Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.

Compressed models for co-reference resolution: enhancing efficiency with debiased word embeddings.

This work presents a comprehensive approach to reduce bias in word embedding vectors and evaluate the impact on various Natural Language Processing (NLP) tasks. Two GloVe variations (840B and 50) are debiased by identifying the gender direction in the word embedding space and then removing or reducing the gender component from the embeddings of target words, while preserving useful semantic information. Their gender bias is assessed through the Word Embedding Association Test. The performance of co-reference resolution and text classification models trained on both original and debiased embeddings is evaluated in terms of accuracy. A compressed co-reference resolution model is examined to gauge the effectiveness of debiasing techniques on resource-efficient models. To the best of the authors' knowledge, this is the first attempt to apply compression techniques to debiased models. By analyzing the context preservation of debiased embeddings using a Twitter misinformation dataset, this study contributes valuable insights into the practical implications of debiasing methods for real-world applications such as person profiling.

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4-6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5-13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80  µ L of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.

Is it reliable to measure the forearm blood pressure in children?

BACKGROUND: When the upper arm (UA) is inaccessible or a standard-sized blood pressure (BP) cuff is unavailable, some healthcare workers use the forearm (FA) to measure BP with a mercury sphygmomanometer. OBJECTIVE: The objective was to determine the accuracy of BP measurement in the arm and FA. DESIGN: Prospective, randomized study. SETTING: Department of Pediatrics, JNMC, Sawangi (Meghe). PARTICIPANTS: A total of 72 children aged 5-15 years. MEASUREMENTS: Mercury and Automatic (OMRON Tokyo, 108-0075 Japan) BP measurements were recorded from the arm and FA at 2 min intervals. RESULTS: In our study, 72 children of both sexes were enrolled. The mean age of the children was 10.13 ± 2.82 years, and 48% were females. Pearson's correlation coefficient between FA and UA systolic BP (SBP) measured by mercury was 0.782, and for diastolic BP (DBP) it was 0.824. Similarly, Pearson's correlation coefficient between FA and UA SBP measured with an automated device (OMRON) was 0.843, and for DBP it was 0.846. The average readings for the SBP and DBP were higher in the FA than in the UA by approximately 3 mmHg. There was a statistically significant difference in both SBP and DBP. CONCLUSIONS: The FA is an acceptable method of BP monitoring when the UA cannot be accessed. The pressure from FA is probably higher than it would be from UA.