ABSTRACT IMPACT: The first-line chemotherapies used to treat leishmaniasis are highly toxic intravenous antimonials yet drug resistance has begun to develop, causing the use of oral treatment options with high price tags; there is a strong need for new, safe, and effective chemotherapeutic agents to treat leishmaniasis. OBJECTIVES/GOALS: This study was conducted in order to identify novel chemical compounds that exhibit anti-leishmanial activity and to further characterize their efficacy and toxicity in in vitro and in vivo systems in the hopes of future chemotherapeutic developments. METHODS/STUDY POPULATION: A total of 28 unique 1,4-diaryl-pyrazolo-pyridinone (1,4-DAPP) compounds were synthesized and anti-leishmanial efficacy and host cell toxicity were determined using L. donovani mCherry-expressing amastigotes and THP-1 macrophages. Additional pharmacokinetic analyses of a potent 1,4-DAPP compound were conducted, revealing a potential metabolite structure. A select group of the novel compounds were screened in a cutaneous leishmaniasis (CL) murine model using L. major mCherry-expressing parasites and female Balb/C mice. The treatment consisted of 10 intralesional injections of compound over a period of 4 weeks, while lesion growth was monitored via fluorescence and manual measurements. RESULTS/ANTICIPATED RESULTS: Four experimental compounds had IC50 values less than 5 micromolar, providing similar anti-leishmanial activity to Miltefosine. Compound 9279817 had a clearance almost twice the rate of normal hepatic blood flow and had a relatively high volumes of distribution, indicating this compound is rapidly cleared and distributes into tissues. In vitro rat liver microsome assays suggest a rapid metabolism of 9279817 and MS/MS results suggest this metabolite is most likely formed via oxidation of the sulfur on the lower aryl ring. This sulfoxide metabolite has similar efficacy as the parent compound and does not exhibit toxicity in vitro. Three of the experimental compounds behaved similarly to the antimony positive control in the murine CL model. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study revealed a novel structural class of compounds that have anti-leishmanial activity. Experiments show compounds with similar efficacy to Miltefosine while having significantly less cytotoxicity, suggesting that the 1,4-DAPP structural class could be further developed as a potential chemotherapeutic.

OBJECTIVES/GOALS: The preclinical stage of Alzheimer disease (AD) is a clinically silent period that can be detected through neuroimaging and biofluid biomarkers. The goal of this study was to determine whether performance of complex daily tasks is associated with plasma biomarkers of brain amyloidosis or neuroaxonal injury in cognitively normal (CN) older adults. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing longitudinal cohort study. CN older adults performed three complex daily tasks (shopping, checkbook balancing, medication management) from the Performance Assessment of Self-Care Skills in their home. Tasks were scored for independence, with more assistance required indicating worse performance. Participants had a plasma sample obtained within two years of completing the tasks. Plasma amyloid (Aβ42 and Aβ40) were evaluated by high precision immunoprecipitation mass spectrometry assays and neurofilament light (NfL) was measured with single molecule array (Simoa) assays. Nonparametric partial correlations were used to quantify the associations between task performance and plasma AD biomarkers, controlling for age and gender. RESULTS/ANTICIPATED RESULTS: 105 CN participants (mean age 74.7 years, 55% female, 88% white) were included. After controlling for age and gender, worse performance of complex daily tasks (more assistance required) was associated with increased plasma NfL (Spearman’s: 0.23, p=0.04) but not plasma Aβ42/Aβ40. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks in CN older adults may be associated with increased plasma NfL a marker of neuroaxonal injury, but not with plasma amyloid. These findings could lead to a better understanding of clinical changes that may occur prior to the onset of noticeable memory symptoms in AD or related dementias.

