A scientometric analysis of research trends on targeting mTOR in breast cancer from 2012 to 2022

Over the past decade, thousands of articles have been published on the mechanistic target of rapamycin (mTOR) and its role in breast cancer. However, the variability and heterogeneity of academic data may impact the acquisition of published research information. Due to the large number, heterogeneity, and varying quality of publications related to mTOR and breast cancer, sorting out the present state of the research in this area is critical for both researchers and clinicians. Therefore, scientometric techniques and visualization tools were employed to analyze the large number of bibliographic metadata related to the research area of mTOR and breast cancer. The features of relevant publications were searched from 2012 to 2022 to evaluate the present status of research and the evolution of research hotspots in this particular field. Web of Science was utilized to extract all relevant publications from 2012 to 2022. Subsequently, Biblioshiny and VOSviewer were utilized to obtain data on the most productive countries, authors, and institutions, annual publications and citations, the most influential journals and articles, and the most frequently occurring keywords. In total, 1,471 publications were retrieved, comprising 1,167 original articles and 304 reviews. There was a significant rise in publications between 2015 and 2018, followed by a sharp decline in 2019 and a rebound since then. The publication with the highest number of citations was a 2012 review authored by Baselga et al. The United States had the highest number of publications, citations and connections among all countries. Oncotarget had the highest number of published articles among all the journals, and José Baselga had the strongest links with other authors. Excluding the search topics, the most frequently used words were “expression” (n = 297), “growth” (n = 228), “activation” (n = 223), “pathway” (n = 205), and “apoptosis” (n = 195). mTOR is crucially involved in breast cancer pathogenesis, but its exact mechanism of action remains controversial and warrants further investigation. The scientometric analysis provides a distinct overview of the existing state of research and highlights the topical issues that deserve further exploration

m6A modification patterns and tumor immune landscape in clear cell renal carcinoma

Background Recent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive.Methods We comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore.Results We identified three m6Aclusters—characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC.Conclusions This study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients

ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer

Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is highly expressed in various human malignant tumors. However, the exact function and mechanism of TET3 in breast cancer remain unclear. In this study, we investigated TET3 expression in breast cancer and its correlation with clinicopathological characteristics of breast cancer patients. The results presented that TET3 expression was significantly increased in breast cancer and associated with the PAM50 subtype. Subsequently, we performed receiver operating characteristic, survival, and Cox hazard regression analyses. These results suggest that TET3 expression is associated with a poor prognosis and may be an indirect independent prognostic indicator in breast cancer. We also established a protein-protein interaction (PPI) network of TET3 and executed enrichment analyses of TET3 co-expressed genes, revealing their primary association with the cell cycle. Moreover, we identified noncoding RNAs (ncRNAs) contributing to TET3 overexpression using expression, correlation, and survival analyses. We identified the LINC01521/hsa-miR-29a-3p axis as the primary TET3 upstream ncRNA-related pathway in breast cancer. Furthermore, TET3 expression was positively associated with immune cell infiltration, immune cell biomarkers, and eight immune checkpoint gene expressions in breast cancer. TET3 expression also correlated with patient responses to immunotherapy. Finally, we conducted subcellular localization and immunohistochemical staining analysis of TET3 in breast cancer. We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer

Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 − metastatic or advanced breast cancer patients: a network meta-analysis

Abstract Background This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). Methods We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. Results Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. Conclusions Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies

Data_Sheet_1_Global research into the relationship between electronic waste and health over the last 10 years: A scientometric analysis.docx

IntroductionThe aims of this research were to conduct the first holistic and deep scientometric analysis of electronic waste and health and provide with the prediction of research trends and hot topics.MethodA comprehensive literature search was conducted via the Web of Science Core collection databases on 26 August 2022 to identify all articles related to electronic waste and health. A total of 652 records have been extracted from the Web of Science after applying inclusion and exclusion criteria and were analyzed using bibliometrix software of R-package, VOSviewer, and CiteSpace, visualized by tables and diagrams.ResultThe number of publications and total citations had shown a general growth trend from 2012 to 2021, with an average annual growth rate of 23.74%. Mainland China was the significant nation with the greatest number of publications, citations, and international links. The journal publishing the most was “Science of the Total Environment” (n = 56). Huo X and Hu XJ were the top two author contributing to this field with the highest h-index (23). Over time, the focus in this field shifted to exposure to heavy metal, polychlorinated biphenyls, polybrominated biphenyl ethers, and poly- and perfluorinated alkyl substances from electronic waste, and managements, such as hydrometallurgy.DiscussionBy this scientometric analysis, we found that the most active country, journal, organization and author contributing to this filed, as well as high impact documents and references and research hotspots. Also, we found that the hotspots might be exposure to toxic substances from electronic waste procession, its impact on human health and relevant managements. And evironmentally friendly materials to replace heavy metal mate rials, and environmentally friendly and effective recycling methods of electronic waste need to be further studied.</p

Systematic genome editing of the genes on zebrafish Chromosome 1 by CRISPR/Cas9

Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes. Meanwhile, by high-throughput bioinformatics analysis, we found that sequence features play pivotal roles in effective gRNA targeting at specific genes of interest, while the success rate of gene targeting positively correlates with GC content of the target sites. Moreover, we found that nearly one-fourth of all mutants are related to human diseases, and several representative CRISPR/Cas9-generated mutants are described here. Furthermore, we tried to identify the underlying mechanisms leading to distinct phenotypes between genetic mutants and antisense morpholino-mediated knockdown embryos. Altogether, this work has generated the first chromosome-wide collection of zebrafish genetic mutants by the CRISPR/Cas9 technology, which will serve as a valuable resource for the community, and our bioinformatics analysis also provides some useful guidance to design gene-specific gRNAs for successful gene editing

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to &lt; 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of &amp; GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P &lt; 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo