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Objective: To explore genes related to costimulatory molecule related to the prognosis of bladder cancer, and to construct and evaluate prognosis model based on costimulatory molecule-based signature (CMS). Methods: Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database (GSE31684), and costimulatory molecule-related genes were retrieved from the literature. The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model. Forecast accuracy of model was verified in TCGA training group, TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve (ROC). Considering risk score and clinical characteristics, we constructed a nomogram and evaluated its performance by consistency analysis and ROC. CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration, and gene set enrichment analysis (GSEA) was performed to explore the potential mechanism. Results: Four prognostic-related CMSs were found: TNFRSF14, CD276, ICOS and TMIGD2, of which three were included in the risk score construction. Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients. Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy. Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state. GSEA results suggested that genes in high risk group were enriched in extracellular matrix (ECM) receptors interaction, cell cycle and other pathways. Conclusion:TNFRSF14, CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients. CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment. [ABSTRACT FROM AUTHOR]

Aims: N6‐methyladenosine (m6A) modification is a critical posttranscriptional event in gene regulation. Thus, identifying methyltransferase, demethylase, or m6A binding protein‐mediated m6A modifications in cancer or noncancer transcriptomes has become a promising novel strategy for disease therapy development. However, novel insights into m6A modification in partial bladder outlet obstruction (pBOO) and detailed information about the drivers of bladder remodeling remain to be elucidated. Here, we first characterized the m6A modification landscape in pBOO and investigated potential actionable pharmaceutical targets for future therapies. Methods: We generated an improved animal model of pBOO in SD rats with urethral meatus stricture induced by suturing. Urodynamic investigations and cystometry were carried out to evaluate the physiologic changes elicited by pBOO. Whole‐transcriptome sequencing (RNA‐seq) and m6A‐modified RNA immunoprecipitation sequencing (MeRIP‐seq) were subsequently performed to analyze the expression pattern associated with bladder remodeling in pBOO. Results: The cystometric evaluation of bladder function demonstrated obvious increases in pressure‐related parameters in the pBOO group. Hematoxylin and eosin staining and Masson's trichrome staining validated the occurrence of bladder remodeling. A global elevation in m6A RNA methylation levels was observed in parallel to a increased expression of METTL3 in the pBOO group. High‐throughput sequencing revealed the differences in expression patterns between the pBOO and sham‐operated groups. Furthermore, potential m6A‐modified genes, including CCN2, may serve as new pharmaceutical targets to reverse bladder remodeling. Conclusions: Exploring the roles of m6A‐modified genes identified as associated with bladder remodeling by integrating RNA‐seq and MeRIP‐seq data can offer new insights for developing promising treatments for pBOO patients. [ABSTRACT FROM AUTHOR]

Bladder cancer (BLCA) is a common and difficult‐to‐manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA. [ABSTRACT FROM AUTHOR]

