bluuebunny/crossref_metadata_2025_split huggingface dataset:
ProBDNF is a Novel Mediator of the Interaction Between MDA-MB- 231 Breast Cancer Cells and Brain Microvascular Endothelial Cells
Authors: Alhusban Laila , Ayoub Nehad M. , Alhusban Ahmed 
Published: November 2020

Aim:
The current work aims to assess the role of proBDNF/BDNF in the
interaction between brain microvascular endothelial cells and the MDA-MB-231 breast
cancer cell line that has been consistently reported to cause brain metastasis.

Background:
Breast cancer brain metastasis (BM) is a significant health problem with
limited therapeutic options. The development of BM is a multistep process that requires
constant interaction with brain vasculature and the development of tumor blood supply.
The benefits of anti-angiogenic modalities, based on antagonizing vascular endothelial
growth factor in breast cancer metastasis, did not prove to be effective. Brain-derived
neurotrophic factor (BDNF) is a neurotrophin with a reported angiogenic effect. There is
a lack of data regarding the involvement of BDNF in metastatic breast cancer interaction
with brain microvascular endothelial cells (HBEC-5i).

Methods:
Using an adaptive transfer design, the cross-talk between HBEC-5i and MDAMB-
231 cell was investigated. HBEC-5i were treated with MDA-MB-231-conditioned
media, and the involvement of BDNF/proBDNF in the interaction was assessed using
both release and inhibitor-based assays in migration and in vitro tube formation assay.

Results:
MDA-MB-231 and HBEC-5i released total BDNF (250 vs. 80 pg/ml,
respectively). MDA-MB-231 conditioned media inhibited the migration of HBEC-5i by
more than 80% (p<0.05) and tube formation by 75% (p<0.05). Neutralizing mature
BDNF did not alter the MDA-MB-231 induced anti-angiogenic effect, which was
completely blunted by antagonizing proBDNF. MDA-MB-231 released proBDNF (131.5
pg/ml), and more than 60% of total BDNF released was in the pro-form.

Conclusion:
proBDNF is a novel mediator of breast cancer-induced anti-angiogenic
effect in brain endothelial cells.
Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs
Authors: He Xi , Hu Wenjun , Meng Fanhua , Li Xingzhou 
Published: November 2020

Background:
The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum
antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation
product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the
low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant
first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide.

Objective:
Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the
acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated
that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system
exposure of tizoxanide.

Method:
These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model
for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities.

Results:
The results indicated that the plasma concentration and the systemic exposure of tizoxanide
(T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced
by the equimolar dosage of nitazoxanide. It was also found that the plasma concentration and
the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide.

Conclusion:
Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide
prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the
active ingredient tizoxanide.
Synthesis of N-acyl Derivatives of Aminocombretastatin A-4 and Study of their Interaction with Tubulin and Downregulation of c-Myc
Authors: Agut Raül , Falomir Eva , Murga Juan , Martín-Beltrán Celia , Gil-Edo Raquel , Pla Alberto , Carda Miguel , Díaz J. Fernando , Josa-Prado Fernando , Marco J. Alberto 
Published: November 2020

Background:
Six N-acyl derivatives of aminocombretastatin A-4 have been synthesized
and evaluated according to their interaction with tubulin and as c-Myc downregulators.

Aims:
In search of new promising anti-cancer agents.

Objective:
This study is focused on the synthesis and the biological evaluation of N-acyl derivatives
of aminocombretastatin A-4 (CA-4). Docking studies were carried out to find out whether the synthetic
derivatives could bind to tubulin at the colchicine site in a conformation similar to that of CA-
4. The synthetic derivatives' effect on the proliferation of several cancer cells and non-cancer cells
has been measured. Their effect on tubulin polymerization, cell cycle distribution, the microtubule
network and c-Myc expression has also been evaluated.

Method:
A set of six N-acyl derivatives was achieved by means of a peptide-type coupling of aminocombretastatin
A-4 and the corresponding carboxylic acid. The synthetic compounds' ability to
inhibit cell proliferation was measured by MTT assay against three human carcinoma cell lines (colorectal
HT-29, lung A549, and breast adenocarcinoma MCF-7) and one non-tumor cell line (HEK-
293). Turbidimetry time-course measurements evaluated the inhibition of tubulin polymerization.
The action of the synthetic derivatives on cell cycle distribution was measured by flow cytometry and
their effects on the microtubule network were determined by immunofluorescence microscopy. Finally,
the downregulation of the synthetic derivatives on c-Myc protein was quantified by ELISA
assay, while the effect on c-Myc gene was measured by RT-qPCR analysis.

