bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of propensity score matching to assess the effectiveness of the endometrial receptivity analysis in patients with recurrent implantation failure
Authors: Yu Shuang , Zhang Yongjie , Li Na , Su Zhuolun , Li Wenjing , Lou Hua , Guan Yichun 
Published: January 2025

BackgroundOne potential cause of implantation failure is abnormal endometrial receptivity, and how to objectively evaluate endometrial receptivity has been a matter of great concern. Endometrial receptivity analysis (ERA), a next-generation sequencing-based test that assesses endometrial gene expression, may be valuable in predicting endometrial receptivity, but whether ERA improves pregnancy outcomes in patients with recurrent implantation failure (RIF) is currently controversial. The purpose of this study was to investigate the effect of ERA on pregnancy outcomes in patients with RIF.MethodsWe performed a retrospective cohort study analysis for a population of patients with RIF undergoing frozen embryo transfer (FET) cycles in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2019 to December 2022(n=1598). FET cycles with personalized embryo transfer (PET) under ERA guidance were included in the ERA group (n=43); after using propensity score matching (PSM), a total of 120 FET cycles were included as a control group. Pregnancy outcomes were compared between the two groups. Further, the relationship between the number of previous implant failures and the rate of implant window displacement was discussed. The factors affecting the window of implantation (WOI) displacement were also assessed.ResultsThere was no statistically significant difference in embryo implantation rate, clinical pregnancy rate, spontaneous abortion rate, and live birth rate between the ERA group and the matched control patients (P &gt; 0.05). There was no significant difference in the rate of WOI displacement between patients in the moderate or severe groups (P &gt; 0.05) and no significant difference in pregnancy outcome ( P&gt;0.05). Finally, analysis of the clinical data of patients in the receptive and non-receptive groups did not uncover any factors influencing WOI displacement.ConclusionThe results of the study showed no significant difference in pregnancy outcomes in patients who received ERA compared to those who did not.
A trend of osteocalcin in diabetes mellitus research: bibliometric and visualization analysis
Authors: Liu Zixu , Mao Yuchen , Yang Kangping , Wang Shukai , Zou Fang 
Published: January 2025

BackgroundOsteocalcin has attracted attention for its potential role in diabetes management. However, there has been no bibliometric assessment of scientific progress in this field.MethodsWe analysed 1680 articles retrieved from the Web of Science Core Collection (WoSCC) between 1 January 1986 and 10 May 2024 using various online tools. ResultThese papers accumulated 42,714 citations,with an average of 25.43 citations per paper. Publication output increased sharply from 1991 onwards. The United States and China are at the forefront of this research area.DiscussionThe keywords were grouped into four clusters: ‘Differential and functional osteocalcin genes’, ‘Differential expression of osteocalcin genes in relation to diabetes mellitus’, ‘Role of osteocalcin in the assessment of osteoporosis and diabetes mellitus’, and ‘Indirect involvement of osteocalcin in metabolic processes’. Analysis using the VoS viewer suggests a shift in research focus towards the correlation between osteocalcin levels and diabetic complications, the clinical efficacy of therapeutic agents or vitamins in the treatment of osteoporosis in diabetic patients, and the mechanisms by which osteocalcin modulates insulin action. The proposed focus areas are “osteocalcin genes”, “insulin regulation and osteoporosis “, “different populations”, “diabetes-related complications” and “type 2 diabetes mellitus”,“effect of osteocalcin expression on insulin sensitivity as well as secretion”,“osteocalcin expression in different populations of diabetic patients and treatment-related studies”.
Identification of a pancreatic stellate cell gene signature and lncRNA interactions associated with type 2 diabetes progression
Authors: Qiu Jinjun , Zhu Peng , Shi Xing , Xia Jinquan , Dong Shaowei , Chen Liqun 
Published: January 2025

