Machine learning predictions of the adverse events of different treatments in patients with ischemic left ventricular systolic dysfunction.

This study aimed to develop several new machine learning models based on hibernating myocardium to predict the major adverse cardiac events(MACE) of ischemic left ventricular systolic dysfunction(LVSD) patients receiving either percutaneous coronary intervention(PCI) or optimal medical therapy(OMT). This study included 329 LVSD patients, who were randomly assigned to the training or validation cohort. Least absolute shrinkage and selection operator(LASSO) regression was used to identify variables associated with MACE. Subsequently, various machine learning models were established. Model performance was compared using receiver operating characteristic(ROC) curves, the Brier score(BS), and the concordance index(C-index). A total of 329 LVSD patients were retrospectively enrolled between January 2016 and December 2021. Utilizing LASSO regression analysis, five factors were selected. Based on these factors, RSF, GBM, XGBoost, Cox, and DeepSurv models were constructed. In the development and validation cohorts, the C-indices were 0.888 vs. 0.955 (RSF). The RSF model (0.991 vs. 0.982 vs. 0.980) had the highest area under the ROC curve (AUC) compared with the other models. The BS (0.077 vs. 0.095vs. 0.077) of RSF model were less than 0.25 at 12, 18, and 24 months. This study developed a novel predictive model based on RSF to predict MACE in LVSD patients who underwent either PCI or OMT.

Efficacy and safety of drug-coated balloons in chronic total coronary occlusion recanalization: a systematic review and meta-analysis.

BACKGROUND: With advancements in chronic total coronary occlusion (CTO) recanalization techniques and concepts, the success rate of recanalization has been steadily increasing. However, the current data are too limited to draw any reliable conclusions about the efficacy and safety of drug-coated balloons (DCBs) in CTO percutaneous coronary intervention (PCI). Herein, we conducted a meta-analysis to confirm the efficacy of DCB in CTO PCI. METHODS: We systematically searched PubMed, Web of Science and Embase from inception to July 25, 2023. The primary outcome was major advent cardiovascular events (MACE), including cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR). The follow-up angiographic endpoints were late lumen enlargement (LLE), reocclusion and restenosis. RESULTS: Five studies with a total of 511 patients were included in the meta-analysis. Across studies, patients were predominantly male (72.9-85.7%) and over fifty years old. The summary estimate rate of MACE was 13.0% (95% CI 10.1%-15.9%, I2 = 0%, p = 0.428). The summary estimate rates of cardiac death and MI were 2.2% (95% CI 0.7%-3.7%, I2 = 0%, p = 0.873) and 1.2% (95% CI -0.2-2.6%, I2 = 13.7%, p = 0.314), respectively. Finally, the pooled incidences of TLR and TVR were 10.1% (95% CI 5.7%-14.5%, I2 = 51.7%, p = 0.082) and 7.1% (95% CI 3.0%-11.2%, I2 = 57.6%, p = 0.070), respectively. Finally, the summary estimate rates of LLE, reocclusion and restenosis were 59.4% (95% CI 53.5-65.3%, I2 = 0%, p = 0.742), 3.3% (95% CI 1.1-5.4%, I2 = 0%, p = 0.865) and 17.5% (95% CI 12.9-22.0%, I2 = 0%, p = 0.623), respectively. CONCLUSION: Accordingly, DCB has the potential to be used as a treatment for CTO in suitable patients.

Bioinformatics analysis of signature genes related to cell death in keratoconus.

Keratoconus is corneal disease in which the progression of conical dilation of cornea leads to reduced visual acuity and even corneal perforation. However, the etiology mechanism of keratoconus is still unclear. This study aims to identify the signature genes related to cell death in keratoconus and examine the function of these genes. A dataset of keratoconus from the GEO database was analysed to identify the differentially expressed genes (DEGs). A total of 3558 DEGs were screened from GSE151631. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they mainly involved in response to hypoxia, cell-cell adhesion, and IL-17 signaling pathway. Then, the cell death-related genes datasets were intersected with the above 3558 DEGs to obtain 70 ferroptosis-related DEGs (FDEGs), 32 autophagy-related DEGs (ADEGs), six pyroptosis-related DEGs (PDEGs), four disulfidptosis-related DEGs (DDEGs), and one cuproptosis-related DEGs (CDEGs). After using Least absolute shrinkage and selection operator (LASSO), Random Forest analysis, and receiver operating characteristic (ROC) curve analysis, one ferroptosis-related gene (TNFAIP3) and five autophagy-related genes (CDKN1A, HSPA5, MAPK8IP1, PPP1R15A, and VEGFA) were screened out. The expressions of the above six genes were significantly decreased in keratoconus and the area under the curve (AUC) values of these genes was 0.944, 0.893, 0.797, 0.726, 0.882 and 0.779 respectively. GSEA analysis showed that the above six genes mainly play an important role in allograft rejection, asthma, and circadian rhythm etc. In conclusion, the results of this study suggested that focusing on these genes and autoimmune diseases will be a beneficial perspective for the keratoconus etiology research.

