bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Clinical Features of Autosomal Dominant and Recessive TMC1-Associated Hearing Loss.
Authors: Nishio Shin-ya , Usami Shin-ichi
Published: June 2021

TMC1 is a causative gene for both autosomal dominant non-syndromic hearing loss (DFNA36) and autosomal recessive non-syndromic hearing loss (DFNB7/11). To date, 125 pathogenic variants in TMC1 have been reported. Most of the TMC1 variants are responsible for autosomal recessive hearing loss, with only 7 variants reported as causative for DFNA36. Here we reported the prevalence of TMC1-associated hearing loss in a large non-syndromic hearing loss cohort of about 12,000 subjects. As a result, we identified 26 probands with TMC1-associated hearing loss and the estimated prevalence of TMC1-associated hearing loss in the Japanese hearing loss cohort to be 0.18% among all patients. Among the 26 probands with TMC1-associated hearing loss, 15 cases were identified from autosomal dominant hearing loss families. By using the audiometric data from the probands, family members and previously reported cases, we evaluated the hearing deterioration speed for DFNA36 patients. In addition, we performed haplotype analysis for 11 unrelated autosomal dominant hearing loss families carrying the same variant TMC1: NM_138691:c.1627G > A:p.D543N. The results clearly indicated that the same haplotype was present despite of families being unrelated, supporting the contention that this variant occurred by founder mutation.
Coblation Versus Diode Laser Tonsillectomy: A Comparative Study
Authors: Alaqeedy Ameer A. , Rashid Rasheed Ali , Al-Ani Raid M.
Published: June 2021

Introduction: The study aimed to compare the 2 procedures of tonsillectomy (coblation and diode laser) concerning the operative time, the amount of blood loss, postoperative pain, and other complications. Materials and Methods: A comparative study was conducted at many Private Hospitals, Baghdad, Iraq from February 2019- February 2020. Coblation and laser tonsillectomy were performed on the same patient (one for each side) which was blinded to the patients or their caregivers and the surgeon who did the tonsillectomy. Data concerning the age, gender, indications for tonsillectomy, operative time, the amount of the blood loss, post-tonsillectomy pain by VAS scores, and other complications were recorded for each patient. Results: Out of 62 participants, there were 34 (54.8%) females. The majority were from the age group ≤18 years (n=54, 87.1%). The operative time and amount of the intraoperative blood loss were significantly lower in the coblation than a diode laser tonsillectomy. However, the postoperative pain scores in the diode laser were a statistically significant difference less than the coblation group at the periods 3 hours, 8 hours, 24 hours, and 7 days (P-value<0.05). While there was no statistically significant difference between the two groups at 2 weeks postoperative period (P-value=0.392). No primary or secondary postoperative bleeding in all patients. Conclusion: coblation was better than diode laser because of shorter operative time and less intraoperative blood loss. However, the diode laser technique had lesser postoperative pain at the postoperative periods 3 hours, 8 hours, 24 hours, and 7 days than coblation.
Nanopillar templating of biopolymer hydrogels augments stiffness and strength
Authors: Heedy Sara , Pineda Juviarelli , Yee Albert
Published: June 2021

In nature, structural biopolymers are highly organized to allow for the development of complex tissues within a living entity, including the human body. To match the properties found in these fibrous structural tissues, synthetic biomimetic hydrogels must have an optimal combination of stiffness, strength, and toughness; though an ideal combination remains challenging to achieve. Here, we report a general strategy to design stiff, strong, and tough hydrogels by confining biopolymers with a balance of rigid and weak domains into nanopillar topography. The confinement within nanopillars templates the fiber assembly process throughout the bulk of the film. Compared to a flat control, the application of the nanopillar topography increases the bulk stiffness ~ 160% to 20 MPa, strength ~ 350% to 36 MPa, and toughness ~ 450% to 8,500 kJ m− 3. This simple templating strategy is suitable for a vast range of hydrogels, opening up the potential applications for a diverse array of materials.
Tyrosine Kinase Inhibitors and Reduced-Dose Chemotherapy for Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Authors: wu chunping , zeng mengting , chen yuanzhong , wu yong
Published: June 2021

Purpose: To compare the outcomes of tyrosine kinase inhibitors in combination with reduced-dose chemotherapy with those of standard induction chemotherapy and to compare the outcomes between TKIs with chemotherapy regimen and transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia Methods: We retrospectively reviewed all patients treated with tyrosine kinase inhibitors in combination with chemotherapy. These patients were divided into the TKIs with reduced-dose chemotherapy group (62 patients) and the TKIs with standard chemotherapy group (143 patients). In further treatment, patients were divided into the transplant group (55 patients) and the non-transplant group (143 patients).Results: The complete remission rate (88.7% vs 83.9%, P=0.372) and early mortality rate (3.2% vs 3.5%, P=0.922) were similar between the TKIs with reduced-dose chemotherapy group and the TKIs with standard chemotherapy group. The proportions of lung infection (P=0.047) and bloodstream infection (P=0.024) and the proportion of patients with >21 days of hospitalization (P<0.001), on >4 types of antibiotics (P=0.003), and on restrictive tigecycline and/or polymyxin (P=0.031) were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. For cost analysis, the total costs and antimicrobial costs were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. The 3-year overall survival rates and 3-year disease-free survival rates were significantly better in the transplant group than in the non-transplant group. Conclusion: An induction regimen combining TKIs with reduced-dose chemotherapy and transplantation in first CR remains a good option for patients with Ph+ALL.
Developing machine learning models to predict CO2 trapping performance in deep saline aquifers
Authors: Thanh Hung Vo , Lee Kang-Kun
Published: June 2021

