Least Absolute Shrinkage And Selection Operator Research Articles

Exosome-related gene identification and diagnostic model construction in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) may cause severe hepatic impairment, acute hepatic insufficiency, and multiorgan system collapse. Exosomes can alleviate HIRI. Therefore, this study explored the role of exosomal-related genes (ERGs) in HIRI using bioinformatics to determine the underlying molecular mechanisms and novel diagnostic markers for HIRI. We merged the GSE12720, GSE14951, and GSE15480 datasets obtained from the Gene Expression Omnibus (GEO) database into a combined gene dataset (CGD). CGD was used to identify differentially expressed genes (DEGs) based on a comparison of the HIRI and healthy control cohorts. The impact of these DEGs on HIRI was assessed through gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). ERGs were retrieved from the GeneCards database and prior studies, and overlapped with the identified DEGs to yield the set of exosome-related differentially expressed genes (ERDEGs). Functional annotations and enrichment pathways of these genes were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Diagnostic models for HIRI were developed using least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM) algorithms. Key genes with diagnostic value were identified from the overlap, and single-sample gene-set enrichment analysis (ssGSEA) was conducted to evaluate the immune infiltration characteristics. A molecular regulatory interaction network was established using Cytoscape software to elucidate the intricate regulatory mechanisms of key genes in HIRI. Finally, exosome score (Es) was obtained using ssGSEA and the HIRI group was divided into the Es_High and Es_Low groups based on the median Es. Gene expression was analyzed to understand the impact of all genes in the CGD on HIRI. Finally, the relative expression levels of the five key genes in the hypoxia-reoxygenation (H/R) model were determined using quantitative real-time PCR (qRT-PCR). A total of 3810 DEGs were identified through differential expression analysis of the CGD, and 61 of these ERDEGs were screened. Based on GO and KEGG enrichment analyses, the ERDEGs were mainly enriched in wound healing, MAPK, protein kinase B signaling, and other pathways. GSEA and GSVA revealed that these genes were mainly enriched in the TP53, MAPK, TGF[Formula: see text], JAK-STAT, MAPK, and NFKB pathways. Five key genes (ANXA1, HNRNPA2B1, ICAM1, PTEN, and THBS1) with diagnostic value were screened using the LASSO regression and SVM algorithms and their molecular interaction network was established using Cytoscape software. Based on ssGSEA, substantial variations were found in the expression of 18 immune cell types among the groups (p < 0.05). Finally, the Es of each HIRI patient was calculated. ERDEGs in the Es_High and Es_Low groups were enriched in the IL18, TP53, MAPK, TGF[Formula: see text], and JAK-STAT pathways. The differential expression of these five key genes in the H/R model was verified using qRT-PCR. Herein, five key genes were identified as potential diagnostic markers. Moreover, the potential impact of these genes on pathways and the regulatory mechanisms of their interaction network in HIRI were revealed. Altogether, our findings may serve as a theoretical foundation for enhancing clinical diagnosis and elucidating underlying pathogeneses.

Construction and evaluation of two nomograms for screening major depressive disorder and subthreshold depression individuals based on anxiety, depression, and sleep items

BackgroundCurrent evidence is insufficient to support specific tools for screening Major Depressive Disorder (MDD). Early detection of subthreshold depression (SD) is crucial in preventing its progression to MDD. This study aims to develop nomograms that visualize the weights of predictors to improve the performance of screening tools. MethodsParticipants were recruited from Peking University Sixth Hospital and Beijing Physical Examination Center between October 2022 and April 2024. The Mini-International Neuropsychiatric Interview (MINI) 5.0.0 was employed as the diagnostic gold standard, and Generalized Anxiety Disorder questionnaire-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Pittsburgh Sleep Quality Index (PSQI) were employed to assess anxiety, depression, and sleep state. The nomograms were constructed by incorporating optimal predictors, selected through the Least Absolute Shrinkage and Selection Operator (LASSO), into a multivariate logistic regression model to estimate the probability of MDD and SD. ResultsAfter matching age and education, 164 participants were included in each group for analysis. Both nomograms demonstrated superior discrimination, calibration, and clinical applicability compared to PHQ-9. Anxiety emerged as a most significant predictor for SD, while sleep problems exhibited high rankings for both SD and MDD. The two predictors subsequently affect concentration and daytime functioning. LimitationsWith a lack of external validation data, the performance of nomograms may be overestimated. ConclusionsThis study is the first attempt to develop a nomogram for predicting SD, while also providing a nomogram for MDD. The crucial predictors offer valuable insights into potential variables for clinical intervention.

