Background: SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear.Method: We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19.Results: Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both.Conclusions: Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines.Funding: This work was supported by the National Institutes for Health (NIH) grants 1R01DK107585-01A1, 3R01DK107585-05S1 (to SD); R01-AI141630, CA100768 and CA160911 (to PG) and R01-AI 155696 (to PG, DS and SD); R00-CA151673 and R01-GM138385 (to DS), R01- HL32225 (to PT), UCOP-R00RG2642 (to SD and PG), UCOP-R01RG3780 (to P.G. and D.S) and a pilot award from the Sanford Stem Cell Clinical Center at UC San Diego Health (P.G, S.D, D.S). GDK was supported through The American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists. L.C.A's salary was supported in part by the VA San Diego Healthcare System. This manuscript includes data generated at the UC San Diego Institute of Genomic Medicine (IGC) using an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).
Background Firefighters are at increased risk for select cancers. However, many studies are limited by relatively small samples, with virtually no data on the cancer experience of female firefighters. This study examines cancer risk in over 100,000 career Florida firefighters including 5000 + females assessed over a 34‐year period. Methods Florida firefighter employment records (n = 109 009) were linked with Florida Cancer Data System registry data (1981‐2014; ~3.3 million records), identifying 3760 male and 168 female‐linked primary cancers. Gender‐specific age and calendar year‐adjusted odds ratios (aOR) and 95% confidence intervals for firefighters vs non‐firefighters were calculated. Results Male firefighters were at increased risk of melanoma (aOR = 1.56; 1.39‐1.76), prostate (1.36; 1.27‐1.46), testicular (1.66; 1.34‐2.06), thyroid (2.17; 1.78‐2.66) and late‐stage colon cancer (1.19;1.00‐1.41). Female firefighters showed significantly elevated risk of brain (2.54; 1.19‐5.42) and thyroid (2.42; 1.56‐3.74) cancers and an elevated risk of melanoma that approached statistical significance (1.68; 0.97‐2.90). Among male firefighters there was additional evidence of increased cancer risk younger than the age of 50 vs 50 years and older for thyroid (2.55; 1.96‐3.31 vs 1.69; 1.22‐2.34), prostate (1.88; 1.49‐2.36 vs 1.36; 1.26‐1.47), testicular (1.60; 1.28‐2.01 vs 1.47; 0.73‐2.94), and melanoma (1.87; 1.55‐2.26 vs 1.42; 1.22‐1.66) cancers. Conclusion Male career firefighters in Florida are at increased risk for five cancers with typically stronger associations in those diagnosed younger than the age of 50, while there was evidence for increased thyroid and brain cancer, and possibly melanoma risk in female firefighters. Larger cohorts with adequate female representation, along with the collection of well‐characterized exposure histories, are needed to more precisely examine cancer risk in this occupational group.
SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19 which can be immediately utilized to investigate COVID-19 pathogenesis, and vet new therapies and vaccines.
We draw upon social disorganization theory to examine the effects of community characteristics on the distribution of offsite alcohol outlets in San Diego County, California. Of particular interest is whether alcohol availability varies according to neighborhood racial/ethnic composition once measures of social disorganization (socioeconomic disadvantage, residential instability, and racial/ ethnic heterogeneity) are controlled. Using data from the 1990 Census and 1993 alcohol license reports, we estimate a series of negative binomial regression models with corrections for spatial autocorrelation. The results show that percent Asian is associated with lower offsite alcohol outlet density. Once socioeconomic disadvantage is controlled, percent Latino is related to lower alcohol availability. Although similar suppressor patterns are observed, percent Black is generally unrelated to outlet density. Consistent with social disorganization theory, socioeconomic disadvantage and residential instability predict increased alcohol availability. Neighborhood racial/ethnic composition is either unrelated or inversely related to outlet density once social disorganization and other neighborhood characteristics are taken into account. KeywordsAlcohol outlets; alcohol availability; race and ethnicity; social disorganization theory; neighborhoods Alcohol availability, measured by the distribution of alcohol outlets in neighborhoods and communities, is a major public health concern. Studies show that alcohol availability or alcohol outlet density is associated with higher rates of sexually transmitted infections (Scribner, Cohen and Farley, 1998), driving under the influence (Treno, Grube and Martin, 2003), lethal and non-lethal violence (e.g., Gorman, Zhu and Horel, 2005;Hipp, 2007;Nielsen and Martinez, 2003;Peterson, Krivo and Harris, 2000), alcohol-related hospital admissions (Tatlow, Clapp and Hohman, 2000), and mortality from liver disease, cardiovascular disease, and homicide *Direct Correspondence to: Amie L. Nielsen, Associate Professor, University of Miami, Department of Sociology, P.O. Box 248162, Coral Gables, FL 33124-2030; Phone: 305-284-6158; Fax: 305-284-5310; email: nielsen@miami.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptSoc Sci Res. Author manuscript; available in PMC 2011 January 1. (Cohen, Mason and Farley, 2004;Scribner, Mackinnon and Dwyer, 1994;Watts and Rabow, 1983; but see Jones-Webb et al., 2008). Given the apparent public health significance of alcohol availability and related concerns for environmental justi...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.