Deep saline formations are considered as potential sites for geological carbon storage (GCS). To better understand the CO2 trapping mechanism in saline aquifers, it is necessary to develop robust tools to evaluate CO2 trapping efficiency. This paper introduces the application of Gaussian process regression (GPR), support vector machine (SVM), and random forest (RF) to predict CO2 trapping efficiency in saline formations. First, the uncertainty variables, including geologic parameters, petrophysical properties, and other physical characteristics data were utilized to create a training dataset. A total of 101 reservoir simulation samples were then performed, and the residual trapping, solubility trapping, and cumulative CO2 injection were collected. The predicted results indicate that three machine learning (ML) models that evaluate performance from high to low: GPR, SVM, and RF can be selected to predict the CO2 trapping efficiency in deep saline formations. The GPR model has an excellent CO2 trapping prediction efficiency with the highest correlation factor (R2 = 0.992) and lowest root mean square error (RMSE = 0.00491). The accuracy and stability of the GPR models were verified for an actual reservoir in offshore Vietnam. The predictive models obtained a good agreement between the simulated field and the predicted trapping index. These findings indicate that the GPR ML models can support the numerical simulation as a robust predictive tool for estimating the performance of CO2 trapping in the subsurface.
Mythologeme of the Road in Armenian Media Texts
Authors:   Yerevan State University, David V. Petrosyan
Published: June 2021

The spiritual dimensions of the road accompanied a person not only in the pre-Gutenberg (oral communication) but also in the post-Gutenberg era. Its mythological manifestations are still relevant today, when communication dominates the Internet space. The research topic is conditioned by this topic. The article presents a mythological image of a road, a number of components of which are woven into the structural and semantical layers of modern media texts. The purpose of the article is to highlight important aspects of this phenomenon based on an analysis of the cultural and political texts of modern Armenian media. In the process of research, we used content and discourse analyses. About thirty publications were selected from different websitesin which through discourse analysis, the substantive features of the mythologeme of the road in Armenian media texts were revealed.His formulation of the problem presupposed the initial presentation of a number of general attributes of the road mythologeme (sacred structure, the road as a “meeting place” of space and time, the presence of horizontal and vertical planes in mythological ideas about the road, the soul’s journey into the inner consciousness and into the world of one’s own “I” , etc. on the basis of which the analysis of cultural and political publications on Armenian websites was made. The research topic is promising, since in its interdisciplinary context it can suggest new ideas not only to media researchers but also to specialists in cultural studies, philosophy, and psychology.In publications on cultural themes, the mythologeme is expensive and enriches the dynamic picture of Armenian cultural life contributing through its spatial-temporal perspective and the author’s inner “I” to the national self-knowledge of the audience. In political publications, where “the road of Thought” is paramount, the culture of internal polemics, the search for the continuation of the key points of the mental road play an important role. The author’s word is transmitted to the reader with the division of time at certain intervals. Thanks to these important criteria, the spiritual and mental picture of the road asserts its distinctive presence in the Armenian media space. Keywords: road, Armenian, media discourse, media text, mythologeme, cultural, political publications
Psychological Information in the Content of a Modern Journal
Authors:   Saint Petersburg State University, Anastasia N. Grishanina , Valeria V. Angel’cheva ,   Saint Petersburg State University
Published: June 2021

The article is the result of a study of the significance of expert psychological information, as well as information of a socio-psychological plan for journalistic materials; the work was carried out by the editorial office of Gatchinskaya Pravda newspaper (Leningrad Oblast). Psychological information in the media as an object of linguistic research has not been studied previously, the novelty of the work lies in the psycho-linguistic approach to the study of the question and to attempt correlation comparative studies of the authors with the study of peculiarities of perception of media texts of the contemporary audience. The article deals with verbal forms of social and psychological information presentation in the media, mainly in journal publications as a form of dialogue or monologue with the reader on a certain topic; the reasons for the audience’s access to psychological information in a modern magazine and the intent of the demand for texts containing such information are studied. To do this, we first studied the level of readers’ awareness of the types and forms of media information, as well as the degree of demand for knowledge of a socio-psychological orientation. The main object of research is language markers of psychological information. The relevance of the topic is explained by the great interest of magazine readers, as shown by media ratings, to psychological information. As part of the study of modern psychological techniques of media influence, the authors analyzed the results of research by psychologists and psychiatrists, who state an increase in the level of anxiety in the current psychological and emotional state of people. Doctors associate the causes of some anxiety disorders with the consumption of media information, the imposition of advice, recommendations, and lifestyle at the angle of presentation as psychological information. The article describes the results of media research; it is noted that information of a socio-psychological plan plays an important role in shaping the audience’s worldview and has a socio-psychological impact on it. The features and types of this influence are considered; the results of surveys of magazine readers are given, since the magazine is one of the mass media that publishes analytical and informative materials. The authors make an attempt to explain a certain degree of obsession with psychological information to the reader in the media; they indicate the reasons identified in the course of research for this communicative psychological strategy, bordering on and sometimes directly related to the manipulative actions of the author or publisher. Keywords: media text, mass communication media, personality, language tools, psycholinguistics, information, psychological information
The Image of the Other as a Structural Characteristic of the Cultural Border on the Example of Ukraine and Donbass
Authors:   Lugansk State Academy of Culture and Arts named after M. Matusovsky, Nina S. Ishchenko , Elena A. Zaslavskaja ,   Lugansk State Academy of Culture and Arts named after M. Matusovsky
Published: June 2021

