Black patients referred to a lung cancer screening program experience lower rates of screening and longer time to follow-up.

BACKGROUND: Racial disparities are well-documented in preventive cancer care, but they have not been fully explored in the context of lung cancer screening. We sought to explore racial differences in lung cancer screening outcomes within a lung cancer screening program (LCSP) at our urban academic medical center including differences in baseline low-dose computed tomography (LDCT) results, time to follow-up, adherence, as well as return to annual screening after additional imaging, loss to follow-up, and cancer diagnoses in patients with positive baseline scans. METHODS: A historical cohort study of patients referred to our LCSP was conducted to extract demographic and clinical characteristics, smoking history, and lung cancer screening outcomes. RESULTS: After referral to the LCSP, blacks had significantly lower odds of receiving LDCT compared to whites, even while controlling for individual lung cancer risk factors and neighborhood-level factors. Blacks also demonstrated a trend toward delayed follow-up, decreased adherence, and loss to follow-up across all Lung-RADS categories. CONCLUSIONS: Overall, lung cancer screening annual adherence rates were low, regardless of race, highlighting the need for increased patient education and outreach. Furthermore, the disparities in race we identified encourage further research with the purpose of creating culturally competent and inclusive LCSPs

Food allergy: recent advances in pathophysiology and treatment

Food allergies are adverse immune reactions to food proteins that affect up to 6% of children and 3-4% of adults. A wide range of symptoms can occur depending on whether IgE or non-IgE mediated mechanism are involved. Many factors influence the development of oral tolerance, including route of exposure, genetics, age of the host, and allergen factors. Advances have been made in the understanding of how these factors interact in the pathophysiology of food allergy. Currently, the mainstay of treatment for food allergies is avoidance and ready access to emergency medications. However, with the improved understanding of tolerance and advances in characterization of food allergens, several therapeutic strategies have been developed and are currently being investigated as potential treatments and/or cures for food allergy

The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.This project was supported by the Global Parkinson’s Genetics Program (GP2). GP2 is funded by the Aligning Science Against Parkinson’s (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson’s Research (https://gp2.org).Open Access funding provided by the National Institutes of Health (NIH).This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services; project numbers ZO1 AG000535 and ZO1 AG000949, as well as the National Institute of Neurological Disorders and StrokePeer reviewe

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

173 - Julie Lake

What Are Microgreens? Microgreens are edible vegetable, herb and flower plants that are harvested between 7 – 15 days after germination. Only the hypocotyl (stem), cotyledons (seed leaves) and up to two 'true leaves' are eaten. Why Are Microgreens Important? High Nutrient Content: Studies have shown that microgreens have up to 40% higher nutrient concentrations than their mature counterparts. Xiao, Z., Lester, G., Luo, Y., & Wang, Q. (2012). Assessment of vitamin and carotenoid concentrations of emerging food products: Edible microgreens. Journal of Agricultural and Food Chemistry, 60 (31), 7644-51. Versatility of Growing Requirements: Can be grown in about any location, using a variety of growing methods, and in small or large quantities. Research Objective: Evaluate types of growing media used to cultivate arugula (Eruca sativa) microgreens to determine which media maximizes plant growth and minimizes water use. Methods: Three separate, randomized replications were completed in a greenhouse setting. All three replications contained six different types of 5"x 5" squares of growing media, randomly placed on a growing tray. Seven grams of microgreen arugula seeds, from Johnny's Selected Seeds, were evenly dispersed on top of each type of media. Each type of growing media in all three replications received the same amount of water (measured in ml and distributed daily), sunlight and indoor environmental conditions. The arugula microgreens were harvested sixteen days after seeds were planted. The microgreens were measured by harvesting and weighing plant material from each type of media, to determine the quantity produced for each media in all three replications. The growing media performance and microgreen production results were compared. Results: The germinating mix and the seed starter mix had the highest harvest weight totals and required the least amount of water, overall. The coconut coir mat required the most amount of water. The hydroponic grow mat produced the least amount of microgreens. One type of microgreen crop was chosen for this study. Arugula (Eruca sativa) microgreen seeds were sourced from the company, Johnny’s Selected Seeds in Maine; www.johnnyseeds.com. According to the seed package the seed germination rate expected would be 95 percent. Three separate replications were randomized. The microgreen replications were grown in a 9.14 x 18.29 meters (or 30 x 60 feet/1,800 square feet), privately owned, free-standing, standard gable roof with a gutter height of 12 feet, polycarbonate sheeting over galvanized steel structure greenhouse; located near downtown Colorado Springs, Colorado in July of 2018. The average daily temperature and humidity of the greenhouse was chosen by the greenhouse operator. The overall average daily temperature inside the greenhouse was 79.88 degrees Fahrenheit. The overall average daily humidity level was 50.25 percent. The cooling system for the greenhouse environment consisted of a re-circulating evaporative pad cooling system located on the east side of the building with two mechanical fans located at the opposite end of the greenhouse, on the west wall. The three different replications of microgreen crops were planted in three 2.5H x 25.4W x 50.8L cm, shallow, seed starting, plant germination trays with slotted holes used for growing microgreens. These three slotted trays were then set into three non-slotted trays of the same size but with a greater height of 5.08 cm, to allow for water drainage from the media. After the seeds were sown, the three replications trays were completely covered for the first three days with a clear plastic humidity dome cover to allow full sunlight on the growing media and seeds; but also helped to retain humidity in the enclosure to keep the media and seeds moist. From the fourth through eighth days the clear dome cover was replaced by a similar cover but one with holes to allow some air flow to the growing seedlings but keep media moist as not all seeds germinated at the same rate depending on the type of media they were sown on. Starting on day nine through harvest, no cover of any kind was used on any of the three replication trays. Each of the six different types of growing media for each of the three replications were sized as a 32.26 cm square, with the loose media (Jiffy seed starter and Johnny’s germination media, 340 gm of loose media in each clear container) contained in 2.5 cm high clear containers with drainage holes that were then set in the slotted growing trays with the rest of the media. They were then randomly placed with one type of media in each tray using a random number generator website. All the media were soaked with the same amount of tap water prior to seed dispersal. Arugula seeds were sown by evenly dispersing 7 grams of seed onto each 32.26 cm square type of media in all three trials, leaving the seeds directly on top of the media (without covering the seeds with additional media). The three trials were placed on the greenhouse bench closest to the evaporative pad cooling system on the east side of the greenhouse.College of Agricultural Sciences/Department of Horticulture and Landscape Architecture/Master of Horticulture/Colorado State University.Microgreens are edible vegetable, herb, and even flower plants that are harvested between 7 to 15 days after germination, when cotyledons and/or two ‘true’ leaves have emerged. Harvest parameters often vary depending on the type of plant being produced. The seedlings are harvested by cutting the hypocotyl just above the grow media, leaving the radicle behind. The hypocotyl, cotyledons, and often emerging first two 'true leaves' are the parts of the plant that are consumed. Plants in this early stage of development have a much higher nutritional content than their mature counterparts. Microgreens can be produced using a variety of growing methods, are easily grown in small or large quantities, and can be grown in almost any location. These factors make microgreens a quick growing source of nutritious food in the U.S. and globally. Researching different possible methods that can be used to grow microgreens could benefit future food supplies. Three separate, randomized replications were completed in a greenhouse setting. Each replication contained six different types of media, the grow media performance and microgreen production results were compared. Results showed the seed starter mix and the germinating media mix had the highest harvest volumes and required the least amount of water overall. Future research can include more media options, such as rockwool, vermicompost, perlite/vermiculite mix, coconut coir fibers/dust (not in a mat form), and sugarcane filter cake