The Hunga Tonga‐Hunga Ha'apai (hereafter HTHH) submarine volcano erupted at 04:14:45 UT on 15 January 2022, causing ionospheric disturbances. This paper uses carrier phase observations from GNSS tracking stations in New Zealand and Australia to calculate the vertical total electron content. At 06:10, the ground‐based GNSS tracking station in New Zealand observes a maximum amplitude of 2.26 TECU anomaly caused by a mesoscale traveling ionospheric disturbance (MSTID) with a wavelength of 200–250 km, a period of 6–13 min, and a maximum propagation velocity of 330 m/s. The anomaly developed with time along the north‐south island direction toward the south island and lasted for about three and a half hours, with the ionosphere returning to pre‐eruption levels after 09:50, indicating a correlation between ionospheric activity and volcanic eruption. An ionospheric anomaly caused by an MSTID was also observed off the east coast of Australia around 08:11, with a maximum amplitude of 3.17 TECU and a maximum propagation velocity of 356 m/s. The ionospheric anomaly in Australia spreads out in a plane. In the process of propagation, it continuously impacts the area it passes through, and the entire anomaly process lasts for more than 7 hr. Still, the anomalous propagation velocities are more significant than in New Zealand, indicating that the Lamb waves excited by the eruption of the HTHH submarine volcano are directional in propagation speed; westward travels faster than southward. This finding will provide more references for scholars to study the mechanism and characteristics of anomaly propagation. Plain Language Summary: This paper reports on the Hunga Tonga‐Hunga Ha'apai submarine volcanic eruption event at Tonga on 15 January 2022, which caused air pressure waves in the form of Lamb waves to propagate to ionospheric heights and caused traveling ionospheric disturbances. Analysis of the filtered total electron content in the ionosphere using dense GNSS tracking stations in Australia and New Zealand revealed large‐scale, intense ionospheric disturbances. The propagation of the anomaly is also directional, with the New Zealand ionospheric anomaly initially propagating from north to south in a ripple pattern with a maximum mesoscale traveling ionospheric disturbance (MSTID) propagation velocity of ∼330 m/s. The impact of Lamb waves on the ionosphere in Australia is more pronounced, with the disturbance unfolding in a faceted pattern from east to west for up to 7 hr, during which the maximum MSTID propagation velocity is ∼356 m/s. In addition, the anomaly is affected by small‐amplitude gravity waves and excites multiple ionospheric disturbance phenomena during its propagation in both locations. This result confirms the natural phenomenon of ionospheric disturbances induced by extreme natural hazards and shows that severe explosive events can have a lasting and far‐reaching impact on the ionosphere. Key Points: Evidence of widespread traveling ionospheric disturbances caused by volcanic eruptionsThe propagation of the anomaly is directional, propagating westward at a greater rate than southwardSmall‐scale gravity waves have caused multiple transient ionospheric disturbances in both New Zealand and Australia [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is one of the most common tumours of the urinary system, and is insidious and not susceptible to chemoradiotherapy. As the most common subtype of RCC (70–80% of cases), clear cell renal cell carcinoma (ccRCC) is characterized by the loss of von Hippel–Lindau and the accumulation of robust lipid and glycogen. For advanced RCC, molecular‐targeted drugs, tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitors (ICIs) have been increasingly recommended and investigated. Due to the existence of a highly dynamic, adaptive and heterogeneous tumour microenvironment (TME), and due to the glucose and lipid metabolism in RCC, this cancer may be accompanied by various types of resistance to TKIs and ICIs. With the increased production of lactate, nitric oxide, and other new by‐products of metabolism, novel findings of the TME and key metabolic enzymes drived by HIF and other factors have been increasingly clarified in RCC carcinogenesis and therapy. However, there are few summaries of the TME and tumour metabolism for RCC progression and therapy. Here, we summarize and discuss the relationship of the important implicated characteristics of the TME as well as metabolic molecules and RCC carcinogenesis to provide prospects for future treatment strategies to overcome TME‐related resistance in RCC. [ABSTRACT FROM AUTHOR]

Background: Competitive endogenous RNAs (ceRNAs) have revealed a new mechanism of interaction between RNAs. However, an understanding of the ceRNA regulatory network in Wilms tumour (WT) remains limited. Methods: The expression profiles of mRNAs, miRNAs and lncRNAs in Wilms tumour samples and normal samples were obtained from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. The EdgeR package was employed to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses via the ClusterProfile R package were performed, and the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape. Subsequently, the correlation between the ceRNA network and overall survival was analysed. Results: A total of 2037 lncRNAs, 154 miRNAs and 3609 mRNAs were identified as differentially expressed RNAs in Wilms tumour. Of those, 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in the ceRNA regulatory network. The results of Gene Ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in terms related to response to mechanical stimuli, transcription factor complexes, and transcription factor activity (related to RNA polymerase II proximal promoter sequence-specific DNA binding). The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DEGs were mainly enriched in pathways related to the cell cycle. The survival analysis results showed that 16 out of the 205 lncRNAs, 1 out of 26 miRNAs and 5 out of 143 mRNAs were associated with overall survival in Wilms tumour patients (P < 0.05). Conclusions: CeRNA networks play an important role in Wilms tumour. This finding might provide effective, novel insights for further understanding the mechanisms underlying Wilms tumour. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias. Results: A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers' levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469–9.698, p = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774–8.304, p = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315–5.898, p = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017–1.577, p = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly. Conclusions: The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship. [ABSTRACT FROM AUTHOR]