The article is devoted to the specifics of the cultural frontier of Russian culture. The relevance of the article is due to the strengthening in the post-Soviet period of cultural conflicts on the border of Russian civilization. These conflicts on cultural grounds even lead to military action against the bearers of Russian culture, as has been the case in the Ukrainian war against Donbass since 2014. The article examines the borderland as a zone of intercultural interaction, carries out a cultural analysis of the border between cultures and identities, highlights the structural characteristic of the cultural border ‒ the image of the Other. Based on the conducted cultural analysis, the structure of the cultural space of Ukraine and the Donbass, including the wartime situation since 2014 is investigated. The study of the media content of Ukrainian information projects and similar projects in the LPR is carried out on the basis of an information-analytical methodology. Two permanent Ukrainian media projects of the Internews-Ukraine: Revision of History and Propagandarium, which work intensively in the Russian-speaking regions of Ukraine creating and broadcasting the image of the Russian as the Other by methods of aggressive anti-Russian propaganda are considered. We also analyze the activity of the Lugansk cultural site “Dandelion”, which has been operating in Lugansk since 2015 and reflects the cultural life of the city and the republic during this period. An analysis of the site’s materials shows that in the republic in wartime conditions, Russian and world culture is preserved and mastered, intensive work is underway to integrate the republics of Donbass into the cultural space of modern Russia, relying on the historical memory of these territories. The article substantiates that Ukrainian culture is currently a borderland culture, since the image of the Other as the Russian dominates its structure and is imposed on the Russians of Ukraine by propaganda methods. At the same time, the culture of modern Donbass is developing as Russian culture in which the image of the Other as a modern Ukrainian, a carrier of anti-Russian identity is formed. Keywords: Russia, Ukraine, Donbass, borderland culture, the image of the Other, anti-Russian propaganda
A Man in the Era of Digitalization of Society
Authors:   Transbaikal State University, Marina B. Liga , Irina A. Shchetkina ,   Transbaikal State University
Published: June 2021

Currently, one of the trends in the development of countries is the process of digital transformation, which affects all spheres of society. The transformation of countries’ economies is carried out with the help of such technologies as robotics, artificial intelligence, the Internet of Things, and big data groups. The transformation process, being global, gets its specific name in each country. In Russia, this is “digital economy”, which is defined in the Decree of the President of the Russian Federation “On National goals and strategic objectives of the development of the Russian Federation for the period up to 2024” as a strategy for the future development of Russia In Germany, it is “Industry 4.0”, represented by the concept of K. Schwab, in the United States, the concept of transforming society based on digital technologies is called “Industrial Internet Consortium”. In Japan, the Government has developed the “Society 5.0” strategy in conjunction with the Keidanren Association of Japan. The result of the digitalization process will be the creation of a new world based on digital technologies, in which new values and management technologies arise. The purpose of this article is to analyze the digital age as a space for the emergence of digital risks, to identify their impact on modern people. The study uses general philosophical methods that make it possible to describe modern digital civilization. Within the framework of the risk concept, digital risks arising in various spheres of society’s life are described. The positive effects of the development of the digital economy, which forms a new digital world and a new person are highlighted and described. Today, the future of civilization is determined by the development of the digital economy, which determines the basic mechanisms of society’s existence. At the same time, it will be a world filled with various kinds of risks, threats to society, the economy and the individual. The article raises questions related to the impact of the digital economy on a person living in the conditions of the global information space. Keywords: digital economy, digital risks, digital age, risk, digitalization, digital generation, competencies
Modern Dance in the Digital Space: A Screen Dance in the Context of the COVID-19 Pandemic
Authors:   Transbaikal State University, Diana V. Schultz
Published: June 2021

Modern dance is developing in the face of new threats and opportunities. Like any other social phenomenon, it is affected by external conditions that can affect its content, development and forms. The COVID-19 pandemic has become the most global condition in recent times, the impact of which has become tangible for all spheres of society. Like other branches of art, Contemporary Dance was put into new conditions, which led not only to negative consequences but also caused a surge in the use of information technologies to bring the results of creative research to the viewer. It was the pandemic conditions that contributed to the intensive development of new forms of interaction between the professional choreographic community and the new stage of the development of the screen dance as one of the forms of Contemporary Dance. The article is devoted to the impact of the restrictive conditions of the pandemic on the development of contemporary dance and its form such as a screen dance. We analyzed the few available approaches to determining the essence of a screen dancer, as well as the experience of choreographers in creating dance performances in conditions of self-isolation. The research is based on the analysis of the scientific literature covering problems of development of modern dance and screen dance in the conditions of COVID-19 pandemic. We concluded that representatives of the professional community of choreographers were able to use the conditions of self-isolation to implement new creative ideas, and the screen dance became more popular. Keywords: contemporary dance, screen dance, digital space, pandemic
Osteossíntese a fio de aço do ângulo mandibular e bloqueio maxilo-mandibular: relato de caso
Authors: Oliveira Carla Beatriz Fernandes de , Costa Karolina Braga , Aguillera Maísa de Oliveira , Mendonça José Carlos Garcia de , Pelissaro Gustavo Silva , Paiva-Oliveira Janayna Gomes , Silva Julio Cesar Leite da , Gaetti Jardim Ellen Cristina , Costa Karolina Braga
Published: June 2021

