Recent Patterns and Trends in Global Prostate Cancer Incidence and Mortality: An Update.

Background And Objective: Our aim was to examine worldwide patterns and trends for prostate cancer (PC) incidence and mortality using high-quality, up-to-date, population-based data.

Methods: We analyzed age-standardized PC incidence and mortality rates by country and region from the 2022 GLOBOCAN estimates and temporal trends in incidence (50 countries/territories) and mortality (59 countries/territories) rates using data from the Cancer Incidence in Five Continents series and the World Health Organization mortality database.

Key Findings And Limitations: Estimated PC rates across regions in 2022 varied 13-fold for incidence and 9.

Lung cancer incidence rates in young women and men by state in the United States.

Previous studies reported higher lung cancer incidence in women than men among persons aged 35-54 years in the United States, a reversal of historically higher rates in men. We examined whether this pattern varies by state. Based on lung cancer incidence (2015-2019) data among adults aged 35-54 years from Cancer in North America database and historical cigarette smoking prevalence data (2004-2005) among adults 20-39 years from the Behavioral Risk Factor Surveillance System, incidence rates in women were equal to or higher than rates in their male counterparts in 40 of 51 states, with statistically significant differences in 20 states (two-sided, p < .

Changes in cancer incidence rates by stage during the COVID-19 pandemic in the US.

The coronavirus disease 2019 (COVID-19) pandemic led to health care disruptions and declines in cancer diagnoses in the United States. However, the impact of the pandemic on cancer incidence rates by stage at diagnosis and race and ethnicity is unknown. This cross-sectional study calculated delay- and age-adjusted incidence rates, stratified by stage at diagnosis and race and ethnicity, and rate ratios (RRs) comparing changes in year-over-year incidence rates (eg, 2020 vs 2019) from 2016 to 2020 for 22 cancer types based on data obtained from the Surveillance, Epidemiology, and End Results 22-registry database.

Changes in cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic in the USA: a cross-sectional nationwide assessment.

Background: The emergence of COVID-19 disrupted health care, with consequences for cancer diagnoses and outcomes, especially for early stage diagnoses, which generally have favourable prognoses. We aimed to examine nationwide changes in adult cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic by cancer type and key sociodemographic factors in the USA.

Methods: In this cross-sectional study, adults (aged ≥18 years) newly diagnosed with a first primary malignant cancer between Jan 1, 2018, and Dec 31, 2020, were identified from the US National Cancer Database.

Disparities and Trends in Genitourinary Cancer Incidence and Mortality in the USA.

Background: Previous studies have reported on incidence and mortality patterns for individual genitourinary cancers in the USA. However, these studies addressed individual cancer types rather than genitourinary cancers overall.

Objective: To comprehensively examine disparities and trends in the incidence and mortality for the four major genitourinary cancers (bladder, kidney, prostate, and testis) in the USA.

Residues within the Foot-and-Mouth Disease Virus 3D Nuclear Localization Signal Affect Polymerase Fidelity.

Many RNA viruses encode a proof-reading deficient, low-fidelity RNA-dependent polymerase (RdRp), which generates genetically diverse populations that can adapt to changing environments and thwart antiviral therapies. 3D, the RdRp of the foot-and-mouth disease virus (FMDV), is responsible for replication of viral genomes. The 3D N terminus encodes a nuclear localization signal (NLS) sequence,MRKTKLAPT, important for import of the protein to host nucleus.

Foot-and-mouth disease virus 5'-terminal S fragment is required for replication and modulation of the innate immune response in host cells.

The S fragment of the FMDV 5' UTR is predicted to fold into a long stem-loop structure and it has been implicated in virus-host protein interactions. In this study, we report the minimal S fragment sequence required for virus viability and show a direct correlation between the extent of the S fragment deletion mutations and attenuated phenotypes. Furthermore, we provide novel insight into the role of the S fragment in modulating the host innate immune response.

Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity.

Novel 6xHis tagged foot-and-mouth disease virus vaccine bound to nanolipoprotein adjuvant via metal ions provides antigenic distinction and effective protective immunity.

Here, we engineered two FMD viruses with histidine residues inserted into or fused to the FMDV capsid. Both 6xHis viruses exhibited growth kinetics, plaque morphologies and antigenic characteristics similar to wild-type virus. The 6xHis tag allowed one-step purification of the mutant virions by Co(2+) affinity columns.

Analysis of the interaction between host factor Sam68 and viral elements during foot-and-mouth disease virus infections.

Background: The nuclear protein Src-associated protein of 68 kDa in mitosis (Sam68) is known to bind RNA and be involved in cellular processes triggered in response to environmental stresses, including virus infection. Interestingly, Sam68 is a multi-functional protein implicated in the life cycle of retroviruses and picornaviruses and is also considered a marker of virus-induced stress granules (SGs). Recently, we demonstrated the partial redistribution of Sam68 to the cytoplasm in FMDV infected cells, its interaction with viral protease 3C(pro), and found a significant reduction in viral titers as consequence of Sam68-specific siRNA knockdowns.

