Least Absolute Shrinkage Selection Operator Research Articles

System Analysis Based on Pancreatic Cancer Progression Identifies BRINP2 as a Novel Prognostic Biomarker.

Pancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system, which develops rapidly and has no obvious early symptoms. This study aims to discover the biomarkers associated with PAAD development. We obtained RNA expression of PAAD patient samples and corresponding clinical data from The cancer genome atlas (TCGA), and screened out BMP/RA-inducible neural-specific protein 2 (BRINP2) gene which is highly associated with PAAD severity. Then, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and single-sample gene set enrichment analysis (ssGSEA) analysis were performed to explore the biological functions of BRINP2. Subsequently, long non-coding RNA (lncRNAs) associated with BRINP2 were screened out via correlation analysis, and Cox regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were used to construct the risk prediction model. We further validated the expression level of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in vitro. We proposed that BRINP2 might be correlated to the tumor immune microenvironment and could also be used as a biomarker for PAAD progression. GO enrichment analysis and KEGG pathway analysis showed that the prognostic model was highly correlated to immune microenvironment-related pathways. Additionally, we established a BRINP2-associated lncRNAs prognostic model consisting of three lncRNAs. We validated the expression trends of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in PAAD cells with various severity of metastatic potential using the quantitative real-time PCR (qRT-PCR). Meanwhile, pRRophetic R package was employed to predict potential therapeutic drugs for BRINP2-associated lncRNAs prognostic model of PAAD. The results suggest that BRINP2 can be used as a novel prognostic biomarker for PAAD.

Development of Radiomic-Based Model to Predict Clinical Outcomes in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.

Purpose: We aimed to assess the ability of radiomics features extracted from baseline (PET/CT0) and follow-up PET/CT scans, as well as their evolution (delta-radiomics), to predict clinical outcome (durable clinical benefit (DCB), progression, response to therapy, OS and PFS) in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. Methods: 83 NSCLC patients treated with immunotherapy who underwent a baseline PET/CT were retrospectively included. Response was assessed at 6−8 weeks (PET/CT1) using PERCIST criteria and at 3 months with iPERCIST (PET/CT2) or RECIST 1.1 criteria using CT. The predictive performance of clinical parameters (CP), standard PET metrics (SUV, Metabolic Tumor volume, Total Lesion Glycolysis), delta-radiomics and PET and CT radiomics features extracted at baseline and during follow-up were studied. Seven multivariate models with different combinations of CP and radiomics were trained on a subset of patients (75%) using least absolute shrinkage, selection operator (LASSO) and random forest classification with 10-fold cross-validation to predict outcome. Model validation was performed on the remaining patients (25%). Overall and progression-free survival was also performed by Kaplan−Meier survival analysis. Results: Numerous radiomics and delta-radiomics parameters had a high individual predictive value of patient outcome with areas under receiver operating characteristics curves (AUCs) >0.80. Their performance was superior to that of CP and standard PET metrics. Several multivariate models were also promising, especially for the prediction of progression (AUCs of 1 and 0.96 for the training and testing subsets with the PET-CT model (PET/CT0)) or DCB (AUCs of 0.85 and 0.83 with the PET-CT-CP model (PET/CT0)). Conclusions: Delta-radiomics and radiomics features extracted from baseline and follow-up PET/CT images could predict outcome in NSCLC patients treated with immunotherapy and identify patients who would benefit from this new standard. These data reinforce the rationale for the use of advanced image analysis of PET/CT scans to further improve personalized treatment management in advanced NSCLC.

