bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DNMT3B Inhibitor Nanaomycin A as a Neuroblastoma Therapeutic
Agent
Authors: Izumi Kazuya , Aoki Hiromasa , Kakita Hiroki , Takeshita Satoru , Ueda Hiroko , Inoue Yasumichi , Hayashi Hidetoshi , Yamada Yasumasa , Aoyama Mineyoshi 
Published: May 2023

Background:
Neuroblastoma is one of the most common childhood solid tumors. Because
tumor suppressor genes are often hypermethylated in cancers, DNA methylation has emerged as a target
for cancer therapeutics. Nanaomycin A, an inhibitor of DNA methyltransferase 3B, which mediates
de novo DNA methylation, reportedly induces death in several types of human cancer cells.

Objective:
To study the antitumor activity of nanaomycin A against neuroblastoma cell lines and its
mechanism.

Methods:
The anti-tumor effect of nanaomycin A on neuroblastoma cell lines was evaluated based on
cell viability, DNA methylation levels, apoptosis-related protein expression, and neuronal-associated
mRNA expression.

Results:
Nanaomycin A decreased genomic DNA methylation levels and induced apoptosis in human
neuroblastoma cells. Nanaomycin A also upregulated the expression of mRNAs for several genes related
to neuronal maturation.

Conclusions:
Nanaomycin A is an effective therapeutic candidate for treating neuroblastoma. Our
findings also suggest that the inhibition of DNA methylation is a promising anti-tumor therapy strategy
for neuroblastoma.
The Mutation and Low Expression of ARID1A are Predictive of a Poor
Prognosis and High Immune Infiltration in Triple-negative Breast Cancer
Authors: Wang Yuejing , Chen Zhuo , Wu Jing , Yan Hong , Wang Yiran , He Jie 
Published: May 2023

Background:
Triple-negative breast cancer (TNBC) has the poorest prognosis among all
breast cancer subtypes. While several tumor types are excepted to have a curative response to immunotherapy
through the AT-rich interaction domain 1A (ARID1A) gene, its role in TNBC remains unclear.

Methods:
The expression of the ARID1A gene and immune infiltration in TNBC were analyzed by
way and function enrichment analysis. Additionally, 27 gene mutations, including ARID1A mutation,
were detected in paraffin-embedded TNBC specimens and normal breast specimens using Next Generation
Sequencing (NGS). Immunohistochemical staining was employed to detect the expression of
AIRD1A, TP53, Ki67, CD4, CD8, and PD-L1 proteins in TNBC and the adjacent normal tissue samples.

Results:
The bioinformatics analysis revealed that ARID1A was mutated in TNBC and significantly
associated with tumor immune infiltration. NGS analysis showed a high mutation rate of ARID1A
(35%) in TNBC, but the mutation status of ARID1A was not associated with age at onset, lymph node
metastasis, pathological grade, or Ki67 index. Low expression or loss of AIRD1A was more commonly
observed in TNBC tissues (36/108) as compared to normal tissues (3/25). Positive expression of
CD8 and PD-L1 was observed in TNBC tissues with low ARID1A expression. ARID1A mutation was
associated with low protein expression, and patients with ARID1A mutation or low protein expression
had shorter progression-free survival.

Conclusion:
The ARID1A mutation and low expression are associated with poor prognosis and high
immune infiltration in TNBC, and might be biomarkers for TNBC prognosis and immunotherapy efficacy.
The FJQR Has Synergistic Effect with Fluoropyrimidine in the Maintenance
Treatment for HER-2 Negative Gastric Cancer
Authors: Kong Fanming , Zhao Lu , Wang Na , Zhang Dou , Wang Ziwei , Mei Qingyun , Yu Yongchao , Jia Yingjie 
Published: May 2023

Introduction:
Maintenance therapy aimed to strengthen the first-line chemotherapy and
improve quality of life is needed for gastric cancer (GC). Currently, many clinical studies have
confirmed the important role of fluoropyrimidine in the maintenance stage. Our team has created
patented prescriptions “Fuzheng jiedu Quyu Method” recipe (FJQR), which was considered as an
adjuvant therapeutic scheme (reduce toxicity and increase the efficacy of chemotherapy). This
study aimed to evaluate the efficacy and safety of FJQR combined with fluoropyrimidine as a
maintenance treatment in HER-2 negative GC patients.

