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Exploring the complexity of the epithelial-to-mesenchymal transition (EMT) unveils a diversity of potential cell fates; however, the exact timing and mechanisms by which early cell states diverge into distinct EMT trajectories remain unclear. Studying these EMT trajectories through single-cell RNA sequencing is challenging due to the necessity of sacrificing cells for each measurement. In this study, we employed optimal-transport analysis to reconstruct the past trajectories of different cell fates during TGF-beta-induced EMT in the MCF10A cell line. Our analysis revealed three distinct trajectories leading to low EMT, partial EMT, and high EMT states. Cells along the partial EMT trajectory showed substantial variations in the EMT signature and exhibited pronounced stemness. Throughout this EMT trajectory, we observed a consistent downregulation of the EED and EZH2 genes. This finding was validated by recent inhibitor screens of EMT regulators and CRISPR screen studies. Moreover, we applied our analysis of early-phase differential gene expression to gene sets associated with stemness and proliferation, pinpointing ITGB4, LAMA3, and LAMB3 as genes differentially expressed in the initial stages of the partial versus high EMT trajectories. We also found that CENPF, CKS1B, and MKI67 showed significant upregulation in the high EMT trajectory. While the first group of genes aligns with findings from previous studies, our work uniquely pinpoints the precise timing of these upregulations. Finally, the identification of the latter group of genes sheds light on potential cell cycle targets for modulating EMT trajectories.
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Transición Epitelial-Mesenquimal , Análisis de la Célula Individual , Transición Epitelial-Mesenquimal/genética , Humanos , Análisis de la Célula Individual/métodos , Linaje de la Célula/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genéticaRESUMEN
Background: Studies comparing carpal tunnel release with ultrasound guidance (CTR-US) to mini-open CTR (mOCTR) are limited. This randomized trial compared the efficacy and safety of these techniques. Methods: In this multicenter randomized trial, patients were randomized (2:1) to unilateral CTR-US or mOCTR. Outcomes included Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) and Functional Status Scale (BCTQ-FSS), numeric pain scale (0-10), EuroQoL-5 Dimension 5-Level (EQ-5D-5L), scar outcomes, and complications over 1 year. Results: Patients received CTR-US (nâ =â 94) via wrist incision (mean 6 mm) or mOCTR (nâ =â 28) via palmar incision (mean 22 mm). Comparing CTR-US with mOCTR, the mean changes in BCTQ-SSS (-1.8 versus -1.8; P = 0.96), BCTQ-FSS (-1.0 versus -1.0; P = 0.75), numeric pain scale (-3.9 versus -3.8; P = 0.74), and EQ-5D-5L (0.13 versus 0.12; P = 0.79) over 1 year were comparable between groups. Freedom from scar sensitivity or pain favored CTR-US (95% versus 74%; P = 0.005). Complications occurred in 2.1% versus 3.6% of patients (P = 0.55), all within 3 weeks postprocedure. There was one revision surgery in the CTR-US group, and no revisions for persistent or recurrent symptoms in either group. Conclusions: CTR-US and mOCTR demonstrated similar improvement in carpal tunnel syndrome symptoms and quality of life with comparable low complication rates over 1 year of follow-up. CTR-US was performed with a smaller incision and associated with less scar discomfort.
