Search

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Online instructional delivery has always been viewed as beneficial due to its flexibility in settings and times, but the COVID-19 pandemic produced an essential need for the ability to engage in learning without direct contact with others. For students with Autism Spectrum Disorder and Intellectual Disability (ASD and ID) who have extensive support needs, developing the skills required to engage with online content is critical for utilizing and interacting with distance learning platforms and resources. Using a visual task analysis, least-to-most prompting, and reinforcement, students with ASD and ID can be taught to use technological devices for virtual instruction without adult support. By teaching students to access and use point-of-view video modeling for online instructional delivery, teachers can facilitate skills their students need to access evidence-based practices and meet diverse learning goals and objectives.

In this paper, an application of open-ended textual feedback is presented as a tool to evaluate the perceptions and needs of teachers tasked with implementing computational thinking in the K-12 curriculum. Semantic analysis tools, including sentiment analysis and thematic analysis, facilitated the identification of common themes in openended textual feedback. Results show that semantic analysis techniques can be useful in evaluating formative assessment data or open-ended feedback to discover response patterns, which may aid in determining actionable insights related to adult learner perceptions, interests, and self-efficacy. Formative assessment data were collected from a unique professional development workshop to promote computational thinking and curriculum integration in core subjects, including writing, math, science, and social studies, with the goal of discovering the barriers that rural teachers face in developing and implementing lesson plans for grades 3-8 teachers in a rural midwestern state in the USA to promote computational thinking and curriculum integration in core subjects, including writing, math, science, and social studies, with the goal of discovering the barriers that rural teachers face in developing and implementing lesson plans.

Many machine learning techniques are used as drug discovery tools with the intent to speed characterization by determining relationships between compound structure and biological function. However, particularly in anticancer drug discovery, these models often make only binary decisions about the biological activity for a narrow scope of drug targets. We present a feed-forward neural network, PECAN (Prediction Engine for the Cytostatic Activity of Natural product-like compounds), that simultaneously classifies the potential antiproliferative activity of compounds against 59 cancer cell lines. It predicts the activity to be one of six categories, indicating not only if activity is present but the degree of activity. Using an independent subset of NCI data as a test set, we show that PECAN can reach 60.1% accuracy in a six-way classification and present further evidence that it classifies based on useful structural features of compounds using a within-one measure that reaches 93.0% accuracy.

The PI3K enzymes modify phospholipids to regulate cell growth and differentiation. Somatic variants in PI3K are recurrent in cancer and drive a proliferative phenotype. Somatic mosaicism of PIK3R1 and PIK3CA are associated with vascular anomalies and overgrowth syndromes. Germline PIK3R1 variants are associated with varying phenotypes, including immunodeficiency or facial dysmorphism with growth delay, lipoatrophy, and insulin resistance associated with SHORT syndrome. There has been limited study of the molecular mechanism to unify our understanding of how variants in PIK3R1 drive both undergrowth and overgrowth phenotypes. Thus, we compiled genomic variants from cancer and rare vascular anomalies and sought to interpret their effects using an unbiased physics-based simulation approach for the protein complex. We applied molecular dynamics simulations to mechanistically understand how genetic variants affect PIK3R1 and its interactions with PIK3CA. Notably, iSH2 genetic variants associated with undergrowth destabilize molecular interactions with the PIK3CA receptor binding domain in simulations, which is expected to decrease activity. On the other hand, overgrowth and cancer variants lead to loss of inhibitory interactions in simulations, which is expected to increase activity. We find that all disease variants display dysfunctions on either structural characteristics or intermolecular interaction energy. Thus, this comprehensive characterization of novel mosaic somatic variants associated with two opposing phenotypes has mechanistic importance and biomedical relevance and may aid in future therapeutic developments.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Abstract PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants—for example how they affect gene expression profiles—remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome.

