bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Endoplasmic Reticulum Stress Reverses Synaptic Plasticity Deficits in Striatum of DYT1 Dystonia Mice
Authors: Cai Huaying , Ni Linhui , Hu Xingyue , Ding Xianjun
Published: February 2021

Background & objectiveStriatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model.Methods & resultsLong-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in Tor1a+/- striatum. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents.ConclusionThe current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.
Analysis of Soil and Microbial Characteristics and Microbial Response in Rare Earth Mining Areas in Jiangxi Province, China.
Authors: Liang Zhentian , Zhang Wenjing , Yang Yuesuo , Ma Jincai , Li Shuxin , Wen Zong
Published: February 2021

There is a certain connection between the microbial community and functional flora in rare earth mining areas, but the pollution characteristics and pollution metabolic pathways in the mining area are still unclear. The conditions of heavy metals, rare earth elements, and microorganisms after the mining of rare earth mines were studied in this paper. It was found that after mining, all the sampling areas showed low pH and low total organic carbon(TOC), accompanied by high iron and aluminum concentrations. The development of vegetation is closely related to the development level of microorganisms. In the complex environment of rare earth mining areas, the Proteobacteria showed an absolute competitive advantage. In the process of mine environmental recovery, the relative abundance of Acidobacteria will increase significantly, but with the further development of restoration, the relative abundance of Firmicutes in rare earth mining areas will gradually decrease. There are many genera of bacteria related to the N cycle and heavy metal metabolism in the study area, indicating important metabolic pathways of ammonia nitrogen and heavy metals in rare earth mining areas. At the same time, the study found that there are bacterial genera that promote plant nitrogen fixation in the area, further revealing the nitrogen cycle.
Risk of SARS-CoV2-related Mortality in Non-small Cell Lung Cancer Patients Treated With First-line Immunotherapy Alone or in Combination With Chemotherapy
Authors: Banna Giuseppe Luigi , Cantale Ornella , Friedlaender Alex , Yusof Harliana , Addeo Alfredo
Published: February 2021

Background: Patients with cancer are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the impact of solid cancer types and systemic anticancer treatments on its related mortality is still debatable.Methods: To weigh the real impact of immune-checkpoint inhibitors (ICIs) by exploring the risk of SARS-CoV-2-related mortality in a retrospective analysis of patients with non-small-cell lung cancer (NSCLC) treated with first-line Pembrolizumab or in combination with chemotherapy (ChT) during the first surge of the pandemic. Results: The risk of death was significantly higher in the group of patients treated with ChT+Pembrolizumab than with Pembrolizumab alone (OR 2.43 (1.23-4.82, p=0.01). The SARS-CoV-2-related mortality rate was 8% and significantly associated with ChT+Pembrolizumab as compared to Pembrolizumab alone (18% vs. 0%, respectively, p=0.03). Patients dead because of SARS-CoV-2 were older than 70 years (100 vs. 34%, respectively, p=0.03) and tended to have a heavier smoking history (67 vs. 29% of current smokers, respectively, p=0.17). Higher baseline values of neutrophil-to-lymphocyte ratio (NLR) (with 67 vs. 50% ≥ 4.0, p=0.58) and systemic immune-inflammation index (SII) (with 67 vs. 50% ≥ 1236, p=0.58) were observed in patients dead due to the SARS-CoV-2.Conclusions: Immunotherapy might not impact the risk of SARS-CoV-2-related mortality, whilst the addition of ChT was either associated with an overall increased risk of mortality and to the risk of SARS-CoV-2-related mortality. The co-existence of other clinical factors may have contributed to the latter.
On the evolution equation with a dynamic Hardy-type potential
Authors: Chern Jann-Long , Hwang Gyeongha , Takahashi Jin , Yanagida Eiji
Published: February 2021

Motivated by the celebrated paper of Baras and Goldstein (1984), we study the heat equation with a dynamic Hardy-type singular potential. In particular, we are interested in the case where the singular point moves in time. Under appropriate conditions on the potential and initial value, we show the existence, non-existence and uniqueness of solutions, and obtain a sharp lower and upper bound near the singular point. Proofs are given by using solutions of the radial heat equation, some precise estimates for an equivalent integral equation and the comparison principle.
The Influence of Friction Blocks Connection Configuration on High-speed Railway Brake Systems Performance
Authors: Yin Jiabao , Wu Yuanke , Lu Chun , Chen Wei , Mo Jiliang , Zhou Zhongrong
Published: February 2021

The influence of friction blocks connection configuration on the interfacial tribology behavior and FIVN (friction-induced vibration and noise) of high-speed railway braking system is systematically investigated with a scaled brake test bench. The potential relationship among interface contact status, friction, wear, pressure distribution, heat distribution and vibration noise of the system is studied under dragging test condition. The results indicate that the connection configuration of the friction blocks has a significant impact on systematic interfacial tribology behavior, heat distribution and vibration noise. A floating connection mode can suppress the vibration noise of brake system. The interfacial heat distribution and systematic vibration noise are quite relevant with the contact status, interfacial wear and pressure distribution. The increase of interfacial wear will lead to an expansion of pressure concentration area and an aggravation of vibration noise. The result of this research is helpful for a further design optimization and noise reduction of railway brake system.
Prevalence of High-Riding Vertebral Arteries and Narrow C2 Pedicles Among Central-European Population: A Computed Tomography-Based Study
Authors: Klepinowski Tomasz , Żyłka Natalia , Pala Bartłomiej , Poncyljusz Wojciech , Sagan Leszek
Published: February 2021

