bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of China's Health Expenditure Growth: Based on Baumol’s Cost Disease Theory
Authors: Wang Linan , Chen Yuqian
Published: March 2021

Background During the past four decades, China's total health expenditure and health expenditure per capita have both experienced a dramatically increase in growth rate. It is essential to understand the driven force of this growth with the new economic context. This study aims to explore the determinants of health expenditure growth and the influencing mechanism of these determinants, with considering the productivity efficiency represented by Baumol's cost disease. Methods Based on the longitudinal data of 30 provincial-level administrative regions in China, from 2010 to 2017, multi-variates regression models were constructed to assess the determinants, including demography, income, Baumol's cost disease, technology, their effects on per capital total health expenditure growth and the three financing sources: government, society and out-of-pocket health expenditure. Moreover, the Spatial Durbin Model was used to analyze the influence mechanism of each factor on the increase of health expenditure across provinces.Results Among 210 province-year observations, all of the average growth rate of total health expenditure (12.78%) was much higher than the growth rate of per capita real GDP (8.06%). According to the statistical analysis, we found that:(1) Income and Baumol’s cost disease have significant positive impact on health expenditure growth(P<0.01). The impact of technical factors on government health expenditure is significantly positive. (2) The determinants affected the growth of health costs in different regions variably, the eastern region is mainly driven by Baumol's cost disease and technical factors, while the central and western regions are mainly affected by income factors and Baumol's cost disease. (3) There is a significant spatial spillover effect on the health expenditure growth between regions. The income factor and Baumol’s cost disease have a positive impact on the health expenditure growth in its own region as well as in other regions.Conclusions Income and Baumol's cost disease significantly contributed to China health expenditure increase growth. The health expenditure determinants showed spatial varies effect and space spillover effect on the neighborhood areas. Which indicates that a reasonable salary system should be contrasted to meet the changeling from the Baumol's cost disease, and the necessary of equity in health resource allocation among provinces in China.
Culture Systems of Isolated Pancreatic Islets with Extracellular Matrix Biomimetics as Tissue-Engineered Constructs of the Pancreas
Authors: Sevastianov Victor I , Baranova Natalia V , Kirsanova Lyudmila A , Ponomareva Anna S , Nemets Eugene A , Gautier Sergey V
Published: March 2021

The creation of a tissue-engineered structure of the pancreas based on isolated pancreatic islets is hindered by problems associated with maintaining their viability and insulin-producing function. Both biopolymer and tissue-specific scaffolds can contribute to the preservation of the structure and function of pancreatic islets in vitro and in vivo. Comparative morphofunctional analysis in vitro of two different types of tissue-engineered structures of the pancreas, which represent culture systems of isolated islets with biomimetics of an extracellular matrix - a biopolymer collagen-containing scaffold and a tissue-specific scaffold obtained as a result of pancreatic decellularization, - was performed. The results showed that the use of scaffolds in the creation of a tissue-engineered design of the pancreas contributes not only to the preservation of the viability of the islets, but also to the prolongation of their insulin-producing functions, compared to the monoculture of the islets in vitro. A significant increase was found in the basal and stimulated (under glucose load) insulin concentrations in the tissue of engineered structures studied, at the same time the advantage of using a tissue-specific scaffold compared to a biopolymer collagen-containing scaffold was shown. We think that these studies will become a platform for creating a tissue-engineered design of the human pancreas for treatment of type 1 diabetes mellitus.
Health technology assessment in low- and middle-income countries: a case study of trastuzumab for early and locally advanced HER-2 positive breast cancer in Tunisia
Authors: Dequen-O'Byrne Pascale , Sculpher Mark , Hawkins Neil , Thompson Juliette C , Abrams Keith R
Published: March 2021

The role of health technology assessment (HTA) in low- and middle-income countries (LMICs) has become increasingly important in order to inform resource allocation and wider health policy decision-making. Using the case study of Tunisia’s first published HTA on trastuzumab in early and locally advanced HER2 positive breast cancer, we aim to evaluate how the key principles and elements of HTA might be applied in the assessment of health interventions undertaken by emerging HTA agencies in LMICs, in light of likely capacity and resource constraints. We critically evaluate the Tunisian HTA in the context of widely cited ‘best practice’ guidelines to determine how the assessment conducted by the Tunisian National Authority for Assessment and Accreditation in Healthcare aligns with recommended HTA methods. We find the Tunisian trastuzumab HTA to be an encouraging example of the ability of a newly established agency to conduct a transparent and scientifically rigorous evidence driven assessment. We draw on lessons learned in other countries and present a number of ongoing research and policy initiatives to promote the implementation of HTA, given resource constraints; in order to formulate recommendations for future HTA practice in Tunisia and LMICs, respectively. We discuss the sharing of evidence and resources and the potential of stakeholder engagement in building and strengthening HTA capacity worldwide.
Expression of Mitochondrial Progesterone Receptor (PR-M) in Ovarian Cancer and Its Effect on Cell Metastasis Induced by Progesterone
Authors: Yang Qingqing , Duan Chang , Wang Haofan , Jiang Dongyuan , Wang Yaping , Tian Qingfeng , Feng Quanling
Published: March 2021