Methods:
We performed the analysis of 129 patients with HER-2 negative GC who entered the
maintenance stage in our hospital and Tianjin Cancer Hospital between January 2018 and December
2020. Out of the 129 eligible patients, 64 were categorized into the maintenance treatment
group with FJQR+fluoropyrimidine, and 65 patients were assigned to the control group if they
received fluoropyrimidine alone. Capecitabine was orally 1000mg/m2, Qd, half an hour after
meals, and FGQR was 15g Bid after capecitabine. The primary endpoint was progression-free survival
(PFS). The secondary endpoints were overall survival (OS), overall remission rate (ORR),
quality of Life (QOL), TCM syndrome and safety.

Results:
The mPFS in the treatment group was significantly prolonged compared with the control
group (6.3 vs. 5.0 months, p = 0.03), while the mOS was not substantially improved (11.4 vs. 10.5
months, p = 0.38). Gastrointestinal symptoms and pain became better in the treatment group. The
number of distant metastatic organs, first-line chemotherapy cycles, and lymph node metastasis
were independent risk predictors for PFS. Blood stasis syndrome may be the protective factor. In
terms of safety, treatment-related adverse events (AEs) in the treatment group were relatively
lighter, and the incidence of grade III-IV AEs could be significantly reduced.

Conclusion:
FJQR and fluoropyrimidine have synergistic effects as maintenance treatment in
HER-2 negative GC, with good efficacy and safety.
Lipid Profiles and Atrial Fibrillation in Ischemic Stroke Patients Treated
with Thrombectomy: Experience from a Tertiary Italian Stroke Hospital
Authors: Bravi Maria Cristina , Pilato Fabio , Crupi Domenica , Mangiardi Marilena , Pezzella Francesca Romana , Siniscalchi Antonio , Cotroneo Enrico , Bertaccini Luca , Alessiani Michele , Anticoli Sabrina 
Published: May 2023

Objectives:
To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk
factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke
(AIS).

Methods:
We performed a retrospective analysis of the lipid profile and vascular risk factor in
1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021.
To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein
cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were
obtained the day after admission. We also examined the association between lipid profile, AF and
EVT in multivariate logistic regression analysis.

Results:
Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and
26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n = 370; 22.57 %; 95% CI, 20.6-24.7)
showed no difference in age (median 73 years (IQR; 63-80) versus 74 years (IQR; 63-82)),
HbA1c levels (median 5.8 (IQR; 5.4-6.2) versus 5.9 (IQR; 5.4-6.4)), TG/HDL ratio (median 2.40
(IQR; 1.65-3.48) versus 2.51 (IQR; 1.73-3.64)), diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension
(OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to
non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl (IQR; 139-
187) versus 173 mg/dl (IQR; 148-202); p <0.001), LDL-C (105 mg/dl (IQR; 80-133) versus 113
mg/dl (IQR; 88-142); p <0.01), TG (98 mg/dl (IQR; 76-126) versus 107 mg/dl (IQR; 85-139); p
<0.001), non-HDL-C (117 mg/dl (IQR; 94-145) versus 127 mg/dl (IQR; 103-154); p <0.001), HC
(8.3 mmol/l (IQR; 6-11) versus 10 mmol/l (IQR; 7.3-13.5); p <0.001) than non-EVT patients.
Multivariate logistic regression analysis showed an independent association of EVT with TC (OR
0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and
NIHSS (OR 1.17, 95% CI 0.14-1.19).

Conclusion:
Total cholesterol and all cholesterol-related measures were significantly lower in patients
undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was
significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly
linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different
causes. AIS patients may have different pathogenesis and their understanding may improve
the discovery of specific and tailored preventive treatments.
Integrated Bioinformatics Approach for Disclosing Autophagy Pathway as a Therapeutic Target in Advanced KRAS Mutated/Positive Lung Adenocarcinoma
Authors: Dodin Yasmeen 
Published: May 2023

Background:
Lung cancer is the leading cause of cancer-related deaths, accounting for 1.8 million deaths (18%). Nearly 80%-85% of lung cancer cases are non-small cell lung cancers (NSCLC). One of the most frequent genetic mutations in NSCLC is the Kirsten Rat Sarcoma Oncogene Homolog (KRAS) gene mutation. In recent years, autophagy has drawn substantial attention as a potential pathway that can be targeted in cancer driven by KRAS gene mutation to efficiently improve the therapeutic profile of different treatments.

