bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the pathogenesis, biomarkers, and potential drugs for type 2 diabetes mellitus and acute pancreatitis through a comprehensive bioinformatic analysis
Authors: Zhong Lei , Yang Xi , Shang Yuxuan , Yang Yao , Li Junchen , Liu Shuo , Zhang Yunshu , Liu Jifeng , Jiang Xingchi 
Published: November 2024

BackgroundType 2 diabetes mellitus (T2DM) is a chronic metabolic disease that accounts for &gt; 90% of all diabetes cases. Acute pancreatitis (AP) can be triggered by various factors and is a potentially life-threatening condition. Although T2DM has been shown to have a close relationship with AP, the common mechanisms underlying the two conditions remain unclear.MethodsWe identified common differentially expressed genes (DEGs) in T2DM and AP and used functional enrichment analysis and Mendelian randomization to understand the underlying mechanisms. Subsequently, we used several machine learning algorithms to identify candidate biomarkers and construct a diagnostic nomogram for T2DM and AP. The diagnostic performance of the model was evaluated using ROC, calibration, and DCA curves. Furthermore, we investigated the potential roles of core genes in T2DM and AP using GSEA, xCell, and single-cell atlas and by constructing a ceRNA network. Finally, we identified potential small-molecule compounds with therapeutic effects on T2DM and AP using the CMap database and molecular docking.ResultsA total of 26 DEGs, with 14 upregulated and 12 downregulated genes, were common between T2DM and AP. According to functional and DisGeNET enrichment analysis, these DEGs were mainly enriched in immune effector processes, blood vessel development, dyslipidemia, and hyperlipidemia. Mendelian randomization analyses further suggested that lipids may be a potential link between AP and T2DM. Machine learning algorithms revealed ARHGEF9 and SLPI as common genes associated with the two diseases. ROC, calibration, and DCA curves showed that the two-gene model had good diagnostic efficacy. Additionally, the two genes were found to be closely associated with immune cell infiltration. Finally, imatinib was identified as a potential compound for the treatment of T2DM and AP.ConclusionThis study suggests that abnormal lipid metabolism is a potential crosstalk mechanism between T2DM and AP. In addition, we established a two-gene model for the clinical diagnosis of T2DM and AP and identified imatinib as a potential therapeutic agent for both diseases.
Transcriptome combined with Mendelian randomization to screen key genes associated with mitochondrial and programmed cell death causally associated with diabetic retinopathy
Authors: Jiang Shule , Han Xuemei 
Published: November 2024

BackgroundMitochondrial dysfunction in the retina can induce apoptosis of retinal capillary cells, leading to diabetic retinopathy (DR). This study aimed to explore key genes related to programmed cell death (PCD) and mitochondria in DR via bioinformatic analysis.MethodsA differential analysis was performed to identify differentially expressed genes (DEGs) between DR and control samples using the GSE94019 dataset from the Gene Expression Omnibus (GEO) database. Pearson correlation analysis was then utilized to select genes linked to mitochondrial function and PCD (M-PCD). Candidate genes were identified by overlapping DR-DEGs and M-PCD genes, followed by functional annotation. Mendelian randomization (MR) analysis was employed to identify genes with causal relationships to DR. Key genes were identified through protein-protein interaction (PPI) analysis using six algorithms (DEgree, DMNC, EPC, MCC, Genes are BottleNeck, and MNC) within Cytoscape software. The expression patterns of these genes were validated using GSE94019 and GSE60436 datasets, as well as RT-qPCR. Enrichment analysis provided insights into the function and pathways of these key genes in DR. Differential immune cell profiles were determined via immune infiltration analysis, followed by exploring the relationships between immune cells, cytokines, and the identified genes. Correlations between key genes and apoptosis genes were also examined. In vivo experiments using RT-PCR, immunohistochemistry (IHC), and western blot analysis confirmed that MYC and SLC7A11 expression was significantly elevated in DR rat retinal tissues.ResultsFrom 658 candidate genes, 12 showed significant causal associations with DR. MYC and SLC7A11 were particularly notable, showing upregulated expression in DR samples and involvement in apoptosis and diabetes-related pathways. These genes were significantly associated with apoptotic genes and correlated positively with altered immune cell types and cytokines, suggesting a link between immune response and DR pathogenesis. In vivo findings confirmed that MYC and SLC7A11 expression was elevated in DR rat retinal tissues.ConclusionKey genes (MYC and SLC7A11) associated with mitochondrial function and PCD in DR were identified, offering insights into DR’s pathological mechanisms and potential targets for diagnostic and therapeutic strategies.
Factors related to type 2 diabetic retinopathy and their clinical application value
Authors: Lian Xue-Nan , Zhu Ming-Ming 
Published: November 2024