BackgroundType 2 diabetes (T2D) has become a significant global health threat, yet its precise causes and mechanisms remain unclear. This study aims to identify gene expression patterns specific to T2D pancreatic islet cells and to explore the potential role of pancreatic stellate cells (PSCs) in T2D progression through regulatory networks involving lncRNA-mRNA interactions.MethodsIn this study, we screened for upregulated genes in T2D pancreatic islet samples using bulk sequencing (bulkseq) datasets and mapped these gene expression profiles onto three T2D single-cell RNA sequencing (scRNAseq) datasets. The identified T2D-specific gene features were further validated in an additional T2D scRNAseq dataset, a T1D scRNAseq dataset, and a T2D bulkseq dataset. To investigate regulatory networks, we analyzed the potential lncRNA-mRNA interactions within T2D peripheral blood mononuclear cell (PBMC) bulkseq data.ResultsOur analysis identified a specific gene panel—COL1A2, VCAN, and SULF1—that was consistently upregulated in T2D pancreatic islet samples. Expression of this gene panel was strongly associated with the activation of pancreatic stellate cells (PSCs), suggesting a unique T2D-specific signature characterized by COL1A2hi/VCANhi/SULF1hi PSCs. This signature was exclusive to T2D and was not observed in Type 1 diabetes (T1D) samples, indicating a distinct role for activated PSCs in T2D progression. Furthermore, we identified six long non-coding RNAs (lncRNAs) that potentially interact with the COL1A2hi/VCANhi/SULF1hi PSCs. These lncRNAs were mapped to a lncRNA-mRNA network, suggesting they may modulate immune responses and potentially reshape the immune microenvironment in T2D.DiscussionOur findings highlight the potential immune-regulatory role of PSCs in T2D and suggest that PSC-related lncRNA-mRNA networks could serve as novel therapeutic targets for T2D treatment. This research provides insights into PSCs as a modulator in T2D progression, paving the way for innovative treatment strategies.
Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations
Authors: Tooming M. , Mertsina P. , Kahre T. , Teek R. , Vainumäe I. , Lilles S. , Wojcik M. H. , Ilves P. , Õunap K. 
Published: January 2025

IntroductionPIK3CA related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the PIK3CA gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.MethodsConventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues. In this study, we conducted comprehensive genomic profiling on a cohort of individuals with PRD to address these diagnostic challenges.ResultsOur analysis revealed significant diagnostic challenges posed by somatic mosaicism in PRD. The comprehensive genomic profiling allowed for the meticulous evaluation of potentially pathogenic gene variants in affected individuals and their corresponding tissues.DiscussionOur findings advocate for the adoption of comprehensive genomic profiling in clinical practice to improve the detection and management of PRD. This approach can enhance patient care by providing a more accurate diagnosis and better understanding of the genetic underpinnings of PRD.
Identification and validation of BATF as a prognostic biomarker and regulator of immune cell infiltration in acute myeloid leukemia
Authors: Zhao Zhe , Wang Dongmei , Sheng Xue , Li Shuying , Liu Tingting , Chang Mengyuan , Feng Lei , Zhang Di , Ji Chunyan , Lu Fei , Ye Jingjing 
Published: January 2025

