cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Biobehavioral Intervention to Reduce Adverse Outcomes in Young Adult Latinos with Testicular Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Testicular cancer (TC) diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in young adulthood. In fact, the prevalence of depressive symptoms in TC exceeds the general population, and young Latino men are at high risk for adverse outcomes after treatment. In fact, the majority of young adult cancer survivors will experience impairing, distressing, and modifiable physical, behavioral, and psychosocial adverse outcomes that persist long after the completion of medical treatment. Yet, few targeted, tailored, culturally-relevant interventions exist to assist young Latino survivors in re-negotiating life goals and regulating cancer-related emotions and none focus on reducing cancer burden via biobehavioral mechanisms. Young or “emerging” adulthood is marked by goal attainment. Chronic illness experienced as “off time” in the lifespan interrupts goal pursuits and threatens valued life directions. As young adults return to goal pursuits, re-entry to post-cancer life can be a critical point in the survivorship trajectory. Behavioral intervention at this time is well positioned to confer longer-term impact. Emergent from our group’s preliminary research, we developed and pilot-tested Goal-focused Emotion-Regulation Therapy (GET) as a behavioral intervention to enhance self-regulation through improved goal navigation skills, sense of purpose, and ability to regulate emotional responses in young adults with TC. Responsive the need for feasible, effective, and scalable interventions that meet the need of ethnic minority men, 25 Latino young adults (ages 18-39) with TC will receive 6 sessions of GET. This pilot study aims to establish feasibility, clinically-meaningful (not statistically significant) change, and guidance for cultural adaptation. We predict that GET, and our ability to detect meaningful change, will be feasible in Latino young adult TC survivors. We expect GET to be associated with reduced distress and reductions in adverse biobehavioral indicators (dysregulated stress hormones, elevated inflammation). We also expect that greater endorsement of culturally-relevant factors (i.e., familism, simpatia, acculturation/acculturative stress, machismo/caballerismo) will condition the impact of GET on primary and secondary outcomes and that qualitative data will identify culturally-relevant adaptation.
Jaekelotodus Menner 1928
Creators: name: Ebersole, Jun A.
name: Cicimurri, David J.
name: Stringer, Gary L.
Publisher: name: Zenodo
Year: 2019
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Chondrichthyes
Lamniformes
Jaekelotodus

description: Genus Jaekelotodus Menner, 1928
Type species
Hypotodus trigonalis Jaekel, 1895, Oligocene, Russia.
description: Published as part of Ebersole, Jun A., Cicimurri, David J. & Stringer, Gary L., 2019, Taxonomy and biostratigraphy of the elasmobranchs and bony fishes (Chondrichthyes and Osteichthyes) of the lower-to-middle Eocene (Ypresian to Bartonian) Claiborne Group in Alabama, USA, including an analysis of otoliths, pp. 1-274 in European Journal of Taxonomy 585 on page 47, DOI: 10.5852/ejt.2019.585, http://zenodo.org/record/3660259
Advancing VCP inhibitors as experimental therapeutics in ovarian cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Protein quality control (PQC) pathways are important for protein and organelle homeostasis and essential for the fitness of cancer cells in the face of genomic instability, thus creating a cancer cell dependency. Components of PQC, such as heat shock proteins, also provide an adaptive response to cancer therapy and contribute to resistance. Therefore, PQC represents a point of vulnerability for cancer cells and a therapeutic target to potentiate the efficacy of current cancer therapies. Underscoring this point is a series of reports indicating that various components of PQC are identified as synthetic lethal targets in cancer cells. Among them, valosin-containing protein (VCP, also known as p97 AAA-ATPase) was identified as a lineage-specific dependency gene in ovarian cancer. VCP participates in various cellular functions of protein and organelle homeostasis, and we have shown that VCP inhibition induces ER stress, the terminal unfolded protein response and cytotoxicity in ovarian cancer cells. A previous clinical lead, CB-5083 (CB), inhibits VCP activity in nanomolar concentrations and produces cytotoxicity in over 300 cancer cell lines at low micromolar concentrations. Despite promising in vitro and in vivo anti-cancer activities, a recent first-in-human Phase I clinical trial with CB was stopped due to off-target effects on PDE6, a protein critical for phototransduction, which manifested as ocular side effects. We propose to circumvent the off-target issues using two approaches: (1) nanoformulation of CB to optimize delivery to tumor tissues and (2) the development of CB derivatives as VCP degraders. In the first approach, we will use hydrophobic porphyrin that forms the drug-loadable core with PEG forming the lipid-soluble micelle. Pegylated cross-linked nanoparticles (NPs) are pH-sensitive due to the presence of a Schiff base. In the acidic tumor microenvironment, smaller NPs are released due to the cleavage of the cross-links, thereby limiting drug delivery to the eye. In the second approach, we will synthesize the CB-based VCP degraders using drug design called proteolysis-targeting chimera (PROTAC). These PROTAC molecules can be designed such at it will specifically target VCP but not PDE6 for degradation. These two approaches will overcome current clinical limitations of CB.