Chemerin attracts neutrophil reverse migration by interacting with C-C motif chemokine receptor-like 2.

Neutrophil reverse migration (rM) is a recently identified phenomenon in which neutrophils migrate away from the inflammatory site back into the vasculature following initial infiltration, which involved in the resolution of loci inflammatory response or dissemination of inflammation. Present study was aimed to explore the mechanisms in neutrophil rM. By scRNA-seq on the white blood cells in acute lung injury model, we found rM-ed neutrophils exhibited increased gene expression of C-C motif chemokine receptor-like 2 (Ccrl2), an atypical chemokine receptor. Furthermore, an air pouch model was established to directly track rM-ed neutrophils in vivo. Air pouches were generated by 3 ml filtered sterile air injected subcutaneously for 3 days, and then LPS (2 mg/kg) was injected into the pouches to mimic the inflammatory state. For the rM-ed neutrophil tracking system, cell tracker CMFDA were injected into the air pouch to stain the inflammatory loci cells, and after 6 h, stained cells in blood were regarded as the rM-ed neutrophil. Based on this tracking system, we confirmed that rM-ed neutrophils showed increased CCRL2. We also found that the concentrations of the CCRL2 ligand chemerin in plasma was increased in the late stage. Neutralizing chemerin decreased the rM-ed neutrophil ratio in the blood. These results suggest that circulating chemerin attracts neutrophils to leave inflammatory sites by interacting with CCRL2, which might involve in the dissemination of inflammation.

Comparison of intravascular lithotripsy versus rotational atherectomy for the treatment of severe coronary artery calcification.

BACKGROUND: Calcified lesions are one of the most challenging cases for PCI, where optimal angiographic results and satisfying outcomes are hard to achieve. METHODS: We evaluated the baseline clinical, procedures characteristics and outcomes of patients with severe coronary artery calcification (CAC) who underwent coronary intravascular lithotripsy (IVL) and rotational atherectomy (RA). RESULTS: Respectively 152 and 238 patients who underwent IVL and RA are enrolled from January 2023 to November 2023. Regarding demographic characteristics, the gender proportion, medical history of PCI and smoke history among groups reach statistical significance. Left anterior descending and right coronary artery were the main vessels treated in both groups. The 2.5 and 3.0 mm IVL balloons and 1.5 mm burr were the most commonly used. 99.3% cases were successfully implanted drug-eluting stents after IVL balloon pre-treatment, which was higher than in the group treated with RA. During hospitalization, there were no serious adverse events in the IVL group, but there were two adverse events in the RA group. Procedural complications were higher in the RA group than the IVL group (5.5% vs. 0.7%, P = 0.027). CONCLUSIONS: IVL appears to be safe and effective for the treatment of severe CAC lesions compared to RA.

Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy.