Abstract Recognition of viral infection often relies on the detection of double-stranded RNA (dsRNA), a process that is conserved in many different organisms. In mammals, proteins such as MDA5, RIG-I, OAS, and PKR detect viral dsRNA, but struggle to differentiate between viral and endogenous dsRNA. This study investigates an shRNA targeting DDX54’s potential to activate PKR, a key player in the immune response to dsRNA. Knockdown of DDX54 by a specific shRNA induced robust PKR activation in human cells, even when DDX54 is overexpressed, suggesting an off-target mechanism. Activation of PKR by the shRNA was enhanced by knockdown of ADAR1, a dsRNA binding protein that suppresses PKR activation, indicating a dsRNA-mediated mechanism. In vitro assays confirmed direct PKR activation by the shRNA. These findings emphasize the need for rigorous controls and alternative methods to validate gene function and minimize unintended immune pathway activation.

Seminal fluid extracellular vesicles (SFEVs) have previously been shown to interact with spermatozoa and influence their fertilisation capacity. Here, we sought to extend these studies by exploring the functional consequences of SFEV interactions with human spermatozoa. SFEVs were isolated from the seminal fluid of normozoospermic donors prior to assessing the kinetics of sperm-SFEV binding in vitro, as well as the effects of these interactions on sperm capacitation, acrosomal exocytosis, and motility profile. Biotin-labelled SFEV proteins were transferred primarily to the flagellum of spermatozoa within minutes of co-incubation, although additional foci of SFEV biotinylated proteins also labelled the mid-piece and head domain. Functional analyses of high-quality spermatozoa collected following liquefaction revealed that SFEVs did not influence sperm motility during incubation at pH 5, yet SFEVs induced subtle increases in total and progressive motility in sperm incubated with SFEVs at pH 7. Additional investigation of sperm motility kinematic parameters revealed that SFEVs significantly decreased beat cross frequency and increased distance straight line, linearity, straightness, straight line velocity, and wobble. SFEVs did not influence sperm capacitation status or the ability of sperm to undergo acrosomal exocytosis. Functional assessment of both high- and low-quality spermatozoa collected prior to liquefaction showed limited SFEV influence, with these vesicles inducing only subtle decreases in beat cross frequency in spermatozoa of both groups. These findings raise the prospect that, aside from subtle effects on sperm motility, the encapsulated SFEV cargo may be destined for physiological targets other than the male germline, notably the female reproductive tract. Lay Summary A male’s influence over the biological processes of pregnancy extends beyond the provision of sperm. Molecular signals present in the ejaculate can influence the likelihood of pregnancy and healthy pregnancy progression, but the identity and function of these signals remain unclear. In this study, we wanted to understand if nano-sized particles present in the male ejaculate, called seminal fluid extracellular vesicles, can assist sperm in traversing the female reproductive tract to access the egg. To explore this, we isolated seminal fluid extracellular vesicles from human semen and incubated them with sperm. Our data showed that seminal fluid extracellular vesicles act to transfer molecular information to sperm, but this resulted in only subtle changes to the movement of sperm.

Abstract Single crystal paleointensity (SCP) reveals that the Moon lacked a long-lived core dynamo, though mysteries remain. An episodic dynamo, seemingly recorded by some Apollo basalts, is temporally and energetically problematic. We evaluate this enigma through study of ~3.7 billion-year-old (Ga) Apollo basalts 70035 and 75035. Whole rock analyses show unrealistically high nominal magnetizations, whereas SCP indicate null fields, illustrating that the former do not record an episodic dynamo. However, deep crustal magnetic anomalies might record an early lunar dynamo. SCP studies of 3.97 Ga Apollo breccia 61016 and 4.36 Ga ferroan anorthosite 60025 also yield null values, constraining any core dynamo to the Moon’s first 140 million years. These findings suggest that traces of Earth’s Hadean atmosphere, transferred to the Moon lacking a magnetosphere, could be trapped in the buried lunar regolith, presenting an exceptional target for future exploration.

In England and Wales, diocesan inspectors are charged with assessing the overall quality of Catholic education provided by Catholic schools. As part of this assessment, inspectors are required to give an account of the liturgical life of the school. Often the reports which result from these inspections refer to the degree of students' "active participation" in liturgy. This terminology has its roots in Biblical and patristic theological literature. Its meaning has evolved over time and has been used to describe a wide range of seemingly diffuse human behaviours. This article casts light on the meaning of "active participation" in the context of Diocesan inspectors and offers some reflections on how this term could be refined in order to make diocesan inspections more informative.