Methods:
In this study, we have investigated the potential of targeting the autophagy pathway as a treatment approach in advanced KRAS-mutated lung adenocarcinoma using gene expression data from The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) project.

Results:
Compared to KRAS wild-type lung adenocarcinoma, there were found 11 differentially expressed autophagy-related genes (DEARGs), with 5 upregulated and 6 downregulated DEARGs (threshold of adjusted p-value <0.05).

Conclusion:
These DEARGs can be investigated as potential genes that can be targeted by different autophagy inhibitors.
Current Physiotherapy Approaches for Patellofemoral Pain Syndrome: A systematic review
Authors: Fuhad Aslinda , Zahari Zarina , Justine Maria , Wen Qiang Sun 
Published: May 2023

Background PFPS is a common knee-flexion-induced pain among young people who attend physiotherapy. Significant This study focused on PT management on PFPS. Methods The papers were retrieved via an electronic search of year-round databases. The McMaster Critical Review Form for Quantitative Research and the Cochrane (EPOC) were utilised for quality and risk assessments. Limitations Small evidence on Blood flow restrictions, kinesiophobia, and patient education could be due to lack of investigation. Findings More trials on the effect of various types of PFPS intervention. Implications Physiotherapy improves pain, physical function, and kinesiophobia, but further research is needed for clinicalÂ applicability.
Economic Security, Sanctions and Reorientation of Russian Foreign Trade Flows
Authors: Anisimova Y. A. , Plotnikov V. A. 
Published: May 2023

Relevance. Under the conditions of sanctions pressure, Russia needs to protect its economic interests and strengthen economic security. Therefore, the reorientation of foreign trade flows requires additional analysis. The purpose is to consider the direction of reorientation of Russian foreign trade flows in the context of anti‒ Russian sanctions.Objectives: to determine the main agenda of world trade policy; to identify common priorities of world trade; to provide quantitative data on the volume of trade of countries, to analyze the specifics of trade agreements over a decade, to identify the main economic method of pressure on states; to provide data on Russia's trade with other countries; to consider the Russian export commodity structure; to identify the relationship between the share in the commodity structure goods and growth rates in stable and crisis periods; identify priority export Russian goods in modern conditions.Methodology. The research methodology included the use of methods of analysis of quantitative and qualitative characteristics, correlation analysis, description, retrospective analysis, abstraction, generalization of the analyzed information.Results. The reasons for the forced change in the direction of foreign trade flows are not only direct pressure on the Russian economy, but also global trends of deglobalization and regionalization. The current trading partners, despite the restrictions imposed, continue to trade with Russia. When finding potential allies, the focus is primarily on the reliability, security and strength of partners on the world stage. The Russian economy should not deviate from the current export structure, as the demand for energy resources continues to be high. And Russia retains the role of one of the guarantors of global energy security.Conclusions. The issue of reorientation of Russian trade flows to alternative directions will remain one of the prevailing ones today. This is able to stabilize the economy and protect the economic interests of the country, to ensure the economic security of Russia. By diversifying and transforming trade flows by changing channels, the Russian economy will be able to discover new opportunities for the development of the world market.
A Modern Approach to the Selection and Implementation of an ERP System at an Enterprise as an Effective IT Solution in Business Management
Authors: Tronina I. A. , Semenikhina A. V. , Tatenko G. I. , Morozova O. I. 
Published: May 2023

Relevance. A modern enterprise as a complex socio-economic system exists today in the mode of constant changes to adequately respond to the challenges of the external environment. The development of production and personnel potential, the growth of profitability, and the improvement of competitiveness are the key objectives of the strategic development of the enterprise, which requires the optimization of its business processes, the reorganization of work with business partners, customers, and employees. Hence, there is a need for systematic business renewal through the introduction of new IT products.The purpose is a theoretical and methodological justification of the need to integrate an ERP system into the current activities of a modern enterprise in the face of environmental challenges. The objectives: to consider the possibilities and mechanism of implementing an ERP system for the functioning and development of enterprises; to investigate the key elements of an ERP system for building a modern IT architecture of an enterprise in accordance with the principles of digitalization; to highlight the advantages and disadvantages of classical and flexible approaches in the ERP-system implementation project.Methodology. Methods of statistical and comparative analysis, illustrative-graphical method, methods of generalization and logic based on a systematic approach are used in the work.Results. In the course of the study, it was found that the problems of implementing an ERP system in the activities of a modern enterprise must be solved on the basis of a project approach involving the use of mechanisms of both the traditional Waterfall methodology and the Agile methodology. The main thing is to understand the potential opportunities and assess the expected risks when making decisions about the implementation of an IT product.Conclusions. The introduction of an ERP system in an enterprise will improve and optimize business processes, focus on the competence abilities of line managers and employees. This is important in order to get the most out of the potential of an ERP system. The starting point is the process of developing and implementing standards of work with a clear description of the desired result. At the same time, the project team should pay considerable attention to changing the mentality and behavior of employees with ongoing changes in the motivation system and organizational culture.
EVALUASI IMPLEMENTASI KEBIJAKAN TATA KELOLA KEPESERTAAN PBI DAERAH JAMINAN KESEHATAN NASIONAL DI KABUPATEN KAYONG UTARA DAN KABUPATEN KETAPANG PROVINSI KALIMANTAN BARAT
Authors: Dedet Triwahyudi  , Firdaus Hafidz As Shidieq  , Laksono Trisnantoro  
Published: May 2023

Background:
The management of the Regional Health Insurance was merged into BPJS Health after the implementation of the 2014 National Health Insurance program. Kayong Utara Regency and Ketapang Regency are part of the Regency that combines regional
health insurance participation into BPJS Health. The implementation of regional PBI governance needs to be supported by adequate regulations, a strong stakeholder vision, communication between stakeholders that is in line with the policies of regional leaders.
Objective: The general objective of this research was to explore the ability of stakeholders in implementing the governance of PBI participation in the National Health Insurance Region.
Methods: This study used a realist evaluation approach with a descriptive case study design. The study used purposive sampling, the research subjects were 24 people. Data was collected by means of in-depth interviews and document review.
Results: The implementation of the JKN Program is a strategic policy. North Kayong Regency insures the rich and the poor at BPJS Health, while Ketapang Regency only insures the poor or the poor. Based on the Context, Mechanism, and Outcome hypothesis, the management of PBI participants responded differently in the two
districts. In the implementation of non-comprehensive regulatory influences, the Regional PBI Management had not been good in the two districts, a strategic vision that was not accompanied by a strategic plan and partial communication (mechanism) contributes to the results or in ensuring health insurance for the poor (outcomes).
Conclusion: The government of Kayong Utara and Kabupaten Ketapang have a strong commitment to managing health insurance for the poor. The implementation of the Regional PBI in the two districts faces challenges in the form of regulations that are not yet comprehensive. Comprehensive regulations, clear targets, and cross-structure coordination are needed in the management of Regional PBI in North Kayong Regency and Ketapang Regency so that it can be carried out properly.
GDF15 Mediates the Effect of Skeletal Muscle Contraction on Glucose-Stimulated Insulin Secretion
Authors: Zhang Hui , Mulya Anny , Nieuwoudt Stephan , Vandanmagsar Bolormaa , McDowell Ruth , Heintz Elizabeth C. , Zunica Elizabeth R.M. , Collier J. Jason , Bozadjieva-Kramer Nadejda , Seeley Randy J. , Axelrod Christopher L. , Kirwan John P. 
Published: May 2023

Exercise is a first-line treatment for type 2 diabetes and preserves β-cell function by hitherto unknown mechanisms. We postulated that proteins from contracting skeletal muscle may act as cellular signals to regulate pancreatic β-cell function. We used electric pulse stimulation (EPS) to induce contraction in C2C12 myotubes and found that treatment of β-cells with EPS-conditioned medium enhanced glucose-stimulated insulin secretion (GSIS). Transcriptomics and subsequent targeted validation revealed growth differentiation factor 15 (GDF15) as a central component of the skeletal muscle secretome. Exposure to recombinant GDF15 enhanced GSIS in cells, islets, and mice. GDF15 enhanced GSIS by upregulating the insulin secretion pathway in β-cells, which was abrogated in the presence of a GDF15 neutralizing antibody. The effect of GDF15 on GSIS was also observed in islets from GFRAL-deficient mice. Circulating GDF15 was incrementally elevated in patients with pre- and type 2 diabetes and positively associated with C-peptide in humans with overweight or obesity. Six weeks of high-intensity exercise training increased circulating GDF15 concentrations, which positively correlated with improvements in β-cell function in patients with type 2 diabetes. Taken together, GDF15 can function as a contraction-induced protein that enhances GSIS through activating the canonical signaling pathway in a GFRAL-independent manner.

Article Highlights
Exercise improves glucose-stimulated insulin secretion through direct interorgan communication. Contracting skeletal muscle releases growth differentiation factor 15 (GDF15), which is required to synergistically enhance glucose-stimulated insulin secretion. GDF15 enhances glucose-stimulated insulin secretion by activating the canonical insulin release pathway. Increased levels of circulating GDF15 after exercise training are related to improvements in β-cell function in patients with type 2 diabetes.
Activation of METTL3 Promotes White Adipose Tissue Beiging and Combats Obesity
Authors: Xie Renxiang , Yan Sujun , Zhou Xiaoling , Gao Yunyi , Qian Yu , Hou Jingyu , Chen Zhanghui , Lai Kairan , Gao Xiangwei , Wei Saisai 
Published: May 2023

The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains to be studied. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice. Adipose-specific depletion of the Mettl3 gene undermines WAT beiging and impairs the metabolic capability of mice fed with a high-fat diet. Mechanistically, METTL3-catalyzed m6A installation on thermogenic mRNAs, including Krüppel-like factor 9 (Klf9), prevents their degradation. Activation of the METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate promotes WAT beiging, reduces body weight, and corrects metabolic disorders in diet-induced obese mice. These findings uncover a novel epitranscriptional mechanism in WAT beiging and identify METTL3 as a potential therapeutic target for obesity-associated diseases.

Article Highlights
METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging. Depletion of Mettl3 undermines WAT beiging and impairs thermogenesis. METTL3-mediated m6A installation promotes the stability of Krüppel-like factor 9 (Klf9). KLF9 rescues impaired beiging elicited by Mettl3 depletion. Pharmaceutical activation of the METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate induces WAT beiging. Methyl piperidine-3-carboxylate corrects obesity-associated disorders. The METTL3-KLF9 pathway may serve as a potential therapeutic target for obesity-associated diseases.
Smartphone-Operated Smart Farm Watering System Using Long-Range Communication Technology
Authors: Mog Lee Kyung 
Published: May 2023

Abstract
Keeping proper soil moisture is essential in growing good quality and efficient fruit yield. To that effect, soil moisture level must be controlled, to maintain proper watering. A smartphone application was developed to operate a smart farm watering system. It monitors the soil’s moisture and launches sprayers to water dried areas. The system’s architecture was built in a distributed client-server computing system, in a small computing grid. The grid was built across long range (LoRa) communication networks with the same ID, but different addresses. In terms of integration, the system was built using autonomous microprocessors, which consist of a server and five client microprocessors. A smartphone was used as the server of a central controller, and four moisture detection modules and a water spraying system module were used as autonomous clients. The server was inter-connected with the clients via a star-type topology network in the polling processes. Each client module autonomously analyzes the measured digital voltage of the moisture sensor plugged into the soil. When the server sends queries regarding the status of the moisture level, the client sends the request signal to the server using the LoRa communication technology. The communication between the server and the clients is based on the LoRa communication technology. The LoRa-to-Bluetooth converter is used to connect the Bluetooth and the LoRa signal. The field test was performed in a watermelon field, with an area of approximately 6600 m2. The water spraying system constructed with LoRa communication technology could successfully manage and control the moisture level in the field test.