bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of the Fc-fusion protein refolding method produced from the bacterial expression system
Authors: Astrelina P. S. , Ishchuk S. A. , Kabanova A. V. , Drai R. V. 
Published: February 2025

Introduction. The production of Fc-fused proteins in prokaryotic systems often results in the formation of insoluble aggregates due to improper folding of polypeptide chains. To obtain functional proteins, a refolding step is required. However, developing refolding parameters can be time-consuming. The optimization of renaturation conditions using the Design of Experiments (DoE) approach allows for the calculation of optimal process parameters and the evaluation of contributing factors and their interactions.Aim. This study aims to evaluate the effects of denaturation buffer pH, as well as oxidative and reducing agent concentrations, on the efficiency of Fc-fusion protein refolding in vitro and to determine optimal refolding parameters.Materials and methods. Fc-fusion protein inclusion bodies were obtained from an Escherichia coli BL21 bacterial expression system. The experiment was designed using an orthogonal composite design (Orthogonal Central Composite Design, CCO). Experimental design, statistical data processing, and parameter optimization were conducted using MODDE (v. 12.1, Sartorius Stedim Data Analytics AB, Germany). Chromatographic purity and yield of the target protein, as determined by high-performance size-exclusion chromatography, were used as response variables.Results and discussion. The DoE approach successfully optimized the Fc-fusion protein refolding process. Response surface plots were constructed, and the optimal factor values were determined. The statistical models demonstrated high predictive accuracy and data reproducibility. The refolding process was successfully validated under optimized conditions, resulting in a decrease in high-molecular-weight impurities and improperly folded protein forms. The chromatographic purity of the target protein increased by more than 10 %, as confirmed by high-performance size-exclusion chromatography.Conclusion. The study established significant effects of buffer pH, redox pair concentrations, and their interactions on the yield and chromatographic purity of the Fc-fused protein. The interplay between oxidative and reducing components and buffer pH was demonstrated. Increasing the buffer pH led to improved refolding efficiency.
ANALISIS USER EXPERIENCE DAN INNOVATION RESISTANCE PENGGUNAAN APLIKASI MYPERTAMINA MENGGUNAKAN PENDEKATAN UTAUT2 DAN UCD
Authors: Hairadifa Rifka Putri , Asra Taufik , Sinnun Ahmad 
Published: February 2025

Pertamina Company launched the MyPertamian Application as a solution to the problem of uneven distribution of subsidized fuel and the implementation of non-cash payment innovations during the pandemic. However, the mismatch between the implementation of the innovation and the habits of the community has led to a rejection of the use of the application. Therefore, with this research, it is expected to identify the factors influencing the rejection of innovation usage using the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) approach, with SmartPLS measurement and System Usability Scale (SUS) measurement as the readiness for application usage among 48 respondents through questionnaire completion. The research results show that aspects such as ease of use, usefulness, and perceived value of the MyPertamina application significantly influence user acceptance and the decision to adopt the application. On the other hand, innovation resistance appears in the form of user concerns about change, complexity, and data security. Therefore, design implications and development strategies can be identified to enhance user experience and reduce innovation barriers.
Utilizing bioinformatics and machine learning to identify CXCR4 gene-related therapeutic targets in diabetic foot ulcers
Authors: Zhang Hengyan , Zhou Ye , Yan Heguo , Huang Changxing , Yang Licong , Liu Yangwen 
Published: February 2025

BackgroundDiabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus that manifests as chronic, non-healing wounds that have a significant impact on patients quality of life. Identifying key molecular targets associated with DFUs could help develop targeted therapies to promote wound healing and prevent further complications. The CXCR4 gene is known to play a key role in cell migration, immunology response, and tissue repair, and thus may be an important target for DFU treatment.MethodsWe used the GEO database (Gene Expression Omnibus database) to obtain DFU-related gene expression data, identified differentially expressed genes (DEGs), and performed enrichment analysis to reveal the related biological pathways. Meanwhile, protein-protein interaction (PPI) networks were constructed using STRING to identify core genes. Feature selection methods such as LASSO, SVM-RFE and random forest algorithm were applied to localize possible therapeutic target genes. Finally, We analyzed the molecular pathways of CXCR4 in DFUs by Gene set enrichment analysis (GSEA).ResultsWe identified a total of 751 differential genes, of which 409 genes were significantly upregulated and 342 genes were downregulated in diabetic foot ulcer tissues. Functional enrichment analysis showed that these genes were mainly involved in pathways such as oxidative phosphorylation, phagosome, synaptic vesicle cycle, and pathways of neurodegeneration. We integrated the genes screened by three machine learning models (LASSO, SVM, and Random Forest), and CXCR4 was identified as a key gene with potential therapeutic value in DFUs. Gene set enrichment analysis (GSEA) showed that CXCR4 was closely associated with pathways related to immunology regulation and tissue repair.ConclusionThe findings suggest that CXCR4 and its related pathways play an important role in the pathogenesis of DFUs, providing a new perspective on targeted therapy for wound healing in diabetic patients. Further validation of the role of CXCR4 is expected to establish it as an important target in DFU management.
Predictive biomarkers for cardiometabolic risk in postmenopausal women: insights into visfatin, adropin, and adiponectin
Authors: Cybulska Anna Maria , Schneider-Matyka Daria , Walaszek Ireneusz , Panczyk Mariusz , Ćwiek Dorota , Lubkowska Anna , Grochans Elżbieta , Rachubińska Kamila , Malewicz Katarzyna , Chabowski Mariusz 
Published: February 2025

BackgroundVisfatin, adropin, and adiponectin are involved in many changes associated with obesity and metabolic disorders, and may be related to metabolic syndrome and cardiovascular disease. The selection of visfatin, adropin, and adiponectin as biomarkers is based on their significant roles in metabolic regulation and inflammation, which are critical factors in cardiometabolic risk. Visfatin is known for its pro-inflammatory properties and its ability to modulate insulin resistance. Adropin is involved in energy homeostasis and metabolic health, while adiponectin has anti-inflammatory and insulin-sensitizing effects. During the perimenopausal period, the risk of obesity, and consequently cardiometabolic diseases increases. Therefore, the aim of this study was to assess the relationship between cardiometabolic parameters and circulating levels of visfatin, adropin, and adiponectin in perimenopausal women with regard to their obesity status.Materials and methodsThis study of 168 perimenopausal women utilized a cross-sectional design with non-random sampling. It involved the use of questionnaires, as well as anthropometric and blood pressure measurements. Blood samples were collected to determine the levels of visfatin, adropin, and adiponectin. Statistical analyses, including correlation coefficients, were performed to evaluate the relationship between these biomarkers and cardiometabolic risk factors, such as insulin resistance, lipid profiles, and inflammatory markers.ResultsIn our study, visceral adiposity index and lipid accumulation product negatively correlated with adiponectin levels. Preliminary multivariate linear regression analysis revealed a positive correlation between circulating visfatin and IL-6 levels. Circulating adropin negatively correlated with HbA1C, fasting blood glucose, and insulin. Adiponectin negatively correlated with HbA1C, fasting blood glucose, insulin, and triglycerides. Furthermore, circulating adiponectin positively correlated with HDL, and negatively with HOMA-IR.ConclusionsAdiponectin is a promising biomarker for predicting cardiometabolic risk in postmenopausal women.
HIV and the gut microbiome: future research hotspots and trends
Authors: Wu Zhen , Xie Zhan-Peng , Cui Xin-Xin , Sun Xiang-Bin , Zhao Fang-Yi , Wang Nuo , Li Yu , Wang Haixia , Zhang Li , Shen Jing , Chen Fulei , Sun Haogang , He Jia 
Published: February 2025