A mandíbula é um dos ossos mais acometidos pelo trauma facial em virtude de sua projeção anteriorizada favorecendo o acometimento de fraturas. A localização das fraturas se relaciona às áreas anatômicas de resistência e fragilidade por onde a força do impacto será distribuída. O tratamento baseia-se na redução e fixação dos fragmentos ósseos, para isso existe diversas técnicas descritas na literatura, dentre elas, a combinação de fixação intermaxilar (FIM) e osteossíntese com fio de aço. O objetivo deste trabalho é relatar um caso clínico de paciente com fratura em ângulo de mandíbula, submetido a osteossíntese com fio de aço e FIM. Relato do caso: Paciente, 24 anos, gênero masculino, compareceu ao Hospital Maria Aparecida Pedrossian com histórico de queda de bicicleta há quinze dias com trauma na região de mandíbula esquerda cursando com dificuldade de abertura bucal, dor, apresentando ao exame tomográfico fratura de ângulo da mandíbula no lado esquerdo. Diante do exame clinico e tomográfico, optou-se como conduta terapêutica a FIM e o tratamento cirúrgico sob anestesia geral para osteossíntese com fio de aço, que se mostrou uma técnica alternativa a fixação interna rígida com resultados satisfatórios.
Comparing Non-European Literatures – Dances of Mori Ōgai’s The Dancing Princess and Sabahattin Ali’s Madonna in a Fur Coat to the Music of Goethe
Authors: GÜVEN Devrim Çetin
Published: June 2021

Comparative literature explores the influences of older “texts” on newer ones, through a cross-cultural, interdisciplinary, and multilingual perspective. Another common practice of comparative analysis is to study how Euro-American literary texts inspire non-European ones, and vice versa. Yet, there is a methodological gap concerning the comparative studies that focus on non-European texts with no “direct” intertextual connection. On this basis, arguably, one of the most intriguing and creative ways of comparing two or more non-European works is to spot their common source texts. It is certainly not the only method of comparing non-Western texts, but it is indubitably an efficient method for positivistic intertextual analysis. This article aims to present a “case study” that may serve as a model for comparing non-European literatures. To this end, we focused on two works from Turkish and Japanese literatures that share remarkable resemblances, yet that do not have direct intertextual bonds: Mori Ōgai’s The Dancing Princess and Sabahattin Ali’s Madonna in a Fur Coat. As the major common source text that both refer to is Goethe’s Faust, we traced how these two similar non-European works are affected by Faust, and how their intertextual dances with Faust contributed to their national and international literary reputations.
Sümela Manastırı Kültürel Mirası için Tanımlanması Gereken Miras Alanı ve Tampon Bölgesine Yönelik Öneriler
Authors: ÖZBEY Veysel
Published: June 2021

UNESCO Dünya Kültürel ve Doğal Mirasın Korunmasına Dair Sözleşme’ye taraf devletler, UNESCO Dünya Miras Listesi’ne tanımlamak istedikleri miraslarını kendi UNESCO geçici listelerine yazdırmakla yükümlüdür. Liste için UNESCO Dünya Miras Komitesi’ne sunulacak bir mirasla ilgili dosyanın vazgeçilmez bileşenlerinden birisi de miras alanının ve tampon bölgenin sınırlarını gösterir haritalardır. Bir taraf devlet, ulusal ölçekte yasalar ve diğer yaptırım araçlarını kullanarak sınırlarını belirlediği miras alanlarının korunmasından sorumludur. Çalışmada, UNESCO Dünya Miras Listesi’nde yer alan benzer nitelikteki mimarî mirasların, tanımlanan alanları ve tampon bölgeleri incelenerek Türkiye UNESCO Geçici Listesi’ne 2000 yılında tanımlanan Sümela Manastırı kültürel mirasının alan tanımlamalarına yönelik öneriler geliştirilmiştir. Liste’de yer alan miraslarda, büyük ölçekli ve ilişki kurdukları doğal çevrelerini içeren alan tanımlaması uygulandığı tespit edilmiştir. Sümela Manastırı’nın bulunduğu Maçka İlçesi’nin de Liste’deki miraslara benzer nitelikte, Altındere Vadisi Millî Parkı, Sümela-Altındere Vadisi Doğal Sit Alanı gibi doğal mirasları ve tarih içerisinde Sümela Manastırı ile etkileşim içerisinde olan Vazelon, Panagia Keramesta ve Kuştul Manastırları gibi benzer nitelikteki kültürel mirasları barındırdığı gözlemlenmiştir. Adaylık dosyası için tanımlanacak miras alanı ve tampon bölgesinin, bahsi geçen miraslarla birlikte ele alınmasının, Liste’nin mevcut durumuna daha uygun düşeceği ve yerel getirilerinin daha fazla olacağı sonucuna varılmıştır.
Risk ve Toplum
Authors: ALKIN Ruhi Can
Published: June 2021

