bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel STAT3/ NFκB p50 axis regulates stromal-KDM2A to promote M2 macrophage-mediated chemoresistance in breast cancer
Authors: Chen Jia-Shing , Teng Yu-Ning , Chen Cheng-Yi , Chen Jing-Yi 
Published: October 2023

Abstract
Background
Lysine Demethylase 2A (KDM2A) plays a crucial role in cancer cell growth, differentiation, metastasis, and the maintenance of cancer stemness. Our previous study found that cancer-secreted IL-6 can upregulate the expression of KDM2A to promote further the transition of cells into cancer-associated fibroblasts (CAFs). However, the molecular mechanism by which breast cancer-secreted IL-6 regulates the expression of KDM2A remains unclear. Therefore, this study aimed to elucidate the underlying molecular mechanism of IL-6 in regulating KDM2A expression in CAFs and KDM2A-mediated paclitaxel resistance in breast cancer.

Methods
The ectopic vector expression and biochemical inhibitor were used to analyze the KDM2A expression regulated by HS-578 T conditioned medium or IL-6 in mammary fibroblasts. Immunoprecipitation and chromatin immunoprecipitation assays were conducted to examine the interaction between STAT3 and NFκB p50. M2 macrophage polarization was assessed by analyzing M2 macrophage-specific markers using flow cytometry and RT-PCR. ESTIMATE algorithm was used to analyze the tumor microenvironment-dominant breast cancer samples from the TCGA database. The correlation between stromal KDM2A and CD163 + M2 macrophages was analyzed using the Pearson correlation coefficient. Cell viability was determined using trypan blue exclusion assay.

Results
IL-6 regulates gene expression via activation and dimerization of STAT3 or collaboration of STAT3 and NFκB. However, STAT3, a downstream transcription factor of the IL-6 signaling pathway, was directly complexed with NFκB p50, not NFκB p65, to upregulate the expression of KDM2A in CAFs. Enrichment analysis of immune cells/stromal cells using TCGA-breast cancer RNA-seq data unveiled a positive correlation between stromal KDM2A and the abundance of M2 macrophages. CXCR2-associated chemokines secreted by KDM2A-expressing CAFs stimulated M2 macrophage polarization, which in turn secreted CCL2 to increase paclitaxel resistance in breast cancer cells by activating CCR2 signaling.

Conclusion
This study revealed the non-canonical molecular mechanism of IL-6 secreted by breast cancer upregulated KDM2A expression in CAFs via a novel STAT3/NFκB p50 axis, which STAT3 complexed with NFκB p50 in NFκB p50 binding motif of KDM2A promoter. KDM2A-expressing CAFs dominantly secreted the CXCR2-associated chemokines to promote M2 macrophage polarization and enhance paclitaxel resistance in breast cancer. These findings underscore the therapeutic potential of targeting the CXCR2 or CCR2 pathway as a novel strategy for paclitaxel-resistant breast cancer.
Advancing sustainable agriculture: a critical review of smart and eco-friendly nanomaterial applications
Authors: Balusamy Sri Renukadevi , Joshi Abhayraj S. , Perumalsamy Haribalan , Mijakovic Ivan , Singh Priyanka 
Published: October 2023

AbstractUndoubtedly, nanoparticles are one of the ideal choices for achieving challenges related to bio sensing, drug delivery, and biotechnological tools. After gaining success in biomedical research, scientists are exploring various types of nanoparticles for achieving sustainable agriculture. The active nanoparticles can be used as a direct source of micronutrients or as a delivery platform for delivering the bioactive agrochemicals to improve crop growth, crop yield, and crop quality. Till date, several reports have been published showing applications of nanotechnology in agriculture. For instance, several methods have been employed for application of nanoparticles; especially metal nanoparticles to improve agriculture. The physicochemical properties of nanoparticles such as core metal used to synthesize the nanoparticles, their size, shape, surface chemistry, and surface coatings affect crops, soil health, and crop-associated ecosystem. Therefore, selecting nanoparticles with appropriate physicochemical properties and applying them to agriculture via suitable method stands as smart option to achieve sustainable agriculture and improved plant performance. In presented review, we have compared various methods of nanoparticle application in plants and critically interpreted the significant differences to find out relatively safe and specific method for sustainable agricultural practice. Further, we have critically analyzed and discussed the different physicochemical properties of nanoparticles that have direct influence on plants in terms of nano safety and nanotoxicity. From literature review, we would like to point out that the implementation of smaller sized metal nanoparticles in low concentration via seed priming and foliar spray methods could be safer method for minimizing nanotoxicity, and for exhibiting better plant performance during stress and non-stressed conditions. Moreover, using nanomaterials for delivery of bioactive agrochemicals could pose as a smart alternative for conventional chemical fertilizers for achieving the safer and cleaner technology in sustainable agriculture. While reviewing all the available literature, we came across some serious drawbacks such as the lack of proper regulatory bodies to control the usage of nanomaterials and poor knowledge of the long-term impact on the ecosystem which need to be addressed in near future for comprehensive knowledge of applicability of green nanotechnology in agriculture.
Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis
Authors: Cui Qian , Li Wentao , Wang Dong , Wang Shuangcui , Yu Jianchun 
Published: October 2023