Targeting energy metabolism for cancer control
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cancer metabolism and its therapeutic manipulation are important areas of cancer research. A major characteristic of cancer cells is their increased reliance on glycolysis to maintain cellular homeostasis (Warburg effect). Interestingly, however, cancer stem cells were shown to have a unique metabolic flexibility to switch back to oxidative phosphorylation (oxphos), which is critical for their maintenance. Furthermore, the oxphos pathway is required for migration and metastasis of malignant cancer cells. These results collectively support the notion that despite the well-appreciated Warburg effect, the oxphos pathway remains critical for cancer cell survival, and may be a promising therapeutic target. Mitochondrial oxphos inhibitors were shown to have anti-cancer activity but their toxic side effects have prevented their use in cancer treatment in the past. Our recent study indicates that cancer cells increase their metabolic reliance on oxphos in order to survive in the presence of DNA damage when poly(ADP-ribosyl)ase 1 (PARP1) is activated, and that the normal cells appear to be relatively resistant to this possibly because of their high basal oxphos level. Thus, we hypothesize that by understanding and manipulating the metabolic response to DNA damage, increasing the cancer cell sensitivity to mitochondria oxphos inhibitors with minimum side effect on non-cancerous cells may be possible. While PARP inhibitors are effective anti-cancer drugs, the emergence of PARPi-resistant cancers is becoming a problem. Our strategy to activate PARP (rather than to inhibit PARP) may provide an effective alternative treatment option in these resistant cancers. Thus, our goal is to further our understanding of dynamics of cancer metabolism, and explore a novel effective cancer treatment method. Specific Aims are (1) to determine how general this sensitivity to perturbation of oxphos in response to DNA damage among different cancer types, and (2) to address the underlying mechanism of sensitivity and resistance using genetic screening. The successful outcome of this project may provide new insight into cancer metabolism and lead to possible discovery of novel therapeutic targets and potentially effective treatment for difficult-to-treat cancers.
Supramolecular Cyclodextrin Frameworks for immunoprotein immobilization
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Over the past century, tumor treatment has predominantly focused on radio and chemotherapy. Since the beginning of the new millennium, new treatments have been developed using immunotherapy, which enhances the immune response of the body against cancer. Many types of proteins, such as antigens, antibodies and immunomodulators, can be used to create an immune response and have been gaining interest in the field of research, diagnosis and treatment of cancer. Despite the remarkable results in the lab, the application of immunoproteins has been limited by their low structural stability, propensity to aggregate, and degradation by enzymes. Significant efforts have been made to eliminate these effects through immobilization of the immunoproteins onto a matrix, however, no matrix currently exists which tackles all of these limitations. In this project, we will address all of the limitations using a combined matrix approach, that’s uses cyclodextrin (CDs) and metal-organic frameworks (MOFs). Cyclodextrins-proteins complexes, have been shown to reduce protein aggregation and provide higher structural stability to physical perturbation. MOFs have been shown to provide protection against other enzymes, increase protein activity and provide control of the delivery of their carrying molecules. However, both individual matrices present limitations, the CD approach only provides short term storage and are not protective against enzymes. The MOF approach only provides structural stability for a very limited number of enzymes which are compatible with the MOF pores and is not widely applicable to immunotherapy. Despite the fact that a combined CD-MOF approach to immunoproteins immobilization is a logical way to accelerate their use in cancer treatment, there have been no current efforts to do so. In this project we will develop a simple immobilization strategy for immuno-related proteins using a combination of CDs and MOFs. Specifically, the CD-MOF will be designed so that the CD and MOF will serve as a synergistic structural shield against any type of physical, chemical and biological perturbation.
A polygenic score for prediction of aggressive and fatal prostate cancer in multi-ethnic populations
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: When detected in its early stages, prostate cancer is curable, but it still causes over 350,000 deaths per year. Screening with a blood test to measure prostate-specific antigen (PSA) leads to earlier detection and has been shown to reduce cancer deaths. However, PSA testing of the entire male population leads to many false positives and many diagnoses of slow-growing cancers that are unlikely to cause significant problems. A test is needed to help physicians decide whether a given patient would benefit from screening—and what age to start that screening. Such personalized decisions might be made by measuring each man’s genetic risk for aggressive forms of prostate cancer. A genetic score (called a polygenic hazard score, or PHS) has been developed and tested in a dataset of thousands of men. The PHS was strongly associated with aggressive prostate cancer. While promising, the PHS was developed and validated with only data from men of European ancestry, reflecting data availability at the time.