Purpose: Corneal injury (CI) resulting in corneal opacity remains a clinical challenge. Exosomes (Exos) derived from bone marrow mesenchymal stem cells (BMSCs) have been proven effective in repairing various tissue injuries and are also considered excellent drug carriers due to their biological properties. Recently, microRNA-29b (miR-29b) was found to play an important role in the autophagy regulation which correlates with cell inflammation and fibrosis. However, the effects of miR-29b and autophagy on CI remain unclear. To find better treatments for CI, we used Exos to carry miR-29b and investigated its effects in the treatment of CI. Methods: BMSCs were transfected with miR-29b-3p agomir/antagomir and negative controls (NCs) to obtain Exos-29b-ago, Exos-29b-anta, and Exos-NC. C57BL/6J mice that underwent CI surgeries were treated with Exos-29b-ago, Exos-29b-anta, Exos-NC, or PBS. The autophagy, inflammation, and fibrosis of the cornea were estimated by slit-lamp, hematoxylin and eosin (H&E) staining, immunofluorescence, RT‒qPCR, and Western blot. The effects of miR-29b-3p on autophagy and inflammation in immortalized human corneal epithelial cells (iHCECs) were also investigated. Results: Compared to PBS, Exos-29b-ago, Exos-29b-anta, and Exos-NC all could ameliorate corneal inflammation and fibrosis. However, Exos-29b-ago, which accumulated a large amount of miR-29b-3p, exerted excellent potency via autophagy activation by inhibiting the PI3K/AKT/mTOR pathway and further inhibited corneal inflammation via the mTOR/NF-κB/IL-1ß pathway. After Exos-29b-ago treatment, the expressions of collagen type III, α-smooth muscle actin, fibronectin, and vimentin were significantly decreased than in other groups. In addition, overexpression of miR-29b-3p prevented iHCECs from autophagy impairment and inflammatory injury. Conclusions: Exos from BMSCs carrying miR-29b-3p can significantly improve the therapeutic effect on CI via activating autophagy and further inhibiting corneal inflammation and fibrosis.

Biolimus-coated versus paclitaxel-coated balloons for coronary in-stent restenosis (BIO ASCEND ISR): a randomised, non-inferiority trial.

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23±0.37 mm compared to 0.25±0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32±1.04 mm2 in the BCB group compared to 2.37±0.93 mm2 in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm2; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB. (ClinicalTrials.gov: NCT04733443).

Current advances and future trends of hormesis in disease.

Hormesis, an adaptive response, occurs when exposure to low doses of a stressor potentially induces a stimulatory effect, while higher doses may inhibit it. This phenomenon is widely observed across various organisms and stressors, significantly advancing our understanding and inspiring further exploration of the beneficial effects of toxins at doses both below and beyond traditional thresholds. This has profound implications for promoting biological regulation at the cellular level and enhancing adaptability throughout the biosphere. Therefore, conducting bibliometric analysis in this field is crucial for accurately analyzing and summarizing its current research status. The results of the bibliometric analysis reveal a steady increase in the number of publications in this field over the years. The United States emerges as the leading country in both publication and citation numbers, with the journal Dose-Response publishing the highest number of papers in this area. Calabrese E.J. is a prominent person with significant contributions and influence among authors. Through keyword co-occurrence and trend analysis, current hotspots in this field are identified, primarily focusing on the relationship between hormesis, oxidative stress, and aging. Analysis of highly cited references predicts that future research trends may center around the relationship between hormesis and stress at different doses, as well as exploring the mechanisms and applications of hormesis. In conclusion, this review aims to visually represent hormesis-related research through bibliometric methods, uncovering emerging patterns and areas of focus within the field. It provides a summary of the current research status and forecasts trends in hormesis-related research.

Development of a Novel Nomogram to Predict Major Adverse Cardiac Events in Patients with Chronic Total Occlusion.

Objectives: To create a nomogram using single photon emission computed tomography (SPECT) myocardial perfusion imaging and 18F-FDG positron emissions tomography (PET) gated myocardial metabolism imaging to forecast major adverse cardiovascular events (MACE) in chronic total occlusion (CTO) patients treated with optimal medical therapy (OMT). Methods: A total of 257 patients who received OMT between January 2016 and December 2021 were included in this retrospective study. Patients were randomly divided into development (n=179) and validation (n=78) cohorts. A thorough evaluation was conducted, encompassing clinical features and imaging analysis, which involved assessing myocardial perfusion and metabolism. Independent risk factors were identified using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses. Calibration curves and decision curve analysis (DCA) were used to evaluate the clinical usefulness. Results: In the development cohort, 53 patients (29.6%) experienced MACE out of 179 patients, while in the validation cohort, MACE occurred in 23 (29.5%) patients out of 78. The PET-left ventricular end-systolic volume (P-ESV) (HR 1.01; 95% CI 1.003-1.017; p=0.003), hibernating myocardium / total perfusion defect (HM/TPD) (HR 1.053; 95% CI 1.038-1.069; p<0.001), PET-left ventricular ejection fraction (P-LVEF) (HR 0.862; 95% CI 0.788-0.943; p=0.001), and left anterior descending branch (LAD) (HR 2.303; 95% CI 1.086-4.884; p=0.03) were significantly associated with MACE and were used to develop the nomogram. The nomogram demonstrated excellent discrimination with C-indexes of 0.931 and 0.911 in the development and validation cohorts. DCA determined that the model exhibited a considerably superior net advantage in predicting MACE. Conclusion: A new nomogram integrating clinical factors and imaging features was created to predict the risk of MACE in patients with CTO.

