bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demand of Governmental Employees for Social Health Insurance and Associated Factors in Takusa woreda, Amhara National Regional State, Ethiopia
Authors: Getahun Tamyalew , Alemneh Mekuanint , Amare Getasew , Yitayal Mezegebu , Feleke Amsalu 
Published: January 2021

Abstract
Objective: The main aim of this study was to assess the demand of governmental employees for social health insurance and associated factors in Takusa district, Northwest Ethiopia.Methods: Institution-based cross-sectional triangulated with the phenomenological study was conducted. A simple random and a purposive sampling technique were used to recruit 324 employees. Binary logistic regression was performed, and P < 0.05 was considered statistically significant. In the qualitative study, data were analyzed using thematic analysis. Results: 61.1% of employees had a good demand for social health insurance. Employees who had 5-6 family sizes were 5.5 times more likely to have a demand for SHI than counterparts. Also, employees who live in a rural area were 3.3 times more likely to have SHI demand than urban residents. In the qualitative analysis, lack of awareness, fear of poor-quality health service provision, the unpreparedness of health institutions, lack of inputs, poverty etc. were the main constraints for the poor demand for SHI. Conclusion: In general, the higher demand for SHI in this study was more than half of the Ethiopians but less than abroad. Therefore, the concerned body shall intervene on the factors by implementing a SHI program cooperatively.
Interaction of Sirtuin 1 (SIRT1) candidate longevity gene and particulate matter (PM2.5) on all-cause mortality: a longitudinal cohort study in China
Authors: Yao Yao , Liu Linxin , Guo Guang , Zeng Yi , Ji John S. 
Published: January 2021

Abstract
Background The SIRT1 gene was associated with the lifespan in several organisms through inflammatory and oxidative stress pathways. Long-term air particulate matter (PM) is detrimental to health through the same pathways. Methods We used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) to investigate whether there is a gene-environment (G×E) interaction of SIRT1 and air pollution on mortality in an older cohort in China. Among 7,083 participants with a mean age of 81.1 years, we genotyped nine SIRT1 alleles for each participant and assessed PM2.5 concentration using 3-year average concentrations around each participant's residence. We used Cox-proportional hazards models to estimate the independent and joint effects of SIRT1 polymorphisms and PM2.5 exposure on all-cause mortality, adjusting for a set of confounders. Results There were 2,843 deaths over 42,852 person-years. The mortality hazard ratio (HR) and 95% confidence interval (CI) for each 10 μg/m³ increase in PM2·5 was 1.08 (1.05-1.11); for SIRT1_391 was 0.77 (0.61, 0.98) in the recessive model after adjustment. In stratified analyses, participants carrying two SIRT1_391 minor alleles had a significantly higher HR for each 10 μg/m³ increase in PM2.5 than those carrying zero minor alleles (1.323 (95% CI: 1.088, 1.610) vs. 1.062 (1.028, 1.096) p for interaction = 0.03). Moreover, the interaction of SIRT1 and air pollution on mortality is significant among women but not among men. We did not see significant relationships for SIRT1_366, SIRT1_773, and SIRT1_720. Conclusion We found a gene-environment interaction of SIRT1 and air pollution on mortality, future experimental studies are warranted to depict the mechanism observed in this study.
Baseline Global Longitudinal Strain Predictive of Anthracycline-Induced Cardiotoxicity
Authors: Araujo-Gutierrez Raquel , Chitturi Kalyan R. , Xu Jiaqiong , Wang Yuanchen , Kinder Elizabeth , Senapati Alpana , Chebrolu L Bindu , Kassi Mahwash , Trachtenberg Barry H. 
Published: January 2021

