bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does green finance promote the improvement of regional eco-efficiency? Direct and spillover effects
Authors: Zhang Yuze , Zhang Jisong , Liu Yuqing 
Published: December 2024

IntroductionGreen finance plays a pivotal role in advancing China’s ecological civilization construction and achieving sustainable economic and social development.MethodsUsing panel data from 30 provinces in China from 2009 to 2021, this study applies the entropy weighting method and the super-efficiency slack-based measure (Super-SBM) model to assess the levels of green finance and eco-efficiency in each province. Employing spatial statistical methods such as the spatial standard deviation ellipse (SSDE) and the spatial Markov chain, the study reveals the spatiotemporal evolution characteristics of green finance and eco-efficiency. Additionally, the spatial Durbin model is used to analyze the direct effects, spatial spillover effects, and spatial heterogeneity features of green finance on regional eco-efficiency.ResultsThe results show that (1) From 2009 to 2021, green finance and regional eco-efficiency levels exhibited an overall upward trend, though with notable spatiotemporal differences. (2) The direct and spatial spillover effects of green finance on regional eco-efficiency followed a notable inverted U–shaped relationship. However, in most provinces, green finance levels had not yet reached the turning point during the study period, and the impact of green finance on regional eco-efficiency remained largely positive. (3) The effects of green finance on regional eco-efficiency showed considerable structural differences due to regional heterogeneity, with the strongest effects observed in the Eastern regions.DiscussionThis study provides policymakers with strategies to enhance regional eco-efficiency through the development of green finance, offering valuable insights for promoting ecological civilization construction and achieving sustainable development.
Navigating diversity: primer impact on arthropod recovery in molecular environmental monitoring in tropical Amazon
Authors: Penner Fernanda Valente , Lynggaard Christina , Argolo Leandro Araujo , da Silva Yorranna Kelly Rossy , de Oliveira Guilherme Corrêa , Bohmann Kristine , Gastauer Markus 
Published: December 2024

IntroductionThe urgent need for effective environmental monitoring amid the escalating biodiversity crisis has prompted the adoption of molecular techniques like DNA metabarcoding. Through sequencing of taxonomically informative mitochondrial markers in bulk arthropod samples, metabarcoding allows assessment of arthropod diversity, which is crucial for ecosystem health evaluations, especially in threatened regions like the Amazon. However, challenges such as primer biases and reference database limitations persist. MethodsHere, we assess the performance of four metabarcoding primer sets, two COI markers (ZBJ-ArtF1c/ZBJ-ArtR2c [Zeale]: 157bp, targeting arthropods, and mlCOIintF/jgHCO2198 [Leray]: 313bp, targeting metazoans) and two 16S markers (Ins16S_1shortF/Ins16S_1shortR [Ins16S]: 150bp, targeting insects, and Coleop_16Sc/Coleop_16Sd [EPP]: 105bp, targeting arthropods, mainly Coleoptera) in amplifying the taxonomic constituents of bulk arthropod samples, collected across different natural and anthropogenic habitats from the Brazilian Amazon biome. To evaluate primer performance, we used the indicators (i) amplification efficiency, (ii) primer specificity, i.e., the amount of non-target sequences, (iii) detected OTU richness, (iv) group coverage and (v) taxonomic resolution. Finally, we (vi) estimated the refinement in taxa recovery by additional amplifications. ResultsDespite lower specificity and contrasting results regarding OTU richness, the primer pairs returning larger fragments showed higher taxonomic resolution (Ins16S) and broader taxonomic coverage (Leray) than Zeale and EPP did. Furthermore, results demonstrated the complementarity of the Leray and the Ins16S primer sets from taxon-dependent studies. ConclusionsDespite limitations, combining these primers could enhance biodiversity monitoring in the region. Considering incomplete reference gene banks, primers maximizing OTU richness (EPP and Leray) may be the best choice for taxon-independent surveys. These findings underscore the importance of primer selection and highlight the ongoing efforts to refine DNA metabarcoding for robust environmental assessments.
Real-world efficacy and safety of combined first-line treatment with PARP inhibitors and novel hormonal therapy in mCRPC patients with HRR gene mutations
Authors: Guo Andong , Wu Chenrui , Cao Jishuang , Zhu Kejia , Ding Sentai 
Published: December 2024

