Triple-negative breast cancers (TNBC) lack estrogen, progesterone, and express little, if any, HER2 receptors on their surface. No targeted therapies exist for this aggressive form of breast cancer. A library of enriched fractions from marine organisms was screened in a multi-parametric cytotoxicity assay using MDA-MB-231 and MDA-MB-468 TNBC cells, grown as spheroids (3D cultures). Spheroids better resemble tumors and are considered more clinically predictive. The assay measures apoptosis via the cleavage of caspase 3/7, viability via DNA content, and loss of membrane integrity via 7AAD staining at 24 h of treatment. Fractions were also tested in a traditional 2D MTT assay at 72 h. A fraction from the sponge Aplysina was active in the 3D assay. Aplysinamisine I was identified as the compound responsible for the activity. Aplysinamisine I induces apoptosis in MDA-MB-268 spheroids with an IC50 of 2.9 ± 0.28 µM at 24 h. This novel activity is the most potent for the compound to date. Its IC50 in the MTT assay at 72 h is >80 µM. Striking synergy with Taxol™ is shown in both cell lines. Proteomic analysis led to a differential protein expression profile. Through bioinformatics, this profile led to the hypothesis that the inhibition of nucleophosmin is the potential mode of action of the compound. However, initial studies show only a modest decrease in nucleophosmin expression in spheroids treated with aplysinamisine I.

Marine sponges are the source of numerous bioactive natural products that serve as chemical defenses and provide pharmaceutical leads for drug development. For some of the compounds, symbiotic bacteria have been established as the actual producers. Among the known sponge symbionts, 'Candidatus Entotheonella' members stand out because of their abundant and variable biosynthetic gene clusters (BGCs). Here, to obtain broader insights into this producer taxon, we conduct a comparative analysis on eight sponges through metagenomic and single-bacterial sequencing and biochemical studies. The data suggest sets of biosynthetic genes that are largely unique in 14 'Entotheonella' candidate species and a member of a sister lineage named 'Candidatus Proxinella'. Four biosynthetic loci were linked in silico or experimentally to cytotoxins, antibiotics and the terpene cembrene A from corals. The results support widespread and diverse bacterial roles in the chemistry of sponges and aid the development of sustainable production methods for sponge-derived therapeutics.

BackgroundMyelin oligodendrocyte glycoprotein-associated disorders (MOGAD) is an autoimmune central nervous system disease. Antigen-specific immune tolerance using nanoparticles such as Polylactic-co-glycolic acid (PLGA) have recently been used as a new therapeutic tolerization approach for CNS autoimmune diseases. We examined whether MOG1-125 conjugated with PLGA could induce MOG-specific immune tolerance in an experimental autoimmune encephalitis (EAE) mouse model. EAE was induced in sixty C57BL/6 J wild-type mice using MOG1-125 peptide with complete Freund's Adjuvant. The mice were divided into 12 groups (n = 5 each) to test the ability of MOG1-125 conjugated PLGA intervention to mitigate the severity or improve the outcomes from EAE with and without rapamycin compared to antigen alone or PLGA alone. EAE score and serum MOG-IgG titers were compared among the interventions.Kindly check and confirm the processed Affiliation "4" is appropriate.I confirmed the Aff 4.Affiliation: Corresponding author information have been changed to present affiliation. Kindly check and confirm.I checked and confirmed the Corresponding author's information.ResultsMice with EAE that were injected intraperitoneally with MOG1-125 conjugated PLGA + rapamycin complex showed dose-dependent mitigation of EAE score. Intraperitoneal and intravenous administration resulted in similar clinical outcomes, whereas 80% of mice treated with subcutaneous injection had a recurrence of clinical score worsening after approximately 1 week. Although there was no significant difference in EAE scores between unconjugated-PLGA and MOG-conjugated PLGA, serum MOG-IgG tended to decrease in the MOG-conjugated PLGA group compared to controls.ConclusionIntraperitoneal administration of PLGA resulted in dose-dependent and longer-lasting immune tolerance than subcutaneous administration. The induction of immune tolerance using PLGA may represent a future therapeutic option for patients with MOGAD.

Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear. To investigate the role of the anti-AQP4 immunoglobulin (AQP4-IgG)/AQP4 immunocomplex on the induction and profile of ex vivo cytokine and surface marker expression in peripheral blood mononuclear cells (PBMC) culture. Isolated PBMCs obtained from 18 patients with AQP4-IgG-seropositive-NMOSD (8 treatment-naive, 10 rituximab-treated) or ten healthy controls were cultured with AQP4-immunocomplex with or without complement. Changes in PBMC surface markers and cytokine expression were profiled using flow cytometry and ELISA. PBMCs derived from treatment-naive NMOSD patients stimulated with a complex mixture of serum complement proteins produced significant elevations of IL-17A and IL-6. Rituximab-treated patients also exhibited higher IL-6 but not IL-17A release. IL-6 and IL-17A elevations are not observed without complement. Co-stimulation of PBMCs with AQP4-IgG/AQP4 immunocomplex and complement prompts a Th17-biased response consistent with the inflammatory paradigm observed in NMOSD. A possible inflammation model is proposed via antigen-specific autoreactive peripheral blood cells, including NK/NKT cells.

IntroductionOpioid overdose epidemic is a public health crisis that is impacting communities around the world. Overdose education and naloxone distribution programs equip and train lay people to respond in the event of an overdose. We aimed to understand factors to consider for the design of naloxone distribution programs in point-of-care settings from the point of view of community stakeholders.MethodsWe hosted a multi-stakeholder co-design workshop to elicit suggestions for a naloxone distribution program. We recruited people with lived experience of opioid overdose, community representatives, and other stakeholders from family practice, emergency medicine, addictions medicine, and public health to participate in a full-day facilitated co-design discussion wherein large and small group discussions were audio-recorded, transcribed and analysed using thematic approaches.ResultsA total of twenty-four participants participated in the multi-stakeholder workshop from five stakeholder groups including geographic and setting diversity. Collaborative dialogue and shared storytelling revealed seven considerations for the design of naloxone distribution programs specific to training needs and the provision of naloxone, these are: recognizing overdose, how much naloxone, impact of stigma, legal risk of responding, position as conventional first aid, friends and family as responders, support to call 911.ConclusionTo create an naloxone distribution program in emergency departments, family practice and substance use treatment services, stigma is a central design consideration for training and naloxone kits. Design choices that reference the iconography, type, and form of materials associated with first aid have the potential to satisfy the need to de-stigmatize overdose response.

Objective: To clarify if NK and NKT cells are activated via complement receptors in NMOSD. Background: Inhibition of terminal complement in neuromyelitis optica spectrum disorder (NMOSD) using eculizumab helps prevent relapses, but the exact mechanism of action of the drug remains unclear. Similarly, genetic variants in the Fc Gamma receptor 3A (FCGR3A), also known as CD16, are correlated with outcomes in NMOSD, but the immune cells expressing those CD16 are unknown. We compared CD16 expression on immune cells modulated by complement activity in Natural Killer (NK) cells and Natural Killer-T (NKT) cells in NMOSD to disease and normal-healthy controls. Design/Methods: Peripheral blood cell (PBMC) samples from 45 patients with NMOSD with aquaporin 4 (AQP4)-IgG, 18 disease controls, and 19 normal controls were analyzed for CD16 expression and complement receptors in vitro. Results: At baseline, the number of NKT cells was increased in NMOSD (p < 0.001), but the proportion that was CD16 positive was lower compared to normal and disease controls (p=0.0012). NK cell count was normal, but the ratio that was CD16 positive was also significantly lower (p < 0.001). In both NK cells and NKT cells from NMOSD, C5 complement receptor expression was much higher than normal and disease controls (p < 0.001 for both). We also evaluated activation markers CD69 and CD83, which were also significantly higher in NK and NKT cells from NMOSD patients. FCGR3A p158 V/V genotype group in NMOSD patients showed decreased NK cell proportion with activation, and fewer CD16 expressed NKT cells than the F/F genotype group. Conclusions: Our results support an immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulates CD16 expression that binds to antibody/antigen complexes. In the context of NMOSD, these complement-sensitive cells may be responsible for the escalating autoimmune activity. Disclosure: Dr. Nishiyama has nothing to disclose. Ms. Wright has nothing to disclose. Dr. Lotan has nothing to disclose. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe PC (MTPC). The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aarhus University. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CELGENE. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACRELION. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizter. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck Serono. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.