Abstract
Background: Cancer therapy-related cardiac dysfunction (CTRD) is a major source of morbidity and mortality in long-term cancer survivors. Decreased GLS predicts decreased left ventricular ejection fraction (LVEF) in patients receiving anthracyclines, but knowledge regarding the clinical utility of baseline GLS in patients at low-risk of (CTRD) is limited.Objectives: The purpose of this study was to investigate whether baseline echocardiographic assessment of global longitudinal strain (GLS) before treatment with anthracyclines is predictive of (CTRD) in a broad cohort of patients with normal baseline LVEF.Methods: Study participants comprised 188 patients at a single institution who underwent baseline 2-dimensional (2D) speckle-tracking echocardiography before treatment with anthracyclines and at least one follow-up echocardiogram 3 months after chemotherapy initiation. Patients with a baseline LVEF <55% were excluded from the analysis. The primary endpoint, (CTRD), was defined as an absolute decline in LVEF >10% from baseline and an overall reduced LVEF <50%. Potential and known risk factors were evaluated using univariable and multivariable Cox proportional hazards regression analysis.Results: Twenty-three patients (12.23%) developed (CTRD). Among patients with (CTRD), the mean GLS was -17.51% ± 2.77%. The optimal cutoff point for (CTRD) was -18.05%. The sensitivity was 0.70 and specificity was 0.70. The area under ROC curve was 0.70. After adjustment for cardiovascular and cancer therapy related risk factors, GLS or decreased baseline GLS ≥-18% was predictive of (CTRD) (adjusted hazards ratio 1.17, 95% confidence interval 1.00, 1.36; p=0.044 for GLS, or hazards ratio 3.54; 95% confidence interval 1.34, 9.35; p = 0.011 for decreased GLS), along with history of tobacco use, pre-chemotherapy systolic blood pressure, and cumulative anthracycline dose.Conclusions: Baseline GLS or decreased baseline GLS was predictive of (CTRD) before anthracycline treatment in a cohort of cancer patients with a normal baseline LVEF. This data supports the implementation of strain-protocol echocardiography in cardio-oncology practice for identifying and monitoring patients who are at elevated risk of (CTRD)
Mišrusis jungtinis Selbergo klasės L funkcijų ir periodinių Hurvico dzeta funkcijų universalumas
Authors: Jasas Mindaugas , Macaitienė Renata 
Published: January 2021

2007 m. H. Mišu (Mishou) pirmasis įrodė mišriojo universalumo teoremą Rymano ir Hurvico dzeta funkcijoms. Plačiąja prasme mišrusis universalumas suprantamas kaip jungtinis funkcijų, turinčių ir neturinčių Oilerio sandaugos pagal pirminius skaičius, universalumas.Straipsnyje tęsiamas universalumo klausimo dzeta ir L funkcijų rinkiniams nagrinėjimas. Tiksliau, įrodoma Selbergo klasės funkcijų (užrašomų Dirichlė eilute ir tenkinančių tam tikras specifines sąlygas (tarp kurių ir Oilerio sandaugos egzistavimas)) ir periodinių Hurvico dzeta funkcijų (kurios neturi Oilerio sandaugos pagal pirminius skaičius) mišraus universalumo savybė. Mišraus universalumo rezultatas gali būti panaudotas nagrinėtų funkcijų funkcinio nepriklausomumo savybės įrodymui.Straipsnis parengtas M. Jaso magistro darbo pagrindu [4].
The Computational Intervention of Macrolide Antibiotics in the Treatment of COVID-19
Authors: Anwar Firoz , Altayb Hisham N. , Al-Abbasi Fahad A. , Kumar Vikas , Kamal Mohammad A. 
Published: January 2021

Background:
The spike (S) glycoprotein of SARS corona virus (SARS-CoV-2) and human Angiotensin-
converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection.
The present work is an effort for computational target to block the spike proteins (S) and ACE2 receptor proteins
with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY)
along with RNA-dependent RNA polymerase (RdRp).

Methods:
Three-dimensional structure of the SARS-CoV-2RdRp was built by the SWISS-MODEL server, the
generated structure showed 96.35% identity to the available structure of SARS-Coronavirus NSP12 (6NUR),
for model validity, we utilized the SWISS-model server quality parameters and Ramachandran plots.

Results:
These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep
grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site.
Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value
exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp
inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor.
At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to
block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2
but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three
Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by
ERY plays an important role for RdRp inactivation, that can prevent the rise of newly budded progeny virus.
These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and
catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues
(Tyr343, and His235) of Endoribonuclease (NSP15) protein.

