bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic profiling for prognostic stratification and personalized therapy in breast cancer
Authors: Guo Xiao , Feng Chuanbo , Xing Jiaying , Cao Yuyan , Liu Tengda , Yang Wenchuang , Mu Runhong , Wang Tao 
Published: January 2025

BackgroundThe rising incidence of breast cancer and its heterogeneity necessitate precise tools for predicting patient prognosis and tailoring personalized treatments. Epigenetic changes play a critical role in breast cancer progression and therapy responses, providing a foundation for prognostic model development.MethodsWe developed the Machine Learning-derived Epigenetic Model (MLEM) to identify prognostic epigenetic gene patterns in breast cancer. Using multi-cohort transcriptomic datasets, MLEM was constructed with rigorous machine learning techniques and validated across independent datasets. The model’s performance was further corroborated through immunohistochemical validation on clinical samples.ResultsMLEM effectively stratified breast cancer patients into high- and low-risk groups. Low-MLEM patients exhibited improved prognosis, characterized by enhanced immune cell infiltration and higher responsiveness to immunotherapy. High-MLEM patients showed poorer prognosis but were more responsive to chemotherapy, with vincristine identified as a promising therapeutic option. The model demonstrated robust performance across independent validation datasets.ConclusionMLEM is a powerful prognostic tool for predicting breast cancer outcomes and tailoring personalized treatments. By integrating epigenetic insights with machine learning, this model has the potential to improve clinical decision-making and optimize therapeutic strategies for breast cancer patients.
A c-type lectin HcLec1 with dual function of immunology and mineralization from the freshwater oyster (Hyriopsis cumingii Lea)
Authors: Chen Xiaofeng , Shen Xiaoya , Liu Shijun , Li Wenjuan , Wang He , Li Jiale , Bai Zhiyi 
Published: January 2025

BackgroundShell and pearl formation in bivalves is a sophisticated biomineralization process that encompasses immunological and mineralization aspects, particularly during shell repair and the initial stages of pearl cultivation when a nucleus is inserted. Here, we describe a novel C-type lectin, HcLec1, isolated and characterized from the freshwater pearl mussel Hyriopsis cumingii Lea. MethodsImmune challenge, RNA interference (RNAi) experiments, ELISA, and antibacterial assays were employed to investigate the role of HcLec1 in innate immunity. We also established shell damage repair and pearl nucleus insertion models to examine the impact of HcLec1 on the biomineralization process in Hyriopsis cumingii Lea. In vitro calcium carbonate crystallization assays were conducted to explore the direct role of HcLec1 in calcium carbonate crystal formation.ResultsThe HcLec1 gene sequence is a full-length cDNA of 1552 bp, encoding 240 amino acids. HcLec1 comprises an N-terminal signal peptide and a carbohydrate-recognition domain (CRD), with QPD (Gln-Pro-Asp) and MND (Met-Asn-Asp) motifs for polysaccharide binding. Tissue expression analysis showed that HcLec1 is predominantly expressed in the gill tissue of Hyriopsis cumingii Lea under normal conditions, and its expression is significantly elevated in both gill and pearl sac tissues following nucleus insertion for pearl cultivation (P &lt; 0.05). After immune stimulation with Aeromonas hydrophila and lipopolysaccharides (LPS), HcLec1 expression levels significantly increased in both cases (P &lt; 0.01), indicating a role in bivalve innate immunity. RNA interference (RNAi)-mediated knockdown of HcLec1 led to a significant decrease in the expression levels of immune-related genes (WAP, α2m, and Lyso) and mineralization-related genes (CA, CHS, Nacrein, and Pif) (P &lt; 0.05). In animal models for shell damage and nucleus insertion in pearl cultivation, HcLec1 showed a consistent expression pattern, with an initial significant decrease followed by a marked increase, peaking at day 14 (P &lt; 0.05). This suggests a role for HcLec1 in pearl formation and shell repair. The recombinant HcLec1 protein demonstrated binding affinity to LPS and PGN, a robust ability to agglutinate Escherichia coli, Staphylococcus aureus, Aeromonas veronii, and Aeromonas hydrophila, and significantly inhibited bacterial growth (P &lt; 0.05). Moreover, rHcLec1 promoted calcite crystal formation in saturated calcium carbonate solutions and altered crystal morphology.DiscussionThe HcLec1 gene plays a pivotal role in both innate immunity and biomineralization in the triangle sail mussel. This study enhances our understanding of the functional diversity of C-type lectins and provides a foundation for future studies on shell repair and pearl growth.
Immunometabolic alterations in type 2 diabetes mellitus revealed by single-cell RNA sequencing: insights into subtypes and therapeutic targets
Authors: Li Huahua , Zou Lingling , Long Zhaowei , Zhan Junkun 
Published: January 2025