Objectives/Goals: Highlight the importance of community engagement: Showcase how the involvement of Promotoras de Salud is critical for fostering trust and encouraging participation in clinical trials. Cultural relevance and adaptation: Underline the importance of cultural and contextual relevance in developing and refining clinical research tools. Methods/Study Population: The theater test, an interactive evaluation approach akin to a dress rehearsal in theater, was conducted with approximately 60 Promotoras de Salud at a community center near the US-Mexico border. The Promotoras were divided into four groups, each focusing on one domain of the toolkit and facilitated discussions provided critical feedback on the materials and methods. A community engagement liaison with the University of New Mexico Health Sciences Center played a key role in introducing the EXPLORE team to these community leaders, leveraging long-standing relationships that predate this project. Results/Anticipated Results: Post-testing evaluations showed that 97% of the Promotoras were likely to encourage clinical trials in their communities, and 86% saw significant benefits for their community members. The Promotoras provided key insights and recommendations to enhance the toolkit’s cultural and contextual relevance. The community engagement liaison created a bilingual infographic to share these insights, which was presented at a Promotoras meeting, fostering meaningful discussion about clinical trials. Discussion/Significance of Impact: This project underscores the importance of community voices in research, transforming feedback into actionable insights for public health. Engaging Promotoras through theater testing validated the EXPLORE Toolkit and strengthened ties between clinical research and communities impacted by the opioid crisis.

OBJECTIVES/GOALS: Congenital anomalies (CAs) affect 3% of live births, yet the cause of 80% of CAs is unknown and for the 20% with an identified cause, variability in penetrance suggests additional risk drivers exist. Our method for identifying and categorizing CAs in electronic health record (EHR) linked biobank databases can expand and improve CA etiologic research. METHODS/STUDY POPULATION: We identified individuals with CAs in three groups: 1. Those with at least one CA 2. Those with multiple CAs (MCA), those with two or more ‘major’ CAs, and 3. Those with CAs in a specific organ system. We also created a novel quantitative approach, using phenome-wide association studies (pheWAS), for determining CA-associated genetic disease billing codes in order to separate individuals that have a known genetic cause for their CAs from those with idiopathic CAs. We updated CA phecodes, aggregates of clinical billing codes, which we used to identify CA cases in Vanderbilt’s EHR-linked biobank database, BioVU. We create a new phecode, ‘All CAs’, for researchers to quickly identify all individuals with at least one CA. We evaluate the definition of MCA using pheWAS analyses to compare ‘minor’ vs ‘major’ CA. RESULTS/ANTICIPATED RESULTS: The new CA phecode nomenclature includes 5.8 times more codes for CAs compared with the previous version (365 vs 56), improving granularity. 85 (19.7%) CA-associated genetic disease billing codes were identified through literature review. PheWAS analyses revealed an additional 16 (3.7%) genetic disease billing codes with one or more significant (p< 2.75 x10-5) association with CA-related phecodes. Identifying CA-associated genetic disease billing codes allows researchers to differentiate between idiopathic CAs and those that have a known genetic cause. PheWAS analyses of individuals with previously considered “minor” CAs showed many associated severe health problems, revealing that the differentiation between “minor” vs “major” CAs when identifying individuals with MCA in the EHR is arbitrary. DISCUSSION/SIGNIFICANCE: Our CA identification method is scalable for the growing number of EHR-linked biobanks. Differentiating between idiopathic CAs from those with known causes will increase power in studies discovering additional genetic drivers of CAs. Our novel method allows for expansion and acceleration of CA epidemiological research in EHR-linked biobank data.

OBJECTIVES/GOALS: The spectrum of disease caused by SARS-CoV-2 ranges from asymptomatic detection to severe illness, with varying presentations by age. Therefore, we aimed to compare the clinical characteristics between children and adults with SARS-CoV-2. METHODS/STUDY POPULATION: From March 20, 2020, to August 18, 2021, we conducted SARS-CoV-2 surveillance in individuals from metropolitan Nashville, TN. Children with multisystem inflammatory syndrome were excluded. Analyses were restricted to individuals with SARS-CoV-2 infection confirmed by detection of viral RNA in nasal specimens using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and/or by detection of serum IgG to the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assay (ELISA). Those with negative RT-qPCR results, but a positive ELISA within 4-6 weeks of symptom onset, were classified as SARS-CoV-2 positive. Clinical characteristics between children and adults were compared with Pearson’s chi square. Illness duration was compared using Kaplan Meier estimators. RESULTS/ANTICIPATED RESULTS: Overall, 426/826 (49%) individuals (children: 57 [13%); adults: 369 [87%]) were SARS-CoV-2 positive, with median ages of 12 and 41 years, respectively. Most individuals were female (54%) and white, non-Hispanic (79%). Compared to adults, children were more likely to be asymptomatic (children: 16% vs. adults: 5%; p=0.001). In contrast, symptomatic adults were more likely to report cough (71% vs. 56%), wheezing (21% vs. 8%), shortness of breath (45% vs. 19%), ageusia (67% vs. 23%), and anosmia (64% vs 27%) than symptomatic children (p<0.05). Mean illness duration was shorter in children than adults: 7 days (95% CI: 5.1, 8.9) vs. 14 days (95% CI: 12.4,15.0), respectively. A total of 5% (18/352) of adults reported symptoms lasting ? 4 weeks (range: 31-96 days), whereas all symptoms in children resolved by 31 days. DISCUSSION/SIGNIFICANCE: Overall, children with SARS-CoV-2 present with a shorter and milder disease course compared to adults. Further studies are needed to understand SARS-CoV-2 illness severity across the lifespan.

