B cell and antibody targeting of transplant alloantigen epitopes is supported by both self and allo-recognition.

Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) proteins mismatched between kidney transplant donors and recipients cause allograft loss. Using single-cell, molecular, structural, and proteomic techniques, we profiled the HLA-specific (alloreactive) B cell response in kidney and blood of a transplant recipient with antibody-mediated rejection (AMR). We identified 14 distinct alloreactive B cell lineages, which spanned the rejected organ and blood and expressed high-affinity anti-donor HLA-specific B cell receptors, many of which were clonally linked to circulating DSA. The alloreactive B cell response was focused on exposed, solvent-accessible mismatched HLA residues, while also demonstrating extensive contacts with self-HLA residues. Consistent with structural evidence of self-recognition, measurable self-reactivity by donor-specific B cells was common and positively correlated with anti-donor affinity maturation. Thus, allo- and self-reactive signatures appeared to converge, suggesting that during AMR, the recognition of non-self and breaches of tolerance conspire to produce a pathogenic donor-specific adaptive response.

Aerosol Measurement Degradation in Low-Cost Particle Sensors Using Laboratory Calibration and Field Validation.

Increasing concern over air pollution has led to the development of low-cost sensors suitable for wide-scale deployment and use by citizen scientists. This project investigated the AirU low-cost particle sensor using two methods: (1) a comparison of pre- and post-deployment calibration equations for 24 devices following use in a field study, and (2) an in-home comparison between 3 AirUs and a reference instrument, the GRIMM 1.109. While differences (and therefore some sensor degradation) were found in the pre- and post-calibration equation comparison, absolute value changes were small and unlikely to affect the quality of results. Comparison tests found that while the AirU did tend to underestimate minimum and overestimate maximum concentrations of particulate matter, ~88% of results fell within ±1 µg/m3 of the GRIMM. While these tests confirm that low-cost sensors such as the AirU do experience some sensor degradation over multiple months of use, they remain a valuable tool for exposure assessment studies. Further work is needed to examine AirU performance in different environments for a comprehensive survey of capability, as well as to determine the source of sensor degradation.

Uric acid and metabolic syndrome: Findings from national health and nutrition examination survey.

Introduction: Hyperuricemia commonly associated with Gout has been proposed as an independent risk factor for Metabolic Syndrome (MetS). Objective: The purpose of the study was to determine if there is a relationship between hyperuricemia and MetS. Methods: An analysis of cross-sectional data was conducted using the 2013-2018 National Health and Nutrition Examination Survey (NHANES) datasets. Sample weights were assigned by NHANES researchers to each participant allowing researchers to generalize results to all non-institutionalized United States (US) civilians. The analysis included 6,432 individuals, which were representative of 94,729,059 US citizens. Results: Pearson's correlations, chi-square tests, and logistic regression equations were calculated to determine the association between hyperuricemia and MetS. In an unadjusted regression analysis, individuals with hyperuricemia (above 7.0 mg/dL in males and 6.0 mg/dL in females) were 3.19 times more likely to have MetS compared to those with normal uric acid (UA) levels. When controlling for various confounding variables those with hyperuricemia were 1.89 and 1.34 times more likely to have MetS than those with normal UA levels in two additional logistic regression models. Conclusion: In this large cross-sectional study, hyperuricemia was found to be associated with MetS. Additional analyses that controlled for various risk factors previously identified as predictive of MetS still demonstrated hyperuricemia independently associated with MetS. The results of this study suggest a need to understand the metabolic pathways of UA more clearly to further explain the contribution to MetS. Additional research should include prospective clinical trials assessing the effects of UA and the control of UA on MetS and concomitant medical outcomes.

Intrathymic differentiation of natural antibody-producing plasma cells in human neonates.

The thymus is a central lymphoid organ primarily responsible for the development of T cells. A small proportion of B cells, however, also reside in the thymus to assist negative selection of self-reactive T cells. Here we show that the thymus of human neonates contains a consistent contingent of CD138+ plasma cells, producing all classes and subclasses of immunoglobulins with the exception of IgD. These antibody-secreting cells are part of a larger subset of B cells that share the expression of signature genes defining mouse B1 cells, yet lack the expression of complement receptors CD21 and CD35. Data from single-cell transcriptomic, clonal correspondence and in vitro differentiation assays support the notion of intrathymic CD138+ plasma cell differentiation, alongside other B cell subsets with distinctive molecular phenotypes. Lastly, neonatal thymic plasma cells also include clones reactive to commensal and pathogenic bacteria that commonly infect children born with antibody deficiency. Thus, our findings point to the thymus as a source of innate humoral immunity in human neonates.

Metabolic Health, Obesity, and Renal Function: 2013-2018 National Health and Nutrition Examination Surveys.