ObjectiveThis study evaluated the real-world efficacy and safety of combining PARP inhibitors with novel hormonal therapy (NHT) as a first-line treatment in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations.MethodsWe enrolled 41 mCRPC patients who received at least 1 month of combined treatment with PARP inhibitors and NHT. Patients were divided into two groups: Cohort A (mutations in BRCA1, BRCA2, or ATM genes) and Cohort B (mutations in other HRR genes). The primary endpoint was imaging-based progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), PSA50 response, and adverse events (AEs). To ensure accurate research results and control confounding factors, we will employ multivariate Cox proportional hazards models to evaluate key variables affecting mCRPC patient survival outcomes.ResultsThis study enrolled 41 patients, 22 in Cohort A and 19 in Cohort B. The median PFS for all patients was 21.8 months, and the median OS had yet to be reached. The overall ORR was 48.8%, and the DCR was 61.0%. Specifically, the median PFS for Cohort A was 21.8 months compared to 14.5 months for Cohort B. The median OS had yet to be reached for either cohort. Regarding efficacy, 81.8% of patients in Cohort A and 73.7% in Cohort B achieved a PSA50 response. Imaging assessments showed ORRs of 54.6% for Cohort A and 42.1% for Cohort B, with DCRs of 72.7% and 47.4%, respectively. 85.4% of patients experienced grade 1 or 2 adverse events, and 51.2% encountered grade 3 or 4. In the multivariate Cox regression analysis focusing on PFS, the Gleason score was identified as a significant predictor (HR = 5.8, 95% CI: 1.65–20.2, p = 0.006).ConclusionCombined first-line treatment with PARP inhibitors and NHT is effective and well-tolerated in mCRPC patients with HRR gene mutations, particularly those with BRCA1, BRCA2, or ATM mutations. These findings underscore the potential of this therapeutic combination in managing mCRPC in the Chinese population, suggesting a favorable outcome for those with specific genetic backgrounds.
Preparing patient navigators and assessing the impact of patient navigation in promoting cervical cancer screening uptake, knowledge, awareness, intention, and health beliefs: a protocol for a randomized controlled trial
Authors: Mboineki Joanes Faustine , Chen Changying 
Published: December 2024

AimThere are limited studies in Tanzania concerning the modality of preparing patient navigators and the influence of patient navigation strategies on cervical cancer screening. This protocol describes the preparation of patient navigators and assesses the impact of a patient navigation strategy on promoting cervical cancer screening uptake, knowledge, awareness, intention, and health beliefs.DesignThis is a protocol for a community-based randomized controlled trial.MethodsThe method is categorized into two phases. (1) Preparing patient navigators, which will involve the training of five patient navigators guided by a validated training manual. The training will be conducted over three consecutive days, covering the basic concepts of cervical cancer screening and guiding navigators on how to implement a patient navigation strategy in the communities. (2) Delivering a patient navigation intervention to community women (COMW) which will involve health education, screening appointments, navigation services, and counseling. The study will recruit 202 COMW who will be randomized 1:1 by computer-based blocks to either the patient navigation intervention group or the control group.Public contributionThe study will prove that the trained patient navigators are easily accessible and offer timely and culturally acceptable services to promote cervical cancer screening uptake in communities.
Hypoxia reconstructed colorectal tumor microenvironment weakening anti-tumor immunity: construction of a new prognosis predicting model through transcriptome analysis
Authors: Zhang Ruizhi , Gao Yisong , Li Chong , Tao Ruikang , Mao Gan , Song Tianyu , Nie Wenxiang , Liu Suao , Tao Kaixiong , Li Wei 
Published: December 2024