Results:
Derivatives bearing pentanoyl (compound 2), hexanoyl (compound 3), and heptanoyl (compound
4) side chains show anti-proliferative activities on the HT-29 line in the low nanomolar range,
with values similar to that exhibited by AmCA-4 but far exceeding those of CA-4. Compounds 1
(butanoyl side chain) and 2-3 inhibit tubulin polymerization in vitro in a manner similar to that of
CA-4 and AmCA-4 whereas compounds 4, 5 (octanoyl side chain) and 6 (dodecanoyl side chain)
may be considered as partial inhibitors of tubulin polymerization. While all derivatives are able to
accumulate cells in G2/M phase, compounds with the longest acyl chains (5 and 6) are the least active
ones in this particular action. Moreover, compounds 2-3 were the most active ones as c-Myc
downregulators.

Conclusion:
Our studies show that the most active compounds in the disruption of the microtubule
network are also the most potent ones in the downregulation of c-Myc expression.

Other:
Compounds 2 and 3 are good candidates for in vivo studies as they combine the best antimitotic
and c-Myc downregulation activities at low doses.
Antibody Immobilization Techniques in Mass Sensitive Immunosensor:
Enhanced Sensitivity through Limited Mass Load
Authors: Kırali Kübra , Brimo Nura , Serdaroğlu Dilek Çökeliler 
Published: November 2020

Background:
Biosensors are analytical devices that include a sample-delivery approach between a
biological recognition element and a transducer required to convert the physicochemical change produced from the
interaction of biological molecules-receptor interaction into signal. The immunosensor is a special type of biosensors that
includes an antibody as a biorecognition element to detect analyte as antigens. In mass-sensitive sensors, antigen-antibody
interactions can be specified by measuring the frequency change and most commonly knowns are surface acoustic wave,
bulk acoustic wave, quartz crystal microbalance and microcantilevers.

Methods:
Different methods for antibody immobilization including functionalization of the transducer surface with
specific groups have been reported for antibody immobilization. This stage affects the limit of detection and overall
performance. In this review, perspectives on immobilization strategies of mass sensitive immunosensors according to
transducer types will be presented. The choice of immobilization methods and their impact on performance in terms of
capture molecule loading, orientation and signal improvement is will also be discussed.

Results:
One of the most critical point during configuration of the biorecognition layer is to improve the sensitivity.
Therefore, we initially focused on comparisons of the antibody immobilization strategies in the biorecognition layer in
terms of mass load level and high sensitivity.

Conclusion:
The lack of significant data on the mass accumulations up to the functionalization and antibody
immobilization steps, which are the basis of immusensor production, has been identified. However, mass sensitive
immunosensors have the potential to become more common and effective analytical devices for many application areas.
New Strategies for Clinical Trials in Autism Spectrum Disorder
Authors: Pauly Rini , Ziats Catherine A. , Abenavoli Ludovico , Schwartz Charles E. , Boccuto Luigi 
Published: November 2020

Background:
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that poses several
challenges in terms of clinical diagnosis and investigation of molecular etiology. The lack of knowledge on the pathogenic
mechanisms underlying ASD has hampered the clinical trials that so far have tried to target ASD behavioral symptoms. In
order to improve our understanding of the molecular abnormalities associated with ASD, a deeper and more extensive
genetic profiling of targeted individuals with ASD was needed.

Methods:
The recent availability of new and more powerful sequencing technologies (third-generation sequencing) has
allowed to develop novel strategies for characterization of comprehensive genetic profiles of individuals with ASD. In
particular, this review will describe integrated approaches based on the combination of various omics technologies that
will lead to a better stratification of targeted cohorts for the design of clinical trials in ASD.

Results:
In order to analyze the big data collected by assays such as whole genome, epigenome, transcriptome, and
proteome, it is critical to develop an efficient computational infrastructure. Machine learning models are instrumental to
identify non-linear relationships between the omics technologies and therefore establish a functional informative network
among the different data sources.

Conclusion:
The potential advantage provided by these new integrated omics-based strategies is to better characterize the
genetic background of ASD cohorts, identify novel molecular targets for drug development, and ultimately offer a more
personalized approach in the design of clinical trials for ASD.
Implementation of Problem- Based Learning Model Assisted by E-Modules on Students' Critical Thinking Ability
Authors: Rahmat M Rahmat , Arip Asep Ginanjar , Nur Sofyan H. 
Published: November 2020

Education is a significant factor to shape human beings as a whole. The ability to think for humans plays an important role to develop information. The issue of lack of ability to think critically in Sahida Lemah Abang Vocational High School needed to be addressed. One learning model that can be utilized to guide students to think critically is Problem Based Learning (PBL) using an e-module as the resource of learning material. The study aims to examine the implementation of Problem Based Learning model using e-module and its influence on students' critical thinking ability. This study used a quasi-experiment with nonequivalent control group design as its research design. In using the research design, two observations have been conducted; one was before the experiment called Pre-Test (O1) and one after the experiment of this study called the post-test (O2). There are two samples in this study; one is the experimental group and the other is the control group. The study was done in Sahida Lemah Abang Vocational High School. The data was gathered by using tests and observation sheets of the learning process. The result in this study shows averagely that the implementation in each of the learning stages has gained 95.7% which is in the category of very good value. The most significant difference is from the fifth indicator "developing strategy and tactic", n gain of experimental class and control class is 5.83 and 0.23 respectively. As the result of the hypothesis test is Sig. 0.035 which means that there is a significant difference in students' ability to think critically between the students in the experimental class and the control class, the students in the experimental class think more critically than the students in the control class.
Engaging Students’ Information Literacy Ability On The 1945 Constitution Toward Android (Gejog Lesung) Based E-Learning Media
Authors: Rukmana Isna Sari , Marzuki Marzuki , Fenditasari Kharisma 
Published: November 2020

This study aims to analyze students' information literacy ability enhancement using android (gejog lesung) based e-learning media on the 1945 constitution. The method used in this study was a quasi-experimental method. This research used 35 students as subjects. The test used in this study aims to collect data consisting of pretest and posttest information literacy questions with HOTs criteria for information literacy skills and consisting of ten multiple-choice questions according to high order thinking skills criteria then checked for the Content Validity Index. Data analysis is using a t-test. The result of this study is gejog lesung it is able to improve students’ information literacy ability on the 1945 constitution of 1,4 in the high category. So, it can be concluded that engaging students’ ability of information literacy on the 1945 constitution toward android (gejog lesung) based e-learning media has a great influence on improving students’ information literacy ability.
Two Suns? The State of Amazon? Bezonomics, market control and the algorithmic state.
Authors: Cleave Peter 
Published: November 2020

Why do people vote? What do they need?
The book Bezonomics by Brian Dumaine has got me back to thinking about such questions. People might vote for better quality of life and Amazon, the company founded by Bezos might now be supplying this according to what people like. Amazon offers options to prefer across their lives.
Twenty Years of the Remedy of Reinstatement in the Law of Unfair Dismissal in South Africa: Some Preliminary, Jurisprudential and Sundry Issues
Authors: Okpaluba Chuks , Budeli-Nemakonde Mpfariseni 
Published: November 2020

Reinstatement as a remedy for unfair dismissal was known to and applied by the Industrial Court of the bygone labour relations regime of 1956. It was, however, the Labour Relations Act 66 of 1995 (LRA) that entrenched this remedy in the modern South African labour relations system designed essentially to do justice between the employer and the employee and, fundamentally, to achieve industrial justice. After two decades of the operation of the adjudicative institutions established by the 1995 Act, it is time to evaluate the ways in which the labour arbitrators, the Labour Courts and the Labour Appeal Court, have interpreted and applied the provisions of the LRA relating to reinstatement. This evaluation exercise also extends to the immense contributions of the Supreme Court of Appeal and the Constitutional Court to the jurisprudence surrounding reinstatement as an unfair dismissal remedy in contemporary South African labour law. This article starts by defining reinstatement, distinguishing the remedy of re-employment and, further, the Constitutional Court’s judicial activist innovation to the labour relations lexicon—‘instatement’. Then it settles down to tackle issues that are preliminary and jurisprudential in nature—issues that were probably not contemplated by the enabling legislation, but which have arisen in adjudication. These include resignation and its effect on reinstatement, automatic reinstatement in the form of a declaration, and whether a court is able to order either ‘interim reinstatement’ or ‘semi-urgent interim relief’. The latter part of this article examines those non-statutory obstacles to accessing the remedy of reinstatement. These include the employer’s non-compliance with the order of reinstatement, as was the issue in the protracted litigation concerning Myers v National Commissioner of the SAPS ((2013) 34 ILJ 1729 (SCA); Myers v National Commissioner of the SAPS [2014] 5 BLLR 461 (LC); Myers v National Commissioner of the SAPS [2015] ZALCCT 68); whether the Prescription Act applies to claims for reinstatement; and such sundry issues as whether arrear wages could be recovered as a judgment debt. Finally, we consider whether an employee nearing the retirement age who is unfairly dismissed is entitled to reinstatement.
APPLICATION OF GIS ATTO JUSTIFICATION PREPARATION FOR THE RECOGNITION OF DEAD BURIED WARRIORS, REPORTED MISSING
Authors: Щекотилов Владимир Геннадьевич , Лазарев Олег Евгеньевич , Шалаева Мария Владимировна , Щекотилова Светлана Николаевна 
Published: November 2020

