Palliative Care Landscape in the COVID-19 Era: Bibliometric Analysis of Global Research.

Despite the increasing number of publications globally, the COVID-19 pandemic has underscored significant research gaps that should be resolved, including within PC-related research. This study aimed to map and understand the global trends in palliative care (PC)-related COVID-19 research and provide quantitative evidence to guide future studies. We systematically searched four databases between 1st January 2020 and 25th April 2022. The VOSviewer, Gephi, and R software were utilized for data analysis and results visualization. A total of 673 articles were identified from the databases between 1st January 2020 and 25th April 2022. Canada (6.2%), Australia (5.4%), and the United Kingdom (3.8%) were the most productive countries regarding articles published per million confirmed COVID-19 cases. A lack of international collaborations and an uneven research focus on PC across countries with different pandemic trajectories was observed. The PC research in question focused on cancer, telehealth, death and dying, and bereavement. This study's conclusions support the recommendation for international collaboration to facilitate knowledge and practice transformation to support countries with unmet PC needs during the pandemic. Further studies are required on the grief and bereavement support of families, healthcare professionals and patients with other life-threatening illnesses.

Deciphering the evolution of composite-type GSKIP in mitochondria and Wnt signaling pathways.

We previously revealed the origin of mammalian simple-type glycogen synthase kinase interaction protein (GSKIP), which served as a scavenger and a competitor in the Wnt signaling pathway during evolution. In this study, we investigated the conserved and nonconserved regions of the composite-type GSKIP by utilizing bioinformatics tools, site-directed mutagenesis, and yeast two-hybrid methods. The regions were denoted as the pre-GSK3ß binding site, which is located at the front of GSK3ß-binding sites. Our data demonstrated that clustered mitochondria protein 1 (CLU1), a type of composite-type GSKIP that exists in the mitochondria of all eukaryotic organisms, possesses the protein known as domain of unknown function 727 (DUF727), with a pre-GSK3ß-binding site and a mutant GSK3ß-binding flanking region. Another type of composite-type GSKIP, armadillo repeat containing 4 (ARMC4), which is known for cilium movement in vertebrates, contains an unintegrated DUF727 flanking region with a pre-GSK3ß-binding site (115SPxF118) only. In addition, the sequence of the GSK3ß-binding site in CLU1 revealed that Q126L and V130L were not conserved, differing from the ideal GSK3ß-binding sequence of simple-type GSKIP. We further illustrated two exceptions, namely 70 kilodalton heat shock proteins (Hsp70/DnaK) and Mitofilin in nematodes, that presented an unexpected ideal GSK3ß-binding region with a pre-GSK3ß sequence; this composite-type GSKIP could only occur in vertebrate species. Furthermore, we revealed the importance of the pre-GSK3ß-binding site (118F or 118Y) and various mutant GSK3ß-binding sites of composite-type GSKIP. Collectively, our data suggest that the new composite-type GSKIP starts with a DUF727 domain followed by a pre-GSK3ß-binding site, with the subsequent addition of the GSK3ß-binding site, which plays vital roles for CLU1, Mitofilin, and ARMC4 in mitochondria and Wnt signaling pathways during evolution.

Correction: Inflammation Promotes Expression of Stemness-Related Properties in HBV-Related Hepatocellular Carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0149897.].

Inflammation Promotes Expression of Stemness-Related Properties in HBV-Related Hepatocellular Carcinoma.

The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC). We observed positive immunorecognition for macrophage chemoattractant protein 1 (MCP-1)/CD68 and OCT4/NANOG in HBV-HCC tissues. The inflammation-conditioned medium (inflamed-CM) generated by lipopolysaccharide-stimulated U937 human leukemia cells significantly increased the mRNA and protein levels of OCT4/NANOG preferentially in HBV-active (HBV+HBsAg+) HCC cells. The inflamed-CM also increased the side population (SP) cell percentage, green fluorescent protein (GFP)-positive cell population, and luciferase activity of OCT4 promoter-GFP/luciferase in HBV-active HCC cells. Furthermore, the inflamed-CM upregulated the expressions of insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) and activated IGF-IR/Akt signaling in HBV-HCC. The IGF-IR phosphorylation inhibitor picropodophyllin (PPP) suppressed inflamed-CM-induced OCT4 and NANOG levels in HBV+HBsAg+ Hep3B cells. Forced expression of OCT4 significantly increased the secondary sphere formation and cell migration, and reduced susceptibility of HBV-HCC cells to cisplatin, bleomycin, and doxorubicin. Taking together, our results show that niche inflammatory mediators play critical roles in inducing the expression of stemness-related properties involving IGF-IR activation, and the upregulation of OCT4 contributes to cancer migration and drug resistance of HBV-HCC cells. Findings in this paper would provide potential targets for a therapeutic strategy targeting on inflammatory environment for HBV-HCC.