BackgroundThe use of highly active antiretroviral therapy has transformed AIDS into a chronic infectious disease, but issues of chronic inflammation and immune system activation persist. Modulating the gut microbiome of patients may improve this situation, yet the specific association mechanisms between HIV and the gut microbiome remain unclear. This study aims to explore the research hotspots and trends of the HIV and the gut microbiome, providing direction for future research.MethodsWe conducted a search of the Web of Science Core Collection database up to April 30, 2024 to retrieve articles related to the relationship between the HIV and the gut microbiome. The scientific achievements and research frontiers in this field were analyzed using CiteSpace, VOSviewer, and Bibliometrix statistical software.ResultsAs of April 30, 2024, a total of 379 articles met the inclusion criteria. The number of publications in this field peaked in 2023, and the number of articles published after 2020 declined. The country with the highest number of publications was the United States (184 articles), and the institution with the most publications was the University of Colorado (USA) (21 articles). The author with the most publications was Routy Jean-Pierre (Canada) (14 articles). High-frequency keywords, aside from the key terms, included “HIV,” “inflammation,” “immune activation,” “gut microbiota,” and “translocation.” Keyword burst results indicated that short-chain fatty acids, T cells and obesity might become the focus of future research.ConclusionThe research hotspots in this field should prioritize examining the role of the primary gut microbiome metabolite, short-chain fatty acids, in reducing immune system activation and inflammation. Another emerging area of interest could be the investigation into the annual increase in obesity rates within this field. Furthermore, understanding the metabolic mechanisms of short-chain fatty acids in T cells is essential. Additionally, multi-omics analysis holds potential.
Potential pathogenic and protective genotypes and phenotypes of vitamin D binding protein in multiple sclerosis
Authors: Al-Shammri Suhail , Chattopadhyay Arpita , Mustafa Abu Salim 
Published: February 2025

BackgroundThe main carrier protein of vitamin D and its metabolites in plasma is vitamin D binding protein (VDBP) or group-specific component (Gc). Two single nucleotide polymorphisms, rs7041, and rs4588 in the GC gene result in three major VDBP/Gc genotypes, GC1F (c.1296T, c.1307C), GC1S (c.1296G, c.1307C), GC2 (c.1296T, c.1307A), and phenotypes, Gc1F (p.432Asp, p.436Thr), Gc1S (p.432Glu, p.436Thr), and Gc2 (p.432Asp, p.436Lys). This study investigated frequencies of GC genotypes and phenotypes in Kuwaiti multiple sclerosis (MS) patients and healthy controls, and their associations with serum levels of 25 hydroxyvitamin D [25(OH)vitamin D] and VDBP.MethodsThe genomic DNA was isolated from blood samples of drug-naïve MS patients (N = 151) and controls (N = 127). DNA regions covering the targeted mutations were amplified by PCR, sequenced by the Sanger method, and analyzed to determine GC genotypes and phenotypes. Serum 25(OH)vitamin D and VDBP levels were measured by enzyme immunoassay. SPSS used for statistical analyses. Differences between independent and related groups tested by Mann–Whitney U and Wilcoxon signed-rank tests respectively, Genotype and phenotype frequencies were calculated; p &lt; 0.05 considered significant.ResultsThe study detected four Gc genotypes/phenotypes, namely GC1F/Gc1F (c.1296T, c.1307C/p.432Asp, p.436Thr), GC1S/Gc1S (c.1296G, c.1307C/p.432Glu, p.436Thr), GC2/Gc2 (c.1296T, c.1307A/p.432Asp, p.436Lys), and GC3/Gc3 (c.1296G; c.1307A/p.432Glu, p.436Lys) in both subjects. The frequencies of GC3 genotype (control: 5.51%; patient: 28.48%) and Gc3-containing phenotypic groups (Gc1S/Gc3 + Gc2/Gc3 + Gc3/Gc3) were significantly higher in patients. Moreover, frequencies of GC1F genotype (control: 27.17%; patients: 5.30%) and Gc1F-containing phenotypic groups (Gc1F/Gc1F + Gc1S/Gc1F + Gc2/Gc1F) were higher in controls. Vitamin D levels were deficient in both groups. However, VDBP concentrations were significantly low in MS patients only.ConclusionThe VDBP/GC genotypes and phenotypes are associated with MS. Common genotype GC1F might be protective, and GC3, the novel variant found in MS patients appeared to be pathogenetic. Hypovitaminosis-D is prevalent in MS patients and controls.
High-dose thiamine supplementation ameliorates obesity induced by a high-fat and high-fructose diet in mice by reshaping gut microbiota
Authors: Xia Yu , Wang Lulu , Qiu Yanyan , Ge Weihong 
Published: February 2025