Abstract
Background
The main types of PD-L1 in the blood include soluble PD-L1 (sPD-L1), exosomal PD-L1 (exoPD-L1), and PD-L1 in circulating tumor cells (CTCs). However, the predictive and prognostic values of these three indicators in patients with non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy are unclear, warranting a systematic meta-analysis.

Methods
A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) values were extracted from the included studies to investigate the correlation between the three PD-L1 indicators and overall survival (OS) or progression-free survival (PFS). The Newcastle–Ottawa Scale (NOS) was used to examine the quality of the included studies. Subgroup analyses were employed to investigate the heterogeneity. The publication bias of the included studies was assessed using Begg's and Egger's tests. P < 0.05 was regarded as significantly different.

Results
The pooled results revealed that high pre-treatment sPD-L1 levels were significantly associated with inferior OS (HR = 2.32, 95% CI = 1.68–3.18, P < 0.001) and PFS (HR = 2.52, 95% CI = 1.72–3.68, P < 0.001). However, dynamic changes in sPD-L1 after immunotherapy were not statistically significant for OS (HR = 1.46, 95% CI = 0.65–3.26, P > 0.05) or PFS (HR = 1.62, 95% CI = 0.92–2.86, P > 0.05). Meanwhile, the upregulated pre-treatment exoPD-L1 levels were significantly associated with poor PFS (HR = 4.44, 95% CI = 2.87–6.89, P < 0.001), whereas the post-treatment dynamic upregulation of exoPD-L1 was significantly correlated with superior PFS (HR = 0.36, 95% CI = 0.24–0.54, P < 0.001) and OS (HR = 0.20, 95% CI = 0.07–0.53, P < 0.001). For PD-L1 in CTCs, the pooled results indicated that PD-L1 expression in CTCs was not significantly correlated with OS (HR = 0.75, 95% CI = 0.49–1.13, P = 0.170) and PFS (HR = 0.79, 95% CI = 0.59–1.06, P = 0.12).

Conclusions
Blood-based PD-L1 analysis is a potential strategy for predicting treatment efficacy and prognosis in patients with cancer.
Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology
Authors: Liu Shanshan , Liu Yongting , Wu Xue , Liu Zhengqi 
Published: October 2023

AbstractBackgroundGout is the most common inflammatory arthritis and closely related to metabolic syndrome, leading to excruciating pain and the decline in quality of patients’ life. However, the pathogenesis of gout is still unclear, and novel biomarkers are demanded for the early prediction and diagnosis of gout.ObjectiveThis study aimed at profiling the dysregulated metabolic pathways in asymptomatic hyperuricemia (AHU) and gout and elucidating the associations between AHU, gout and metabolomics, which may aid in performing gout screening.MethodsA total of 300 participants, including 114 healthy controls, 92 patients with AHU, and 94 patients with gout, were analyzed by using a combination of dried blood spot (DBS) sampling and mass spectrometry (MS) technology. Multiple algorithms were applied to characterize altered metabolic profiles in AHU and gout. The mainly altered metabolites were identified by random forest analysis.ResultsThere were significant differences in AHU and gout compared with control group. The altered metabolites were involved in oxidation of fatty acids, carnitine synthesis, urea cycle, and amino acid metabolism in AHU and gout. Random forest classification of 16 metabolites yielded 3 important features to distinguish gout from AHU.ConclusionsDistinct metabolomic signatures were observed in AHU and gout. The selected metabolites may have the potential to improve the early detection of gout.
Acceptance of human papillomavirus vaccination and parents’ willingness to vaccinate their adolescents in Ethiopia: a systematic review and meta-analysis
Authors: Derbie Awoke , Mekonnen Daniel , Misgan Eyaya , Maier Melanie , Woldeamanuel Yimtubezinash , Abebe Tamrat 
Published: October 2023

Abstract
Introduction
Despite the global vaccination campaign to prevent HPV-related morbidity, HPV vaccination uptake remains unacceptably low in the developing world, like Ethiopia. For strong interventional measures, compiled data in the field is required which is otherwise missed in the Ethiopian context. Therefore, this systematic review aimed to provide an estimate of the HPV vaccination uptake, mothers‘ willingness to vaccinate their adolescent girls, and associated factors in Ethiopia.

