bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of SARS-COV-2 Drug Targets and Pharmacological
Aspects in Treating the COVID-19
Authors: Bhavaniramya Sundaresan , Ramar Vanajothi , Vishnupriya Selvaraju , Palaniappan Ramasamy , Sibiya Ashokkumar , Vaseeharan Baskaralingam 
Published: August 2021

:
Corona viruses are enveloped, single-stranded RNA (Ribonucleic acid) viruses, and they
cause pandemic diseases having a devastating effect on both human healthcare and the global economy.
To date, six corona viruses have been identified as pathogenic organisms, which are significantly
responsible for the infection and cause severe respiratory diseases. Among them, the novel
SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) caused a major outbreak of
coronavirus diseases in 2019 (COVID-19). Coronaviridae family members can affect both humans
and animals. In humans, coronaviruses cause a severe acute respiratory syndrome with mild to severe
outcomes. Several structural and genomics aspects have been investigated, and the genome encodes
about 30 proteins most of them with unknown function though they share remarkable sequence
identity with other proteins. There are no potent drugs against SARS-CoV-2 and several
trials are underway to investigate the possible therapeutic agents against viral infection. However,
some of the antiviral drugs that have been investigated against SARS-CoV-2 are under clinical
trials. In the current review, we comparatively emphasize the emergence and pathogenicity of the
SARS-CoV-2 and their infection, and discuss the various putative drug targets of both viral and
host receptors for developing effective vaccines and therapeutic combinations to overcome the viral
outbreak.
SK1 Inhibitor RB005 Induces Apoptosis in Colorectal Cancer Cells
through SK1 Inhibition Dependent and Independent Pathway
Authors: Shrestha Jitendra , Shamshiddinova Maftuna , Lee Yong-Moon , Oh Yoon Sin , Baek Dong Jae , Park Eun-Young 
Published: August 2021

Background and Objective:
Colorectal cancer (CRC) is the fourth leading cause of cancer-
related death globally, with a high incidence rate in economically fast-growing countries. Sphingosine-
1-phosphate (S1P) is a bioactive lipid mediator that plays critical roles in cancer cell proliferation,
migration, and angiogenesis converted by the isoforms of sphingosine kinase (SK1 and
SK2). SK1 is highly expressed in colorectal cancer; its inhibitors suppress the formation of S1P
and increase ceramide levels having a pro-apoptotic function. RB005 is a selective SK1 inhibitor
and a structural analog of PP2A activator FTY720. The purpose of this study is to test whether
RB005, an SK1 inhibitor, can be used as an anticancer agent by inhibiting the growth of colon cancer
cells.

Methods:
We performed MTT and colony-forming assay using colon cancer cell lines HT29 and
HCT116 cells to examine the cell toxicity effect of RB005. To determine whether apoptosis of
RB005 in colon cancer cell line is due to SK1 inhibition or other mechanisms due to its structural
similarity with FTY720, we conducted LC/MS, siRNA knockdown, and PP2A activity experiments.

Results:
RB005 notably inhibited CRC cell growth and proliferation compared to PF543 and
ABC294640 by inducing the mitochondria-mediated intrinsic apoptotic pathway. Apoptotic cell
death is caused by increased mitochondrial permeability Initiated by the activation of pro-apoptotic
protein BAX, increased ceramides, and activation of PP2A. Also, RB005 treatment in HT29 cells
did not change the expression level of SK1, but strikingly decreased SK1 activity and S1P levels.
All these events of cell death and apoptosis were less effective when SK1 was knocked down by
siRNA.

Conclusion:
This result indicates that RB005 shows the in-vitro anti-CRC effect by inhibiting SK1
activity and PP2A activation, increasing proapoptotic ceramide levels following the activation of
the intrinsic apoptotic pathway.
Progress in Analgesic Development: How to Assess its Real Merits?
Authors: Kissin Igor 
Published: August 2021

Background:
Assessing analgesic drugs developed over preceding 50 years demonstrated
that very intensive efforts directed at diverse molecular pain targets produced thousands of
PubMed articles and the introduction of more than 50 new analgesics. Nevertheless, these analgesics
did not have a sufficiently broad spectrum of action and level of effectiveness to demonstrably
affect the use of opioids or nonsteroidal anti-inflammatory drugs for the treatment of pain. Analgesics
in current are only modestly effective in chronic pain (at least with respect to neuropathic
pain), and the widespread application of mu-opioid receptor agonists for this purpose culminated in
the global “opioid crisis”. The introduction of every new drug is regarded as an important success,
at least initially. Assessing the merit of a new analgesic is extremely complicated.