IntroductionThiamine (vitamin B1) in the gut is crucial for maintaining intestinal homeostasis and host health. Our previous study identified significantly lower levels of fecal thiamine in individuals with obesity; however, its potential and mechanisms for alleviating obesity induced by a high-fat and high-fructose diet (HFFD) remain unclear. Therefore, in the present study, the effects of high-dose thiamine supplementation on HFFD-induced obesity and gut microbiota dysbiosis were investigated.MethodsHFFD-fed mice were supplemented with high-dose thiamine for eight weeks. Biochemical analysis and histological analysis were conducted to assess phenotypic changes. Fecal 16S rRNA gene sequencing was performed to analyze alterations in the gut microbiota.ResultsThe results showed that high-dose thiamine supplementation for eight weeks could significantly alleviate symptoms of HFFD-induced obesity and improve HFFD-induced intestinal epithelial barrier dysfunction by enhancing the tight junction function. Furthermore, oral administration of high-dose thiamine also regulated HFFD-induced gut microbiota dysbiosis by reshaping its structure and composition of gut microbiota, such as increasing the relative abundance of Actinobacteria and Bifidobacterium pseudolongum, and reducing the relative abundance of Proteobacteria and Ruminococcus gnavus, accompanied by decreased level of gut-derived endotoxin. Finally, significant correlations were found between obesity-related phenotypes and gut microbiota through correlation analysis.ConclusionOur findings suggest that the potential mechanism by which high-dose thiamine supplementation alleviated HFFD-induced obesity might involve reshaping gut microbiota and restoring the intestinal barrier, thereby ameliorating gut microbiota-related endotoxemia.
A comprehensive analysis and comparative study of the trends in thyroid cancer burden in China and globally from 1990 to 2021, with projections for the next 15 Years
Authors: Yin Yulai , Zhang Xiaoyu 
Published: February 2025

ObjectiveThis study aims to analyze the trends in incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of thyroid cancer across gender and age groups in China and globally from 1990 to 2021, using data from the Global Burden of Disease (GBD) database. Additionally, it projects the trends in thyroid cancer burden for the next 15 years for both China and the global population.Materials and methodsThyroid cancer-related data were extracted from the 2021 GBD dataset. The average annual percentage change (AAPC) and the corresponding 95% confidence intervals (95% CI) were calculated using Joinpoint regression to reflect trends in the thyroid cancer burden. R software was used to perform a gender- and age-specific analysis and visualize the trends in thyroid cancer burden for both China and the global population. Furthermore, the Autoregressive Integrated Moving Average (ARIMA) model was employed to project the trends in thyroid cancer burden over the next 15 years.ResultsThe results indicate a rising trend in the incidence and prevalence of thyroid cancer both in China and globally. Conversely, the mortality rate and DALYs show a declining trend over the same period. Age-specific analysis revealed that thyroid cancer is most prevalent among individuals aged 50–64. Gender-specific analysis indicated that the incidence rate is higher in females than in males. Projections for the next 15 years show that the age-standardized incidence rates for both males and females are expected to continue rising in China and globally. While the age-standardized mortality rate for females is projected to decline significantly, the mortality rate for males is predicted to stabilize.ConclusionBetween 1990 and 2021, the number of thyroid cancer cases has increased both in China and globally, while the mortality rate has shown a marked decline. This trend is expected to persist over the next 15 years. The growing population affected by thyroid cancer reflects a substantial disease burden, making thyroid cancer a significant global public health concern. The formulation of proactive and effective health policies is urgently needed.
Public attitudes and the socio-political divide surrounding onshore wind power in Norway
Authors: Kraft Pål , Kraft Brage 
Published: February 2025