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Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors such as palbociclib are approved for the treatment of metastatic estrogen receptor-positive (ER+) breast cancer in combination with endocrine therapies and significantly improve outcomes in patients with this disease. However, given the large number of possible pairwise drug combinations and administration schedules, it remains unclear which clinical strategy would lead to best survival. Here, we developed a computational, cell cycle-explicit model to characterize the pharmacodynamic response to palbociclib-fulvestrant combination therapy. This pharmacodynamic model was parameterized, in a Bayesian statistical inference approach, using in vitro data from cells with wild-type estrogen receptor (WT-ER) and cells expressing the activating missense ER mutation, Y537S, which confers resistance to fulvestrant. We then incorporated pharmacokinetic models derived from clinical data into our computational modeling platform. To systematically compare dose administration schedules, we performed in silico clinical trials based on integrating our pharmacodynamic and pharmacokinetic models as well as considering clinical toxicity constraints. We found that continuous dosing of palbociclib is more effective for lowering overall tumor burden than the standard, pulsed-dose palbociclib treatment. Importantly, our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment strategies in search of optimal combination dosing strategies of other cell-cycle inhibitors in ER+ breast cancer. SIGNIFICANCE: We created a computational modeling platform to predict the effects of fulvestrant/palbocilib treatment on WT-ER and Y537S-mutant breast cancer cells, and found that continuous treatment schedules are more effective than the standard, pulsed-dose palbociclib treatment schedule.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Fulvestrant , Receptores de Estrógenos/análisis , Teorema de BayesRESUMEN
Exposure characterization of crude oils, especially in time-sensitive circumstances such as spills and disasters, is a well-known analytical chemistry challenge. Gas chromatography-mass spectrometry is commonly used for "fingerprinting" and origin tracing in oil spills; however, this method is both time-consuming and lacks the resolving power to separate co-eluting compounds. Recent advances in methodologies to analyze petroleum substances using high-resolution analytical techniques have demonstrated both improved resolving power and higher throughput. One such method, ion mobility spectrometry-mass spectrometry (IMS-MS), is especially promising because it is both rapid and high-throughput, with the ability to discern among highly homologous hydrocarbon molecules. Previous applications of IMS-MS to crude oil analyses included a limited number of samples and did not provide detailed characterization of chemical constituents. We analyzed a diverse library of 195 crude oil samples using IMS-MS and applied a computational workflow to assign molecular formulas to individual features. The oils were from 12 groups based on geographical and geological origins: non-US (1 group), US onshore (3), and US Gulf of Mexico offshore (8). We hypothesized that information acquired through IMS-MS data would provide a more confident grouping and yield additional fingerprint information. Chemical composition data from IMS-MS was used for unsupervised hierarchical clustering, as well as machine learning-based supervised analysis to predict geographic and source rock categories for each sample; the latter also yielded several novel prospective biomarkers for fingerprinting of crude oils. We found that IMS-MS data have complementary advantages for fingerprinting and characterization of diverse crude oils and that proposed polycyclic aromatic hydrocarbon biomarkers can be used for rapid exposure characterization. Environ Toxicol Chem 2023;42:2336-2349. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
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Petróleo , Petróleo/análisis , Espectrometría de Movilidad Iónica , Espectrometría de Masas , Cromatografía de Gases y Espectrometría de Masas/métodos , BiomarcadoresRESUMEN
BACKGROUND: Comparative studies of carpal tunnel release with ultrasound guidance (CTR-US) vs. mini-open CTR (mOCTR) are limited, prompting development of this randomized trial to compare efficacy and safety of these techniques. RESEARCH DESIGN AND METHODS: Patients were randomized (2:1) to CTR-US or mOCTR, treated by experienced hand surgeons (median previous cases: 12 CTR-US; 1000 mOCTR), and followed for 3 months. RESULTS: Among 149 randomized patients, 122 received CTR-US (n = 94) or mOCTR (n = 28). Mean incision length was 6 ± 2 mm in the wrist (CTR-US) vs. 22 ± 7 mm in the palm (mOCTR) (p < 0.001). Median time to return to daily activities (2 vs. 2 days; p = 0.81) and work (3 vs. 4 days; p = 0.61) were similar. Both groups reported statistically significant and clinically important improvements in Boston Carpal Tunnel Questionnaire Symptom Severity and Functional Status Scales, Numeric Pain Scale, and EuroQoL-5 Dimension 5-Level, with no statistical differences between groups. Freedom from wound sensitivity and pain favored CTR-US (61.1% vs. 17.9%; p < 0.001). Adverse event rates were low in each group (2.1% vs. 3.6%; p = 0.55). CONCLUSIONS: The efficacy and safety of CTR-US were comparable to mOCTR despite less previous surgical experience with CTR-US. The choice of CTR technique should be determined by shared decision-making between patient and physician. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05405218.