Objective:
The aim of this article is to describe an approach that combines very different categories
of drug evaluation – multifactorial approach for the assessment of new analgesics. It is based on
conclusiveness of clinical trials, novelty of a drug’s molecular target, a drug’s commercial appeal,
and the interest in a drug reflected by scientometric indices.

Results:
This approach was applied to analgesics developed in 1982-2016. It shows that although
several new agents have completely novel mechanisms of action, all newly approved drugs, and
drug candidates, demonstrated the same persistent problems: relatively low therapeutic advantage
over previous treatment and narrow spectrum of use in different types of pain, compared to opioids
or NSAIDs.

Conclusion:
The use of the suggested multifactorial approach to drug assessment may provide a
better view of the whole spectrum of analgesics advantages and disadvantages.
The correlation between hope with acceptance of parents toward children with special needs in the special education school in all districts of Ngawi
Authors: Anjasari Hana , Sari Erma Kumala , Priyono Priyono 
Published: August 2021

This research aims to determine the relationship between hope and acceptance of parents toward children with special needs in special education school in all district of Ngawi. This research’s design used quantitative, with correlational research types. The subject in this research were parents of children with special needs who are at junior high and senior high special school levels, amounting to 52 people. Determination of subject used purposive sampling technique. The data collection technique used two attitude scale, namely parents hope scale (α=0,873) and parents acceptance scale (α=0,877). Data analysis used product moment correlation between Pearson. The result of correlation test showed a correlation coefficient value of 0,688 with value rtabel of 0,279, so rhit > rtabel (ρ<0,05) for a significance level of 5%. The result of correlation test is that there was a positive significant relationship between hope and acceptance of parents toward children with special needs who are at junior high and senior high special school levels in special education school in all districts of Ngawi.
Kendala mahasiswa dalam identifikasi dan asesmen anak dengan gangguan emosi dan perilaku selama pandemi COVID-19
Authors: Prabawati Wening , Mahabbati Aini 
Published: August 2021

Identifikasi dan asesmen anak dengan gangguan emosi dan perilaku atau emotional and behavior disorders (EBD) merupakan tahapan awal dalam menentukan layanan pendidikan yang sesuai bagi anak dengan EBD. Tujuan penelitian ini yakni mengetahui apakah mehasiswa mengalami kendala selama melakukan identifikasi dan asesmen anak dengan EBD selama pandemi Covid-19. Jenis penelitian ini yakni penelitian studi kasus. Subjek penelitian ini yakni delapan orang mahasiswa semester enam. Teknik pengumpulan data yakni obervasi, wawancara, dan dokumentasi. Analisis data yang digunakan yakni analisis deskriptif. Hasil penelitian menunjukkan bahwa mahasiswa mengalami kendala selama mengumpulkan data-data yang digunakan untuk identifikasi dan asesmen pada anak dengan EBD selama pembelajaran daring. Kendala yang dialami mahasiswa yakni kesulitan dalam menghubungi sumber seperti guru dan orang tua, tidak bisa bertemu dengan anak secara langsung, data yang diperoleh terbatas. Kesimpulan penelitian yakni adanya kendala yang dialami mahasiswa sehingga menghambat mahasiswa dalam melakukan identifikasi dan asesmen pada anak dengan EBD selama pandemi Covid-19.
A Text Message Intervention for Adolescents With Depression and Their Parents or Caregivers to Overcome Cognitive Barriers to Mental Health Treatment Initiation: Focus Groups and Pilot Trial
Authors: Suffoletto Brian , Goldstein Tina , Brent David 
Published: August 2021

Background
Many adolescents with depression do not pursue mental health treatment following a health care provider referral. We developed a theory-based automated SMS text message intervention (Text to Connect [T2C]) that attempts to reduce cognitive barriers to the initiation of mental health care.

Objective
In this two-phase study, we seek to first understand the potential of T2C and then test its engagement, usability, and potential efficacy among adolescents with depression and their parents or caregivers.