Repeated exposure to 5D9, an inhibitor of 3D polymerase, effectively limits the replication of foot-and-mouth disease virus in host cells.

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock caused by a highly variable RNA virus (FMDV) that has seven serotypes and more than sixty subtypes. Both prophylactic and post-infection means of controlling the disease outbreak, including universally applicable vaccines and emergency response measures such as therapeutic treatments, are on high demand. In this study, we analyzed the long-term exposure outcome to a previously identified inhibitor of 3D polymerase (FMDV 3Dpol) for controlling FMDV infection and for the selection of resistance mutants.

The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells.

Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C(pro) induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm.

Inhibitors of foot and mouth disease virus targeting a novel pocket of the RNA-dependent RNA polymerase.

Background: Foot-and-Mouth Disease Virus (FMDV) is a picornavirus that infects cloven-hoofed animals and leads to severe losses in livestock production. In the case of an FMD outbreak, emergency vaccination requires at least 7 days to trigger an effective immune response. There are currently no approved inhibitors for the treatment or prevention of FMDV infections.

Dendritic cells infected with vpr-positive human immunodeficiency virus type 1 induce CD8+ T-cell apoptosis via upregulation of tumor necrosis factor alpha.

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) plays a crucial role in viral replication and pathogenesis by inducing cell cycle arrest, apoptosis, translocation of preintegration complex, potentiation of glucocorticoid action, impairment of dendritic cell (DC) maturation, and T-cell activation. Recent studies involving the direct effects of Vpr on DCs and T cells indicated that HIV-1 containing Vpr selectively impairs phenotypic maturation, cytokine network, and antigen presentation in DCs and dysregulates costimulatory molecules and cytokine production in T cells. Here, we have further investigated the indirect effect of HIV-1 Vpr(+) virus-infected DCs on the bystander CD8(+) T-cell population.

Antiviral effects of mifepristone on human immunodeficiency virus type-1 (HIV-1): targeting Vpr and its cellular partner, the glucocorticoid receptor (GR).

The HIV-1 viral protein R, Vpr, increases virus replication in T cells and is necessary for the optimal infection of primary monocytes/macrophages and other non-dividing cells. Vpr interacts with the cellular glucocorticoid receptor (GR) and transactivates the HIV-1 LTR through glucocorticoid response element (GRE), an event that can be blocked by the GR antagonist, mifepristone. Results demonstrated that Vpr-induced transactivation of the HIV-1 LTR was inhibited by mifepristone in a dose-dependent manner by >60% at a 10 microM concentration.

Molecular and functional characterization of a novel splice variant of ANKHD1 that lacks the KH domain and its role in cell survival and apoptosis.

Multiple ankyrin repeat motif-containing proteins play an important role in protein-protein interactions. ANKHD1 proteins are known to possess multiple ankyrin repeat domains and a single KH domain with no known function. Using yeast two-hybrid system analysis, we identified a novel splice variant of ANKHD1.

Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation: implications for viral immune escape.

Antigen presentation and T-cell activation are dynamic processes involving signaling molecules present in both APCs and T cells. Effective APC function and T-cell activation can be compromised by viral immune evasion strategies, including those of human immunodeficiency virus type 1 (HIV-1). In this study, we determined the effects of HIV-1 Vpr on one of the initial target of the virus, dendritic cells (DC), by investigating DC maturation, cytokine profiling, and CD8-specific T-cell stimulation function followed by a second signal.

Structure-functional analysis of human immunodeficiency virus type 1 (HIV-1) Vpr: role of leucine residues on Vpr-mediated transactivation and virus replication.

HIV-1 Vpr has been shown to transactivate LTR-directed expression through its interaction with several proteins of cellular origin including the glucocorticoid receptor (GR). Upon activation, steroid receptors bind to proteins containing the signature motif LxxLL, translocate into the nucleus, bind to their response element, and activate transcription. The presence of such motifs in HIV-1 Vpr has prompted us to undertake the analysis of the role of specific leucine residue(s) involved in Vpr-GR interaction, subcellular localization and its effect on Vpr-GR-mediated transactivation.

Differential regulation of host cellular genes by HIV-1 viral protein R (Vpr): cDNA microarray analysis using isogenic virus.

HIV-1 Vpr is a protein with multiple functions. It has been suggested that such pleiotropic effects by a viral protein may be mediated by its association with viral and cellular proteins or through modulation of expression of specific cellular genes. To address this, we used cDNA microarray techniques to analyze the regulation of a panel of host cellular genes by HIV-1 Vpr using isogenic HIV-1 either with or without Vpr expression.