bluuebunny/crossref_metadata_2025_split huggingface dataset:
A microarray data analysis investigating the pathogenesis and potential biomarkers of autophagy and ferroptosis in intervertebral disc degeneration
Authors: Kuang Wenhao , Jiang Cong , Yu Cheng , Hu Jinwei , Duan Yang , Chen Zhong 
Published: January 2023

Background: Intervertebral disc degeneration (IDD) entails complex pathological changes and causes lower back pain (LBP). However, there is still a lack of understanding of the mechanisms involved in IDD, particularly regarding the roles of autophagy and ferroptosis. The current study used microarray data to investigate the pathogenesis of IDD and potential biomarkers related to autophagy and ferroptosis in IDD.Methods: Differentially expressed genes (DEGs) were identified by analyzing the mRNA and miRNA expression profiles of IDD patients from the Gene Expression Omnibus (GEO). The protein-protein interaction network, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were utilized. The Human Autophagy Database (HADb) and Ferroptosis Database were used in conjunction with hub genes to identify autophagy- and ferroptosis-related genes. The Transcription Factor -hub gene-miRNA network was constructed. Lastly, the expression of DEGs in normal and degenerated nucleus pulposus cells (NPCs) was investigated via the quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results: A total of 362 DEGs associated with IDD were identified. GO and KEGG analyses indicated that oxidative stress, extracellular matrix, PI3K-AKT signaling pathway, and ferroptosis were key factors in IDD occurrence. GSEA indicated that IDD was associated with changes in autophagy, iron ion homeostasis, extracellular matrix, and oxidative stress. Eighty-nine hub genes were obtained, including five that were autophagy-related and three that were ferroptosis-related. Of these, TP53 and SESN2 were the intersections of autophagy- and ferroptosis-related genes. In qRT-PCR analysis, CANX, SLC38A1, and TP53 were downregulated in degenerative NPCs, whereas GNAI3, SESN2, and VAMP3 were upregulated.Conclusion: The current study revealed aspects of autophagy- and ferroptosis-related genes involved in IDD pathogenesis, warranting further investigation.
Breast cancer detection: Shallow convolutional neural network against deep convolutional neural networks based approach
Authors: Das Himanish Shekhar , Das Akalpita , Neog Anupal , Mallik Saurav , Bora Kangkana , Zhao Zhongming 
Published: January 2023

Introduction: Of all the cancers that afflict women, breast cancer (BC) has the second-highest mortality rate, and it is also believed to be the primary cause of the high death rate. Breast cancer is the most common cancer that affects women globally. There are two types of breast tumors: benign (less harmful and unlikely to become breast cancer) and malignant (which are very dangerous and might result in aberrant cells that could result in cancer).Methods: To find breast abnormalities like masses and micro-calcifications, competent and educated radiologists often examine mammographic images. This study focuses on computer-aided diagnosis to help radiologists make more precise diagnoses of breast cancer. This study aims to compare and examine the performance of the proposed shallow convolutional neural network architecture having different specifications against pre-trained deep convolutional neural network architectures trained on mammography images. Mammogram images are pre-processed in this study's initial attempt to carry out the automatic identification of BC. Thereafter, three different types of shallow convolutional neural networks with representational differences are then fed with the resulting data. In the second method, transfer learning via fine-tuning is used to feed the same collection of images into pre-trained convolutional neural networks VGG19, ResNet50, MobileNet-v2, Inception-v3, Xception, and Inception-ResNet-v2.Results: In our experiment with two datasets, the accuracy for the CBIS-DDSM and INbreast datasets are 80.4%, 89.2%, and 87.8%, 95.1% respectively.Discussion: It can be concluded from the experimental findings that the deep network-based approach with precise tuning outperforms all other state-of-the-art techniques in experiments on both datasets.
Identification of oncogenes and tumor-suppressor genes with hepatocellular carcinoma: A comprehensive analysis based on TCGA and GEO datasets
Authors: Zhu Yue , Wang Yanfei , Hu Mengyao , Lu Xiaoting , Sun Guoping 
Published: January 2023

Aim: Existing targeted therapies for hepatocellular carcinoma (HCC) are resistant and have limitations. It is crucial to find new HCC-related target genes.Methods: RNA-sequencing data of HCC were gathered from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Initially, differentially expressed genes between normal and tumor tissues were identified from four Gene Expression Omnibus datasets, GSE36376, GSE102079, GSE54236, and GSE45267. GO terms and KEGG pathway enrichment analyses were performed to explore the potential biological functions of differentially expressed genes. A PPI network was constructed by using the STRING database, and up-regulated and down-regulated hub genes were defined through 12 topological approaches. Subsequently, the correlation bounded by up-regulated genes and down-regulated genes in the diagnosis, prognosis, and clinicopathological features of HCC was analyzed. Beyond a shadow of doubt, the key oncogene PBK and tumor suppressor gene F9 were screened out, and the specific mechanism was investigated through GSEA enrichment analysis and immune correlation analysis. The role of PBK in HCC was further verified by western blot, CCK8, transwell, and tube formation experiments.Results:CDCA5, CDC20, PBK, PRC1, TOP2A, and NCAPG are good indicators of HCC diagnosis and prognosis. The low expressions of F9, AFM, and C8B indicate malignant progression and poor prognosis of HCC. PBK was found to be closely related to VEGF, VEGFR, and PDGFR pathways. Experiments showed that PBK promotes HCC cell proliferation, migration, invasion, and tube formation in HUVEC cells. F9 was negatively correlated with the degree of immune infiltration, and low expression of F9 suggested a poor response to immunotherapy.Conclusion: The role of HCC-related oncogenes and tumor-suppressor genes in diagnosis and prognosis was identified. In addition, we have found that PBK may promote tumor proliferation through angiogenesis and F9 may be a predictor of tumor immunotherapy response.
Identification of an unrecognized circRNA associated with development of renal fibrosis
Authors: Zhu Yun , Yan Weimin , Xu Shuangyan , Yu Xiaochao , Sun Shuo , Zhang Shaoxiong , Zhao Ran , Tao Jiayue , Li Yunwei , Li Cuie 
Published: January 2023

Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive.Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly.Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis.Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.
The altered metabolites contributed by dysbiosis of gut microbiota are associated with microbial translocation and immune activation during HIV infection
Authors: Zhang Yu , Xie Zhiman , Zhou Jie , Li Yanjun , Ning Chuanyi , Su Qisi , Ye Li , Ai Sufang , Lai Jingzhen , Pan Peijiang , Liu Ningmei , Liao Yanyan , Su Qijian , Li Zhuoxin , Liang Hao , Cui Ping , Huang Jiegang 
Published: January 2023

BackgroundThe immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported.MethodsWe conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples.ResultsThe pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation.ConclusionsMetabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.
The relevance between hypoxia-dependent spatial transcriptomics and the prognosis and efficacy of immunotherapy in claudin-low breast cancer
Authors: Sun Huizhi , Li Yanlei , Zhang Yanhui , Zhao Xiulan , Dong Xueyi , Guo Yuhong , Mo Jing , Che Na , Ban Xinchao , Li Fan , Bai Xiaoyu , Li Yue , Hao Jihui , Zhang Danfang 
Published: January 2023

IntroductionHypoxia is an important characteristic of solid tumors. However, spatial transcriptomics (ST) of hypoxia-associated heterogeneity is not clear.MethodsThis study integrated Spatial Transcriptomics (ST) with immunofluorescence to demonstrate their spatial distribution in human claudin-low breast cancer MDA-MB-231 engraft. ST spots were clustered with differentially expression genes. The data were combined with hypoxia-specific marker and angiogenesis marker-labeled serial sections to indicate the spatial distribution of hypoxia and hypoxia-inducted transcriptional profile. Moreover, marker genes, cluster-specific hypoxia genes, and their co-essential relationship were identified and mapped in every clusters. The clinicopathological association of marker genes of hypoxia-dependent spatial clusters was explored in 1904 breast cancers from METABRIC database.ResultsThe tumor from center to periphery were enriched into five hypoxia-dependent subgroups with differentially expressed genes, which were matched to necrosis, necrosis periphery, hypoxic tumor, adaptive survival tumor, and invasive tumor, respectively. Different subgroups demonstrated distinct hypoxia condition and spatial heterogeneity in biological behavior and signaling pathways. Cox regression analysis showed that the invasive tumor (cluster 0) and hypoxic tumor (cluster 6) score could be served as independent prognostic factors in claudin-low patients. KM analysis indicated that high invasive tumor (cluster 0) and hypoxic tumor (cluster 6) score was associated with poor prognoses of claudin-low patients. Further analysis showed that hypoxia-induced immune checkpoints, such as CD276 and NRP1, upregulation in invasive tumor to block infiltration and activation of B cells and CD8+ T cells to change tumor immune microenvironment. DiscussionThis study reveals hypoxia-dependent spatial heterogeneity in claudin-low breast cancer and highlights its potential value as a predictive biomarker of clinical outcomes and immunotherapy response. The molecules found in this study also provided potential molecular mechanisms and therapeutic targets for subsequent studies.
Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis
Authors: Zhu Youwen , Liu Kun , Qin Qun , Zhu Hong 
Published: January 2023