Предложена и практически реализована методика подготовки обоснования для признания погибшими считавшихся 75 лет пропавшими без вести воинов. Методика основывается на использовании ГИС с архивными и современными картами, а также архивных материалов из базы данных системы «Память народа» и Центрального архива Министерства обороны. В качестве основного документа для принятия решения о гибели воинов использованы книги погребения, в которых найдены записи по воинам, считающимся пропавшими без вести. Сформирована практика направления в военные комиссариаты ходатайств с приложением печатных и электронных материалов. В 2019 г. Военные комиссариаты приняли 30 решений о дате, месте первичного и текущего захоронения 170 воинов.
A methodology has been proposed and implemented to prepare a justification for the recognition of 75 years of missing persons as dead. The methodology is based on the use of GIS with archival and commercial maps, as well as archival materials from the database of the Memory of the People system and the Central Archive of the Ministry of Defense. In the quality of the main document, burial books were used to decide on the death of warriors, in which records on soldiers were found to be missing. The practice of sending applications with the application of printed and electronic materials to military agencies has been established. In 2019, the military commissariats made 30 decisions on the date, place of the primary and current burial of 170 soldiers.
ECOLOGICAL AND GEOCHEMICAL ASSESSMENT OF BIOGENIC AND ACCUMULATIVE WATER COMPLEXES OF UPPER VOLGA RESERVOIRS
Authors: Тихомиров Олег Алексеевич 
Published: November 2020

В статье приводится эколого-геохимическая характеристика биогенноаккумулятивных аквальных комплексов, рассматриваются вопросы накопления органических веществ и тяжелых металлов в аквальных комплексах верхневолжских водохранилищ. Приводится экологогеохимическая оценка состояния аквальных комплексов разной степени зарастания.
The article presents the ecological and geochemical characteristics of biogenic accumulative aquatic complexes, discusses the accumulation of organic substances and heavy metals in the aquatic complexes of the upper Volga reservoirs. An ecological and geochemical.
CLIMATE CHANGE IN ARCTICA: LOCAL AND GLOBAL IMPACT ON THE ENVIRONMENT
Authors: Сердитова Наталья Евгеньевна 
Published: November 2020

В работе сделан обзор последних научных исследований в области изменения климата в полярных районах и связанных с этими изменениями рисками. Отмечен ускоренный характер потепления в арктическом регионе и высокая чувствительность окружающей среды и инженерной инфраструктуры к происходящим изменениям. Рассмотрены возможные пути адаптации к этим изменениям, смягчение их последствий и информационно-образовательные аспекты.
Results of recent research on climate change in polar regions and the risks associated are reviewed. The accelerated nature of warming in the Arctic region and the high sensitivity of the environment and engineering infrastructure to the changes are noted. Possible ways of adaptation to these changes, mitigation of their consequences, and informational and educational aspects are considered.
MECHANOCHEMICAL SYNTHESIS OF CHROMIUM (III) MOLYBDATES ON THE BASIS OF VARIOUS PRECURSORS
Authors: Батанов Александр Александрович , Румянцев Руслан Николаевич , Горянская Виктория Алексеевна , Ильин Александр Александрович , Ильин Александр Павлович 
Published: November 2020

Проведен анализ влияния прекурсоров (оксид молибдена (VI) и парамолибдат аммония) на физико-химические и каталитические свойства синтезированных образцов молибдатов хрома (III). Исследован фазовый состав и удельная поверхность данных образцов. Методами рентгенофазового, рентгеноструктурного, синхронного термического анализов, газовой хроматографии изучен процесс механохимического синтеза молибдатов хрома. Установлено, что в зависимости от источника молибдена, образуется молибдат хрома (III) различной структуры. Показана каталитическая активность и селективность молибдатов хрома (III) в реакции окислительного дегидрирования метанола. Установлены побочные продукты, образующиеся в ходе данной реакции. Степень конверсии для всех образцов составила более 80 %. Показано, что селективность молибдата хрома (III), полученного с использованием парамолибдата аммония значительно превосходит данный показатель у образца, полученного из оксида молибдена (VI), и достигает ~80%.
The influence of precursors (molybdenum (VI) oxide and ammonium paramolybdate) on the physicochemical and catalytic properties of the synthesized samples of chromium (III) molybdates is analyzed. The phase composition and specific surface of these samples were studied. The process of mechanochemical synthesis of chromium molybdates. studied by methods of X-ray phase, X-ray diffraction, thermal synchronous analysis, gas chromatography. It was demonstrated that depending on the source of molybdenum, chromium (III) molybdate of various structures is formed. The catalytic activity and selectivity of chromium (III) molybdates in the oxidative dehydrogenation of methanol is shown. The by-products formed during this reaction have been identified. The degree of conversion for all samples was more than 80%. It was shown that the selectivity of chromium (III) molybdate obtained using ammonium paramolybdate significantly exceeds that of a sample obtained from molybdenum (VI) oxide and reaches ~ 80%.