bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key Mutant Genes and Biological Pathways Involved in Aspirin Resistance
in the Residents of the Chinese Plateau Area
Authors: Wu Jinchun , Chang Rong , Liu Yanmin 
Published: April 2023

Introduction:
Aspirin is used to prevent and treat cardiovascular diseases; however,
some patients develop aspirin resistance.

Aim:
We aimed to explore the potential molecular mechanisms underlying aspirin resistance in
people living in the Chinese plateau area.

Methods:
In total, 91 participants receiving aspirin treatment from the Qinghai plateau area were
divided into the aspirin resistance and aspirin sensitivity groups. Genotyping was performed using
the Sequence MASSarray. Differentially mutated genes between the two groups were analyzed using
MAfTools. The annotation of differentially mutated genes was conducted based on the
Metascape database.

Results and Discussion:
In total, 48 differential SNP and 22 differential InDel mutant genes between
the aspirin resistance and aspirin sensitivity groups were screened using Fisher’s exact test
(P < 0.05). After the χ2 test, a total of 21 SNP mutant genes, including ZFPL1 and TLR3, and 19
InDel mutant genes were found to be differentially expressed between the two groups (P < 0.05).
Functional analysis revealed that these differential SNP mutations were mainly enriched in aspirin
resistance pathways, such as the Wnt signaling pathway. Furthermore, these genes were related to
many diseases, including various aspirin indications.

Conclusion:
This study identified several genes and pathways that could be involved in arachidonic
acid metabolic processes and aspirin resistance progression, which will provide a theoretical
understanding of the molecular mechanism of aspirin resistance.
Study on the Mechanism of Estrogen Regulating Endometrial
Fibrosis After Mechanical Injury Via MIR-21-5P/PPARΑ/FAO Axis
Authors: Ding Shuning , Hu Yunyun , Mao Peiyu , Lin Qiu , Yao Zhitao 
Published: April 2023

Background:
Intrauterine adhesion (IUA) caused by endometrial mechanical
injury has been found as a substantial risk factor for female infertility (e.g., induced
abortion). Estrogen is a classic drug for the repair of endometrial injury, but its action
mechanism in the clinical application of endometrial fibrosis is still unclear.

Objective:
To explore the specific action mechanism of estrogen treatment on IUA.

Methods:
The IUA model in vivo and the isolated endometrial stromal cells (ESCs)
model in vitro were built. Then CCK8 assay, Real-Time PCR, Western Blot and Dual-
Luciferase Reporter Gene assay were applied to determine the targeting action of
estrogen on ESCs.

Results:
It was found that 17β-estradiol inhibited fibrosis of ESCs by down-regulating
miR-21-5p level and activating PPARα signaling. Mechanistically, miR-21-5p
significantly reduced the inhibitory effect of 17β-estradiol on fibrotic ESCs (ESCs-F) and
its maker protein (e.g., α-SMA, collagen I, and fibronectin), where targeting to PPARα 3’-
UTR and blocked its activation and transcription, thus lowering expressions of fatty acid
oxidation (FAO) associated key enzyme, provoking fatty accumulation and reactive
oxygen species (ROS) production, resulting in endometrial fibrosis. Nevertheless, the
PPARα agonist caffeic acid counteracted the facilitation action of miR-21-5p on ESCs-F,
which is consistent with the efficacy of estrogen intervention.

Conclusion:
In brief, the above findings revealed that the miR-21-5p/PPARα signal axis
played an important role in the fibrosis of endometrial mechanical injury and suggested
that estrogen might be a promising agent for its progression.
IL1R2 is a Novel Prognostic Biomarker for Lung Adenocarcinoma
Authors: Zhang Ying , Ma Danyu , Gong Yile , Wang Fan , Wu Jingping , Wu Chen 
Published: April 2023

Aims:
The aim of this study is to figure out the role of IL1R2 in LUAD (lung
adenocarcinoma).

Background:
IL1R2, a special member of IL-1 receptor family, binds to IL-1 and plays
an important role in inhibiting IL-1 pathway, which seems to be involved in
tumorigenesis. Emerging studies demonstrated higher IL1R2 expression levels in
several malignancies.

Objective:
In the present study, we assessed the expression of IL1R2 in LUAD tissues
with immunohistochemistry and explored various databases to determine whether it
could be a potential prognostic biomarker and therapeutic target.

Methods:
The expression level of IL1R2 in lung adenocarcinoma was analyzed by
Immunohistochemistry and UALCAN database. The correlation between IL1R2
expression and the patient prognosis was identified by Kaplan-Meier plotter. The
correlation of IL1R2 expression with immune infiltrates was clarified by TIMER database.
The protein-protein interaction network and gene functional enrichment analysis were
constructed and performed by STRING and Metascape database.