Conclusion:
The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins
or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of
COVID-19 till some better option available.
Exosomal hsa-miR-129-2 and hsa-miR-889 from a 6-microRNA Signature
Might be a Potential Biomarker for Predicting the Prognosis of Papillary
Thyroid Carcinoma
Authors: Yu Kun , Xin Ying , Meng Kexin , Guo Haiwei , Chen Bin , Zheng Chuanming , Shou Xin 
Published: January 2021

Background:
Papillary thyroid carcinoma (PTC) is a subtype of thyroid cancer with increasing incidence over time.

Objective:
This study aimed to build a risk score (RS) system for PTC patients.

Methods:
PTC microRNA (miRNA) and messenger RNA (mRNA) expression data were extracted from The Cancer Genome Atlas (TCGA) database. The 491 PTC samples were randomly divided into training and validation sets. Using the limma software package, differentially expressed mRNAs (DEGs) and miRNAs (DEMs) between the tumor and control groups were screened. In order to construct an RS system, a survival package was used to select independent miRNAs related to prognosis. Enrichment analysis was performed, and a miRNA-mRNA co-expression network was constructed. High-throughput sequencing was also used to verify the prognostic miRNAs in exosomes.

Results:
We found 1363 DEGs and 171 DEMs between the tumor and control groups. After identifying 26 DEMs that were significantly related to prognosis, 6 independent prognosis-associated miRNAs were selected to build an RS system. The areas under the curves of the overall survival rates of the training, validation, and entire sets were 0.847, 0.772, and 0.819, respectively. By conducting pathway analysis using the miRNA-mRNA co-expression network, one overlapping factor and five overlapping pathways were obtained. In addition, high-throughput sequencing revealed that the hsa-miR-129-2, hsa-miR-548j, hsa-miR-6734, and hsa-miR-889 expression levels in TCGA tumor tissues and exosomes were consistent, and those of hsa-miR-129-2 and hsa-miR-889 between patients and controls were significantly different in exosomes.

Conclusion:
The six-miRNA RS system in exosomes may comprise independent signatures for predicting PTC patient prognosis.
Recent Advances in the Discovery of GSK-3 Inhibitors from Synthetic Origin in the Treatment of Neurological Disorders
Authors: Saha Supriyo , Pal Dilipkumar , Nimse Satish B. 
Published: January 2021

Background:
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase enzyme
that controls neuronal functions such as neurite outgrowth, synapse formation, neurotransmission,
and neurogenesis. The enzyme has two subunits as GSK-3α and GSK-3β. 4ACC, 1Q3D, 3AFG,
1UV5, and 1Q5K are the important GSK-3 receptors isolated from Homo sapiens and Mus musculus.
This enzyme mainly phosphorylates Tau protein with the increased amount in neuronal fibres
together with beta-amyloid plaques that cause neuronal diseases like Alzheimer's, Parkinson’s and
many more.

Objective:
We investigated the developments of various synthetic GSK-3 inhibitors responsible for
the prevention and treatment of neurological disorders, like Alzheimer's disease, bipolar disorders,
acting as antidepressants, neuroprotective, etc.

Results and Conclusion:
It has been observed that structures of the GSK-3 inhibitors are comprised
of benzopyridine, benzothiazole, pyrazole, pyrazine, dioxolo-benzoxazine, oxadiazole, and
benzimidazole in the skeletal with cyclopropyl amide, phenyl carbamothioate, 3-[(propan-
2-yl)oxy]propan-1-amine in the side chain. The molecules were evaluated against the effectivity
of GSK-3, human adenosine kinase, cyclin-dependent kinase, and phosphodiesterase-4 along
with tail suspension test forced swim test, percent neuronal survival and other cognitive behaviours.
The observations confirmed the remarkable effects of the synthesized molecules to conquer
Alzheimer, Parkinson’s depression, psychosis and other forms of neurological disorders.
Radioprotectors: Nature’s Boon
Authors: Lang Damanpreet Kaur , Singh Harwinder , Arora Arpita , Arora Rashmi , Saini Balraj , Arora Sandeep , Kaur Rajwinder 
Published: January 2021

Objective:
To reduce the chances of toxicity, reduction in radiation dose or reducing the frequency of the therapy is done
which usually leads to a therapeutically poor outcome. The most feasible method is to protect the normal cells by
administration of radioprotective agents either before or after the exposure. These agents have been tested on animals and
human cellmodels for evaluating theirsafety window and toxicityprofile at the cellular level. The study aims to compile the
effective natural radioprotective agents available which can be further exploited by using certain QSAR studies to increase
their potency.