Methods
Articles were systematically searched using comprehensive search strings from PubMed/Medline, SCOPUS, and grey literature from Google Scholar. Two reviewers assessed study eligibility, extracted data, and assessed the risk of bias independently. Meta-analysis was performed using STATA v 14 to pool the vaccination uptake and mothers‘ willingness toward HPV vaccination in Ethiopia.

Results
We included 10 articles published between 2019 and 2022 covering reports of 3,388 adolescent girls and 2,741 parents. All the included articles had good methodological quality. The pooled estimate of the proportion of good knowledge about HPV vaccination and the agreement of girls to get the vaccine was 60% (95%CI: 59–62) and 65% (95%CI: 64–67), respectively. The pooled estimate of vaccination uptake of at least one dose of HPV vaccine among girls was 55% (95%CI: 53–57). Positive attitudes to the vaccine, higher maternal education, and having knowledge about HPV and its vaccine were reported as statistically significant predictors. On the contrary, not having adequate information about the vaccine and concerns about possible side effects were reported as reasons to reject the vaccine. Likewise, the pooled estimate of mothers who were knowledgeable about HPV vaccination, who had a positive attitude, and willing to vaccinate their children were 38% (95%CI: 36–40) 58% (95%CI: 56–60), and 74% (95%CI: 72–75), respectively.

Conclusions
Knowledge about the HPV vaccine among girls and their vaccination uptake is suboptimal that falls short of the 2030 WHO targets. Therefore, stakeholders need major efforts in rolling out vaccination programs and monitoring their uptake. Social mobilization towards primary prevention of HPV infection should focus on adolescents. The existing strategies need to address the predictors of uptake by educating girls and parents.
Value of 18F-FDG-PET/CT radiomics combined with clinical variables in the differential diagnosis of malignant and benign vertebral compression fractures
Authors: Wang Xun , Zhou Dandan , Kong Yu , Cheng Nan , Gao Ming , Zhang Guqing , Ma Junli , Chen Yueqin , Ge Shuang 
Published: October 2023

Abstract
Background
Vertebral compression fractures (VCFs) are common clinical problems that arise from various reasons. The differential diagnosis of benign and malignant VCFs is challenging. This study was designed to develop and validate a radiomics model to predict benign and malignant VCFs with 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT).

Results
Twenty-six features (9 PET features and 17 CT features) and eight clinical variables (age, SUVmax, SUVpeak, SULmax, SULpeak, osteolytic destruction, fracture line, and appendices/posterior vertebrae involvement) were ultimately selected. The area under the curve (AUCs) of the radiomics and clinical–radiomics models were significantly different from that of the clinical model in both the training group (0.986, 0.987 vs. 0.884, p < 0.05) and test group (0.962, 0.948 vs. 0.858, p < 0.05), while there was no significant difference between the radiomics model and clinical–radiomics model (p > 0.05). The accuracies of the radiomics and clinical–radiomics models were 94.0% and 95.0% in the training group and 93.2% and 93.2% in the test group, respectively. The three models all showed good calibration (Hosmer–Lemeshow test, p > 0.05). According to the decision curve analysis (DCA), the radiomics model and clinical–radiomics model exhibited higher overall net benefit than the clinical model.

Conclusions
The PET/CT-based radiomics and clinical–radiomics models showed good performance in distinguishing between malignant and benign VCFs. The radiomics method may be valuable for treatment decision-making.
Physical layer security analysis of IRS-based downlink and uplink NOMA networks
Authors: Le Si-Phu , Nguyen Hong-Nhu , Nguyen Nhat-Tien , Van Cuu Ho , Le Anh-Tu , Voznak Miroslav 
Published: October 2023

AbstractIn recent years, the development of intelligent reflecting surface (IRS) in wireless communications has enabled control of radio waves to reduce the detrimental impacts of natural wireless propagation. These can achieve significant spectrum and energy efficiency in wireless networks. Non-orthogonal multiple access (NOMA) technology, on the other hand, is predicted to improve the spectrum efficiency of fifth-generation and later wireless networks. Motivated by this reality, we consider the IRS-based NOMA network in the downlink and uplink scenario with a pernicious eavesdropper. Moreover, we investigated the physical layer security (PLS) of the proposed system by invoking the connection outage probability (COP), secrecy outage probability (SOP), and average secrecy rate (ASR) with analytical derivations. The simulation results reveal that (i) it is carried out to validate the analytical formulas, (ii) the number of meta-surfaces in IRS, transmit power at the base station, and power allocation parameters all play an essential role in improving the system performance, and (iii) it demonstrates the superiority of NOMA to the traditional orthogonal multiple access (OMA).
FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma
Authors: Tang Xiaowei , Luo Bei , Huang Shu , Jiang Jiao , Chen Yuan , Ren Wensen , Shi Xiaomin , Zhang Wei , Shi Lei , Zhong Xiaolin , Lü Muhan 
Published: October 2023

Abstract
Background
Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC.