OBJECTIVES/GOALS: Cadmium is a widespread neurotoxic metal pollutant; however prior study results of Cd and later-life cognition are mixed. We investigated association of urinary cadmium on Alzheimer’s Disease (AD) mortality risk, accounting for key co-pollutants smoking and lead, in the presence of competing risks. METHODS/STUDY POPULATION: We included 5692 persons, 60 years old from the 1998-2018 National Health and Nutrition Examination Survey. Underlying cause of death was determined via linked 1999-2019 National Death Index data. Urinary cadmium (UCD) reflects prolonged exposure and was adjusted for creatinine. We used multiple imputation (5 iterations) to recapture substantial model observation drop-out (N=782). We used three Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence interval (CI) per unit increase in UCD and time to AD mortality: a competing risks model, a survey-weighted model, and a baseline model including neither, all adjusted for demographic characteristics, lead, and smoking. RESULTS/ANTICIPATED RESULTS: Follow-up ranged from 0 to 20.8 years (mean 8.2 years), with a total of 1,987 individuals deceased (14,232 person-years at-risk), including 88 individuals dying from AD. Mean UCD was 0.50 μg/g creatinine (standard error=0.01). In baseline and survey-weighted models fully adjusted for NHANES cycle, poverty income ratio, age, race/ethnicity, sex, marital status, education, smoking status, and blood lead levels, a per unit increase in UCD was associated with approximately twice the rate of AD mortality (baseline model HR: 1.92, 95% CI: 1.28, 2.89; survey-weighted model HR: 2.08, 95% CI: 1.42, 3.06). In the competing risks model, this association was attenuated (HR: 1.58, 95% CI 1.06 2.36). DISCUSSION/SIGNIFICANCE: Our study finds chronic cadmium exposure associated with AD mortality even after accounting for competing risks of AD mortality and confounding effects of cigarette smoking and lead exposure, strengthening the evidence that long-term cadmium exposure adversely affects later-life cognitive health.

OBJECTIVES/SPECIFIC AIMS: Our research hypothesis is that resting state fMRI (rsfMRI) data can be used to identify regions of the brain which are associated with cognitive decline in patients – thereby providing a tool by which to characterize AD progression in patients. METHODS/STUDY POPULATION: We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to analyze Mini-Mental State Examination (MMSE) questionnaire scores from 14 patients diagnosed with AD at two measurement occasions. RsfMRI data was available at the first of these occasions for these patients. These rsfMRI data were summarized into 264 node-based graph theory measures of clustering coefficient and eigenvector centrality. To address our research hypothesis, we modeled changes in patient MMSE scores over time as a function of these rsfMRI data, controlling for relevant confounding factors. This model accounted for the high-dimensionality of our predictor data, the longitudinal nature of the outcome, and our desire to identify a subset of regions in the brain most associated with the MMSE outcome. RESULTS/ANTICIPATED RESULTS: The use of either the clustering coefficient or eigenvector centrality rsfMRI predictors in modeling MMSE scores for patients over time resulted in the identification of different subsets of brain regions associated with cognitive decline. This suggests that these predictors capture different information on patient propensity for cognitive decline. Further work is warranted to validate these results on a larger sample of ADNI patients. DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that different rsfMRI graph theory measures capture different aspects of cognitive function and decline in patients, which could be a future consideration in clinical practice.

