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Using the activated HPHT-sintering of diamond powders with addition of n-layered graphene of the N002-PDR grade, was produced a novel superhard composite polycrystalline material that does not contain free silicon and has a strength by 35% higher and wear-resistance by 7 times higher than samples produced without addition of graphene. [ABSTRACT FROM AUTHOR]

The content of ATP in scalp hair bulbs in humans was measured in the hair roots from 15 healthy volunteers. Light and electron microscopy confirmed the presence of outer and an inner root sheaths in the root of pulled out anagen hair. Incubation of samples in buffer solution led to extraction of ATP, which was measured by the chemiluminescent method. Mechanic disintegration of hair bulbs and their freezing-defrosting did not increase ATP output. The results of microscopy indicated that ATP extraction procedure was associated with separation of the outer radical sheath from the inner one without impairing the structure of the inner sheath. The mean content of ATP was 12±2 pmol per bulb. The use of pulled out hair bulbs for ATP measurements simplified the procedure as involved no surgical removal of follicles. [ABSTRACT FROM AUTHOR]

The paper addresses the effect of pressure and a chromium diboride additive on shrinkage and shrinkage rate in hot pressing and on mechanical properties of the resulting diamond-containing composites based on Fe, Cu, Ni, and Sn powders. The shrinkage rate curves are found to have a stepwise trend. The shrinkage rate variations are shown to be associated with the phase and structural changes that occur in this system. The authors have determined the initial composition and p, T-conditions that ensure process activation and simultaneous improvement in mechanical properties of the composite. [ABSTRACT FROM AUTHOR]

Background: The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut., Objective: We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay., Methods: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from α-/β-gliadin, γ-gliadin, ω-5-gliadin, and high- and low-molecular-weight glutenin were commercially synthesized and coupled to LumAvidin beads (Luminex Corporation, Austin, Tex). Machine learning methods were used to identify diagnostic epitopes, and performance was evaluated using the DeLong test., Results: The analysis included 122 children (83 wheat-allergic and 39 wheat-tolerant; 57.4% male). Machine learning coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1, to be the most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis showed lower es-IgG1 binding intensity than did all the other groups. A set of 4 informative epitopes from ω-5-gliadin and γ-gliadin were the best predictors of wheat allergy, with an area under the curve of 0.908 (sensitivity, 83.4%; specificity, 88.4%), higher than the performance exhibited by wheat-specific IgE (area under the curve = 0.646; P < .001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 nonallergic), with an area under the curve of 0.908 (sensitivity, 75.9%; specificity, 90.5%)., Conclusions: The wheat bead-based epitope assay demonstrated greater diagnostic accuracy compared with existing specific IgE tests for wheat allergy., Competing Interests: Disclosure statement This research project was supported by a grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University (grant no. Internal Order [IO] R016232026) and by the David H. and Julia Koch Research Program in Food Allergy Research. Disclosure of potential conflict of interest: M. Suárez-Fariñas reports consultancy feeds from DBV Technologies. M. Suprun is currently an employee at Janssen Pharmaceutical. H. A. Sampson reports funding to his institution for grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases; has received consulting fees from DBV Technologies, N-Fold Therapeutics, LLC, and Siolta, Inc; and has received stock options from DBV Technologies and N-Fold Therapeutics, LLC. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, induces histological and molecular resolution of psoriatic plaques by 12 weeks. However, the long-term effects of secukinumab on the molecular resolution of psoriatic inflammation remain unknown., Objectives: To investigate the molecular resolution of psoriasis following 52 weeks of secukinumab treatment., Methods: This was a two-part phase II randomized double-blinded placebo-controlled 52-week study of patients with moderate-to-severe psoriasis receiving secukinumab 300 mg (NCT01537432). Psoriatic lesional and nonlesional skin biopsies were obtained at baseline and at weeks 12 and 52, and the composition of the residual disease genomic profile (RDGP; i.e. 'molecular scar') of biopsies from secukinumab responders analysed., Results: After 52 weeks of treatment, 14 of 24 enrolled patients were considered to be clinical responders [≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75)], 4 of 24 were considered to be nonresponders (< PASI 75) and 6 of 24 patients were lost to follow-up; both the histological and transcriptomic profiles of PASI 75 responders improved from week 12 to week 52. RDGP transcripts of histological responders only partially overlapped between weeks 12 and 52, despite a similar number of transcripts in each RDGP; specifically, four novel transcript subsets showed distinct expression dynamics between weeks 12 and 52 ('slow-resolving', 'recurring', 'persistent' and 'resolved'), with anti-inflammatory and immunomodulatory genes (e.g. SOCS1, CD207 and IL37) notably restored at week 52. Shorter disease duration prior to secukinumab treatment coincided with greater transcript improvements at weeks 12 and 52., Conclusions: Secukinumab improves the histological and molecular phenotype of psoriatic lesional skin up to 52 weeks of treatment; these results suggest possible mechanisms that drive long-term control of psoriasis., Competing Interests: Conflicts of interest F.K., N.H., T.P., A.G. and M.M. are all employed by Novartis Pharma AG, Basel, Switzerland. M.S.-F. and L.E.T. have been supported by Novartis Pharma AG through an institutional research grant. K.A.W. is a former employee of and shareholder in Ultivue, Novartis and Leica Biosystems/Danaher, and is a current employee of Roche Diagnostics Solutions. J.G.K. received grants from Novartis, Pfizer, Amgen, Lilly, Boehringer, Innovaderm, Bristol Myer Squibbs, Janssen, AbbVie, Paraxel, LEO Pharma, Vitae, Akros, Regeneron, Allergan, Novan, Biogen MA, Sienna, UCB, Celgene, Botanix, Incyte, Avillion and Exicure; and has received honoraria from Novartis, Pfizer, Amgen, Lilly, Boehringer, Biogen IDEC, AbbVie, LEO Pharma, Escalier, Valeant, Aurigne, Allergan, Asana, UCB, Sienna, Celgene, Nimbus, Menlo, Aristea, Sanofi, Sun Pharma, Almirall, Arena, BMS, Ventyx, Aclaris and Galapagos. M.S. declares no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23 + IgG1 + memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23 + IgG1 + memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of "type 2-marked" IgG1 + memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)- and IL-13-regulated genes, such as FCER2 / CD23 + , IL4R , and germline IGHE , and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of "type 2-marked" IgG1 + memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23 + IgG1 + memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy.

