Search

Davide De Battista,1 Fausto Zamboni,2 Hannah Gerstein,1 Shinya Sato,1 Tovah E Markowitz,3,4 Justin Lack,3,4 Ronald E Engle,1 Patrizia Farci1 1Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA; 2Liver Transplantation Center, Azienda Ospedaliera Brotzu, Cagliari, Italy; 3NIAID Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA; 4Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD, 21702, USACorrespondence: Patrizia FarciHepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USATel +1 240-669-5921Fax +1 301-402-0524Email pfarci@niaid.nih.govIntroduction: HCC is the third leading cause of cancer-related death worldwide, with chronic viral hepatitis accounting for more than 70% of the cases. Therapeutic options are limited and ineffective. The increasing use of immune-based therapies in solid tumors highlights the need to expand our knowledge on the immunologic microenvironment of HCC.Methods: Access to liver samples from 20 well-characterized patients with HCC associated with HCV (n = 9) or HBV (n = 11) gave us the opportunity to study the immunologic landscape in these tumors. For each patient, RNA-sequencing was performed on the tumor and surrounding nontumorous tissue.Results: We found that both HCV- and HBV-HCC are associated with a predominance of downregulated genes (74% and 67%, respectively). Analysis of the immune landscape using a curated gene list showed 216 of 2481 (9%) immune genes in HCV-HCC and 164 of 2560 (6%) in HBV-HCC. However, only 8 immune genes (4%) were upregulated in HCV-HCC and 27 (16.5%) in HBV-HCC. HCV-HCC was characterized by an enrichment of downregulated genes related to T-cell activation and oxidative stress. The dramatic downregulation of immune genes related to T-cell activation in HCV-HCC prompted us to perform an extensive immunohistochemistry analysis on paraffin-embedded liver specimen. Interestingly, we found a significant reduction of immune-cell infiltration (CD3, CD8 and CD20 positive cells) within the tumor. Moreover, we observed that HCV-HCC is characterized by an enrichment of M2-like CD68-positive cells. These data are consistent with the dramatic downregulation of immune-cell infiltration seen in HCV-HCC. Conversely, HBV-HCC was characterized by upregulation of genes related to monocyte/macrophage activation and cell cycle control, and downregulation of genes involved in various cell metabolisms.Conclusion: This study demonstrates a distinctive molecular signature and immune landscape in HCC of different viral etiology, which could provide new insights into pathogenesis and lead to the development of novel immune-based therapies.Keywords: hepatocellular carcinoma, hepatitis C virus, hepatitis B virus, RNA-sequencing, molecular signature, immune landscape

Oral nicotine pouches is a rapidly growing product category that potentially offers less risk than combustible tobacco products. Nicotine pouches may provide harm reduction for smokers because they contain no tobacco and have reduced harmful constituents compared to traditional tobacco product categories. Any potential public health benefit must weigh the likelihood that current tobacco users will switch to the lower-risk product against the likelihood that nonusers will start using tobacco products. To our knowledge, no existing studies provide population-level estimates of purchase intent or product appeal across tobacco user groups or how product characteristics might affect those variables.

The evolution of politics and communication in the information society has generated a series of complex challenges and opportunities. This study analyzes the paradigmatic shift in political communication in a context where information is accessible through a myriad of digital channels. Through an interdisciplinary perspective that encompasses communication, political science, and sociology, this work examines the role of new media and digital platforms and focuses on the emerging power dynamics in digital politics. The implications of this transformation will be discussed, highlighting the various interconnected interpretive interplays to ensure informed and responsible political participation in the information society. The primary goal of this study is to provide a comprehensive framework of the ongoing dynamics, enabling a critical reflection on the future direction of politics and communication in the information age.

Novel strategies with NRTIs‐sparing regimen in antiretroviral naïve HIV‐infected patients are currently used in clinical trials [1]. We previously presented preliminary results of this study [2] and here we present the 48‐weeks final results. Prospective, open‐label, randomised (1:1), multicenter, proof‐of‐concept trial. HIV‐infected naïve patients were assigned to once daily maraviroc (MVC) plus lopinavir/ritonavir (LPV/r) or to tenofovir/emtricitabine (TDF/FTC) plus LPV/r. Objectives of the study were the 48‐weeks virological and immunological efficacy. Data were collected at baseline (BL) and at 4, 12, 24, 36 and 48 weeks. T cell subsets from frozen peripheral blood mononuclear cells collected at BL, 4 and 48 weeks were also evaluated. ANOVA for repeated measures performed and Greenhouse‐Geisser probabilities calculated. Results reported as median (Q1–Q3) or frequency (%). Fifty patients (26 in MVC group and 24 in TDF/FTC group) were enrolled and reached week 48. Similar BL characteristics were observed in the two study groups; age: 39.1 (34.2–44) years, 2/50 (4%) females, infected since 2.9 (0.8–5.3) years, CD4+ nadir 266 (242–315) cells/µL, BL CD4+ 295 (260–369) cells/µL; CD4% 18.6 (14.6–23), HIV‐RNA 4.4 (3.9–4.8) log[sub.10] copies/mL. At W48, all patients in MVC group and 22/24 (96%) in TDF/FTC group had HIV‐RNA, References Kozal MJ, Lupo S, DeJesus E, Molina JM, McDonald C, Raffi F, et al. A nucleoside‐ and ritonavir‐sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment‐naïve HIV‐infected patients: SPARTAN [...]