ObjectiveTo compare the differences in clinical-related factors between patients with type 2 diabetes (T2DM) and those without diabetic retinopathy (DR) and to explore the risk factors or protective factors affecting DR in T2DM patients.MethodsWe performed a retrospective analysis of 380 patients with type 2 diabetes admitted to Handan Central Hospital from June 2023 to May 2024. Clinical data collected included baseline characteristics, hematological tests, metabolic indicators, and information on diabetic complications and comorbidities.ResultsOur findings identified intervention, neck vascular disease, bilateral lower limb venous thrombosis, high creatinine, high glomerular filtration rate, high chloride, high fasting C-peptide, and high lactate dehydrogenase as risk factors for DR. In contrast, High 2-hour postprandial C-peptide is a protective factor for diabetic retinopathy. A logistic regression model was constructed using stepwise regression to predict DR occurrence, achieving an accuracy of 0.80 and an AUC of 0.83.
Case report: A case of holocarboxylase synthetase deficiency with respiratory tract as the initial symptom
Authors: Zou Haiying , Yang Li , Zhang Renlong , Qin Yao 
Published: November 2024

IntroductionHolocarboxylase synthetase deficiency (HLCSD) is a rare autosomal recessive genetic disorder caused by mutations in the holocarboxylase synthetase (HLCS) gene, which affects multiple systems. Common clinical manifestations include metabolic acidosis, rash, feeding difficulties, and growth retardation, with predominant involvement of the nervous system, skin, and hair. However, respiratory symptoms as the initial manifestation are relatively rare.Case PresentationWe report the case of a 1 year and 4-month-old Chinese male patient who presented with a 2-day history of cough, followed by half a day of wheezing and shortness of breath. Despite supportive treatment with antibiotics upon admission, the infant continued to experience rapid and deep breathing accompanied by groaning, and obvious wheezing. Blood gas analysis revealed metabolic acidosis that was difficult to correct. Blood tandem mass spectrometry showed elevations in C50H, C3, C4OH, and urine organic acid analysis revealed elevations in lactate, 3-hydroxybutyric acid, 3-hydroxyisovaleric acid, acetoacetic acid, 3-methylcrotonylglycine, and methylcitric acid. Genetic testing revealed two variants in the HLCS gene in the infant: NM_001352514: exon6: c.1088T&gt;A: p.V363D variant and exon11: c.2434C&gt;T: p.R812* heterozygous variant, resulting in HLCSD. Ultimately, the diagnosis of HLCSD was established, and oral biotin treatment achieved good clinical efficacy.ConclusionThis article summarizes the clinical data of a case of HLCSD in an infant, primarily presenting with respiratory symptoms. It provides a comprehensive summary of the etiology, diagnosis, and treatment, offering insights for the diagnosis of rare diseases by clinical physicians.
Comparative study of the three-dimensional genomes of granulosa cells in germinal vesicle and metaphase II follicles
Authors: Mao Rurong , Cai Zhongkun , Wang Tao , Li Yan , Tian Shilin , Li Diyan , Li Penghao 
Published: November 2024