BackgroundHypoxia in the tumor microenvironment (TME) plays a pivotal role in the progression and prognosis of colorectal cancer (CRC). However, effective methods for assessing TME hypoxia remain lacking. This study aims to develop a novel hypoxia-related prognostic score (HPS) based on hypoxia-associated genes to improve CRC prognostication and inform treatment strategies.MethodsTranscriptomic data from CRC patients were analyzed using Lasso regression to identify hypoxia-associated genes with the strongest prognostic significance. The identified genes were validated in vitro by assessing their expression under normoxic and hypoxic conditions in normal intestinal epithelial cells and CRC tumor cell lines. Functional relevance was explored through differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) network construction. The association of HPS with extracellular matrix (ECM) composition, immune cell infiltration, and immune suppression was also investigated.ResultsSeven hypoxia-associated signature genes were identified, each demonstrating a strong correlation with CRC prognosis. The hypoxia-related prognostic score (HPS), derived from these genes, was significantly linked to changes in the TME. Specifically, HPS values were associated with alterations in ECM composition and distinct immune cell infiltration patterns. Higher HPS values corresponded to increased infiltration of immune-suppressive cells and reduced presence of anti-tumor immune cells. This imbalance promoted an immune-suppressive TME, facilitating tumor progression and immune evasion.ConclusionsThe hypoxia-related prognostic score (HPS) captures the regulatory influence of TME hypoxia on immune responses, offering valuable insights into its role in tumor progression. HPS holds promise as a prognostic tool and a guide for developing personalized treatment strategies in CRC.
Effects of PGK1 on immunoinfiltration by integrated single-cell and bulk RNA-sequencing analysis in sepsis
Authors: Liu Yu , Li Weijie , Lei Lei , Zhou Yaoliang , Huang Mingcheng , Li Yide , Zhang Xiaoying , Jiang Yingyu , Wu Haiqi , Zheng Zhihua , Ma Kongyang , Tang Chun 
Published: December 2024

BackgroundSepsis, a life-threatening organ dysfunction caused by a dysregulated immune response to infection, remains a significant global health challenge. Phosphoglycerate kinase 1 (PGK1) has been implicated in regulating inflammation and immune cell infiltration in inflammatory conditions. However, the role of PGK1 in sepsis remains largely unexplored.MethodsFour microarray datasets and a high throughput sequencing dataset were acquired from GEO database to reveal the PGK1 expression in patients of sepsis. Quantitative real-time PCR and western blotting was then used to validate the PGK1 level. Additionally, microarray and single-cell RNA sequencing data integration, including gene set enrichment analysis (GSEA), KEGG and GO functional enrichment analysis, immune infiltration analysis, and single-cell sequencing analysis, were performed to elucidate the role of PGK1 in sepsis.ResultsOur results revealed a significant upregulation of PGK1 in sepsis patients, with the area under the ROC curve (AUC) exceeding 0.9 across multiple datasets, indicating PGK1’s strong potential as a diagnostic biomarker. Notably, PGK1 was enriched in key immune-related pathways, including the TNF signaling pathways, and leukocyte transendothelial migration, suggesting its involvement in immune regulation. Furthermore, PGK1 expression showed a positive correlation with the levels of inflammatory mediators CXCL1, CXCL16, and the chemokine receptor CCR1. In terms of immune cell infiltration, PGK1 was positively correlated with naive B cells, resting memory CD4 T cell, gamma delta T cells, M0 macrophages, eosinophils and negatively correlated with plasma cells, CD8 T cells, activated memory CD4 T cell, Tregs, activated dendritic cells.ConclusionsThis study concluded that PGK1 served as a novel diagnostic biomarker for sepsis, with potential implications for prognosis and immune regulation. The significant upregulation of PGK1 in sepsis patients and its association with immune-related pathways and cell types highlight its potential role in the pathogenesis of sepsis.
Mid-term follow-up results of neoadjuvant sintilimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma
Authors: Cai Haibo , Chen Liji , Huang Junjun , Ma Hongmei , Zhang Shifa , Zhong Kaize , Yang Dongbao , Sun Jiuhe , Liu Hongfeng , Song Ru 
Published: December 2024