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Síndrome del Túnel Carpiano , Humanos , Resultado del Tratamiento , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/cirugía , Mano , Ultrasonografía , DolorRESUMEN
Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of â¼15 months. Targeted approaches have not been successful in this tumor type due to the large extent of intratumor heterogeneity. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor. To uncover the relationships between genetically diverse subpopulations of GBM cells and their native tumor microenvironment, we employ highly multiplexed spatial protein profiling coupled with single-cell spatial mapping of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA. Single-cell FISH analysis of a total of 35,843 single nuclei reveals that tumors in which amplifications of EGFR and CDK4 more frequently co-occur in the same cell exhibit higher infiltration of CD163+ immunosuppressive macrophages. Our results suggest that high-throughput assessment of genomic alterations at the single-cell level could provide a measure for predicting the immune state of GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patología , Amplificación de Genes , Hibridación Fluorescente in Situ , Receptores ErbB/genética , Receptores ErbB/metabolismo , Oncogenes , Neoplasias Encefálicas/metabolismo , Microambiente Tumoral , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismoRESUMEN
BACKGROUND: The COVID-19 pandemic forced healthcare institutions and many clinical research programs to adopt telehealth modalities in order to mitigate viral spread. With the expanded use of telehealth, there is the potential to increase access to genomic medicine to medically underserved populations, yet little is known about how best to communicate genomic results via telehealth while also ensuring equitable access. NYCKidSeq, a multi-institutional clinical genomics research program in New York City, launched the TeleKidSeq pilot study to assess alternative forms of genomic communication and telehealth service delivery models with families from medically underserved populations. METHODS: We aim to enroll 496 participants between 0 and 21 years old to receive clinical genome sequencing. These individuals have a neurologic, cardiovascular, and/or immunologic disease. Participants will be English- or Spanish-speaking and predominantly from underrepresented groups who receive care in the New York metropolitan area. Prior to enrollment, participants will be randomized to either genetic counseling via videoconferencing with screen-sharing or genetic counseling via videoconferencing without screen-sharing. Using surveys administered at baseline, results disclosure, and 6-months post-results disclosure, we will evaluate the impact of the use of screen-sharing on participant understanding, satisfaction, and uptake of medical recommendations, as well as the psychological and socioeconomic implications of obtaining genome sequencing. Clinical utility, cost, and diagnostic yield of genome sequencing will also be assessed. DISCUSSION: The TeleKidSeq pilot study will contribute to innovations in communicating genomic test results to diverse populations through telehealth technology. In conjunction with NYCKidSeq, this work will inform best practices for the implementation of genomic medicine in diverse, English- and Spanish-speaking populations.
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Residents and advocacy groups began voicing concerns over the environmental quality located in the neighborhoods of Kashmere Gardens, Fifth Ward, and Denver Harbor in Houston, TX, following the confirmation of a cancer cluster in 2019 and another in 2021. These neighborhoods are in close proximity to a railyard and former wood treatment plant known to have utilized coal tar creosote and contain polycyclic aromatic hydrocarbons (PAHs). This research took core soil samples in September and October 2020 from 46 sites to assess for the presence and concentration of the U.S. Environmental Protection Agency's (USEPA) 7 Carcinogenic PAHs. Results showed the cumulative concentration of these PAHs in each sample was variable with a range of 13,767 ng/g to 328 ng/g and a mean of 2,517.2 ng/g ± 3122. A regional soil screening evaluation revealed that 40 of the 46 soil samples were in excess of the USEPAs most conservative screening levels of 1.0 × 10-6 increased cancer risk, but none exceeding levels considered actionable for remediation. This study is a fundamental first step for quantifying the environmental pollutants in this minority-majority community. Findings revealed a low risk of cancer risk based on current PAH concentrations alone but cannot assess contributions from other contaminants or from past, possibly higher, levels of contamination. Further research is needed to identify the potential casual pathways of the observed cancer cluster and to explore possible remediation needs.