Value of portal venous gas and a nomogram for predicting severe neonatal necrotizing enterocolitis.

Whether portal venous gas (PVG) is a sign of severe neonatal necrotizing enterocolitis (NEC) and predicts poor prognosis remains uncertain. Patients from two centres were randomly assigned to a training set or a validation set. A nomogram model for predicting severe NEC was developed on the basis of the independent risk factors selected by least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate logistic regression analysis. The model was evaluated based on the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). A total of 585 patients met the study criteria, and propensity score matching resulted in 141 matched pairs for further analysis. Patients with PVG had a greater risk of surgical intervention or death compared with patients without PVG. A prediction model for severe NEC was established based on PVG, invasive mechanical ventilation (IMV), serum platelet count (PLT) and pH <7.35 at the onset of NEC. The model had a moderate predictive value with an AUC > 0.8. The calibration curve and DCA suggested that the nomogram model had good performance for clinical application. A prediction nomogram model based on PVG and other risk factors can help physicians identify severe NEC early and develop reasonable treatment plans. PVG is an important and common imaging manifestation of NEC. Controversy exists regarding whether PVG is an indication for surgical intervention and predicts poor prognosis. Our study suggested that patients with PVG had a greater risk of surgical intervention or death compared with patients without PVG. PVG, IMV, PLT and pH <7.35 at the onset of NEC are independent risk factors for severe NEC. A prediction nomogram model based on PVG and other risk factors may help physicians identify severe NEC early and develop reasonable treatment plans.

Smooth Operator: Nanotextured Breast Tissue Expanders Are Associated with Lower Rates of Capsular Contracture

Background: Continuous research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has introduced a focus on surface texturizations and a shift towards smooth breast devices, yet outcomes comparing the complication profiles of differently textured tissue expanders (TEs) remain conflicting. The study aim was to compare the complication profile of a new nanotextured and MRI-compatible TE to micro- and macrotextured TEs and to identify possible predictors for complications. Methods: A retrospective analysis of women undergoing expander-based breast reconstruction after mastectomy between January 2016 and March 2022 was conducted. The primary endpoint was the development of capsular contracture. Possible predictors were analyzed in a mixed-effects model using the least absolute shrinkage and selection operator (LASSO). Moreover, a comparison of complications and an evaluation of predictors were carried out. Results: A total of 147 breasts, encompassing 82 nanotextured, 43 microtextured and 22 macrotextured TEs, were analyzed. Breasts with nanotextured TEs were less likely to develop capsular contracture overall (OR, 0.12; 95%CI 0.05–0.28, p &lt; 0.001). Post-mastectomy radiotherapy (PMRT) was identified as a predictor for capsular contracture (OR, 4.67; 95%CI 1.86–11.71, p &lt; 0.001). Breasts with nanotextured TEs showed a higher rate of seroma, but lower rates of malposition and pain. Predictors for developing postoperative complications included higher mastectomy weight (p = 0.008). Conclusions: Breasts with nanotextured TEs exhibited the lowest rate of capsular contracture compared to micro- and macrotextured TEs. Together with its MRI-compatibility and improved oncologic follow-up, the nanotextured TE seems to be a favorable device for expander-based breast reconstruction.

Prediction Model of Delayed Hemothorax in Patients with Traumatic Occult Hemothorax Using a Novel Nomogram.