 We have obtained access to a large, multi-ethnic dataset, through collaboration with the international PRACTICAL consortium. We propose here to test the original PHS to see whether it performs well in a new dataset and whether performance is affected by race/ethnicity. Rather than self-reported race/ethnicity, we will use genetic ancestry (European, African, or Asian) determined by the individual’s own DNA. We will evaluate whether PHS is associated with age at diagnosis of aggressive prostate cancer and with lifetime risk of death from prostate cancer. PHS will be compared to family history and other risk factors for prostate cancer. Our preliminary results suggest that the original PHS works in men of multiple racial/ethnic backgrounds, but performance is best in genetic Europeans.

 After formally testing the original PHS in each genetic subgroup, we will use the multi-ethnic data to optimize the score for each genetic ancestry. We will do this by searching for genetic markers within each genetic ancestry that are associated with age of onset of prostate cancer and incorporating them into an enhanced PHS.

 Ultimately, PHS could guide personalized prostate cancer screening decisions for men of all races/ethnicities, thus saving lives through early detection.
Investigating metabolic mechanisms promoting growth of primary and metastatic disease
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cancers commonly dysregulate metabolic processes to support growth. A tumor cell’s ability to modulate its metabolites influences multiple key aspects of a tumor’s behavior, such as cellular signaling, differentiation and metastatic potential. Although the concept of targeting metabolic vulnerabilities has appeal from a therapeutic standpoint, delineation of critical vulnerabilities defined by both gene and specific metabolic context remains a barrier. Using a novel ATP-sensor that enables FACS-mediated isolation of cells on the basis of intracellular ATP levels, we performed CRISPRi screens to identify ATP-modifying genes operating under specific metabolic contexts in human cancer cells (manuscript under revision for Nature Communications). These studies revealed candidate molecules that function as critical participants in tumor metabolic reprogramming. We then expressed our CRISPRi library in multiple human lung cancer cell lines and performed an in vivo growth screen, which identified a class of genes as being critical to growth in multiple in vivo tumor models. Notably, these genes are not well-characterized functionally or linked to cancer biology. However our data suggest important new roles for this class of genes, and this proposal, which represents a new area of study for our laboratory, we will test top candidate genes in pre-clinical studies using a novel in vivo tumor paradigm.
title: Effect of Passive Flow-Control Devices on the Drug of a Tractor-Trailer Model
Creators: name: Ahuja, Jagjit K.
Publisher: name: Old Dominion University
publisherIdentifier: https://ror.org/04zjtrb98
publisherIdentifierScheme: ROR
Year: 1991

description: The aerodynamic drag of tractor trailers is responsible for approximately half of the fuel consumption at highway speeds (55m.p.h.). Thus, it is important that vehicle drag be reduced in order to reduce operating costs and to conserve fuel. The purpose of the subject research conducted in the Old Dominion University Low-Speed Wind Tunnel was to determine the effect of various add-on flow-control devices, such as a cab-mounted flow deflector and gap seals between the tractor and the trailer. In addition, the effect of trailer rear-edge shaping has been studied. This was accomplished by contouring the trailer's rear end. It has been previously demonstrated by other researchers that introducing longitudinal vortices into the wake of a blunt body energizes the flow, resulting in a base pressure increase and a decrease to the total pressure drag. Various types of vortex generators have been investigated, including V-grooves, wishbones and doublets. Total drag on the 1/16 th scale tractor trailer model has been measured with a one-dimensional drag balance especially designed for drag-reduction research. Tests have been conducted up to speeds of 80 m.p.h. Findings of this study indicated that an elliptical rear edge modification can reduce drag of a baseline model by 20%. Wishbone and doublet vortex generators as well as longitudinal V-grooves have shown a drag reduction up to 15% on the baseline model.
Wnt-regulated Macropinocytosis in an Axin Mutation Model of Hepatocellular Carcinoma
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: It is currently emerging that the Wnt pathway, in addition to nuclear beta-catenin stabilization, is a major regulator of endocytosis. We discovered that the Wnt growth factor causes massive uptake and digestion of extracellular proteins. Recent work has shown that this is due to an increase in macropinocytosis, the actin-regulated cell drinking process that engulfs large volumes of liquid into the cellular fluid space.