Methods
In phase 1, we conducted focus groups with adolescents with depression (n=9) and their parents or caregivers (n=9) separately, and transcripts were examined to determine themes. In phase 2, we conducted an open trial of T2C comprising adolescents with depression referred to mental health care (n=43) and their parents or caregivers (n=28). We assessed usability by examining program engagement, usability ratings, and qualitative feedback at the 4-week follow-up. We also assessed potential effectiveness by examining changes in perceived barriers to treatment and mental health care initiation from baseline to 4 weeks.

Results
In phase 1, we found that the themes supported the T2C approach. In phase 2, we observed high engagement with daily negative affect check-ins, high usability ratings, and decreased self-reported barriers to mental health treatment over time among adolescents. Overall, 52% (22/42) of the adolescents who completed follow-up reported that they had attended an appointment with a mental health care specialist. Of the 20 adolescents who had not attended a mental health care appointment, 5% (1/20) reported that it was scheduled for a future date, 10% (2/20) reported that the primary care site did not have the ability to help them schedule a mental health care appointment, and 15% (3/20) reported that they were no longer interested in receiving mental health care.

Conclusions
The findings from this study suggest that T2C is acceptable to adolescents with depression and most parents or caregivers; it is used at high rates; and it may be helpful to reduce cognitive barriers to mental health care initiation.
The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes
Authors: Lachin John M. , Bebu Ionut , Nathan David M. 
Published: August 2021

OBJECTIVE
The principal aim is to estimate the benefits of earlier versus later implementation of intensive therapy in type 1 diabetes with respect to the long-term risks of progression of a renal (microvascular) and cardiovascular (macrovascular) complication in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

RESEARCH DESIGN AND METHODS
Cox proportional hazards regression models estimated the 20-year cumulative incidence (absolute risk) and the 20-year relative risk of cardiovascular disease (CVD) and reduced estimated glomerular filtration rate (eGFR) over the first 20 years of EDIC follow-up as a function of the mean HbA1c.

RESULTS
A hypothetical patient treated earlier with 10 years of intensive therapy and a mean HbA1c of 7% (53 mmol/mol) followed by 10 years with a mean of 9% (75 mmol/mol) would have a 33% reduction in the risk of CVD and a 52% reduction in reduced eGFR compared with a patient with a mean HbA1c of 9% (75 mmol/mol) over the first 10 years followed by later intensive therapy over 10 years with an HbA1c of 7% (53 mmol/mol). Despite both patients having the same average glycemic exposure over the 20 years, the patient with the lower HbA1c over the first 10 years had a lower risk of progression of complications over the 20 years than the patient who had the higher value initially.

CONCLUSIONS
While implementation of intensive therapy at any time in type 1 diabetes will be beneficial, within the 20-year period modeled, earlier relative to later implementation is associated with a greater reduction in the risks of kidney and cardiovascular complications.
TECTONIC LANDSLIDE ARRAYSTHE CENTRAL CAUCASUS
Authors: Кюль Е.В. 
Published: August 2021

В статье приводятся результаты инвентаризации основных тектонических оползневых массивов Центрального Кавказа. Вначале на основе проведённого тектонического районирования выделяются основные тектонические структуры исследуемой территории. При этом в пределах данных структур приводятся данные по скорости современных тектонических движений и сейсмической активности. Площадная оценка оползневой деятельности по основным административным районам субъектов-республик, а также основным речным бассейнам, проводится с учётом результатов тектонического районирования. Дана подробная характеристика основных тектонических оползневых массивов. При этом выявлена их приуроченность к главным тектоническим структурам: выделены 3 зоны тектонических сейсмодислокаций, к которым приурочены наиболее крупные оползневые массивы исследуемой территории.
The article presents the results of the inventory of major tectonic landslide slopes of the Central Caucasus. First, based on the tectonic zoning and highlights the main tectonic structures of the study area. Within these structures provides data on the speed of modern tectonic movements and seismic activity. Areal assessment of landslide activities on the main administrative districts of the constituent entities-republics, as well as the main river basin is carried out based on the results of tectonic zoning. Detailed characteristics of major tectonic landslide slopes. At the same time revealed their location to the main tectonic structures: there are 3 zones of tectonic seismic dislocation which dedicated the largest landslide arrays of the study area.
MATHEMATICAL MODELING OF SEISMIC VIBRATIONS OF THE DAM AND UNDERFOUNDATION LAYERS OF THE SOIL MASSIF TAKING INTO ACCOUNT THE INFLUENCE OF WATER IN THE RESERVOIR
Authors: Музаев Н.И. , Харебов К.С. , Музаев И.Д. 
Published: August 2021

