Impact of Frailty on Survival and Neurological Outcomes After Cardiac Arrest: A Systematic Review and Meta-Analysis.

To synthesize the evidence on the associations of frailty with the risk of mortality and neurological outcomes in patients with cardiac arrest undergoing cardiopulmonary resuscitation. We conducted a literature search on PubMed, EMBASE, and Scopus. We included observational studies on adult participants (18 years or older) with cardiac arrest. The eligible studies reported frailty assessments using standard tools, and the comparator group comprised nonfrail participants. We used random-effects models for all analyses and expressed pooled effect sizes as odds ratios (ORs) with 95% confidence intervals (CIs). We included data from 12 studies in our analysis. Individuals with frailty exhibited a significantly higher risk of in-hospital mortality (OR, 2.18; 95% CI, 1.62-2.94), and increased 30-day mortality (OR, 1.43; 95% CI, 1.12-1.84) and 12-month mortality (OR, 4.16; 95% CI, 2.32-7.47) than the nonfrail individuals. Frail individuals also displayed lower odds of achieving favorable neurological outcomes upon hospital discharge (OR, 0.32; 95% CI, 0.20-0.50) and at the 30-day follow-up (OR, 0.42; 95% CI, 0.23-0.78). Additionally, they had lower odds of return of successful spontaneous circulation (OR, 0.49; 95% CI, 0.34-0.72). The observed associations between frailty and a higher risk of mortality reduced odds of favorable neurological outcomes, and lower odds of return of successful spontaneous circulation underscore the value of identifying frailty in individuals to achieve more accurate prognoses. Our findings highlight the importance of including frailty assessments as a component of the management plan for patients experiencing cardiac arrest.

Relationships between childhood trauma and mental health during the COVID-19 pandemic: a network analysis.

Background: Childhood trauma has been found to have an important impact on mental health. However, little is known regarding the intercorrelations between childhood trauma and mental health during the COVID-19 pandemic. This study aimed to investigate such complex interplay between childhood trauma, depression, anxiety, post-traumatic stress level during the COVID-19 pandemic, and fear of COVID-19 using network analysis. Methods: A total of 1,247 college students were recruited and were asked to complete a series of questionnaires, including the Childhood Trauma Questionnaire, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, Post-traumatic Stress Checklist-Civilian version, and Fear of COVID-19 Scale. The Gaussian graphical model with the scores of the questionnaires as nodes was estimated. The partial correlations between nodes were calculated as edges. Moreover, network comparison tests were conducted to compare the network patterns between participants with high levels of childhood trauma and low levels of childhood trauma. Results: Childhood trauma was found to be connected to depression, anxiety, and post-traumatic stress level. The node of childhood trauma exhibited the strongest strength and the highest expected influence in the network. Participants with high levels of childhood trauma and participants with low levels of childhood trauma showed comparable network structure and global strength. Conclusion: Our findings revealed a complex network pattern between childhood trauma and different mental health problems, indicating that childhood trauma might be a risk factor for mental health during the COVID-19 pandemic.

Development and validation of a personalized classifier to predict the prognosis and response to immunotherapy in glioma based on glycolysis and the tumor microenvironment.

Background: Glycolysis is closely associated with cancer progression and treatment outcomes. However, the role of glycolysis in the immune microenvironment, prognosis, and immunotherapy of glioma remains unclear. Methods: This study investigated the role of glycolysis on prognosis and its relationship with the tumor microenvironment (TME). Subsequently, we developed and validated the glycolysis-related gene signature (GRS)-TME classifier using multiple independent cohorts. Furthermore, we also examined the prognostic value, somatic alterations, molecular characteristics, and potential benefits of immunotherapy based on GRS-TME classifier. Lastly, the effect of kinesin family member 20A (KIF20A) on the proliferation and migration of glioma cells was evaluated in vitro. Results: Glycolysis was identified as a significant prognostic risk factor in glioma, and closely associated with an immunosuppressive microenvironment characterized by altered distribution of immune cells. Furthermore, a personalized GRS-TME classifier was developed and validated by combining the glycolysis (18 genes) and TME (seven immune cells) scores. Patients in the GRSlow/TMEhigh subgroup exhibited a more favorable prognosis compared to other subgroups. Distinct genomic alterations and signaling pathways were observed among different subgroups, which are closely associated with cell cycle, epithelial-mesenchymal transition, p53 signaling pathway, and interferon-alpha response. Additionally, we found that patients in the GRSlow/TMEhigh subgroup exhibit a higher response rate to immunotherapy, and the GRS-TME classifier can serve as a novel biomarker for predicting immunotherapy outcomes. Finally, high expression of KIF20A is associated with an unfavorable prognosis in glioma, and its knockdown can inhibit the proliferation and migration of glioma cells. Conclusions: Our study developed a GRS-TME classifier for predicting the prognosis and potential benefits of immunotherapy in glioma patients. Additionally, we identified KIF20A as a prognostic and therapeutic biomarker for glioma.