Results:
Immunohistochemistry showed that the expression of IL1R2 was higher in
tumor tissues of LUAD patients and that patients with lower IL1R2 level have a better
prognosis than their counterparts. We validated our findings in several online databases
and found that IL1R2 gene was also positively correlated with B cells and neutrophils
and biomarkers of CD8+T cells and exhausted T cells. PPI network and gene enrichment
analyses showed that expression of IL1R2 was also associated with complex functionspecific
networks involving IL-1 signal, NF-KappaB transcription factors.

Conclusion:
According to these findings, we demonstrated that IL1R2 was involved in
the progression and prognosis of LUAD and the underlying mechanism needs further
investigation.
Adenovirus 36 Coinfection in People Living with HIV and its Impact on
Lipohypertrophy
Authors: Schuelter-Trevisol Fabiana Armando , Gonçalves e Silva Helena Caetano , da Silva Jaime Fernandes , Cancelier Ana Carolina Lobor , Trevisol Daisson José , Sakae Thiago Armando Mamôru , Atkinson Richard L. 
Published: April 2023

Background:
Previous studies have implicated human adenovirus 36 (Adv36) as a potential
contributor to overweight and obesity. People living with HIV have an altered body composition
compared to healthy individuals. There is still no evidence to confirm the relationship of Adv36
as one of the causes of lipohypertrophy. The main objective of this study was to verify the viral
Adv36 infection as a factor associated with the presence of lipohypertrophy in HIV-infected individuals.

Methods:
A case-control study on people with HIV treated at a specialized public health service in
southern Brazil. Subjects underwent interviews, diagnostic tests, and anthropometry to determine
lipodystrophy and its classification. Demographic and clinical data were examined to investigate
the presence of Adv36. The cases were participants with lipohypertrophy, and the controls were
eutrophic participants.

Results:
101 participants were included (38 cases and 63 controls), and the frequency of Adv36
infection was 10.9%. There was a statistically significant association between lipohypertrophy and
the female sex (p < 0.001), and a trend for the presence of Adv36 (p = 0.059) and lipohypertrophy.
After adjustment for confounders, Adv36 has not considered an independent risk factor for lipohypertrophy.
Lower levels of glucose were associated with Adv36 infection.

Conclusion:
There was a significant association between lipohypertrophy and the female sex, and
no association with lipohypertrophy and Adv36, perhaps due to the small sample size.
Perceptions and Experiences of Midwives During the COVID-19 Pandemic
in Iran: A Qualitative Exploration
Authors: Manouchehri Elham , Alirezaei Somayeh , Roudsari Robab Latifnejad 
Published: April 2023

Background:
The COVID-19 pandemic affected both the maternity care and services provided by healthcare providers. Midwives are among the health professionals who are fighting on the
frontlines of the COVID-19 pandemic.

Objective:
This study aimed to explore Iranian midwives' perceptions and experiences of the COVID19 pandemic.

Methods:
This qualitative description was carried out between March and May 2020 in Mashhad,
Northeast Iran. Through purposive sampling, 15 midwives were selected from Corona Centers. Semistructured face-to-face interviews were used for data collection. Graneheim & Lundman's conventional content analysis approach was used to analyze the data. The data organization was performed using
MAXQDA 12 software. Guba and Lincoln's elements of rigor, including credibility, dependability,
confirmability, and transferability were considered

Results:
Four overarching categories emerged based on the analysis of midwives' perceptions and experiences including "Facing challenges in confrontation with pregnant women", "Inefficiency of crisis
management", "providing solutions and strategies to improve the current situation ", and "being affected by the pandemic in all aspects of life".

Conclusion:
Midwives faced different challenges since all aspects of pregnancy and childbirth care
were influenced by the COVID-19 outbreak. Like other medical staff, midwives were on the frontline
of health care during the COVID-19 pandemic, and it made problems for their personal feelings and
professional responsibilities. Comprehensive support, promoting working status, and motivating midwives are vital in maintaining high-quality midwifery care.
A Case Report of Cefixime, Paracetamol, and Nimesulide Induced Toxic
Epidermal Necrolysis in a Woman with Dengue Infection without any
Other Associated Comorbidities
Authors: Munshi Renuka , Maurya Miteshkumar 
Published: April 2023

Background:
Toxic Epidermal Necrolysis (TEN) is a rare, acute, and life-threatening
mucocutaneous disease that occurs after the administration of certain drugs, resulting in extensive
keratinocyte cell death, skin involvement at the dermal-epidermal junction, and extensive bullous
skin eruptions and sloughing. Many published case reports have observed the presence of fever
with a viral infection, drug, and/or genetic association as a possible trigger for TEN but associated
with other comorbidities. Physicians still struggle to predict which individuals could be predisposed
to TEN. The case report that we present had a history of multiple drug intake and fever due
to dengue virus infection but was not associated with any other comorbidity.