BackgroundHigh-riding vertebral artery (HRVA) and narrow C2 pedicles (C2P) pose a great risk of injuring the vessel during C2 pedicle or transarticular screw placement. Recent meta-analysis revealed a paucity of European studies regarding measurements and prevalence of these anatomical variants.Methods383 consecutive cervical spine CT scans with 766 potential screw insertion sites were analyzed independently by two trained observers. C2 internal height (C2InH), C2 isthmus height (C2IsH), and C2P width were measured. Kappa statistics for inter- and intraobserver reliability as well as for inter-software agreement were calculated. HRVA was defined as C2IsH of ≤ 5 mm and/or C2InH of ≤ 2 mm. Narrow C2P was defined as C2P width ≤ 4 mm. STROBE checklist was followed.ResultsAt least 1 HRVA was found in 25,3% (95% CI 21,1-29,8) of patients (16,7% of potential sites). At least 1 narrow C2P was seen in 36,8% (95% CI 32,1-41,7) of patients (23,8% of potential sites). Among those with HRVA, unilateral HRVA was present in 68,0% (95% CI 58,4-77,0), whereas bilateral HRVA in 32,0% (95% CI 23,0-41,6). No difference in terms of laterality (right or left) was seen neither for HRVA nor narrow C2P. Significant differences were found between females and males for all measurements. Each parameter showed either good or excellent inter- or intraobserver, and inter-software agreement coefficients. Conclusions﻿HRVA and narrow C2P are common findings in Central-European population and should be appreciated at the planning stage before craniocervical instrumentation. Measurements can be consistently reproduced by various observers at varying intervals using different software.
Kraken: A wirelessly controlled octopus-like hybrid robot utilizing stepper motors and fishing line artificial muscle for grasping underwater
Authors: Almubarak Yara , Schmutz Michelle , Perez Miguel , Shah Shrey , Tadesse Yonas
Published: February 2021

Underwater exploration or inspection requires suitable robotic systems capable of maneuvering, manipulating objects, and operating untethered in complex environmental conditions. Traditional robots have been used to perform many tasks underwater. However, they have limited degrees of freedom, manipulation capabilities, portability, and have disruptive interactions with aquatic life. Research in soft robotics seeks to incorporate ideas of the natural flexibility and agility of aquatic species into man-made technologies to improve the current capabilities of robots using biomimetics. In this paper, we present a novel design, fabrication, and testing results of an underwater robot known as Kraken that has tentacles to mimic the arm movement of an octopus. To control the arm motion, Kraken utilizes a hybrid actuation technology consisting of stepper motors and twisted and a coiled fishing line polymer muscle (TCP FL ). TCPs are becoming one of the promising actuation technologies due to their high actuation stroke, high force, light weight, and low cost. We have studied different arm stiffness configurations of the tentacles tailored to operate in different modalities (curling, twisting, and bending), to control the shape of the tentacles and grasp irregular objects delicately. Kraken uses an onboard battery, a wireless programmable joystick, a buoyancy system for depth control, all housed in a three-layer 3D printed dome-like structure. Here, we present Kraken fully functioning underwater in an Olympic-size swimming pool using its servo actuated tentacles and other test results on the TCP FL actuated tentacles in a laboratory setting. This is the first time that an embedded TCP FL actuator within elastomer has been proposed for the tentacles of an octopus-like robot along with the performance of the structures. Further, as a case study, we showed the functionality of the robot in grasping objects underwater for field robotics applications.
Laboratory Diagnosis and Management of Covid-19 Cases: Creating A Safe Testing Environment
Authors: Lekan-Agunbiade Titilayo Tosin , Agunbiade Olalekan Isaiah
Published: February 2021