Background: PR-M refers to a novel truncated progesterone receptor located on the outer membrane of mitochondria, capable of facilitating the proliferation of leiomyoma cells and breast cancer cells, as well as inhibiting apoptosis as impacted by progesterone or progesterone agonists. However, its role in ovarian tumors has not yet been elucidated.Objective: To study the expression of PR-M in different ovarian tumor tissues and normal tissues, and the effect exerted by progesterone on the proliferation and migration of SKOV-3 cells that achieve high PR-M expression.Methods: Real- time PCR and Western blot were employed for determining PR-M levels in cell lines, non-cancer tissues and ovarian cancer tissues. By immunohistochemistry, PR-M protein expression in benign tumor, borderline tumor and epithelial carcinoma was detected, and the clinicopathological characteristics between PR-M and cancer were analyzed. Furthermore, CCK-8 and scratch test were performed to explore the proliferation and migration of SKOV-3 cells exhibiting high PR-M expression.Results: PR-M increased significantly in cancer tissues and ovarian cancer cell lines, in comparison to normal cells and non-cancer tissues. The abnormal expression showed a significant correlation with intraperitoneal metastasis, lymph node metastasis, clinically related stage and CA125 level, suggesting that high PR-M expression may affect the progression of ovarian tumors. During the cell experiment, PR-M achieved the maximum expression in SKOV-3 cells (PR-A / B(-)). As impacted by progesterone, SKOV-3 cells (PR-A / B(-)) achieved the enhanced proliferation and migration. Besides, the enhancing effect was dose and time-dependent.Conclusion: PR-M is critical to develop ovarian cancer. Progesterone may facilitate the proliferation and migration of ovarian cancer cells exhibiting high PR-M expression.
Potential of household photobioreactor for algae cultivation
Authors: Osama Ashrakat , Hosney Hadeel , Moussa M. S.
Published: March 2021

Biotechnology harbors stunning potential to provide cutting-edge solutions that can mitigate arising environmental issues which impact developing countries more severely. Although considerable projects have been implemented in these developing nations to reduce the consequences of climate change, global warming, and food insecurity, most of the initiatives are deemed unsustainable or unfulfilling. Consequently, millions of individuals are still suffering from unhealthy environments and others have limited access to clean technologies. Accordingly, this manuscript is developed to act as a one-stop source for technical perspectives of microalgae cultivation and proposes the potential of scaling down of a photobioreactor (PBR) from industrial to household level to alleviate adverse environmental implications. The household PBR proposal is concerned with microalgae cultivation that contributes to mitigating CO2 from the surrounding environment and synthesizing a product that could be of high nutritional value. Additionally, the business model of household PBR is developed in accordance to low and middle-income countries’ demands to facilitate future projects in this scope. The value proposition of this model relies on decreasing climate change impacts, enhancing wellbeing, and providing natural supplements. Scale of economy, appropriate technology, and socio-economic challenges for household PBR are highlighted.
Donor-transmitted Anterior Myocardial Ischaemia in a Teenager: How to Proceed?
Authors: Göbölös Laszlo , Hogan Maurice , El-Banna Mosaad , Bader Feras , Tuzcu Emin Murat , Bhatnagar Gopal
Published: March 2021

Background:

Heart transplantation remains the treatment of choice for end-stage heart failure patients, owing to the associated dual improvements in quality of
life, and prognosis. The discrepancy between higher demand and supply of donor organs is the limiting factor, and is established universally.
Increasing consideration of donor populations up to 65 years of age and marginal donor hearts has helped to facilitate the availability of potential
grafts. However, grafts from older donors carry the mid-term increased risk of coronary allograft vasculopathy, including donor-transmitted
coronary disease.

Case report:

A 15-year-old female underwent orthotopic heart transplantation for non-ischaemic cardiomyopathy, the donor was a 44-year-old male. The
recipient developed anterior wall ischaemia within a year requiring coronary angioplasty and stent implantation to treat the severe obstruction in
the left anterior descending coronary artery. However, two months later, the patient was readmitted with in-stent restenosis.
Therefore, to optimally revascularise the left anterior descending coronary artery, and minimise risks associated with re-sternotomy, a minimally
invasive direct coronary artery by pass grafting of the left internal mammary artery to the left anterior descending artery was performed.

Conclusion:

Surgical revascularisation in generalised coronary allograft vasculopathy is an inadequate option; repeat heart transplantation is the treatment of
choice, albeit given its morbidity, should be reserved for a highly selected patient population. In localised coronary lesions, conventional coronary
bypass surgery may be a feasible choice in selected patients with left anterior descending artery lesions. Minimal invasive techniques, such as
minimally invasive direct coronary artery bypass grafting rather than robotic techniques, would be preferable for ease of approach and to limit the
surgical re-do trauma.
Chronic Inflammation and Cancer: The Role of Endothelial Dysfunction and Vascular Inflammation
Authors: Malhab Lara J. Bou , Saber-Ayad Maha M. , Al-Hakm Ranyah , Nair Vidhya A. , Paliogiannis Panagiotis , Pintus Gianfranco , Abdel-Rahman Wael M.
Published: March 2021

Long-lasting subclinical inflammation is associated with a wide range of human diseases, particularly
at a middle and older age. Recent reports showed that there is a direct causal link between inflammation and
cancer development, as several cancers were found to be associated with chronic inflammatory conditions. In
patients with cancer, healthy endothelial cells regulate vascular homeostasis, and it is believed that they can limit
tumor growth, invasiveness, and metastasis. Conversely, dysfunctional endothelial cells that have been exposed
to the inflammatory tumor microenvironment can support cancer progression and metastasis. Dysfunctional
endothelial cells can exert these effects via diverse mechanisms, including dysregulated adhesion, permeability,
and activation of NF-κB and STAT3 signaling. In this review, we highlight the role of vascular inflammation
in predisposition to cancer within the context of two common disease risk factors: obesity and smoking. In
addition, we discuss the molecular triggers, pathophysiological mechanisms, and the biological consequences
of vascular inflammation during cancer development and metastasis. Finally, we summarize the current therapies
and pharmacological agents that target vascular inflammation and endothelial dysfunction.
The Art of Total Synthesis of Bioactive Natural Products via Microwaves
Authors: Majhi Sasadhar
Published: March 2021

Natural products are the most effective source of potential drug leads. The total
synthesis of bioactive natural products plays a crucial role in confirming the hypothetical
complex structure of natural products in the laboratory. The total synthesis of rare bioactive
natural products is one of the great challenges for the organic synthetic community due to
their complex structures, biochemical specificity, and difficult stereochemistry. Subsequently,
the total synthesis is a long process in several cases, and it requires a substantial amount of
time. Microwave irradiation has emerged as a greener tool in organic methodologies to reduce
reaction time from days and hours to minutes and seconds. Moreover, this non-classical
methodology increases product yields and purities, improves reproducibility, modifications of
selectivity, simplification of work-up methods, and reduces unwanted side reactions. Such
beneficial qualities have stimulated this review to cover the application of microwave irradiation in the field of the
total synthesis of bioactive natural products for the first time during the last decade. An overview of the use of microwave
irradiation, natural sources, structures, and biological activities of secondary metabolites is presented elegantly,
focusing on the involvement of at least one or more steps by microwave irradiation as a green technique.
A New Prognostic Strategy Based on four DNA Repair-Associated
lncRNAs for Hepatocellular Carcinoma
Authors: Liu Li , Zeng Hanyi , Liu Chengdong , Zhou Xiaohan
Published: March 2021

Background:

Hepatocellular carcinoma (HCC) is a malignant tumour with a poor
prognosis. The effect of DNA repair on prognosis cannot be ignored, and long non-coding RNA
(lncRNA) can regulate the DNA repair process.

Objective: :

To obtain DNA repair-associated lncRNA (DR-lncRNA) prognostic signature for
improving the ability to predict HCC prognosis.

Methods:

Our study used the Cancer Genome Atlas database. Gene set variation analysis was
performed to differentiate high and low levels of DNA repair to identify DR-lncRNAs. By
performing univariate Cox regression, LASSO regression, and multivariate Cox regression
analyses, we finally obtained a DR-lncRNA prognostic signature and constructed a nomogram
prognostic model. Time-dependent receiver operating characteristic (ROC) curves, calibration
plots, decision curve analysis (DCA), and clinical impact curves were used to assess predictive
ability and clinical utility. Differentially expressed genes (DEGs) functional enrichment analysis
was performed to further explore the underlying mechanisms that influence HCC prognosis.

Results:

We obtained the following DR-lncRNA prognostic signature:AP002478.1, AC116351.1,
LINC02580, and LINC00861. The ROC curves and calibration plots showed good discrimination
and calibration properties. Combining the DR-lncRNA prognostic signature and tumour stages, we
established a nomogram prognostic model. DCA and clinical impact curves showed the clinical
utility of this model. DEGs of high-risk and low-risk groups predicted by the prognostic DRlncRNA
were significantly associated with cell cycle, various metabolic pathways and biological
processes, such as the oxidation-reduction process and cell division.

Conclusion:

We identified a DR-lncRNA prognostic signature and constructed a nomogram
prognostic model, which could be a beneficial prognostic strategy for HCC.
Relationship Between Clinical, Demographic and Socioeconomic Factors
with Suicide Ideation; A Cross-sectional Study
Authors: Ghazizadeh Hamideh , Khorasani Mahdiyeh Yaghooti , Shabani Niloofar , Sahranavard Toktam , Zare-Feyzabadi Reza , Mohammadi-Bajgiran Maryam , Timar Ameneh , Oladi Mohammad Reza , Moazedi Sara , Mosalman-Zadeh Negin , Khedmatgozar Hamed , Rohban Mohadeseh , Hasanzadeh Elahe , Javandoost Ali , Nazarpour Shahin , Bahrami Afsane , Ferns Gordon A. , Haghdoost Ali Akbar , Esmaily Habibollah , Ghayour-Mobarhan Majid
Published: March 2021

Background:

Suicide has grown in global prevalence as a public health problem. We
aimed to evaluate the association of socioeconomic factors, biochemical and hematologic tests, and
suicide ideation.

Methods:

In this cross-sectional study, 8267 Iranian adults aged 35 – 65 years old were enrolled.
The assessment of suicide ideation was made by the completion of Beck’s depression inventory
(BDI) questionnaire; according to one specific item on the questionnaire: “have you ever decided
to suicide in the past week?”

Results:

According to our results, 6.9 % of subjects had ideation of suicide. The results showed
high levels of FBG, RBC, MCHC, and hs-CRP were associated with suicide ideation. Obese,
single subjects, and current-smokers had a higher risk of suicide ideation.