Delayed hemothorax (dHTX) can occur unexpectedly, even in patients who initially present without signs of hemothorax (HTX), potentially leading to death. We aimed to develop a predictive model for dHTX requiring intervention, specifically targeting those with no or occult HTX. This retrospective study was conducted at a level 1 trauma center. The primary outcome was the occurrence of dHTX requiring intervention in patients who had no HTX or occult HTX and did not undergo closed thoracostomy post-injury. To minimize overfitting, we employed the least absolute shrinkage and selection operator (LASSO) logistic regression model for feature selection. Thereafter, we developed a multivariable logistic regression (MLR) model and a nomogram. In total, 688 patients were included in the study, with 64 cases of dHTX (9.3%). The LASSO and MLR analyses revealed that the depth of HTX (adjusted odds ratio [aOR], 3.79; 95% confidence interval [CI], 2.10-6.85; p<0.001) and the number of totally displaced rib fractures (RFX) (aOR, 1.90; 95% CI, 1.56-2.32; p<0.001) were significant predictors. Based on these parameters, we developed a nomogram to predict dHTX, with a sensitivity of 78.1%, a specificity of 76.0%, a positive predictive value of 25.0%, and a negative predictive value of 97.1% at the optimal cut-off value. The area under the receiver operating characteristic curve was 0.832. The depth of HTX on initial chest computed tomography and the number of totally displaced RFX emerged as significant risk factors for dHTX. We propose a novel nomogram that is easily applicable in clinical settings.

Development and validation of machine learning models for diagnosis and prognosis of lung adenocarcinoma, and immune infiltration analysis.

The aim of our study was to develop robust diagnostic and prognostic models for lung adenocarcinoma (LUAD) using machine learning (ML) techniques, focusing on early immune infiltration. Feature selection was performed on The Cancer Genome Atlas (TCGA) data using least absolute shrinkage and selection Operator (LASSO), random forest (RF), and support vector machine (SVM) algorithms. Six ML algorithms were employed to construct the diagnostic models, which were evaluated through receiver operating characteristic (ROC) curves, precision-recall curves (PRC), and classification error (CE), and validated on the GSE7670 dataset. Additionally, a lasso cox prognostic model was built on the TCGA-LUAD dataset and externally validated using independent Gene Expression Omnibus datasets (GSE30219, GSE31210, GSE50081, and GSE37745). Single-sample gene set enrichment analysis (ssGSEA) was performed to assess immune cell infiltration in stage I LUAD samples, revealing significant differences in immune cell types. These findings demonstrate a positive correlation between immune infiltration in stage I LUAD and Th2 cells, Tcm cells, and T helper cells, while a negative correlation was observed with Macrophages, Eosinophils, and Tem cells. These insights provide novel perspectives for clinical diagnosis and treatment of LUAD.

Identification of ferroptosis biomarkers and immune infiltration landscapes in atrial fibrillation: A bioinformatics analysis.

Ferroptosis has been recognized as a critical factor in the development of atrial fibrillation (AF), but its precise mechanisms remain unclear. We downloaded the GSE115574 dataset from the gene expression omnibus database to analyze the expression levels of ferroptosis-related genes (FRGs) and identify differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) machine learning techniques were employed to identify key genes associated with AF. The diagnostic performance of these genes was evaluated using Receiver operating characteristic curves (ROC) and validated in an independent AF dataset. miRNA and lncRNA predictions for potential binding to these key genes were conducted using miRBase, miRDB, and TargetScan. Furthermore, gene set enrichment analysis (GSEA) enrichment analysis, immune cell infiltration analysis, and targeted drug prediction were performed. The intersection of LASSO regression and SVM-RFE analyses identified 7 DEGs significantly associated with AF. Validation through ROC and an additional dataset confirmed the importance of MAPK14, CAV1, and ADAM23. Significant infiltration of memory B cells, regulatory T cells, and monocytes was observed in atrial tissues. Seventy-two miRNAs were predicted to potentially target MAPK14, and 2 drugs were identified as targeting CAV1. This study underscores the involvement of FRGs in AF through machine learning and validation approaches. The observed immune cell infiltration suggests a potential link between immune response and AF. The predicted ceRNA network offers new insights into gene regulation, presenting potential biomarkers and therapeutic targets for AF.

Development and validation of a risk prediction model for older adults with social isolation in China

BackgroundOlder adults are vulnerable to social isolation due to declining physical and cognitive function, decreased interpersonal interactions, and reduced outdoor activities after retirement. This study aimed to develop and validate a predictive model to assess the risk of social isolation among older adults in China.MethodsUsing data from the 2011 China Health and Retirement Longitudinal Study (CHARLS). The study cohort was randomly divided into training and validation groups in a 70:30 ratio. We used least absolute shrinkage and selection operator (LASSO) regression analysis with tenfold cross-validation to identify optimal predictive factors and examined the correlates of social isolation using logistic regression. A nomogram was constructed for the predictive model, and its accuracy was assessed using calibration curves. The predictive performance of the model was assessed using area under the receiver operating characteristic (ROC) curve and decision curve analysis (DCA).ResultsFrom the 2011 CHARLS database, 4,747 older adults were included in the final analysis, of whom 1,654 (34.8%) experienced social isolation. Multifactorial logistic regression identified educational level, marital status, gender, physical activity, physical self -maintenance ability, and number of children as predictive factors for social isolation. The predictive model achieved an AUC of 0.739 (95%CI = 0.722–0.756) in the training set and 0.708 (95%CI = 0.681–0.735) in the validation set. The Hosmer-Lemeshow test yielded P values of 0.111 and 0.324, respectively (both P > 0.05), indicating significant agreement between the nomogram and observed outcomes. The nomogram showed excellent predictive ability according to ROC and DCA.ConclusionsThe predictive model developed to assess the risk of social isolation in the Chinese older adults shows promising utility for early screening and intervention by clinical healthcare professionals.

Identifying predictors of multi-year cannabis vaping in U.S. Young adults using machine learning

IntroductionIncreasing number of current cannabis users report using a vaporized form of cannabis and young adults are most likely to vape cannabis. However, the number of studies on cannabis vaping is limited, and predictors of cannabis vaping among U.S. young adults remain unclear. Previous studies on cannabis vaping have known limitations, as they (1) relied heavily on regression-based approaches that often fail to examine complex and non-linear interactive effects, (2) focused on examining cannabis vaping initiation but not on its use over multiple years, and (3) failed to account for recreational cannabis legalization (RCL) status. MethodsThis study was a secondary analysis of the restricted use files of the Population Assessment of Tobacco and Health Study, Waves 4–6 (December 2016-November 2021). A two-stage machine learning approach, which included Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Tree (CART), was used to identify predictors of multi-year cannabis vaping while accounting for state-level RCL status among a representative sample of U.S. young adults. ResultsStratified CART created a five-terminal-node prediction model for states with RCL (split by cannabis use, cigarette use, bullying behavior, and ethnicity) and a different five-terminal-node prediction model for states without RCL (split by cannabis use, heroin use, nicotine vaping, and hookah use). ConclusionsCharacteristics predicting multi-year cannabis vaping appear to differ from those of cannabis vaping initiation. Results also highlight the importance of accounting for RCL status because predictors of cannabis vaping may differ for individuals living in states with and without RCL.

Exploring and validating the necroptotic gene regulation and related lncRNA mechanisms in colon adenocarcinoma based on multi-dimensional data.

Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research.

Unveiling the impact of estrogen exposure on ovarian cancer: a comprehensive risk model and immune landscape analysis

This study examines the impact of estrogenic compounds like bisphenol A (BPA), estradiol (E2), and zearalenone (ZEA) on human ovarian cancer, focusing on constructing a risk model, conducting gene set variation analysis (GSVA), and evaluating immune infiltration. Differential gene expression analysis identified 980 shared differentially expressed genes (DEGs) in human ovarian cells exposed to BPA, E2, and ZEA, indicating disruptions in ribosome biogenesis and RNA processing. Using the cancer genome atlas ovarian cancer (TCGA-OV) dataset, a least absolute shrinkage and selection operator (LASSO)-based risk model was developed incorporating prognostic genes 4-hydroxyphenylpyruvate dioxygenase like (HPDL), Thy-1 cell surface antigen (THY1), and peptidase inhibitor 3 (PI3). This model effectively stratified ovarian cancer patients into high-risk and low-risk categories, showing significant differences in overall survival, disease-specific survival, and progression-free survival. GSVA analysis linked HPDL expression to pathways related to the cell cycle, DNA damage, and repair, while THY1 and PI3 were associated with apoptosis, hypoxia, and proliferation pathways. Immune infiltration analysis revealed distinct immune cell profiles for high and low-expression groups of HPDL, THY1, and PI3, indicating their influence on the tumor microenvironment. The findings demonstrate that estrogenic compounds significantly alter gene expression and oncogenic pathways in ovarian cancer. The risk model integrating HPDL, THY1, and PI3 offers a strong prognostic tool, with GSVA and immune infiltration analyses providing insights into the interplay between these genes and the tumor microenvironment, suggesting potential targets for personalized therapies.

