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The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma are not well understood. We investigated whether the ambient levels of fine PM with aerodynamic diameter ≤ 2.5 microns (PM ) are associated with alterations in circulating monocytes in children with or without asthma. Increased exposure to ambient PM was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or LPS. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

The naive T cell compartment undergoes multiple changes across age that associate with altered susceptibility to infection and autoimmunity. In addition to the acquisition of naive-like memory T cell subsets, mouse studies describe substantial molecular reprogramming of the naive compartment in adults compared with adolescents. However, these alterations are not well delineated in human aging. Using a new trimodal single cell technology (TEA-seq), we discovered that the composition and transcriptional and epigenetic programming of the naive T cell compartment in children (11-13 yrs) is distinct from that of older adults (55-65 yrs). Naive CD4 T cells, previously considered relatively resistant to aging, exhibited far more pronounced molecular reprogramming than naive CD8 T cells, in which alterations are preferentially driven by shifts in naive-like memory subsets. These data reveal the complex nature of the naive T cell compartment that may contribute to differential immune responses across the spectrum of human age.One Sentence Summary:The naive CD8 and CD4 T cell compartments in humans are heterogeneous and impacted differently with age, in which naive CD8 T cell subsets dramatically shift in composition and true naive CD4 T cells display significant molecular re-programming.

Background It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS‐CoV‐2. Methods All patients over 28 days old testing positive for SARS‐CoV‐2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub‐cohort was followed prospectively to evaluate long‐term COVID‐19 symptoms. Results 168,190 patients underwent SARS‐CoV‐2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS‐CoV‐2‐positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non‐allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID‐19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub‐cohort followed longitudinally, asthmatics and non‐asthmatics had similar time to resolution of COVID‐19 symptoms, particularly lower respiratory symptoms. Conclusions Asthma is not a risk factor for more severe COVID‐19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID‐19 compared with non‐allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID‐19 disease trajectory. Recovery was similar among asthmatics and non‐asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post‐infection., Asthma is not a risk factor for more severe COVID‐19 disease. Allergic asthmatics are half as likely to be hospitalized compared with non‐allergic asthmatics and lower levels of eosinophil counts (allergic biomarkers) are associated with a more severe COVID‐19 disease trajectory. Recovery is similar among asthmatics and non‐asthmatics.

Motivation For immune system monitoring in large-scale studies at the single-cell resolution using CyTOF, (semi-)automated computational methods are applied for annotating live cells of mixed cell types. Here, we show that the live cell pool can be highly enriched with undefined heterogeneous cells, i.e. ‘ungated’ cells, and that current semi-automated approaches ignore their modeling resulting in misclassified annotations. Result We introduce ‘CyAnno’, a novel semi-automated approach for deconvoluting the unlabeled cytometry dataset based on a machine learning framework utilizing manually gated training data that allows the integrative modeling of ‘gated’ cell types and the ‘ungated’ cells. By applying this framework on several CyTOF datasets, we demonstrated that including the ‘ungated’ cells can lead to a significant increase in the precision of the ‘gated’ cell types prediction. CyAnno can be used to identify even a single cell type, including rare cells, with higher efficacy than current state-of-the-art semi-automated approaches. Availability and implementation The CyAnno is available as a python script with a user-manual and sample dataset at https://github.com/abbioinfo/CyAnno. Supplementary information Supplementary data are available at Bioinformatics online.

Food allergies have been rising in prevalence since the 1990s, imposing substantial physical, psychosocial, and economic burdens on affected patients and their families. Until recently, the only therapy for food allergy was strict avoidance of the allergenic food. Recent advances in translational studies, however, have led to insights into allergic sensitization and tolerance. This article provides an overview of cutting-edge research into food allergy and immune tolerance mechanisms utilizing mouse models, human studies, and systems biology approaches. This research is being translated and implemented in the clinical setting to improve diagnosis and reduce food allergy's public health burden.

