bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA PCGsEM1 Contributes to the Proliferation, Migration and Invasion of Non-small Cell Lung Cancer Cells via acting as a Sponge for miR-152-3p
Authors: Huang Jianhui , Lou Jian , Liu Xueni , Xie Yanru 
Published: August 2021

Background:
Long non-coding RNAs (lncRNAs) have been reported to play important roles in cellular
biological function. Aberrant expression of lncRNAs has been found to be related to the progression of
various diseases. LncRNA prostate cancer gene expression marker 1 (PCGEM1) has been demonstrated to be
involved in the initiation and progression of human cancers. However, to date, the clinical and functional significance
of PCGEM1 expression in NSCLC progression remains unknown.

Methods:
The expression of LncRNA PCGEM1 and miR-152-3p in NSCLC tissues and cells was analyzed using
quantitative real-time RT-PCR. Experiments using NSCLC cells were conducted to explore the influence of
PCGEM1 on tumor cell proliferation, migration and invasion.

Results:
Increased expression of PCGEM1 was observed in NSCLC tissues and cells compared with the corresponding
controls (all P <0.001). PCGEM1 expression was associated with NSCLC patients’ lymph node metastasis
and TNM stage (all P <0.05), and the knockdown of PCGEM1 in NSCLC cells led to inhibited cell
proliferation, migration and invasion. The further luciferase reporter assay and expression results showed that
miR-152-3p might be a target gene of PCGEM1 and mediate the effects of PCGEM1 on cell proliferation, migration
and invasion in NSCLC.

Conclusion:
Thus, the findings from the present study indicate that the NSCLC patients have significantly increased
PCGEM1 and decreased miR-152-3p expression and that the knockdown of PCGEM1 may inhibit
NSCLC cell proliferation, migration and invasion by sponging miR-152-3p. The PCGEM1/miR-152-3p axis
may provide novel therapeutic targets for NSCLC treatment.
In Vitro Cytotoxicity and Aromatase Inhibitory Activity of Flavonoids: Synthesis, Molecular Docking and In silico ADME Prediction
Authors: Shah Umang , Patel Samir , Patel Mehul , Jain Neeraj , Pandey Nilesh , Chauhan Alex , Patel Ashish , Patel Sandip 
Published: August 2021

Background:
Many natural and synthetic flavonoids have been studied and documented by inhibiting aromatase
enzymes for their anti-cancer activity against breast carcinoma. The aromatase enzyme is a possible target for
the estrogen's positive breast cancer receptor.

Objective:
Hence, a series of flavonoids have been synthesized and assessed for their in vitro cytotoxicity and aromatase
inhibitory activity.

Methods:
39 Flavonoids were synthesized and characterized by spectroscopic techniques, and their computational
study was performed using the maestro version of the Schrodinger. In-silico ADME properties were checked by
QikProp software. A total of 18 compounds were evaluated based on the docking score using cytotoxicity assay in
human breast cancer cell line MCF-7.

Results:
Of the 18 compounds tested, 07 compounds, namely 2b, 8b, 14b, 15b, 19b, 24b, and 30b flavonoids were
found to be more active with their IC50 values of 20.73 μM, 1.636 μM, 16.08 μM, 22.02 μM, 15.75 μM, 0.345 μM and
16.08 μM, respectively, compared with the reference drug letrozole. The in-vitro aromatase inhibitory activity of six
compounds 2b, 8b, 14b, 19b, 24b, and 30b was conducted using a fluorogenic assay kit. The values of IC50 for compounds
2b and 24b were found to be 0.31 μM and 0.36 μM, respectively.

Conclusion:
Therefore, it was concluded that compounds 2b and 24b had a potent inhibitory effect of aromatase compared
with letrozole with an IC50 value of 0.86 μM. At the same time, the other compounds 8b, 14b, 30b, and 19b were
considered to have similar aromatase inhibitory activity. Hence, their essential aromatase inhibitory activities make
them good lead candidates for developing potent inhibitors of aromatase.
The Effects and Regulatory Mechanism of Flavonoids from Stems and
Leaves of Scutellaria baicalensis Georgi in Promoting Neurogenesis and Improving
Memory Impairment Mediated by the BDNF-ERK-CREB Signaling
Pathway in Rats
Authors: Shengkai Ding , Qianqian Liu , Yazhen Shang 
Published: August 2021

Background:
It is well known that Alzheimer's Disease (AD) is a neurodegenerative disease
accompanied by memory impairment and major pathological changes of the extracellular Senile
Plaque (SP) and intracellular Neurofibrillary Tangles (NFTs). However, many pieces of evidence
indicate that neurogenesis disorders are also regarded as a new opinion in AD.