 The present proposal focuses on the function of Axin, a major tumor suppressor that when mutated activates the Wnt pathway in a hepatocellular carcinoma (HCC) model cell line. We found that Alexander HCC cells (ATCC CRL-8024) have robust macropinocytosis that fuels the growth of these avid cells. We established a cell system in which a stable Alexander HCC cell line reconstituted with Axin1-Flag loses Wnt signaling and macropinocytosis, even after 40 years in culture. Wnt signaling is a driver of liver cancer, with beta-catenin stabilizing mutations present in 19% and Axin1 inactivating mutations in 9.6% of HCCs.
 In Aim 1, we will characterize this HCC±Axin1 model system with respect to macropinocytosis of nutrients caused by the presence or absence of a single tumor suppressor gene, and study the changes in lysosomal activity resulting from increased macropinocytosis.
 In Aim 2, we will study the effect on the metabolome and proteome of the presence or absence of Axin1, in collaboration with Heather Christofk and James Wohlschlaeger. We will also explore in HCC±Axin1 cells the effects of the GSK3 inhibitors Lithium chloride (LiCl) and CHIR99021, which we recently found are sufficient to trigger macropinocytosis and lysosomal activation in other cell lines.
 In Aim 3, HCC±Axin1 subcutaneous xenografts will provide a setting for pilot testing of macropinocytosis inhibitors on Wnt-driven tumor growth in immune-deficient NSG mice, in collaboration with the Christofk lab.
 The proposed work is relevant to cancer, not only of the liver, but also for many other cancers resulting from Wnt signaling activation. Our cell biological approach focusing on endocytosis could reveal new therapeutic avenues. Funding from CRCC would greatly help cover a gap in funding due to the loss of our generous 25-year support by the HHMI in November 2019.
The genomic landscape of cutaneous squamous cell carcinoma
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cutaneous squamous cell carcinoma (cSCC) is a form of skin cancer, originating from keratinocytes, that kills an estimated 8000 people per year in the United States. Compared to other cancers with similar death tolls, our understanding of the somatic mutations driving cSCC is limited. Comprehensive genomic studies of other tumor subtypes have markedly accelerated drug development, opened new avenues of treatment, and revealed fundamental insights into their basic biology – similar caliber studies are warranted for cutaneous squamous cell carcinoma. The overarching goal of this grant is to define the driver genes in cutaneous squamous cell carcinoma. cSCCs were not included in large-scale sequencing initiatives, such as The Cancer Genome Atlas (TCGA) program, but there are 9 small-scale studies, cumulatively encompassing 162 tumors, with exome or genome sequencing data. For this grant, we will perform a meta-analysis, aggregating and reanalyzing the data from these smaller studies. We will also supplement this data by additionally sequencing the exomes of 27 tumors from our own institution. In aggregate, our analysis will be nearly five times the size of the largest individual study to date. Aside from the small size of most studies, another obstacle to cancer gene discovery is that cutaneous squamous cell carcinomas have high mutation burdens, primarily from UV radiation, making it difficult to distinguish driver mutations from the overwhelming number of passenger mutations in these tumors. Not long ago, the melanoma community was afflicted with similar challenges, and I was at the forefront of efforts to overcome this challenge. Here, we will invoke similar strategies by applying state-of-the-art cancer gene discovery tools to identify the driver genes in cutaneous squamous cell carcinoma. The research proposed here is well-matched for this award mechanism because it will produce a rich resource of hypothesis-generating data to support future grants. Moreover, this grant is feasible for an award of this size in large part because it leverages a resource of pre-existing data. In closing, genomic studies have proven fundamental in advancing our understanding of other cancers – here, we will address this gap in knowledge for cSCC.
Effects of tobacco and cannabis policy implementation on consumption
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Between 2016 and 2018, California changed multiple policies addressing substance use by legalizing recreational use of cannabis, increasing the minimum age of legal access for tobacco to 21 years, regulating electronic nicotine delivery systems as tobacco products, and expanding access to treatment. The extent to which cannabis policies would be implemented was left to local governments, and varies significantly within the state, with some counties banning retail sales while others allow broad commercialization. As a result, the public health impacts of these changes have been difficult to assess. In particular, stricter tobacco control policies intended to reduce cancer risk may be affected by increased access to cannabis, leading to increased co-use, tobacco-to-cannabis substitution, or both at once in different subpopulations. In this pilot study, we propose to classify tobacco and cannabis policies in California counties and identify associated consumption patterns. We hypothesize that local policies can be classified by the degree to which they restrict access and subsidize treatment, and that policies that do so are associated with reduced consumption of both tobacco and cannabis. We propose the following aims: 1) Map local tobacco and cannabis policies in California and classify their comprehensiveness; and 2) Determine the association between local policies and tobacco and cannabis consumption patterns. We will collect policy data for California counties using data collected by the American Nonsmokers Rights Foundation (ANRF; tobacco) and the Orange County Register (cannabis). We will classify local policies by the degree to which they restrict access to and subsidize treatment for tobacco and cannabis, including treatment policies for co-use. Using data from the 2018 California Health Interview Survey (CHIS), we will analyze the association between local policies and health outcomes: 1) past-month tobacco and cannabis use; 2) modes of use (e.g. smoking, vaping, edibles, dissolvables); and 3) co-use of tobacco and cannabis, (both single-occasion and concurrent). California’s choice to devolve implementation of cannabis policies to local governments makes it possible to determine how substance use policies interact to change consumption, and will inform governments within and outside California seeking policy interventions to prevent cancer.