The global epidemiology of asthma among patients with coronavirus disease 2019 (COVID-19) presents striking geographic differences, defining prevalence zones of high and low co-occurrence of asthma and COVID-19.We aimed to compare asthma prevalence among hospitalized patients with COVID-19 in major global hubs across the world by applying common inclusion criteria and definitions.We built a network of 6 academic hospitals in Stanford (Stanford University)/the United States; Frankfurt (Goethe University), Giessen (Justus Liebig University), and Marburg (Philipps University)/Germany; and Moscow (Clinical Hospital 52 in collaboration with Sechenov University)/Russia. We collected clinical and laboratory data for patients hospitalized due to COVID-19.Asthmatic individuals were overrepresented among hospitalized patients with COVID-19 in Stanford and underrepresented in Moscow and Germany as compared with their prevalence among adults in the local community. Asthma prevalence was similar among patients hospitalized in an intensive care unit and patients hospitalized in other than an intensive care unit, which implied that the risk for development of severe COVID-19 was not higher among asthmatic patients. The numbers of males and comorbidities were higher among patients with COVID-19 in the Stanford cohort, and the most frequent comorbidities among these patients with asthma were other chronic inflammatory airway disorders such as chronic obstructive pulmonary disease.The observed disparity in COVID-19-associated risk among asthmatic patients across countries and continents is connected to the varying prevalence of underlying comorbidities, particularly chronic obstructive pulmonary disease.

Background: The global epidemiology of asthma among COVID-19 patients presents striking geographic differences defining high and low [asthma and COVID-19] co-occurrence prevalence zones (1). The objective of the present study was to compare asthma prevalence among hospitalized COVID-19 patients in major global hubs across the world with the application of common inclusion criteria and definitions. Methods: We built a network of six academic hospitals in Stanford (Stanford University)/USA, Frankfurt (Goethe University), Giessen (Justus Liebig University) and Marburg (Philipps University)/Germany, and Moscow (Clinical Hospital 52 in collaboration with Sechenov University)/Russia. We collected clinical and laboratory data for patients hospitalized due to COVID-19. Comorbidities reported were based on the 2020 International Classification of Diseases-10th Revision codes. Results: Asthmatics were overrepresented among hospitalized COVID-19 patients in Stanford and underrepresented in Moscow and Germany as compared to the prevalence among adults in the local community. Asthma prevalence was similar among ICU and hospital non-ICU patients, which implied that the risk for developing severe COVID-19 was not higher among asthmatics. The number of males and comorbidities was higher among COVID-19 patients in the Stanford cohort, and the most frequent comorbidities among these asthma patients were other chronic inflammatory airway disorders such as chronic obstructive pulmonary disease (COPD). Conclusion: Observed disparity in COVID-19-associated risk among asthmatics across countries and continents is connected to varying prevalence of underlying comorbidities, particularly COPD. Public health policies in the future will need to consider comorbidities with an emphasis on COPD for prioritization of vaccination and preemptive treatment.

Aging is characterized by a loss of bone marrow hematopoietic tissue, systemic chronic inflammation, and higher susceptibility to infectious and noninfectious diseases. We previously reported the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in adult rhesus macaques aged 3 to 19 yr (equivalent to approximately 10 to 70 yr of age in humans). In the current study, we observed an earlier release of recently dividing neutrophils from bone marrow and greater in-group variability of neutrophil kinetics based on in vivo BrdU labeling in a group of older rhesus macaques of 20–26 yr of age. Comparing neutrophil numbers and circulating cytokine levels in rhesus macaques spanning 2 to 26 yr of age, we found a negative correlation between age and blood neutrophil counts and a positive correlation between age and plasma G-CSF levels. Hierarchic clustering analysis also identified strong associations between G-CSF with the proinflammatory cytokines, IL-1β and MIP-1α. Furthermore, neutrophils from older macaques expressed less myeloperoxidase and comprised higher frequencies of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) compared to the young adult macaques. In summary, we observed an earlier release from bone marrow and a reduced production of neutrophils despite the increased levels of plasma G-CSF, especially in the elderly rhesus macaques. This lower neutrophil production capacity associated with increased production of proinflammatory cytokines as well as an earlier release of less mature neutrophils and PMN-MDSCs may contribute to the chronic inflammation and greater susceptibility to infectious and noninfectious diseases during aging.

Food allergies have been rising in prevalence since the 1990s, imposing substantial physical, psychosocial, and economic burdens on affected patients and their families. Until recently, the only therapy for food allergy was strict avoidance of the allergenic food. Recent advances in translational studies, however, have led to insights into allergic sensitization and tolerance. This article provides an overview of cutting-edge research into food allergy and immune tolerance mechanisms utilizing mouse models, human studies, and systems biology approaches. This research is being translated and implemented in the clinical setting to improve diagnosis and reduce food allergy's public health burden.