IntroductionFollicle development is a critical process in the female reproductive system, with significant implications for fertility and reproductive health. Germinal vesicle (GV) oocytes are primary oocytes that are arrested in the dictyate stage, also known as the diplotene stage of meiotic prophase I. Metaphase II (MII) is the stage at which the oocyte is typically retrieved for assisted reproductive technologies such as in vitro fertilization (IVF). The granulosa cells play a pivotal role in follicle development processes. 3D chromatin organization is a fundamental aspect of cellular biology that has significant implications for gene regulation and cellular function.MethodsIn this study, we investigated 3D chromatin organization in granulosacells from GV and MII follicles, which is essential for understanding the regulatory mechanisms governing oocyte development.ResultsThe results revealed distinct compartmentalization patterns,including stable genomic regions and transitions during oocyte maturation. Notably, there was a significant shift in functional gene activation, particularly in processes related to hormone metabolic pathways. Furthermore, alterations in topologically associating domains (TADs) were observed, with differential expression observed in genes that are involved in crucial biological processes. The analysis also identified a subset of genes with altered promoter-enhancer interactions (PEIs), reflecting a regulatory shift in gene expression related to reproductive processes.DiscussionThese findings provide valuable insights into 3D genome organization in granulosa cells with implications for reproductive health and the development of assisted reproductive technologies. Understanding spatial genome organization at different stages of follicular development may help realize novel strategies for enhancing success rates in assisted reproductive technologies.
COVID-19 mitigates the response to TKIs in patients with CML via the inhibition of T-cell immunity
Authors: He Na , Li Guosheng , Liu Jinting , Liu Wancheng , Tian Ruifeng , Ma Daoxin 
Published: November 2024

IntroductionChronic myeloid leukemia (CML) is a severe hematological malignancy characterized by BCR-ABL fusion gene. The advent of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL has improved the landscape of CML treatment dramatically. The occurrence of coronavirus disease 2019 (COVID-19) has challenged many cancers. However, its effect on TKI therapy of CML remains unknown.MethodsIn this study, we collected peripheral blood from chronic phase CML patients treated with TKIs at low-level BCR-ABL P210 during COVID-19 pandemic, and determined the alterations of BCR-ABL P210 by applying the well-established BCR-ABL P210 detection system.ResultsOur results showed that the level of BCR-ABL P210 of CML patients was significantly elevated shortly after contracting COVID-19, and then recovered to pre-infection level within one month. The elevated degree of P210 was positively correlated with the duration of COVID-19. And the level of P210 was elevated in CML patients that took COVID-19 vaccination. Furthermore, lymphocyte subsets and cytokine detections were performed by flow cytometry to analyze the alteration of immune responses. Our results showed that effector CD8+ T (Teff) cells were significantly downregulated while naïve CD8+ T cells or Treg cells were obviously upregulated in P210-elevated CML patients after contracting COVID-19 compared to that in P210-unchanged or decreased CML patients. Moreover, the SARS-CoV-2 pseudovirus was constructed to further determine its effects. The results showed that the level of BCR-ABL P210 was upregulated upon transfection of SARS-CoV-2 pseudovirus into blood samples of CML patients.DiscussionOur results demonstrate that COVID-19 suppresses the immune activity and consequentially elevates the level of BCR-ABL P210 of CML patients.
Integrated single-cell and bulk RNA sequencing reveals immune-related SPP1+ macrophages as a potential strategy for predicting the prognosis and treatment of liver fibrosis and hepatocellular carcinoma
Authors: Li Bangjie , Hu Jialiang , Xu Hanmei 
Published: November 2024

BackgroundLiver fibrosis is a pathological response to liver damage induced by multiple etiologies including NASH and CCl4, which may further lead to cirrhosis and hepatocellular carcinoma (HCC). Despite the increasing understanding of liver fibrosis and HCC, clinical prognosis and targeted therapy remain challenging.MethodsThis study integrated single-cell sequencing analysis, bulk sequencing analysis, and mouse models to identify highly expressed genes, cell subsets, and signaling pathways associated with liver fibrosis and HCC. Clinical prediction models and prognostic genes were established and verified through machine learning, survival analysis, as well as the utilization of clinical data and tissue samples from HCC patients. The expression heterogeneity of the core prognostic gene, along with its correlation with the tumor microenvironment and prognostic outcomes, was analyzed through single-cell analysis and immune infiltration analysis. In addition, the cAMP database and molecular docking techniques were employed to screen potential small molecule drugs for the treatment of liver fibrosis and HCC.ResultWe identified 40 pathogenic genes, 15 critical cell subsets (especially Macrophages), and regulatory signaling pathways related to cell adhesion and the actin cytoskeleton that promote the development of liver fibrosis and HCC. In addition, 7 specific prognostic genes (CCR7, COL3A1, FMNL2, HP, PFN1, SPP1 and TENM4) were identified and evaluated, and expression heterogeneity of core gene SPP1 and its positive correlation with immune infiltration and prognostic development were interpreted. Moreover, 6 potential small molecule drugs for the treatment of liver fibrosis and HCC were provided.ConclusionThe comprehensive investigation, based on a bioinformatics and mouse model strategy, may identify pathogenic genes, cell subsets, regulatory mechanisms, prognostic genes, and potential small molecule drugs, thereby providing valuable insights into the clinical prognosis and targeted treatment of liver fibrosis and HCC.
Associations between human milk EV-miRNAs and oligosaccharide concentrations in human milk
Authors: Holzhausen Elizabeth A. , Patterson William B. , Wong Benjamin H. , Kim Sewan , Kupsco Allison , Howe Caitlin G. , Bode Lars , Goran Michael I. , Alderete Tanya L. 
Published: November 2024