Conclusion:

Increased physical activity, obesity, and smoking are associated with a high risk of
suicide ideation; whilst, a high MCHC is related to a low risk of suicide ideation in Iranian adults.
Hutchinson-Gilford Progeria Syndrome: An Overview of the Molecular Mechanism, Pathophysiology and Therapeutic Approach
Authors: Rahman Md. Mominur , Ferdous Kazi Sayma , Ahmed Muniruddin , Islam Mohammad Touhidul , Khan Md. Robin , Perveen Asma , Ashraf Ghulam Md. , Uddin Md. Sahab
Published: March 2021

Lamin A/C encoded by the LMNA gene is an essential component for maintaining the
nuclear structure. Mutation in the lamin A/C leads to a group of inherited disorders is known as
laminopathies. In the human body, there are several mutations in the LMNA gene that have been
identified. It can affect diverse organs or tissues or can be systemic, causing different diseases. In
this review, we mainly focused on one of the most severe laminopathies, Hutchinson-Gilford progeria
syndrome (HGPS). HGPS is an immensely uncommon, deadly, metameric ill-timed laminopathies
caused by the abnormal splicing of the LMNA gene and production of an aberrant protein
known as progerin. Here, we also presented the currently available data on the molecular mechanism,
pathophysiology, available treatment, and future approaches to this deadly disease. Due to
the production of progerin, an abnormal protein leads to an abnormality in nuclear structure, defects
in DNA repair, shortening of telomere, and impairment in gene regulation which ultimately results
in aging in the early stage of life. Now some treatment options are available for this disease,
but a proper understanding of the molecular mechanism of this disease will help to develop a more
appropriate treatment which makes it an emerging area of research.
The Long Non-coding RNA Cytoskeleton Regulator (CYTOR) Sponges microRNA- 206 (miR-206) to Promote Proliferation and Invasion of HP75 Cells
Authors: Keqi Hu , Handong Liu
Published: March 2021

Background:

The role and mechanism of long non-coding RNA cytoskeleton regulator
(CYTOR) in Invasive Pituitary Adenomas (IPA) have not been elucidated previously.

Objective:

This study aimed to investigate the interaction between CYTOR and miR-206 and their
roles in IPA using HP75 cells as the model.

Methods:

The expression levels of CYTOR and miR-206 were detected by quantitative real-time
polymerase chain reaction (qRT-PCR) in IPA tissues and cell lines. The Chi-square test was used
to analyze the correlation between CYTOR expression and clinical-pathological parameters. HP75
cell proliferation was detected by Cell Counting Kit-8 assay and colony formation assay. Scratch
healing experiments and Transwell assay were used to detect migration and invasion of HP75 cells.
The relationship between CYTOR and miR-206 was predicted by bioinformatics and verified by
qRT-PCR and the dual-luciferase reporter gene method.

Result:

CYTOR is up-regulated in IPA tissues and cell lines. The high expression of CYTOR is
associated with adenoma invasiveness and adenoma size of the patients. Down-regulation of CYTOR
decreases the proliferation, migration and invasion of HP75 cells, while up-regulation of
miR-206 can inhibit proliferation, migration and invasion of HP75 cells. MiR-206 is identified as a
target of CYTOR and could be negatively regulated by it in IPA.

Discussion:

CYTOR, as a tumor-promoting factor, facilitates the proliferation, migration and invasion
of HP75 cells through sponging miR-206.

Conclusion:

The CYTOR-miR-206 axis provides new insights into the diagnosis and treatment of
IPA.
By Discontinuing Beta-Blockers Before an Exercise Test, We may Precipitate a Rebound Phenomenon
Authors: Koracevic Goran , Micic Sladjana , Stojanovic Milovan
Published: March 2021

Background:

There is a need to analyse the current approach to beta-blocker (BB) use in relation to exercise-based stress tests.

Objective:

We compared various guidelines regarding recommending abrupt vs. gradual discontinuation of BB prior to exercise tests. We also analyse the shortcomings of the currently recommended approach and suggest a new approach to avoid BB rebound.

Methods:

A narrative review is used to analyse this topic due to lack of valid randomized clinical trials.

Results:

Omitting the BB therapy prior to exercise-based test has been recommended in guidelines for many years. Although reasonable, this approach has potential disadvantages since sudden BB withdrawal may induce a rebound phenomenon, which is also acknowledged in several guidelines.

Conclusions:

We observed inconsistency among relevant guidelines; there is no homogenous approach regarding BB use before exercise tests. Most guidelines recommend BB withdrawal for a couple of days before the test; they do not advise BB dose tapering. This approach is not standardised and raises the risk of BB rebound phenomenon before and during the test. Therefore, we suggest using half the prescribed BB dose at the usual time of administration (in the morning, prior to the exercise test).
Diselenides and Selenocyanates as Versatile Precursors for the Synthesis of
Pharmaceutically Relevant Compounds
Authors: Kostić Marina D. , Divac Vera M.
Published: March 2021

:

Organoselenium chemistry has undergone extensive development during the past decades, mostly due to the unique chemical properties of organoselenium compounds that have been widely explored in a number of synthetic transformations, as well as due to the interesting biological properties of these compounds. Diselenides and selenocyanates constitute the promising classes of organoselenium compounds that possess interesting biological effects and that can be used in the preparation of other selenium compounds. The combination of diselenide and selenocyanate moieties with other biologically relevant molecules (such as heterocycles, steroids, etc.) is a way for the development of compounds with promising pharmaceutical potential. Therefore, the aim of this review is to highlight the recent achievements in the use of diselenides or selenocyanates as precursors for the synthesis of pharmaceutically relevant compounds, preferentially compounds with antitumor and antimicrobial activities.
The Recovery of an Elderly Woman with Asthma and Diabetes from
COVID-19 Infection: A Case Report
Authors: Ghaysouri Abas , Safari Maryam , Mohammadyari Elham , Balavandi Firooz , Nazari Ali , Feizi Jalil , Karimian Mohamad , Bastani Elham , Salimi Ebrahim , Tavan Hamed
Published: March 2021

Introduction:

COVID-19 has caused a great deal of fear indifferent communities. In this study, we reported the recovery of a diabetic elderly woman with a history of asthmafromCOVID-19 infection.