Küreselleşme ile birlikte risk olgusu, toplumsal ve ekonomik yaşantının merkezi bir konumuna taşınmıştır. Gündelik yaşantıdan siyasal alana değin hemen her toplumsal organizasyon, geç modern dönem ile farklı toplumsal sınıflar açısından farklı bağlamlardaki (iş, sağlık, eğitim, vb.) riskleri beraberinde getirmektedir. David Denney’in Risk ve Toplum adlı eseri, küreselleşme, toplum ve risk ilişkisini ele almaktadır. Eserde risk toplumu kuramcılarının argümanları detaylı bir şekilde ele alınmış ve günümüzde değişen risk olgusu sosyal bilimsel bir perspektifle ortaya konulmuştur.
Removal of Disperse Orange and Disperse Blue dyes present in textile mill effluent using zeolite synthesized from cenospheres
Authors: Markandeya  , Shukla Sheo Prasad , Srivastav Arun Lal
Published: June 2021

In this research, an efficient, ecofriendly method of using coal fly ash in the form of zeolite to treat wastewater containing dyes was studied. Response surface methodology involving Box–Behnken design was applied to a batch process to evaluate the effect of process parameters such as contact time, dye concentration, agitation speed, pH, and adsorbent dosage onto zeolite. Disperse Orange 25 (DO) dye showed a maximum of 96% removal under optimal conditions of contact time of 119 min, dye concentration of 38.00 mg/L, agitation speed of 158 rpm, pH of 6.10, and adsorbent dosage of 0.67 g/L, whereas 95.23% of Disperse Blue 79:1 (DB) dye removal was observed at adsorbent dose of 1.05 g/L, dye concentration of 26.72 mg/L, agitation speed of 145 rpm, pH of 5.68, and contact time of 122 min. It was concluded that cenosphere-derivatized zeolite adsorbent is efficient, ecofriendly, and economical and has high potential for the removal of DO and DB dyes from aqueous solutions.
Indicios de fibrogénesis en hígado esteatósico no alcohólico de pacientes con componentes del síndrome metabólico
Authors: Pérez-Jorge Genesy , Lambis-Anaya Lina , Puello-Ramos Walter , Solana-Tinoco José , Suarez-Causado Amileth
Published: June 2021

La esteatosis no alcohólica es asociada con pronóstico benigno. Sin embargo, puede progresar a fibrosis, aunque no se comprende completamente el comportamiento de los genes que contribuyen a esta progresión. El objetivo de esta investigación fue analizar los indicios tempranos de fibrogénesis en la esteatosis no alcohólica en pacientes obesos frente a no obesos. Se realizó un estudio descriptivo prospectivo que incluyó a pacientes con esteatosis no alcohólica. Estos fueron divididos en dos grupos: obesos y no obesos. Se obtuvo información sociodemográfica, antropométrica y de padecimientos de componentes del síndrome metabólico. Se determinaron parámetros bioquímicos y niveles de expresión de los genes TNF-α, NF-kβ, CYP2E1, TGF-β, OPN, COL4α5 y HGF por RT-PCR. Los resultados muestran diferencias significativas en los niveles de expresión del gen CYP2E1, siendo mayor en pacientes obesos que padecían síndrome metabólico completo. Además, en pacientes no obesos sin componentes del síndrome metabólico se activa TGF-β como participante de vías fibrogénicas, y en pacientes obesos con síndrome metabólico completo el nivel de expresión significativo de CYP2E1 podría indicar una señal de alarma por un posible progreso de la enfermedad. Debe prestarse especial atención y seguimiento de la esteatosis en pacientes obesos.
Biological Mechanisms of Atypical and Melancholic Major Depressive Disorder
Authors: Tarasov Vadim V. , Ivanets Nikolay N. , Svistunov Andrey A. , Chubarev Vladimir N. , Kinkulkina Marina A. , Tikhonova Yuliya G. , Syzrantsev Nikita S. , Chubarev Ivan V. , Muresanu Cristian , Somasundaram Siva G. , Kirkland Cecil E. , Aliev Gjumrakch
Published: June 2021

Background:

This review summarizes recent findings in molecular biology and neuroimaging and
their applicability to the classification and identification of depression. We discuss whether there is reliable evidence
that could become a basis for biomarkers or subtyping that may enhance our understanding of the biological
foundations of depression and may be useful for clinical practice with respect to diagnosis and prognosis as
well as the selection of treatments.

Objective:

The purpose of this investigation is to present molecular mechanisms that contribute to different origins
of depressions that could prove useful in the daily psychiatric clinic-based practices.

Methods:

The authors have analyzed and summarized electronic publications available in PubMed, Science Direct,
Google Scholar, and Scopus.

Results:

The introduction of molecular diagnostic methods into medical practice is a promising method to improve
the accuracy of the diagnosis of depression in clinical settings. The literature analysis revealed structural
changes in some areas of the brain, its neuroplasticity, as well as changes at the molecular, epigenetic, and genetic
levels. However, there are no current reliable biomarkers for differential diagnosis of the types and subtypes
of depression.