BackgroundType 2 Diabetes Mellitus (T2DM) represents a major global health challenge, marked by chronic hyperglycemia, insulin resistance, and immune system dysfunction. Immune cells, including T cells and monocytes, play a pivotal role in driving systemic inflammation in T2DM; however, the underlying single-cell mechanisms remain inadequately defined.MethodsSingle-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from 37 patients with T2DM and 11 healthy controls (HC) was conducted. Immune cell types were identified through clustering analysis, followed by differential expression and pathway analysis. Metabolic heterogeneity within T cell subpopulations was evaluated using Gene Set Variation Analysis (GSVA). Machine learning models were constructed to classify T2DM subtypes based on metabolic signatures, and T-cell-monocyte interactions were explored to assess immune crosstalk. Transcription factor (TF) activity was analyzed, and drug enrichment analysis was performed to identify potential therapeutic targets.ResultsIn patients with T2DM, a marked increase in monocytes and a decrease in CD4+ T cells were observed, indicating immune dysregulation. Significant metabolic diversity within T cell subpopulations led to the classification of patients with T2DM into three distinct subtypes (A-C), with HC grouped as D. Enhanced intercellular communication, particularly through the MHC-I pathway, was evident in T2DM subtypes. Machine learning models effectively classified T2DM subtypes based on metabolic signatures, achieving an AUC &gt; 0.84. Analysis of TF activity identified pivotal regulators, including NF-kB, STAT3, and FOXO1, associated with immune and metabolic disturbances in T2DM. Drug enrichment analysis highlighted potential therapeutic agents targeting these TFs and related pathways, including Suloctidil, Chlorpropamide, and other compounds modulating inflammatory and metabolic pathways.ConclusionThis study underscores significant immunometabolic dysfunction in T2DM, characterized by alterations in immune cell composition, metabolic pathways, and intercellular communication. The identification of critical TFs and the development of drug enrichment profiles highlight the potential for personalized therapeutic strategies, emphasizing the need for integrated immunological and metabolic approaches in T2DM management.
Curvilinear association between Framingham Steatosis Index and chronic kidney disease: a nationwide cross-sectional study
Authors: Jiang Chunqi , Wang Bo , Wang Jun , Qu Yinuo , Zhang Xin 
Published: January 2025

IntroductionFatty liver disease is potentially linked to chronic kidney disease (CKD), yet the association between the Framingham Steatosis Index (FSI) and CKD remains uncharted. Our study thoroughly investigated the correlation between FSI and CKD, aiming to elucidate the underlying links between these two conditions.MethodsThe relationship between FSI and CKD was evaluated using a weighted multivariate logistic regression model, and the curvilinear relationship between FSI and CKD was explored through smooth curve fitting. We engaged a recursive partitioning algorithm in conjunction with a two-stage linear regression model to determine the inflection point. By conducting stratified analyses, the heterogeneity within subpopulations was explored.ResultsIn the fully adjusted Model 3, which accounted for all covariates, the odds ratios (ORs) (95% CI) for the association between FSI and CKD were 1.01 (0.97, 1.06), indicating no significant statistical association. Sensitivity analysis confirms the stability of the relationship between FSI and CKD. Smooth curve fitting discloses a non-linear association between FSI and CKD. The two-piecewise linear regression model, applied to explore this non-linearity, identified an inflection point at an FSI value of −3.21. Below this threshold, the OR (95% CI) was 0.25 (0.17, 0.37), signifying an inverse correlation between FSI and CKD. Above the inflection point, the OR (95% CI) was 1.19 (1.13, 1.25), suggesting a positive correlation. In the stratified curve analysis, the results were essentially consistent with the overall findings, except for the subgroups with BMI &gt; 30 and age &gt; 50.ConclusionWe found a curvilinear relationship between FSI and CKD.
Ocular inoculation of toad venom: toxic cataract and proteomic profiling
Authors: Lyu Danni , Ni Shuang , Xu Jia , Zhu Sha , Xu Jing-Wei , Feng Yixuan , Shi Ce , Xu Wen 
Published: January 2025