Epigenetic landscape of DNA methylation in pancreatic cancer progression
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Pancreatic cancer is one of the deadly human malignancies, owing in part due its early onset of metastasis. Key driver mutations for pancreatic cancer metastasis have not been identified, and alteration of epigenetic pathways has been suggested as a potential mechanism. We have established the innovative pancreatic cancer organoid cultures derived from both patients and genetically engineered mouse models. Pancreatic organoid cultures are amenable for genetic manipulations and suitable for high throughput ‘omics’ approaches, allowing us to dissect the underlying molecular mechanisms. Using the pancreatic organoid models, we have reported that epigenetic reprogramming as a potential factor in pancreatic cancer metastasis. Two major epigenetic changes are histone modifications and DNA methylation. Previously, we have extensively profiled the key histone modifications in pancreatic cancer organoids. However, another key epigenetic regulation, alterations of DNA methylation landscape remains to be determined in pancreatic cancer progression. Here, we propose to profile genome-wide DNA methylation in both human and mouse pancreatic organoid models and identify functionally important epigenetic changes of DNA methylation in metastasis. We have performed the Reduced Representation Bisulfite Sequencing (RRBS) in the murine organoid models for pancreatic cancer. We will investigate how DNA methylation pattern changes in pancreatic cancer progression (normal, PanIN, tumor and metastasis). In addition, we will intersect DNA methylation data with transcriptional profiles and key histone modifications in the promoter and enhancer regions. This will provide mechanistic insights in how differential DNA methylation contributes to gene expression and disease progression. To determine the effect of the differential DNA methylation in individual genes, we will employ CRISPR-dCas-DNMT or -TET system to methylate or demethylate specific regions of interest, respectively. This will enable us to identify functionally important DNA methylation for pancreatic cancer metastasis. In sum, the proposed study will elucidate the epigenetic landscape of DNA methylation in pancreatic cancer progression using pancreatic organoid models. Furthermore, genes associated with differentially methylated regions can be exploited for the development of novel diagnostic and therapeutic strategies.
A DNA DAMAGE DEPENDENT REGULATION OF APOBEC3A BY THE INNATE IMMUNE SYSTEM IN CANCER CELLS
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: A critical issue in cancer research is understanding tumor heterogeneity, a major cause of resistance to chemotherapy drugs as well as metastasis development. Overcoming resistance and preventing metastasis are the biggest challenges that must be solved to successfully fight cancers and extend patients’ lives. Within the same tumor from the same patient, individual tumor cells can dramatically differ from each other. Heterogeneity greatly complicates clinical treatment as some of the cancer cells respond to therapy while others do not. Therefore, there is a critical need to define mechanisms that drive tumor heterogeneity in order to develop new strategies to attenuate tumor evolution and adaptation.

 Recently, APOBEC3A (A3A) has been identified as a major driver of tumor heterogeneity. While the importance of A3A in cancer evolution has been clearly established, A3A regulation in cancer cells remains poorly understood which has prevented mechanistic insight in tumor heterogeneity as well as the development of therapeutic approaches that counteract drug resistance. A3A directly attacks genomic DNA causing the deamination of cytosine to uracil and inducing mutations. With its unique ability to rewrite genomic information, A3A is beneficial for tumors because it increases diversity in the tumor, promotes disease progression, and increases resistance to various therapies. Consequently, in patients, A3A mutations are associated with poor prognosis and low survival rate. Ironically, A3A is rarely expressed in tumor patient samples, whereas mutations caused by A3A are commonly found in many types of cancer. From this paradox, we hypothesize that A3A is tightly regulated at the transcriptional level. We propose to identify the initial stress responsible for the up-regulation of A3A expression in tumors and to characterize the molecular mechanism that regulates A3A expression. Our goal is to uncover the molecular mechanisms that govern A3A regulation. Our long-term goal is to develop therapeutic strategies to suppress mutations in the genome caused by A3A leading to tumor heterogeneity.