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

OBJECTIVES/GOALS: Suicide is a growing public health problem with the rate of suicide increasing 33% since 1999. Physicians are not immune to this growing problem. Physicians represent a unique population that has been understudied with respect to suicide. The aim of the study is to investigate risk factors unique to physicians compared to the general population. METHODS/STUDY POPULATION: Using data from the National Violent Death Reporting System, a nationwide CDC database which aggregates information on violent deaths, we extracted demographic and circumstantial data on 172,135 suicide decedents ≥ 25 years old in participating states from 2003-2017. Of these, we found complete information regarding demographics, occupation, and circumstance for 160,159 suicide decedents. We separated suicide decedents by physician-status and compared 795 physicians to 159,364 non-physician decedents using chi-squared test. We then used multivariate logistic regression to examine differences in suicide method and circumstance by physician-status status, controlling for age, sex, and race. RESULTS/ANTICIPATED RESULTS: Compared to non-physicians, physicians were more likely to be male (84.5% vs 77.3%, p<0.001) and older (45.1% ≥65 vs. 17.8%, p<0.001). Controlling for demographics, physicians were less likely to complete suicide by firearm (aOR=0.60, 95%CI=0.51-0.71) but were more likely to suicide by overdose (aOR=1.41, 95%CI=1.13-1.77) or cutting (aOR=2.81, 95%CI=2.03-3.88). Physicians were more likely to have job related stressors (aOR=2.24, 95%Cl=1.83-2.74) and legal problems (aOR=2.34, 95%Cl=1.70-3.21). Physicians were also more likely to leave a suicide note (aOR=1.48, 95%Cl=1.26-1.73) but were less likely to be intoxicated on alcohol at time of death (aOR=0.76, 95%Cl=0.62-0.93). Physicians were no different than non-physicians in terms of financial or relational stressors. DISCUSSION/SIGNIFICANCE: Physicians are more likely to be male and older. Given their medical training, overdose and cutting may be more accessible and lethal methods for physicians. Physicians are more likely to leave a suicide note and less likely to be intoxicated, which may imply less impulsivity. Job stressors and legal problems may also contribute to physician suicide.

ABSTRACT IMPACT: Optimization of primary septal-hippocampal co-cultures facilitates studying central cholinergic synapse formation and dysfunction OBJECTIVES/GOALS: Septal cholinergic innervation to the hippocampus is critical for normal learning and memory and is severely degenerated in Alzheimer’s disease. To understand the molecular events underlying this loss, we optimized a primary septal-hippocampal co-culture system that facilitates the study of central cholinergic synapses. METHODS/STUDY POPULATION: We developed an optimized in vitro septal-hippocampal co-culture system modified from previously published protocols. Briefly, hippocampal and septal tissue were harvested from embryonic day 19 (E19) Sprague-Dawley rats, digested with 0.1% trypsin, and an equal number of cells from each region plated onto coverslips coated with poly-D-lysine and laminin at a final density of 300 cells/mm2. We use immunostaining with validated primary antibodies and a fluorescent binding assay, together with confocal microscopy, to determine the structure of cholinergic synapses that are 1) native, 2) mammalian, 3) CNS derived, 4) comprised of physiological synaptic partners, and 5) developmentally mature. RESULTS/ANTICIPATED RESULTS: After DIV21, co-cultures maintained a healthy morphology. A subpopulation of neurons strongly expressed the cholinergic markers vesicular ACh transporter (vAChT), choline acetyltransferase (ChAT), and the high-affinity choline transporter (ChT1), whereas most neurons lacked vAChT expression and were presumably glutamatergic or GABAergic. The percentage of cholinergic neurons attained in the co-culture is ˜5-7%. The size of these cholinergic neurons is strikingly similar to that reported for BFCNs in the intact brain (mean 30μm, range 18-43μm). All sampled cholinergic neurons (28/28 neurons) also expressed molecular machinery necessary for GABA release. Staining for a cholinergic postsynaptic marker shows that 63% of the contacts made with are synaptic. DISCUSSION/SIGNIFICANCE OF FINDINGS: Primary septal-hippocampal co-cultured neurons have not been exploited extensively in the field, perhaps due to the difficulty in maintaining such cultures for extended periods. Here, we optimized an in vitro septal-hippocampal co-culture system, a powerful tool to comprehensively analyze central cholinergic synapse formation and dysfunction.

