ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines.

IntroductionBreast cancer detection using mammography has improved clinical outcomes for many women, because mammography can detect very small (5 mm) tumors early in the course of the disease. However, mammography fails to detect 10 - 25% of tumors, and the results do not distinguish benign and malignant tumors. Reducing the false positive rate, even by a modest 10%, while improving the sensitivity, will lead to improved screening, and is a desirable and attainable goal. The emerging application of magnetic relaxometry, in particular using superconducting quantum interference device (SQUID) sensors, is fast and potentially more specific than mammography because it is designed to detect tumor-targeted iron oxide magnetic nanoparticles. Furthermore, magnetic relaxometry is theoretically more specific than MRI detection, because only target-bound nanoparticles are detected. Our group is developing antibody-conjugated magnetic nanoparticles targeted to breast cancer cells that can be detected using magnetic relaxometry.MethodsTo accomplish this, we identified a series of breast cancer cell lines expressing varying levels of the plasma membrane-expressed human epidermal growth factor-like receptor 2 (Her2) by flow cytometry. Anti-Her2 antibody was then conjugated to superparamagnetic iron oxide nanoparticles using the carbodiimide method. Labeled nanoparticles were incubated with breast cancer cell lines and visualized by confocal microscopy, Prussian blue histochemistry, and magnetic relaxometry.ResultsWe demonstrated a time- and antigen concentration-dependent increase in the number of antibody-conjugated nanoparticles bound to cells. Next, anti Her2-conjugated nanoparticles injected into highly Her2-expressing tumor xenograft explants yielded a significantly higher SQUID relaxometry signal relative to unconjugated nanoparticles. Finally, labeled cells introduced into breast phantoms were measured by magnetic relaxometry, and as few as 1 million labeled cells were detected at a distance of 4.5 cm using our early prototype system.ConclusionsThese results suggest that the antibody-conjugated magnetic nanoparticles are promising reagents to apply to in vivo breast tumor cell detection, and that SQUID-detected magnetic relaxometry is a viable, rapid, and highly sensitive method for in vitro nanoparticle development and eventual in vivo tumor detection.

A new method is presented for quantitative mapping of ventilation-to-perfusion ratios (V A /Q) in the lung: MRI of the 19 F longitudinal relaxation time (T 1 ) of an inert fluorinated gas at thermal polarization. The method takes advantage of the dependence of the 19 F T 1 on the local SF 6 partial pressure, which depends on the local value of V A /Q. In contrast to hyperpolarized noble gases, with very long T 1 s, the T 1 of SF 6 in mammal lungs is 0.8 -1.3 ms. Thus, rapid signal averaging overcomes the low thermal equilibrium polarization. T 1 imaging of a phantom consisting of four different SF 6 /air mixtures with known T 1 values validates the modified Look-Locker T 1 imaging sequence. To demonstrate the method in vivo, partial obstruction of the left bronchus was attempted in three rats; 3D free induction decay (FID)-projection T 1 images (2 mm isotropic resolution) revealed obstructed ventilation in two of the animals. In those images, Ϸ1700 lung voxels contained sufficient SF 6 for analysis and T 1 was determined in each voxel with a standard error of 8 -10%. For comparison, independent V A /Q images of the same animals were obtained using a previously described SF 6 MRI technique, and good agreement between the two techniques was obtained. Relative to the previous technique the resolution achieved using the T 1 method is lower (for similar V A /Q precision and imaging time); however, the T 1 method offers the potential advantages of eliminating the need for image coregistration and allowing patients with impaired lung function to breathe a 70% O 2 gas mixture during the entire imaging procedure. A crucial feature of a well-functioning lung is the locationby-location matching of ventilation (V A , gas replacement rate, L/min) and perfusion (Q, blood flow rate, L/min), which ensures that the arterial blood is fully oxygenated (1). The dimensionless ventilation-to-perfusion ratio (V A /Q) is therefore a key parameter for characterizing lung function. In healthy lungs the narrow distribution of V A /Q values is log normal, with a mean of Ϸ0.85, and a width (standard deviation [SD] of log V A /Q) of 0.15-0.30 (2,3). In lung disease the average V A /Q value may change, but of more importance is the increase in the width of the distribution of V A /Q values (i.e., V A and Q become mismatched in an increasing volume of the lung). In diseases such as chronic obstructive pulmonary disease (COPD) and asthma, obstructed ventilation results in regions of belownormal V A /Q. These regions are particularly important because there is significant blood flow, but the blood is not fully oxygenated before entering the arterial system, reducing arterial blood oxygen levels. Because of the critical importance of the heterogeneity of V A /Q in characterizing lung function, noninvasive methods capable of quantifying the spatial variation of V A and V A /Q are desired to enable a more detailed understanding of the progression and treatment of lung disease. In this article we present a new technique for quantitative mapping of v...

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