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An evolutionary arms race occurs between viruses and hosts. Hosts have developed an array of antiviral mechanisms aimed at inhibiting replication and spread of viruses, reducing their fitness, and ultimately minimising pathogenic effects. In turn, viruses have evolved sophisticated counter-measures that mediate evasion of host defence mechanisms. A key aspect of host defences is the ability to differentiate between self and non-self. Previous studies have demonstrated significant suppression of CpG and UpA dinucleotide frequencies in the coding regions of RNA and small DNA viruses. Artificially increasing these dinucleotide frequencies results in a substantial attenuation of virus replication, suggesting dinucleotide bias could facilitate recognition of non-self RNA. The interferon-inducible gene, zinc finger antiviral protein (ZAP) is the host factor responsible for sensing CpG dinucleotides in viral RNA and restricting RNA viruses through direct binding and degradation of the target RNA. Herpesviruses are large DNA viruses that comprise three subfamilies, alpha, beta and gamma, which display divergent CpG dinucleotide patterns within their genomes. ZAP has recently been shown to act as a host restriction factor against human cytomegalovirus (HCMV), a beta-herpesvirus, which in turn evades ZAP detection by suppressing CpG levels in the major immediate-early transcript IE1, one of the first genes expressed by the virus. While suppression of CpG dinucleotides allows evasion of ZAP targeting, synonymous changes in nucleotide composition that cause genome biases, such as low GC content, can cause inefficient gene expression, especially in unspliced transcripts. To maintain compact genomes, the majority of herpesvirus transcripts are unspliced. Here we discuss how the conflicting pressures of ZAP evasion, the need to maintain compact genomes through the use of unspliced transcripts and maintaining efficient gene expression may have shaped the evolution of herpesvirus genomes, leading to characteristic CpG dinucleotide patterns.

Animal models that accurately reflect COVID-19 are vital for understanding mechanisms of disease and advancing development of improved vaccines and therapeutics. Pigs are increasingly recognized as valuable models for human disease due to their genetic, anatomical, physiological, and immunological similarities to humans, and they present a more ethically viable alternative to non-human primates. However, pigs are not susceptible to SARS-CoV-2 infection which limits their utility as a model. To address this, we have developed transgenic pigs expressing human ACE2 that are susceptible to SARS-CoV-2 infection. Following challenge, clinical signs consistent with COVID-19, including fever, coughing and respiratory distress were observed, with virus replication detected in the nasal turbinates, trachea and lungs up to the study endpoint, seven days post-infection. Notably, examination of tissues revealed immunopathology in the lungs consistent with histological changes observed in fatal human COVID-19 cases. This study establishes human ACE2 transgenic pigs as a large animal model that accurately reflects many aspects of COVID-19 disease. Long Fung Chau and colleagues report the generation of transgenic pigs expressing human ACE2, and show that they exhibit clinical signs and immunopathology consistent with COVID-19 following infection with SARS-CoV-2, suggesting that human ACE2 transgenic pigs are a viable large animal model for COVID-19.

No research thus far has attempted to examine ethical decision-making in corporate entrepreneurial organizations. Results of such study would provide management executives with insights on what action, if any, is essential for achieving business ethics and corporate entrepreneurship simultaneously. This paper argues, theoretically, that the work characteristics, organizational characteristics, and some individual characteristics in a corporate entrepreneurial organization are conductive to ethical decisions. These characteristics help mitigate the adverse impact of the turbulent environments on ethical decision-making behavior. Based on these arguments, a tentative model of ethical decision-making in corporate entrepreneurial organization is constructed.

This article reports on an evaluation of an educational Website specifically developed for teaching Internet market research. The evaluation results reveal that students perceive the information content of the Website as important and useful, but believe that the Website should be technically easy to master. Thus, to encourage students to use the Internet, a new technology and medium for marketing research, marketing educators should motivate students to learn, use, and master Internet technology. Also, marketing educators should identify the degree of the Internet literacy of their students and develop educational Website accordingly.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.Conclusions: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Background: According to the World Health Organization (WHO), as of April 9, 2022, there had been 494,587,638 confirmed COVID-19 cases and 6,170,283 deaths reported worldwide. In Hong Kong, in recent outbreak, ~55% of confirmed cases were residential care home (RCH) residents and >800 staff were infected. In 2016, ~15% of people aged ≥80 years were living in residential care homes. Objectives: To assess healthcare worker (HCW) knowledge level and attitudes about PPE use in residential care homes. Methods: This cross-sectional study, included participants who worked in the residential care homes, registered as healthcare workers (HCWs). HCWs who were part-time staff or worked <3 months in the residential care home were excluded. Ethical review approval from the faculty research committee of the university was obtained in January 2022. The Knowledge, Attitude, Practical (KAP) questionnaire was adapted. The questionnaire has 33 items pertaining to knowledge, attitude, and practice regarding PPE. Results: In total, 50 questionnaires were received; 32 respondents (64%) were female and 18 (36%) were male. Nearly half of the participants had completed a high diploma course, and 32% had graduated from secondary school. Using ANOVA, there were no significant differences of education level of participants or participant knowledge level of PPE [F(2,47) = .181; P = .835], attitudes [F(2,47) = 1.995; P = .147] and practice [F(2,47) = .459; P = .635]. The Pearson correlation was used to measure the relationship between knowledge level and PPE practices. Our results indicated a significant difference and moderate correlation between knowledge level and PPE practice among HCWs. Conclusions: Knowledge level does not directly affect HCW practice regarding PPE. PPE practice skills have been influenced by various factors during the pandemic situation, such as availability of PPE, manpower, workload, and communication.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1-2, and no linvencorvir-related serious adverse events were reported. Conclusions: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient. (Clin Mol Hepatol 2024;30:191-205)

Numerous studies have suggested associations between depression and cardiometabolic abnormalities or diseases, such as coronary artery disease and type 2 diabetes. However, little is known about the mechanism underlying this comorbidity, and whether the relationship differs by depression subtypes. Using the polygenic risk score (PRS) approach and linkage disequilibrium (LD) score regression, we investigated the genetic overlap of various depression-related phenotypes with a comprehensive panel of 20 cardiometabolic traits. GWAS results for major depressive disorder (MDD) were taken from the PGC and CONVERGE studies, with the latter focusing on severe melancholic depression. GWAS results on general depressive symptoms (DS) and neuroticism were also included. We also identified the shared genetic variants and inferred enriched pathways. In addition, we looked for drugs over-represented among the top shared genes, with an aim to finding repositioning opportunities for comorbidities. We found significant polygenic sharing between MDD, DS and neuroticism with various cardiometabolic traits. In general, positive polygenic associations with CV risks were observed for most depression phenotypes except MDD-CONVERGE. Counterintuitively, PRS representing severe melancholic depression was associated with reduced CV risks. Enrichment analyses of shared SNPs revealed many interesting pathways, such as those related to inflammation, that underlie the comorbidity of depressive and cardiometabolic traits. Using a gene-set analysis approach, we also revealed a number of repositioning candidates, some of which were supported by prior studies, such as bupropion and glutathione. Our study highlights shared genetic bases of depression with cardiometabolic traits, and suggests the associations vary by depression subtypes. To our knowledge, this is the also first study to make use of human genomic data to guide drug discovery or repositioning for comorbid disorders.