A nomogram for enhanced risk stratification for predicting cervical lymph node metastasis in papillary thyroid carcinoma patients

BackgroundCervical lymph node metastasis (CLNM) significantly impacts the prognosis of papillary thyroid carcinoma (PTC) patients. Accurate CLNM prediction is crucial for surgical planning and patient outcomes. This study aimed to develop and validate a nomogram-based risk stratification system to predict CLNM in PTC patients.MethodsThis retrospective study included 1069 patients from Zhongshan Hospital and 253 from the Qingpu Branch of Zhongshan Hospital. Preoperative ultrasound (US) data and various nodule characteristics were documented. Patients underwent lobectomy with central lymph node dissection and lateral dissection if suspicious. Multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) regression, and the random forest algorithm were used to identify CLNM risk factors. A nomogram was constructed and validated internally and externally. Model performance was assessed via receiver operating characteristic (ROC) curves, calibration plots, DeLong’s test, decision curve analysis (DCA), and the clinical impact curve (CIC).ResultsSix independent CLNM risk factors were identified: age, sex, tumor size, calcification, internal vascularity, and US-reported CLNM status. The model's area under the curve (AUC) was 0.77 for both the training and the external validation sets. Calibration plots and Hosmer‒Lemeshow (HL) tests showed good calibration. The optimal cutoff value was 0.57, with a sensitivity of 58.02% and a specificity of 83.43%. Risk stratification on the basis of the nomogram categorized patients into low-, intermediate-, and high-risk groups, effectively differentiating the likelihood of CLNM, and an online calculator was created for clinical use.ConclusionThe nomogram accurately predicts CLNM risk in PTC patients, aiding personalized surgical decisions and improving patient management.

Assessing Prospective Molecular Biomarkers and Functional Pathways in Severe Asthma based on a Machine Learning method and Bioinformatics Analyses

Background Severe asthma, which differs significantly from typical asthma, involves specific molecular biomarkers that enhance our understanding and diagnostic capabilities. The objective of this study is to assess the biological processes underlying severe asthma and to detect key molecular biomarkers. Methods We used Weighted Gene Co-Expression Network Analysis (WGCNA) to detect hub genes in the GSE143303 dataset and indicated their functions and regulatory mechanisms using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) annotations. In the GSE147878 dataset, we used Gene Set Enrichment Analysis (GSEA) to determine the regulatory directions of gene sets. We detected differentially expressed genes in the GSE143303 and GSE64913 datasets, constructed a Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and validated the model using the GSE147878 dataset and real-time quantitative PCR (RT-qPCR) to confirm the molecular biomarkers. Results Using WGCNA, we discovered modules that were strongly correlated with clinical features, specifically the purple module (r = 0.53) and the midnight blue module (r = -0.65). The hub genes within these modules were enriched in pathways related to mitochondrial function and oxidative phosphorylation. GSEA in the GSE147878 dataset revealed significant enrichment of upregulated gene sets associated with oxidative phosphorylation and downregulated gene sets related to asthma. We discovered 12 commonly regulated genes in the GSE143303 and GSE64913 datasets and developed a LASSO regression model. The model corresponding to lambda.min selected nine genes, including TFCP2L1, KRT6A, FCER1A, and CCL5, which demonstrated predictive value. These genes were significantly upregulated or under expressed in severe asthma, as validated by RT-qPCR. Conclusion Mitochondrial abnormalities affecting oxidative phosphorylation play a critical role in severe asthma. Key molecular biomarkers like TFCP2L1, KRT6A, FCER1A, and CCL5, are essential for detecting severe asthma. This research significantly enhances the understanding and diagnosis of severe asthma.