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Neoplasias , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Humanos , Suelo , Carbón Mineral/análisis , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Monitoreo del Ambiente/métodos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Texas/epidemiología , Justicia Ambiental , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Medición de Riesgo , ChinaRESUMEN
BACKGROUND: Friedreich's ataxia (FRDA) is an autosomal recessive disease, whereby homozygous inheritance of an expanded GAA trinucleotide repeat expansion in the first intron of the FXN gene leads to transcriptional repression of the encoded protein frataxin. FRDA is a progressive neurodegenerative disorder, but the primary cause of death is heart disease which occurs in 60% of the patients. Several functions of frataxin have been proposed, but none of them fully explain why its deficiency causes the FRDA phenotypes nor why the most affected cell types are neurons and cardiomyocytes. METHODS: To investigate, we generated iPSC-derived neurons (iNs) and cardiomyocytes (iCMs) from an FRDA patient and upregulated FXN expression via lentivirus without altering genomic GAA repeats at the FXN locus. RESULTS: RNA-seq and differential gene expression enrichment analyses demonstrated that frataxin deficiency affected the expression of glycolytic pathway genes in neurons and extracellular matrix pathway genes in cardiomyocytes. Genes in these pathways were differentially expressed when compared to a control and restored to control levels when FRDA cells were supplemented with frataxin. CONCLUSIONS: These results offer novel insight into specific roles of frataxin deficiency pathogenesis in neurons and cardiomyocytes.
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Ataxia de Friedreich , Células Madre Pluripotentes Inducidas , Humanos , Ataxia de Friedreich/genética , Ataxia de Friedreich/metabolismo , Ataxia de Friedreich/patología , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Expresión Génica , Neuronas/metabolismo , Neuronas/patología , FrataxinaRESUMEN
Natural gas constitutes a growing share of global primary energy due to its abundant supply and lower CO2 emission intensity compared to coal. For many natural gas reserves, CO2 contamination must be removed at the wellhead to meet pipeline specifications. Here, we demonstrate the potential of the diamine-appended metal-organic framework ee-2-Mg2(dobpdc) (ee-2 = N,N-diethylethylenediamine; dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) as a next-generation CO2 capture material for high-pressure natural gas purification. Owing to a cooperative adsorption mechanism involving formation of ammonium carbamate chains, ee-2-Mg2(dobpdc) can be readily regenerated with a minimal change in temperature or pressure and maintains its CO2 capacity in the presence of water. Moreover, breakthrough experiments reveal that water enhances the CO2 capture performance of ee-2-Mg2(dobpdc) by eliminating "slip" of CO2 before full breakthrough. Spectroscopic characterization and multicomponent adsorption isobars suggest that the enhanced performance under humid conditions arises from preferential stabilization of the CO2-inserted phase in the presence of water. The favorable performance of ee-2-Mg2(dobpdc) is further demonstrated through comparison with a benchmark material for this separation, zeolite 13X, as well as extended pressure cycling. Overall, these results support continued development of ee-2-Mg2(dobpdc) as a promising adsorbent for natural gas purification.