PurposeTo report a singular case of cataract caused by toad venom inoculation and to scrutinize the pathological mechanisms through proteomic sequencing of the lens specimen.MethodsA young Chinese male presented with progressively deteriorating vision in his right eye subsequent to a history of toad venom inoculation. He was diagnosed with a toxic cataract, and underwent phacoemulsification cataract surgery. Anterior capsule, nucleus, and cortex specimens from the patient (designated as PT_CAP, PT_PHACO, and PT_CTX, respectively) and age-related cataract controls (C_CAP, C_PHACO, and C_CTX, respectively) were collected and subjected to 4D label-free quantitative proteomics.ResultsA multitude of differentially expressed proteins (DEPs) were identified in the patient’s lens compared to those in the controls. Specifically, a total of 204 DEPs were identified in PT_CAP compared to C_CAP, with MYH6, MYL2, MYL3, STAT1, and ANK1 among the foremost regulated DEPs. The DEPs of PT_CAP were principally affiliated with functions including “transportation of small molecules,” “regulation of metal ion transport,” and “import into cell.” A sum of 109 DEPs were delineated in PT_CTX compared to C_CTX, with TPM1 among the top-10 downregulated DEPs. Ninety-five DEPs were pinpointed in PT_PHACO compared to C_PHACO, with hexokinase among the top 10 downregulated DEPs. These proteins were ascertained to be linked with Na+/K+-ATPase activity.ConclusionThis study introduced the first documented case of toxic cataract caused by toad venom inoculation. Proteomic sequencing indicated a correlation between cataract and alterations in Na+/K+-ATPase activity, providing insights for the clinical management of ocular toad venom inoculation in subsequent cases.
Association between body esteem and sugar-sweetened beverage intake among Chinese undergraduate students: a cross-sectional study
Authors: Zhu Jiawen , Zhu Yuanyuan , Zhao Zihe , Huang Qianling , Liu Changju , Zeng Zhi 
Published: January 2025

BackgroundHigh intake of sugar-sweetened beverages has been linked to a range of physical, psychological, and emotional issues. Although there were various factors influencing sugar-sweetened beverage intake, the relationship between body esteem and sugar-sweetened beverage intake remains unclear. This study aimed to investigate the association between three dimensions of body esteem (body esteem-appearance, body esteem-attribution, and body esteem-weight) and the likelihood of high sugar-sweetened beverage intake.MethodsA cross-sectional study was conducted among undergraduate students at Nanjing University of Chinese Medicine. Logistic regression analyses were used to assess the association between the three dimensions of body esteem and the risk of high sugar-sweetened beverage intake. Additionally, restricted cubic splines and subgroup analyses were implemented to further explore the associations.ResultsA total of 969 participants were included in the study, with 771 females (79.6%). The mean age of the participants was 20.07 years (standard deviation [SD] = 1.65). After adjusting for covariates, body esteem-appearance was found to be negatively associated with high sugar-sweetened beverage intake (OR = 0.962, 95% CI = 0.935–0.989, p = 0.007), while body esteem-attribution was positively associated with high sugar-sweetened beverage intake (OR = 1.091, 95% CI = 1.046–1.139, p &lt; 0.001). However, no significant association was found between body esteem-weight and high sugar-sweetened beverage intake (p = 0.781). Restricted cubic spline plots showed no non-linear associations between any dimensions of body esteem and the risk of high sugar-sweetened beverage intake (p-nonlinear was 0.912, 0.225, 0.109, respectively). Subgroup analyses revealed no significant interactions.ConclusionThese findings underscored the significance of targeted health promotion strategies and provided references for educational institutions or governmental bodies to steer undergraduate beverage consumption toward healthier patterns.
Machine learning for predicting neoadjuvant chemotherapy effectiveness using ultrasound radiomics features and routine clinical data of patients with breast cancer
Authors: Zhou Pu , Qian Hongyan , Zhu Pengfei , Ben Jiangyuan , Chen Guifang , Chen Qiuyi , Chen Lingli , Chen Jia , He Ying 
Published: January 2025