Case Presentation:

A 61-year-old woman was hospitalized due to dyspnea and low blood O2 saturation and later diagnosed with COVID-19, as confirmed by PCR. The patient had a history of asthma and diabetes and used salbutamol and Atrovent spray. She also had a history of hospitalization at one month prior to the current admission. Despite all these, COVID-19was successfully managed, and she was discharged with a good clinical condition after the improvement of respiratory complications.

Conclusion:

Despite having an advanced age and underlying diseases (diabetes and asthma), the recovery of this elderly woman shows that even such patientscandefeatCOVID-19 as long as the disease is not progressed to advanced phases and appropriate therapeutic measures are taken. By reporting such cases, it is possible to give people hope and motivation and reduce their fear of the disease.
Radiomics - Quantitative Biomarker Analysis for Breast Cancer Diagnosis and Prediction: A Review
Authors: Moyya Priscilla Dinkar , Asaithambi Mythili
Published: March 2021

Background:

Breast cancer has become a global problem. Though concerns regarding
early detection and accurate diagnosis have been raised, continued efforts are required for the development
of precision medicine. In the past years, the area of medicinal imaging has seen an unprecedented
growth that has led to an advancement of radiomics, which provides countless quantitative
biomarkers extracted from modern diagnostic images, including a detailed tumor characterization
of breast malignancy.

Discussion:

In this review, we have presented the methodology and implementation of radiomics
together with its future trends and challenges on the basis of published papers. Radiomics could
distinguish malignant from benign tumors, predict prognostic factors, molecular subtypes of breast
carcinoma, treatment response to neoadjuvant chemotherapy (NAC), and recurrence survival. The
incorporation of quantitative knowledge with clinical, histopathological, and genomic information
will enable physicians to afford customized care of treatment for patients with breast cancer.

Conclusion:

This review was intended to help physicians and radiologists gain fundamental knowledge
regarding radiomics, and also to work collaboratively with researchers to explore evidence for
its further usage in clinical practice.
Metabolic Characteristics of SM-1, a Novel PAC-1 Derivative, in Human Liver Microsomes
Authors: Gong Ya , Wang Peiqi , Li Jianming , Jingbinin Huang , Ding Jinsong
Published: March 2021

Background and Objectives:

SM-1 is a new synthetic small molecule compound with antitumor activity. The metabolism of SM-1 is a key parameter that needs to be evaluated to provide further insight into drug safety and efficacy in the early phases of drug development.

Methods and Results:

In this study, the biotransformation process of SM-1, including the metabolic pathways
and major metabolites, was investigated based on a liquid chromatography-mass spectrometry
method. Upon incubation of SM-1 with human liver microsomes, five metabolites were identified,
namely dihydrodiol formation (R1), hydroxylation (R2, R3, and R5), and debenzylation (R4)
of SM-1, with R1 and R4 being the major metabolites. The enzyme kinetic parameters of SM-1
were determined by a liquid chromatography-tandem mass spectrometry method. The enzyme kinetics
of SM-1 obeyed the Michaelis-Menten equation. The Vmax, Km, and CLint of SM-1 in HLMs
were 14.5 nmol/mg protein/h, 6.32 μM, and 2.29 mL/mg protein/h, respectively.

Results:

The chemical inhibition studies showed that CYP450 isoenzymes were responsible for
SM-1 metabolism in HLMs, and CYP3A4 was the major CYP450 isoenzyme involved in the metabolism
of SM-1; these findings were confirmed by using the human recombinant CYP3A4.

Conclusion:

Through the identification of the biotransformation pathways and enzyme kinetics of
SM-1, the metabolic enzymes for SM-1 in HLMs are characterized.
Hepatitis B Virus X Protein Modulates Chemokine CCL15 Upregulation in Hepatocellular Carcinoma
Authors: Li Ying , Wang Chaomin , Zhao Ting , Cui Ranliang , Hu Linfei , Chang Luchen , Wei Xi , Zhang Jin , Li Yueguo
Published: March 2021

Background:

Hepatitis B virus X protein (HBx) is an indispensable progression factor in Hepatocellular
Carcinoma (HCC). CCL15 could be a peculiar proteomic biomarker of HCC with tumorigenesis and tumor
invasion.

Objective:

The aim of study was to explore the relationship between HBx and CCL15 expression in HCC.

Methods:

HBV-positive HCC pathological tissue samples and corresponding adjacent non-tumor liver tissues
were collected. The expression of HBx and CCL15 was analyzed by immunohistochemistry, real-time Polymerase
Chain Reaction (PCR), and western blot analysis in tissues or in vitro.

Results:

The levels of CCL15 mRNA and protein expression in HCC samples were observably higher than
those of adjacent non-tumor liver tissues. The CCL15 was significantly associated with the expression of HBx
in HBV-positive HCC samples. The up-regulation of HBx induced CCL15 expression in vitro. The high expression
score of CCL15 was significant associated with the poor prognosis of HCC patients.