The identification of molecular structure is essential for understanding chemical diversity and for developing drug leads from small molecules. Nevertheless, the structure elucidation of small molecules by Nuclear Magnetic Resonance (NMR) experiments is often a long and non-trivial process that relies on years of training. To achieve this process efficiently, several spectral databases have been established to retrieve reference NMR spectra. However, the number of reference NMR spectra available is limited and has mostly facilitated annotation of commercially available derivatives. Here, we introduce DeepSAT, a neural network-based structure annotation and scaffold prediction system that directly extracts the chemical features associated with molecular structures from their NMR spectra. Using only the 1H-13C HSQC spectrum, DeepSAT identifies related known compounds and thus efficiently assists in the identification of molecular structures. DeepSAT is expected to accelerate chemical and biomedical research by accelerating the identification of molecular structures.

Abstract The absence or presence of a lunar paleomagnetosphere is important because it bears directly on the volatile content of the regolith and exploration targets for Artemis and other missions to the Moon. Recent paleointensity study of samples from the Apollo missions has readdressed this question. Multiple specimens from a young 2-million-year-old glass shows a strong magnetization compatible with that induced by charge-separation in an impact plasma, whereas paleointensities of single crystals yield evidence for null magnetizations spanning 3.9 to 3.2 Ga. Together, these data are consistent with an impact mechanism for the magnetization of some lunar samples, and absence of a long-lived lunar core dynamo and paleomagnetosphere recorded in other samples. Here, we present a dataset that allows researchers to examine replicates of these measurements. For the glass, we present data from specimens that fail standard paleointensity selection criteria but nevertheless imply a complex, changing magnetic field environment. For the single crystals, the replicate measurements further illustrate the initial zero magnetization state of these materials.

Abstract Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

Abstract Background Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection. Methods A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection. Results A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%–78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%). Conclusion Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects. Trial registration NCT06170320 (retrospectively registered on December 21, 2023).

Abstract Background The joint evidence of the cost and the effectiveness of family-based therapies is modest. Objective To study the cost-effectiveness of family therapy (FT) versus treatment-as-usual (TAU) for young people seen after self-harm combining data from an 18-month trial and hospital records up to 60-month from randomisation. Methods We estimate the cost-effectiveness of FT compared to TAU over 5 years using a quasi-Markov state model based on self-harm hospitalisations where probabilities of belonging in a state are directly estimated from hospital data. The primary outcome is quality-adjusted life years (QALY). Cost perspective is NHS and PSS and includes treatment costs, health care use, and hospital attendances whether it is for self-harm or not. Incremental cost-effectiveness ratios are calculated and deterministic and probabilistic sensitivity analyses are conducted. Results Both trial arms show a significant decrease in hospitalisations over the 60-month follow-up. In the base case scenario, FT participants incur higher costs (mean +£1,693) and negative incremental QALYs (-0.01) than TAU patients. The associated ICER at 5 years is dominated and the incremental health benefit at the £30,000 per QALY threshold is -0.067. Probabilistic Sensitivity Analysis finds the probability that FT is cost-effective is around 3 − 2% up to a maximum willingness to pay of £50,000 per QALY. This suggest that the extension of the data to 60 months show no difference in effectiveness between treatments. Conclusion Whilst extended trial follow-up from routinely collected statistics is useful to improve the modelling of longer-term cost-effectiveness, FT is not cost-effective relative to TAU and dominated in a cost-utility analysis.

Abstract Earth’s magnetic field was in a highly unusual state when macroscopic animals of the Ediacara Fauna diversified and thrived. Any connection between these events is tantalizing but unclear. Here, we present single crystal paleointensity data from 2054 and 591 Ma pyroxenites and gabbros that define a dramatic intensity decline, from a strong Proterozoic field like that of today, to an Ediacaran value 30 times weaker. The latter is the weakest time-averaged value known to date and together with other robust paleointensity estimates indicate that Ediacaran ultra-low field strengths lasted for at least 26 million years. This interval of ultra-weak magnetic fields overlaps temporally with atmospheric and oceanic oxygenation inferred from numerous geochemical proxies. This concurrence raises the question of whether enhanced H ion loss in a reduced magnetic field contributed to the oxygenation, ultimately allowing diversification of macroscopic and mobile animals of the Ediacara Fauna.

