NCI Cancer Research Data Commons: Core Standards and Services.

The NCI Cancer Research Data Commons (CRDC) is a collection of data commons, analysis platforms, and tools that make existing cancer data more findable and accessible by the cancer research community. In practice, the two biggest hurdles to finding and using data for discovery are the wide variety of models and ontologies used to describe data, and the dispersed storage of that data. Here, we outline core CRDC services to aggregate descriptive information from multiple studies for findability via a single interface and to provide a single access method that spans multiple data commons. See related articles by Wang et al., p. 1388, Pot et al., p. 1396, and Kim et al., p. 1404.

Law Enforcement Officer Knowledge of, Attitudes Toward, and Willingness to Use Extreme Risk Protection Orders.

Importance: Understanding knowledge of, attitudes toward, and willingness to use extreme risk protection order (ERPO) laws among law enforcement officers (LEOs) can inform efforts to improve implementation of this underused firearm violence prevention strategy. Objective: To characterize LEOs' knowledge of, attitudes toward, and willingness to use ERPOs across a range of scenarios. Design, Setting, and Participants: A cross-sectional online survey, fielded from April 5 to August 30, 2021, was conducted in all 19 states and the District of Columbia with an ERPO law in 2021. A nonprobability sample of active-duty LEOs was used. Exposure: Being a LEO in a state with an ERPO law. Main Outcomes and Measures: Survey participants answered questions about their familiarity with and opinions on ERPO laws, as well as whether they would agree with using an ERPO in a variety of specific case scenarios. The analysis included an exploration of whether within-scenario differences, such as ERPO respondent race or gender, affected agreement by randomly assigning survey participants to 1 of 2 versions of each scenario. Results: A total of 600 eligible individuals started the survey, and 283 survey participants were included in the analysis. The analytic sample consisted mostly of cisgender men (85.2%) and non-Hispanic White (71.4%) LEOs. Participants represented 14 states and the District of Columbia, with 53.7% living in California. Most participants (81.3%) were very or somewhat familiar with ERPO laws and 56.2% had received ERPO training. Opinions about ERPO laws were generally favorable but varied by self-identified political ideology. Across all scenarios, most participants supported using an ERPO; however, support was highest in cases involving intimate partner violence (71.4%-78.6%) and lowest in cases involving suicidality (54.2%-73.3%). Across all scenarios, LEOs with ERPO training or experience were substantially more likely to agree with using ERPOs than those without. None of the randomly assigned within-scenario differences were associated with differences in ERPO support. Conclusions and Relevance: In this survey study of LEOs in states with ERPO laws, many officers had not received training on their use. Additionally, while conservative political ideology was associated with less favorable views of ERPOs, training and experience with ERPOs was associated with greater support for their use across a range of scenarios. These findings suggest that LEO training on ERPOs may promote their uptake and improve implementation.

Effects of Comprehensive Background-Check Policies on Firearm Fatalities in 4 States.

Despite promising results from individual-level studies, state-level studies of the effectiveness of comprehensive background-check (CBC) policies in reducing firearm fatalities have yielded null results in multiple states. These prior studies focused on CBC laws adopted in the 1990s, when record keeping was far less complete. We estimated the effect of the implementation of CBC policies on state-level firearm homicide and suicide rates in states implementing CBC policies from 2013 to 2015 (Colorado, Delaware, Oregon, and Washington). We compared age-adjusted firearm homicide and suicide rates, measured annually from 15 years prior to policy implementation until 2019, in each treated state to rates in control groups constructed using the synthetic control group method. Differences in firearm homicide rates for Colorado, Oregon, and Washington post treatment were all small (0.09 to 0.18 per 100,000 residents per year) and not well distinguished from natural variation. Oregon had on average 0.80 per 100,000 fewer firearm suicides per year than did synthetic Oregon post treatment. However, these results were inconsistent across modeling approaches and not well distinguished from natural variation. Our models produced poor fit for Delaware. Coupled with previous null results from Indiana, California, Maryland, Pennsylvania, and Tennessee, the present results suggest that extending background check requirements to private transfers alone and implementing these policies as is currently done is not sufficient to achieve significant state-level reductions in firearm fatalities.

Making Common Fund data more findable: catalyzing a data ecosystem.

The Common Fund Data Ecosystem (CFDE) has created a flexible system of data federation that enables researchers to discover datasets from across the US National Institutes of Health Common Fund without requiring that data owners move, reformat, or rehost those data. This system is centered on a catalog that integrates detailed descriptions of biomedical datasets from individual Common Fund Programs' Data Coordination Centers (DCCs) into a uniform metadata model that can then be indexed and searched from a centralized portal. This Crosscut Metadata Model (C2M2) supports the wide variety of data types and metadata terms used by individual DCCs and can readily describe nearly all forms of biomedical research data. We detail its use to ingest and index data from 11 DCCs.