Objective:
This study aims to investigate the effects and regulatory mechanism of flavonoids from
the stems and leaves of Scutellaria baicalensis Georgi in promoting neurogenesis and improving
memory impairment mediated by BDNF-ERK-CREB signaling pathway in rats.

Methods:
Male Wistar rats were intracerebroventricularly injected with amyloid-beta protein 25-35
(Aβ25-35) in combination with Aluminum Trichloride (Alcl3) and recombinant human transforming
growth factor-β1 (RHTGF-β1) (composited Aβ), to establish an AD model. Morris water maze was
used to screen AD model rats and measure the learning and memory ability of model rats. The expression
of Ki67 protein, which is involved in cell neurogenesis, in the hippocampal gyrus of rats
was detected by the immunohistochemical method. The mRNA and protein expression levels of Grb2,
SOS1, Ras, ERK, and BDNF, in the BDNF-ERK-CREB signaling pathway, in the hippocampus
and cerebral cortex regions of rats were assayed by the Quantitative real-time PCR (qPCR) and
Western blotting methods, respectively.

Results:
Intracerebroventricular injection of composited Aβ could induce rats’ memory impairment,
decrease the protein expression of Ki67 in the hippocampal gyrus, and increase the mRNA
and protein expression levels of Grb2, SOS1, Ras, ERK, and BDNF in the hippocampus and cerebral
cortex. However, SSF could significantly ameliorate rats’ memory impairment induced by
composited Aβ, lower the Ki67 protein expression in the hippocampal gyrus, and regulate the abnormal
mRNA and protein expression levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus
and cerebral cortex regions of rat brains.

Conclusion:
Composited Aβ induced memory impairment, decreased neurogenesis and initiated
the abnormal mRNA and protein expressions of Grb2, SOS1, Ras, ERK, and BDNF in the BDNF-
ERK-CREB signaling pathway. The effects of SSF in promoting neurogenesis and improving
memory impairment may be related to the regulation of the abnormal expressions of Grb2, SOS1,
Ras, ERK, and BDNF molecules in the BDNF-ERK-CREB signaling pathway.
Flavonoids from Stems and Leaves of Scutellaria baicalensis Georgi Regulate
the Brain Tau Hyperphosphorylation at Multiple Sites Induced by
Composited Aβ in Rats
Authors: Shengkai Ding , Yazhen Shang 
Published: August 2021

Background:
Neurofibrillary Tangles (NFTs), formed by hyperphosphorylation of Tau
protein in Alzheimer's Disease (AD), arethe main pathomechanisms of neuronal degeneration,
which indicate a sign of brain disorder. NFTs are positively correlated with the degree of cognitive
impairment in AD.

Objective:
The objective of this study isto investigate the effect of flavonoids from the stems and
leaves of Scutellaria baicalensis Georgi (SSF) on the hyperphosphorylated expression levels at
multiple sites of Tau protein induced by β-amyloid protein 25-35 (Aβ25-35) in combination with aluminum
trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1)
(composited Aβ) in rats.

Methods:
The AD rat models were established by intracerebroventricular injection of Aβ25-35 and
AlCl3 combined with RHTGF-β1. On day 45, after the operation, the Morris water maze test was
conducted to screen the memory impairment of AD models. The successful model rats were randomly
divided into the model group and the three-dose drug group. The drug group rats were orally
administered SSF daily for 38 days. Western blotting was performed to detect the protein expression
of P-Tau (Thr 181), P-Tau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P--
Tau (Ser 396), and P-Tau (Ser 404) in the hippocampus and cerebral cortex of rats.