Supplemental material, sj-pdf-1-ctj-10.1177_1740774520988298 for Clinical trials in a COVID-19 pandemic: Shared infrastructure for continuous learning in a rapidly changing landscape by Haley Hedlin, Ariadna Garcia, Yingjie Weng, Ziyuan He, Vandana Sundaram, Bryan Bunning, Vidhya Balasubramanian, Kristen Cunanan, Kristopher Kapphahn, Santosh Gummidipundi, Natasha Purington, Mary Boulos and Manisha Desai in Clinical Trials

Background: Clinical trials, conducted efficiently and with the utmost integrity, are a key component in identifying effective vaccines, therapies, and other interventions urgently needed to solve the COVID-19 crisis. Yet launching and implementing trials with the rigor necessary to produce convincing results is a complicated and time-consuming process. Balancing rigor and efficiency involves relying on designs that employ flexible features to respond to a fast-changing landscape, measuring valid endpoints that result in translational actions and disseminating findings in a timely manner. We describe the challenges involved in creating infrastructure with potential utility for shared learning. Methods: We have established a shared infrastructure that borrows strength across multiple trials. The infrastructure includes an endpoint registry to aid in selecting appropriate endpoints, a registry to facilitate establishing a Data & Safety Monitoring Board, common data collection instruments, a COVID-19 dedicated design and analysis team, and a pragmatic platform protocol, among other elements. Results: The authors have relied on the shared infrastructure for six clinical trials for which they serve as the Data Coordinating Center and have a design and analysis team comprising 15 members who are dedicated to COVID-19. The authors established a pragmatic platform to simultaneously investigate multiple treatments for the outpatient with adaptive features to add or drop treatment arms. Conclusion: The shared infrastructure provides appealing opportunities to evaluate disease in a more robust manner with fewer resources and is especially valued during a pandemic where efficiency in time and resources is crucial. The most important element of the shared infrastructure is the pragmatic platform. While it may be the most challenging of the elements to establish, it may provide the greatest benefit to both patients and researchers.

Supplemental material, sj-pdf-2-ctj-10.1177_1740774520988298 for Clinical trials in a COVID-19 pandemic: Shared infrastructure for continuous learning in a rapidly changing landscape by Haley Hedlin, Ariadna Garcia, Yingjie Weng, Ziyuan He, Vandana Sundaram, Bryan Bunning, Vidhya Balasubramanian, Kristen Cunanan, Kristopher Kapphahn, Santosh Gummidipundi, Natasha Purington, Mary Boulos and Manisha Desai in Clinical Trials

BACKGROUND: There has been a striking generational increase in the prevalence of food allergies. We have proposed that this increase can be explained, in part, by alterations in the commensal microbiome. METHODS: To identify bacterial signatures and metabolic pathways that may influence the expression of this disease, we collected fecal samples from a unique, well-controlled cohort of twins concordant or discordant for food allergy. Samples were analyzed by integrating 16S rRNA gene amplicon sequencing and liquid chromatography–tandem mass spectrometry metabolite profiling. RESULTS: A bacterial signature of 64 operational taxonomic units (OTUs) distinguished healthy from allergic twins; the OTUs enriched in the healthy twins were largely taxa from the Clostridia class. We detected significant enrichment in distinct metabolite pathways in each group. The enrichment of diacylglycerol in healthy twins is of particular interest for its potential as a readily measurable fecal biomarker of health. In addition, an integrated microbial-metabolomic analysis identified a significant association between healthy twins and Phascolarctobacterium faecium and Ruminococcus bromii, suggesting new possibilities for the development of live microbiome-modulating biotherapeutics. CONCLUSION: Twin pairs exhibited significant differences in their fecal microbiomes and metabolomes through adulthood, suggesting that the gut microbiota may play a protective role in patients with food allergies beyond the infant stage. TRIAL REGISTRATION: Participants in this study were recruited as part of an observational study (ClinicalTrials.gov NCT01613885) at multiple sites from 2014 to 2018. FUNDING: This work was supported by the Sunshine Charitable Foundation; the Moss Family Foundation; the National Institute of Allergy and Infectious Diseases (NIAID) (R56AI134923 and R01AI 140134); the Sean N. Parker Center for Allergy and Asthma Research; the National Heart, Lung, and Blood Institute (R01 HL 118612); the Orsak family; the Kepner family; and the Stanford Institute for Immunity, Transplant and Infection.

This paper proposes a novel frequency reconfigurable antenna based on the liquid crystal material because of the dielectric anisotropy. The antenna applies double layer structure so that liquid crystal can be easily injected on the second substrate. Experimental results show that when changing the effective dielectric constant of the liquid crystal, the center resonant frequency of antenna can be tuned continuously from 6.02 GHz to 5.91 GHz meaning that this antenna achieves a frequency tunability about 1.9%. Besides, in the whole adjustment process, the antenna's matching characteristics remains good. Thus, this kind of antennas are very feasible to be applied in the reconfigurable communication system. Furthermore, antenna designed in this article separates RF circuit from DC feed circuit by using a simple way, which makes the design efficient and more convenient.

Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2′-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5–10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 × 109 cells/l/d), basophils (1.78 ± 0.30 d, 5.89 × 106 cells/l/d), and CD14+CD16− classical monocytes (1.01 ± 0.15 d, 3.09 × 108 cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4–5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.

Aging is characterized with a loss of hematopoietic tissue in bone marrow, systemic chronic inflammation, and higher susceptibility to infectious diseases. We previously showed the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in rhesus macaques aged 3 to 19 years old. Here we extended that study to further investigate the effect of aging on kinetics and production of neutrophils in more elderly rhesus macaques. We observed a neutrophil kinetics shift and higher in-group variability in rhesus macaques above 20 years old (equivalent to 70 years or more in humans) by in vivo BrdU pulse-chase labeling. In a cross-sectional study, we also measured complete blood cell counts and plasma cytokine levels from a group of 126 outdoor-housed captive Indian-ancestry rhesus macaques between 2 to 23 years old and found that aging negatively correlated with neutrophil counts and positively correlated with plasma G-CSF levels. Hierarchical clustering analysis suggested that G-CSF was strongly associated with pro-inflammatory cytokines IL-1b and MIP-1a. In elderly rhesus macaques, neutrophils expressed less myeloperoxidase and there was a higher frequency of PMN-MDSCs compared to the young adult macaques. In summary, there appears to be a dysregulated feedback mechanism wherein increased levels of G-CSF failed to restore neutrophil production in elderly rhesus macaques that was associated with induced production of pro-inflammatory cytokines and earlier release of less mature neutrophils and PMN-MDSCs. Together, these findings may contribute to the understanding of the chronic inflammation and greater susceptibility to infectious diseases in the elderly.

A recent method proposed by L. L. Guo, H. Deng, and B. Himed in “Waveform Optimization for Transmit Beamforming with MIMO Radar Antenna Arrays,” IEEE Trans. Antennas Propag. vol. 63, no. 2, pp. 543–552, Feb. 2015, claims that the multiple-input multiple-output (MIMO) radar can form a transmit beam pattern with nulls in specific directions to alleviate the clutter and make the radar signals undetectable with initial phase optimization. However, it lacks some of the important aspects and may create an incorrect impression about transmit beamforming of MIMO radars. This comment shows that the virtual transmit beam pattern cannot reflect the practical radiation energy of the radar array. Even the virtual transmit beam pattern has nulls in the preselected directions, the clutter from these directions cannot be alleviated at the radar receiver, and the MIMO radar signals would still be detectable in these directions.

Myeloid cells are continuously produced via bone marrow hematopoiesis and then cleared from the circulation to maintain homeostasis. To better understand the kinetics of such cell movement, we applied in vivo BrdU pulse-chase labeling and flow cytometry analysis to follow the kinetics of cell division during homeostasis of each subset of myeloid cells in peripheral blood in rhesus macaques. Results were applied to a mathematical model to estimate the half-life and daily production of each subset as follows; neutrophils (1.63±0.16 days, 1.42×109cells/L/day), basophils (1.78±0.30 days, 5.89×106 cells/L/day), classical monocytes (1.01±0.15 days, 3.09×108 cells/L/day), intermediate monocytes (1.23±0.14 days, 2.90×107 cells/L/day), non-classical monocytes (3.45±0.93 days, 1.58×107 cells/L/day), CD1c+ myeloid dendritic cells (DCs) (1.11±0.16 days, 1.65×107 cells/L/day), CD123+ plasmacytoid DCs (2.69±0.38 days, 9.67×105 cells/L/day). Unlike monocytes which were released into the blood circulation as soon as 1 day after dividing, neutrophils required ~4–5 days in bone marrow before being released. Interestingly, even within the granulocyte population, neutrophils and basophils exhibited distinct kinetics in peripheral blood and different bone marrow maturation times. We also applied our model to healthy rhesus macaques ranging from 3 to 19 years of age and observed that while the half-life of neutrophils did not change with increasing age, the older animals produced fewer neutrophils per day. In addition to neutrophils and monocytes, the non-classical (inflammatory) monocytes, pDCs and mDCs, as well as basophils, were relatively shorter-lived cells that may contribute to protection and homeostasis at steady state.