Составлена математическая модель совместных сейсмических колебаний высоконапорной плотины, водохранилища и двух слоев массива грунта под основаниями плотины и водохранилища. Модель представляет контактную краевую задачу математической физики в которой учтены взаимозависимости колебательных процессов в грунтовой толще, в плотине и в водохранилище при распространении гармонической сейсмической волны в рассматриваемой системе. В результате решения поставленной задачи получены расчетные формулы для вычисления относительных амплитуд сейсмических колебаний гребня и основания плотины.
The mathematical model of the co-seismic vibrations of high-pressure dams, reservoirs and two layers of soil under the foundations of the dam and reservoir is created. The model represents the contact boundary value problem of mathematical physics which takes into account the interdependence of oscillatory processes in soil, in the dam and in the reservoir during the propagation of harmonic seismic waves in the system under consideration. As a result of solving the tasks the formulae are derived to calculate the relative amplitudes of the oscillations of the top and the base of the dam.
SEISMIC AND ACOUSTIC MONITORING IN VOROTILOVSKAYA DEEP WELL: TECHNIQUE AND RESULTS
Authors: Беляков А.С. , Диденкулов И.Н. , Жигалин А.Д. , Лавров В.С. , Малеханов А.И. , Николаев А.В. 
Published: August 2021

Наблюдения вариаций сейсмоакустического шума Земли показали эффективность пассивного сейсмического мониторинга при изучении эндогенных геодинамических процессов и связи их с интенсивностью сейсмоакустической эмиссии. В Воротиловской глубокой скважине (Нижегородская обл., Россия) регистрируется «шум Земли» в диапазоне частот от 1 Гц до 5 кГц. Шумы такого рода обычно связываются с особенностями тектоники и петрофизическими свойствами горных пород. В середине августа 2016 г. были зарегистрированы неординарные сейсмоакустические сигналы, которые предположительно связываются с взаимодействием высокоэнергичных частиц, в частности, нейтрино, с горными породами или возможным влиянием неопознанных источников, в том числе техногенных.
Observations of variations in seismic and acoustic noise of the Earth has shown the effec-tiveness of passive seismic monitoring in the study of endogenous geodynamic processes and their connection with the intensity of acoustic emission. In Vorotilovskaya deep well (Nizhny Novgorod region, Russia) recorded the «earth noise» in the frequency range from 1 Hz to 5 kHz. The noise of this kind is usually associated with the features of tectonics and petrophysical prop-erties of rocks. In mid-August, 2017 extraordinary seismoacoustical signals were registered that are presumably associated with the interaction of highly energetic particles, in particular, neutri-nos with the rocks or the possible influence of unidentified sources, including technogenic.
GENETIC TYPES OF CATASTROPHIC AVALANCHE-LIKE FLOW AND DYNAMIC TYPES OF THE GLACIERS, WHICH ARE HAZARDOUS FOR THEIR MANIFESTATION
Authors: Бергер М.Г. 
Published: August 2021