Results:
Compared with the sham group, the expression of P-Tau (Thr 181), P-Tau (Thr 217), P--
Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404)was significantly
increased in the hippocampus and cerebral cortex of the model group (P < 0.01). However,
the three doses of SSF, i.e., 35, 70, and 140 mg/kg, regulated the expression of phosphorylated Tau
proteinto varying degrees in the hippocampus and cerebral cortex of AD model rats (P < 0.01).

Conclusion:
SSF could significantly reduce the protein expression levels of P-Tau (Thr 181), PTau
(Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser
404), induced by the intracerebroventricular injection of composited Aβ, in rats’ brain. These results
indicated that the neuro-protection and the improvement in the impaired memory of rats by
SSF were due to the inhibition of hyperphosphorylation of Tau protein at multiple sites in rats'
brain.
Erlotinib Hydrochloride Novel Drug Delivery Systems: A Mini Review Unravelling the Role of Micro- and Nanocarriers
Authors: Taiwade Chaitali , Fulfager Aditi , Bhargave Hardik , Soni Govind , Yadav Khushwant 
Published: August 2021

:
Erlotinib is a tyrosine kinase inhibitor and it can treat tumors, such as pancreatic and locally
advanced lung cancer or metastatic cancer. The traditional formulation of erlotinib currently
available is an oral delivery type that presents serious side effects such as hepatotoxicity, skin rashes,
gastrointestinal disturbance, renal dysfunction, drug resistance and hematological symptoms.
Besides this, other disadvantages of erlotinib provided mostly by oral administration are the comprehensive
metabolism, low bioavailability, poor solubility and off-target impact. Overcoming
such unfavorable attributes of the medication, innovative medication delivery mechanisms like
nanocapsules, liposomes, microspheres, microparticles solid lipid nanoparticles, nanosponge, and
nanoparticles have been studied that have really shown their lead over traditional formulations.
This article summarizes the novel erlotinib drug delivery systems to boost its clinical efficacy and
reduce systemic toxicity. Novel formulations of erlotinib will offer positive outcomes in cancer
therapy and will play an important part in improving the drug's therapeutic potential.
Block Batik from Natural Material of Soil on Fabric Dyes
Authors: Samin Mohd Azhar , Ramli Nor Azrin , Legino Rafeah 
Published: August 2021

Natural elements of soil are a potential medium for block batik. The local batik producers usually use synthetic dyes, which contributed pollute the environment. There is a need for more natural dye options in block batik fabric dyeing. The practices effectively reduce waste emissions. This option will support an alternative to the batik industries, which is the current issues dealing with environmental challenges that sparked this project. This study employs an experimental textile approach. This study aims to identify soil types that can be used as colourants on fabrics suitable for batik block printing. This study will introduce eco-friendly dyes to the local batik industry.
Keywords: Batik; Block; Dyes; Fabric; Natural material; Soil
eISSN: 2398-4287© 2021. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians/Africans/Arabians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.
DOI: https://doi.org/10.21834/ebpj.v6iSI5.2934
Digital Technology Tools to Examine Patient Adherence to a Prescription-Only Omega-3 Polyunsaturated Fatty Acid Therapy To Mitigate Cardiovascular Risk: Protocol for a Prospective Observational Study and Preliminary Demographic Analysis
Authors: Arutyunov Gregory P , Arutyunov Alexander G , Ageev Fail T , Fofanova Tatiana V 
Published: August 2021

Background
Sustained adherence and persistence with prescription medications is considered essential to achieve maximal treatment benefit for patients with major chronic, noncommunicable diseases such as hyperlipidemia and lipid-associated cardiovascular disease. It is widely documented, however, that many patients with these conditions have poor long-term adherence to their treatments. The population of Russia is affected by poor adherence in the same ways as populations elsewhere and continues to have high rates of cardiovascular disease.

Objective
The purpose of this study was to examine patient adherence to a prescription-only preparation of highly purified omega-3 polyunsaturated fatty acids (1.2 to 1 eicosapentaenoic acid to docosahexaenoic ratio, 90% purity) in a large sample of patients at risk for cardiovascular diseases using digital technology to monitor patient behavior and as an outreach facility for patient education and engagement.