BACKGROUNDCOVID-19 disease has had a profound impact worldwide since it was discovered in Wuhan, China, in December 2019. Laboratory testing is crucial to prompt identification of positive cases, initiation of treatment and management strategies. However, medical scientists are vulnerable to infection due to the risk of exposure in the laboratory and the community. This study sought to determine the awareness of laboratory safety measures, assess the personal efforts of medical scientists in creating a safe laboratory environment for testing and examine the laboratory safety enabling factors.METHODSAn internet-broadcasted and validated questionnaire was developed to obtain data from 131 medical scientists in Nigeria. The data generated were analyzed using IBM SPSS Statistics version 25.RESULTSThe majority of the respondents had a high awareness of laboratory safety measures (60.3%, mean ± SD= 52.4 ±2.4) and demonstrated good personal efforts in creating a safe laboratory testing environment (63%, mean ± SD= 48.5±5.9). The level of awareness of laboratory safety measures was significantly associated with respondents’ level of education (χ2 = 6.143; p = 0.046) and influences respondents’ efforts in creating a safe laboratory testing environment (F-ratio = 7.529, p = 0.007).However, just a few respondents could convincingly attest to the availability of adequate and appropriate PPE with proper utilization training (45.1%), adequate rest and other welfare packages (45.8%) as well as access to appropriate Biological Safety Cabinets (BSCs) and other essential equipment in their laboratories (48.8%). Furthermore, a significant association existed between the availability of laboratory safety enabling factors and respondents’ efforts in creating a safe environment for testing with the p-value ranging between <0.0001 to 0.003. CONCLUSION This study revealed that despite the high awareness of safety measures and good personal efforts of the study participants in creating a safe laboratory-testing environment, there was poor availability of safety facilities, equipment, support and welfare packages required to enhance their safety. It is, therefore, crucial to provide necessary laboratory biosafety equipment and PPE in order not to compromise medical scientists’ safety as they perform their duties in COVID-19 pandemic response.
Anti-cancer effect of orally absorbable heparin on orthotopically induced exocrine and endocrine pancreatic cancer
Authors: Hwang Hae Hyun , Jeong Hee Jeong , Yoon Sangwoo , Byun Youngro , Okano Teruo , Kim Sung Wan , Lee Dong Yun
Published: February 2021

Pancreatic cancers are classified based on where they occur into those derived from exocrine glands and endocrine glands, thereby showing different anti-cancer effect with medication. Therefore, it is necessary to develop anti-cancer drugs that can inhibit both of these types. To this end, we developed a heparin-taurocholate conjugate, i.e., LHT, to suppress tumor growth via its anti-angiogenic activity. Here we conducted a study to determine the anti-cancer efficacy of LHT on various types of pancreatic cancer, i.e., human pancreatic ductal adenocarcinoma (PDAC) and human pancreatic neuroendocrine tumor (PNET), at orthotopic animal model. LHT reduced not only proliferation of all three cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. Especially, these effects of LHT were much stronger to PNET (RINm cells). Also, LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Eventually LHT reduced strongly ~ 50% tumor weights and tumor volumes of all three cancer cells at orthotopic model via anti-proliferation of cancer cells and anti-angiogenesis of endothelial cells. Interestingly, LHT was highly effective to PNET tumor tissue in vivo. Collectively, these findings demonstrated that LHT could be a potential anti-pancreatic cancer medication, regardless of pancreatic cancer types.
Lung adenocarcinoma radiosensitivity depends on EGFR signaling pathway or other pathways? —— a research based on gene sequencing and data-independent acquisition (DIA) mass spectrometry
Authors: Jiang Chang , Wang Yi-ting , Zhu Xue-ru , Feng Wen , Yu Wen , Sun Li , Sun Qian , Jiang Hao , Fu Xiao-long
Published: February 2021

Background: To investigate the biological basis of radiosensitivity difference in lung adenocarcinoma cells, EGFR mutant or a wide variety of signal pathways？﻿Methods: There were fourteen lung adenocarcinoma cell lines used to carry out experiments in this study. The SF2 experimental test data of fourteen cell lines used in this study are from the previous work we did. EGFR mutation in each cell line detected by Next-Generation Sequencing. Statistical difference in SF2 about fourteen cells used the Kruskal-Wallis test. Correlation between EGFR mutant or not and SF2 analyzed by Student’s t-test. The proteomes of the 14 lung adenocarcinoma organisms were identified by DIA in LC-MS/MS proteomic technology. P < 0.05 showed statistical significance. R language software was used to perform the bioinformatics analysis.Results: The SF2(Surviving fractional 2Gy ) median value is 0.351(0.122-0.825). The number of cell lines in the EGFR mutatant-type is five, wild-type is nine. We obtained a mean coverage of 5425 proteins from fourteen lung adenocarcinoma cell lines. There are thirty-nine different expression proteins in total. Significant differences of SF2 was found among fourteen cell lines (P=0.004 < 0.05). showed that there is no correlation between the EGFR mutant-type group and the EGFR wild-type group（P=0.822> 0.05）. The R language analyzed based on proteomic explored that there were thirty-nine DEPs(differently expresse proteins) and four KEGG pathways: ECM-receptor interaction, Focal adhesion, Hematopoietic cell lineage, and Prion diseases. LAMC1, ITGB4/ITGA6, and CD44 participated in multiple signaling pathways. PPI examined that LAMC1, ITGB4/ITGA6, CD44, FLNB, CD59, PRNP interacted more concentratedly.Conclusion: The inherent radiosensitivity of lung adenocarcinoma cell lines is not determined by the status of EGFR mutant, maybe by other signal pathways such as LAMC1, ITGB4/ITGA6, CD44, and PRNP.
The tragedy of the cows: exploring the short and long-term warming effect of methane emissions in agricultural mitigation
Authors: Domínguez Ignacio Pérez , Prado Agustin del , Mittenzwei Klaus , Hristov Jordan , Frank Stefan , Tabeau Andrzej , Witzke Peter , Havlik Petr , Meijl Hans Van , Lynch John , Stehfest Elke , Pardo Guillermo , Barreiro-Hurle Jesus , Koopman Jason , Sánchez María José Sanz
Published: February 2021