Construction and validation of an angiogenesis-related scoring model to predict prognosis, tumor immune microenvironment and therapeutic response in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with high morbidity and mortality. Identifying an effective marker for predicting the prognosis and therapeutic response is extremely meaningful. Angiogenesis-related genes (ARGs) play important roles in the tumor progression and immune-suppressive microenvironment formation. The differential expressed ARGs associated with the prognosis of HCC were identified in the TCGA dataset. Univariate Cox and least absolute shrinkage selection operator (LASSO) regression were applied to construct a ARGs Scoring model. The prognostic value of the ARGs Scoring model was assessed by Cox regression, Kaplan-Meier (KM) and ROC curve analyses. Then the model was further validated in an external dataset, ICGC dataset. The patients were split into two groups based on the ARGs Score and the clinical features were compared. TIMER, CIBERSORT and xCell algorithms were utilized to analyze the correlation between the ARGs Score and tumor immune microenvironment (TIME). Furthermore, we analyzed the efficacy of the model in predicting the therapeutic response for immunotherapy, targeted therapy and TACE treatment in different cohorts. A total of 97 differential expressed ARGs were identified relating to the prognosis of HCC patients from the TCGA dataset. Then the ARGs Scoring model based on a 9-gene signature was constructed using the Cox and LASSO regression analyses. Higher ARGs Score had a poor clinical outcome and was considered to be an independent prognostic predictor for HCC in the multivariate Cox analysis. The ARGs Score was related to the enrichment of various immune cells, such as CD4+ T cells, Treg, macrophage, neutrophil and dendritic cells, exhibiting a more immunosuppressive phenotype. Higher ARGs Score was correlated with higher expression of immune checkpoint genes and poor response to immunotherapy. Furthermore, higher ARGs Score indicated poor therapeutic response in the sorafenib and TACE treatment cohorts, individually. The ARGs Scoring model exhibited robust predictive value for the prognosis and TIME for HCC patients. Higher ARGs Score indicated poor therapeutic response of the immunotherapy, sorafenib and TACE treatment. The ARGs Scoring model could be used as a biomarker to help physicians to develop more individualized treatment for HCC patients.

Risk prediction model of polypharmacy for community-dwelling elderly patients: An assessment tool for early detection.

Background: Polypharmacy has become a major and growing public health issue, with significant implications for health outcomes and expenditure on healthcare resources. In this study, a risk prediction model of polypharmacy represented by a nomogram for community-dwelling elderly patients based on the Chinese population was constructed. Methods: A cross-sectional study was conducted in Shanghai, China. The variables data affecting polypharmacy were fetched from the information system database of health government departments in Shanghai. The Least Absolute Shrinkage Selection Operator (LASSO) regression analysis was used to select the predictor variables, and multivariate logistic regression was used to establish the prediction model. A visual tool of the nomogram was established for predicting the risk of polypharmacy in the elderly population. In addition, the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to estimate the performance of the model. Results: A total of 80,012 elderly patients were included in this study. Eight variables, containing age, residential area, preferred medical institutions, number of visits to tertiary hospitals, number of visits to secondary hospitals, number of visits to community health centers, number of diagnoses, and main types of disease, were included in the risk prediction model of nomogram. The area under the curve (AUC) of the nomogram was 0.782 in both sets, demonstrating that the model has a good discriminant ability. The calibration chart shows that the prediction model fits well with the validation set. DCA results displayed that the threshold probabilities of the two sets in the prediction model reached up to 90%, implying that the model had a preferable application value. Conclusion: This study explored the risk factors for polypharmacy among the elderly in Shanghai, China, and applied the nomogram to establish a predictive model via eight variables, which provided an effective tool for early screening and timely prevention of polypharmacy. Family physicians or pharmacists could scientifically use the tool to closely observe community-dwelling elderly patients, decreasing the adverse health effects caused by medication for the elderly.

A nomogram to predict hyperkalemia in patients with hemodialysis: a retrospective cohort study

BackgroundHyperkalemia increases the risk of mortality and cardiovascular-related hospitalizations in patients with hemodialysis. Predictors of hyperkalemia are yet to be identified. We aimed at developing a nomogram able to predict hyperkalemia in patients with hemodialysis.MethodsWe retrospectively screened patients with end-stage renal disease (ESRD) who had regularly received hemodialysis between Jan 1, 2017, and Aug 31, 2021, at Lishui municipal central hospital in China. The outcome for the nomogram was hyperkalemia, defined as serum potassium [K+] ≥ 5.5 mmol/L. Data were collected from hemodialysis management system. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA). This model was validated internally by calculating the performance on a validation cohort.ResultsA total of 401 patients were enrolled in this study. 159 (39.65%) patients were hyperkalemia. All participants were divided into development (n = 256) and validation (n = 145) cohorts randomly. Predictors in this nomogram were the number of hemodialysis session, blood urea nitrogen (BUN), serum sodium, serum calcium, serum phosphorus, and diabetes. The ROC curve of the training set was 0.82 (95%CI 0.77, 0.88). Similar ROC curve was achieved at validation set 0.81 (0.74, 0.88). The calibration curve demonstrated that the prediction outcome was correlated with the observed outcome.ConclusionThis nomogram helps clinicians in predicting the risk of PEW and managing serum potassium in the patients with hemodialysis.