Nail Salon Worker Health and Safety Research Conference
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: In recent years, considerable public attention has focused on the safety of personal care products, which has been largely unregulated, despite the potentially harmful compounds they contain, including carcinogens and endocrine disruptors. Health concerns, including breast cancer has been a particular concern for cosmetology workers who provide hair and nail care services. There is a need to inform the current animated public policy debates over restricting the use of these agents in consumer products.

 The California Healthy Nail Salon Collaborative (CHNSC) proposes to organize a conference to discuss the current state of science on occupational chemical exposures for nail and hair salon workers and potential breast cancer risk and other health risks, with the intention to inform, guide, and build upon current efforts in California and across the nation. Notably, the conference provides an opportunity for an interdisciplinary approach to the safety of personal care products because of the harmful compounds they contain. This has been an issue that has received high public interest and research efforts focused on this workforce may also have implications for the general population of consumers. Since the conference is intended to target a wide audience that includes manicurists, hair stylists, public health advocates, community organizations, environmental justice advocates, policymakers, government agency representatives, researchers, and breast cancer advocates it provides a venue for input into the research agenda by different stakeholders.

 CHNSC spearheaded a similar convening of nail salon experts in 2009. Direct results of the conference include the initial development of the Healthy Nail Salon Recognition Program, research initiatives such as the 5-year National Institute of Health grant led by Dr. Thu Quach titled “Keeping a Healthy Occupational Environment & Developing Empowerment Program” and a national dialogue on chemical exposure and health issues faced by nail salon workers, and the creation of a national Scientific Advisory Committee, which is a cross-disciplinary group of scientific experts that supports and advises the CHNSC’s efforts. This has been an issue that has received high public interest and research efforts focused on this workforce may also have implications for the general population of consumers.
Hormones And Meat: does Beef Under-Regulation Generate Estrogenic Residues? (HAMBURGER)
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Hormones And Meat: does Beef Under-Regulation Generate Estrogenic Residues? (HAMBURGER)
 In the U.S., it is legal to dose cattle with hormones such as estrogen and related chemicals. The drugs cause the animals to gain weight more quickly and get to market faster. Estrogens are known to increase the risk of breast cancer, so there is reason to be concerned about potential hormone residues in beef. Unfortunately, there is very little information about hormones in meat. No prior studies have been done in California, and studies in other areas used now-outdated and insensitive lab methods on very small numbers of samples. This study will conduct testing using state-of-the-art methods to assess at least 100 samples of beef purchased from many different stores in three major regions of California: the San Francisco Bay area, Fresno area, and Los Angeles area. We will combine the testing with analysis of dietary data to focus our sampling on cuts of meat consumed by women from multiple ethnic groups in California. Ultimately, our results should be sufficient to support estimates of hormone consumption from beef in California women. In partnership with breast cancer prevention advocates, we will disseminate our results broadly. If we find significant residues, we will use our findings to advocate for policy change.
Novel Use of Human iPSC Derived Airway Progenitor Cells to Measure E-cigarette Toxicity
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Recent studies have reported that peripheral blood stem cells can be cultured in a stepwise fashion to generate cells that are precursors to lung cells. Lung progenitor cells grown in a petridish (i.e., in vitro cultures) present a unique opportunity to investigate the impact of environmental toxicants on the airways in a high through-put but relevant manner. To determine whether human stem cell-derived airway precursor cells can be effectively and efficiently utilized to test for toxicity to the respiratory tract, we propose to assess a panel of e-cigarette liquids using cultures that recapitulate the cell lining of the upper or lower lung. The aims of our pilot proposal will (1) measure the toxicity and growth impacts of a panel of e-cigarette liquids (diluents, flavorings, nicotine, tetrahydrocannabinol, the psychoactive component in marijuana) in human stem cell-derived cultures that represent cells from the upper lung and (2) measure the toxicity and growth impacts of a panel of e-cigarette liquids (diluents, flavorings, nicotine, tetrahydrocannabinol) in human stem-cell derived cultures that represents cells from the lower lung. A significant advantage of stem cell-derived lung cultures is the ability to assess the impact of potential toxicants on the cells of the lower lung, which are particularly challenging to maintain in a petridish. Moreover, stem-cell derived cultures are amenable to genetic labeling and modification, which readily allows tracking of cell characteristics and determination of mechanisms by which toxins damage cells. An important outcome of these aims is to provide a strategy to rapidly and effectively assess the toxicity of a broad spectrum of e-cigarette liquids using a cell type that is most relevant for e-cigarette induced lung injury in humans.