Methods
We conducted a 6-month prospective observational study (DIAPAsOn) at >100 centers in the Russian Federation. A bespoke electronic data capture and patient engagement system were developed with a well-established Russian technology supplier that enables information obtained during clinic visits to be supplemented by remote patient self-reporting. Other aspects of the program included raising patients' awareness about their condition via educational materials available in personal patient accounts in the electronic system.

Results
From an initial cohort of 3000 patients, a safety population of 2572 patients (age: mean 60 years) with an equal proportion of men and women has been characterized. There was widespread concomitant cardiovascular pathology and commensurate use of multiple classes of cardiovascular medication, notably lipid-modifying and antihypertensive drugs. The program was completed by 1975 patients, of whom 780 were prescribed highly purified omega-3 polyunsaturated fatty acid supplements for secondary prevention after myocardial infarction and 1195 were prescribed highly purified omega-3 polyunsaturated fatty acid supplements for hypertriglyceridemia. Data collection and analysis have been completed.

Conclusions
DIAPAsOn will provide insights into patient adherence with prescription-grade omega-3 polyunsaturated fatty acid therapy and perspectives on the role of mobile technology in monitoring and encouraging adherence to therapy.
Patient-Level Cancer Prediction Models From a Nationwide Patient Cohort: Model Development and Validation
Authors: Lee Eunsaem , Jung Se Young , Hwang Hyung Ju , Jung Jaewoo 
Published: August 2021

Background
Nationwide population-based cohorts provide a new opportunity to build automated risk prediction models at the patient level, and claim data are one of the more useful resources to this end. To avoid unnecessary diagnostic intervention after cancer screening tests, patient-level prediction models should be developed.

Objective
We aimed to develop cancer prediction models using nationwide claim databases with machine learning algorithms, which are explainable and easily applicable in real-world environments.

Methods
As source data, we used the Korean National Insurance System Database. Every Korean in ≥40 years old undergoes a national health checkup every 2 years. We gathered all variables from the database including demographic information, basic laboratory values, anthropometric values, and previous medical history. We applied conventional logistic regression methods, light gradient boosting methods, neural networks, survival analysis, and one-class embedding classifier methods to effectively analyze high dimension data based on deep learning–based anomaly detection. Performance was measured with area under the curve and area under precision recall curve. We validated our models externally with a health checkup database from a tertiary hospital.

Results
The one-class embedding classifier model received the highest area under the curve scores with values of 0.868, 0.849, 0.798, 0.746, 0.800, 0.749, and 0.790 for liver, lung, colorectal, pancreatic, gastric, breast, and cervical cancers, respectively. For area under precision recall curve, the light gradient boosting models had the highest score with values of 0.383, 0.401, 0.387, 0.300, 0.385, 0.357, and 0.296 for liver, lung, colorectal, pancreatic, gastric, breast, and cervical cancers, respectively.

Conclusions
Our results show that it is possible to easily develop applicable cancer prediction models with nationwide claim data using machine learning. The 7 models showed acceptable performances and explainability, and thus can be distributed easily in real-world environments.
Advancing Intersectional Discrimination Measures for Health Disparities Research: Protocol for a Bilingual Mixed Methods Measurement Study
Authors: Scheim Ayden I , Bauer Greta R , Bastos João L , Poteat Tonia 
Published: August 2021