Purpose: Targeted ferroptosis is a reliable therapy to inhibit tumor growth and enhance immunotherapy. This study generated a novel prognostic risk signature based on ferroptosis-related genes (FRGs), and explored the ability in clinic for clear cell renal cell carcinoma (ccRCC).Materials and Methods: The expression profile of mRNA and FRGs for ccRCC patients were exacted from The Cancer Genome Atlas (TCGA) database. A ferroptosis-related prognostic risk signature was constructed based on univariable and multivariable Cox-regression analysis. Kaplan-Meier (KM) survival curves and receiver operating characteristic (ROC) curves were performed to access prognostic value of riskscore. A nomogram integrating riskscore and clinical features was established to predict overall survival (OS). Based on differentially expressed genes between high- and low-OS groups with 5-year OS, function enrichment analyses and single-sample gene set enrichment analysis (ssGSEA) were investigated to immune status.Results: A 9-FRGs prognostic risk signature was constructed based on 37 differentially expressed FRGs. ROC and KM curves showed that riskscore has excellent reliability and predictive ability; Cox regression disclosed the riskscore as an independent prognosis for ccRCC patients. Then, the C-index and calibration curve demonstrated the good performance of nomogram in training and validation cohort, and its predictive ability better than other features. Immune-related biological processes were enriched by function enrichment analysis, and the immune-related cells and functions were differential by ssGSEA between high- and low-OS groups.Conclusion: Our study identified and verified a novel 9-FRGs prognostic signature and nomogram to predict OS, providing a novel sight to explore targeted therapy of ferroptosis for ccRCC. [ABSTRACT FROM AUTHOR]

Purpose: In this meta-analysis, we aimed to compared efficacy and safety of supracostal and infracostal access for percutaneous nephrolithotomy (PCNL).Materials and Methods: We included eligible studies from PubMed, EMBASE, Cochrane Library, Web of Science and China National Knowledge Infrastructure. Literature searching, quality assessment and data extraction were performed by two independent reviewers. Data were analyzed by RevMan software. Binary and continuous variables were calculated as odds ratios (OR) and mean difference (MD).Results: Two prospective comparative studies and seven retrospective observational studies were included in the meta-analysis, which contained 1,024 cases of supracostal access and 1,249 cases of infracostal access for PCNL. The supracostal access resulted in a significant reduced mean hemoglobin (95% CI: 0.26-3.46, MD = 1.86 g/L, P = .02) and a higher incidence of hydrothorax (95% CI: 4.77-22.95: OR = 10.47, P < .00001) compared to infracostal access. However, there no difference between supracostal and infracostal access regarding additional procedures (95% CI: 0.70-1.69, OR = 1.09, P = .71), stone-free rate (95% CI: 0.80-1.72, OR = 1.18, P = .41), length of hospital stay (95% CI: -0.03-0.37, MD = 0.17 day, P = .10), and occurrence of fever (95% CI: 0.95-2.03, OR = 1.39, P = .09) and blood transfusion (95% CI: 0.45-1.70, OR = 0.88, P = .70). No publication bias was identified in the study.Conclusion: Supracostal access was effective, but not as safe as infracostal access PCNL due to a higher risk of reduced hemoglobin and hydrothorax. Therefore, infracostal access should be the preferred safe and effective approach recommended for PCNL. When a supracostal puncture is performed, essential precautions to avoid hemoglobin loss and hydrothorax should be used. [ABSTRACT FROM AUTHOR]