AI diagnostics in bone oncology for predicting bone metastasis in lung cancer patients using DenseNet-264 deep learning model and radiomics

This study aims to predict bone metastasis in lung cancer patients using radiomics and deep learning. Early prediction of bone metastasis is crucial for timely intervention and personalized treatment plans. This can improve patient outcomes and quality of life. By integrating advanced imaging techniques with artificial intelligence, this study seeks to enhance predictive accuracy and clinical decision-making. MethodsWe included 189 lung cancer patients, comprising 89 with non-bone metastasis and 100 with confirmed bone metastasis. Radiomic features were extracted from CT images, and feature selection was performed using Minimum Redundancy Maximum Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO). We developed and validated a radiomics model and a deep learning model using DenseNet-264. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Statistical comparisons were made using the DeLong test. ResultsThe radiomics model achieved an AUC of 0.815 on the training set and 0.778 on the validation set. The DenseNet-264 model demonstrated superior performance with an AUC of 0.990 on the training set and 0.971 on the validation set. The DeLong test confirmed that the AUC of the DenseNet-264 model was significantly higher than that of the radiomics model (p < 0.05). ConclusionsThe DenseNet-264 model significantly outperforms the radiomics model in predicting bone metastasis in lung cancer patients. The early and accurate prediction provided by the deep learning model can facilitate timely interventions and personalized treatment planning, potentially improving patient outcomes. Future studies should focus on validating these findings in larger, multi-center cohorts and integrating clinical data to further enhance predictive accuracy.

Ultrasound-based Radiomics Analysis for Assessing Risk Factors Associated With Early Recurrence Following Surgical Resection of Hepatocellular Carcinoma

ObjectiveThe aim of this study was to explore the value of ultrasound-based radiomics analysis for early recurrence (ER) after surgical resection of hepatocellular carcinoma (HCC). MethodsThis retrospective study included 127 patients who underwent primary surgical resection for HCC between October 2019 and November 2021. The patients were subsequently divided into training and validation sets (7:3 ratio). All patients received preoperative routine ultrasound and contrast-enhanced ultrasound (CEUS), with postoperative pathological confirmation of HCC. Radiomics features were extracted from maximum section of two-dimensional ultrasound image. The least absolute shrinkage and selection operation (LASSO) logistic regression algorithm with 10-fold cross-validation was employed to establish ultrasonic radiomics features. Logistic regression modeling was employed to build models based on clinical and ultrasonic features (model 1, clinical-ultrasonic model), radiomics signature (model 2, ultrasonic radiomics model), and the combination (model 3, clinical-ultrasonic-radiomics model). Then a nomogram model was established to predict the risk of ER, and the application value of nomogram through internal verification was evaluated. ResultsModel 3 showed optimal diagnostic performance in both training set (AUC=0.907) and validation set (AUC=0.925), followed by the model 1 in training set (AUC=0.846) and validation set (AUC=0.855), both above two models performed better than model 2 in training set (AUC=0.751) and validation set (AUC=0.702) (p<0.05). In training set and validation set of model 3, the sensitivity were 83.3%, 77.8%, the specificity ware 95.8%, 100.0% and the C-index were 0.791, 0.778. ConclusionThe preoperative clinical-ultrasonic-radiomics model is anticipated to be a reliable tool for predicting the ER of surgical resection of HCC.

Identification of a novel immune infiltration-related gene signature, MCEMP1, for coronary artery disease.

This study aims to identify a novel gene signature for coronary artery disease (CAD), explore the role of immune cell infiltration in CAD pathogenesis, and assess the cell function of mast cell-expressed membrane protein 1 (MCEMP1) in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL). To identify differentially expressed genes (DEGs) of CAD, datasets GSE24519 and GSE61145 were downloaded from the Gene Expression Omnibus (GEO) database using the R "limma" package with p < 0.05 and |log2 FC| > 1. Gene ontology (GO) and pathway analyses were conducted to determine the biological functions of DEGs. Hub genes were identified using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO). The expression levels of these hub genes in CAD were validated using the GSE113079 dataset. CIBERSORT program was used to quantify the proportion of immune cell infiltration. Western blot assay and qRT-PCR were used to detect the expression of hub genes in ox-LDL-treated HUVECs to validate the bioinformatics results. Knockdown interference sequences for MCEMP1 were synthesized, and cell proliferation and apoptosis were examined using a CCK8 kit and Muse® Cell Analyzer, respectively. The concentrations of IL-1β, IL-6, and TNF-α were measured with respective enzyme-linked immunosorbent assay (ELISA) kits. A total of 73 DEGs (four down-regulated genes and 69 up-regulated genes) were identified in the metadata (GSE24519 and GSE61145) cohort. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that these DEGs might be associated with the regulation of platelet aggregation, defense response or response to bacterium, NF-kappa B signaling pathway, and lipid and atherosclerosis. Using SVM-RFE and LASSO, seven hub genes were obtained from the metadata. The upregulated expression of DIRC2 and MCEMP1 in CAD was confirmed in the GSE113079 dataset and in ox-LDL-treated HUVECs. The associations between the two hub genes (DIRC2 and MCEMP1) and the 22 types of immune cell infiltrates in CAD were found. MCEMP1 knockdown accelerated cell proliferation and suppressed cell apoptosis for ox-LDL-treated HUVECs. Additionally, MCEMP1 knockdown appeared to decrease the expression of inflammatory factors IL-1β, IL-6, and TNF-α. The results of this study indicate that MCEMP1 may play an important role in CAD pathophysiology.