Implementation and perceived effectiveness of gun violence restraining orders in California: A qualitative evaluation.

BACKGROUND: Uptake of gun violence restraining orders (GVROs), which temporarily prohibit the possession and purchase of firearms and ammunition from individuals at particularly high risk of harming themselves or others with a firearm, has been slow and heterogenous across California. Insights into the implementation process and perceived effectiveness of the law could guide implementation in California and the many states that have enacted or are considering enacting such a law. METHODS: We conducted 21 semi-structured interviews with 27 key informants, including judges, law enforcement officers, city and district attorneys, policy experts, and firearm violence researchers. Analysis of transcripts was guided by grounded theory and the Consolidated Framework for Implementation Research (CFIR). FINDINGS: The following constructs emerged within 4 CFIR domains as salient features of implementation: 1) implementation characteristics: risk of violence, cost, and adaptability; 2) outer setting: interagency coordination and local firearm ideology; 3) inner setting: readiness for implementation and law enforcement firearm culture; and 4) implementation process: planning and engaging with those involved in implementation. Key informants perceived the law to be effective, particularly for preventing firearm suicide, but agreed that more research was needed. While most indicated that the law resulted in positive outcomes, concerns about the potential for class- and race-based inequities were also raised. CONCLUSIONS: Implementation of the GVRO law in California was hampered by a lack of funding to support local proactive implementation efforts. This resulted in ad hoc policies and procedures, leading to inconsistent practices and widespread confusion among those responsible for implementation. In states that have not begun implementation, we recommend dedicating funding for implementation and creating local procedures statewide prior to the law's rollout. In California, recommendations include providing training on the GVRO law-including an explication of agency-specific roles, responsibilities, and procedures-to officers, city attorneys, and civil court judges.

Firearm ownership in California: A latent class analysis.

OBJECTIVE: To examine whether firearm ownership and ownership-related motivations and practices can be classified into reasonably distinct types. METHODS: Cross-sectional data on firearm owners (n=429) were obtained from the 2018 California Safety and Well-Being Survey, a state-representative web-based survey. We conducted a latent class analysis using six self-reported indicators of firearm ownership: (1) number of firearms owned, (2) types of firearms owned, (3) primary reason for firearm ownership, (4) firearm storage, (5) loaded handgun carrying and (6) high-capacity magazine ownership. RESULTS: We identified five markedly different classes of firearm ownership. There were two classes of single-firearm owners and three classes of multiple-firearm owners. Only members of one class (9% of owners) were likely to have carried a loaded handgun and to own high-capacity magazines or assault-type weapons. Members of this class were also likely to own 5+ firearms, own for protection against people, and store a firearm in the least secure manner (loaded and unlocked). CONCLUSION: There were distinct classes of firearm ownership in California, and all higher-risk behaviours studied were exhibited disproportionately by members of a single class. This latent class structure, which may help identify higher-risk groups of firearm owners, could inform future research on risk assessment and on focused interventions to reduce firearm injury and death.

FAIRshake: Toolkit to Evaluate the FAIRness of Research Digital Resources.

As more digital resources are produced by the research community, it is becoming increasingly important to harmonize and organize them for synergistic utilization. The findable, accessible, interoperable, and reusable (FAIR) guiding principles have prompted many stakeholders to consider strategies for tackling this challenge. The FAIRshake toolkit was developed to enable the establishment of community-driven FAIR metrics and rubrics paired with manual and automated FAIR assessments. FAIR assessments are visualized as an insignia that can be embedded within digital-resources-hosting websites. Using FAIRshake, a variety of biomedical digital resources were manually and automatically evaluated for their level of FAIRness.

California Public Opinion On Health Professionals Talking With Patients About Firearms.

Medical and public health organizations have recommended that health professionals discuss firearm safety with patients at risk for gun-related injury, yet few health professionals do so. Concerns that patients may view conversations about firearms as inappropriate have been reported in prior studies. Using state-representative data from the 2018 California Safety and Wellbeing Survey, this study found that most Californians report gun safety conversations with health professionals to be at least sometimes appropriate when these conversations involved a patient who had a known risk factor for firearm-related harm (depending on the risk factor, 83.7-90.2 percent among all respondents and 70.0-91.2 percent among firearm owners). Majorities of respondents also found intervention by health professionals for those at imminent risk to be at least sometimes appropriate (depending on the intervention, 84.0-89.9 percent among all respondents and 82.6-91.0 percent among firearm owners). These findings can inform health policy and education on clinical strategies for preventing firearm-related harm.

Weed evolution: Genetic differentiation among wild, weedy, and crop radish.