BackgroundThe study was conducted in order to investigate whether neoadjuvant immunotherapy combined with chemotherapy can bring survival benefits to patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) in the real world.MethodsWe retrospectively analysed patients with locally advanced resectable ESCC who underwent surgery at the Jining First People’s Hospital from April 2020 to April 2022. Based on their medical history, the enrolled patients were divided into a neoadjuvant immunochemotherapy plus surgery group (nICT group) and a surgery-only group (S group). Primary endpoints were the two-year overall survival (OS) and disease-free survival (DFS) rates. Secondary endpoints were the safety and efficacy of neoadjuvant immunochemotherapy for patients with locally advanced esophageal cancer, and compared the surgery and postoperative outcomes between the two groups.ResultsA total of 47 patients in the nICT group and 73 patients in the S group were included for further analysis, the stage of the nICT group was more advanced than that of the S group. In the group nICT, 8 patients (17%) achieved the complete pathological response (pCR), 29 patients (61.7%) achieved major pathological response (MPR), including 6 patients (12.8%) with a primary tumor achieving pCR but had residual tumor cells in the lymph nodes (pT0N+), and the treatment-related AES was manageable. The surgery and postoperative outcomes were comparable in both groups. The two-year OS and DFS rates for the nICT group were 91.5% and 85.5% respectively, while those for the S group were 71.2% and 68.5%, and Kaplan–Meier survival analysis and log-rank test revealed significant differences in DFS and OS between the two groups. Patients who achieved MPR in the nICT group showed better DFS and OS, while the Three-cycle subgroup did not exhibit any survival benefit compared to the Two-cycle subgroup.ConclusionsNeoadjuvant sintilimab combined with chemotherapy has promising efficacy and safety in the treatment of locally advanced resectable ESCC. The treatment modality has the potential to become a standard therapy for locally advanced resectable ESCC.
The pan-cancer landscape of aldo-keto reductase1B10 reveals that its expression is diminished in gastric cancer
Authors: Wu Anqi , Li Hao , Gao Mengnan , Liang Juan , Huang Jiaqi , Farrés Jaume , Cao Deliang , Li Guoqing 
Published: December 2024

IntroductionAldo-keto reductase 1B10 (AKR1B10) is a multifunctional enzyme, which is important in cancer development and progression, but the landscape of AKR1B10 in pan-cancers and in tumor microenvironment is unclear.MethodThis study integrated the sequencing data of 33 cancer types, including gastric cancer, from TCGA project to explored the expression pattern and genetic and epigenetic alterations of AKR1B10. The association of AKR1B10 expression with clinical progression of cancers was evaluated by Kaplan-Meier analysis; the potential role of AKR1B10 in tumor microenvironment (TME) and immune-related gene expression were analyzed by PURITY, ESTIMATE, TIMER and CIBERSORT algorithms. The expression of AKR1B10 and immune cell markers in gastric cancer were evaluated with multiplex immunofluorescence staining.ResultResults indicated that AKR1B10 was highly expressed in the gastrointestinal tract in health donors, but the expression of AKR1B10 was significantly changed in most of cancer types, which may be ascribed to DNA methylation in its promoter. The AKR1B10 expression in cancers and its value in disease progression was bidirectional and functionally enriched in metabolism in pan-cancers. In tumor microenvironment, AKR1B10 was significantly correlated with immune cell infiltrations and immune gene expression. In the stomach, along with the diminishing of AKR1B10 expression, CD68+ macrophage increased and CD19+ B cell decreased in gastric cancer.DiscussionThese data indicates that AKR1B10 may be an important factor in the development and progression and a potential therapeutic target for multiple cancers, but plays as a protector in the gastric tissues.
Cytokine profiling reveals HLA-linked Th2 and Th17 driven immune activation in pemphigus vulgaris patients and genetically susceptible healthy controls
Authors: Schwartz Rebekah R. , Seiffert-Sinha Kristina , Sinha Animesh A. 
Published: December 2024