Multimodal Ultrasound Radiomic Technology for Diagnosing Benign and Malignant Thyroid Nodules of Ti-Rads 4-5: A Multicenter Study

This study included 468 patients and aimed to use multimodal ultrasound radiomic technology to predict the malignancy of TI-RADS 4-5 thyroid nodules. First, radiomic features are extracted from conventional two-dimensional ultrasound (transverse ultrasound and longitudinal ultrasound), strain elastography (SE), and shear-wave-imaging (SWE) images. Next, the least absolute shrinkage and selection operator (LASSO) is used to screen out features related to malignant tumors. Finally, a support vector machine (SVM) is used to predict the malignancy of thyroid nodules. The Shapley additive explanation (SHAP) method was used to intuitively analyze the specific contributions of radiomic features to the model’s prediction. Our proposed model has AUCs of 0.971 and 0.856 in the training and testing sets, respectively. Our proposed model has a higher prediction accuracy compared to those of models with other modal combinations. In the external validation set, the AUC of the model is 0.779, which proves that the model has good generalization ability. Moreover, SHAP analysis was used to examine the overall impacts of various radiomic features on model predictions and local explanations for individual patient evaluations. Our proposed multimodal ultrasound radiomic model can effectively integrate different data collected using multiple ultrasound sensors and has good diagnostic performance for TI-RADS 4-5 thyroid nodules.

ZNF429 Participates in the Progression of Coronary Heart Disease through Regulating Inflammatory and Adhesive Factors

Background: Coronary heart disease (CHD) is an intricate and multifaceted cardiovascular disorder that contributes significantly to global morbidity and mortality. Early and accurate identification and diagnosis of CHD are paramount to ensuring patients receive optimal therapeutic interventions and satisfactory outcomes. Methods: Data on CHD gene expression were obtained from the Gene Expression Omnibus (GEO) repository and potential hub genes were screened through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analyses. Functional validation of these hub genes was conducted by interfering with them in human umbilical vein endothelial cells (HUVECs). Cell proliferation and apoptosis were assessed through cell counting kit-8 (CCK-8) and flow cytometry assays, respectively, while enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR), Western blot, and immunofluorescence were used to measure the expression of key indicators. Results: We identified 700 upregulated differentially expressed genes (DEGs) and 638 downregulated DEGs in CHD, and utilized LASSO analyses to screen disease potential biomarkers, such as zinc finger protein 429 (ZNF429). Interference with ZNF429 in HUVECs mitigated the CHD-induced decrease in cell proliferation and increase in apoptosis. Moreover, the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), cluster of differentiation 62E (CD62E), and cluster of differentiation 62P (CD62P) was reduced, leading to decreased cellular inflammation and adhesion. Conclusions: CHD-associated biomarker ZNF429 was identified through bioinformatics analysis to potentially regulate the expression of inflammatory factors IL-6, IL-1β, and TNF-α, along with adhesion molecules ICAM-1, VCAM-1, CD62E, and CD62P. This modulation influence was subsequently found to impact the progression of CHD. These findings offered valuable insights into potential targets for further investigation and therapeutic interventions for CHD management.