LINC00536 knockdown inhibits breast cancer cells proliferation, invasion, and migration through regulation of the miR-4282/centromere protein F axis.

Breast cancer (BC) poses a huge threat to women's health. Growing evidence has shown lncRNAs play critical roles in BC progression. However, the effect of LINC00536 in BC remains unknown. LINC00536, miR-4282, and centromere protein F (CENPF) expressions in BC cells were determined using qPCR assay. Colony formation assay was employed to evaluate the cell proliferation of BC cells. Besides, cell migration and invasion were evaluated using the transwell assay. FISH assay was employed to analyze LINC00536 and miR-4282 locations in BC cells. Additionally, dual luciferase reporter gene assay was performed to verify the binding relationships between LINC00536 and miR-4282, miR-4282 and CENPF. Here, our results displayed that LINC00536 and CENPF were overexpressed in BC cells, while miR-4282 was downregulated. LINC00536 could negatively regulate miR-4282 expression via directly binding to miR-4282. LINC00536 silence suppressed the proliferation, migration, and invasion of BC cells, which was abolished by miR-4282 inhibition. Additionally, miR-4282 could negatively regulate CENPF expression via directly binding to CENPF. MiR-4282 overexpression suppressed BC development, which was abolished by CENPF overexpression. Finally, we proved that LINC00536 silencing suppressed BC growth via regulating the miR-4282/CENPF axis in vivo. Our research displayed that LINC00536 acted as an oncogene in BC. LINC00536-enhanced BC cell proliferation, migration, and invasion. Moreover, LINC00536 functioned as a ceRNA to exert malignant characteristics in BC via the miR-4282-CENPF axis. Collectively, our results demonstrated that the LINC00536-miR-4282-CENPF axis was a critical player in BC development and was a promising target for BC therapy.

Long noncoding RNA HCP5 promotes osteosarcoma cell proliferation, invasion, and migration via the miR-29b-3p-LOXL2 axis.

Osteosarcoma (OS) is the second most common primary malignant bone tumors in adolescents that causes cancer-related deaths. Previous studies have confirmed the promoting role of lncRNA HCP5 in the development of OS, but the specific mechanism is still not well understood. MiRNA levels were measured via RT-qPCR and protein expression was detected via western blotting. Cell proliferation was analyzed by CCK-8 assays and colony formations assay were conducted to measure colony formation ability. Dual-luciferase reporter assay was performed to detect the targeting relationship between HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2. Wound healing assays and Transwell assays were conducted to verify the migration and invasion abilities of OS cells. Correlations between the levels of HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2 were determined by Pearson correlation coefficient analysis. MiR-29b-3p expression was decreased and HCP5 and LOXL2 levels were increased in OS tissues and cell lines. MiR-29b-3p could directly act on LOXL2 and knockdown of LOXL2 restrained the proliferation, migration, and invasion of OS cells. Moreover, transfection with sh-HCP5-1 and sh-HCP5-2 suppressed the malignant biological behavior of OS cells. HCP5 directly targeted miR-29b-3p, and promoted OS proliferation, migration, and invasion via the miR-29b-3p/LOXL2 axis. The lncRNA HCP5 may upregulate LOXL2 expression by targeting miR-29b-3p, thereby promoting OS proliferation, migration, and invasion.

Retraction Note: Downregulated poly-C binding protein-1 is a novel predictor associated with poor prognosis in acute myeloid leukemia.

This article [1] is retracted at request of the Editor.

DRAMP: a comprehensive data repository of antimicrobial peptides.

The growing problem of antibiotic-resistant microorganisms results in an urgent need for substitutes to conventional antibiotics with novel modes of action and effective activities. Antimicrobial peptides (AMPs), produced by a wide variety of living organisms acting as a defense mechanism against invading pathogenic microbes, are considered to be such promising alternatives. AMPs display a broad spectrum of antimicrobial activity and a low propensity for developing resistance. Therefore, a thorough understanding of AMPs is essential to exploit them as antimicrobial drugs. Considering this, we developed a comprehensive user-friendly data repository of antimicrobial peptides (DRAMP), which holds 17349 antimicrobial sequences, including 4571 general AMPs, 12704 patented sequences and 74 peptides in drug development. Entries in the database have detailed annotations, especially detailed antimicrobial activity data (shown as target organism with MIC value) and structure information. Annotations also include accession numbers crosslinking to Pubmed, Swiss-prot and Protein Data Bank (PDB). The website of the database comes with easy-to-operate browsing as well as searching with sorting and filtering functionalities. Several useful sequence analysis tools are provided, including similarity search, sequence alignment and conserved domain search (CD-Search). DRAMP should be a useful resource for the development of novel antimicrobial peptide drugs.

Downregulated Poly-C binding protein-1 is a novel predictor associated with poor prognosis in Acute Myeloid Leukemia.