Cancer cells grown in 3D spheroid cultures are considered more predictive for clinical efficacy. The marine natural product dragmacidin D induces apoptosis in MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) spheroids within 24 h of treatment while showing no cytotoxicity against the same cells grown in monolayers and treated for 72 h. The IC50 for cytotoxicity based on caspase 3/7 cleavage in the spheroid assay was 8 ± 1 µM in MDA-MB-231 cells and 16 ± 0.6 µM in MDA-MB-468 cells at 24 h. No cytotoxicity was seen at all in 2D, even at the highest concentration tested. Thus, the IC50 for cytotoxicity in the MTT assay (2D) in these cells was found to be >75 µM at 72 h. Dragmacidin D exhibited synergy when used in conjunction with paclitaxel, a current treatment for TNBC. Studies into the signaling changes using a reverse-phase protein array showed that treatment with dragmacidin D caused significant decreases in histones. Differential protein expression was used to hypothesize that its potential mechanism of action involves acting as a protein synthesis inhibitor or a ribonucleotide reductase inhibitor. Further testing is necessary to validate this hypothesis. Dragmacidin D also caused a slight decrease in an invasion assay in the MDA-MB-231 cells, although this failed to be statistically significant. Dragmacidin D shows intriguing selectivity for spheroids and has the potential to be a treatment option for triple-negative breast cancer, which merits further research into understanding this activity.

The Indian River Lagoon (IRL), a 156-mile-long estuary located on the eastern coast of Florida, experiences phytoplankton bloom events due to increased seasonal temperatures coupled with anthropogenic impacts. This study aimed to gather data on the toxicity to human cells and to identify secondary metabolites found in water samples collected in the IRL. Water samples from 20 sites of the IRL were collected during the wet and dry seasons over a three-year period. A panel of cell lines was used to test cytotoxicity. Hemagglutination, hemolysis, and inhibition of protein phosphatase 2A (PP2A) were also measured. Cytotoxic blooms were seen both in the south (Microcystis) and the north (Pyrodinium) of the IRL. Each toxin induced a consistent pattern of cytotoxicity in the panel of human cell lines assayed. During blooms, cytotoxicity due to a single type of toxin is obvious from this pattern. In the absence of blooms, the cytotoxicity seen reflected either a mixture of toxins or it was caused by an unidentified toxin. These observations suggest that other toxins with the potential to be harmful to human health may be present in the IRL. Moreover, the presence of toxins in the IRL is not always associated with blooms of known toxin-producing organisms.

The COVID-19 infodemic is an overwhelming amount of information that has challenged pandemic communication and epidemic response. WHO has produced weekly infodemic insights reports to identify questions, concerns, information voids expressed and experienced by people online. Publicly available data was collected and categorized to a public health taxonomy to enable thematic analysis. Analysis showed three key periods of narrative volume peaks. Understanding how conversations change over time can help inform future infodemic preparedness and prevention planning.