BackgroundThis study explores the clinical value of a machine learning (ML) model based on ultrasound radiomics features of primary foci, combined with clinicopathologic factors to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) for patients with breast cancer (BC).MethodWe retrospectively analyzed ultrasound images and clinical information from 231 participants with BC who received NAC. These patients were randomly assigned to training and validation cohorts. Tumor regions of interest (ROI) were delineated, and radiomics features were extracted. Z-score normalization, Pearson correlation analysis, and the least absolute shrinkage selection operator (LASSO) were utilized for further screening ultrasound radiomics and clinical features. Univariate and multivariate logistic regression analysis were performed to identify the CFs that were independently associated with pCR. We compared 10 ML models based on radiomics features: support vector machine (SVM), logistic regression (LR), random forest, extra trees (ET), naïve Bayes (NB), k-nearest neighbor (KNN), multilayer perceptron (MLP), gradient boosting ML (GBM), light GBM (LGBM), and adaptive boost (AB). Diagnostic performance was evaluated using the receiver operating characteristic (ROC) area under the curve (AUC), accuracy, sensitivity, and specificity, and the Rad score was calculated. Subsequently, construction of clinical predictive models and Rad score joint clinical predictive models using ML algorithms for optimal diagnostic performance. The diagnostic process of the ML model was visualized and analyzed using SHapley Additive exPlanation (SHAP).ResultsOut of 231 participants with BC, 98 (42.42%) achieved pCR, and 133 (57.58%) did not. Twelve radiomics features were identified, with the GBM model demonstrating the best predictive performance (AUC of 0.851, accuracy of 0.75, sensitivity of 0.821, and specificity of 0.698). The clinical feature prediction model using the GBM algorithm had an AUC of 0.819 and an accuracy of 0.739. Combining the Rad score with clinical features in the GBM model resulted in superior predictive performance (AUC of 0.939 and an accuracy of 0.87). SHAP analysis indicated that participants with a high Rad score, PR-negative, ER-negative and human epidermal growth factor receptor-2 (HER-2) positive were more possibly to reach pCR. Based on the decision curve analysis, it was shown that the combined model of GBM provided higher clinical benefits.ConclusionThe GBM model based on ultrasound radiomics features and routine clinical date of BC patients had high performance in predicting pCR. SHAP analysis provided a clear explanation for the prediction results of the GBM model, revealing that patients with a high Rad score, PR-negative status, ER-negative status and HER-2-positive status are more likely to achieve pCR.
Application value of different imaging methods in the early diagnosis of small hepatocellular carcinoma: a network meta-analysis
Authors: Dong Jian , Wang Zhen , Wang Si-Rui , Zhao Huan , Li Jun , Ma Ting 
Published: January 2025

ObjectiveTo determine the diagnostic value of ultrasound, multi-phase enhanced computed tomography, and magnetic resonance imaging of small hepatocellular carcinoma.MethodsExperimental studies on diagnosing small hepatocellular carcinoma in four databases: PubMed, Cochrane Library, Web of Science, and Embase, were comprehensively searched from October 2007 to October 2024. Relevant diagnostic accuracy data were extracted and a Bayesian model that combined direct and indirect evidence was used for analysis.Results16 original studies were included and data from 2,447 patients were collated to assess the diagnostic value of 10 different methods. The methodological quality of the included studies was good and there was no obvious publication bias. The pooled DOR of all diagnostic methods was 19.61, which was statistically significant (I2 = 76.0%, P &lt; 0.01, 95% CI:13.30 - 28.92). Normal US + CEUS + ultrasonic elastic imaging had the highest specificity (92.9), accuracy (93.6), and positive predictive value (94.4). Unenhanced MRI + Contrast-enhanced MRI had the highest sensitivity (96.6) and negative predictive value (96.6), but specificity (12.5) and positive predictive value (34.4) were extremely poor. Contrast-enhanced MRI had the highest diagnostic value in individual imaging methods (sensitivity: 66, specificity: 55.5, accuracy: 67.9, positive predictive value: 64.4, negative predictive value: 66.5). There was significant inconsistency and high heterogeneity in this study.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024507883.
Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review
Authors: Zhang Lei , Hall Gentzon , Han Peitong , Li Chunzhen , Cui Jieyuan 
Published: January 2025

BackgroundPrimary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS).MethodsFour SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing.ResultsClinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease.ConclusionsCOQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.
“I think we're on a cusp of some change:” coping and support for mental wellness among Black American women
Authors: McCall Terika , Foster Meagan , Tomlin Holly , Adepoju Bolatito , Bolton-Johnson Mckenzie , Bellamy Chyrell D. 
Published: January 2025

IntroductionPublic discussions in the media (e.g., social media and reality shows) about Black women's mental health have become more common. Notably, celebrities have become more vocal about their own mental health challenges and sought to normalize seeking care. This study aimed to gain a better understanding of Black women's: (1) past and current causes of stress, anxiety, and depression, and coping skills used; (2) their attitudes and perceptions toward mental health and receiving mental health treatment; and (3) times in their life they felt anxious or depressed, and what type of support or resources would have been helpful to have access to.MethodsFocus groups were conducted with 20 women (mean age 36.6 years, SD 17.8 years), with 5 participants per group. Descriptive qualitative content analysis of the focus group transcripts was conducted.ResultsResults consistently showed that intersectional identities of being both Black and a woman resulted in feelings of both hypervisibility and invisibility, representation matters when it comes to mental health providers, an increased openness to therapy across age groups, and a willingness to try digital health tools (e.g., smartphone app) for mental health needs. There is still work to be done to normalize mental health treatment among Black women.DiscussionSubgroups within the community (e.g., young adults) have less stigma around mental health and are acting as catalysts for change. Intentional inclusion of Black women in mental health research and evolving treatment paradigms is important to eliminate inequities in access to culturally relevant mental health care.