Conclusions:

The CCL15 expression was observably associated with HBx in HCC patients. The CCL15 may be
considered as an indicator in the clinical management of HBV-associated HCC.
PERAN GURU SEJARAH DALAM PENDIDIKAN KARAKTER DI ERA REVOLUSI INDUSTRI 4.0
Authors: Suyanti Suyanti
Published: March 2021

Guru adalah pendidik profesional dengan tugas mengajar, mendidik, membimbing, melatih, dan menilai peserta didik. Peran guru sejarah semakin kompleks pada era Revolusi 4.0. Guru bukan hanya dituntut untuk menguasai materi pembelajaran maupun kompetensi penunjang pembelajaran, namun guru juga dituntut untuk mananamkan karakter nasionalisme. Di era revolusi 4.0  perkembangan teknologi semakin cepat dan guru sejarah diharapkan tidak hanya  memberikan ilmu pengetahuan saja tetapi harus menginternalisasi nilai-nilai karakter yang tidak bisa digantikan oleh teknologi secanggih apapun. Maka dari itu, sebagai guru sejarah harus bisa mengembangkan kompetensinya mengikuti perkembangan zaman dan bisa memainkan peran demi keberhasilan belajar peserta didik.Kata kunci: Guru sejarah, pendidikan karakter, Revolusi Industri 4.0
Nastanak i liječenje gigantskih kamenaca ileocekalnog urinskog spremnika u pacijenta liječenog cistektomijom zbog intersticijskog cistitisa
Authors: Crnić Matilda , Kurosch Martin , Dotzauer Robert , Markić Dean
Published: March 2021

Cilj: Cilj ovoga rada je prikazati pacijenta s intersticijskim cistitisom u kojega je došlo do stvaranja kamenaca u novoformiranom urinskom spremniku. Prikaz slučaja: Pacijent star 48 godina obrađivan je zbog recidivnih infekcija mokraćnog sustava. Prethodno mu je zbog intersticijskog cistitisa, koji je znatno utjecao na njegovu kvalitetu života, učinjena cistektomija uz oblikovanje urinskog spremnika (Mainz-pouch I). Urološkom obradom pronađena su u području urinskoga spremnika dva velika kamenca dimenzija 77 × 74 mm te 76 × 62 mm uz obostranu hidronefrozu. Kako bi se riješio uzrok rekurentnih urinarnih infekcija, učinjena mu je otvorenim pristupom ekstrakcija oba kamenca. Poslijeoperacijski tijek bio je uredan te je pacijent nastavio s provođenjem intermitentne samokateterizacije uz značajno poboljšanu kvalitetu života. Zaključak: U pacijenata s teškim oblikom intersticijskog cistitisa u obzir dolazi učiniti cistektomiju s urinarnom derivacijom. Pojava kamenaca u urinskome spremniku u takvih pacijenata nije česta, a liječenje ovisi o veličini litijaze (otvoreni odnosno endoskopski pristup).
Branding Cannabis in Canada: Challenges for theCannabis Act's Promotion Restrictions
Authors: Asquith Kyle
Published: March 2021

Background:This article examines how Canadian cannabis companies promoted their new brands after legalization in late-2018.

Analysis:Nearly 4,000 items were collected from the websites and social media of 20 cannabis brands and triangulated with insight from the trade press. The promotional practices are contextualized in two areas: the history of tobacco advertising in Canada, as legal precedent for the Cannabis Act, and theories of branding.

Conclusion and implications:Brands are navigating the Cannabis Act’s promotion restrictions by embodying what it means to be a brand in the twenty-first-century media environment. This reveals an incompatibility between regulations and contemporary marketing.
Pemantauan Jarak Jauh Menggunakan Mikrokontroler
Authors: Sudir Mat
Published: March 2021

Fenomena fisika yang tergolong indikator kenyamanan suatu ruang. Secara fisik, manusia dapat merasakan keadaan panas dan atau gerah melalui peristiwa sensing indera dan dikategorikan data kualitatif. Akan tetapi, secara kuantitatif, dibutuhkan data yang dapat diolah dan ditampilkan secara visual sebagai dasar intepretasi dalam suatu sistem. Pada penelitian ini akan dirancang simulasi koneksi dari pemantauan jarak jauh dengan menggunakan mikrokontroler. Sistem pemantauan waktu nyata berbasis Internet of Things (IoT) yang akan memantau fenomena fisika berupa suhu dan kelembaban di ruang. Data akan diolah untuk dilakukan visualisasi ulang. Untuk kemudian dihitung nilai selisih dari masing pengukuran (dalam identitas waktu yang sama). Nilai selisih ini akan dipergunakan untuk menghitung tingkat pergeseran informasi situs (hasil akuisisi NodeMCU) dengan pengukuran lokal (hasil akuisisi). Sistem berbasis Internet of Things (IoT) adalah sistem yang memanfaatkan teknologi internet sebagai wadah distribusi informasi. Pemanfaatan mikrokontroler sudah banyak diterapkan pada kegiatan yang melingkupi aktivitas umum masyarakat. Mulai dari otomasi bangunan sampai ke pembuatan bangunan cerdas. Simulasi alur koneksi tersebut akan di kaji lebih lanjut dalam evaluasi sistem yang akan di bangun nantinya.
DISAIN PEMBELAJARAN ONLINE PADA ERA DAN PASCA COVID-19
Authors: Marbun Purim
Published: March 2021