IntroductionHuman milk contains human milk oligosaccharides (HMOs) and microRNAs (miRNAs), which are key bioactive components. HMOs are indigestible carbohydrates that impact infant growth and development. miRNAs are small, non-coding RNAs that regulate post-transcriptional gene expression. miRNAs are abundant in human milk and can be contained in extracellular vesicles (EVs). There is evidence that miRNAs are synthesized in the mammary epithelium and may influence mammary gland development and milk synthesis. However, the relationships between miRNAs and HMOs have yet to be fully characterized.MethodsThis study examined the associations between 210 human milk EV-miRNAs and 19 HMOs in a cohort of 98 Latina mothers. HMO measures included summary measures and concentrations of 19 HMOs. Relationships between EV-miRNAs and HMOs were examined using principal components analysis and associations between individual EV-miRNAs and HMOs were assessed.ResultsOverall patterns of EV-miRNA levels, summarized using principal components, were associated with HMO summary measures and concentrations. Levels of individual EV-miRNAs were associated with HMO summary measures and individual concentrations of 2’FL, 3FL, 3’SL, 6’SL, FLNH, LNFP I, and LNH.DiscussionResults from this study suggest that human milk EV-miRNAs are associated with the concentration of HMOs, which may have important effects on infant growth and development.
Single-cell RNA sequencing reveals key molecular drivers and immune landscape in uveal melanoma: implications for targeted therapy and prognostic modeling
Authors: Song Zeyu , Shao Wenwen , Xiahou Zhikai , Xu Yue , Zhang Xiaofeng 
Published: November 2024

BackgroundUveal melanoma (UM), arising from melanocytes in the choroid, accounts for 3% to 5% of all melanocytic tumors and over 70% of intraocular malignancies. Despite effective local treatments, metastasis remains a significant challenge, with more than half of patients developing metastatic disease within ten years. Conventional therapies often yield poor outcomes, highlighting the urgent need for novel therapeutic strategies to enhance survival and prognosis for UM patients.MethodsWe conducted a detailed analysis of the GSE139829 dataset, focusing on scRNA-seq data from eight primary UM patients and three with metastatic disease. Through clustering and marker gene expression analyses, we identified distinct subtypes of UM tumor cells and examined their transcriptional, metabolic, and intercellular communication profiles. We developed a novel prognostic model, PCOLCE TCs Risk Score (PTRS), centered on the C5 PCOLCE+ tumor cells, which was validated through in vitro functional assays. Additionally, we performed immune infiltration and metabolic pathway analyses to elucidate tumor-immune interactions and their clinical significance.ResultsWe identified eight distinct cell types in UM and classified tumor subpopulations into six subgroups. The C5 PCOLCE+ TCs subpopulation was highlighted as crucial in UM malignancy, demonstrating high differentiation potential and a significant role in tumor progression. CellChat analysis revealed substantial communication between C5 PCOLCE+ TCs and fibroblasts, suggesting their involvement in tumor growth and extracellular matrix remodeling. Metabolic pathway analysis indicated enhanced oxidative phosphorylation and glutathione metabolism in this subpopulation. Additionally, we developed a PTRS model based on C5 PCOLCE+ TCs, identifying CITED1 as a high-risk gene that promotes UM cell proliferation, invasion, and migration in vitro.ConclusionThis study provides insights into UM metastasis via single-cell analysis, identifying C5 PCOLCE+ TCs as key malignancy drivers associated with oxidative phosphorylation and immune interactions. Our PTRS model highlights CITED1 as a high-risk gene that promotes UM cell proliferation, paving the way for new prognostic models and therapeutic targets to enhance patient outcomes.
Near-inertial ocean response to a typhoon on a continental slope in the Northern South China Sea
Authors: Zhang Han , Wu Renhao , Liu Fu , Ni Xiaobo , Tian Di 
Published: November 2024