Rising rates of metabolic syndrome, obesity, and mortality from chronic kidney disease (CKD) have prompted further investigation into the association between metabolic phenotypes and CKD. Purpose: To report the frequency of strictly defined metabolic phenotypes, renal function within each phenotype, and individual risk factors associated with reduced renal function. We utilized the 2013-2018 National Health and Nutrition Examination Surveys (NHANES) and complex survey sample weighting techniques to represent 220 million non-institutionalized U.S. civilians. Metabolic health was defined as having zero of the risk factors defined by the National Cholesterol Education Program with the exception of obesity, which was defined as BMI ≥ 30 kg/m2 in non-Asians and BMI ≥ 25 kg/m2 in Asians. The metabolically healthy normal (MUN) phenotype comprised the highest proportion of the population (38.40%), whereas the metabolically healthy obese (MHO) was the smallest (5.59%). Compared to the MHN reference group, renal function was lowest in the strictly defined MUN (B = -9.60, p < 0.001) and highest in the MHO (B = 2.50, p > 0.05), and this persisted when an increased number of risk factors were used to define metabolic syndrome. Systolic blood pressure had the strongest correlation with overall eGFR (r = -0.25, p < 0.001), and individuals with low HDL had higher renal function compared to the overall sample. The MUN phenotype had the greatest association with poor renal function. While the MHO had higher renal function, this may be due to a transient state caused by renal hyperfiltration. Further research should be done to investigate the association between dyslipidemia and CKD.

Metabolic Constellations, Clusters, and Renal Function: Findings from the 2013-2018 National Health and Nutrition Examination Surveys.

Metabolic syndrome (MetS) is associated with decreased renal function and chronic kidney disease (CKD). To date, no research regarding the sixteen possible constellations resulting in the diagnosis of MetS has been elucidated. The purpose of this study is to report renal function in sixteen metabolic constellations grouped into four metabolic clusters. Individuals (n = 2767; representing 86,652,073 individuals) from the 2013-2018 National Health and Nutrition Examination Surveys who met the criteria for MetS were included. Sixteen possible constellations of three or more risk factors were analyzed for renal function. Four metabolic clusters representing MetS with hyperglycemia (Cluster I), MetS with hypertension (Cluster II), MetS with hyperglycemia and hypertension (Cluster III), or MetS with normoglycemia and normotension (Cluster IV) were assessed for renal function and CKD status. Cluster III had the highest odds of CKD (OR = 2.57, 95% CL = 1.79, 3.68). Clusters II and III had the lowest renal function and were not different from one another (87.82 and 87.28 mL/min/1.73 m2, p = 0.71). The constellation with the lowest renal function consisted of hypertension, high triglycerides, and a large waist circumference (82.86 mL/min/1.73 m2), whereas the constellation with the highest renal function consisted of hyperglycemia, low HDL, and a large waist circumference (107.46 mL/min/1.73 m2). The sixteen constellations of MetS do not have the same effects on renal function. More research is needed to understand the relationship between the various iterations of MetS and renal function.

Recommendations for standards of monitoring during anaesthesia and recovery 2021: Guideline from the Association of Anaesthetists.

This guideline updates and replaces the 5th edition of the Standards of Monitoring published in 2015. The aim of this document is to provide guidance on the minimum standards for monitoring of any patient undergoing anaesthesia or sedation under the care of an anaesthetist. The recommendations are primarily aimed at anaesthetists practising in the UK and Ireland, but it is recognised that these guidelines may also be of use in other areas of the world. Minimum standards for monitoring patients during anaesthesia and in the recovery phase are included. There is also guidance on monitoring patients undergoing sedation and during transfer. There are new sections specifically discussing capnography, sedation and regional anaesthesia. In addition, the indications for processed electroencephalogram and neuromuscular monitoring have been updated.

Metabolic Phenotypes and Chronic Kidney Disease: A Cross-Sectional Assessment of Patients from a Large Federally Qualified Health Center.

The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index >30 kg/m2 and renal health as an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2. Linear and logistic regressions were used to analyze the data. The metabolically healthy overweight (MHO) phenotype had the highest eGFR (104.86 ± 28.76 mL/min/1.72 m2) and lowest unadjusted odds of chronic kidney disease (CKD) (OR = 0.46, 95%CI = 0.168, 1.267, p = 0.133), while the metabolically unhealthy normal weight (MUN) phenotype demonstrated the lowest eGFR (91.34 ± 33.28 mL/min/1.72 m2) and the highest unadjusted odds of CKD (OR = 3.63, p < 0.0001). After controlling for age, sex, and smoking status, the metabolically unhealthy obese (MUO) (OR = 1.80, 95%CI = 1.08, 3.00, p = 0.024) was the only phenotype with significantly higher odds of CKD as compared to the reference. We demonstrate that the metabolically unhealthy phenotypes have the highest odds of CKD compared to metabolically healthy individuals.

Metabolic Health, Obesity, and Cardiovascular Disease: 2015-2016 National Health and Nutrition Examination Survey.

