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Beebe Jokumsen posted an update 6 months, 3 weeks ago
Radioproteomics is the integration of proteomics, the systematic study of the protein expression of an organism, with radiomics, the extraction and analysis of large numbers of quantitative features from medical images. This article examines this developing field, and it’s application in high grade serous ovarian carcinoma. Seminal proteomic studies in the area of ovarian cancer, such as the PROVAR and CPTA studies are discussed, along side recent research, such as that highlighting the central role of methyltransferase nicotinamide N-methyltransferase as the metabolic regulation of cancer progression in the tumour stroma. Finally, this article considers a novel, hypothesis generating approach to integrate CT-based qualitative and radiomic features with proteomic analysis, and the future direction of the field. Combined advances in radiomic, proteomic and genomic analysis has the potential to signal the age of true precision medicine, where treatment is centered specifically on the molecular profile of the tumour, rather than based on empirical knowledge, thus altering the course of a disease that has the highest mortality of all cancers of the female reproductive system.
The double-blind, placebo-controlled, phase III TOURMALINE-MM1 study demonstrated a statistically significant improvement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed or refractory multiple myeloma. We report the final analyses for overall survival (OS).
Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of prior therapies (1
2 or 3), previous proteasome inhibitor (PI) exposure (yes
no), and International Staging System disease stage (I or II
III). OS (intent-to-treat population) was a key secondary end point.
With a median follow-up of 85 months, median OS with ixazomib-Rd versus placebo-Rd was 53.6 versus 51.6 months (hazard ratio, 0.939;
= .495). Lower hazard ratios, indicating larger magnitude of OS benefit with ixazomib-Rd versus placebo-Rd, were seen in predefined subgroups refractory to any (0.794) or last (0.742) treatment line; age > 65-75 years (ceived, especially PIs and daratumumab.
Median OS values in both arms were the longest reported in phase III studies of Rd-based triplets in relapsed or refractory multiple myeloma at the time of this analysis; progression-free survival benefit with ixazomib-Rd versus placebo-Rd did not translate into a statistically significant OS benefit on intent-to-treat analysis. OS benefit was greater in subgroups with adverse prognostic factors. OS interpretation was confounded by imbalances in subsequent therapies received, especially PIs and daratumumab…
Coronary allograft vasculopathy (CAV) is a devastating sequela of heart transplant in which arterial intimal thickening limits coronary blood flow. There are currently no targeted therapies to prevent or reduce this pathology that leads to transplant failure. Vascular smooth muscle cell (VSMC) phenotypic plasticity is critical in CAV neointima formation. TET2 (TET methylcytosine dioxygenase 2) is an important epigenetic regulator of VSMC phenotype, but the role of TET2 in the progression of CAV is unknown.
We assessed TET2 expression and activity in human CAV and renal transplant samples. We also used the sex-mismatched murine aortic graft model of graft arteriopathy (GA) in wild-type and inducible smooth muscle-specific
knockout mice; and in vitro studies in murine and human VSMCs using knockdown, overexpression, and transcriptomic approaches to assess the role of TET2 in VSMC responses to IFNγ (interferon γ), a cytokine elaborated by T cells that drives CAV progression.
In the present study, we foulopathy or IFNγ stimulation. Promoting TET2 activity in vivo with systemic ascorbic acid reduces VSMC apoptosis and intimal thickening. Caspofungin in vitro These data suggest that promoting TET2 activity in CAV may be an effective strategy for limiting CAV progression.
TET2 is repressed in CAV and GA, likely mediated by IFNγ. TET2 serves to protect VSMCs from apoptosis in the context of transplant vasculopathy or IFNγ stimulation. Promoting TET2 activity in vivo with systemic ascorbic acid reduces VSMC apoptosis and intimal thickening. These data suggest that promoting TET2 activity in CAV may be an effective strategy for limiting CAV progression.California has focused on health equity in the state’s COVID-19 reopening plan. The Blueprint for a Safer Economy assigns each of California’s 58 counties into 1 of 4 tiers based on 2 metrics test positivity rate and adjusted case rate. To advance to the next less-restrictive tier, counties must meet that tier’s test positivity and adjusted case rate thresholds. In addition, counties must have a plan for targeted investments within disadvantaged communities, and counties with more than 106 000 residents must meet an equity metric. California’s explicit incorporation of health equity into its reopening plan underscores the interrelated fate of its residents during the COVID-19 pandemic and creates incentives for action. This article evaluates the benefits and challenges of this novel health equity focus, and outlines recommendations for other US states to address disparities in their reopening plans. (Am J Public Health. Published online ahead of print June 10, 2021 e1-e8. https//doi.org/10.2105/AJPH.2021.306263).Public health surveillance can have profound impacts on the health of populations, with COVID-19 surveillance offering an illuminating example. Surveillance surrounding COVID-19 testing, confirmed cases, and deaths has provided essential information to public health professionals about how to minimize morbidity and mortality. In the United States, surveillance has also pointed out how populations, on the basis of geography, age, and race and ethnicity, are being impacted disproportionately, allowing targeted intervention and evaluation. However, COVID-19 surveillance has also highlighted how the public health surveillance system fails some communities, including sexual and gender minorities. This failure has come about because of the haphazard and disorganized way disease reporting data are collected, analyzed, and reported in the United States, and the structural homophobia, transphobia, and biphobia acting within these systems. We provide recommendations for addressing these concerns after examining experiences collecting race data in COVID-19 surveillance and attempts in Pennsylvania and California to incorporate sexual orientation and gender identity variables into their pandemic surveillance efforts.
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