic review from Rodrigo et al. only included qualitative synthesis from four interventional studies. Early administration of methylprednisolone can be beneficial; however, low number and poor methodological quality of the studies question the validity of this review. Duggal et al. stated that there was no significant difference in the therapeutic effects of early high-dose corticosteroids (P ³ 0.05; 95% CI: 0.81–1.37), early low-dose corticosteroids (P ³ 0.05; 95% CI: 0.3–1.03), and late low-dose corticosteroids (P ³ 0.05; 95% CI: 0.11–2.52). Limited number of studies and high statistical heterogeneity, however, are major drawbacks for this review.

Conclusion: Evidence about the role of high-dose corticosteroids in severe leptospirosis patients with pulmonary complications, especially their benefits, is still limited. Additional randomized, controlled trials with adequate statistical power still need to be conducted.
THE EFFECT OF LUNASIN ON LIVER HISTOPATHOLOGY OF MICE INDUCED BY AZOXIMETHANE (AOM) AND DEXTRAN SODIUM SULPHATE (DSS)
Authors: KUSMARDI1  , KHIPUTRA HERIYANTO , SALINAH
Published: January 2020

Objective: Azoximethane (AOM) and dextran sodium sulfate (DSS) are commonly used to induce colorectal cancer, but have side effects on the liver. AOM can induce hepatic histopathological changes such as the appearance of microvesicular steatosis and necrosis. DSS plays a role in causing inflammation and indirect scarring through colitis. This study aimed to determine in mice the effect of lunasin on the liver histopathology induced by AOM and DSS.

Methods: This was an experimental study conducted in BALB/c mice. The data analyzed were the results of quantification of foci of necrosis, steatosis, and dysplasia from liver preparations of mice given lunasin extract at doses of 20, 30, and 40 mg/kg and control group.

Results: This study showed a significant decrease in the number of foci of necrosis in the group given 30 mg/kg lunasin, with a mean score of 9.0±3.4 compared with the control group mean score of 14.0±0.8 (P = 0.017). There was also a significant decrease in the number of foci of steatosis in the group given 30 mg/kg lunasin with a mean score of 3.8±1.3 compared with the control group mean score of 11.5±1.9 (P = 0.002).

Conclusion: The results of this study indicate that lunasin at doses above 30 mg/kg can inhibit the formation of foci of necrosis and steatosis induced in mouse liver by AOM and DSS.
QUERCETIN IMPROVES THE EFFICACY OF SORAFENIB IN TRIPLE NEGATIVE BREAST CANCER CELLS THROUGH THE MODULATION OF DRUG EFFLUX TRANSPORTERS EXPRESSIONS
Authors: LOUISA MELVA , WARDHANI BANTARI WK
Published: January 2020

Objective: This study aimed to investigate whether quercetin is able to improve the efficacy of sorafenib in triple negative breast cancer cells and explore the possibility of drug efflux transporters modulation by quercetin.

Methods: We exposed MDA-MB-231, a triple negative breast cancer cell line, to several groups: sorafenib alone, quercetin alone, a combination of sorafenib-quercetin, and control. We determined cell viability over control weekly up to 4 w. At the end of the fourth week, mRNA expressions of drug efflux transporters (P-glycoprotein and breast cancer resistance protein [BCRP] and MRP2 [multidrug resistance-associated protein-2]) were examined.

Results: Sorafenib alone was shown to maintain its efficacy for only two weeks, while quercetin alone was able to maintain its effect for four weeks. A combination of sorafenib-quercetin showed the best cytotoxicity effects compared with sorafenib or quercetin alone and was able to maintain its efficacy for four weeks. There were increased mRNA expressions of P-glycoprotein, BCRP, and MRP2 after four weeks of treatment with sorafenib, while treatment with quercetin decreased the drug efflux transporters expressions. A combination of sorafenib-quercetin decreased the mRNA expressions of both P-glycoprotein and BCRP, compared with sorafenib alone.

