There is little data describing trends in the use of hydroxychloroquine for COVID-19 following publication of randomized trials that failed to demonstrate a benefit of this therapy. We identified 13,957 patients admitted for active COVID-19 at 85 U.S. hospitals participating in a national registry between March 1 and August 31, 2020. The overall proportion of patients receiving hydroxychloroquine peaked at 55.2% in March and April and decreased to 4.8% in May and June and 0.8% in July and August. At the hospital-level, median use was 59.4% in March and April (IQR 48.5-71.5%, range 0-100%) and decreased to 0.3% (IQR 0-5.4%, range 0-100%) by May and June and 0% (IQR 0-1.3%, range 0-36.4%) by July and August. The rate and hospital-level uniformity in deimplementation of this ineffective therapy for COVID-19 reflects a rapid response to evolving clinical information and further study may offer strategies to inform deimplementation of ineffective clinical care.Magnetic nanorobots (MNRs) based on paramagnetic nanoparticles/nanoclusters for the targeted therapeutics of anticancer drugs have been highlighted for their efficiency potential. Controlling the locomotion of the MNRs is a key challenge for effective delivery to the target legions. Here, we present a method for controlling paramagnetic nanoclusters through enhanced tumbling and disaggregation motions with a combination of rotating field and gradient field generated by external electromagnets. The mechanism is carried out via an electromagnetic actuation system capable of generating MNR motions with five degrees of freedom in a spherical workspace without singularity. The nanocluster swarm structures can successfully pass through channels to the target region where they can disaggregate. The results show significantly faster response and higher targeting rate by using rotating magnetic and gradient fields. The mean velocities of the enhanced tumbling motion are twice those of the conventional tumbling motion and approximately 130% higher than the gradient pulling motion. The effects of each fundamental factor on the locomotion are investigated for further MNR applications. The locomotion speed of the MNR could be predicted by the proposed mathematical model and agrees well with experimental results. The high access rate and disaggregation performance insights the potentials for targeted drug delivery application.Quantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3-5 h and then migrate to the liver and spleen for up to 2-3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.The estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.In this work, the optical properties of asymmetric nanoshells with different geometries are comprehensively investigated in the quasi-static regime by applying the dipolar model and effective medium theory. The plasmonic behaviors of these nanostructures are explained by the plasmon hybridization model. Asymmetric hybrid nanoshells, composed of off-center core or nanorod core surrounded by a spherical metallic shell layer possess highly geometrically tunable optical resonances in the near-infrared regime. click here The plasmon modes of this nanostructures arise from the hybridization of the cavity and solid plasmon modes at the inner and outer surfaces of the shell. The results reveal that the symmetry breaking drastically affects the strength of hybridization between plasmon modes, which ultimately affects the absorption spectrum by altering the number of resonance modes, their wavelengths and absorption efficiencies. Therefore, offsetting the spherical core as well as changing the internal geometry of the nanoparticle to nanorod not only shift the resonance frequencies but can also strongly modify the relative magnitudes of the absorption efficiencies.