IntroductionNorway's goal to significantly increase onshore wind power production requires building public trust and addressing societal concerns.ObjectiveThis study investigated Norwegian attitudes toward onshore wind power at national and local levels, examining the influence of socioeconomic factors, the “Anywhere-Somewhere” worldview, climate change denial, and materialism.MethodsA representative survey of 1,029 Norwegian adults (aged 18 years and above) was conducted.ResultsPublic opinion on national onshore wind power development was almost evenly divided, although negative attitudes tended to be more extreme. However, local opposition was significantly higher (60%), primarily because of concerns about environmental impacts (harm to wildlife, visual impacts, noise, and land use). Socioeconomic factors did not predict attitudes, but opposition strongly correlated with a “Somewhere” worldview; this relationship was not mediated by climate change denial or materialism.ConclusionSignificant public opposition to onshore wind power exists in Norway, particularly within marginalized sociocultural groups.ImplicationsAchieving Norway's renewable energy targets requires inclusive policies that address citizen concerns.
DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells
Authors: Leccese Adriana , Ruta Veronica , Panzeri Valentina , Attili Fabia , Spada Cristiano , Cianfanelli Valentina , Sette Claudio 
Published: February 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Late diagnosis and acquisition of chemoresistance contribute to its dismal prognosis. While surgical resection improved the clinical outcome of patients, only ~20% of them are eligible due to advanced disease at diagnosis. Thus, the development of new therapeutic approaches is a master priority for an improved management of this cancer. The helicase DDX21 was proposed as a prognostic marker in several tumors, including PDAC. Methods: DDX21 expression was evaluated in PDAC samples and cell lines; RNA sequencing and bioinformatics analyses of DDX21-depleted PANC-1 silenced cells; functional analyses of autophagy, cell cycle and proliferation. Results: DDX21 is expressed at higher levels in liver metastasis of PDAC patients. Transcriptomics analyses of DDX21-depleted cells revealed an enrichment in genes involved in autophagy and cell cycle progression. The inactivation of DDX21 by RNA interference enhanced the basal autophagic flux and altered the cell cycle by reducing the rate of G1-S transition. Coherently, PDAC cell proliferation and clonogenic activity was significantly reduced. Conclusions: Our results support the oncogenic role of DDX21 in PDAC and uncover a new role for this helicase in the regulation of basal autophagy.
A Continuous Space Path Planning Method for Unmanned Aerial Vehicle Based on Particle Swarm Optimization-Enhanced Deep Q-Network
Authors: Han Le , Zhang Hui , An Nan 
Published: February 2025

In the field of unmanned aerial vehicle (UAV) path planning, the conventional deep Q-network (DQN) algorithm encounters the issue of action space discretization, which results in the generation of unsmooth and inefficient planned paths. To address this issue, we introduce the particle swarm optimization (PSO) algorithm into DQN to convert the discrete action space into a continuous one. This method divides the agent’s surrounding space into discrete and continuous action spaces. The PSO algorithm performs a global search in the continuous space to obtain a continuous candidate solution, while DQN learns a policy in the discrete space to obtain a discrete candidate solution. Then, the two candidate solutions are combined using a weighted vector method to determine a direction that balances global search and policy learning. Additionally, we introduce a novel feature matrix as the state space for DQN, providing more accurate environmental and positional representations. Furthermore, we incorporate a mechanism into the base prioritized experience replay (PER) and N-step updates, which combines the current temporal difference error (TD-error) with historical priorities and includes a policy entropy penalty term, thereby enhancing DQN’s ability to learn long-term dependencies. The performance of the PSO-DQN model is further improved through an enhanced ε-greedy policy and learning rate decay strategy. Simulation results and experiments using the Flightmare simulator demonstrate that the proposed method generates smoother and more efficient paths for drones, exhibiting strong robustness in complex environments.
EFEKTIFITAS BROSUR TERHADAP PENINGKATAN PENDAFTARAN ONLINE DENGAN MOBILE JKN DI RSUD KOTA TEGAL
Authors: Himawan Fatchurrozak , Purwaningsih Tinah , Inayah Maslahatul , Hermawan Didi 
Published: February 2025

Latar Belakang: Inovasi pendaftaran online dirawat jalan tidak akan dirasakan manfaatnya secara maksimal apabila adanya keterbatasan pengetahuan masyarakat, Penggunaan Brosur panduan pendaftaran online diharapkan membantu mengatasi keterbatasan pengetahuan masyarakat. Tujuan: Mengetahui hubungan penggunaan brosur panduan pendaftaran online peserta BPJS dengan jumlah pendaftaran rawat jalan yang menggunakan pendaftaran secara online dengan mobile JKN di RSUD Kota Tegal. Metode penelitian: Jenis penelitian ini adalah penelitian kuantitatif dengan jumlah sampel 40. Desain penelitian yang digunakan kuasi eksperimen dan uji korelasi menggunakan chi square. Hasil: Nilai chi square 0,111 dengan catatan nilai ekpetasi kurang dari 5 sehingga pengambilan keputusan melihat nilai uji fisher exact sebesar 0,182 > 0.05 artinya Ho diterima Tidak ada hubugan pemberian brosur dengan jumlah pendaftaran online melalui aplikasi mobile JKN. Saran: Upaya promosi penggunaan brosur perlu dibarengi dengan upaya sosialisasi yang lain seperti edukasi, atau disediakan pojok layanan pendaftaran online yang dilakukan secara rutin.