OBJECTIVE:COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity. METHODS:This was a retrospective cohort study of pregnant women from March 2020 till October 1st, 2020. The study included patients from 14 obstetric centers in Michigan, USA. Cases were defined as women diagnosed with COVID-19 at any point during their pregnancy. Cases were matched with uninfected women who delivered in the same unit, within 30 d of the delivery of the index case. Outcomes of interest were frequencies of prematurity overall and subcategories of preterm birth (early, spontaneous/medically indicated, preterm labor, and premature preterm rupture of membranes) in cases compared to controls. The impact of modifiers of these outcomes was documented with extensive control for potential confounders. A p value <.05 was used to infer significance. RESULTS:The rate of prematurity was 8.9% in controls, 9.4% in asymptomatic cases, 26.5% in symptomatic COVID-19 cases, and 58.8% among cases admitted to the ICU. Gestational age at delivery was noted to decrease with disease severity. Cases were at an increased risk of prematurity overall [adjusted relative risk (aRR) = 1.62 (1.2-2.18)] and of early prematurity (<34 weeks) [aRR = 1.8 (1.02-3.16)] when compared to controls. Medically indicated prematurity related to preeclampsia [aRR = 2.46 (1.47-4.12)] or other indications [aRR = 2.32 (1.12-4.79)], were the primary drivers of overall prematurity risk. Symptomatic cases were at an increased risk of preterm labor [aRR = 1.74 (1.04-2.8)] and spontaneous preterm birth due to premature preterm rupture of membranes [aRR = 2.2(1.05-4.55)] when compared to controls and asymptomatic cases combined. The gestational age at delivery followed a dose-response relation with disease severity, as more severe cases tended to deliver earlier (Wilcoxon p < .05). CONCLUSIONS:COVID-19 is an independent risk factor for preterm birth. The increased preterm birth rate in COVID-19 was primarily driven by medically indicated delivery, with preeclampsia as the principal risk factor. Symptomatic status and disease severity were significant drivers of preterm birth.

Trust in authorities is important during health emergencies, and there are many factors that influence this. The infodemic has resulted in overwhelming amounts of information being shared on digital media during the COVID-19 pandemic, and this research looked at trust-related narratives during a one-year period. We identified three key findings related to trust and distrust narratives, and a country-level comparison showed less mistrust narratives in a country with a higher level of trust in government. Trust is a complex construct and the findings of this study present results that warrant further exploration.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of Inflammatory central nervous system (CNS) disease. Dark agouti (DA) rats immunized with full-length myelin oligodendrocyte glycoprotein (MOG1-125) typically develop a relapsing-remitting EAE form characterized by predominant demyelinating involvement of the spinal cord and optic nerve. Visually evoked potentials (VEP) are a useful objective tool to assess the optic nerve function and monitor electrophysiological changes in optic neuritis (ON). The current study aimed to assess the VEP changes in MOG-EAE DA rats using a minimally invasive recording device and to correlate them with histological findings. Twelve MOG-EAE DA rats and four controls underwent VEP recording at day 0, 7, 14, 21, and 28 post-EAE induction. Tissue samples were obtained on days 14, 21, and 28 from two EAE rats and one control. The median VEP latencies were significantly higher on days 14, 21, and 28 compared to baseline, with maximal latencies observed on day 21. The histological analyses on day 14 demonstrated inflammation with largely preserved myelin and axonal structures. Inflammation and demyelination with largely preserved axons were evident on days 21 and 28, which correlated with prolonged VEP latencies. These findings suggest that VEPs may be a reliable biomarker reflecting the optic nerve involvement in EAE. Moreover, the use of a minimally invasive device enables observation of VEP changes over time in MOG-EAE DA rats. Our findings may have important implications for testing the potential neuroprotective and regenerative effects of new therapies for CNS demyelinating diseases.

Introduction: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. Methods: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests. Results: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities. Conclusions: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

One novel brominated nocardiopsistin D (1) and two new sulfur-containing nocardiopsistins E-F (2-3) were identified from Nocardiopsis sp. HB-J378. The biosynthetic gene cluster ncd featuring a brominase was identified. Compounds 1-3 exhibited significant anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activities with minimum inhibitory concentrations (MICs) of 0.098, 3.125, and 0.195 μg/mL, respectively. The single bromination in 1 drastically enhanced the anti-MRSA activity by 128-fold without altering cell toxicity and acquired new activities against the bacterial pathogens vancomycin-resistant S. aureus (VRSA), Enterococcus faecium, and Bacillus cereus.