Construction of an endoplasmic reticulum stress and cuproptosis -related lncRNAs signature in chemosensitivity in hepatocellular carcinoma by comprehensive bioinformatics analysis

Endoplasmic reticulum stress (ERS) and cuproptosis have remarkable effects on hepatocellular carcinoma (HCC) leading to a poor prognosis. The current study aimed to explore credible signature for predicting the prognosis of HCC based on ERS and cuproptosis-related lncRNAs. In our study, clinical and transcriptomic profiles of HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. An ERS and cuproptosis-related lncRNA prognostic signature, including NRAV, SNHG3, LINC00839 and AC004687.1, was determined by correlation tests, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) methods. Survival and predictive value were evaluated using Kaplan–Meier and receiver operating characteristic (ROC) curves, while calibration and nomograms curves were developed. Besides the enrichment analyses for ERS and cuproptosis-related lncRNAs, mutational status and immune status were assessed with TMB and ESTIMATE. Additionally, consensus cluster analysis was employed to compare cancer subtype differences, while drug sensitivity and immunologic efficacy were evaluated for further exploration. qRT-PCR and CCK-8 were utilized to verify the alteration of the prognostic lncRNAs expression and proliferation in vitro. High-risk groups exhibited poorer prognosis. The signature exhibited robust predictive value as an independent prognostic indicator and showed significant correlation with clinicopathological features. In the enriched analysis, biological membrane pathways were enriched. Low-risk patients had lower TMB and higher immune status. A cluster analysis revealed that cluster 2 had the best clinical immunological efficacy and most active immune function. In brief, our constructed signature with ERS and cuproptosis-related lncRNAs was associated survival outcomes of HCC, and can be used to predict the clinical classification and curative effect.

Radiomic detection of abnormal brain regions in tuberous sclerosis complex.

Radiomics refers to the extraction of quantitative information from medical images and is most commonly utilized in oncology to provide ancillary information for solid tumor diagnosis, prognosis, and treatment response. The traditional radiomic pipeline involves segmentation of volumes of interest with comparison to normal brain. In other neurologic disorders, such as epilepsy, lesion delineation may be difficult or impossible due to poor anatomic definition, small size, and multifocal or diffuse distribution. Tuberous sclerosis complex (TSC) is a rare genetic disease in which brain magnetic resonance imaging (MRI) demonstrates multifocal abnormalities with variable imaging and epileptogenic features. The purpose of this study was to develop a radiomic workflow for identification of abnormal brain regions in TSC, using a whole-brain atlas-based approach with generation of heatmaps based on signal deviation from normal controls. This was a retrospective pilot study utilizing high-resolution whole-brain 3D FLAIR MRI datasets from retrospective enrollment of tuberous sclerosis complex (TSC) patients and normal controls. Subjects underwent MRI including high-resolution 3D FLAIR sequences. Preprocessing included skull stripping, coregistration, and intensity normalization. Using the Brainnetome and Harvard-Oxford atlases, brain regions were parcellated into 318 discrete regions. Expert neuroradiologists spatially labeled all tubers in TSC patients using ITK-SNAP. The pyradiomics toolbox was used to extract 88 radiomic features based on IBSI guidelines, comparing tuber-affected and non-tuber-affected parenchyma in TSC patients, as well as normal brain tissue in control patients. For model training and validation, regions with tubers from 20 TSC patients and 30 normal control subjects were randomly divided into two training sets (80%) and two validation sets (20%). Additional model testing was performed on a separate group of 20 healthy controls. LASSO (least absolute shrinkage and selection operator) was used to perform variable selection and regularization to identify regions containing tubers. Relevant radiomic features selected by LASSO were combined to produce a radiomic score ω, defined as the sum of squared differences from average control group values. Region-specific ω scores were converted to heat maps and spatially coregistered with brain MRI to reflect overall radiomic deviation from normal. The proposed radiomic workflow allows for quantification of deviation from normal in 318 regions of the brain with the use of a summative radiomic score ω. This score can be used to generate spatially registered heatmaps to identify brain regions with radiomic abnormalities. The pilot study of TSC showed radiomic scores ω that were statistically different in regions containing tubers from regions without tubers/normal brain (p<0.0001). Our model exhibits an AUC of 0.81 (95% confidence interval: 0.78-0.84) on the testing set, and the best threshold obtained on the training set, when applied to the testing set, allows us to identify regions with tubers with a specificity of 0.91 and a sensitivity of 0.60. We describe a whole-brain atlas-based radiomic approach to identify abnormal brain regions in TSC patients. This approach may be helpful for identifying specific regions of interest based on relatively greater signal deviation, particularly in clinical scenarios with numerous or poorly defined anatomic lesions.