Radiomics nomogram for prediction of microvascular invasion in hepatocellular carcinoma based on MR imaging with Gd-EOB-DTPA

To develop a radiomics nomogram for predicting microvascular invasion (MVI) before surgery in hepatocellular carcinoma (HCC) patients. The data from a total of 189 HCC patients (training cohort: n = 141; validation cohort: n = 48) were collected, involving the clinical data and imaging characteristics. Radiomics features of all patients were extracted from hepatobiliary phase (HBP) in 15 min. Least absolute shrinkage selection operator (LASSO) regression and logistic regression were utilized to reduce data dimensions, feature selection, and to construct a radiomics signature. Clinicoradiological factors were identified according to the univariate and multivariate analyses, which were incorporated into the final predicted nomogram. A nomogram was developed to predict MVI of HCC by combining radiomics signatures and clinicoradiological factors. Radiomics nomograms were evaluated for their discrimination capability, calibration, and clinical usefulness. In the clinicoradiological factors, gender, alpha-fetoprotein (AFP) level, tumor shape and halo sign served as the independent risk factors of MVI, with which the area under the curve (AUC) is 0.802. Radiomics signatures covering 14 features at HBP 15 min can effectively predict MVI in HCC, to construct radiomics signature model, with the AUC of 0.732. In the final nomogram model the clinicoradiological factors and radiomics signatures were integrated, outperforming the clinicoradiological model (AUC 0.884 vs. 0.802; p <0.001) and radiomics signatures model (AUC 0.884 vs. 0.732; p < 0.001) according to Delong test results. A robust calibration and discrimination were demonstrated in the nomogram model. The results of decision curve analysis (DCA) showed more significantly clinical efficiency of the nomogram model in comparison to the clinicoradiological model and the radiomic signature model. Depending on the clinicoradiological factors and radiological features on HBP 15 min images, nomograms can effectively predict MVI status in HCC patients.

Construction of prognostic signature of breast cancer based on N7-Methylguanosine-Related LncRNAs and prediction of immune response

Background: Long non-coding RNA (LncRNA) is a prognostic factor for malignancies, and N7-Methylguanosine (m7G) is crucial in the occurrence and progression of tumors. However, it has not been documented how well m7G-related LncRNAs predict the development of breast cancer (BC). This study aims to develop a predictive signature based on long non-coding RNAs (LncRNAs) associated with m7G to predict the prognosis of breast cancer patients. Methods: The Cancer Genome Atlas (TCGA) database provided us with the RNA-seq data and matching clinical information of individuals with breast cancer. To identify the signature of N7-Methylguanosine-Related LncRNAs and create a prognostic model, we employed co-expression network analysis, least absolute shrinkage selection operator (LASSO) regression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. The signature was assessed using the Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curve. A nomogram and principal component analysis (PCA) were employed to confirm the predictive signature's usefulness. Then, we examined the drug sensitivity between the two risk groups and utilized single-sample gene set enrichment analysis (ssGSEA) to investigate the association between predictive factors and the tumor immune microenvironment in high-risk and low-risk groups. Results: Nine m7G-related LncRNAs (LINC01871, AP003469.4, Z68871.1, AC245297.3, EGOT, TFAP2A-AS1, AL136531.1, SEMA3B-AS1, AL606834.2) that are independently associated with the overall survival time (OS) of BC patients make up the signature we developed. For predicting 1-, 3-, and 5-year survival rates, the areas under the ROC curve (AUC) were 0.715, 0.724, and 0.726, respectively. The Kaplan-Meier analysis revealed that the prognosis of BC patients in the high-risk group was worse than that of those in the low-risk group. When compared to clinicopathological variables, multiple regression analysis demonstrated that risk score was a significant independent predictive factor for BC patients. The results of the ssGSEA study revealed a substantial correlation between the predictive traits and the BC patients' immunological status, low-risk BC patients had more active immune systems, and they responded better to PD1/L1 immunotherapy. Conclusion: The prognostic signature, which is based on m7G-related LncRNAs, can be utilized to inform patients' customized treatment plans by independently predicting their prognosis and how well they would respond to immunotherapy.

Identification and validation of ferroptosis-related lncRNA signature as a prognostic model for skin cutaneous melanoma.