Background and objectives Inhibition of terminal complement in neuromyelitis optica spectrum disorder (NMOSD) using eculizumab helps prevent relapses, but the exact mechanism of action of the drug remains unclear. Similarly, genetic variants in the Fc Gamma receptor 3A ( FCGR3A ), also known as CD16, are correlated with outcomes in NMOSD, but the immune cells expressing those CD16 are unknown. We compared CD16 expression on immune cells modulated by complement activity in natural killer (NK) cells and natural killer-T (NKT) cells in NMOSD to disease and normal-healthy controls. Methods Peripheral blood cell (PBMC) samples from 45 patients with NMOSD with aquaporin 4 (AQP4)-IgG, 18 disease controls, and 19 normal controls were analyzed for CD16 expression and complement receptors in vitro. Results At baseline, the number of NKT cells was increased in NMOSD ( p < 0.001), but the proportion that was CD16 positive was lower compared to normal and disease controls ( p = 0.0012). NK cell count was normal, but the ratio that was CD16 positive was also significantly lower ( p < 0.001). In both NK cells and NKT cells from NMOSD, C5 complement receptor expression was much higher than normal and disease controls ( p < 0.001 for both). We also evaluated activation markers CD69 and CD83, which were also significantly higher in NK and NKT cells from NMOSD patients. FCGR3A p158 V/V genotype group in NMOSD patients showed decreased NK cell proportion with activation, and fewer CD16-expressing NKT cells than the F/F genotype group. Discussion Our results support an immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulates CD16 expression that binds to antibody/antigen complexes. In the context of NMOSD, these complement-sensitive cells may be responsible for the escalating autoimmune activity.

Cryptosporidium sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans and valuable livestock. There are no drugs on the market that are effective in the population most severely affected by this parasite. This study is the first high-throughput screen for potent anti-Cryptosporidium natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has a collection of diverse marine organisms some of which have been subjected to medium pressure liquid chromatography to create an enriched fraction library. Numerous active compounds have been discovered from this library, but it has not been tested against Cryptosporidium parvum. A high-throughput in vitro growth inhibition assay was used to test 3764 fractions in the library, leading to the identification of 23 fractions that potently inhibited the growth of Cryptosporidium parvum. Bioassay guided fractionation of active fractions from a deep-sea sponge, Leiodermatium sp., resulted in the purification of leiodolide A, the major active compound in the organism. Leiodolide A displayed specific anti-Cryptosporidium activity at a half maximal effective concentration of 103.5 nM with selectivity indexes (SI) of 45.1, 11.9, 19.6 and 14.3 for human ileocecal colorectal adenocarcinoma cells (HCT-8), human hepatocellular carcinoma cells (Hep G2), human neuroblastoma cells (SH-SY5Y) and green monkey kidney cells (Vero), respectively. The unique structure of leiodolide A provides a valuable drug scaffold on which to develop new anti-Cryptosporidium compounds and supports the importance of screening natural product libraries for new chemical scaffolds.

Previous studies have looked at COVID-19 outcomes in pregnancy and racial disparities among patients with COVID-19, but few have studied racial disparities among pregnant patients with COVID-19. Our goal in this study is to analyze the relationship between race and disparate COVID-19 risk in pregnancy. A retrospective cohort analysis was performed on data collected as part of the COVID-19 in Pregnancy and The Newborn: State of Michigan Collaborative, a database of pregnant patients admitted to 14 institutions in Southern Michigan. Cases were defined as patients with a positive SARS-CoV-2 test result. Controls, those with suspicion of COVID-19 prior to universal screening or a negative PCR test, were matched to cases on the same unit within 30 days of each case. For this analysis, the two primary groups of interest were non-Hispanic Black (Black) vs. non-Hispanic White (White) patients. Potential covariates were age, body mass index (BMI), chronic hypertension, diabetes, asthma, substance use, and smoking; the dependent variable was COVID/non-COVID in a robust Poisson regression model. In addition, 18 symptoms and disease severity (mild/moderate/severe) were compared between the Black and White groups using the same statistical method. Of 1,131 gravidas, 42.9%(n=485) were Black. These patients were at two-fold greater risk for COVID-19 compared with their White counterparts [35.9% vs. 18.3%, RR=1.96(1.6-2.4)]. After adjusting for obesity and diabetes, the risk of COVID-19 in Black patients remained higher compared to the risk among White patients (aRR=2.46 [1.87-3.24]). There were no differences in symptoms nor severity of disease presentation between the groups. In our population, Black patients are more likely to be diagnosed with COVID-19 infection during pregnancy. This finding is not explained by a range of covariates. Other factors, such as social determinants of health, may be important to understand this disparity and warrant further examination.