Method:
Structured literature search from EMBASE, PubMed, Bentham Science, Scopus, and ScienceDirect was done and
appropriate peer-reviewed review articles, as well as certain research articles, were included and compiled in this review
paper.

Conclusion:
As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these
effects radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are
proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile
oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for
their radioprotective action and compiled in the present study.

Conclusion:
As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these
effects radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are
proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile
oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for
their radioprotective action and compiled in the present study.
Efficacy of Gene Therapy to Restore Cognition in Alzheimer’s Disease: A Systematic Review
Authors: Tedeschi Desyrre V. , da Cunha Anderson F , Cominetti Márcia R. , Pedroso Renata Valle 
Published: January 2021

Background:Alzheimer's disease (AD) is the main cause of dementia and it is a progressive neurogenerative disease characterized by the accumulation of neurofibrillary tangles and senile plaques. There is currently no cure; however, some treatments are available to slow down the progression of the disease, including gene therapy, which has been investigated to have great potential for the treatment of AD.Objective:The aim of this review was to identify the efficacy of gene therapy to restore cognition in AD.Methods:A systematic review was carried out using papers published up to May 2020 and available in the Web of Science, Scopus, and Medline/PUBMED databases. Articles were considered for inclusion if they were original researches that investigated the effects of gene therapy on cognition in AD. The methodological quality of the selected studies was evaluated using the Risk of Bias Tool for Animal Intervention Studies (SYRCLE’s Rob tool) and the Jadad Scale.Results:Most preclinical studies obtained positive results in improving memory and learning in mice that underwent treatment with gene therapy. On the other hand, clinical studies have obtained inconclusive results related to the delivery methods of the viral vector used in gene therapy.Conclusion:Gene therapy has shown a great potential for the treatment of AD in preclinical trials, but results should be interpreted with caution since preclinical studies presented limitations to predict the efficacy of the treatment outcome in humans.
Extracellular Vesicles from Stem and Progenitor Cells for Cell-Free
Regenerative Therapy
Authors: Haque Nazmul , Widera Darius , Govindasamy Vijayendran , Soesilawati Pratiwi , Abu Kasim Noor Hayaty 
Published: January 2021

:
Cell-based regenerative therapies involving stem or progenitor cells are considered as possible therapeutic
modalities to treat non-communicable and degenerative diseases. Recently, regenerative outcomes of cell-based therapies
have been linked to paracrine factors and extracellular vesicles [EVs] released by the transplanted cells rather than the
transplanted cells themselves. EVs contain a cargo that includes microRNAs [miRNAs], mRNAs, as well as proteins. Their
role in mediating intercellular communication has been acknowledged in several studies. However, the regenerative
potential of the miRNAs, mRNAs, and proteins that are present in EVs is a matter of ongoing scientific debate. In this
review, we discuss EVs as an alternative to stem cell-based therapy to treat some of the non-communicable and
degenerative diseases. Moreover, we also propose that pre-treatment of the cells could help to produce EVs enriched with
particular miRNAs, mRNAs, and/or proteins that could support the successful regeneration of a targeted organ.
Preparation of Enzymatically Highly Active Pegylated-D-Amino Acid Oxidase and Its Application to Antitumor Therapy
Authors: Nakamura Hideaki , Enoch Appiah , Iwaya Shotaro , Furusho Sakura , Tsunoda Shoko , Haratake Mamoru 
Published: January 2021

Background:
D-amino acid oxidase (DAO) is an H2O2-generating enzyme, and tumor growth suppression by
selective delivery of porcine DAO in tumors via the cytotoxic action of H2O2 has been reported. DAO isolated from
Fusarium spp. (fDAO) shows much higher enzyme activity than porcine DAO, although the application of fDAO for
antitumor treatment has not yet been determined.

Objective:
The purpose of this study was to prepare enzymatically highly active pegylated-fDAO, and to determine whether
it accumulates in tumors and exerts a potent antitumor effect in tumor-bearing mice.

