There is an urgent need for new animal models of SARS CoV-2 infection to improve research and drug development. This brief commentary examines the deficits of current models and proposes several improved alternates. The existing single transgene mouse models poorly mimic the clinical features of COVID-19; those strains get a milder disease than human COVID-19 disease. Many of the current transgenic models utilize random integration of several copies of single ACE2 transgenes, resulting in unnatural gene expression and exhibit rapid lethality. We suggest preparing precision knock-in of selected human mini genes at the mouse initiation codon and knock-out of the mouse homolog as a better option. Three genes critical for infection are suggested targets, ACE2 (the viral cellular receptor), its co-infection protease TMRPSS2, and the primary antibody clearance receptor FcγRT. To offer the best platform for COVID 19 research, preparation of single, double, and triple humanized combinations offers the researcher thIn addition, we propose to create the humanized strains in the C57BL/6J and BALB/c backgrounds. These two backgrounds are Th1 responders and Th2 responders, respectively, and allow modeling of the variability seen in human pathology including lung pathology and late sequelae of COVID-19 disease (BALB/c). We suggest the need to do a thorough characterization of both the short-term and long-term effects of SAR-CoV-2 infection at the clinical, virologic, histopathologic, hematologic, and immunologic levels. We expect the multiply humanized strains will be superior to the single-gene and multiple-gene-copy transgenic models available to date. These mouse models will represent state-of-the-art tools for investigating mechanisms of COVID-19 pathogenesis and immunity and developing vaccines and drugs.Artificial intelligence (AI) refers to the use of computational techniques to mimic human thought processes and learning capacity. The past decade has seen a rapid proliferation of AI developments for cardiovascular computed tomography (CT). These algorithms aim to increase efficiency, objectivity, and performance in clinical tasks such as image quality improvement, structure segmentation, quantitative measurements, and outcome prediction. By doing so, AI has the potential to streamline clinical workflow, increase interpretative speed and accuracy, and inform subsequent clinical pathways. This review covers state-of-the-art AI techniques in cardiovascular CT and the future role of AI as a clinical support tool.Tobacco and cannabis poly-substance and poly-product use is common in adolescents and young adults (AYAs), but few studies have examined developmental trajectories of poly-use. This study characterized the prevalence, patterns, and racial/ethnic and sex differences of developmental trajectories of use and poly-use of 8 different widely-marketed tobacco and cannabis products across adolescence and young adulthood. 3322 AYAs from Los Angeles, California completed 5 surveys from fall of 11th grade (2015) to 1-2 years post-high school (2018-2019). Self-reported past 30-day use of three tobacco (nicotine vaping, cigarette, hookah) and five cannabis (combustible, blunt, edible, vaping, dabbing) products were analyzed using parallel growth mixture modeling to identify tobacco and cannabis use and poly-use trajectories; racial/ethnic and sex differences were evaluated as correlates of trajectory membership. Five trajectories were identified Non-Users (58.6%); Young Adult-Onset Poly-Substance/Poly-Product Users (15.8%); Decreasing Moderate Poly-Substance/Poly-Product Users (9.8%); Increasing Predominant Cannabis Poly-Product Users (8.3%); and Chronic Poly-Substance/Poly-Product Users (7.3%). Within trajectories, developmental patterns of each tobacco and cannabis product were similar. Non-Hispanic White (vs. non-NH White) participants had higher odds of belonging to the Chronic Poly-Substance/Poly-Product Users (vs. Non-Users) trajectory (aOR = 2.24[1.37,3.67]); females (vs. males) had higher odds of belonging to the Young Adult-Onset Poly-Substance/Poly-Product Users (vs. Non-Users) trajectory (aOR = 1.30[1.02-1.66]). Tobacco and cannabis poly-substance use patterns, including use of various products, appear to be a common developmental trajectory during some point in adolescence and young adulthood. The interplay of tobacco and cannabis poly-substance/poly-product use merit attention in prevention and regulatory policies to protect AYA health.Bone marrow mesenchymal stromal cells are a highly heterogenic cell population containing mesenchymal stem cells as well as other cell types. With the advance of single cell transcriptome analysis, several recent reports identified a prominent subpopulation of mesenchymal stromal cells that specifically express adipocyte markers but do not contain lipid droplets. We name this cell type marrow adipogenic lineage precursor, MALP, and consider it as a major cellular component of marrow adipose tissue. Here, we review the discovery of MALPs and summarize their unique features and regulatory roles in bone. We further discuss how these findings advance our understanding of bone remodeling, mesenchymal niche regulation of hematopoiesis, and marrow vasculature maintenance.Biomarkers in COPD may be clinical (prior exacerbation history), physiologic (FEV1), or blood based (eosinophil count or fibrinogen level). Recent interest in using biomarkers to predict response to therapy in clinical practice has emerged.  https://www.selleckchem.com/products/d-4476.html  The benefits of inhaled therapy depend on the correct use of the inhaler, including an appropriate inspiratory flow. Of the available delivery systems, dry powder inhalers are unique because they have an internal resistance, are breath actuated, and are flow dependent. Ideally, the user inhales "forcefully" to generate turbulent energy (determined by an individual's inspiratory flow and the resistance of the device) within the device that disaggregates the powder so that the individual inhales the medication particles into the lower respiratory tract. Because of specific features of dry powder inhalers and the required optimal inspiratory flow, an unmet need exists to identify individuals who are likely or unlikely to benefit from dry powder medications. Peak inspiratory flow, defined as the maximum airflow generated during inhalation against the simulated resistance of a dry powder inhaler, is a physiologic measure that has biological plausibility, has good test characteristics (repeatability and reliability), and is generalizable.