BackgroundBasic leucine zipper ATF-like transcription factor (BATF) is a nuclear basic leucine zipper protein affiliated with the AP-1/ATF superfamily. Previous research has confirmed that BATF expression plays a significant role in the tumour microenvironment. However, the associations between BATF expression and prognoses in acute myeloid leukaemia (AML) patients and their immunological effects remain unclear.MethodsGenomic and clinical AML data were got from the TCGA (TCGA-LAML) and GEO (GSE37642) databases for the subsequent analysis. The expression levels of BATF in AML patients were assessed using GEPIA, and the results were verified by qRT-PCR and Western blotting. In the meantime, the prognostic value of BATF was evaluated using univariate and multivariate analyses, receiver operating characteristic (ROC) curve (AUC) analysis, and Kaplan-Meier (KM) survival analysis. EdU, colony formation, and CCK-8 assays were employed to evaluate the proliferation of cells. Moreover, we detected the association of BATF expression with drug sensitivity through database analysis and in vivo experiments. To further investigate the mechanism of action of BATF in AML, RNA sequencing (RNA-seq) analysis was performed, followed by pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Meanwhile, we detected the connection between BATF expression and the proportions of immune cells via flow cytometry in C1498 mouse model of AML. Finally, we investigated the association between BATF expression and cell-cell communication within the AML cell population using single-cell sequencing.ResultsIn this study, we thoroughly investigated the role of BATF in AML. First, we observed a significant elevation in the expression of BATF in patients and cells in AML. Further analysis revealed an association between high BATF expression and poor prognosis in AML. Additionally, BATF expression was found to promote the proliferative capacity of AML cells. Moreover, the results showed that the expression level of BATF dramatically affected the effect of chemotherapy in AML patients. We also discovered that BATF expression could activate multiple immune-related pathways, altering the proportions of CD8+T cells and NK cells, suggesting that BATF may be a regulator of immune cell infiltration. Finally, there were differences in receptor ligand pairs between AML cells with high and low expression of BATF and immune cells.ConclusionBioinformatics analysis and experimental verification revealed that BATF expression could alter the proportions of CD8+T cells and NK cells in AML and affect drug sensitivity, making it a potential treatment target for AML.
New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
Authors: Liu Lusha , Han Feifei , Du Naiyi , Liu Yakun , Duan Aihong , Kang Shan , Li Bin 
Published: January 2025

BackgroundFerroptosis, a recently discovered iron-dependent cell death, is linked to various diseases but its role in endometriosis is still not fully understood.MethodsIn this study, we integrated microarray data of endometriosis from the GEO database and ferroptosis-related genes (FRGs) from the FerrDb database to further investigate the regulation of ferroptosis in endometriosis and its impact on the immune microenvironment. WGCNA identified ferroptosis-related modules, annotated by GO &amp; KEGG. MNC algorithm pinpointed hub FRGs. Cytoscape construct a ceRNA network, and ROC curves evaluated diagnostic efficacy of hub FRGs. Consensus cluster analysis identified ferroptosis subclusters, and CIBERSORT assessed immune infiltration of these subclusters. Finally, RT-qPCR validated hub FRG expression in clinical tissues.ResultsWe identified two ferroptosis modules of endometriosis, and by enrichment analysis, they are closely linked with autophagy, mTOR, oxidative stress, and FOXO pathways. Furthermore, we identified 10 hub FRGs, and the ROC curve showed better predictive ability for diagnosing. RT-qPCR confirmed that the tissue expression of 10 hub FRGs was mostly consistent with the database results. Subsequently, we developed a ceRNA network based on 4 FRGs (BECN1, OSBPL9, TGFBR1, GSK3B). Next, we identified two ferroptosis subclusters of endometriosis and discovered that they are closely linked with endometriosis stage. Importantly, immune enrichment analysis illustrated that the expression levels of immune cells and immune checkpoint genes were significantly different in the two ferroptosis subclusters. Specifically, the ferroptosis subcluster with stage III-IV of endometriosis is more inclined to the immunosuppressive microenvironment.ConclusionsOur study showed that ferroptosis may jointly promote endometriosis progression by remodeling the immune microenvironment, offering new insights into pathogenesis and therapeutics.
Early transcriptomic changes at the skin interface during Powassan virus transmission by Ixodes scapularis ticks
Authors: Paine Dakota N. , Hermance Meghan , Thangamani Saravanan 
Published: January 2025