This paper investigates how the short-lived character of methane could have important implications for the design of global climate change mitigation policies in agriculture, sector which is often seen to have a limited contribution to a net-zero carbon economy. Motivated by the renewed attention for the short-term versus long-term warming effects of methane, we explore how various appreciations of global warming affect cost-efficient mitigation policies and dietary transitions, and the implied warming. Results show that the choice of a particular metric is decisive if used to determine optimal mitigation options. For instance, focusing on the long-term warming effect of agricultural methane emissions could lead to a higher relevance of low meat diets relative to stringent mitigation policies. Moreover, a combination of stringent mitigation and dietary changes could help reverse the contribution of agriculture to global warming.
Production and quality of watermelon grown under seaweed extract
Authors: Júnior Antonio Francisco de Mendonça , Rodrigues Ana Paula Medeiros dos Santos , Sales Rui , Negreiros Andréia Mitsa Paiva , Bettini Marcos Oliveira , Júnior Esdras de Oliveira França , Neto Álvaro Carlos Gonçalves , Gonçalves Ranoel José de Sousa , França Kevison Rômulo da Silva
Published: February 2021

The use of biofertilizers with macroalgae base has become a viable alternative to conventionally used synthetic fertilizers. Among the advantages of using these extracts is the increase in productivity and improvements in the agronomic performance of the crop. Its use is allowed in organic agriculture as it is a natural product. The objective of this research was to evaluate the influence of the seaweed extract, Ascophyllum nodosum (L.) to the productive development and quality of watermelon plants. A randomized block design with 6 treatments and 4 replications was applied. The treatments comprised of full or divided doses (total of 3.0 ml L-1) of seaweed extract (T1: producer standard; T2: (1.0 – 1.0 – 1.0 mL L-1) applied 2 - 16 - 30 days after transplanting (d.a.t.); T3: (1.5 - 1.5 ml L-1) 2 - 30 (d.a.t.); T4: (1.0 – 1.0 – 1.0 mL L-1) 16 - 30 - 44 (d.a.t.); T5: (1.5 - 1.5 mL L-1) 16 - 30 (d.a.t.) T6: (3.0 mL L-1) 2 (d.a.t.). 100 mL of the prepared solution was used for each experiment. The application of Acadian® improved the yield of water melon in the order of 12.69 to 27.76% and at different periods of the crop cycle.
The 4R management for nitrogen fertilization in tropical forage: A review
Authors: Costa Carolina Marques , Costa Ana Beatriz Graciano da , Theodoro Gustavo de Farias , Difante Gelson dos Santos , Gurgel Antonio Leandro Chaves , Santana Juliana Caroline Santos , Camargo Francisco Carlos , Almeida Emizael Menezes de
Published: February 2021

Most of the tropical soils that are intended for pastures are degraded or are at a certain stage of degradation. In this context, the use of nitrogen fertilization increases the quantity as well as the quality of the fodder produced and also accelerates growth, tillering, leaf production, and consequently, expansion of the aerial region and the root system. The present review of the literature aims to determine how the control of the source, location, time, and the application of a right dose of nitrogen fertilizer influences and benefits the entire ecosystem in tropical pastures with the correct use of 4R management, along with increasing the forage yields in these areas. The results showed that in tropical pastures, the recommended N dose varies with the cultivar used and the expected forage production and ranges from 50 to 500 kg N ha–1 year–1, irrespective of division in grazing cycles, with distribution in the entire pasture area
How to Expand Repurchase Intention? The Intervening Impact of Attitude towards Mobile Shopping
Authors: Nurcholis Lutfi , Ferdianto Raditya
Published: February 2021

The research aimed to investigate and test the attitude toward mobile shopping as a mediating variable at the relationship between perceived usefulness and perceived risk against repurchase intention. The research used a quantitative approach to explain the relationship between research variables. The used sampling technique was purposive sampling, with a total sample of 200 mobile shopping users in Central Java. Data collection was carried out using a questionnaire. The obtained data were processed using the SPSS 16. The results show that perceived usefulness and perceived risk affect attitude in mobile shopping and repurchase intention significantly. Then, attitude toward mobile shopping also influence repurchase intention. Last, it also finds that attitude toward mobile shopping can mediate the relationship between perceived usefulness and perceived risk against repurchase intention.
Sharia and Moon Sighting and Calculation examining moon sighting Controversy in Nigeria
Authors: Hassan-Bello Abdulmajeed Bolade
Published: February 2021