Conclusion:

Major depressive disorder is a biologically and genetically heterogeneous disorder. Given its complexity,
subtyping is worthwhile to identify biological bases of conditions. The literature review provides ample
findings that reveal possible underlying biological mechanisms associated with atypical and melancholic depression.
Additional focused research should be continued with respect to the molecular and genetic biology of different
types of depression. There already are promising findings, but additional research to define biologically
based depressive subtypes is needed and worthwhile.
Comprehensive DNA Methylation-transcriptome Profiles Association Analysis During the Treatment of Acute Myelocytic Leukemia
Authors: Wu Jun , Song Ming-Zhu , Deng Li-Jun , Ye Qian-Ling
Published: June 2021

Background:

Epigenetic modifications have recently attracted much attention in the study of the biological
mechanisms of Acute Myelocytic Leukemia (AML) for therapy and prognosis. However, studies on
DNA methylation changes during AML treatment are limited.

Objective:

The comprehensive DNA methylation-transcriptome profiles association analysis in this study aimed to establish whole-genome DNA methylation profiles and explore DNA methylation-related genes and their potential functions before and after treatment. And more appropriate biomarkers are expected to be identified for therapy strategies in AML.

Methods:

Illumina 450K and RNA-Seq data were obtained from the Cancer Genome Atlas. We performed comprehensive
DNA methylation-transcriptome profiles association analysis, pathway analysis, correlation analysis,
and survival analyses. The StarBase database was utilized to predict interactions between lncRNAs, miRNAs
and target mRNAs.

Results:

In total, 1592 distinct CpG sites and 2419 different expression transcripts were identified between pretreatment
and post-treatment AML. The significantly enriched functions of methylated genes were stem cell differentiation,
cell population maintenance, and cell development. The expression of UGT3A2, MOG, and VSTM1
was correlated with DNA methylation levels (r2
>0.5). Lastly, we identified 4 lncRNAs, 9 miRNAs and 142
mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network.

Conclusion:

Our results revealed that DNA methylation was altered before and after treatment. Alterations in
DNA methylation affected target gene expression and participated in the key biological processes of AML.
Therefore, ceRNA networks may provide further insight into the study of favorable therapeutic markers in
AML.
Rapid Screening of Active Components with Topoisomerase I Inhibitory Activity in Sophora alopecuroides L. Based on Ultrafiltration Coupled with UPLC-QTOF-MS
Authors: Zhang Lin , Yin Xiaoying , Wan Xi , Sun Yun , Cao Menghui , Ouyang Sheng
Published: June 2021

Background:

Topoisomerase I (Topo I) is a key target of many antitumor drugs in vivo. Alkaloids in Sophora alopecuroides L. can reportedly inhibit Topo I activity, but the pharmacodynamic material basis has not yet been determined.

Objective:

This study aimed to rapidly identify active components which inhibit Topo I in S. alopecuroides L.

Methods:

Affinity ultrafiltration coupled with ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UF-UPLC-QTOF-MS) screening system based on Topo I protein was established to screen and isolate a total alkaloid fraction in S. alopecuroides L. Topo I inhibitory activity and anti-tumor proliferation activity of the screened components were evaluated, and their molecular mechanisms were studied.

Results:

Six compounds that bound specifically to Topo I were obtained. Further screening showed that matrine, cytisine, and sophoridine presented higher inhibitory activity on Topo I and were able to inhibit the proliferation of breast cancer MDA-MB-468 cells with IC50 values of 9.40 ± 1.12 mM, 17.4 ± 2.20 mM, and 10.4 ± 1.37 mM, respectively. To the best of our knowledge, their dual molecular mechanisms against Topo I have not discussed to date. In this study, the following dual mechanisms are reviewed for the first time: (1) stabilization of the Topo I-DNA complex and (2) inhibition or blocking of Topo I binding to DNA.

Conclusion:

Matrine, cytisine, and sophoridine from S. alopecuroides L. were defined as the active components possessing Topo I inhibitory activity, and their pharmacological mechanism was confirmed, which provided an important base for further research and development of antitumor components from S. alopecuroides L.
Diet-induced Obesity Differentially Modulates Cardiac
Inflammatory Status in the C57 and FVB Mouse Strains
Authors: Gaisler-Silva Fernanda , Junho Carolina Victoria Cruz , Fredo-da-Costa Izabelle , Christoffolete Marcelo Augusto , Carneiro-Ramos Marcela Sorelli
Published: June 2021

Background:

Cardiovascular diseases correspond to the highest risk of
sudden death worldwide, and obesity is largely related to be an increased risk factor.
There is a higher prevalence of arterial hypertension in obese individuals, including the
presence of cardiac hypertrophy. It is already known the role of toll-like receptors [TLR],
mainly 2 and 4 in heart cells, as fundamental to the process of cardiac hypertrophy.
Obesity has been studied as an activator of damage-associated molecular patterns
[DAMPs], which use the TLR signaling pathway to increase the nuclear factor of
inflammation, NF-kB, increasing cytokine expression in heart tissue. It’s already known
that FVB/N and C57BL/6 mouse strains have different behaviors in relation to
metabolism, but the difference in cardiac tropism and innate immune system modulation
are not clear.