BackgroundMelanoma is a type of skin cancer, which originates from the malignant transformation of epidermal melanocytes, with extremely high lethality. Ferroptosis has been documented to be highly related to cancer pathogenesis and the effect of immunotherapy. In addition, the dysregulation of lncRNAs is greatly implicated in melanoma progression and ferroptosis regulation. However, the significance of ferroptosis-related lncRNA in melanoma treatment and the prognosis of melanoma patients remains elusive.Methods Via Least Absolute Shrinkage Selection Operator (LASSO) regression analysis in the TCGA SKCM database, a cutaneous melanoma risk model was established based on differentially-expressed ferroptosis-related lncRNAs (DEfrlncRNAs). The nomogram, receiver operating characteristic (ROC) curves, and calibration plots were conducted to examine the predictive performance of this model. Sequentially, we continued to analyze the differences between the high- and low-risk groups, in terms of clinical characteristics, immune cell infiltration, immune-related functions, and chemotherapy drug sensitivity. Moreover, the expressions of DEfrlncRNAs, PD-L1, and CD8 were also examined by qRT-PCR and immunohistochemical staining in melanoma tissues to further confirm the potential clinical implication of DEfrlncRNAs in melanoma immunotherapy.Results16 DEfrlncRNAs were identified, and a representative risk score for patient survival was constructed based on these 16 genes. The risk score was found to be an independent prognostic factor for the survival of melanoma patients. In addition, the low-risk group of patients had higher immune cell infiltration in the melanoma lesions, higher sensitivity to chemotherapeutic agents, and a better survival prognosis. Besides, the high expression of the identified 5 DEfrlncRNA in the low-risk group might suggest a higher possibility to benefit from immune checkpoint blockade therapy in the treatment of melanoma.ConclusionThe DEfrlncRNA risk prediction model related to ferroptosis genes can independently predict the prognosis of patients with melanoma and provide a basis for evaluating the response of clinical treatment in melanoma.

Association between vitamin D3 levels and frailty in the elderly: A large sample cross-sectional study.

BackgroundFrailty is recognized as a cornerstone of geriatric medicine. Accurately screening and identifying frailty can promote better quality and personalized medical services for the elderly. Previous studies have shown that the association between vitamin D and frailty in the elderly population is still controversial. More research is needed to explore the association between them.Materials and methodsWe used three waves of data from the National Health and Nutrition Examination Survey (NHANES). Based on the widely accepted AAH FRAIL Scale, we measured and evaluated the participants’ frailty from five aspects: fatigue, resistance, ambulation, illness, and loss of weight. All possible relevant variables are included. Machine learning XGboost algorithm, the Least Absolute Shrinkage Selection Operator (LASSO) regression and univariate logistic regression were used to screen variables, and multivariate logistic regression and generalized additive model (GAM) were used to build the model. Finally, subgroup analysis and interaction test were performed to further confirm the association.ResultsIn our study, XGboost machine learning algorithm explored the relative importance of all included variables, which confirmed the close association between vitamin D and frailty. After adjusting for all significant covariates, the result indicated that for each additional unit of 25-hydroxyvitamin D3, the risk of frailty was reduced by 1.3% with a statisticaldifference. A smooth curve was constructed based on the GAM. It was found that there was a significant negative correlation between 25-hydroxyvitamin D3 and the risk of frailty.ConclusionThere may be a negative correlation between 25-hydroxyvitamin D3 and the risk of frailty. However, more well-designed studies are needed to verify this relationship.

Prediction of TTF-1 expression in non-small-cell lung cancer using machine learning-based radiomics.

To explore the feasibility and performance of machine learning-based radiomics models in predicting thyroid transcription factor-1 (TTF-1) expression in non-small cell lung cancer (NSCLC). A total of 227 NSCLC patients were included in this retrospective study and divided into the training set and test set with a ratio of 8:2 randomly. Lung tumors on CT images were semi-automatic segmented utilizing 3D Slicer. Radiomic features quantifying tumor intensity, shape, texture, and transformed wavelet were extracted using a Python toolkit. Variance threshold (VT), principal component analysis (PCA), and least absolute shrinkage selection operator (LASSO) were used to reduce features; logistic regression (LR), random forest (RF), and support vector machine (SVM) were used to develop classifier, respectively. The performance of the models was evaluated by areas under the curves (AUC) of receiver operating characteristic (ROC) curves. Different models were compared by the Delong test to determine the optimal algorithms. Total 1968 radiomic features were extracted from the lung tumors images, and then 13, 15, and 13 stable features were selected by VT, PCA, and LASSO, respectively. Each classifier could discriminate against the TTF-1-positive groups with average AUC ranging from 0.601 to 0.784 in the training set. Among the models, three models constructed by the LASSO method showed satisfactory performance in the test set with AUC ranging from 0.715 to 0.787. The Delong test showed no significant difference between the LASSO models (P > 0.05). Machine learning-based radiomics model could predict the expression of TTF-1 in NSCLC patients.