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BACKGROUND: Carpal tunnel release (CTR) is a surgical treatment option for patients with carpal tunnel syndrome (CTS) symptoms that are unresponsive to conservative treatment. Most patients experience symptomatic relief after CTR regardless of the surgical technique. However, direct comparisons of the safety and effectiveness between CTR surgical techniques are limited. The purpose of this randomized controlled trial is to compare the safety and effectiveness of CTR with ultrasound guidance (CTR-US) versus mini-open CTR (mOCTR) in subjects with symptomatic CTS. DESIGN AND METHODS: TUTOR (Trial of Ultrasound guided CTR versus Traditional Open Release) is a randomized controlled trial in which 120 subjects at up to 12 sites in the United States will be randomized (2:1) to receive CTR-US or mOCTR. The primary endpoint of the study is the percentage of patients who return to normal daily activities within 3 days of the procedure. Secondary endpoints of the study are median time to return to normal daily activities, percentage of patients who return to work within 3 days of the procedure, median time to return to work, Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) change score at 3 months, BCTQ Functional Status Scale (BCTQ-FSS) change score at 3 months, Numeric Pain Scale change score at 3 months, EuroQoL-5 Dimension 5-Level (EQ-5D-5L) change score at 3 months, and the incidence of device- or procedure-related adverse events at 3 months. Patient follow-up in this trial will continue for 1 year. ETHICS AND DISSEMINATION: This study was approved by a central institutional review board and ongoing trial oversight will be provided by a data safety monitoring board (DSMB). The authors intend to report the results of this trial at medical conferences and peer-reviewed journals. The outcomes of TUTOR will have important clinical and economic implications for all stakeholders involved in treating patients with CTS. STUDY REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov): NCT05405218. LEVEL OF EVIDENCE: 1.
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Síndrome del Túnel Carpiano , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/cirugía , Humanos , Encuestas y Cuestionarios , Ultrasonografía , Ultrasonografía Intervencional , MuñecaRESUMEN
Currently, no standardized system exists for evaluating and testing at-risk family members of decedents with abnormal post-mortem genetic testing in cases of sudden unexpected death (SUD). The goal of this study was to evaluate the outcomes of referrals made by an urban medical examiner's office to a multi-disciplinary cardiogenetics clinic. Relatives of decedents with pathogenic/likely pathogenic (P/LP) variants or variants of unknown significance (VUS) in genes known to be associated with cardiomyopathies and/or arrhythmias were identified by the New York City Office of Chief Medical Examiner and referred to the Cardiogenetics Clinic at Montefiore Medical Center. Familial referrals of 15 decedents (median 15 years, range 2 days to 57 years) were evaluated. Variants in 13 genes were identified among decedents (9 arrhythmia, 5 cardiomyopathy). P/LP variants were identified in both arrhythmia (RYR2, SCN5A) and cardiomyopathy syndrome (MYBPC3 (2), MYH7) genes. Thirty-two family members were referred, and 14 variants were detected. One pathogenic (MYBPC3) and two likely pathogenic (RYR2, MYH7) mutations were identified. Referral of at-risk family members of decedents who experienced SUD based on informative post-mortem genetic testing for cardiac and genetic evaluation is warranted, as family studies help to reclassify variants and prevent additional sudden death.
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[This corrects the article DOI: 10.3389/fphys.2021.778982.].