Methods:

The present study aimed to evaluate the contribution of innate immune
factors to cardiac hypertrophy induced by an experimental model of obesity comparing
two mouse strains: C57BL/6 and FVB/N. Both strains were submitted to a high-fat diet
containing 23% protein, 35.5% carbohydrate, and 35.9% fat for 68 days. Hearts were
collected, weighed, and submitted to RT-qPCR, and the serum was analyzed by
Bioplex.

Results:

We observed an increase in heart mass after 68 days in both strains. This was
followed by an increase of α-actin only in C57BL/6 while ANF was increased in FVB/N.
Gene expression of innate immune components and inflammatory cytokines were only
increased in C57BL/6, but not in FVB/N.

Conclusion:

Based on the results obtained, we verified that C57BL/6 mice had a more
robust action of innate immune system then FVB/N.
Predictive Factors for the Care and Control of Hypertension Based on the Health Belief Model Among Hypertensive Patients During the COVID-19 Epidemic in Sirjan, Iran
Authors: Sadeghi Reza , Masoudi Mahmood Reza , Patelarou Athina , Khanjani Narges
Published: June 2021

Background:

Hypertension is a leading risk factor for morbidity and mortality around the world. Preventing this health problem is considered an important priority. The aim of this study was to investigate the predictive factors for care and control of hypertension (CCH) according to the health belief model (HBM), in patients with hypertension during the COVID-19 epidemic in Sirjan, Iran.

Methods:

In this cross-sectional study, participants were chosen by simple random sampling. Data were collected by a valid and reliable researcher-made questionnaire from 200 patients with high blood pressure aged 30-60 years. Data were analyzed by SPSS21 and analysis based on descriptive statistics, Pearson correlation coefficients, and linear regression was conducted.

Results:

The results of Pearson correlation coefficients showed that there was a significant correlation among almost all constructs of the Health Belief Model (HBM), but the strongest correlations were between self-efficacy and perceived susceptibility (r = 0.940, P ≤ 0.001), and between perceived barriers with perceived benefits (r = -0.615, P ≤ 0.001). According to linear regression, perceived barriers (β = -0.291), cues to action (β = -0.590), and knowledge (β = 0.973) predicted more than 26% of CCH variability. Knowledge had a stronger role than other variables.

Conclusions:

The results of this study show that the constructs of the Health Belief Model can predict CCH in hypertensive patients. This model can be used as a tool for designing and implementing educational interventions to increase CCH among hypertensive patients.
Methylaervine as Potential Lead Compound Against Cervical Carcinoma:
Pharmacologic Mechanism Prediction based on Network Pharmacology
Authors: Dan Wenjia , Xu Yujie , Gu Hongling , Gao Jixiang , Dai Jiangkun
Published: June 2021

Background:

The discovery of therapeutic anticancer agents based on natural products
is one of the current research focuses. Network pharmacology will broaden our understanding of
drug actions by bioinformatics analysis.

Objective:

To explore the potential and provide scientific evidence for methylaervine as a lead compound
against cervical carcinoma.

Methods:

Methylaervine was synthesized, and its activity against four cancer cell lines was evaluated
by MTT assay. Pharmacokinetic properties were obtained by in silico approaches, and the pharmacologic
mechanism was predicted by network pharmacology. Then we validated and investigated
our predictions of candidate targets using a molecular docking study.

Results:

Methylaervine was synthesized with a total yield of 54.9%, which displayed activity
against HeLa (IC50 = 14.8 μM) with good predicted pharmacokinetic properties, thus it was considered
a potential lead compound. The network pharmacology study indicated that methylaervine
could act against cervical carcinoma by regulating the function of multiple pivotal targets, such as
CTNNB1, PTPRJ, RPA1, and TJP1, mainly covering cell growth, cell motility, and cell proliferation.
Moreover, docking analysis showed that hydrogen bonds and hydrophobic interactions were
the main forms of interactions.

Conclusion:

This work would provide new insight into the design of anti-cervical carcinoma drugs
based on methylaervine.
Pre-Clinical Activity of Amino-Alcohol Dimeric Naphthoquinones as Potential Therapeutics
for Acute Myeloid Leukemia
Authors: Ferraris Dana , Lapidus Rena , Truong Phuc , Bollino Dominique , Carter-Cooper Brandon , Lee Michelle , Chang Elizabeth , LaRossa-Garcia Maria , Dash Smaraki , Gartenhaus Ronald , Choi Eun Yong , Kipe Olivia , Lam Vi , Mason Kristopher , Palmer Riley , Williams Elijah , Ambulos Nicholas , Kamangar Farin , Zhang Yuji , Kapadia Bandish , Jing Yin , Emadi Ashkan
Published: June 2021

Background:

The clinical outcomes of patients with Acute Myeloid Leukemia (AML) remain unsatisfactory.
Therefore the development of more efficacious and better-tolerated therapy for AML is critical. We have previously
reported anti-leukemic activity of synthetic halohydroxyl dimeric naphthoquinones (BiQ) and aziridinyl BiQ.

Objective:

This study aimed to improve the potency and bioavailability of BiQ compounds and investigate antileukemic
activity of the lead compound in vitro and a human AML xenograft mouse model.

Methods:

We designed, synthesized, and performed structure-activity relationships of several rationally designed BiQ
analogues with amino alcohol functional groups on the naphthoquinone core rings. The compounds were screened for
anti-leukemic activity and the mechanism as well as in vivo tolerability and efficacy of our lead compound was investigated.