Development of a Human Immunodeficiency Virus Risk Prediction Model Using Electronic Health Record Data From an Academic Health System in the Southern United States.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is underutilized in the southern United States. Rapid identification of individuals vulnerable to diagnosis of HIV using electronic health record (EHR)-based tools may augment PrEP uptake in the region. Using machine learning, we developed EHR-based models to predict incident HIV diagnosis as a surrogate for PrEP candidacy. We included patients from a southern medical system with encounters between October 2014 and August 2016, training the model to predict incident HIV diagnosis between September 2016 and August 2018. We obtained 74 EHR variables as potential predictors. We compared Extreme Gradient Boosting (XGBoost) versus least absolute shrinkage selection operator (LASSO) logistic regression models, and assessed performance, overall and among women, using area under the receiver operating characteristic curve (AUROC) and area under precision recall curve (AUPRC). Of 998 787 eligible patients, 162 had an incident HIV diagnosis, of whom 49 were women. The XGBoost model outperformed the LASSO model for the total cohort, achieving an AUROC of 0.89 and AUPRC of 0.01. The female-only cohort XGBoost model resulted in an AUROC of 0.78 and AUPRC of 0.00025. The most predictive variables for the overall cohort were race, sex, and male partner. The strongest positive predictors for the female-only cohort were history of pelvic inflammatory disease, drug use, and tobacco use. Our machine-learning models were able to effectively predict incident HIV diagnoses including among women. This study establishes feasibility of using these models to identify persons most suitable for PrEP in the South.

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer.

Gastric cancer is the fourth most frequent cancer and has a high death rate. Immunotherapy represented by PD-1 has brought hope for the treatment of advanced gastric cancer. Methylation of the m6A genes is linked to the onset and progression of numerous cancers, but there are few studies on gastric cancer. The main purpose of this study aims to analyze the relationship between m6A RNA methylation regulators, PD-L1, prognosis and tumor immune microenvironment (TIME) in gastric cancer. The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases were used to acquire transcriptomic data and clinical information from gastric cancer patients. The changes in m6A regulator expression levels in gastric cancer tissues and normal tissues were studied. Consensus clustering analysis was used to separate gastric cancer samples into two categories. We employed Least Absolute Shrinkage, Selection Operator (LASSO) Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and cBioPortal to analyze the m6A regulators, PD-L1 and TIME in gastric cancer. In gastric cancer tissues, the majority of m6A regulatory factors are considerably overexpressed. Two gastric cancer subgroups (Cluster1/2) based on consensus clustering of 21 m6A regulators. PD-L1 and PD-1 expression levels were significantly higher in gastric cancer tissues, and they were significantly linked with METTL3, WTAP, HNRNPD, ZC3H7B, METTL14, FTO, PCIF1, HNRNPC, YTHDF1 and YTDHF2. Cluster1 showed a large increase in resting memory CD4+ T cells, regulatory T cells, naïve B cells, active NK cells, and resting Mast cells. Cluster1 and Cluster2 were shown to be involved in numerous critical signaling pathways, including base excision repair, cell cycle, nucleotide excision repair, RNA degradation, and spliceosome pathways. Gastric cancer RiskScores based on prognostic factors have been found as independent prognostic indicators. The amount of tumor-infiltrating immune cells is dynamically affected by changes in the copy number of m6A methylation regulators associated with TIME.

Comparison of Linear and Non-linear Models for Coconut Yield Prediction in Coimbatore Using Weather Parameters and External Factors

Coconut is the world's most significant plantation crop, and it is grown in practically every country. As Coimbatore is the leading producer of coconut in Tamil Nadu, followed by Thanjavur and Kanyakumari, this study is centred on the Coimbatore area. West Coast Tall is a popular cultivar that produces more than other types. The West Coast Tall (WCT) cultivar was used in this research. In this paper, four models were developed such as Ridge, Least Absolute Shrinkage Selection Operator (LASSO), Elastic net (ELNET) regression methods and Artificial Neural Networks (ANN). Further, we validate this model using field-level data from TNAU coconut research farm for two years. The purpose of this communication is to find the best fit model for prediction of coconut yield using weather parameters and external factors in Coimbatore district. The models were selected based on different performance metrics such as RMSE, MAPE, MAE, and R2. Among the four models developed in the study, the ELNET model is found to be best model for prediction of coconut yield based on weather and external factors for the available data in the studied region.