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy.

BACKGROUND: The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). METHODS: A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). RESULTS: After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). CONCLUSION: HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

Development and validation of a predicting nomogram for in-hospital mortality of COVID-19 Omicron variant: A cohort study of 1324 cases in Beijing Anzhen Hospital.

Coronavirus disease 2019 (COVID-19) is continuously posing high global public health concerns due to its high morbidity and mortality. This study aimed to construct a convenient risk model for predicting in-hospital mortality of COVID-19 Omicron variant. A total of 1324 hospitalized patients with Omicron variant were enrolled from Beijing Anzhen Hospital. During hospitalization, the Omicron variant mortality rate was found to be 24.4%. Using the datasets of clinical demographics and laboratory tests, three machine learning algorithms, including best subset selection, stepwise selection, and least absolute shrinkage and selection operator regression analyses were employed to identify the potential predictors of in-hospital mortality. The results found that a panel of twenty-four clinical variables (including age, hyperlipemia, stroke, tumor, and several cardiovascular markers) identified by stepwise selection model exhibited significant performances in predicting the in-hospital mortality of COVID-19. The resultant nomogram showed good discrimination, highlighted by the areas under the curve values of 0.88 for 10 days, 0.81 for 20 days, and 0.82 for 30 days, respectively. Furthermore, decision curve analysis showed a significant reliability and precision for the established stepwise selection model. Collectively, this study developed an accurate and convenience risk model for predicting the in-hospital mortality of COVID-19 Omicron.

Ultrasound and clinical factors predicting central lymph node metastases in patients with unilateral multifocal papillary thyroid carcinoma.

OBJECTIVE: This retrospective study involving a large dataset of unilateral multifocal papillary thyroid carcinoma (UM-PTC) sought to identify factors that predict central lymph node metastases (CLNM) in patients. METHODS: We identified a cohort of 158 patients who underwent cervical ultrasonography followed by UM-PTC diagnosis based on postoperative pathology. The relationship between CLNM and UM-PTC clinical ultrasound features was evaluated using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of total tumor diameter (TTD) to predict CLNM. RESULTS: Among the 158 UM-PTC patients, the incidence of CLNM was 29.7% (47/158). Univariate and multivariate analyses revealed that a number of similarity of sonographic features (NSSF) ≥4 (odds ratio [OR] = 11.335, 95% confidence interval [CI]: 3.95-32.50, p = 0.000), microcalcifications (OR = 3.54, 95% CI: 1.30-9.70, p = 0.014), a TTD of ≥2 cm (OR = 4.48, 95% CI: 1.62-12.34, p = 0.004), number of nodules ≥3 (OR = 13.17, 95% CI: 3.24-53.52, p = 0.000), and Lateral cervical lymph node metastasis (LLNM) (OR = 5.57, 95% CI: 1.59-19.48, p = 0.007) were independently associated with CLNM in UM-PTC. ROC curve analysis revealed that the TTD cut-off of 1.795 cm had a sensitivity of 0.723 and a specificity of 0.676 for predicting CLNM. CONCLUSIONS: Patients with UM-PTC are at high risk of CLNM. NSSF ≥4, microcalcifications, TTD of ≥2 cm, LLNM, and a number of nodules ≥3 were independently associated with CLNM. Our data show that ultrasound may guide surgical decisions in the treatment of UM-PTC.