Case Presentation:
We present an unusual case of a 32-year-old woman of Western Indian origin
who had developed dengue infection and suffered toxic epidermal necrolysis following a five-day
course of a third-generation cephalosporin antibiotic, cefixime and a three-day course of 2 analgesic
drugs, paracetamol (acetaminophen), and nimesulide, with the adverse event occurring on the
fifth day of the dengue infection. The offending drugs were stopped, and patient survived with
supportive management and hydration.

Conclusion:
The presence of comorbidities may not always be the triggering factor for TEN,
though it can affect patient outcomes. Rational drug use is always recommended for patient care.
Further research is required to understand the pathomechanism behind the viral-drug-gene interaction.
Differential Expression of microRNAs and Target Genes Analysis in Olfactory
Ensheathing Cell-derived Extracellular Vesicles Versus Olfactory
Ensheathing Cells
Authors: Yang Yubing , Li Jiaxi , Liu Weidong , Guo Dong , Gao Zhengchao , Zhao Yingjie , Zhao Minchao , He Xijing , Chang Su’e 
Published: April 2023

Introduction:
Olfactory ensheathing cells (OECs) are important transplantable cells for the
treatment of spinal cord injury. However, information on the mechanism of OEC-derived extracellular
vesicles (EVs) in nerve repair is scarce.

Methods:
We cultured OECs and extracted the OEC-derived EVs, which were identified using a transmission
electron microscope, nanoparticle flow cytometry, and western blotting. High throughput RNA
sequencing of OECs and OEC-EVs was performed, and the differentially expressed microRNAs (miRNAs)
(DERs) were analyzed by bioinformatics. The target genes of DERs were identified using miRWalk,
miRDB, miRTarBase, and TargetScan databases. Gene ontology and KEGG mapper tools were
used to analyze the predicted target genes. Subsequently, the STRING database and Cytoscape software
platform were used to analyze and construct miRNA target genes' protein-protein interaction (PPI) network.

Results:
Overall, 206 miRNAs (105 upregulated and 101 downregulated) were differentially expressed in
OEC-EVs (p < 0.05;|log2 (fold change)|>2). Six DERs (rno-miR-7a-5p, rno-miR-143-3p, rno-miR-182,
rno-miR-214-3p, rno-miR-434-5p, rno-miR-543-3p) were significantly up-regulated , and a total of 974
miRNAs target genes were obtained. The target genes were mainly involved in biological processes such
as regulation of cell size, positive regulation of cellular catabolic process and small GTPase-mediated
signal transduction; positive regulation of genes involved in cellular components such as growth cone,
site of polarized growth, and distal axon; and molecular functions such as small GTPase binding and Ras
GTPase binding. In pathway analysis, target genes regulated by six DERs were mainly enriched in axon
guidance, endocytosis, and Ras and cGMP-dependent protein kinase G signaling pathways. Finally, 19
hub genes were identified via the PPI network.

Conclusion:
Our study provides a theoretical basis for treating nerve repair by OEC-derived EVs.
Diosgenin Glucoside Inhibits the Progression of Osteosarcoma MG-63 by Regulating
the PI3K/AKT/mTOR Pathway
Authors: Ruan Siyuan , Gu Liuwei , Wang Yuqi , Huang Xincheng , Cao Hong 
Published: April 2023

Background:
Trillium tschonoskii Maxim (TTM) exerts antitumor effects on a variety of tumour cells.
However, the antitumor mechanism of Diosgenin glucoside (DG) extracted from TTM is not clear.

Objective:
This study aimed to investigate the anti-tumour effects of DG-induced osteosarcoma MG-63 cells and their
molecular mechanism.

Methods:
CCK-8 assay, HE staining, and flow cytometry were used to detect the effects of DG on the proliferation,
apoptosis, and cell cycle of osteosarcoma cells. Wound healing and Transwell invasion assays were used to observe the
effect of DG on the migration and invasion of osteosarcoma cells. The anti-tumour mechanism of DG on osteosarcoma
cells was investigated by immunohistochemistry, Western blot, and RT-PCR.