Methods:
Polyethylene glycol (PEG; Mw. 2000) was conjugated to fDAO to form PEGylated fDAO (PEG-fDAO). PEGfDAO was intravenously administered into S180 tumor-bearing mice, and the body distribution and antitumor activity of
PEG-fDAO was determined.

Results:
The enzyme activity of PEG-fDAO was 26.1 U/mg, which was comparable to that of
fDAO. Intravenously administered PEG-fDAO accumulated in tumors with less distribution in normal
tissue except in the plasma. Enzyme activity in the tumor was 60-120 mU/g-tissue over 7-20 h
after i.v. injection of 0.1 mg of PEG-fDAO. To generate the H2O2 in the tumor tissue, PEG-fDAO
was intravenously administered, and then, D-phenylalanine was intraperitoneally administered after
a lag time. No remarkable tumor suppression effect was observed under conditions used in this
study, compared to the non-treated group.

Conclusion:
The results suggest that PEG-fDAO maintained high enzymatic activity after pegylation. Treatment with PEGfDAO conferred high enzyme activity on tumor tissue; 3–6 fold higher than that of previously reported pDAO; however,
high enzyme activity in the plasma limited repeated treatment owing to lethal toxicity, which seemingly led to poor
therapeutic outcome. Overall, the use of PEG-fDAO is promising for antitumor therapy, although the suppression of DAO
activity in the plasma would also be required rather than only the increase in DAO activity in the tumor for an antitumor
effect.
The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Authors: Ganbat Dariimaa , Jugder Bat-Erdene , Ganbat Lkhamaa , Tomoeda Miki , Dungubat Erdenetsogt , Takahashi Yoshihisa , Mori Ichiro , Shiomi Takayuki , Tomita Yasuhiko 
Published: January 2021

Background:
Redox dysregulation originating from metabolic alterations in cancer cells
contributes to their proliferation, invasion, and resistance to therapy. Conversely, these features represent
a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics.
Amongst them, Vitamin K (VitK) carries the potential against cancer stem cells, in
addition to the rest of tumor mass.

Objectives:
To assess the possible benefits and safety of VitK for cancer treatment using a systematic
review and meta-analysis with a mixed-methods approach.

Methods:
We performed a systematic search on several electronic databases for studies comparing
VitK treatment with and without combination to the control groups. For quantitative studies, fully
or partially reported clinical outcomes such as recurrence rates, survival, overall response and adverse
reactions were assessed. For qualitative studies, a narrative synthesis was accomplished.

Results:
Our analysis suggested that the clinical outcome of efficacy, the pooled hazard ratio for
progression-free survival, and the pooled relative risk for overall survival, and overall response
were significantly higher in the VitK therapy group compared to the placebo group (p<0.05). We
did not observe any significant difference in the occurrence of adverse events between groups.
Among qualitative studies, VitK treatment targeting myelodysplastic syndrome and advanced solid
tumors resulted in 24.1% and 10% of clinical response, respectively.

Conclusion:
VitK not only exerts antitumor effects against a wide range of tumor types, but it also
has excellent synergism with other therapeutic agents.
Piroxicam Analogs: Design, Synthesis, Docking Study and Biological Evaluation as Promising Anti-HIV-1 Agents
Authors: Imani Ali , Soleymani Sepehr , Vahabpour Rouhollah , Hajimahdi Zahra , Zarghi Afshin 
Published: January 2021

Background:Taking the well-known drug, Piroxicam as a lead compound, we designed and synthesized two series of 1,2-benzothiazines 1,1-dioxide derivatives to assay their ability in inhibition of HIV-1 replication in cell culture.Objective:In this study, we describe the synthesis, docking study and biological evaluation of 1,2-benzothiazines 1,1- dioxide derivatives.Results:Most of the new compounds were active in the cell-based anti-HIV-1 assay with EC50 < 50 M. Among them, compounds 7g was found to be the most active molecule. Docking study using 3OYA pdb code on the most active molecule 7g with EC50 values of 10 M showed a similar binding mode to the HIV integrase inhibitors.Conclusion:Since all the compounds showed no remarkable cytotoxicity (CC50> 500 M), the designed scaffold is promising structure for development of new anti-HIV-1 agents.