Penelitian ini dilatarbelakangi situasi dan kondisi pada masa covid-19 mengharuskan setiap orang melakukan kegiatan di rumah. Pemerintah telah menetapkan policy bahwa semua masyarakat stay at home, termasuk kegiatan belajar, bekerja dan beribadah pun dilakukan dari rumah. Dengan instruksi di atas implikasi bagi kegiatan pembelajaran  memerlukan disain pemnbelajan online untuk memastikan berlangsungnya pendidikan dengan baik.  Metode penelitian dalam tulisan ini ialah studi kepustakaan dengan fokus menemukan model-model disain pembelajaran yang efektif dan dapat di gunakan pada era dan pasca covid-19. Hasil penelitian ini diharapkan mampu memberikan pilihan-pilihan model disain pembelajaran online kepada dosen sehingga mampu menyajikan pembelajaran secara efektif dan berkualitas.
Picturing a Thousand Unspoken Words
Authors: Peach Harmony
Published: March 2021

I explore how empathetic visual argument may be the mode best suited for eliciting appropriate force to the reasons given by arguers who face systematic identity prejudices. In the verbal mode, this force is often skewed through epistemic injustice (Fricker 2007), argumentative injustice (Bondy 2010), and discursive injustice (Kukla 2010). Highlighting their reliance on the Aristotelian sense of enthymeme, I show how visual arguments are highly context specific. Using Ian Dove’s Visual Scheming (2016) and the theory of the Retort collective (2004) via case study, I demonstrate how the visual mode can leave the appropriate force in the arguer’s control.
Stability and approximation of solutions in new reproducing kernel Hilbert spaces on a semi-infinite domain
Authors: Hassan Jabar , Grow David E.
Published: March 2021

We introduce new reproducing kernel Hilbert spaces on a trapezoidal
semi-infinite domain $B_{\infty}$ in the plane. We
establish uniform approximation results in terms of the number of nodes
on compact subsets of $B_{\infty}$ for solutions to
nonhomogeneous hyperbolic partial differential equations in one of these
spaces,
$\widetilde{W}(B_{\infty})$.
Furthermore, we demonstrate the stability of such solutions with respect
to the driver. Finally, we give an example to illustrate the efficiency
and accuracy of our results.
Ritual Functions of Sun Wukong’s Hair in Wu Cheng-en’s novel “Journey to the West”
Authors: Seibel N. E.
Published: March 2021

The results of the motivational analysis of Wu Cheng-en’s novel “A Journey to the West” are presented, the mythological meanings of individual object-material images are studied, a set of ritual actions related to hair is considered: pulling out wool, casting a spell, turning around. The idea of a variety of ritual functions of hair, endowed with mystical properties in many mythological systems, is taken as a starting point; they are included in thanatal, carnival and other contexts. It has been proven that all rituals related to hair in the novel combine the archetypal meanings of being chosen, initiation, carnival buffoonery and spiritual formation. A typology of ritual functions of hair and associated miracles is proposed. The first of the selected types of metamorphosis is carried out through manipulations that Sun Wukong masters in training with the sages: this is the creation of a copy of an object or creature with the help of which the hero avoids danger. The second object of the typology is a gift from the Bodhisattva Guanyin, which requires a certain inner work from the hero — choice, bargaining, creating a new object without a ready-made sample. The question is raised about the divine leadership of the process of becoming a hero.
Unexpected Facets of Images of Officials by N. V. Gogol and V. F. Odoevsky
Authors: Sytina Yu. N.
Published: March 2021

The issues on the multifaceted images of officials in the Russian literature of the 1830- 1840s are considered. The results of a comparative analysis of the works of N. V. Gogol and V. F. Odoevsky are presented. Particular attention is paid to Poprishchin from the “Diary of a Madman” and the order Sevastyanich from “The Tale of a Dead Body Who Belongs to No One”. The author draws attention to the fact that the heroes go beyond the behavioral model, as if attributed to them by their social role. It is shown that poetry does not disappear from their existence; officials are capable of creativity and creation of their own works. The irreducibility of the images of officials is proved only to illustrate social reality, the striving for their individualization, drawing a rich inner world is emphasized. The novelty of the research is seen in the fact that unexpected facets of the images of officials in Gogol and Odoevsky are revealed in their relationship. The commonality of the writers’ worldviews and the similarity of their poetics are shown, which is manifested, in particular, in the fact that science fiction occupies an important place in the artistic world of works about officials.
Scenarios for Unison Text Unfolding in Russian Blogosphere
Authors: Kovtunenko I. V. , Bylkova S. V. , Kudryashov I. A. , Korman E. A.
Published: March 2021

The article is devoted to the analysis of scenarios as conceptual structures of a specific type that underlie the pragmatic connectivity of stimulating and reactive messages as part of a blog text in Russian and projecting unison in the current interaction. It has been proven that these scenarios are an essential parameter of the linguistic competence of representatives of virtual communities and are used by the initiator of communication and its respondents to reach agreement and find a common semantic denominator for initially conflicting points of view. The authors dwell on the fact that the implementation of scenarios in computer-mediated communication is predetermined both by the formal capabilities of the lexico-grammatical system of the Russian language (discourse markers) and by linguocultural conventions that the interlocutors adhere to at one stage or another of the joint deployment of the blog text. In this study, the architectonics of scenarios for the connectivity of stimuli and reactions in the composition of the blog text is interpreted as a consequence of the implementation of relay structures. It is emphasized that the initiator of cohesion is the respondent (including the blogger in the function of the respondent) in the course of constructing a responsive message. It is shown that the pragmatic structure of these scenarios includes a foothold in incentive communication and a bond that docks with this foothold in reactive communication.
Paradigmatics and Functioning of German Infinitive (Scientific and Journalistic Texts)
Authors: Bodnaruk E. V.
Published: March 2021