Approximately 200 weed species are responsible for more than 90% of crop losses and these comprise less than one percent of all named plant species, suggesting that there are only a few evolutionary routes that lead to weediness. Agricultural weeds can evolve along three main paths: they can be escaped crops, wild species, or crop-wild hybrids. We tested these three hypotheses in weedy radish, a weed of small grains and an emerging model for investigating the evolution of agricultural weeds, using 21 CAPS and SSR markers scored on 338 individuals from 34 populations representing all major species and sub-species in the radish genus Raphanus. To test for adaptation of the weeds to the agricultural environment, we estimated genetic differentiation in flowering time in a series of common garden experiments with over 2,400 individuals from 43 populations (all but one of the genotyped populations plus 10 additional populations). Our findings suggest that the agricultural weed radish R. r. raphanistrum is most genetically similar to native populations of R. r. raphanistrum and is likely not a feral crop or crop hybrid. We also show that weedy radish flowers more rapidly than any other Raphanus population or cultivar, which is consistent with rapid adaptation to the frequent and severe disturbance that characterizes agricultural fields.

The khmer software package: enabling efficient nucleotide sequence analysis.

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at  https://github.com/dib-lab/khmer/.

Identification of a BAHD acetyltransferase that produces protective acyl sugars in tomato trichomes.

Glandular secreting trichomes on the surface of tomato plants and many of its relatives in the Solanaceae produce a mixture of O-acyl sugars that contribute to insect resistance. The majority of acyl sucroses produced by the cultivated tomato (Solanum lycopersicum) contain three or four short chain aliphatic acyl esters, and tetra-acyl sucroses have an acetyl group as one of the acyl chains. We previously reported overlapping S. lycopersicum × Solanum pennellii introgression lines (ILs) that fail to accumulate high levels of acetylated tetra-acyl sucroses. A survey of the annotated genes in this region of cultivated tomato chromosome 1 revealed three candidate acyltransferases that were tested for function using virus-induced gene silencing. A member of the BAHD family of acyltransferases (Solyc01g105580, SlAT2) was shown to encode an acetyl-CoA-dependent acyltransferase enzyme capable of acyl sucrose acetylation in vitro. RNAi suppression of SlAT2 in transgenic S. lycopersicum cv. M82 resulted in reduced acyl sugar acetylation, whereas expression of the functional S. lycopersicum allele of SlAT2 in the triacyl sucrose producing IL1-3 restored the ability of the IL to synthesize acetylated tetra-acyl sugars. Transgenic plants with the SlAT2 promoter driving GFP expression showed fluorescence in tips cells of long, slender trichomes that is consistent with acyl sugar acetylation occurring in these cells.

Mass spectrometry screening reveals widespread diversity in trichome specialized metabolites of tomato chromosomal substitution lines.

Glandular secreting trichomes of cultivated tomato (Solanum lycopersicum) and close relatives produce a variety of structurally diverse volatile and non-volatile specialized ('secondary') metabolites, including terpenes, flavonoids and acyl sugars. A genetic screen is described here to profile leaf trichome and surface metabolite extracts of nearly isogenic chromosomal substitution lines covering the tomato genome. These lines contain specific regions of the Solanum pennellii LA0716 genome in an otherwise 'wild-type' M82 tomato genetic background. Regions that have an impact on the total amount of extractable mono- and sesquiterpenes (IL2-2) or only sesquiterpenes (IL10-3) or specifically influence accumulation of the monoterpene alpha-thujene (IL1-3 and IL1-4) were identified using GC-MS. A rapid LC-TOF-MS method was developed and used to identify changes in non-volatile metabolites through non-targeted analysis. Metabolite profiles generated using this approach led to the discovery of introgression lines producing different acyl chain substitutions on acyl sugar metabolites (IL1-3/1-4 and IL8-1/8-1-1), as well as two regions that influence the quantity of acyl sugars (IL5-3 and IL11-3). Chromosomal region 1-1/1-1-3 was found to influence the types of glycoalkaloids that are detected in leaf surface extracts. These results show that direct chemical screening is a powerful way to characterize genetic diversity in trichome specialized metabolism.

Monoterpenes in the glandular trichomes of tomato are synthesized from a neryl diphosphate precursor rather than geranyl diphosphate.

We identified a cis-prenyltransferase gene, neryl diphosphate synthase 1 (NDPS1), that is expressed in cultivated tomato (Solanum lycopersicum) cultivar M82 type VI glandular trichomes and encodes an enzyme that catalyzes the formation of neryl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. mRNA for a terpene synthase gene, phellandrene synthase 1 (PHS1), was also identified in these glands. It encodes an enzyme that uses neryl diphosphate to produce beta-phellandrene as the major product as well as a variety of other monoterpenes. The profile of monoterpenes produced by PHS1 is identical with the monoterpenes found in type VI glands. PHS1 and NDPS1 map to chromosome 8, and the presence of a segment of chromosome 8 derived from Solanum pennellii LA0716 causes conversion from the M82 gland monoterpene pattern to that characteristic of LA0716 plants. The data indicate that, contrary to the textbook view of geranyl diphosphate as the "universal" substrate of monoterpene synthases, in tomato glands neryl diphosphate serves as a precursor for the synthesis of monoterpenes.