IntroductionPowassan virus (POWV), a vector-borne pathogen transmitted by Ixodes ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick feeding and salivary factors modulate the host’s immunological responses, facilitating blood feeding and pathogen transmission. However, the mechanisms of immunomodulation during POWV transmission remain inadequately understood. In this study, we investigated the global cutaneous transcriptomic changes associated with tick bites during POWV transmission.MethodsWe collected skin biopsies from the tick attachment sites at 1, 3, and 6 h after feeding by POWV-infected and uninfected ticks, followed by RNA sequencing of these samples. Differentially expressed genes were analyzed for pathway enrichment using gene ontology and pathway enrichment analyses.ResultsOur findings reveal that tick feeding alone significantly impacts the skin transcriptome within the first 1 to 3 h of tick attachment. Although early POWV transmission induces minimal changes in the local environment, a pronounced shift toward a proinflammatory state is observed 6 h after tick attachment, characterized by neutrophil recruitment and interleukin signaling.DiscussionThese transcriptomic data elucidate the dynamic changes at the tick bite site, transitioning from changes that assist blood meal acquisition to a proinflammatory phase that may facilitate viral dissemination.
Targeted intra-tumoral hyperthermia using uniquely biocompatible gold nanorods induces strong immunogenic cell death in two immunogenically ‘cold’ tumor models
Authors: Kennedy Barry E. , Noftall Erin B. , Dean Cheryl , Roth Alexander , Clark Kate N. , Rowles Darren , Singh Kulbir , Pagliaro Len , Giacomantonio Carman A. 
Published: January 2025

IntroductionHyperthermia is an established adjunct in multimodal cancer treatments, with mechanisms including cell death, immune modulation, and vascular changes. Traditional hyperthermia applications are resource-intensive and often associated with patient morbidity, limiting their clinical accessibility. Gold nanorods (GNRs) offer a precise, minimally invasive alternative by leveraging near-infrared (NIR) light to deliver targeted hyperthermia therapy (THT). THT induces controlled tumor heating, promoting immunogenic cell death (ICD) and modulating the tumor microenvironment (TME) to enhance immune engagement. This study explores the synergistic potential of GNR-mediated THT with immunotherapies in immunogenically ‘cold’ tumors to achieve durable anti-tumor immunity.MethodsGNRs from Sona Nanotech Inc.™ were intratumorally injected and activated using NIR light to induce mild hyperthermia (42–48°C) for 5 minutes. Tumor responses were analyzed for cell death pathways and immune modulation. The immunogenic effects of THT were assessed alone and in combination with intratumoral interleukin-2 (i.t. IL-2) or systemic PD-1 immune checkpoint blockade. Immune cell infiltration, gene expression changes, and tumor growth kinetics were evaluated.ResultsTHT reduced tumor burden through cell death mechanisms, including upregulated ICD marked by calreticulin exposure within 48 hours. By 48 hours, CD45+ immune cell levels were increased, including increased levels of immunosuppressive M2 macrophages. While THT led to innate immune cell stimulations highlighted by gene expression upregulation in the STING cGAS pathway and enhanced M1 and dendritic cell levels, tumor regrowth was observed within six days post-treatment. To enhance THT's immunogenic effects, the therapy was combined with intratumoral interleukin-2 (i.t. IL-2) or systemic PD-1 immune checkpoint blockade. Sequential administration of i.t. IL-2 post-THT induced robust CD8+ T-cell infiltration and led to sustained tumor regression in both treated and distant tumors, accompanied by the emergence of memory T cells. However, IL-2-induced immunosuppressive T-reg populations were also sustained to tumor endpoint suggesting that therapy could be further enhanced. Additionally, PD-1 expression, which was upregulated in CD8+ T cells by THT, was targeted with systemic PD-1 inhibition, further augmenting immune engagement within the TME.DiscussionThese combinatory treatments demonstrated synergistic effects, promoting durable anti-tumor responses and immune memory. Collectively, GNR-mediated THT effectively reduces tumor burden and remodels the TME, potentiating systemic immunity and enhancing the impact of complementary immunotherapies.
Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages
Authors: Ko Tun Kiat , Guo Zexi , Kannan Bavani , Lim Boon Yee , Lee Jing Yi , Li Zhimei , Lee Elizabeth Chun Yong , Teh Bin Tean , Chan Jason Yongsheng 
Published: January 2025