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Peracetic acid (PAA, CH3C(O)OOH) has gained significant attention for its use in wastewater disinfection. Wastewater usually contains both metal ions and organic pollutants and understanding reactions after adding PAA to such contaminated water is needed. This paper presents results regarding the effect of interactions between chromium(III) (Cr(III)) and PAA on the degradation of selected pharmaceuticals, mainly trimethoprim (TMP). The degradation of pharmaceuticals by PAA, PAA-Cr(III), and H2O2-Cr(III) under different conditions was examined (pH = 6.0-10.0 and molar ratios of PAA to Cr(III)). The degradation rate of TMP by PAA-Cr(III) was greater than by PAA and H2O2-Cr(III) under alkaline conditions. Degradation studies using quenching agents and probing molecules, and spectroscopic measurements (UV-visible and electron paramagnetic resonance) suggest â¢OH as the major radical species and Cr(IV)/Cr(V) as additional reactive species. The oxidized products of TMP by PAA-Cr(III) were identified and possible pathways proposed. Degradation of other pharmaceuticals having different molecular structures by PAA-Cr(III) and H2O2-Cr(III) systems were also investigated. Most of the pharmaceuticals degraded at faster rates by PAA-Cr(III) and H2O2-Cr(III) than by PAA alone, suggesting that co-present metal ions may play a significant role in PAA oxidation in water treatment.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Cromo , Peróxido de Hidrógeno , Iones , Metales , Oxidación-Reducción , Ácido Peracético , Preparaciones Farmacéuticas , Aguas ResidualesRESUMEN
To address community-driven concerns about lead-contaminated drinking water in residential homes in the Greater Fifth Ward neighborhood in Northeast Houston, Texas utilizing participatory-based research. The study collected survey data and performed lead analysis on drinking water from residents' homes. The Greater Fifth Ward is characterized as a majority-minority environmental justice community and is located within two confirmed cancer clusters. The residents of 172 homes completed a survey and had detectable lead levels in their water samples. Survey results indicated that more than half of the residents (58.2%) were concerned with the water quality and 42.9% rated the drinking water as poor. Water lead levels detected ranged from 0.01 to 22 µg/L. 10.9% of homes exceeding 1 µg/L, and one located exceeded the USEPA's action limit of 15 µg/L. Homes built prior to 1978 without major renovation had significantly higher levels of lead in their drinking water compared to homes built after 1978 (p-value < 0.05). These findings demonstrate the need for lead testing of residential water in low socioeconomic-status communities, as well as demonstrating the benefits of community engagement and participatory research to address environmental health concerns.
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Agua Potable , Plomo , Agua Potable/análisis , Exposición a Riesgos Ambientales/análisis , Salud Ambiental , Plomo/análisis , Características de la Residencia , Calidad del AguaRESUMEN
The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets across coronaviruses and using screening, we identified four structurally distinct lead compounds that inhibit SARS-CoV-2 3CL protease. After evaluation of their binding specificity, cellular antiviral potency, metabolic stability, and water solubility, we prioritized the GC376 scaffold as being optimal for optimization. We identified multiple drug-like compounds with <10 nM potency for inhibiting SARS-CoV-2 3CL and the ability to block SARS-CoV-2 replication in human cells, obtained co-crystal structures of the 3CL protease in complex with these compounds, and determined that they have pan-coronavirus activity. We selected one compound, termed coronastat, as an optimized lead and characterized it in pharmacokinetic and safety studies in vivo. Coronastat represents a new candidate for a small molecule protease inhibitor for the treatment of SARS-CoV-2 infection for eliminating pandemics involving coronaviruses.
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Antivirales , Tratamiento Farmacológico de COVID-19 , Proteasas 3C de Coronavirus , Inhibidores de Proteasas , Antivirales/química , Antivirales/uso terapéutico , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Humanos , Simulación del Acoplamiento Molecular , Pandemias , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , SARS-CoV-2RESUMEN
Although urban community food gardens have the capacity to strengthen and support neighborhoods in need, the benefits of such operations must be considered in tandem with the potential risks associated with urban environmental contamination. Therefore, research is needed to characterize existing community gardens in urban areas. In the present study, a survey of Houston, TX, community gardeners (N = 20) was conducted to better understand their risk-based knowledge and perceptions, current gardening practices, and willingness to implement risk mitigation measures. Soil samples collected from the beds (N = 22) and surrounding grounds (N = 24) of existing community garden sites in Houston, TX, were screened for trace and heavy metals using X-ray fluorescence spectrometry. The survey indicated that community gardeners had few concerns with regard to potential soilborne hazards and were generally willing to use diverse strategies to reduce potential hazards related to garden soil contamination. Ground and garden bed soil collected from community gardens were found to have excess concentrations of arsenic compared to federal health screening limits. The information provided here provides insight into possible discordance between community gardening risk perception and contamination risk that could be addressed through outreach, engagement, and remediation approaches.