Согласно современным представлениям, все лавинообразные потоки генетически однотипны и имеют экзогенную склоново-гравитационную природу. Катастрофические события, произошедшие в последнее время на ледниках Центрального Кавказа и в сопредельных с ними районах перигляциальной зоны, показывают, однако, что такой тип лавинообразных потоков не исчерпывает всего разнообразия существующих в природе их типов. Одним из типов чрезвычайно опасных катастрофических лавинообразных потоков являются газодинамические, генетически связанные с пароксизмальными взрывоподобными направленными газодинамическими выбросами ледников, впервые установленными автором при изучении Колкинской (Геналдонской, Кармадонской) катастрофы 2002 года. К этому же генетическому типу относятся, в частности, Уаскаранские (Перу) катастрофические лавинообразные потоки 1962 и 1970 гг., а также Колкинские (Геналдонские) 1902 и 1752 гг., Девдоракские (Казбекские) 1832 и 1776 гг., Араратские 1840 г. и некоторые другие. Важнейшей особенностью катастрофических лавинообразных потоков этого типа является чрезвычайно высокоскоростное, нередко субгоризонтальное (и даже направленное вверх) движение огромных ледово-каменных масс на значительной части пути по воздуху.
According to the modern concepts, all of the avalanche flows are genetically similar and have exogenous slope-gravitational nature. Catastrophic events happened in recent years on the glaciers of the Central Caucasus and the adjacent areas of periglacial zone indicate, however, that this type of avalanche flows does not exhaust the diversity of their types existing in nature. One of the extremely dangerous catastrophic avalanche types is gas-dynamic one genet-ically associated with paroxysmal explosive directional gas dynamic surge of glaciers, for the first time determined by the author during the study of Kolka (Genaldon, Karmadon) disaster of 2002. In particular, Waskaran (Peru) catastrophic avalanche flows in 1962 and 1970, as well as Kolka (Genaldon) in 1902 and 1752, Devdorak (Kazbek) in 1832 and 1776, Ararat flows in 1840 and some others are referred to the same genetic type. The most important feature of such type of catastrophic avalanche flows is extremely high speed, often sub-horizontal (and even upward) movement of huge ice-rock masses over the air on a large part of the way.
TECTONIC POSITION, SEISMOTECTONIC, MAKROSEISMIC AND SEISMIC MANIFESTATIONS OF THE KURCHALOY EARTHQUAKE 11 OCTOBER 2008 IN THE CHECHEN REPUBLIC
Authors: Рогожин Е.А. 
Published: August 2021

В статье дан анализ причин приуроченности Курчалойского землетрясения к возникшему очагу. Дается логически обоснованное заключение о тектонической природе очаговой зоны и механизме проявления и развития землетрясения. Утверждается, что очаг возникновения характеризуемого землетрясения определяется облаком эпицентров афтершоков, имеющим в плане изометричные очертания, и по кинематике представляется взбросом. Наиболее плотная часть облака приурочена к узлу сочленения Терской антиклинали (развитой над зоной Срединного разлома Терско-Каспийского передового прогиба) и северо-западного линейного, разрывного обрамления горного поднятия Дагестанского клина.
The article provides an analysis of the reasons for the connection between the Kurchaloy earthquake and the resulting focal. Provides a logical conclusion about the tectonic nature of the focal zone and mechanism and development of earthquake. It is alleged that occurrence focus of characterized earthquake is defined by aftershock epicentres cloud with the isometric plan outlines, and kinematically is up thrust. For the most densepart of clouddedicated to the articulation node of the Terek anticline (developed over the area of the Medianfissure of the Terek-Caspian fore land trough) and North-Western linear, discontinuous frame mountain up lift of the Dagestan wedge.
ACTIVE FAULTS IN AZERBAIJAN AND THEIR POTENTIAL IMPACT ON THE OIL AND GAS DEPOSITS OF THE LOWER KURA DEPRESSION
Authors: Етирмишли Г.Д. , Маммадли Т.Я. , Ибрагимова Л.А. 
Published: August 2021

Исследуется возможное влияние сейсмотектонических процессов в активных разломах Нижне-Куринской депрессии Азербайджана и приграничных территорий на углеводородные залежи. По полученным инструментальным данным о многочисленных слабых сейсмических толчках, зарегистрированных обширной сетью цифровых станций, выявлены потенциальные очаговые зоны на территории исследования и оценен их сейсмический потенциал. Полученные результаты показывают, что в Нижне-Куринской депрессии и близлежащих территориях имеется ряд очаговых зон, которые могут генерировать землетрясения интенсивностью в I = IX - X баллов. Разрывные нарушения, образовавшиеся в этих очагах при сильных землетрясениях, могут привести к разрушению структур нефтегазовых залежей и миграции (утечке) нефти и газа.
Explores the possible impact of seismotectonic processes in active faults of Azerbaijan lower Kura depression and bordering territories in hydrocarbon deposits. According to the obtained instrumental data of numerous weak seismic impact registered by extensive network of digital stations, potential endemic zone are identified on site research and their seismic potential are estimated. Obtained results shows, that in the lower Kura depression and bordering territories there are some focal zones, which can generate earthquakes with 10 points intensity. Faults arising in these focal zones when strong earthquakes, can lead to the destruction of oil and gas deposits and migration patterns (leakage) of oil and gas.