BACKGROUND: Depletion of Poly-C binding protein-1(PCBP1) is implicated in various human malignancies. However, the underlying biological effect of PCBP1 in cancers, including acute myeloid leukemia (AML), still remains elusive. The purpose of this study was to examine the expression and clinical outcome of PCBP1in acute myeloid leukemia. METHODS: Bone marrow fluids of 88 newly diagnosed AML patients were sampled, and the PCBP1 mRNA expression level was evaluated using quantitative RT-PCR. The association between PCBP1 expression and clinicopathological features or the survival status of the patients was assessed by Chi-square test and Kaplan-Meier method. RESULTS: Comparing newly diagnosed AML patients to normal healthy donors, PCBP1 expression was significantly decreased in AML patients (P < 0.001). Conversely, PCBP1 expression had accordingly recovered back to normal in patients with complete remission (P < 0.001). Clinical feature analyses showed that PCBP1 expression was negatively correlated with white blood cell count (P = 0.024). In addition, patients with low PCBP1 expression had poor disease-free survival (11.8% vs. 45.3%; P = 0.01) and overall survival (18.2% vs. 42.4%; P = 0.032), respectively. CONCLUSIONS: Taken together, our results showed for the first time that expression of PCBP1 was down-regulated in newly diagnosed AML patients and might be an independent prognostic marker in AML and should to be further investigated.

CLIPdb: a CLIP-seq database for protein-RNA interactions.

BACKGROUND: RNA-binding proteins (RBPs) play essential roles in gene expression regulation through their interactions with RNA transcripts, including coding, canonical non-coding and long non-coding RNAs. Large amounts of crosslinking immunoprecipitation (CLIP)-seq data (including HITS-CLIP, PAR-CLIP, and iCLIP) have been recently produced to reveal transcriptome-wide binding sites of RBPs at the single-nucleotide level. DESCRIPTION: Here, we constructed a database, CLIPdb, to describe RBP-RNA interactions based on 395 publicly available CLIP-seq data sets for 111 RBPs from four organisms: human, mouse, worm and yeast. We consistently annotated the CLIP-seq data sets and RBPs, and developed a user-friendly interface for rapid navigation of the CLIP-seq data. We applied a unified computational method to identify transcriptome-wide binding sites, making the binding sites directly comparable and the data available for integration across different CLIP-seq studies. The high-resolution binding sites of the RBPs can be visualized on the whole-genome scale using a browser. In addition, users can browse and download the identified binding sites of all profiled RBPs by querying genes of interest, including both protein coding genes and non-coding RNAs. CONCLUSION: Manually curated metadata and uniformly identified binding sites of publicly available CLIP-seq data sets will be a foundation for further integrative and comparative analyses. With maintained up-to-date data sets and improved functionality, CLIPdb ( http://clipdb.ncrnalab.org ) will be a valuable resource for improving the understanding of post-transcriptional regulatory networks.

Independent oncogenic and therapeutic significance of phosphatase PRL-3 in FLT3-ITD-negative acute myeloid leukemia.

BACKGROUND: Internal tandem duplication of FMS-like tyrosine kinase (FLT3-ITD) is well known to be involved in acute myeloid leukemia (AML) progression, but FLT3-ITD-negative AML cases account for 70% to 80% of AML, and the mechanisms underlying their pathology remain unclear. This study identifies protein tyrosine phophatase PRL-3 as a key mediator of FLT3-ITD-negative AML. METHODS: A total of 112 FLT3-ITD-negative AML patients were sampled between 2010 and 2013, and the occurrence of PRL-3 hyperexpression in FLT3-ITD-negative AML was evaluated by multivariate probit regression analysis. Overexpression or depletion of endogenous PRL-3 expression with the specific small interfering RNAs was performed to investigate the role of PRL-3 in AML progression. Xenograft models were also used to confirm the oncogenic role of PRL-3. RESULTS: Compared to healthy donors, PRL-3 is upregulated more than 3-fold in 40.2% of FLT3-ITD-negative AML patients. PRL-3 expression level is adversely correlated to the overall survival of the AML patients, and the AML relapses accompany with re-upregulation of PRL-3. Mechanistically, aberrant PRL-3 expression promoted cell cycle progression and enhanced the antiapoptotic machinery of AML cells to drug cytotoxicity through downregulation of p21 and upregulation of Cyclin D1 and CDK2 and activation of STAT5 and AKT. Depletion of endogenous PRL-3 sensitizes AML cells to therapeutic drugs, concomitant with apoptosis by upregulation of cleaved PARP (poly ADP ribose polymerase) and apoptosis-related caspases. Xenograft assays further confirmed PRL-3's oncogenic role in leukemogenesis. CONCLUSIONS: Our results demonstrated that PRL-3 is a novel independent crucial player in both FLT3-ITD-positive and FLT3-ITD-negative AML and could be a potential therapeutic target.