Exosomes and vascular disease risk in new and emerging tobacco products
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Smoking is a leading cause of heart and blood vessel disease. The heart risks of smoking traditional cigarettes are well known but the heart risks of smoking new and emerging tobacco products are less well known. Extracellular vesicles (EV’s) and exosomes are byproducts of the outside layers (membranes) of our bodies cells and can be released by cell stress. Exosomes represent a new chapter in cellular communication and the cellular stress response. Cells and tissues release exosomes into the extracellular space and biological fluids including blood. Exosomes contain important biological cargo including DNA, RNA, proteins, fats, and growth factors. Cigarette smoke can release exosomes into the blood. There is limited information on the role of exosomes in chronic smoking and no information on exosome release by new and emerging tobacco products.

 The work in the proposal will describe the exosomes in smokers using traditional and new and emerging tobacco products and their impact on blood vessel cell function. The work can have a major impact on health policy, disease diagnosis and prevention, and therapeutics for smoking related diseases.
Digital Mixed Methods to Identify and Characterize Vaping Illness in Young Adults in California
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: An alarming number of lung injury cases associated with e-cigarette use or vaping (including 3 in California as of October 2019) has brought “vaping illness” to the center of attention in public health debates on how to respond to the potential negative health impacts of vaping. Despite these sentinel events that have increased national attention to the issue, evidence is emerging that adverse events associated with vaping have been known, particularly in the context of vaping users self-reporting complications or concerning symptoms. However, it remains unclear the specific characteristics of these adverse events, the volume and duration of how they have been reported and discussed, and user sentiment regarding the risks of vaping following recent vaping illness news coverage. In response, this study will use a digital mixed methods approach to identify, characterize, and measure discussions of vaping adverse events and self-reporting of vaping illness among young adults in California. The study will specifically use different approaches in qualitative research through online focus groups conducted with young adult Californians, and big data approaches using machine learning to conduct social media surveillance for tobacco-related behaviors on popular social media platforms Instagram, Twitter, YouTube, and Yelp. Finally, we will combine these results to better establish the specific risk factors, user attitudes and behaviors, and public sentiment about vaping adverse events and vaping illness to inform health behavior change, treatment, and tobacco policy.
Co-Use of Tobacco and Cannabis in Pregnancy
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Health effects of co-use of tobacco and cannabis and of cannabis alone in pregnancy were poorly unexplored until recently, precluding guidelines for public health and clinical efforts to promote healthy pregnancy with regard to cannabis use. Recent survey data consistently show that while high proportions of expectant women now avoid use of tobacco and alcohol, cannabis use during pregnancy is perceived as comparatively benign, or even beneficial for control of nausea and promotion of appetite. Liberalization of availability in several states, including California, makes cannabis products more widely available to women who might elect use, underscoring need for an evidence base to inform decisions regarding cannabis use in pregnancy and lactation.
 Oversight of human subjects research and accompanying safeguards allow studies of cannabis use to be carried out in certain settings without imperiling participants. Early inferences regarding consequences of use in pregnancy demonstrate several concerning associations, including preterm birth and infants born small for gestational age. Both outcomes are associated with later health problems, potentially important consequences yet to be identified. Co-use of tobacco and cannabis in pregnancy is even less understood. A further concern is that studies -- including our own recently conducted in low income medically underserved pregnant women who received care at Los Angeles County University of Southern California (LAC+USC) Medical Center -- show co-use of tobacco and cannabis in pregnancy to be nearly as common as use of cannabis, alone.
 Research to identify consequences of cannabis use and co-use with tobacco in pregnancy would be greatly accelerated by biomarkers of in utero exposure. Using an approach that defined sensitive and specific biomarkers of in utero exposure to tobacco smoke alone, now widely used in research, we propose to discover DNA methylation signatures that distinguish cord blood from infants with three distinct in utero exposure histories: tobacco alone, cannabis alone, tobacco and cannabis. Once validated, such markers would facilitate assessment exposure histories in retrospective studies, potentially accelerating by decades understanding of role of these exposures in a wide range of conditions of infancy, childhood, adolescence, and early adulthood.
Didymocheton nutans Blume, Bijdr. Fl. Ned. Ind.
Creators: name: Holzmeyer, Laura
name: Hauenschild, Frank
name: Mabberley, David J.
name: Muellner-Riehl, Alexandra N.