Identification of diagnostic signatures associated with immune infiltration in Alzheimer's disease by integrating bioinformatic analysis and machine-learning strategies.

ObjectiveAs a chronic neurodegenerative disorder, Alzheimer’s disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology.MethodsThe expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples. Functional enrichment analysis was performed to reveal AD-associated biological functions and key pathways. Besides, we applied the Least Absolute Shrinkage Selection Operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analysis to screen potential diagnostic feature genes in AD, which were further tested in AD brains of the validation cohort (GSE5281). The discriminatory ability was then assessed by the area under the receiver operating characteristic curves (AUC). Finally, the CIBERSORT algorithm and immune cell infiltration analysis were employed to assess the inflammatory state of AD.ResultsA total of 49 DEGs were identified. The functional enrichment analysis revealed that leukocyte transendothelial migration, cytokine receptor interaction, and JAK-STAT signaling pathway were enriched in the AD group. MAF basic leucine zipper transcription factor F (MAFF), ADCYAP1, and ZFP36L1 were identified as the diagnostic biomarkers of AD with high discriminatory ability (AUC = 0.850) and validated in AD brains (AUC = 0.935). As indicated from the immune cell infiltration analysis, naive B cells, plasma cells, activated/resting NK cells, M0 macrophages, M1 macrophages, resting CD4+ T memory cells, resting mast cells, memory B cells, and resting/activated dendritic cells may participate in the development of AD. Additionally, all diagnostic signatures presented different degrees of correlation with different infiltrating immune cells.ConclusionMAFF, ADCYAP1, and ZFP36L1 may become new candidate biomarkers of AD, which were closely related to the pathogenesis of AD. Moreover, the immune cells mentioned above may play crucial roles in disease occurrence and progression.

Severe Acute Respiratory Syndrome Coronavirus 2 Incidence and Risk Factors in a National, Community-Based Prospective Cohort of US Adults.

BackgroundProspective cohort studies of SARS-CoV-2 incidence complement case-based surveillance and cross-sectional seroprevalence surveys.MethodsWe estimated the incidence of SARS-CoV-2 infection in a national cohort of 6,738 U.S. adults, enrolled March-August 2020. Using Poisson models, we examined the association of social distancing and a composite epidemiologic risk score with seroconversion. The risk score was created using LASSO regression to identify factors predictive of seroconversion. The selected factors were household crowding, confirmed case in household, indoor dining, gathering with groups ≥ 10, and no masking in gyms/salons.ResultsAmong 4,510 individuals with ≥1 serologic test, 323 (7.3%, 95% confidence interval [CI] 6.5%-8.1%) seroconverted by January 2021. Among 3,422 participants seronegative in May-September 2020 and retested during November 2020-January 2021, 161 seroconverted over 1,646 person-years of follow-up (9.8 per 100 person-years [95%CI 8.3-11.5]). Seroincidence rate was lower among females compared to males (IRR: 0.69, 95% CI 0.50-0.94) and higher among Hispanic (IRR: 2.09, 95% CI 1.41-3.05) participants compared to White non-Hispanic. In adjusted models, participants who reported social distancing with people they did not know (IRRalways vs. never: 0.42, 95% CI 0.20-1.0) and with people they knew (IRRalways vs. never 0.64, 95%CI 0.39-1.06; IRRsometimes vs. never 0.60, 95% CI 0.38-0.96) had lower seroconversion risk. Seroconversion risk increased with epidemiologic risk score (IRRmedium vs. low 1.68, 95% CI 1.03-2.81; IRRhigh vs. low 3.49, 95% CI 2.26-5.58). Only 29% of those who seroconverted reported isolating and 19% were asked about contacts.ConclusionModifiable risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the U.S.

Five EMT-related genes signature predicts overall survival and immune environment in microsatellite instability-high gastric cancer.

