Aims
Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, ...diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19.
Methods
No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence.
Results
Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31–2.36;
P
= 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held.
Conclusions
Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.
The free-weighting matrix and integral-inequality methods are widely used to derive delay-dependent criteria for the stability analysis of time-varying-delay systems because they avoid both the use ...of a model transformation and the technique of bounding cross terms. This technical note presents a new integral inequality, called a free-matrix-based integral inequality, that further reduces the conservativeness in those methods. It includes well-known integral inequalities as special cases. Using it to investigate the stability of systems with time-varying delays yields less conservative delay-dependent stability criteria, which are given in terms of linear matrix inequalities. Two numerical examples demonstrate the effectiveness and superiority of the method.
: Head and neck squamous cell carcinoma (HNSCC) are head and neck cancers. On the other hand, ferroptosis is a novel iron-dependent and ROS reliant type of cell death observed various disease ...conditions.
: We constructed a prognostic multilncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HNSCC.
: We identified 25 differently expressed lncRNAs associated with prognosis of HNSCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HNSCC. Moreover, the AUC of the lncRNAs signature was 0.782, underscoring their utility in prediction HNSCC prognosis. Indeed, our risk assessment model was superior to traditional clinicopathological features in predicting HNSCC prognosis. GSEA revealed the immune and tumor-related pathways in the low risk group individuals. Moreover, TCGA revealed T cell functions including cytolytic activity, HLA, regulation of inflammationp, co-stimulation, co-inhibition and coordination of type II INF response were significantly different between the low-risk and high-risk groups. Immune checkpoints such as PDCD-1 (PD-1), CTLA4 and LAG3, were also expressed differently between the two risk groups.
A novel ferroptosis-related lncRNAs signature impacts on the prognosis of HNSCC.
This note is concerned with the stability analysis of linear discrete-time system with a time-varying delay. A generalized free-weighting-matrix (GFWM) approach is proposed to estimate summation ...terms in the forward difference of Lyapunov functional, and theoretical study shows that the GFWM approach encompasses several frequently used estimation approaches as special cases. Moreover, an augmented Lyapunov functional with a delay-product type term is constructed to take into account delay changing information. As a result, the proposed GFWM approach, together with the augmented Lyapunov functional, leads to a less conservative delay-variation-dependent stability criterion. Finally, numerical examples are given to illustrate the advantages of the proposed criterion.
The novel coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to a worldwide pandemic. Except representative ...manifestation of pneumonia and acute respiratory symptoms, COVID-19 patients have also shown different levels of liver injury or liver dysfunction. The aim of our study was to explore the probable clinical severity and mortality of COVID-19 patients and their liver dysfunction.
A combination of computer and manual retrieval was used to search in Medline through PubMed, EMBASE and Web of Science. Review Manager 5.3 software was used to examine the heterogeneity among the studies and to calculate the combined effect value (OR, 95CI). Subgroup analysis, sensitivity analysis, and publication bias test were also performed.
We found a significant connection between liver dysfunction and mortality of COVID-19 patients with a pooled OR of 1.98 (95% CI 1.39-2.82; P = 0.0002). There was a significant association between AST and severity of COVID-19 with a pooled OR of 4.48 (95% CI 3.24-7.21; P < 0.001), and a pooled WMD of 3.35 (95% CI, 2.07 to 4.64; P < 0.001). In addition, there was a significant difference between TBIL and severity of COVID-19, with a pooled OR of 1.91 (95% CI 1.40-2.60; P < 0.001), and with a pooled WMD of 1.18 (95% CI, 0.78 to 1.58; P < 0.001).
The mortality and severity of COVID-19 patients are significantly associated with liver dysfunction. The non-survivors and severe COVID-19 patients have elevated serum AST levels than the survivors and non-severe COVID-19 patients. The results of this study form a basis for better clinical liver management of patients with COVID-19.
The integral inequality technique is widely used to derive delay-dependent conditions, and various integral inequalities have been developed to reduce the conservatism of the conditions derived. In ...this study, a new integral inequality was devised that is tighter than existing ones. It was used to investigate the stability of linear systems with a discrete distributed delay, and a new stability condition was established. The results can be applied to systems with a delay belonging to an interval, which may be unstable when the delay is small or nonexistent. Three numerical examples demonstrate the effectiveness and the smaller conservatism of the method.
Head and neck squamous cell carcinoma (HNSCC), a tumor included oral cavity, lips, larynx, oropharynx, and the nasopharynx et al. The cell division cycle-associated (CDCA) protein family (CDCA1-8) ...critical for normal cell function and cancer cell proliferation. We explored the mutation signatures and expression levels of various CDCAs in detail in HNSCC. A comprehensive bioinformatics analysis pipeline based on copy number and gene expressions data from patients with HNSCC in order to given new insights into the possible functions and distinct prognostics that underlie CDCAs regulation. We compared the transcriptional expression of CDCAs in HNSCC and found significantly elevated mRNA expression of CDCA1-8 in HNSCC tissues across multiple datasets. We also found CDCA5/6/8 are over-expressed both transcriptionally and translationally in patients with HNSCC. Our results suggested that that mRNA levels of CDCA1/2/4/7 related to the prognosis and can be used as a new useful biomarker for predicting the survival of HNSCC patients. The top 5 CDCAs neighboring gene alterations in HNSCCs were found in MYC, STAG1, RAD21, KLHL9 and NDC80. Multivariable Cox proportional hazard model also showed that CD8+ T cells were higher (P<0.05) in HNSCC-HPV-pos patients and that this was related to CDCA1/2/3/4/5/7. This study utilizes online tools to conduct specific gene analyses from free open databases, but our study requires more large-scale genomics research and basic research.
Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes ...undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan-Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research.
Breast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular ...accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.
Background. Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal ...cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients. Method. In this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy. Results. We extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk (HR=1.144, 95% CI=1.044~1.251) and the lowest risk (HR=0.580, 95% CI=0.400~0.839) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset. Conclusion. Taken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.
PDF