One of the t important issue Muslims face which needs to be addressed scholarly and juristically  is the issue of whether the start and end of the lunar months through Astronomical Calculations is valid in Islamic Jurisprudence, or is physical moon sighting the only valid opinion. Scholars on the two sides of the divide present arguments and support their views by citing the same sources. In Nigeria moon sighting has been a serious problem for many years. The Islamic calendar is lunar. Lunar calendars follow the phases of the moon, beginning with the crescent moon and ending with the conjunction of the moon. The foundation of legal ruling in Islam is the Qur’an and the Sunnah. It is in the absence of decisively authentic and unequivocal texts that, scholars may resort to ijtihad. There are several positions on moon sighting. The most prominent are regional sighting, physical sighting globally, Mecca time-point for reference and Astronomical Calculation. The popular view among Muslim jurists is actual sighting of the crescent. The paper therefore concludes that all the aforementioned trends, are acceptable. Eid al-adha is independent of Arafah because both are observed on different days, therefore the observance of eid al-adha on Arafah day in any part of the world is allowed and acceptable However, the evidence compels Muslims to follow the opinion of the majority of Muslims in any country. The paper therefore, recommended the establishment of a Federal Ministry of Islamic Affairs to be in charge of moon sighting and Eids.
Transforming Islamic Law in Indonesia from a Legal Political Perspective
Authors: Yani Ahmad , Barthos Megawati
Published: February 2021

This article aims to discuss the transformation of Islamic law in Indonesia. This research is qualitative in the form of a literature study with a political-law approach. The idea of this paper is based on a misunderstanding of Islamic law and Islamic law and fiqh. Issues related to the debate on the application of Islamic law in the contemporary era also contribute to thoughts in this paper. This paper concludes that the transformation of Islamic law into national law is a difficult task. This is because Indonesia is a multi-cultural, multi-ethnic, and multi-religious country. The most important reason is due to the variety of Muslim understanding of religious texts
Investigations on the fouling characteristic of humic acid and alginate sodium in capacitive deionization
Authors: Zhang Huizhong , Tian Jiayu , Hao Xiujuan , Liu Dongmei , Cui Fuyi
Published: February 2021

Capacitive deionization (CDI) has been investigated for brackish water desalination, selective removal of ions, and water softening. We used humic acid (HA) and alginate sodium (SA) to simulate different kinds of natural organic matter to investigate the fouling phenomena during CDI operation. Adsorption amount and energy efficiency were studied. Results showed that both SA and HA could decrease the removal of NaCl during CDI operation. There existed a slight decrease of energy consumption in SA solutions which was opposite to that in HA solutions. HA can compete with ions adsorbed by electrodes and attach to electrodes adhesively, resulting in co-ion repulsion. SA is not sensitive to electrical field and its fouling is not obvious. The amount of adsorbed Mg2+ would increase from 0.927 mg/g to 1.508 mg/g in ten cycles' operation and the increment of Ca2+ was from 1.885 mg/g to 2.878 mg/g in SA solutions. This increase of adsorption was due to the complexation between SA and cations. Simultaneously, energy consumption was decreased. In HA solutions, energy consumption of Mg2+ and Ca2+ adsorption increased. In ten cycles' operations, both HA and SA could reduce the efficiency of CDI operation. The types of organic substances are important factors in fouling of CDI electrodes.
Impacto del programa de alimentacióon escolar Qali Warma sobre la anemia y la desnutrición crónica infantil
Authors: Francke Pedro , Acosta Gustavo
Published: February 2021

Este artículo aporta evidencia del impacto de Qali Warma sobre la anemia y la desnutrición crónica en niños de 3 a 5 años. Los resultados empíricos se obtienen por medio de una evaluación cuantitativa de dos pasos. Primero se usan técnicas de entropy balancing y machine learning para lograr un grupo control comparable que permita obtener estimaciones robustas. Luego se realizan regresiones para estimar el efecto del programa sobre las variables de interés. Se usan datos de la Encuesta Demográfica y de Salud Familiar de los años 2014 a 2017. Al parecer, Qali Warma no tendría efectos sobre la anemia ni sobre la desnutrición crónica, al menos en el rango de edad estudiado.
WAR-INFLUENCED BIOGRAPHY OF TYUMEN MEN OF LETTERS, THE ALUMNI AND FACULTY OF THE UNIVERSITY OF TYUMEN
Authors: Litovchenko Vera P. , ZHIVOTOVA Alyona N.
Published: February 2021

In the face of increasing falsification of the Great Patriotic War facts, the evidence of contemporary witnesses and the objective coverage of those events are becoming increasingly important. In this regard, the creative writing by Russian writers and poets is especially significant, especially first and foremost by those who personally took part in combat during the military operations against the Nazi aggression or worked on the home front.
The following article is devoted to writers and poets of Tyumen, namely to the alumni and faculty from the University of Tyumen, on whose fate and creative writing the Great Patriotic War left its deep trails, becoming the major topic of their writing. Their names and biographies were revealed in the course of research in 2015-2020. The authors have collected the students’ and academic staff’s stories about their parts in the war and their meditations, which has substantially supplemented the data about the University’s history during the war and its contribution to the Victory.
Using the historical biographical and comparative approaches, the authors have studied war-time biographies of the Tyumen authors, presented little known facts of their frontline and working life, as well as analyzed their reflections in the following literary creative work of the Tyumenians, of which memoirs and non-fiction prose have become the most prolific genres. This article comprises biographical data on eleven war veterans, home front workers, and children of war — writers and poets, closely related to one of the leading university of Tyumen and the Tyumen Region.
MEMORIALIZATION OF OBJECTS OF CULTURAL HERITAGE OF FEDERAL SIGNIFICANCE IN TYUMEN
Authors: GOGOLEV Dmitrii A. , MAKAROVA Elena O.
Published: February 2021