Microsatellite instability-high (MSI-H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory cytokines. GC patients with MSI-H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood. RNA expression levels and clinical parameters of GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The data were analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression. In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for the tumor microenvironment study. By ssGSEA and survival analysis, the EMT signaling pathway was identified as a representative pathway, which can stratify the patients with MSI-H GC with significant survival predictive power. Then, a novel representative EMT-related five-gene signature (namely CALU, PCOLCE2, PLOD2, SGCD, and THBS2) was established from EMT signaling gene set, which sensitivity and specificity were further validated in the independent GEO database (GSE62254) cohort for disease outcome prediction. Based on public single-cell data and in situ immunohistochemistry, we found that most of these five genes were abundantly expressed in cancer-associated fibroblasts. Furthermore, patients with high or low risk divided by this five-gene signature exhibited a strong correlation of the distinct patterns of tumor immune microenvironment. By mIHC staining of sections from 30 patients with MSI-H status, we showed that the patients with better prognoses had the increased infiltration of CD8+ cells in the primary tumoral tissue. Our study developed a simple five-gene signature for stratifying MSI-H GC patients with survival predictive power.

Characteristics of Fatty Acid Metabolism in Lung Adenocarcinoma to Guide Clinical Treatment.

BackgroundLung adenocarcinoma (LUAD) has a very high morbidity and mortality rate, and its pathogenesis and treatment are still in the exploratory stage. Fatty acid metabolism plays a significant role in tumorigenesis, progression, and immune regulation. However, the gene expression of fatty acid metabolism in patients with LUAD and its relationship with prognosis remain unclear.MethodsWe collected 309 fatty acid metabolism-related genes, established a LUAD risk model based on The Cancer Genome Atlas (TCGA) using Least Absolute Shrinkage Selection Operator (LASSO) regression analysis, and divided LUAD patients into high-risk and low-risk groups, which were further validated using the Gene Expression Omnibus (GEO) database. The nomogram, principal component analysis (PCA), and receiver operating characteristic (ROC) curves showed that the model had the best predictive performance. The ROC curves and calibration plots confirmed that the nomogram had good predictive power. We further analyzed the differences in clinical characteristics, immune cell infiltration, immune-related functions, chemotherapy drug sensitivity, and immunotherapy efficacy between the high-risk and low-risk groups. We also analyzed the enrichment pathways and protein–protein interaction (PPI) networks of different genes in the high-risk and low-risk groups to screen for target genes and further explored the correlation between target genes and differences in survival prognosis, clinical characteristics, gene mutations, and immune cells.ResultsRisk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three pivotal genes with poor survival prognosis in the high expression group, which were strongly associated with clinical symptoms and immune cells.ConclusionRisk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three survival prognosis-associated target genes that are closely associated with clinical symptoms and immune cells and may be potential targets for immune-targeted therapy in LUAD.

A model to predict a risk of allergic rhinitis based on mitochondrial DNA copy number.

To determine whether mitochondrial DNA copy number (mtDNA-CN) is associated with allergic rhinitis (AR), and further establish a nomogram model for the early diagnosis of AR. We carried out a case-control study involving a total of 134 subjects, including 66 healthy controls and 68 AR patients. The mtDNA-CN in peripheral blood of all subjects was detected by real-time fluorescence quantitative polymerase chain reaction, and general information of patients was recorded. And, least absolute shrinkage selection operator (LASSO) regression was used to screen clinically significant variables, which were substituted into a logistic regression analysis to determine independent risk factors. Next, a nomogrammodelwas developed fortherisk prediction of AR. Then, internalvalidation was performed with the bootstrapresampling. Ultimately, theclinical benefit andvalidityof the nomogram wereassessedby receiver operating characteristic (ROC) curve, bias-corrected curve, and decision curve analysis (DCA). MtDNA-CN and total IgE were determined asindependent risk factors of AR. The final model achieved an area under the ROC curve (AUC) of 0.869, and the DCA curve demonstrated that the nomogram was clinically beneficial for practical application. An increase of the mtDNA-CN was linked to the occurrence risk of AR. The nomogram prediction model based on mtDNA-CN showed the potential clinical utility in improving risk prediction and providing new insights for exploring the pathogenesis of AR.

Preoperative Evaluation of Gd-EOB-DTPA-Enhanced MRI Radiomics-Based Nomogram in Small Solitary Hepatocellular Carcinoma (≤3cm) With Microvascular Invasion: A Two-Center Study.