Oligonucleotide therapies for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) represents a severe disease subtype of nonalcoholic fatty liver disease (NAFLD) that is thought to be highly associated with systemic metabolic abnormalities. It is characterized by a series of substantial liver damage, including hepatocellular steatosis, inflammation, and fibrosis. The end stage of NASH, in some cases, may result in cirrhosis and hepatocellular carcinoma (HCC). Nowadays a large number of investigations are actively under way to test various therapeutic strategies, including emerging oligonucleotide drugs (e.g., antisense oligonucleotide, small interfering RNA, microRNA, mimic/inhibitor RNA, and small activating RNA) that have shown high potential in treating this fatal liver disease. This article systematically reviews the pathogenesis of NASH/NAFLD, the promising druggable targets proven by current studies in chemical compounds or biological drug development, and the feasibility and limitations of oligonucleotide-based therapeutic approaches under clinical or pre-clinical studies.

Mea6/cTAGE5 cooperates with TRAPPC12 to regulate PTN secretion and white matter development.

Mutations of TRAPPC12 are associated with progressive childhood encephalopathy including abnormal white matter. However, the underlying pathogenesis is still unclear. Here, we found that Trappc12 deficiency in CG4 and oligodendrocyte progenitor cells (OPCs) affects their differentiation and maturation. In addition, TRAPPC12 interacts with Mea6/cTAGE5, and Mea6/cTAGE5 ablation in OPCs affects their proliferation and differentiation, leading to marked hypomyelination, compromised synaptic functionality, and aberrant behaviors in mice. We reveal that TRAPPC12 is associated with COPII components at ER exit site, and Mea6/cTAGE5 cKO disrupts the trafficking pathway by affecting the distribution and/or expression of TRAPPC12, SEC13, SEC31A, and SAR1. Moreover, we observed marked disturbances in the secretion of pleiotrophin (PTN) in Mea6-deficient OPCs. Notably, exogenous PTN supplementation ameliorated the differentiation deficits of these OPCs. Collectively, our findings indicate that the association between TRAPPC12 and MEA6 is important for cargo trafficking and white matter development.

Association Between Red Blood Cell Distribution Width and Coronary Calcification in Patients Referred for Invasive Coronary Angiography.

This study aimed to determine whether red cell distribution width (RDW) is associated with coronary calcification. A total of 4796 patients who underwent coronary computed tomography angiography and subsequent invasive coronary angiography were consecutively enrolled. Coronary artery calcium score (CACS), demographic, clinical, and laboratory data were collected from electronic medical records. RDW were expressed in two forms, as a coefficient of variation (CV) or as a standard deviation (SD). Multivariable ordinal logistic regression was used to investigate the association of RDW with CACS grades (CACS 0-99, 100-399, 400-999, and >1000). A significant association was found between elevated RDW-SD and higher CACS grades after full adjustment (adjusted OR per 1-SD increase: 1.11, 95% CI: 1.05-1.18; P < .001), while no significant association was found between RDW-CV and CACS grades. When RDW-SD was analyzed as a categorical variable, it was primarily the 4th quartile of RDW-SD that was associated with elevated CACS grades compared with the 1st quartile (adjusted OR: 1.25, 95% CI: 1.07-1.46; P = .006), while the 2nd and 3rd quartiles showed no significantly higher risk. RDW-SD is a more robust biomarker for coronary calcification compared with RDW-CV.

Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma.

AIMS: This study aimed to improve personalized treatment strategies and predict survival outcomes for patients with uveal melanoma (UM). BACKGROUND: Copy number aberrations (CNAs) have been considered as a main feature of metastatic UM. OBJECTIVE: This study was designed to explore the feasibility of using copy number variation (CNV) in UM classification, prognosis stratification and treatment response. METHODS: The CNV data in the TCGA-UVM cohort were used to classify the samples. The differentially expressed genes (DEGs) between subtypes were screened by the "Limma" package. The module and hub genes related to aneuploidy score were identified by performing weighted gene co-expression network analysis (WGCNA) on the DEGs. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to train the hub genes for developing a prognosis model for UM. Finally, the expression levels of the screened prognostic key genes were verified in UM cells, and the cell migration and invasion abilities were detected using real-time quantitative PCR (qRT-PCR) and transwell assay. RESULTS: The UM samples were divided into 3 CNV subtypes, which differed significantly in overall survival (OS) and disease-specific survival (DSS). C1 had the shortest OS and DSS and the highest level of immune infiltration. A total of 2036 DEGs were obtained from the three subtypes. Eighty hub genes with the closest correlation with aneuploidy scores were selected by WGCNA. Univariate Cox and LASSO regression-based analyses finally determined eight genes as the key prognostic genes, including HES6, RNASEH2C, NQO1, NUDT14, TTYH3, GJC1, FKBP10, and MRPL24. A prognostic model was developed using the eight genes, demonstrating a strong prediction power. Differences in the response to immunotherapy among patients in different risk groups were significant. We found that high-risk patients were more sensitive to two drugs (Palbociclib_ 1054 and Ribociclib_1632), while low-risk patients were more sensitive to AZD1208_1449, ERK_2440_1713, Mirin_1048, and Selumetinib_1736. CONCLUSION: UM in this study was divided into three CNV subtypes, and a model based on eight aneuploidy score-related genes was established to evaluate the prognosis and drug treatment efficacy of UM patients. The current results may have the potential to help the clinical decision-making process for UM management.