IntroductionThe ASTRUM-005 trial (NCT04063163) revealed that combination serplulimab plus chemotherapy (etoposide and carboplatin [EC]) treatment was associated with survival advantages relative to chemotherapy alone in patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC). As these immuno-chemotherapeutic regimens are extremely expensive, however, it is critical that the relative cost-effectiveness of combination serplulimab and chemotherapy treatment as a first-line treatment for ES-SCLC patients be examined in detail.MethodsThe cost-effectiveness of combined serplulimab plus chemotherapeutic treatment was examined using a comprehensive Markov model with a 10-year boundary, enabling the calculation of overall cost, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model instability was interrogated through one-way and probabilistic sensitivity analyses.ResultsSerplulimab plus chemotherapy or chemotherapy alone respectively yielded 1.217 QALYs (2.243 LYs) and 0.885 QALYs (1.661 LYs) with corresponding total costs of $11,202 and $7,194, with an ICER of $12,077 per QALY ($6,883 per LY). This model was most strongly influenced by the utility of progression-free survival. Probabilistic sensitivity analysis showed that serplulimab plus chemotherapy had a 91.6% probability of being cost-effective at a willingness-to-pay (WTP) of $37,653 per QALY (3 × capita gross domestic product of China in 2021). In subgroup analyses, this combination treatment regimen was found to be most cost-effective in patients who were former smokers, had an ECOG performance status of 0, and were diagnosed with brain metastases.ConclusionFrom a payer perspective in China, combination serplulimab plus chemotherapy treatment represents a cost-effective first-line intervention for ES-SCLC patients.
Mannose-modified erythrocyte membrane-encapsulated chitovanic nanoparticles as a DNA vaccine carrier against reticuloendothelial tissue hyperplasia virus
Authors: Feng Yangyang , Tang Feng , Li Sheng , Wu Daiyan , Liu Qianqian , Li Hangyu , Zhang Xinnan , Liu Ziwei , Zhang Linzi , Feng Haibo 
Published: January 2023

IntroductionThe erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs).MethodsIn this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo.ResultsCS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge.ConclusionOverall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects.
A case report of steroid-refractory bullous pemphigoid induced by immune checkpoint inhibitor therapy
Authors: Guan Shasha , Zhang Linlin , Zhang Junyan , Song Wenjing , Zhong Diansheng 
Published: January 2023

The widespread use of immune checkpoint inhibitors in several malignancies has revealed new immune-related adverse events. Bullous pemphigoid (BP) is an antibody-driven autoimmune disease characterized by skin inflammation and fluid-filled bullae. Herein, a 69-year-old man with lung squamous cell carcinoma developed multiple vesicles and tense bullae 3 weeks after the initiation of a programmed death-1 (PD-1) inhibitor, pembrolizumab, and chemotherapy. Biopsy revealed a subepidermal bulla with lymphocytic and eosinophil infiltration, and immunohistochemical studies predominantly showed CD4+ cells, a few CD8+ cells, and the occasional CD20+ lymphocyte. The serum anti-BP180 antibody level, as well as the interleukin-6 and interleukin-10 levels, were elevated compared to the lower levels of tumor necrosis factor-α. Eosinophil levels were high and consistent with the development of blisters. A diagnosis of BP associated with PD-1 inhibitor therapy was made, and the Common Terminology Criteria for Adverse Events classification was grade 3. Immunotherapy was permanently discontinued, and the patient’s bullous lesions failed to react to high-dose systemic corticosteroids combined with minocycline and niacinamide. Intermittent blister recurrence occurred in 2 months, eventually improving with the administration of two courses of intravenous immunoglobulin. At 5 weeks of follow-up, the patient’s tumor was reduced on a computed tomographic scan. Despite stable BP treatment, however, he repeatedly developed complications due to the complexity of his underlying disease and could not be treated with anti-tumor therapy. Early recognition and management of serious immune-related bullous dermatologic toxicity are essential for patient safety.
Comparison of first-line treatments for elderly patients with diffuse large B-cell lymphoma: A systematic review and network meta-analysis
Authors: Wang Yangyang , Ren Xiyang , Huang Keke , Liang Xue , Pu Lianfang , Hu Linhui , Zhai Zhimin 
Published: January 2023

BackgroundThe incidence of DLBCL in elderly patients has been gradually increased. Considering their comorbidities and performance status, the first-line standard treatment hasn’t been determined for the elderly.MethodsWe performed a systemic review and network meta-analysis to compare the efficacy and safety of all eligible regimens as first line treatment for elderly patients with DLBCL. We searched PubMed, Cochrane Library, and Embase Library proceedings up to March 2022.ResultsOur search yielded thirteen trials including 1839 patients. R2CHOP21 showed the best PFS with a statistical difference and the most favorable OS without a statistical difference. RCOMP showed the most clinical benefits in EFS, CR and OR with no significant difference. The point estimate was in favored improved DFS with RCHOP14 than RCHOP21, although this was not statistically significant. In a subgroup analysis concerning 3-4 grade AEs revealed R-COMP was associated with a decrease in grade III/IV neutropenia and cardiac toxic events; RminiCEOP was associated with the lower rates of 3-4 grade anemia, thrombocytopenia and infection; RCHOP21 had the lowest rate of 3-4 grade AE of neurotoxicity.ConclusionThe findings of our meta-analysis indicated that R2CHOP21 provided the best disease control in PFS and represented an optimal first-line treatment option in the elderly with DLBCL. Furthermore, RCOMP, RminiCEOP and RCHOP21 exhibited lower rates in different 3-4 grade AEs and might be reasonable treatment options in the elderly with poor general conditions.
Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19
Authors: Hopkins Francis R. , Govender Melissa , Svanberg Cecilia , Nordgren Johan , Waller Hjalmar , Nilsdotter-Augustinsson Åsa , Henningsson Anna J. , Hagbom Marie , Sjöwall Johanna , Nyström Sofia , Larsson Marie 
Published: January 2023

IntroductionAfter more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.MethodsHere, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.ResultsWe found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.ConclusionBy exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.