IntroductionRecent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear.MethodsWe examined clinical patterns of angiosarcoma patients (n = 176) seen in an Asiantertiary cancer center from 1999 to 2021, and specifically investigated the molecular and immune features of AS-B in comparison to AS-HN. Data from whole genome sequencing (WGS), NanoString gene expression profiling and 10x Genomics Visium spatial transcriptomics were analyzed.ResultsMajority of cases were AS-HN (n = 104; 59.1%), while AS-B (n = 16, all females) accounted for 9.1% of the cases. The median age at diagnosis was 43 years (range, 26 to 74). Based on WGS, 4 of the 7 AS-B had non-synonymous somatic variants in 47 genes (range, 2 to 28 per case). These genes were functionally annotated and were enriched in cancer-related pathways such as regulation of cell differentiation, VEGFR and receptor tyrosine kinases signaling pathways. By NanoString gene expression profiling, ASB, compared to AS-HN, were enriched for angiogenesis, notch signaling and metastasis-associated matrix remodeling pathways. Additionally, AS-B were enriched for macrophages and CD8+ T cells expression signatures. Similarly, Visium spatial transcriptomics showed that AS-B were enriched for macrophages and T-cells.DiscussionIn conclusion, in our AS-B cases, we observed a convergence of both mutational and expression signatures on angiogenic-related pathways. Thus, anti-angiogenic therapy could be an option to treat AS-B.
Single-cell RNA-seq reveals immune cell heterogeneity and increased Th17 cells in human fibrotic skin diseases
Authors: Deng Cheng-Cheng , Xu Xue-Yan , Zhang Yan , Liu Long-Can , Wang Xuan , Chen Jun-Yi , Yao Liu-Yi , Zhu Ding-Heng , Yang Bin 
Published: January 2025

BackgroundFibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix components. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been used to explore the composition and functionality of immune cells present in fibrotic skin diseases. However, these studies detected the gene expression of all cells in fibrotic skin diseases and did not enrich immune cells. Thus, the precise immune cell atlas in fibrotic skin diseases remains unknown. In this study, we plan to investigate the intricate cellular landscape of immune cells in keloid, a paradigm of fibrotic skin diseases.MethodsCD45+ immune cells were enriched by fluorescence-activated cell sorting. Single-cell RNA sequencing was used to analyze the cellular landscape of immune cells in keloid and normal scar tissues. Ki-67 staining, a scratch experiment, real-time PCR, and Western blotting were used to explore the effect of the Th17 cell supernatant on keloid fibroblasts.ResultsOur findings revealed the intricate cellular landscape of immune cells in fibrotic skin diseases. We found that the percentage of Th17 cells was significantly increased in keloids compared to normal scars. All the subclusters of macrophages and dendritic cells (DCs) showed similar proportions between keloid samples and normal scar samples. However, upregulated genes in keloid M1 macrophages, M2 macrophages, and cDC2 are associated with the MHC class II protein complex assembly and antigen assembly, indicating that macrophages and cDC2 are active in keloids. Functional studies suggested that the supernatant of Th17 cells could promote proliferation, collagen expression, and migration of keloid fibroblasts through interleukin 17A. Importantly, increased Th17 cells are also found in other fibrotic skin diseases, such as hypertrophic scars and scleroderma, suggesting this represents a broad mechanism for skin fibrosis.ConclusionIn summary, we built a single-cell atlas of fibrotic skin diseases in this study. In addition, we explored the function of Th17 cell-fibroblast interaction in skin fibrosis. These findings will help to understand fibrotic skin disease pathogenesis in depth and identify potential targets for fibrotic skin disease treatment.