Prognostic Value of a Combined Nomogram Model Integrating 3-Dimensional Deep Learning and Radiomics for Head and Neck Cancer.

OBJECTIVE: The preoperative prediction of the overall survival (OS) status of patients with head and neck cancer (HNC) is significant value for their individualized treatment and prognosis. This study aims to evaluate the impact of adding 3D deep learning features to radiomics models for predicting 5-year OS status. METHODS: Two hundred twenty cases from The Cancer Imaging Archive public dataset were included in this study; 2212 radiomics features and 304 deep features were extracted from each case. The features were selected by univariate analysis and the least absolute shrinkage and selection operator, and then grouped into a radiomics model containing Positron Emission Tomography /Computed Tomography (PET/CT) radiomics features score, a deep model containing deep features score, and a combined model containing PET/CT radiomics features score +3D deep features score. TumorStage model was also constructed using initial patient tumor node metastasis stage to compare the performance of the combined model. A nomogram was constructed to analyze the influence of deep features on the performance of the model. The 10-fold cross-validation of the average area under the receiver operating characteristic curve and calibration curve were used to evaluate performance, and Shapley Additive exPlanations (SHAP) was developed for interpretation. RESULTS: The TumorStage model, radiomics model, deep model, and the combined model achieved areas under the receiver operating characteristic curve of 0.604, 0.851, 0.840, and 0.895 on the train set and 0.571, 0.849, 0.832, and 0.900 on the test set. The combined model showed better performance of predicting the 5-year OS status of HNC patients than the radiomics model and deep model. The combined model was shown to provide a favorable fit in calibration curves and be clinically useful in decision curve analysis. SHAP summary plot and SHAP The SHAP summary plot and SHAP force plot visually interpreted the influence of deep features and radiomics features on the model results. CONCLUSIONS: In predicting 5-year OS status in patients with HNC, 3D deep features could provide richer features for combined model, which showed outperformance compared with the radiomics model and deep model.

A novel enrofloxacin-degrading fungus, Humicola sp. KC0924g, isolated from the rhizosphere sediment of the submerged macrophyte Vallisneria spiralis L.

A novel enrofloxacin-degrading fungus was isolated from a rhizosphere sediment of the submerged macrophyte Vallisneria spiralis L.. The isolate, designated KC0924g, was identified as a member of the genus Humicola based on morphological characteristics and tandem conserved sequence analysis. The optimal temperature and pH for enrofloxacin degradation by strain KC0924g were 28 °C and 9.0, respectively. Under such condition, 98.2% of enrofloxacin with an initial concentration of 1 mg L-1 was degraded after 72 h of incubation, with nine possible degradation products identified. Four different metabolic pathways were proposed, which were initiated by cleavage of the piperazine moiety, hydroxylation of the aromatic ring, oxidative decarboxylation, or defluorination. In addition to enrofloxacin, strain KC0924g also degraded other fluoroquinolone antibiotics (ciprofloxacin, norfloxacin, and ofloxacin), malachite green (an illegal additive in aquaculture), and leucomalachite green. Pretreatment of cells of strain KC0924g with Cu2+ accelerated ENR degradation. Furthermore, it was speculated that a flavin-dependent monooxygenase was involved in ENR degradation, based on the increased transcriptional levels of these two genes after Cu2+ induction. This work enriches strain resources for enrofloxacin remediation and, more importantly, would facilitate studies on the molecular mechanism of ENR degradation with degradation-related transcriptome available.

miR-330-5p Suppress Cell Growth and Invasion via Disrupting HSF4-mediated MACC1/STAT3 Pathway in Colorectal Cancer.