Results:
DG significantly inhibited osteosarcoma cell activity and proliferation, promoted apoptosis and blocked the
G2 phase of the cell cycle. Both wound healing and Transwell invasion assays showed that DG inhibited osteosarcoma
cell migration and invasion. Immunohistochemical and western blot results showed that DG inhibited the activation of
PI3K/AKT/mTOR. We found that DG also significantly downregulated the expression of S6K1 and eIF4F, which
might be associated with the inhibition of protein synthesis.

Conclusion:
DG may inhibit proliferation, migration, invasion, and cell cycle G2 phase arrest of osteosarcoma MG-63
cells and promote apoptosis through the PI3K/AKT/mTOR signalling pathway.
A Case of New-onset Autoimmune Type-1 Diabetes Mellitus Following
COVID-19 Infection
Authors: Taşkaldıran Işılay , Nar Aslı 
Published: April 2023

Background:
After COVID-19 infection, various mechanisms may initiate an increased risk
of developing DM. This study presented a newly developed autoimmune Type 1 DM (T1DM) case in
an adult patient after a SARS-CoV-2 infection.

Case Presentation:
A 48-year-old male patient presented with complaints of weight loss and blurred
vision. His blood sugar and HbA1c were measured as 557 mg/dl and 12.6%, respectively. His medical
records showed no known diagnosis of DM. He had a SARS-CoV-2 infection 4 weeks ago. Then, we
diagnosed DM and started basal-bolus insulin therapy. C-peptides and autoantibodies were requested
from the patient to explore the etiology of diabetes. Glutamic acid decarboxylase (GAD) antibody was >
2000 U/mL (ref: 0-10); therefore, the patient was accepted as having autoimmune T1DM. New-onset
DM cases triggered by COVID-19 have increasingly been reported recently. SARS-CoV-2 virus, using
the ACE2 receptor in the pancreas, can enter beta cells and causes damage to these islets and impaired
insulin secretion, leading to acute diabetes mellitus. In addition, the abnormal immunity elicited by
SARS-CoV-2 can also induce autoimmune destruction of pancreatic islet cells.

Conclusion:
T1DM may be an uncommon but possible complication due to the COVID-19 virus
among genetically predisposed individuals. Overall, the case highlights the importance of preventive
measures, such as vaccination, to protect against COVID-19 and its complications.
Effect of Mixture of Water Hyacinth Compost and Rice Husk Biochar on the Improvement of Alluvial Soil Properties and the Growth of Red Ginger (Zingiber Officinale L.)
Authors: Masulili Agusalim , Paiman Paiman 
Published: April 2023

Background:
Alluvial is the potential soil for agricultural development. However, this soil can inhibit plant growth. One of the ways to improve the physical properties of this soil is through the application of soil amendments.

Objective:
This study aimed to determine the optimum dose of a mixture of water hyacinth compost and rice husk biochar for improving alluvial soil properties and the growth of red ginger.

Methods:
This study was arranged in a completely randomized design (CRD) with four replications. The treatment consisted of a mixture of water hyacinth compost and rice husk biochar (volume ratio of 2:1), which consisted of six doses: 0, 40, 60, 80, 100, and 120 g polybag-1. Then, each replication consisted of three samples. As many as 72 polybags were needed in this study. The observed physical properties of the soil were the bulk density (BD) and the soil pore space. The plant growth parameters included plant height, leaf numbers, tiller numbers, and fresh weight.

Results:
The results showed that applying a mixture of water hyacinth compost and rice husk biochar at a dose of 120 g polybag-1 caused the lowest BD and the most pore space in the soil. However, a dose of 80 g polybag-1 can provide maximum plant height, leaf numbers, tiller numbers, and fresh weight.

Conclusion:
The study findings show that mixing water hyacinth compost and rice husk biochar at 80 g polybag-1 is the optimum dose to support the maximum red ginger growth. However, we recommend that future research is needed to investigate the causes of decreasing BD and increasing soil pores.
Determinants of High Marital Fertility in Malawi: Evidence from 2010 and 2015–16 Malawi Demographic and Health Surveys
Authors: Palamuleni Martin E 
Published: April 2023

Background:
Although the Total Fertility Rate (TFR) has declined from 5.7 in 2010 to 4.6 during 2015-16, fertility in Malawi remains high. The high fertility is responsible for the rapid population growth, which negatively impacts the social and economic development of the country. Available data show that nearly 90% of all births in the country occur among married women.

Objective:
The main objective of the study is to investigate the determinants of fertility among married women (marital fertility) in Malawi.