Publisher: name: Zenodo
Year: 2021
Subjects: Biodiversity
Taxonomy
Plantae
Tracheophyta
Magnoliopsida
Sapindales
Meliaceae
Didymocheton
Didymocheton nutans

description: Didymocheton nutans Blume, Bijdr. Fl. Ned. Ind.: 177. 1825
≡ Dysoxylum nutans (Blume) Miq. in Ann. Mus. Bot. Lugduno-Batavi 4: 17. 1868.
description: Published as part of Holzmeyer, Laura, Hauenschild, Frank, Mabberley, David J. & Muellner-Riehl, Alexandra N., 2021, Confirmed polyphyly, generic recircumscription and typification of Dysoxylum (Meliaceae), with revised disposition of currently accepted species, pp. 1248-1272 in TAXON 70 (6) on page 1257, DOI: 10.1002/tax.12591, http://zenodo.org/record/14047415
Elucidating the mechanism by which cg05575921 predicts lung cancer risk
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Each human being has one genome or “book of instructions” that is identical in all cells. It contains all the instructions any cell could ever need. If all cells have the same book, how can the human body have hundreds of different kinds of cells with different shapes and functions? This is possible because the genome is “annotated”. i.e. marked up with proteins and chemical modifications, similar to how an instruction book could be labeled with paper clips, post-it notes and highlighting. The collection of these markings on the genome is called the epigenome (“epi” means “on top” in Greek). The epigenome of each cell type in the body is different and ensures that each type of cell reads the correct instructions and behaves properly. Damage to the epigenome (i.e. “post-it notes falling off the book”), could make cells confused and could make them access the wrong instructions. That is what happens with tobacco smoke exposure; it changes “DNA methylation”, a chemical mark that is patterned throughout the genome. DNA is made of nucleotides called A, C, G and T. Methylation is present on Cs that are followed by Gs (so-called “CpG dinucleotides”). Smokers show changes in the DNA methylation of their cells, most commonly loss of methylation at one particular CpG called cg05575921. This loss is somehow tied to lung cancer risk; less methylation at this CpG means a greater risk of developing lung cancer. This proposal is aimed at studying why loss of methylation at cg05575921 predicts lung cancer risk. Previous work from the Offringa lab showed that cg05575921 lies next to a gene regulatory element called an enhancer. Enhancers are like remote controls; they can control one or more genes that lie close by on the DNA or far away. Our work also showed that tobacco smoke turns on the enhancer and suggested that this causes the loss of DNA methylation as a side effect. We therefore hypothesize that the enhancer and not the hypomethylation increases a person’s lung cancer risk by turning on a nearby gene, called the aryl hydrocarbon receptor repressor (AHRR). Here we will use state of the art techniques to determine the role of the CpG, the enhancer and the AHRR gene in the cells’ response to tobacco smoke. If we can understand the mechanism linking the CpG to lung cancer risk, perhaps we can mitigate the effects of tobacco smoke exposure and prevent lung cancer.
Social media intervention to stop nicotine and cannabis vaping among adolescents
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: While youth smoking in California is declining, electronic cigarette and cannabis use is increasing. New devices like JUUL have become popular among teens because they are easy to hide, come in fun flavors, and they were promoted on social media like Facebook, Twitter and Instagram. Unfortunately, they also have very high levels of nicotine. While there are new educational campaigns about e-cigarette use (“vaping”), we still need programs to help teens quit vaping. There are a few texting and online programs to help teens quit, but they do not use social media and they do not talk about cannabis. This research proposal will develop and evaluate a social media program to help youth stop vaping nicotine and cannabis. This program is based on our prior work. We have already developed a program to help young adults to quit smoking by joining private groups on Facebook. The Facebook posts in the groups go through all the steps of professional smoking cessation counseling. Over the past four years we have run this program in San Francisco, and this “Commune Smoke-free Social” program was used by almost ten times more young adults compared to calls to the Quitline. We now propose to adapt our program for youth vaping, including both nicotine and cannabis, and test it. Our partners have a lot of experience working with adolescents, developing social media apps for teens on mental health, and doing educational campaigns for teens, including campaigns about vaping. We also have experts who can carry out a rigorous evaluation of the effect on vaping behavior, a pediatrician who is a leader in helping kids and their parents quit tobacco, and many community partners working with teens. We will pilot test the intervention on a social media platform (e.g., Instagram, Snapchat), and then evaluate the intervention in a randomized controlled trial. We think social media will be a good platform for programs to help teens stop vaping because 95% of youth own smartphones and 45% report being online “almost constantly.” Lessons learned in this research can also help us develop better programs for youth in other related health topics, and if this California program is successful, it can be used across the country.