Typhoons are strong natural events that significantly influence the marine environment. In 2018, Typhoon Mangkhut traveled over a moored station with a depth ~1900 m on continental slope in the northern South China Sea, the near-inertial oceanic responses are studied based on the Regional Ocean Modeling System (ROMS) model simulation combined with observation data. Near-inertial currents after Mangkhut can be divided into three layers: near-circular polarized in upper ocean, across-slope polarized in deep ocean and along-slope polarized near the bottom, thickness of the three layers depend on the slope steepness. According to across-slope and along-slope intensified currents, the near-bottom vertical velocities and near-inertial energy were intensified at the moored station. The across-slope forth/back near-inertial flows brought cold/warm and salty/fresh water from deeper/shallower depth, increased vertical excursions of near-bottom temperature/salinity isolines and near-inertial available potential energy. The near-inertial barotropic across-slope currents were much greater than along-slope currents, with net cooling and salinity increase of the whole water column at the moored station. The core responses to Mangkhut were within 100 km around the station. The near-inertial kinetic energy generated both at sea surface and bottom slope, then propagated vertically into ocean interior and horizontally into the South China Sea basin as well as some topography-trapped waves propagated along the slope. This work enriches the understanding of air–sea interactions in coastal regions and the effect of ocean topography, especially after a typhoon.
Diagnostic test accuracy of cellular analysis of bronchoalveolar lavage fluid in distinguishing pulmonary infectious and non-infectious diseases in patients with pulmonary shadow
Authors: Li Jiyang , Wang Ting , Liu Faming , Wang Juan , Qiu Xiaojian , Zhang Jie 
Published: November 2024

PurposeThis study aims to assess the diagnostic accuracy of cellular analysis of bronchoalveolar lavage fluid (BALF) in distinguishing between pulmonary infectious and non-infectious diseases in patients with pulmonary shadows. Additionally, it will develop and validate a novel scoring system based on a nomogram for the purpose of differential diagnosis.MethodsA retrospective analysis was conducted involving data from 222 patients with pulmonary shadows, whose etiological factors were determined at our institution. The cohort was randomly allocated into a training set comprising 155 patients and a validation set of 67 patients, (ratio of 7:3), the least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. The receiver operating characteristic curve (ROC) and calibration curve were utilized to assess the prediction accuracy of the model. Decision curve analysis (DCA) and clinical impact curve (CIC) were employed to evaluate the clinical applicability of the model. Moreover, model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the risk factors.ResultsAmong the relevant predictors, the percentage of neutrophils in BALF (BALF NP) exhibited the most substantial differentiation, as evidenced by the largest area under the ROC curve (AUC = 0.783, 95% CI: 0.713–0.854). A BALF NP threshold of ≥16% yielded a sensitivity of 72%, specificity of 70%, a positive likelihood ratio of 2.07, and a negative likelihood ratio of 0.38. LASSO and multivariate regression analyses indicated that BALF NP (p &lt; 0.001, OR = 1.04, 95% CI: 1.02–1.06) and procalcitonin (p &lt; 0.021, OR = 52.60, 95% CI: 1.83–1510.06) serve as independent predictors of pulmonary infection. The AUCs for the training and validation sets were determined to be 0.853 (95% CI: 0.806–0.918) and 0.801 (95% CI: 0.697–0.904), respectively, with calibration curves demonstrating strong concordance. The DCA and CIC analyses indicated that the nomogram model possesses commendable clinical applicability. In models comparison, ROC analyses revealed that the nomogram exhibited superior discriminatory accuracy compared to alternative models, with DCA further identifying the nomogram as offering the highest net benefits across a broad spectrum of threshold probabilities.ConclusionBALF NP ≥16% serves as an effective discriminator between pulmonary infectious and non-infectious diseases in patients with pulmonary shadows. We have developed a nomogram model incorporating BALF NP and procalcitonin (PCT), which has proven to be a valuable tool for predicting the risk of pulmonary infections. This model holds significant potential to assist clinicians in making informed treatment decisions.