Conclusion: We suggest that decreased expressions of both drug efflux transporters, P-glycoprotein and BCRP, mediated by quercetin ameliorate the efficacy of sorafenib in TNBC. Therefore, the addition of quercetin to sorafenib might be useful in the future in improving the therapeutic efficacy of sorafenib in triple negative breast cancer.
THE EFFECTS OF CURCUMIN ADMINISTRATION ON EXPRESSION PATTERNS OF VEGF AND COX-2 IN FERTILE ENDOMETRIUM: A RANDOMISED CLINICAL TRIAL
Authors: RAJUDDIN RAJUDDIN , WIWEKO BUDI , NUGROHO LUTFI
Published: January 2020

Objective: Curcumin (diferuloylmethane) is a a compound isolated from turmeric with biological activities, including antifertility. Curcumin inhibits COX-2 expression in granulosa cells of ovarian follicles and disrupts vascular endothelial growth factor (VEGF) derived angiogenesis in the endometrium, reducing endometrial receptivity. The purpose of this study was to examine the effects of curcumin on COX-2 and VEGF expression in endometrium of fertile women.

Methods: A prospective double-blind placebo-controlled clinical trial was conducted in a group of fertile women with regular menstrual cycles, aged between 20-30 y, married, and with children. Subjects were divided into a group receiving daily 800 mg encapsulated curcumin. Curcumin orally for ten days, starting on the third day of the first menstrual day, and a control group. Endometrial biopsy was performed using a microcuret and immunohistochemistry was used to assess VEGF and COX-2 expression. The results were analysed using an independent sample t-test.

Results: In the curcumin-treated group, VEGF expression was significantly lower than the control group (p<0.05), and COX-2 expression was higher but not significantly so (p>0.05).

Conclusion: The curcumin causes VEGF expression in endometrium is lower and negatively affects the growth of endometrial stromal cells.
ZINC OXIDE NANOPARTICLES AMELIORATE ALUMINUM CHLORIDE-INDUCED HEPATO-RENAL OXIDATIVE STRESS AND INFLAMMATION IN RATS
Authors: MAHMOUD SAHAR M. , KASSAB RAMI B. , MONEIM AHMED E. ABDEL
Published: January 2020

Objective: The present study was designed to evaluate the effect of zinc oxide nanoparticles (ZnO NPs) on Aluminum chloride (AlCl3)-induced hepato-renal injury. 

Methods: Animals were divided into, I-control group; rats received saline, II-AlCl3 group; animals received 100 mg AlCl3/kg body weight, III-ZnO NPs group; rats received 10 mg ZnO NPs/kg body weight, and IV group ZnO NPs+AlCl3. All rats were administered their respective doses daily for 6 w. Hepatorenal function parameters in sera; aminotransferases, bilirubin, urea, and creatinine were estimated. Lipid peroxide level and nitrite\nitrate ratio, glutathione content, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase activities and interleukin-1β, tumor necrosis factor-α levels were determined in both tissues. The histopathological and the immunohistochemical investigations of nuclear factor-kB expression were carried out. 

Results: ZnO NPs treatment to AlCl3-intoxicated rats significantly reduced Al accumulation (at p<0.05) in the hepatorenal tissue and increased zinc accumulation (at p<0.05) in liver and kidney, respectively, with respect to AlCl3-group, thus inhibiting oxidative stress and inflammation parameters represented by lipid peroxidation and nitric oxide levels (at p<0.05) compared to AlCl3 group and elevated antioxidant parameters (at p<0.05), compared to AlCl3 treated group, while suppressed interleukin-1β, tumor necrosis factor-α levels (at p<0.05) and the nuclear factor-kB activation in liver and kidney, especially in the kidney if compared to AlCl3-treated group. Hepatorenal function indices indicated significant decreases compared to AlCl3 group (at p<0.05).

Conclusion: Results indicated the ameliorative effect of ZnO NPs on aluminum-induced hepato-renal damage.