Method:
This study used data extracted from the 2010 and 2015–16 Malawi demographic and health surveys. Bivariate and multivariate analyses were performed to examine the factors associated with fertility among married women.

Results:
The mean number of children born declined from 3.80 in 2010 to 3.44 in 2015. The background characteristics of the women were found to be accounted for the variation. Poisson regression analysis revealed that the age of respondent, place of residence, contraceptive use, age at first sex, age at marriage, age at birth, marriage duration, wanted last birth, ideal number of children, death of child and education were all factors significantly related to fertility.

Conclusion:
These significant factors should be the focus of programs that aim to further reduce fertility in Malawi.
Molecular Docking, Microwave-Assisted Synthesis, Characterization and
Pharmacological Evaluation of 2,4,5-trisubstituted Imidazole’s
Authors: Goel Tanvi , Bansode Deepali , Abdu Raihan Arikkattel , Dev Sanal 
Published: April 2023

Introduction:
Nitrogen containing heterocycles such as azoles have gained popularity in me-dicinal chemistry research due to their versatile pharmacological activities. Imidazole’s are one such class of adaptable compounds. The aim of the study was to explore pharmacological activities of 2,4,5-trisubstituted imidazole’s and also to develop a novel method of synthesis using microwave chemistry.

Methods:
In the present study, the in-silico studies of 2,4,5-trisubstituted imidazole’s was carried out to predict their anti-leishmanial as well as COX-2 inhibitory activity. Although, the results are not satisfacto-ry for the anti-leishmanial activity, the molecules showed comparable docking scores with standard celecoxib for the COX-2 inhibitory activity. Later, the microwave-assisted green synthesis of tri-substituted imidazole’s was attempted using green catalyst and solvent, molecular iodine and ethanol respectively. The synthesised derivatives (TG-1-4) were purified and characterised.

Results:
The derivatives were subjected to in-vitro COX-2 inhibitory assay, which showed good results. The molecules under study showed exemplary results against COX-2 PDB in molecular docking studies. A novel microwave-irradiation method was developed for the synthesis and also the in-vivo studies car-ried out for testing COX-2 inhibition was fruitful.

Conclusion:
In conclusion, the selected derivatives can be further studied in-vivo to develop new COX-2 inhibitors.
“Design of Novel MgZrO3@Fe2O3@ZnO as a Core-Shell Nano Catalyst: an
Effective Strategy for the Synthesis of Pyranopyrazole Derivatives”
Authors: Shelke Yogita. R. , Bobade Vivek. D. , Tope Dipak. R. , Kushare Sachin. S. , Agashe Jyoti. A. , Borhade Ashok. V. 
Published: April 2023

Background:
Catalysis has been widely applied in pharmaceutical companies in recent years. This paper reports a useful new approach for the synthesis of pyranopyrazoles.

Objectives:
One-pot synthesis of pyranopyrazoles using MgZrO3@Fe2O3@ZnO as a novel-core-shell nanocatalyst which increases reaction rate, selectivity, ease of work-up and recyclability of the supports. Method: The present study deals with the synthesis of MgZrO3@Fe2O3@ZnO core-shell catalyst using the sol-gel method.

Results:
The synthesized MgZrO3@Fe2O3@ZnO core-shell nanoparticles were analysed using XRD, TEM and BET surface area. The nanocatalyst had an average particle size of 20 nm by TEM images and BET Surface area of 58.93 m2/g.

Conclusion:
Novel MgZrO3@Fe2O3@ZnO core-shell nanoparticles have been used as an effi-cient and recoverable catalyst for one-pot synthesis of pyranopyrazoles.
Succinimidium Perchlorate as a Novel and Efficient Brönsted Acidic Ionic
Liquid Promoter for the Synthesis of 5-arylidene Barbituric Acid and pyrano[2,3-d] Pyrimidinone Derivatives
Authors: Haghpanah-Kouchesfehani Sara , Azizi Zahra , Daneshvar Nader , Shirini Farhad , Tajik Hassan 
Published: April 2023

Introduction::
In this article, succinimidinium perchlorate as a new acidic ionic liquid catalyst was prepared and used to synthesize 5-arylidene barbituric acid and pyrano[2,3-d]pyrimidinone derivatives.

Method::
These two derivatives of barbituric acid have a variety of useful properties.

Result::
The advantages of this reagent were high yields, high efficiency, short reaction times, easy performance, easy work-up and reusability.

Conclusion::
Succinimidinium perchlorate, which was made for the first time in this project, was identified with different methods, including FT-IR, 1H NMR, 13C NMR and mass spectroscopic techniques