Results:

We report that a dimeric naphthoquinone (designated BaltBiQ) demonstrated potent nanomolar anti-leukemic
activity in AML cell lines. BaltBiQ treatment resulted in the generation of reactive oxygen species, induction of DNA
damage, and inhibition of indoleamine dioxygenase 1. Although BaltBiQ was tolerated well in vivo, it did not significantly
improve survival as a single agent, but in combination with the specific Bcl-2 inhibitor, Venetoclax, tumor
growth was significantly inhibited compared to untreated mice.

Conclusion:

We synthesized a novel amino alcohol dimeric naphthoquinone, investigated its main mechanisms of
action, reported its in vitro anti-AML cytotoxic activity, and showed its in vivo promising activity combined with a
clinically available Bcl-2 inhibitor in a patient-derived xenograft model of AML.
Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents:
A Review
Authors: Pottoo Faheem Hyder , Joseph Alex , Das Subham , Akbar Saleem , Ahmed Bahar , Dewangan Rikeshwar Prasad , Iqubal Mohammad Kashif , Iqubal Ashif , Chawla Pooja
Published: June 2021

:

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their
derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two
nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries.
Due to its wide range of biological activities against various diseases, it has been identified as a biologically
important heterocyclic scaffold. The treatment of neurological disorders has always been
a difficult task in both the past and present. Therefore, identifying therapeutically effective
molecules for neurological conditions remains an open challenge in biomedical research and development.
For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted
medicinal chemists worldwide. The major focus of research in this area is discovering novel
molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving
the neurological condition. This review mainly covers recent developments in the neuropharmacological
role of pyrazole incorporated compounds, including their structural-activity relationship
(SAR), which also further includes IC50 values (in mM as well as in μM), recent patents,
and a brief history as neuroprotective agents.
Partial Purification of Polyphenol Oxidase (PPO) from Mango Seed Kernel
(MSK) Using Alcohol/Salt-Based Aqueous Two-Phase System (ATPS)
Authors: Lasquite John Leanard M. , Enopia Brendaline C. , Senangote Roger Francis E. , Sabarre Danilo C. , Yagonia-Lobarbio Camila Flor J.
Published: June 2021

Background:

Polyphenol oxidase (PPO) has applications in pharmaceutical, environmental,
and food industries. However, conventional techniques for its purification are considered
costly and laborious. Alternative methods of purification are needed.

Methods:

This study explored the use of an alcohol/salt-based Aqueous Two-Phase System (ATPS)
to partially purify PPO from Mango Seed Kernel (MSK). Specifically, this study determined the
effects of the 1-propanol/potassium phosphate buffer mass ratio on the partition parameters such as
partition coefficients, activity recovery, and purification fold.

Results:

The enzyme partition coefficient (KE) was greater than 1, which signified that more PPO
was partitioned in the top phase due to its hydrophobic nature. Specifically, the 3.22 1-propanol/
PPB mass ratio had the highest K E of 1.91 ± 0.16 and 1.46 ± 0.16 for runs 1 and 2, respectively.
Moreover, the same mass ratio led to the highest activity recovery in the top phase reaching
up to 73.99 ± 1.56% for run 1 and 64.27 ± 2.48% for run 2. In terms of purification fold, runs 1 and
2 had PF values of 0.55 ± 0.05 and 0.70 ± 0.01, respectively. Since the values obtained were low
due to the large number of contaminants extracted together with the target enzyme in the top phase,
the use of a back-extraction step recovered the PPO in the bottom phase and resulted in an activity
recovery of 82.94 ± 1.05% and a purification fold of 7.01 ± 0.95.

Conclusion:

Results have shown that varying the mass ratio had significant effects on the partition
parameters.
New Insights into Gastroretentive Dosage Forms in Delivery of Drugs
Authors: Mathur Pooja , Jhawat Vikas , Dutt Rohit
Published: June 2021

The oral drug delivery route is preferable to deliver the therapeutic agents because of the
low cost, flexibility in dosage form, and easy administration of drugs responsible for a high range
of patient compliance. GRDDS is also an oral route of drug delivery system to prolong gastric residence
time, thereby achieving site-specific drug release in the upper GIT for local or systemic effect.
Various strategies for developing systematic GRDDS include approaches with less density
than stomach contents, systems with high density, swellable and expanding strategies, formulation
of super porous hydrogels, gas generating systems, hydrodynamically balanced, raft forming approaches,
floating drug delivery, and dual working systems. The massive challenge in developing
systemic GRDDS is inter and intra-individual differences in gastric physiology. Despite so many
formulation strategies, these systems might be associated with few benefits as well as drawbacks.
Drawbacks with few approaches can be overthrown by formulating novel dual working systems
such as a Mucoadhesive Floating Drug Delivery System (MFDDS). These systems can form an intimate
contact of the formulation with the stomach's mucosal membrane and increase the dosage formulation's
absorption at the target site. The present compilation aims to outline the stomach's physiological
state, the ideal characteristics of drugs for GRDDS, key factors impacting GRDF efficacy,
and gastroretentive formulation strategies that could become the critical processes in the pharmaceutical
research for target drug delivery. It also explores various marketed products of GRDDS
and future perspectives.