BACKGROUND: The metabolically unhealthy normal weight (MUN) and metabolically healthy obese (MHO) phenotypes are abnormal metabolic states. The purpose of this study was to report the frequency of the strictly defined MHO and MUN phenotypes and the association between metabolic phenotype and 10-year Framingham cardiovascular disease (CVD) risk score using a sample taken from the 2015-2016 National Health and Nutrition Examination Survey. METHODS: A cross-sectional sample of 2,316 participants age 18-79 years with complete metabolic health information were selected from the 2015-2016 dataset and included in the present analysis. Metabolic health was defined as the absence of all metabolic abnormalities as outlined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index ≥30 kg/m2 or waist > 88.9 cm for females or > 101.6 cm for males. RESULTS: Frequency of the MHO phenotype was 5.5% and the MUN was 44.3%. After adjustment for all covariates, Framingham CVD risk score was higher in the MUN (b = 1.74,p < 0.001) and metabolically unhealthy obese (b = 3.32,p < 0.001) phenotypes that used BMI to define obesity, and the MHO phenotype had a slight protective effect (b = -2.25,p < 0.001) when waist circumference was used as the measure of obesity. CONCLUSIONS: Metabolically unhealthy phenotypes had higher CVD risk, while the MHO phenotype was not at any greater risk than the metabolically healthy normal weight.

Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

Ameliorating Chronic Kidney Disease Using a Whole Food Plant-Based Diet.

Novel approaches to ameliorating chronic kidney disease (CKD) are warranted as most patients are undiagnosed until they begin displaying symptoms of kidney failure. There is increasing evidence that a whole food plant-based (WFPB) diet may offer benefits that slow the progression of CKD, decrease the incidence cardiovascular disease, decrease rates of diabetes and obesity, and reduce inflammation and cholesterol, which in turn can delay kidney failure and the initiation of dialysis. While animal-based protein ingestion promotes an acidic environment, inflammation and renal hyperfiltration, study authors report plant-based protein can be alkaline-producing and anti-inflammatory and can contain renoprotective properties. Although there may be benefits to adopting a WFPB diet, macronutrient and micronutrient content should be carefully considered and adjusted to avoid malnutrition in CKD patients. Further research needs to be done in order to establish the biological plausibility and feasibility of a WFPB in individuals with diagnosed CKD.

Fc Receptor-Like 6 (FCRL6) Discloses Progenitor B Cell Heterogeneity That Correlates With Pre-BCR Dependent and Independent Pathways of Natural Antibody Selection.

B-1a cells produce "natural" antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, and differentiation properties conducive for natural Ab generation. Compared to FCRL6- pro B cells, the repressed mitotic, DNA damage repair, and signaling activity of FCRL6+ progenitors, yielded VH repertoires with biased distal Ighv segment accessibility, constrained diversity, and hydrophobic and charged CDR-H3 sequences. Beyond nascent autoreactivity, VH11 productivity, which predominates phosphatidylcholine-specific B-1a B cell receptors (BCRs), was higher for FCRL6+ cells as was pre-BCR formation, which was required for Myc induction and VH11, but not VH12, B-1a development. Thus, FCRL6 revealed unexpected heterogeneity in the developmental origins, regulation, and selection of natural Abs at the pre-BCR checkpoint with implications for autoimmunity and lymphoproliferative disorders.

Datasets for face and object detection in fisheye images.

We present two new fisheye image datasets for training object and face detection models: VOC-360 and Wider-360. The fisheye images are created by post-processing regular images collected from two well-known datasets, VOC2012 and Wider Face, using a model for mapping regular to fisheye images implemented in Matlab. VOC-360 contains 39,575 fisheye images for object detection, segmentation, and classification. Wider-360 contains 63,897 fisheye images for face detection. These datasets will be useful for developing face and object detectors as well as segmentation modules for fisheye images while the efforts to collect and manually annotate true fisheye images are underway.

Development of an Empirical Formula for Describing Human Inhalability of Airborne Particles at Low Wind Speeds and Calm Air.

Based on experiments conducted in low wind speed and calm air environments, the current International Organization for Standardization (ISO) and European Committee for Standardization (CEN) convention modeling human aerosol inhalability (i.e. aspiration efficiency) may not be valid when wind speeds are less than 0.5 ms-1. Additionally, the convention is based primarily on mouth breathing data and aerosols with aerodynamic diameters smaller than 100 µm. Since the convention's development, experimental inhalation data at wind speeds lower than 0.5 ms-1 for nose, mouth, and oronasal breathing have been generated for aerosols in a wider range of sizes (1.5-135 µm). These data were gathered and modeled with the intention of providing a simple convention recommendation for inhalability in low wind speed (>0 to <0.5 ms-1) and calm air (~0 ms-1) conditions to the ISO Technical Committee (TC) 146, Subcommittee 2, Working Group (WG) 1 ('Particle Size-Selective Sampling and Analysis'), as it relates to standard ISO 7708, and to CEN TC 137/WG 3, as it relates to standard EN 481. This paper presents several equations as possibilities, all relating aspiration efficiency to aerodynamic diameter. The equation AE=1+0.000019dae2-0.009788dae stands out as a possible new convention. This polynomial model balances simplicity and fit while addressing the weakness of the current convention.