Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.

The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.

Global absence and targeting of protective immune states in severe COVID-19.

Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between severe and mild phenotypes in the pathology of coronavirus disease 2019 (COVID-19) and its origins, we performed a whole-blood-preserving single-cell analysis protocol to integrate contributions from all major immune cell types of the blood-including neutrophils, monocytes, platelets, lymphocytes and the contents of the serum. Patients with mild COVID-19 exhibit a coordinated pattern of expression of interferon-stimulated genes (ISGs)3 across every cell population, whereas these ISG-expressing cells are systemically absent in patients with severe disease. Paradoxically, individuals with severe COVID-19 produce very high titres of anti-SARS-CoV-2 antibodies and have a lower viral load compared to individuals with mild disease. Examination of the serum from patients with severe COVID-19 shows that these patients uniquely produce antibodies that functionally block the production of the ISG-expressing cells associated with mild disease, by activating conserved signalling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many patients with COVID-19, and perhaps also in individuals with other viral infections. Our findings reveal potential targets for immunotherapies in patients with severe COVID-19 to re-engage viral defence.

Results from Ireland North and South's 2022 report card on physical activity for children and adolescents.

Background: The Ireland North and South Report Card on Physical Activity (PA) for Children and Adolescents aims to monitor progress in PA participation across a range of internationally established indicators. Methods: Data were collated for 11 indicators and graded following the harmonised Active Healthy Kids Global Alliance report card process. Six representative studies (sample size range n = 898 to n = 15,557) were primarily used in the grading, with many indicators supplemented with additional studies and reports. Data collected since the implementation of COVID-19 public health measures in March 2020 were excluded. Results: Grades were awarded as follows: 'Overall physical activity', C-; 'Organised Sport and Physical Activity', C; 'Active Play', INC; 'Sedentary Behaviours', C-; 'Physical Fitness', INC; 'Family and Peers', D+; 'School', C-; 'Physical Education', D; 'Community and Environment', B+ and 'Government', B. Separate grades were awarded for disability as follows; 'Overall physical activity', F; 'Organised Sport and Physical Activity', D; 'Sedentary Behaviours', C-; 'Family and Peers', C; 'School', C- and 'Government', B. 'Active Play', 'Physical Fitness', 'Physical Education' and 'Community and Environment' were all graded INC for disability. Since the last report card in 2016, four grades remained the same, three increased ('Overall physical activity', 'School' and 'Physical Education') and two ('Family and Peers,' and 'Government') were awarded grades for the first time. Conclusion: Grades specific to children and adolescents with disability were generally lower for each indicator. While small improvements have been shown across a few indicators, PA levels remain low across many indicators for children and adolescents.

Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1).

BACKGROUND: Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19. METHODS: Swab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene. RESULTS: Among participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold). CONCLUSIONS: The similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.

COVID-19-associated Lung Microvascular Endotheliopathy: A "From the Bench" Perspective.

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2; inactivated viral particles; or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

Irish Para Report Card on Physical Activity of Children and Adolescents With Disabilities.

For the first time, data on children and adolescents with disabilities in Ireland are reported based on the Active Healthy Kids Global Alliance Para Report Card methodology. The most recent data from the last 10 years were used in the grading process (A+ to F), and indicators with insufficient data were graded as incomplete. Of the 10 indicators from the Global Matrix Para Report Cards, grades were assigned to Overall Physical Activity (F), Organized Sport (D), Active Transport (D-), Sedentary Behaviors (D-), Family & Peers (C), School (C-), Community & Environment (B-), and Government (B). Irish disability sport organizations were invited to assess the research-led audit and provided commentary around the final grading. The contextual discussion of the grades is presented through the lens of strengths, weaknesses, opportunities, and threats with the purpose being to provide direction for the reduction of physical activity disparities among children with disabilities.

The Type 2 Asthma Mediator IL-13 Inhibits Severe Acute Respiratory Syndrome Coronavirus 2 Infection of Bronchial Epithelium.

Asthma is associated with chronic changes in the airway epithelium, a key target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many epithelial changes, including goblet cell metaplasia, are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. We found that IL-13 stimulation of differentiated human bronchial epithelial cells (HBECs) cultured at air-liquid interface reduced viral RNA recovered from SARS-CoV-2-infected cells and decreased double-stranded RNA, a marker of viral replication, to below the limit of detection in our assay. An intact mucus gel reduced SARS-CoV-2 infection of unstimulated cells, but neither a mucus gel nor SPDEF, which is required for goblet cell metaplasia, were required for the antiviral effects of IL-13. Bulk RNA sequencing revealed that IL-13 regulated 41 of 332 (12%) mRNAs encoding SARS-CoV-2-associated proteins that were detected in HBECs (>1.5-fold change; false discovery rate < 0.05). Although both IL-13 and IFN-α each inhibit SARS-CoV-2 infection, their transcriptional effects differed markedly. Single-cell RNA sequencing revealed cell type-specific differences in SARS-CoV-2-associated gene expression and IL-13 responses. Many IL-13-induced gene expression changes were seen in airway epithelium from individuals with type 2 asthma and chronic obstructive pulmonary disease. IL-13 effects on airway epithelial cells may protect individuals with type 2 asthma from COVID-19 and could lead to identification of novel strategies for reducing SARS-CoV-2 infection.

Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants.

Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern/variants of interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV [VEKLURY]) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here, we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein enzyme-linked immunosorbent assay (ELISA) and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with 50% effective concentration (EC50) values 0.30- to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50 values ranging from 0.13- to 2.3-fold of the observed EC50 values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants, with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.

Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum.

Phenotypic switching between 2 opposing cellular states is a fundamental aspect of biology, and fungi provide facile systems to analyze the interactions between regulons that control this type of switch. A long-standing mystery in fungal pathogens of humans is how thermally dimorphic fungi switch their developmental form in response to temperature. These fungi, including the subject of this study, Histoplasma capsulatum, are temperature-responsive organisms that utilize unknown regulatory pathways to couple their cell shape and associated attributes to the temperature of their environment. H. capsulatum grows as a multicellular hypha in the soil that switches to a pathogenic yeast form in response to the temperature of a mammalian host. These states can be triggered in the laboratory simply by growing the fungus either at room temperature (RT; which promotes hyphal growth) or at 37 °C (which promotes yeast-phase growth). Prior worked revealed that 15% to 20% of transcripts are differentially expressed in response to temperature, but it is unclear which transcripts are linked to specific phenotypic changes, such as cell morphology or virulence. To elucidate temperature-responsive regulons, we previously identified 4 transcription factors (required for yeast-phase growth [Ryp]1-4) that are required for yeast-phase growth at 37 °C; in each ryp mutant, the fungus grows constitutively as hyphae regardless of temperature, and the cells fail to express genes that are normally induced in response to growth at 37 °C. Here, we perform the first genetic screen to identify genes required for hyphal growth of H. capsulatum at RT and find that disruption of the signaling mucin MSB2 results in a yeast-locked phenotype. RNA sequencing (RNAseq) experiments reveal that MSB2 is not required for the majority of gene expression changes that occur when cells are shifted to RT. However, a small subset of temperature-responsive genes is dependent on MSB2 for its expression, thereby implicating these genes in the process of filamentation. Disruption or knockdown of an Msb2-dependent mitogen-activated protein (MAP) kinase (HOG2) and an APSES transcription factor (STU1) prevents hyphal growth at RT, validating that the Msb2 regulon contains genes that control filamentation. Notably, the Msb2 regulon shows conserved hyphal-specific expression in other dimorphic fungi, suggesting that this work defines a small set of genes that are likely to be conserved regulators and effectors of filamentation in multiple fungi. In contrast, a few yeast-specific transcripts, including virulence factors that are normally expressed only at 37 °C, are inappropriately expressed at RT in the msb2 mutant, suggesting that expression of these genes is coupled to growth in the yeast form rather than to temperature. Finally, we find that the yeast-promoting transcription factor Ryp3 associates with the MSB2 promoter and inhibits MSB2 transcript expression at 37 °C, whereas Msb2 inhibits accumulation of Ryp transcripts and proteins at RT. These findings indicate that the Ryp and Msb2 circuits antagonize each other in a temperature-dependent manner, thereby allowing temperature to govern cell shape and gene expression in this ubiquitous fungal pathogen of humans.

Factors associated with changes in consumption among smokers and alcohol drinkers during the COVID-19 'lockdown' period.

BACKGROUND: The impact of the COVID-19 public health social measures (PHSM) on health behaviours is poorly understood. We aimed to identify factors associated with changes in alcohol and tobacco consumption during the strictest period of PHSM 'lockdown'. METHODS: Logistic regression analysis was conducted using secondary data from the Central Statistics Office Social Impact Survey collected during the first lockdown in Ireland (23 April- 1 May 2020). RESULTS: Of the 1362 (33.8%) individuals that responded to the survey, 80.6% were current drinkers and 26.0% were smokers. The majority of smokers (60.9%) and drinkers (60.6%) reported no change in consumption. However, 30.5% of smokers and 22.2% of drinkers reported increased consumption. Being concerned about household stress from confinement [adjusted odds ratio (aOR) 1.9, 95% confidence interval (CI) 1.3-2.9, P = 0.002], working from home (aOR 2.1, 95 CI 1.4-3.3, P < 0.001) and urban living (aOR 2.0, 95 CI 1.5-2.9, P < 0.001) were associated with increases in alcohol consumption. Feeling very nervous (aOR 2.2, 95% CI 1.2-4.0, P = 0.009), feeling downhearted/depressed (aOR 2.4, 95% CI 1.3-4.4, P = 0.004), being concerned about someone else's health (aOR 2.0, 95% CI 1.1-3.9, P = 0.031), working from home (aOR 2.3, 95% CI 1.0-5.3, P = 0.046) and increases in alcohol consumption (aOR 3.6, 95% CI 1.7-7.7, P = 0.023) were associated with increases in tobacco consumption. CONCLUSION: A mixed picture was evident in terms of changes in consumption among current smokers and drinkers. Increased consumption was more commonly reported than reductions. Increased consumption was associated with psychological distress and socio-economic factors. Policies and services should consider a response to widening inequalities in harmful consumption.

The use and impact of self-monitoring on substance use outcomes: A descriptive systematic review.

Background: Self-Monitoring (SM), the act of observing ones' own behavior, has been used in substance use treatment because SM may bring conscious awareness to automatized substance use behaviors. Empirical findings regarding SM's effectiveness are mixed. The aim of this study was to synthesize the literature for the efficacy of SM on substance use. Method: A literature search was conducted using MEDLINE/PubMed. Results: Out of 2,659 citations, 41 studies with 126 analyses were included. Among analyses from studies rated Moderate (n = 24) or Strong (n = 3) quality, SM was shown to have a helpful effect (e.g., reducing substance use) 29% of the time; to have no effect 63.0% of the time; and to be detrimental in 8.0% of analyses. SM's helpful effects were associated with methodological characteristics including longer monitoring and Phone/IVR and EMA/Computer methodologies compared to Paper/Pencil. SM was more helpful in non-treatment-seekers (35.0% of analyses showed SM to be helpful compared to 25.0% of analyses with treatment-seekers). Conclusions: Results of this study suggest that SM, under certain circumstances, as the potential to be a low-cost, low-risk research and early intervention strategy for substance users.

Change in Lactate Levels After Hemodialysis in Patients With End-Stage Renal Disease.

STUDY OBJECTIVE: Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels. METHODS: This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions. RESULTS: The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L. CONCLUSION: The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED.

Challenge of intravascular volume assessment in acute ischemic stroke.

INTRODUCTION: Retrospective data indicates that dehydration in acute ischemic stroke patients may be common, even though these patients frequently have elevated blood pressure. We sought to evaluate clinical and laboratory measures of intravascular volume status compared to more objective measures using ultrasound measurements of the inferior vena cava (IVC). METHODS: This was a prospective observation study of acute ischemic stroke patients in the emergency department. Patients with NIH stroke scale ≥4 within 12 h of symptom onset were included. A trained ultrasonographer performed bi-dimensional imaging of the IVC with passive respiration to determine the percent inspiratory collapse and maximum diameter. We defined low intravascular volume as >50% IVC collapse and a maximal diameter < 2.1 cm. Analysis was limited to patients with confirmed ischemic stroke. RESULTS: There were 42 patients, of whom 31 had confirmed acute ischemic stroke. The mean age was 65 ±â€¯15 years, 52% were female, and 71% were hypertensive. The median NIH stroke scale score was 7 (IQR 5-15). Based on IVC ultrasound, low intravascular volume was present in 63% (95% CI 44-80%) of patients. A higher proportion of hypertensive patients had low intrasvascular volume (72% vs. 33%). There was poor correlation between IVC assessment of intrasvascular volume and blinded clinician assessment or laboratory markers of dehydration. CONCLUSION: The majority of ED acute ischemic stroke patients in this sample were hypertensive and demonstrated low intravascular volume based on IVC ultrasound.

National Survey of Medical Spanish Curriculum in U.S. Medical Schools.

BACKGROUND: Patients with limited English proficiency (LEP) may be at risk for medical errors and worse health outcomes. Language concordance between patient and provider has been shown to improve health outcomes for Spanish-speaking patients. Nearly 40 % of Hispanics, a growing population in the United States, are categorized as having limited English proficiency. Many medical schools have incorporated a medical Spanish curriculum to prepare students for clinical encounters with LEP patients. OBJECTIVE: To describe the current state of medical Spanish curricula at United States medical schools. METHODS: The Latino Medical Student Association distributed an e-mail survey comprising 39 items to deans from each U.S. medical school from July 2012 through July 2014. This study was IRB-exempt. RESULTS: Eighty-three percent (110/132) of the U.S. medical schools completed the survey. Sixty-six percent (73/110) of these schools reported offering a medical Spanish curriculum. In addition, of schools with no curriculum, 32 % (12/37) planned to incorporate the curriculum within the next two years. Most existing curricula were elective, not eligible for course credit, and taught by faculty or students. Teaching modalities included didactic instruction, role play, and immersion activities. Schools with the curriculum reported that the diverse patient populations in their respective service areas and/or student interest drove course development. Barriers to implementing the curriculum included lack of time in students' schedules, overly heterogeneous student language skill levels, and a lack of financial resources. Few schools reported the use of validated instruments to measure language proficiency after completion of the curriculum. CONCLUSIONS: Growing LEP patient populations and medical student interest have driven the implementation of medical Spanish curricula at U.S. medical schools, and more schools have plans to incorporate this curriculum in the near future. Studies are needed to reveal best practices for developing and evaluating the curriculum.

Mercury levels in pregnant women, children, and seafood from Mexico City.

BACKGROUND: Mercury is a global contaminant of concern though little is known about exposures in México. OBJECTIVES: To characterize mercury levels in pregnant women, children, and commonly consumed seafood samples. METHODS: Use resources of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohorts to measure total mercury levels in archived samples from 348 pregnant women (blood from three trimesters and cord blood), 825 offspring (blood, hair, and urine) and their mothers (hair), and 91 seafood and canned tuna samples from Mexico City. RESULTS: Maternal blood mercury levels correlated across three trimesters and averaged 3.4 µg/L. Cord blood mercury averaged 4.7 µg/L and correlated with maternal blood from trimester 3 (but not trimesters 1 and 2). In children, blood, hair and urine mercury levels correlated and averaged 1.8 µg/L, 0.6 µg/g, and 0.9 µg/L, respectively. Hair mercury was 0.5 µg/g in mothers and correlated with child's hair. Mean consumption of canned tuna, fresh fish, canned sardine, and shellfish was 3.1, 2.2, 0.5, and 1.0 times per month respectively in pregnant women. Mean mercury content in 7 of 23 seafood species and 5 of 9 canned tuna brands purchased exceeded the U.S. EPA guidance value of 0.3 µg/g. CONCLUSIONS: Mercury exposures in pregnant women and children from Mexico City, via biomarker studies, are generally 3-5 times greater than values reported in population surveys from the U.S., Canada, and elsewhere. In particular, mercury levels in 29-39% of the maternal participants exceeded the biomonitoring guideline associated with the U.S. EPA reference dose for mercury.

Chesapeake DolphinWatch sightings data (2017-2022): Citizen science reports of bottlenose dolphins observed in the Chesapeake Bay, USA.

Atlantic bottlenose dolphins are extensively studied, though little has been published regarding their occurrence patterns in the large and highly urbanized estuary of the Chesapeake Bay, USA. To address this knowledge gap, the Chesapeake DolphinWatch project was initiated in the summer of 2017. Utilizing a citizen science (also known as volunteer science) methodology, members of the public were encouraged to report dolphin sightings through a specialized mobile (iOS and Android) and web-based (https://chesapeakedolphinwatch.org) application. This approach ensured extensive, yet non-invasive and financially-efficient, data collection. The dataset presented here includes bottlenose dolphin sighting reports submitted to Chesapeake DolphinWatch by citizen scientists over five years; from June 28, 2017 through December 9, 2022. These data have been quality checked by researchers at the University of Maryland Center for Environmental Science's (UMCES) Chesapeake Biological Laboratory (CBL) in Solomons, Maryland (USA). This dataset holds potential for various applications, such as analyzing the spatiotemporal patterns of dolphin presence within the Chesapeake Bay, investigating the behavior and movements of bottlenose dolphins in the mid-Atlantic, and serving as a comparative benchmark for studies in other estuarine systems. By integrating community engagement with technological platforms, the provided data showcases the invaluable role of citizen science in advancing marine ecological research.

Three Lessons Learned About Power and Improving Recruitment of Underrepresented Populations in Clinical Trials.

This Open Forum is relevant for investigators who conduct research with historically understudied and marginalized populations. The authors introduce a U.S. Department of Veterans Affairs clinical trial that experienced challenges with recruitment of African American or Black veterans and was terminated for not achieving its recruitment goals. The role of power dynamics in clinical research is discussed, specifically how unequal distributions of power may create recruitment challenges. The authors summarize three lessons learned and offer recommendations for sharing power equitably between investigators and potential participants. By recounting these experiences, the authors seek to promote culturally sensitive, veteran-centered approaches to recruitment in future clinical trials.