The historic monuments of Tyumen are an integral part of the historical and cultural landscape of the city, especially those of them that have the status of the objects of the cultural heritage of the federal significance.
The relevance of this topic lies in commemorative marks being one of the sources of the formation of historical memory. For the first time, there is an attempt to study the commemorative potential using the example of a limited number of cultural heritage sites in Tyumen and compare with its current state.
A comprehensive study of the history of these objects allows identifying their commemorative potential, while the comprehension of the current state of their memorialization aids in developing specific proposals for perpetuating significant events for them.
Using the principles of objectivity and historicism, the authors have studied memorial plaques. Today, they are the only type of commemorative signs located on the cult cultural heritage sites of federal significance in Tyumen. Their texts contain information exclusively about the events of religious life. The reason for this may be the fact that the initiative to install all the memorial signs came from the representatives of the church.
The events related to the history of the iconic monuments of Tyumen were grouped into thematic blocks. They reflect the connection of these objects with facts from the life of indivi¬duals or with the history of the most memorial place. This allows formulating more clearly their proposals for the memorialization of historic objects of cultural heritage of federal significance in Tyumen.
It should be noted that the issue of the current state and prospects of memorialization of the historic objects of cultural heritage of regional significance in Tyumen requires a special study.
A Review on Development and Characterization of a Cost-effective Targeted Quality-driven Antimalarial Product with an Emphasis on Phytosomes
Authors: Bhargav E. , Y Padmanabha Reddy , Koteshwara K.B.
Published: February 2021

Malaria, a protozoan disease, led to numerous deaths and several new million cases
raised due to the development of resistance as per the WHO malaria report 2019. This can be overcome
by the development of an effective targeted plant-based delivery system through phytosomes
that are effective in permeation and bioavailability to treat infected RBCs (parasitic cells). This review
article explained the development of targeted Nanophytosomes to overcome resistance, to improve
efficacy. This review paper also emphasized various quality-driven developmental approaches
in developing an antimalarial product at a reasonable cost. By implementing molecular modeling
techniques in development, a significant phytoconstituent with the capability of acting at the target
(receptor or enzymes) of the parasite and the one with the capability to overcome drug resistance
against resistant strains of parasites can be identified. Absorption Distribution Metabolism
Excretion and Toxicity (ADMET) studies information provide a route to the design and formulation
of a potent antimalarial agent. Efficient, targeted Nanophytosomal formulations can be formulated
by functionalizing or conjugating with suitable targets to direct the phytoconstituent to the infected
RBCs thereby achieving complete parasitic eradication. Artificial Neural Network technology
(ANN), Quality by Design (QbD), molecular dynamics, and simulation studies implementation
improves quality and reduces the cost of the product, as these malarial products are much utilized
in low-income countries. Hence it can be concluded that targeted developmental quality-driven approaches
implementation is essential for effective malarial treatment.
GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma
Authors: Nanda Sitansu S. , Hossain Md I. , Ju Heongkyu , Papaefthymiou Georgia C. , Yi Dong K.
Published: February 2021

Background:

Glycogen syntheis kinase (GSK-3) inhibitors are novel therapeutic agents
for treating various types of cancer, such as breast, lung, and gastric cancer. No pathological
changes have been found by the morphological examination of GSK-3.

Objectives:

This review describes recent procedures using GSK-3 inhibitors, primarily in treating
colon carcinoma. Furthermore, it also explains the mechanism of action of different GSK-3 inhibitors
in treating various types of cancers and proposes some additional mechanisms may be useful
for further research on GSK-3 inhibitors for cancers, including colon carcinoma.

Results:

The majority of the cancerous and pre-cancerous lesions are stimulated by the transformation
of membrane-bound arachidonic acid (AA) to eicosanoids, a transformation that promotes for
the viability, proliferation, and spread of cancer. GSK-3 inhibitors can reinstate hostility to tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL) responsiveness in gastric adenocarcinoma
cells. GSK-3, the final enzyme in glycogen synthesis, is a serine/threonine kinase that phosphorylates
varied sequences that are more than a hundred in number, within proteins in an array of
heterogeneous pathways. It is an essential module of an exceptionally large number of cellular processes,
playing a fundamental role in many metabolic processes and diseases. Many patients diagnosed
with colon cancer achieve long-term remission with outstanding survival through the GSK-3
inhibitors.

Conclusion:

Prior to the extensive application of these proposed mechanisms of GSK-3 inhibitor,
further evaluation and clinical studies are needed. Only after the completion of appropriate clinical
studies and morphological examinations, would extensive application be apprpriate.
Expert Design and Optimization of Ethyl Cellulose-Poly (ε-Caprolactone) Blend Microparticles For Gastro-Retentive Floating Delivery of Metformin Hydrochloride
Authors: Salatin Sara , Jelvehgari Mitra
Published: February 2021

Background:

Metformin Hydrochloride (MH) is an oral anti-hyperglycemic agent belonging
to the biguanide class of drugs.