Background: The Miro Health Mobile Assessment Platform consists of self-administered neurobehavioral and cognitive assessments that measure behaviors typically measured by specialized clinicians. Objective: To evaluate the Miro Health Mobile Assessment Platform’s concurrent validity, test–retest reliability, and mild cognitive impairment (MCI) classification performance. Method: Sixty study participants were evaluated with Miro Health version V.2. Healthy controls (HC), amnestic MCI (aMCI), and nonamnestic MCI (naMCI) ages 64–85 were evaluated with version V.3. Additional participants were recruited at Johns Hopkins Hospital to represent clinic patients, with wider ranges of age and diagnosis. In all, 90 HC, 21 aMCI, 17 naMCI, and 15 other cases were evaluated with V.3. Concurrent validity of the Miro Health variables and legacy neuropsychological test scores was assessed with Spearman correlations. Reliability was quantified with the scores’ intraclass correlations. A machine-learning algorithm combined Miro Health variable scores into a Risk score to differentiate HC from MCI or MCI subtypes. Results: In HC, correlations of Miro Health variables with legacy test scores ranged 0.27–0.68. Test–retest reliabilities ranged 0.25–0.79, with minimal learning effects. The Risk score differentiated individuals with aMCI from HC with an area under the receiver operator curve (AUROC) of 0.97; naMCI from HC with an AUROC of 0.80; combined MCI from HC with an AUROC of 0.89; and aMCI from naMCI with an AUROC of 0.83. Conclusion: The Miro Health Mobile Assessment Platform provides valid and reliable assessment of neurobehavioral and cognitive status, effectively distinguishes between HC and MCI, and differentiates aMCI from naMCI.

Background The COVID-19 pandemic has been accompanied by an infodemic: excess information, including false or misleading information, in digital and physical environments during an acute public health event. This infodemic is leading to confusion and risk-taking behaviors that can be harmful to health, as well as to mistrust in health authorities and public health responses. The World Health Organization (WHO) is working to develop tools to provide an evidence-based response to the infodemic, enabling prioritization of health response activities. Objective In this work, we aimed to develop a practical, structured approach to identify narratives in public online conversations on social media platforms where concerns or confusion exist or where narratives are gaining traction, thus providing actionable data to help the WHO prioritize its response efforts to address the COVID-19 infodemic. Methods We developed a taxonomy to filter global public conversations in English and French related to COVID-19 on social media into 5 categories with 35 subcategories. The taxonomy and its implementation were validated for retrieval precision and recall, and they were reviewed and adapted as language about the pandemic in online conversations changed over time. The aggregated data for each subcategory were analyzed on a weekly basis by volume, velocity, and presence of questions to detect signals of information voids with potential for confusion or where mis- or disinformation may thrive. A human analyst reviewed and identified potential information voids and sources of confusion, and quantitative data were used to provide insights on emerging narratives, influencers, and public reactions to COVID-19–related topics. Results A COVID-19 public health social listening taxonomy was developed, validated, and applied to filter relevant content for more focused analysis. A weekly analysis of public online conversations since March 23, 2020, enabled quantification of shifting interests in public health–related topics concerning the pandemic, and the analysis demonstrated recurring voids of verified health information. This approach therefore focuses on the detection of infodemic signals to generate actionable insights to rapidly inform decision-making for a more targeted and adaptive response, including risk communication. Conclusions This approach has been successfully applied to identify and analyze infodemic signals, particularly information voids, to inform the COVID-19 pandemic response. More broadly, the results have demonstrated the importance of ongoing monitoring and analysis of public online conversations, as information voids frequently recur and narratives shift over time. The approach is being piloted in individual countries and WHO regions to generate localized insights and actions; meanwhile, a pilot of an artificial intelligence–based social listening platform is using this taxonomy to aggregate and compare online conversations across 20 countries. Beyond the COVID-19 pandemic, the taxonomy and methodology may be adapted for fast deployment in future public health events, and they could form the basis of a routine social listening program for health preparedness and response planning.