OBJECTIVES/GOALS: Multiple induction agents can facilitate rapid sequence intubation (RSI) in management of refractory status epilepticus (rSE), many which have anti-seizure properties. We examine the anti-seizure efficacy and safety of induction agents used during RSI in the management of rSE. METHODS/STUDY POPULATION: We conducted a single-center retrospective review of patients admitted to the neuro-ICU intubated for management of rSE. Propofol, ketamine and benzodiazepines were considered anti-seizure medication (ASMs), etomidate was not. Patients were treated with propofol or midazolam following intubation. Our primary outcome was clinical or electrographic recurrence of SE within 12 hours of intubation. Exploratory outcomes included time to recover command following, duration of mechanical ventilation (MV) and complications related to intubation. We used multivariable logistical regression to evaluate outcomes between patients induced with ASMs and etomidate. A Fisher exact test was used to compare rSE cessation in a subset of patients with continuous electroencephalography (cEEG) at the time of intubation. RESULTS/ANTICIPATED RESULTS: We identified 149 induced for RSI in management of rSE: 88 patients intubated using ASMs (propofol,n=56; ketamine,n=14; benzodiazepines,n=18) and 61 patients intubated with etomidate. Forty-one patients had recurrence (29.9% ASMS, 24.6% etomidate). The induction agent was not associated with recurrence of SE, time to command following, or duration of MV. Twenty-seven patients had cEEG monitoring at the time of intubation. Sixteen of the 22 patients induced with ASMs had cessation of rSE with induction, while 1 of 5 intubated with etomidate had cessation (Fisher exact test, p=0.047). There were 34 patients with post-induction hypotension (22.9% ASMs, 22.9% etomidate (Fisher exact test, p=1)). DISCUSSION/SIGNIFICANCE: Induction with an anti-seizure medication during intubation was more likely to halt rSE, but did not decrease the likelihood of clinical or electrographic recurrence of rSE and may not affect time to recovery of command following or duration of MV.

OBJECTIVES/GOALS: Platform trials gain efficiency by sharing placebo controls among different study arms. However, the varying routes of administration make it unclear whether participants exposed to different placebos have similar outcomes. As such, we seek to compare outcomes between participants receiving tablet and inhaler placebos in the ACTIV-6 trial. METHODS/STUDY POPULATION: ACTIV-6 is a large, decentralized platform trial exploring repurposed drugs for the treatment of adults with mild to moderate COVID-19. Enrolled participants were randomly assigned to a study arm vs. placebo and then mailed the study drug. They were monitored until symptom resolution or Day 28. Here, we compare outcomes for control participants contributing to the fluticasone furoate study arm, in which 251 were assigned to a tablet placebo and 370 an inhaler placebo. Time to sustained recovery and time to resolution of individual symptoms are compared between groups using Kaplan-Meier curves and unadjusted log-rank tests. A step-down procedure is applied to control the false discovery rate. RESULTS/ANTICIPATED RESULTS: Control participants assigned to tablet placebos had shorter time to sustained recovery (adjusted hazard ratio (HR) 1.34 (95% CI 1.11, 1.62)). When examining each of the eleven individually reported symptoms on study Day 14, nasal symptoms (adjusted odds ratio (OR) 0.44 (0.27, 0.72), p<0.01), dyspnea (OR 0.44 (0.22, 0.87), p = 0.02), and cough (OR 0.54 (0.35, 0.83), p<0.01) were identified as symptoms in which the tablet-placebo group performed notably better than those who received inhaler-placebos. In the follow-up, longitudinal analysis, we anticipate similar results. DISCUSSION/SIGNIFICANCE: Among ACTIV-6 control participants, those receiving a tablet placebo had a significantly shorter time to sustained recovery than those receiving an inhaler placebo. Platform trials using shared controls should consider efficiency in the context of the additional variability when sharing controls with a different route of administration.

