Boyetteyusuf3323
This article has an associated 'The people behind the papers' interview.
The coronavirus disease pandemic has disproportionately affected poor and racial/ethnic minority individuals and communities, especially Indigenous Peoples. The object of this study is to understand the spatially varying associations between socioeconomic disadvantages and the number of confirmed COVID-19 cases in New Mexico at the ZIP code level.
We constructed ZIP code-level data (n=372) using the 2014-2018 American Community Survey and COVID-19 data from the New Mexico Department of Health (as of 24 May 2020). The log-linear Poisson and geographically weighted Poisson regression are applied to model the number of confirmed COVID-19 cases (total population as the offset) in a ZIP code.
The number of confirmed COVID-19 cases in a ZIP code is positively associated with socioeconomic disadvantages-specifically, the high levels of concentrated disadvantage and income inequality. It is also positively associated with the percentage of American Indian and Alaskan Native populations, net of other potential clean and safe water, and the dissemination of educational materials aimed at COVID-19 prevention in non-English language including Indigenous languages.We determined the seroprevalence of SARS-CoV-2 antibodies in NHS healthcare workers (HCWs) in a cross-sectional study from a large general hospital located in a double-sited rural and semi-rural area. The sample size of 3,119 HCWs (mean age 43±13) consisted of 75.2% women, 61.1% White individuals and predominantly (62.4%) asymptomatic individuals. Seroprevalence of SARS-CoV-2 antibodies was 19.7%. Determinants of seropositivity were preceding symptomatic infection and non-White ethnicity. Regardless of staff role or sex, multivariate regression analysis revealed that non-White HCWs were three times (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.53-3.86, P less then 0.001) more likely to have antibodies than White staff, and seven times (OR 7.10, 95% CI 5.72-8.87, P less then 0.001) more likely if there was a history of preceding symptoms. We report relatively high rates of seropositivity in all NHS healthcare workers. Non-White symptomatic HCWs were significantly more likely to be seropositive than their colleagues, independent of age, sex or staff role.
Single-agent pembrolizumab treatment of hormone receptor-positive metastatic breast cancer (MBC) has demonstrated modest clinical responses. Little is known about potential biomarkers or mechanisms of response to immune checkpoint inhibitors (ICIs) in patients with HR+ MBC. The present study presents novel immune correlates of clinical responses to combined treatment with CDK4/6i and ICI.
A combined analysis of two independent phase I clinical trials treating patients with HR+ MBC was performed. Patients treated with the combination of the CDK4/6i palbociclib+the ICI pembrolizumab+the aromatase inhibitor (AI) letrozole (palbo+pembro+AI) were compared with patients treated with pembrolizumab+AI (pembro+AI). Peripheral blood mononuclear cells collected at pretreatment, 3 weeks (cycle 2 day 1) and 9 weeks (cycle 4 day 1) were characterized by high-parameter flow cytometry to assess baseline immune subset composition and longitudinal changes in response to therapy.
In the peripheral blood, higher pretreatmeh palbociclib. We also demonstrated that in palbociclib-treated patients, cDC1 and cMO displayed increased CD83 and human leukocyte antigen-DR isotype (HLA-DR) expression, respectively, suggesting increased maturation and antigen presentation capacity.
Pre-existing circulating effector CD8
and CD4
T cells and dynamic modulation of circulating myeloid cell composition denote response to combined pembrolizumab and palbociclib therapy for patients with HR+ MBC.
NCT02778685 and NCI02648477.
NCT02778685 and NCI02648477.
MYC oncogene is deregulated in 70% of all human cancers and is associated with multiple oncogenic functions including immunosuppression in the tumor microenvironment. The role of MYC in the immune microenvironment of neuroblastoma and melanoma is investigated and the effect of targeting Myc on immunogenicity of cancer cells is evaluated.
Immune cell infiltrates and immunogenic pathway signatures in the context of MYCN amplification were analyzed in human neuroblastoma tumors and in metastatic melanoma. Dose response and cell susceptibility to MYC inhibitors (I-BET726 and JQ1) were determined in mouse cell lines. The influence of downregulating Myc in tumor cells was characterized by immunogenic pathway signatures and functional assays. Navitoclax Myc-suppressed tumor cells were used as whole cell vaccines in preclinical neuroblastoma and melanoma models.
Analysis of immune phenotype in human neuroblastoma and melanoma tumors revealed that MYCN or c-MYC amplified tumors respectively are associated with suppressed immune cell infiltrates and functional pathways. Targeting Myc in cancer cells with I-BET726 and JQ1 results in cell cycle arrest and induces cell immunogenicity. Combining vaccination of Myc-inhibited tumor cells with checkpoint inhibition induced robust antitumor immunity and resulted in therapeutic cancer vaccine therapy in mouse neuroblastoma tumors. Despite vigorous antitumor immunity in the mouse melanoma model, upregulation of immunosuppressive pathways enabled tumor escape.
This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.
This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.Despite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.