IntroductionCytokines and chemokines direct the inflammatory response and may serve as markers of immune dysregulation in Pemphigus vulgaris (PV), an autoimmune blistering skin disorder. Previous studies on limited numbers of patients and cytokine profiles in PV have produced equivocal results regarding the role these mediators play in disease.MethodsIn this study, we interrogated serum samples from 116 PV patients and 29 healthy controls by multiplexed bead array assays across a comprehensive set of cytokines and chemokines covering several functional categories, including IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IL-21, IL-22, IL-23, TNFα, IFNγ, MCP-1, and Eotaxin.ResultsWe found that patients with PV generally display an activated cytokine and chemokine immune response compared to controls, but also show remarkable interindividual heterogeneity in terms of cytokine levels, with a limited activation of different T helper cell pathways in different patients. Surprisingly, we also found that healthy individuals that carry the PV susceptibility alleles HLA DR4 (DRB1*0402) and/or DR6 (DQB1*0503) (HLA-matched controls) show an upregulation of cytokine and chemokine levels that are on par with those seen in PV patients for certain pro-inflammatory, Th2, and Th17 mediators and IL-8, while healthy controls that did not carry the PV susceptibility alleles (HLA-unmatched controls) express significantly lower levels of these cytokines and chemokines.DiscussionOur data suggest the existence of a limited immune activation linked to the presence of key PV associated HLA alleles regardless of disease status. Interestingly, the cytokines IL-10 and IL-15 were found to be significantly downregulated in the HLA-matched control group, suggesting the presence of a possible counter-regulatory function in genetically susceptible but disease-free individuals.
Integrative multi-omics analysis reveals a novel subtype of hepatocellular carcinoma with biological and clinical relevance
Authors: Li Shizhou , Lin Yan , Gao Xing , Zeng Dandan , Cen Weijie , Su Yuejiao , Su Jingting , Zeng Can , Huang Zhenbo , Zeng Haoyu , Huang Shilin , Tang Minchao , Li Xiaoqing , Luo Min , Huang Zhihu , Liang Rong , Ye Jiazhou 
Published: December 2024

BackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and the development of accurate predictive models for prognosis and drug sensitivity remains challenging.MethodsWe integrated laboratory data and public cohorts to conduct a multi-omics analysis of HCC, which included bulk RNA sequencing, proteomic analysis, single-cell RNA sequencing (scRNA-seq), spatial transcriptomics sequencing (ST-seq), and genome sequencing. We constructed a tumor purity (TP) and tumor microenvironment (TME) prognostic risk model. Proteomic analysis validated the TP-TME-related signatures. Joint analysis of scRNA-seq and ST-seq revealed characteristic clusters associated with TP high-risk subtypes, and immunohistochemistry confirmed the expression of key genes. We conducted functional enrichment analysis, transcription factor activity inference, cell-cell interaction, drug efficacy analysis, and mutation information analysis to identify a novel subtype of HCC.ResultsOur analyses constructed a robust HCC prognostic risk prediction model. The patients with TP-TME high-risk subtypes predominantly exhibit hypoxia and activation of the Wnt/beta-catenin, Notch, and TGF-beta signaling pathways. Furthermore, we identified a novel subtype, XPO1+Epithelial. This subtype expresses signatures of the TP risk subtype and aligns with the biological behavior of high-risk patients. Additional analyses revealed that XPO1+Epithelial is influenced primarily by fibroblasts via ligand-receptor interactions, such as FN1-(ITGAV+ITGB1), and constitute a significant component of the TP-TME subtype. Moreover, XPO1+Epithelial interact with monocytes/macrophages, T/NK cells, and endothelial cells through ligand-receptor pairs, including MIF-(CD74+CXCR4), MIF-(CD74+CD44), and VEGFA-VEGFR1R2, respectively, thereby promoting the recruitment of immune-suppressive cells and angiogenesis. The ST-seq cohort treated with Tyrosine Kinase Inhibitors (TKIs) and Programmed Cell Death Protein 1 (PD-1) presented elevated levels of TP and TME risk subtype signature genes, as well as XPO1+Epithelial, T-cell, and endothelial cell infiltration in the treatment response group. Drug sensitivity analyses indicated that TP-TME high-risk subtypes, including sorafenib and pembrolizumab, were associated with sensitivity to multiple drugs. Further exploratory analyses revealed that CTLA4, PDCD1, and the cancer antigens MSLN, MUC1, EPCAM, and PROM1 presented significantly increase expression levels in the high-risk subtype group.ConclusionsThis study constructed a robust prognostic model for HCC and identified novel subgroups at the single-cell level, potentially assisting in the assessment of prognostic risk for HCC patients and facilitating personalized drug therapy.