A complex characteristic of the structural and functional features of the infinitive in the texts of the German journalistic and scientific discourses is presented. The novelty of the research lies in the fact that it reveals the ratio of the infinitive forms presented in these discourses (infinitives I and II in the active and passive voice). The dependence of the use of forms on the semantics of the type of infinitive is considered. Particular attention is paid to the description of the syntactic functions in which the infinitive is used, to the identification of the most demanded of them. The correlation of syntactic functions with the temporal characteristics of the infinitive is determined. The relevance of the study is due to the use of a comparative discursive approach for the analysis of the infinitive. It is noted that the functioning of the infinitive in publicistic and scientific discourse reveals both similarities and differences. The author concludes that the differences in the use of the infinitive are due to the main differential features of journalistic and scientific texts, while the similarities indicate the common features that are characteristic of the German infinitive as a whole and distinguish it from other linguistic phenomena.
Analisis Key Opinion Leaders di Media Sosial dalam Membentuk Opini Khalayak
Authors: Jacksen Jacksen , Susanto Eko Harry , Pandrianto Nigar
Published: March 2021

Content is a new way of doing promotions that have various forms, such as videos and images. This research discusses the process of creating content created by a key opinion leader. The person who acts as the key opinions leader is the owner of his own business. The theories used in this study are advertising, social media, marketing content, key opinion leaders, two-stage communication, diffusion of innovation and opinion. The method used is case study with qualitative approach and using interview, observation, and documentation techniques. The results of this study can be known that the content created by a key opinion leader must be diverse in order to attract the attention of the audience. The diversity of content produced must have a clear purpose, so that later the message can be conveyed properly and the goal can be achieved. Content created by engaging business owners directly will increase credibility in the business. Therefore, it can be concluded that the creation of a content must be diverse, informative, educational. While content involving its own business owners will increase high credibility.Konten merupakan cara baru seseorang dalam melakukan promosi yang memiliki berbagai macam bentuk, seperti video dan gambar. Penelitian ini membahas tentang proses pembuatan konten yang diciptakan seorang key opinion leaders. Orang yang berperan sebagai key opinions leader adalah pemilik bisnisnya sendiri. Teori yang digunakan pada penelitian ini adalah periklanan, media sosial, marketing content, key opinion leaders, komunikasi dua tahap, difusi inovasi dan opini. Metode yang digunakan adalah studi kasus dengan pendekatan kualitatif dan menggunakan teknik wawancara, observasi, serta dokumentasi. Hasil penelitian ini dapat diketahui bahwa konten yang diciptakan oleh seorang key opinion leader harus lah beragam agar dapat menarik perhatian penontonnya. Keberagaman konten yang dihasilkan harus memiliki tujuan yang jelas, sehingga nantinya pesan dapat tersampaikan dengan baik dan tujuan dapat tercapai. Konten-konten yang diciptkana dengan melibatkan pemilik bisnisnya secara langsung akan meningkatkan kredibilitas pada bisnis yang dijalani. Untuk itu dapat disimpulkan bahwa pembuatan sebuah konten harus lah beragam, informatif, mengedukasi. Sedangkan konten yang melibatkan pemilik bisnisnya sendiri akan meningkatkan kredibilitas yang tinggi.
Resepsi Remaja terhadap Konten @BotakTikTok di Media Sosial TikTok
Authors: Kesuma Steven , Tamburian Daniel
Published: March 2021

TikTok is an application that gives users access to create short videos with their creations and creativity. In the TikTok application, there are lots of content creators who create content - content ranging from positive content to negative content. The author focuses more on @BotakTikTok creator content because this creator's content is unique, namely having 3 TikTok accounts. The purpose of this study is to describe the reception of adolescents to the content of @BotakTikTok on social media. The research method used in this research is a qualitative approach with phenomenological research. Phenomenological research is used by the author because it allows to find out and understand about the meaning of content in social media (TikTok). The results of the data were obtained through direct interviews with 3 sources, direct observation and literature study. Observation is used by the author by making direct observations so that the author can find out how the subject sees the object under study. The result of this research is that the meaning received by adolescents in positive content is denotative meaning and the meaning that is received by adolescents in negative content is the connotative meaning and the reception of adolescents is included in the hegemonic - dominant position.TikTok merupakan aplikasi yang memberikan akses kepada penggunanya untuk membuat video berdurasi pendek dengan kreasi dan kreativitas yang dimiliki. Dalam aplikasi TikTok terdapat banyak sekali konten kreator yang membuat konten mulai dari konten positif hingga konten negatif. Penulis lebih memfokuskan kepada konten kreator @BotakTikTok karena konten kreator ini memiliki keunikan yaitu memiliki tiga akun TikTok. Tujuan penelitian ini adalah untuk mendeskripsikan resepsi remaja terhadap konten @BotakTikTok dalam media sosial. Metode penelitian yang digunakan dalam penelitian ini adalah metode pendekatan kualitatif dengan penelitian fenomenologi. Penelitian fenomenologi digunakan oleh penulis karena memungkinkan untuk mencari tahu dan memahami mengenai pemaknaan konten dalam media sosial (TikTok). Hasil data diperoleh melalui wawancara langsung dengan tiga narasumber, observasi langsung serta studi kepustakaan. Observasi digunakan oleh penulis dengan cara melakukan pengamatan langsung agar penulis bisa mengetahui cara pandang subjek terhadap objek yang diteliti. Hasil dari penelitian ini adalah makna yang diterima remaja dalam konten positif merupakan makna denotatif dan makna yang diterima remaja dalam konten negatif merupakan makna konotatif serta resepsi remaja termasuk kedalam posisi hegemonik-dominan.