Objective:

The present study involves the formulation and evaluation of gastro-retentive floating
microparticles containing MH as a model drug for the prolongation of absorption time.

Methods:

Three levels of a three-factor, Box-Behnken design were used to evaluate the critical formulation variables.
Microparticles were prepared using a water-in-oil-in-water double-emulsion solvent evaporation method and examined in
terms of production yield, particle size, entrapment efficiency, floating ability, morphology, FTIR (Fourier transform
infrared spectroscopy), and in vitro drug release.

Results:

The optimum conditions for preparing MH microparticles were predicted to be the content
of ethyl cellulose content (150 mg),poly (ε-caprolactone) (150 mg), and polyvinyl alcohol
(1%w/v).The optimized MH microparticles were found to be spherical with a mean size of 350.2
μm. Entrapment efficiency was 58.62% for microparticles. 63.94% of microparticles showed floating
properties. The FTIR analysis confirmed no chemical linkage between microparticle components.
in vitro release study showed a controlled release for up to 8h.

Conclusion:

These results demonstrated that MH microparticles, as a drug delivery system, may
be useful to achieve a controlled drug release profile suitable for oral administration and may help
to reduce the dose of the drug and to improve patient compliance.
Montelukast Efficacy for Improvement of Adult Acute Phase Mild-Moderate Asthma Attack: A Clinical Trial Study
Authors: Motamed Hassan , Verki Mohammadreza Maleki , Barzegari Hassan , Shariat Siamak , Hesam Saeed
Published: February 2021

Background:

Asthma, an inflammatory disease of the respiratory tract, is one of the
most frequent causes of referral to emergency departments. The aim of this study is to evaluate the
efficacy of montelukast as a member of LTRAs for the improvement of pulmonary function and
clinical symptoms of patients with asthma.

Methods:

The study was conducted on 80 patients with acute mild- moderate asthma, divided randomly
into two groups of 40 subjects. A double-blind clinical trial was conducted on asthmatic patients
who encounter an acute phase asthma attack. The experimental group received two montelukast
5 mg chewable tablets at arrival, accompanied by standard mild-moderate asthma treatment
consisting of oxygen and nebulization with albuterol 2.5 mg and ipratropium bromide 0.5 mg
in 3 doses for 60 minutes. The control group received standard mild-moderate asthma treatment
plus placebo chewable tablets at the beginning without any leukotriene inhibitors. Pulmonary function
tests, hemodynamic variables and Borg Dyspnea Scale were evaluated and analyzed at 0, 30,
60, 90 and 150 minutes in both case and control groups.

Results:

No significant differences were observed between the case and the control group in terms
of PEFR and FEV1 measurements during the study at different time points [P > 0.05]. There were
no significant differences in terms of hemodynamic variables [blood pressure, pulse and respiration
rate, pressure of oxygen in arterial blood] and Borg Dyspnea Scale in both groups as well.

Conclusion:

The study findings showed that the montelukast administration in mild-moderate
acute asthma attack setting had no significant impact on pulmonary function tests and clinical
symptoms of the studied patients rather than standard asthma treatment.
Cellular Functions of Small Heat Shock Proteins (HSPB) in Hepatocellular Carcinoma
Authors: Yamada Noriko , Matsushima-Nishiwaki Rie , Kobayashi Kaido , Takahata Shota , Toyoda Hidenori , Kumada Takashi , Kozawa Osamu
Published: February 2021

Heat shock proteins (HSPs) play an essential role as molecular chaperones in
proteostasis. Small HSPs are a group of low-molecular-weight HSPs in the range of 12-
43 kDa and are classified as HSPB. Within the ten members of the family,
HSPB1(HSP27), HSPB5 (αB-crystallin), HSPB6 (HSP20), and HSPB8 (HSP22)
ubiquitously exist in various tissues, including liver tissue. These small HSPs undergo
phosphorylation as a post-translational modification, and their functions are modulated.
Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the fourth
leading cause of cancer-related death worldwide. HSPs play a cytoprotective role as
molecular chaperones. Thus, HSPB has been generally considered to protect HCC cells
and help the progression of HCC. On the other hand, recent studies from our
laboratories have demonstrated suppressive roles of phospho-HSPB1, HSPB6, and
HSPB8 in the progression of HCC. These findings may provide a basis for a novel
defense system by HSPB against HCC progression. This review focuses on the cellular
functions of HSPB in HCC and summarizes the current research.
Phase 1 Clinical Trials of Small Molecules: Evolution and State of the Art
Authors: Sramek John J. , Murphy Michael F. , Adcock Sherilyn , Stark Jeffrey G. , Cutler Neal R.
Published: February 2021

Background:

Phase 1 studies comprise the first exposure of a promising new chemical entity in healthy volunteers or, when appropriate, in patients. To assure a solid foundation for subsequent drug development, this first step must carefully assess the safety and tolerance of a new compound and often provide some indication of potential effect, so that a safe dose or dose range can be confidently selected for the initial Phase 2 efficacy study in the target patient population.