OBJECTIVES/SPECIFIC AIMS: Retinitis pigmentosa (RP) is a hereditary retinal degeneration disease that affects ~1 in 4000 individuals globally, and there are currently no effective treatment options available. In order to identify potential drug treatments, we optimized our existing a behavioral assay around a transgenic zebrafish carrying a truncated human rhodopsin transgene [Tg(rho:Hsa.RH1_Q344X)]. This line was also crossed with the Tg(-3.7rho:EGFP) reporter for rod visualization. The Q344X larvae experiences significant rod photoreceptor death by 7 days postfertilization (dpf) (Nakao et al., 2012). METHODS/STUDY POPULATION: To assess the vision of the Q344X zebrafish, the VMR assay was run under a dim-light condition based on recorded rod b-waves in larval fish (Moyano et al., 2013) and the minimum cone activation threshold in mice (Cachafeiro et al., 2010). Specifically, Q344X and control larvae at 7 dpf were placed into a 96-well plate and acclimated to a dim-light source (1.802e-05 μ W/cm2 at 500 nm) for 1 hour. The VMR was tracked and quantified during light offset. The total distance traveled was averaged and analyzed at 1 second poststimulus. Retinas were dissected from Q344X and control larvae and whole-mounted to validate the rod degeneration in the Q344X model. RESULTS/ANTICIPATED RESULTS: We found that the Q344X larvae displayed an attenuated VMR (0.121±0.041 cm) to the dim-light offset as compared with the control larvae (0.2751±0.038 cm) (two-sample t-test; p-value=4.619e-14, n=19). Analysis of whole-mounted retinae indicated significant rod degeneration at 7 dpf compared with controls (control: 87 rods/retina, Q344X: 9.3 rods/retina, Welch two-sample t-test, p-value=1.4e4). It is unlikely that the cones of the zebrafish contributed to this VMR since the light intensity of the assay was below the cone detection threshold of mice. As the only apparent difference between the 2 groups of larvae is significant rod degeneration, it can be concluded that the behavioral phenotype was a result of the degeneration. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the attenuated Q344X VMR is a result of the rod photoreceptor death. This behavioral phenotype can be taken advantage of to develop a drug screening assay. Future steps will screen chemical libraries to identify compounds that ameliorate the rod degeneration. Compounds that prevent degeneration are expected to result in a significant increase in locomotion in response to the dim visual stimulus.

Navigating the research domain at an academic medical center can be challenging, even for seasoned investigators. To address this, Duke University launched two initiatives: (1) a research navigation “hotline” to provide brief assistance with a variety of research questions; and (2) researcher onboarding and consultation, a one-to-one tailored offering to ensure that researchers are equipped to navigate research resources and processes effectively. The services are provided by the myRESEARCHnavigators (MRN) team, funded by Duke’s CTSA. The diverse scientific backgrounds of the six team members align well with those of the research community, allowing for a good match between the researcher and MRN team member. The MRN team answers approximately 30 questions per month, and has provided consultations to almost 400 researchers. Both services receive high satisfaction ratings (4 or 5 stars [out of 5 stars] given to 90% of hotline answers, and 99% of researcher onboarding/consultation sessions). As of July 2019, the School of Medicine has determined that the consultations are critical to their mission and have made them a requirement for new research faculty. The team will continue marketing both services to encourage adoption.

Given the rapidly progressing coronavirus disease 2019 (COVID-19) pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is highly important and immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome, and admission to the intensive care unit, and also replicated data from China suggesting an association between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease.

When the emergency committee of the World Health Organization declared that the outbreak of COVID-19 meets the criteria of a “Public Health Emergency of International Concern” on January 30th, 2020, no one could ever imagine how soon it will spread globally, and a health crisis would turn to a social crisis that affects everything including higher education. However, during this uncertainty, Tehran University of Medical Sciences (TUMS) tried to respond quickly. In this study, we explain how a nerve center has helped TUMS respond to this crisis and ensure safety to keep key operations going, and set up a functional decision-making system for the future. We also share perspectives on the critical issues, the challenges ahead, and the opportunities emerging in the “new normal.”