Preoperative evaluation of microvascular invasion (MVI) in small solitary hepatocellular carcinoma (HCC; maximum lesion diameter ≤ 3 cm) is important for treatment decisions. To apply gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI to develop and validate a nomogram for preoperative evaluation of MVI in small solitary HCC and to compare the effectiveness of radiomics evaluation models based on different volumes of interest (VOIs). Retrospective. A total of 196 patients include 62 MVI-positive and 134 MVI-negative patients were enrolled (training cohort, n=105; testing cohort, n=45; external validation cohort, n=46). 3.0 T, fat suppressed fast-spin-echo T2-weighted and Gd-EOB-DTPA-enhanced T1-weighted magnetization-prepared rapid gradient-echo sequences. Radiomics features were extracted on T2-weighted, arterial phase (AP), and hepatobiliary phase (HBP) images from different VOIs (VOIintratumor and VOIintratumor+peritumor ) and filtered by the least absolute shrinkage selection operator (LASSO) regression. From VOIintratumor and VOIintratumor+peritumor , eight radiomics models were constructed based on three MRI sequences (T2-weighted, AP, and HBP) and fused sequences (combined of three sequences). Nomograms were constructed of a clinical-radiological (CR) model and a clinical-radiological-radiomics (CRR) model. One-way analysis of variance, independent t-test, Chi-square test or Fisher's exact test, Wilcoxon rank-sum test, LASSO, logistic regression analysis, area under the curve (AUC), nomograms, decision curve, net reclassification improvement (NRI), integrated discrimination improvement (IDI) analyses, and DeLong test. Among eight radiomics models, the fused sequences-based VOIintratumor+peritumor radiomics model showed the best performance. The CRR model containing the best performance radiomics model and CR model with the AUC values were 0.934, 0.889, and 0.875, respectively. NRI and IDI analyses showed that the CRR model improved evaluation efficacy over the CR model for all three cohorts (all P-value <0.05). The CRR model nomogram could preoperatively evaluate MVI in small solitary HCC. The radiomics model based on VOIintratumor+peritumor might achieve better evaluation results. 4 TECHNICAL EFFICACY STAGE: 2.

AGTR1, PLTP, and SCG2 associated with immune genes and immune cell infiltration in calcific aortic valve stenosis: analysis from integrated bioinformatics and machine learning.

Background: Calcific aortic valve stenosis (CAVS) is a crucial cardiovascular disease facing aging societies. Our research attempts to identify immune-related genes through bioinformatics and machine learning analysis. Two machine learning strategies include Least Absolute Shrinkage Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE). In addition, we deeply explore the role of immune cell infiltration in CAVS, aiming to study the potential therapeutic targets of CAVS and explore possible drugs. Methods: Download three data sets related to CAVS from the Gene Expression Omnibus. Gene set variation analysis (GSVA) looks for potential mechanisms, determines differentially expressed immune-related genes (DEIRGs) by combining the ImmPort database with CAVS differential genes, and explores the functions and pathways of enrichment. Two machine learning methods, LASSO and SVM-RFE, screen key immune signals and validate them in external data sets. Single-sample GSEA (ssGSEA) and CIBERSORT analyze the subtypes of immune infiltrating cells and integrate the analysis with DEIRGs and key immune signals. Finally, the possible targeted drugs are analyzed through the Connectivity Map (CMap). Results: GSVA analysis of the gene set suggests that it is highly correlated with multiple immune pathways. 266 differential genes (DEGs) integrate with immune genes to obtain 71 DEIRGs. Enrichment analysis found that DEIRGs are related to oxidative stress, synaptic membrane components, receptor activity, and a variety of cardiovascular diseases and immune pathways. Angiotensin II Receptor Type 1(AGTR1), Phospholipid Transfer Protein (PLTP), Secretogranin II (SCG2) are identified as key immune signals of CAVS by machine learning. Immune infiltration found that B cells naï ve and Macrophages M2 are less in CAVS, while Macrophages M0 is more in CAVS. Simultaneously, AGTR1, PLTP, SCG2 are highly correlated with a variety of immune cell subtypes. CMap analysis found that isoliquiritigenin, parthenolide, and pyrrolidine-dithiocarbamate are the top three targeted drugs related to CAVS immunity. Conclusion: The key immune signals, immune infiltration and potential drugs obtained from the research play a vital role in the pathophysiological progress of CAVS.