Methods:

This review was based on a literature search using both Google Scholar and PubMed, dated back to 1970, using search terms including “healthy volunteers”, “Phase 1”, and “normal volunteers”, and also based on the authors’ own experience conducting Phase 1 clinical trials. This paper reviews the history of Phase 1 studies of small molecules and their rapid evolution, focusing on the critical single and multiple dose studies, their designs, methodology, use of pharmacokinetic and pharmacodynamic modeling, application of potentially helpful biomarkers, study stopping criteria, and novel study designs.

Results:

We advocate for determining the safe dose range of a new compound by conducting careful dose escalation in a well-staffed inpatient setting, defining the maximally tolerated dose (MTD) by reaching the minimally intolerated dose (MID). The dose immediately below the MID is then defined as the MTD. This is best accomplished by using appropriately screened patients for the target indication, as patients in many CNS indications often tolerate doses differently than healthy non-patients. Biomarkers for safety and pharmacodynamic measures can also assist in further defining a safe and potentially effective dose range for subsequent clinical trial phases.

Conclusion:

Phase 1 studies can yield critical insights into the pharmacology of a new compound in man and offer perhaps the only development period in which the dose range can be safely and thoroughly explored. Phase 1 studies often contain multiple endpoint objectives, the reconciliation of which can present a dilemma for drug developers and study investigators alike, but which can crucially determine whether a compound can survive to the next step in the drug development process.
Management of Leaks Following Laparoscopic Sleeve Gastrectomy Using Specifically Designed Large Covered Metal Stents
Authors: Luigiano Carmelo , Di Leo Milena , Eusebi Leonardo Henry , Barabino Matteo , De Nicola Enrico , Giovenzana Marco , Opocher Enrico , Iabichino Giuseppe , Palamara Maria Angela , Giacobbe Giuseppa , Tortora Andrea , Virgilio Clara , Abenavoli Ludovico , Pallio Socrate , Consolo Pierluigi
Published: February 2021

Background:

Leaks are the major complication associated with laparoscopic sleeve gastrectomy.

Objective:

The study aimed to assess the efficacy and safety of specifically designed large covered
metal stents for the management of post-laparoscopic sleeve gastrectomy leaks.

Methods:

Prospectively collected databases from three Italian Endoscopy Units were reviewed.
The primary outcome of the study was to evaluate the clinical success of stents placement, defined
as complete resolution of clinical and laboratory signs of sepsis with radiological evidence of leak
closure. Secondary outcomes were stent-related adverse events and mortality.

Results:

Twenty-one patients (67% females, mean age 45 years) were included in the study and a
total of 26 stents were placed. Technical success of stent placement was achieved in all cases
(100%). Clinical success was observed in 85.5% of patients. Stent-related adverse events occurred
in 9 patients (43%), with stent migration as the most frequent complication (33%). Adverse events
were more frequently observed in patients who had undergone bariatric surgery prior to laparoscopic
sleeve gastrectomy compared to patients without previous surgery (83% et al. 27%, p=0.018).

Conclusions:

The placement of specifically designed covered metal stents appears to be an effective
and safe therapeutic approach for post-laparoscopic sleeve gastrectomy leaks. Stent migration
can be a frequent complication.
Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of Cannabis sativa in Breast Cancer
Authors: Kikiowo Babatomiwa , Ogunleye Adewale J. , Iwaloye Opeyemi , Ijatuyi Taiwo T. , Adelakun Niyi S. , Alashe Wasiu O.
Published: February 2021

Background:

Breast Cancer (BC), a common fatal disease and the deadliest cancer next
to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy
is marked by targeting the activities of some receptors such as Estrogen Receptor alpha
(ER-α). At present, one of the most commonly used and approved marketed therapeutic drugs for
BC is tamoxifen. Despite the short-term success of tamoxifen usage, its long time treatment has
been associated with significant side effects. Therefore, there is a pressing need for the development
of novel anti-estrogens for the prevention and treatment of BC.

Objective:

In this study, we evaluate the inhibitory effect of Cannabis sativa phytoconstituents on
ER-α.

Methods:

Glide and induced fit docking followed by ADME, automated QSAR and binding free
energy (ΔGbind) studies were used to evaluate anti-breast cancer and ER-α inhibitory activity of
Cannabis sativa, which has been reported to be effective in inhibiting breast cancer cell proliferation.

Results:

Phyto-constituents of Cannabis sativa possess lower docking scores and good ΔGbind when
compared to that of tamoxifen. ADME and AutoQSAR studies revealed that our lead compounds
demonstrated the properties required to make them promising therapeutic agents.

Conclusion:

The results of this study suggest that naringenin, dihydroresveratrol, baicalein, apigenin
and cannabitriol could have relatively better inhibitory activity than tamoxifen and could be
a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo
and/or in vitro assays could be conducted to verify the ability of these compounds.