BackgroundGuided by intersectionality frameworks, researchers have documented health disparities at the intersection of multiple axes of social status and position, particularly race and ethnicity, gender, and sexual orientation. To advance from identifying to intervening in such intersectional health disparities, studies that examine the underlying mechanisms are required. Although much research demonstrates the negative health impacts of perceived discrimination along single axes, quantitative approaches to assessing the role of discrimination in generating intersectional health disparities remain in their infancy. Members of our team recently introduced the Intersectional Discrimination Index (InDI) to address this gap. The InDI comprises three measures of enacted (day-to-day and major) and anticipated discrimination. These attribution-free measures ask about experiences of mistreatment because of who you are. These measures show promise for intersectional health disparities research but require further validation across intersectional groups and languages. In addition, the proposal to remove attributions is controversial, and no direct comparison has ever been conducted.ObjectiveThis study aims to cognitively and psychometrically evaluate the InDI in English and Spanish and determine whether attributions should be included.MethodsThe study will draw on a preliminary validation data set and three original sequentially collected sources of data: qualitative cognitive interviews in English and Spanish with a sample purposively recruited across intersecting social status and position (gender, sexual orientation, race and ethnicity, socioeconomic status, age, and nativity); a Spanish quantitative survey (n=500; 250/500, 50% sexual and gender minorities); and an English quantitative survey (n=3000), with quota sampling by race and ethnicity (Black, Latino/a/x, and White), sexual or gender minority status, and gender.ResultsThe study was funded by the National Institute on Minority Health and Health Disparities in May 2021, and data collection began in July 2021.ConclusionsThe key deliverables of the study will be bilingual measures of anticipated, day-to-day, and major discrimination validated for multiple health disparity populations using qualitative, quantitative, and mixed methods.International Registered Report Identifier (IRRID)PRR1-10.2196/30987
Applying Butterfly Method in the Learning of Addition and Subtraction of Fractions
Authors: Laidin Dalilah Rauqah , Tengah Khairul Amilin 
Published: August 2021

Several researches attempt to improve the performance in addition and subtraction of fraction by focusing on students’ understanding, such as applying fraction tiles manipulatives and number line in the teaching, or using visual aids such as area model and drawings or virtual diagrams. Similarly, few studies focus on adopting simple procedures that will facilitate students in attempting the topic. Butterfly Method is an approach that not only simplifies the pedagogical approach of learning addition and subtraction of fraction, but also indirectly promotes students’ conceptual understanding in the topic. Yet this approach is not commonly practiced in Brunei. This action research employed quantitative approach involving fourty-one Year 9 IGCSE level students from a government secondary school in Brunei Darussalam. The study aimed to investigate the effect on applying Butterfly Method in the learning of addition and subtraction of fraction through pre-test and post-test. The study revealed a significant improvement in students’ performance through Wilcoxon Signed rank test (Z = 4.2332, p-value < 0.05), with large effect size (r = 0.6611). This is also supported with the improvement of the overall mark distribution of students from pre-test to post-test, with Hake’s normalised gain values indicated majority of the participants achieved high (56.1%), medium (7.32%) and low (2.44%) improvements. Item analysis also indicated overall improvement of correct attempts in questions related to addition and subtraction of fraction, most apparently on fraction problems involving denominators not multiple of each other, improper fractions and mixed numbers. Thus, applying Butterfly Method significantly improved the overall students’ performance in the learning of addition and subtraction of fractions.
Tendencias temporales del cáncer de cuello uterino invasivo en mujeres entre 20 y 39 años en Manizales, Colombia. 2003-2018
Authors: Arango Arango María Del Pilar 
Published: August 2021

Objetivo: Analizar la tendencia de la incidencia de cáncer de cuello uterino invasivo en mujeres entre 20 y 39 años en Manizales, Colombia, 2003-2018.
Materiales y métodos: Estudio observacional, descriptivo, retrospectivo, de base poblacional. Se evaluaron las tendencias temporales en la incidencia (con referencia a Población Segi, por 100.000 mujeres/año) utilizando la regresión de Joinpoint (Joint Point Regression Program v. 4.7.0.0 del National Cancer Institute de los EEUU) para estimar los cambios porcentuales anuales y años de variación significativa en las tendencias.
Resultados: Se realizó el estudio con un total de 116 pacientes, cuya edad promedio al momento del diagnóstico fue 33.7 años. Sólo se hallaron 3 casos de cáncer invasivo en mujeres entre 20 y 25 años. El mayor número de casos se presentó en el grupo de mujeres de 35 a 39 años. El tipo histológico más frecuente fue el carcinoma escamocelular. El 45.6% de los casos se diagnosticaron en etapas tempranas. El Cambio Porcentual Anual Promedio calculado mediante el modelo de regresión Joinpoint mostró un descenso de 7,9% en la tasa de incidencia entre 2003 y 2018, con un punto de quiebre en el año 2010. Conclusiones: El cáncer de cuello uterino en Manizales tiene escasa frecuencia en mujeres menores de 25 años y para edades entre 20 y 39 años muestra una tendencia a la disminución en el tiempo, en particular desde el año 2010 en adelante.