Background Pregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this increased morbidity and its potential effect on the developing fetus is not well understood. Methods We assessed placental histology, ACE2 expression, and viral and immune dynamics at the term placenta in pregnant women with and without respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Findings The majority (13 of 15) of placentas analyzed had no detectable viral RNA. ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term, suggesting that low ACE2 expression may protect the term placenta from viral infection. Using immortalized cell lines and primary isolated placental cells, we found that cytotrophoblasts, the trophoblast stem cells and precursors to syncytiotrophoblasts, rather than syncytiotrophoblasts or Hofbauer cells, are most vulnerable to SARS-CoV-2 infection in vitro . To better understand potential immune mechanisms shielding placental cells from infection in vivo , we performed bulk and single-cell transcriptomics analyses and found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited robust immune responses, including increased activation of natural killer (NK) and T cells, increased expression of interferon-related genes, as well as markers associated with pregnancy complications such as preeclampsia. Conclusions SARS-CoV-2 infection in late pregnancy is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. Funding NIH (T32GM007205, F30HD093350, K23MH118999, R01AI157488, U01DA040588) and Fast Grant funding support from Emergent Ventures at the Mercatus Center.

Radiomics has shown promise in improving models for predicting patient outcomes. However, to maximize the information gain of the radiomics features, especially in larger patient cohorts, the variability in radiomics features owing to differences between scanners and scanning protocols must be accounted for. To this aim, the imaging variability of radiomics feature values was evaluated on 100 computed tomography scanners at 35 clinics by imaging a radiomics phantom using a controlled protocol and the commonly used chest and head protocols of the local clinic. We used a linear mixed-effects model to determine the degree to which the manufacturer and individual scanners contribute to the overall variability. Using a controlled protocol reduced the overall variability by 57% and 52% compared to the local chest and head protocols respectively. The controlled protocol also reduced the relative contribution of the manufacturer to the total variability. For almost all variabilities (manufacturer, scanner, and residual with different preprocesssing), the controlled protocol scans had a significantly smaller variability than the local protocol scans did. For most radiomics features, the imaging variability was small relative to the inter-patient feature variability in non–small cell lung cancer and head and neck squamous cell carcinoma patient cohorts. From this study, we conclude that using controlled scans can reduce the variability in radiomics features, and our results demonstrate the importance of using controlled protocols in prospective radiomics studies.

There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer’s disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, obesity-associated inflammatory cytokines, and obesity-associated gut hormones have been associated with learning, memory, and general cognitive function. To date, examination of obesity-associated biology with brain function has primarily occurred in animal models. The few studies examining such biologically-mediated pathways in adult humans have corroborated the animal data, but this body of work has gone relatively unrecognized by the pediatric literature. Despite the fact that differences in these biomarkers have been found in association with obesity in children, the possibility that obesity-related biology could affect brain development in children has not been actively considered. We review obesity-associated biomarkers that have shown associations with neurocognitive skills, specifically executive functioning skills which have far-reaching implications for child development. Understanding such gut-brain associations early in the lifespan may yield unique intervention implications.

Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro. Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (∼13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.

Doxorubicin-loaded hollow nanoshells (Dox@PEG-HAuNS) increases the efficacy of photothermal ablation (PTA) by not only mediating efficient PTA but also through chemotherapy, and therefore have potential utility for local anticancer therapy. However, in vivo real-time monitoring of Dox release and temperature achieved during the laser ablation technique has not been previously demonstrated before. In this study, we used fluorescence optical imaging to map the release of Dox from Dox@PEG-HAuNS and photoacoustic imaging to monitor the tumor temperature achieved during near-infrared laser–induced photothermal heating in vitro and in vivo. In vitro, treatment with a 3-W laser was sufficient to initiate the release of Dox from Dox@PEG-HAuNS (1:3:1 wt/wt, 1.32×1012 particles/mL). Laser powers of 3 and 6 W achieved ablative temperatures of more than 50 °C. In 4T1 tumor–bearing nude mice that received intratumoral or intravenous injections of Dox@PEG-HAuNS, fluorescence optical imaging (emission wavelength = 600 nm, excitation wavelength = 500 nm) revealed that the fluorescence intensity in surface laser–treated tumors 24 h after treatment was significantly higher than that in untreated tumors (p=0.015 for intratumoral, p=0.008 for intravenous). Similar results were obtained using an interstitial laser to irradiate tumors following the intravenous injection of Dox@PEG-HAuNS (p=0.002 at t=24h). Photoacoustic imaging (acquisition wavelength = 800 nm) revealed that laser treatment caused a substantial increase in tumor temperature, from 37 °C to ablative temperatures of more than 50 °C. Ex vivo analysis revealed that the fluorescence intensity of laser-treated tumors was twice as high as that of untreated tumors (p=0.009). Histological analysis confirmed that intratumoral injection of Dox@PEG-HAuNS and laser treatment caused significantly more tumor necrosis compared to tumors that were not treated with laser (p<0.001). On the basis of these findings, we conclude that fluorescence optical imaging and photoacoustic imaging are promising approaches to assessing Dox release and monitoring temperature, respectively, after Dox@PEG-HAuNS–mediated thermal ablation therapy.