Plate tectonics is a fundamental factor in the sustained habitability of Earth, but its time of onset is unknown, with ages ranging from the Hadaean to Proterozoic eons1-3. Plate motion is a key diagnostic to distinguish between plate and stagnant-lid tectonics, but palaeomagnetic tests have been thwarted because the planet's oldest extant rocks have been metamorphosed and/or deformed4. Herein, we report palaeointensity data from Hadaean-age to Mesoarchaean-age single detrital zircons bearing primary magnetite inclusions from the Barberton Greenstone Belt of South Africa5. These reveal a pattern of palaeointensities from the Eoarchaean (about 3.9 billion years ago (Ga)) to Mesoarchaean (about 3.3 Ga) eras that is nearly identical to that defined by primary magnetizations from the Jack Hills (JH; Western Australia)6,7, further demonstrating the recording fidelity of select detrital zircons. Moreover, palaeofield values are nearly constant between about 3.9 Ga and about 3.4 Ga. This indicates unvarying latitudes, an observation distinct from plate tectonics of the past 600 million years (Myr) but predicted by stagnant-lid convection. If life originated by the Eoarchaean8, and persisted to the occurrence of stromatolites half a billion years later9, it did so when Earth was in a stagnant-lid regime, without plate-tectonics-driven geochemical cycling.

This mixed methods research design focuses on post-secondary institutions in Saskatchewan, Canada, its employees' experiences of working remotely, and the impact of the global COVID-19 pandemic on school leadership. Presented are the perceived challenges as well as the benefits of the "new" workplace since the COVID-19 crisis. Administrative and instructional leadership had changed dramatically. Most identified their quality of work as better or the same because of having fewer distractions, interruptions, and less wasted time at the workplace. The participants' interviews and survey responses describe the necessary adaptation, flexibility, mental health and wellness, accountability, workload intensification, and future expectations of the workplace and leadership once the pandemic is over.

Background: Women experiencing substance use during their pregnancies or after the birth of a child report being fearful of losing their children based on care, stigmatized when seeking assistance, and barriers to care such as having to provide the same information to different providers, and having to repeat their lived experiences with substance use in detail. Particularly these service barriers can be confusing, complicated, and difficult to follow, which could lead to non-compliance or not seeking services. Objectives: We evaluated components of a service coordination program for women experiencing substance use, their children, and larger families who help with caregiving. We examined stakeholder interest in the program, feasibility providing services over time, and initial program effectiveness. Design: Participant enrollment and outcomes as well as service coordination activities provided over a 4-year period was gathered across three demonstration site locations (a birthing hospital, reunification program, and home visiting program). Methods: Program information was gathered from needs assessment data, health survey data from enrolled caregivers and infants, training evaluations, and budget recordings of direct aid. In this mixed method design, we examined potential differences between baseline and the last assessment for women and children enrolled in the program. We also utilized univariate analyses of variance to examine the main effects of maternal and infant characteristics on final maternal and infant outcomes. Results: Three sites enrolled 182 women and families for program services. Patient navigators provided direct aid, training, goal setting, and service coordination and planning. Families remained in the program, on average, 655 days and were satisfied with the services received. Respondents thought the program elements were easy to implement within the rural setting. The program effectively addressed basic needs, violence ( p

I had the privilege to learn from Dr Sharon Henry, the American Association for the Surgery of Trauma (AAST) vice president, over the past year as the AAST Associate Membership Mentoring Scholarship recipient. This essay serves as a reflection on my year and was presented at the 2024 AAST Annual Meeting. Mentorship breaks down into two stages: finding a mentor and keeping a mentor. Finding a mentor can occur through a formal mentorship process or relationships formed organically. It takes a connection between two people and time for a relationship to form. Keeping a mentor takes effort and intentionality. Mentorship doesn’t end when the scholarship does. It is fluid, without direction, without a timeline, and it will evolve. It will take effort and intention to keep a mentor, but the reward is so great for all that effort put in. Often, what we receive out of mentorship cannot be quantified but the impact is profound.

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.