BACKGROUND: Recently, miRNAs are demonstrated to restrain mRNA translation through novel pattern with bind complementary sites in the coding sequence (CDS). Heat Shock Transcription Factor 4 (HSF4) has been newly described as a tumor-associated transcription factor. Therefore, the present study intends to explore miRNAs that bind CDS region of HSF4, and identify the function of their interactions in the malignant biological behavior of colorectal cancer (CRC). METHODS: Prognostic value of HSF4 and correlation between HSF4 and MACC1 expression were estimated via bioinformatics with the Cancer Genome Atlas (TCGA) data. HSF4 and downstream MACC1/STAT3 signaling cascade was characterized by immunoblotting. To characterize the effects of miR-330-5p and HSF4 on the malignant phenotype of CRC cells by functional experiments. The binding activity of miR-330-5p to coding sequence (CDS) of HSF4 was identified using DIANA-microT-CDS algorithm and dual-luciferase reporter assay. RESULTS: HSF4 was aberrantly overexpressed and associated with poor outcomes of CRC patients. Overexpression of HSF4 was correlated with Tumor Node Metastasis stage, and positively regulated malignant behaviors such as growth, migration, invasion of CRC cells. Moreover, miR-330-5p suppressed CRC cell growth, colony formation, migration and invasive. Interestingly, miR-330-5p recognized complementary sites within the HSF4 CDS region to reduce HSF4 expression. In rescue experiments, restoration of HSF4 expression functionally alleviated miR-330-5p-induced inhibition of cell growth, colon formation, invasion, and wound healing of CRC cells. HSF4 was associated positively with the well-known oncogenic factor MACC1 in TCGA cohort CRC samples, and knockdown of HSF4 resulted in downregulation of MACC1. In mechanism, MACC1 was suppressed upon miR-330-5p-induced downregulation of HSF4, leading to inactivation of phosphorylation of downstream STAT3. CONCLUSION: miR-330-5p suppresses tumors by directly inhibiting HSF4 to negatively modify activity of MACC1/STAT3 pathway.

Machine learning-based coronary artery calcium score predicted from clinical variables as a prognostic indicator in patients referred for invasive coronary angiography.

OBJECTIVES: Utilising readily available clinical variables, we aimed to develop and validate a novel machine learning (ML) model to predict severe coronary calcification, and further assessed its prognostic significance. METHODS: This retrospective study enrolled patients who underwent coronary CT angiography and subsequent invasive coronary angiography. Multiple ML algorithms were used to train the models for predicting severe coronary calcification (cardiac CT-measured coronary artery calcium [CT-CAC] score ≥ 400). The ML-based CAC (ML-CAC) score derived from the ML predictive probability was stratified into quartiles for prognostic analysis. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Overall, 5785 patients were divided into training (80%) and test sets (20%). For clinical practicability, we selected the nine-feature support vector machine model with good and satisfactory performance regarding both discrimination and calibration based on five repetitions of the 10-fold cross-validation in the training set (mean AUC = 0.715, Brier score = 0.202), and based on the test in the test set (AUC = 0.753, Brier score = 0.191). In the test set cohort (n = 1137), the primary endpoint was observed in 50 (4.4%) patients during a median 2.8 years' follow-up. The ML-CAC system was significantly associated with an increased risk of the primary endpoint (adjusted hazard ratio for trend 2.26, 95% CI 1.35-3.79, p = 0.002). There was no significant difference in the prognostic value between the ML-CAC and CT-CAC systems (C-index, 0.67 vs. 0.69; p = 0.618). CONCLUSION: ML-CAC score predicted from clinical variables can serve as a novel prognostic indicator in patients referred for invasive coronary angiography. CLINICAL RELEVANCE STATEMENT: In patients referred for invasive coronary angiography who have not undergone preoperative CT-measured coronary artery calcium scoring, machine learning-based coronary artery calcium score assessment can serve as an alternative for predicting the prognosis. KEY POINTS: • The coronary artery calcium (CAC) score, a solid prognostic indicator, can be predicted using non-CT methods. • We developed a machine learning (ML)-CAC model utilising nine clinical variables to predict severe coronary calcification. • The ML-CAC system offers significant prognostic value in patients referred for invasive coronary angiography.