Methods
The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein–protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed.

Results
Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia.

Conclusion
Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.
Gregory P. Thomas and Helen J. Boon: Challenges in science education: global perspectives for the future
Authors: Gusti Utari Akhir , Komariah Mia 
Published: October 2023

AbstractScience education is one of the most important materials that students learn in their lives. Through this subject, they will learn about the phenomena that might be happening on the earth. A book by Gregory P. Thomas and Helen J. Boon with the title Challenges in Science Education: Global Perspectives for The Future delivered everything about how teachers could teach science to students in this century. This book will give the readers knowledge about how science can be taught in many ways and for different purposes. Besides that, this book also gives some ideas about the challenges that might teachers face during the learning process.
Effect of daily stressors and collective efficacy on post-traumatic stress symptoms among internally displaced persons in post-war northern Sri Lanka
Authors: Somasundaram Daya , Jayasuriya Rohan , Perera Ruwanthi , Thamotharampillai Umaharan , Wickremasinghe Rajitha , Tay Alvin Kuowei 
Published: October 2023

Background
Daily stressors have been shown to mediate the relationship of war trauma and trauma-related distress among refugees and internally displaced persons exposed to war and conflict.

Aims
To examine the extent to which the relationship between war-related trauma and mental distress was mediated by daily stressors and collective efficacy among internally displaced communities a decade after exposure to war.

Method
In a cross-sectional study, we recruited a random sample of residents in villages severely affected by conflict in five districts in the Northern Province of Sri Lanka. Measures of war trauma, daily stressors, collective efficacy and post-traumatic stress symptoms (PTSS) were examined. Statistical analyses of the mediating and moderating effects of daily stressors were conducted using regression based methods.

Results
Daily stressors mediated the association of war trauma and PTSS, as both paths of the indirect effect, war trauma to daily stressors and daily stressors to PTSS, were significant. The predictive effect of war trauma on PTSS was positive and significant at moderate and high levels of daily stressors but not at low levels. Higher levels of neighbourhood informal social control, a component of collective efficacy, function as a protective factor to reduce effects of war trauma and daily stressors on mental distress in this population.

Conclusions
Daily stressors are an important mediator in the well-established relationship between war exposure and traumatic stress among internally displaced persons, even a decade after the conflict. Mental health and psychosocial support programmes that aim to address mental distress among war-affected communities could reduce daily stressors and enhance collective efficacy in this context.
Circulating Tumor DNA in Colorectal Cancer Liver Metastasis: Analysis of Patients Receiving Liver Resection and Transplant
Authors: Wehrle Chase J. , Raj Roma , Aykun Nihal , Orabi Danny , Stackhouse Kathryn , Chang Jenny , Estfan Bassam , Kamath Suneel , Krishnamurthi Smitha , Walsh R. Matthew , Kwon David Choon Hyuck , Aucejo Federico 
Published: October 2023

PURPOSE Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool. METHODS Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit. ctDNA was obtained using the Guardant360 platform. Tumor mutational burden (TMB) is defined as the number of identified mutations per megabase of genome analyzed. RESULTS Fifty-two patients had available ctDNA, with 34 (65%) tested preoperatively and 18 (35%) postoperatively; nine patients had sequential pre- and postoperative testing. The median time to test result was 12 days (IQR, 10-13.5). There were a greater number of somatic mutations identified preoperatively (n = 29 v n = 11) and a greater genomic heterogeneity ( P = .0069). The mean TMB score was 12.77 in those without pathologic response to cytotoxic therapy and 6.0 in those with pathologic response ( P = .10). All nine patients with sequential testing were positive preoperatively, compared with just three (33.3%) postoperatively ( P = .0090). Positive postoperative ctDNA was associated with the increased likelihood of disease recurrence after resection (57%) versus negative ctDNA (0%, P = .0419). CONCLUSION Routine ctDNA screening in patients with CCLM is logistically feasible. Liver resection and/or transplant may be associated with clearance of detectable ctDNA and a reduction in TMB or genomic heterogeneity. Persistence of ctDNA alterations postresection appears predictive of disease recurrence. Further studies are necessary to confirm these findings, and longitudinal ctDNA testing is needed to monitor changing tumor biology.