With advances in molecular and computational science, epitope-specific IgE antibody profiling has been developed and recently brought into clinical practice. Epitope-based testing detects IgE antibodies that directly bind to antigenic sites of an allergen, providing increased resolution specificity and fewer false-positive results for diagnosing food allergy. Epitope-binding profiles may also serve as prognostic markers of food allergy and help predict quantities of allergen that would provoke a reaction (ie, eliciting dose, possible severity of a reaction after allergen ingestion, and outcomes of treatment options such as oral immunotherapy [OIT]). Future studies are under way to discover additional applications of epitope-specific antibodies for multiple food allergens., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether an individual's degree of psychological resilience can be determined from physiological metrics passively collected from a wearable device., Materials and Methods: Data were analyzed in this secondary analysis of the Warrior Watch Study dataset, a prospective cohort of healthcare workers enrolled across 7 hospitals in New York City. Subjects wore an Apple Watch for the duration of their participation. Surveys were collected measuring resilience, optimism, and emotional support at baseline., Results: We evaluated data from 329 subjects (mean age 37.4 years, 37.1% male). Across all testing sets, gradient-boosting machines (GBM) and extreme gradient-boosting models performed best for high- versus low-resilience prediction, stratified on a median Connor-Davidson Resilience Scale-2 score of 6 (interquartile range = 5-7), with an AUC of 0.60. When predicting resilience as a continuous variable, multivariate linear models had a correlation of 0.24 ( P  = .029) and RMSE of 1.37 in the testing data. A positive psychological construct, comprised of resilience, optimism, and emotional support was also evaluated. The oblique random forest method performed best in estimating high- versus low-composite scores stratified on a median of 32.5, with an AUC of 0.65, a sensitivity of 0.60, and a specificity of 0.70., Discussion: In a post hoc analysis, machine learning models applied to physiological metrics collected from wearable devices had some predictive ability in identifying resilience states and a positive psychological construct., Conclusions: These findings support the further assessment of psychological characteristics from passively collected wearable data in dedicated studies., Competing Interests: DC is a coinventor on patents filed by the Icahn School of Medicine at Mount Sinai (ISMMS) relating to the treatment for treatment-resistant depression, suicidal ideation, and other disorders. ISMMS has entered into a licensing agreement with Janssen Pharmaceuticals, Inc, and it has received and will receive payments from Janssen under the license agreement related to these patents for the treatment of treatment-resistant depression and suicidal ideation. Consistent with the ISMMS Faculty Handbook (the medical school policy), DC is entitled to a portion of the payments received by the ISMMS. Because SPRAVATO has received regulatory approval for treatment-resistant depression, through the ISMMS, DC will be entitled to additional payments beyond those already received under the license agreement. DC is a named coinventor on several patents filed by ISMMS for a cognitive training intervention to treat depression and related psychiatric disorders. The ISMMS has entered into a licensing agreement with Click Therapeutics, Inc and has received and will receive payments related to the use of this cognitive training intervention for the treatment of psychiatric disorders. In accordance with the ISMMS Faculty Handbook, DC has received a portion of these payments and is entitled to a portion of any additional payments that the medical school may receive from this license with Click Therapeutics. DC is a named coinventor on a patent application filed by the ISMMS for the use of intranasally administered Neuropeptide Y for the treatment of mood and anxiety disorders. This intellectual property has not been licensed. DC is a named coinventor on a patent application in the United States and several issued patents outside the United States filed by the ISMMS related to the use of ketamine for the treatment of posttraumatic stress disorder. This intellectual property has not been licensed. EPB reports consultancy agreements with Deloitte and Roland Berger; ownership interest in Digital Medicine E. Böttinger GmbH, EBCW GmbH, and Ontomics, Inc; receiving honoraria from Bayer, Bosch Health Campus, Sanofi, and Siemens; and serving as a scientific advisor or member of Bosch Health Campus and Seer Biosciences Inc. LK declares research funding from Abbvie and Pfizer, consulting for Abbvie and Pfizer, and equity ownership/stock options in MetaMe Health and Trellus Health. MS-F declares research support from Novartis and Allergenis. GNN reports employment with, consultancy agreements with, and ownership interest in Pensieve Health and Renalytix AI; receiving consulting fees from AstraZeneca, BioVie, GLG Consulting, and Reata; and serving as a scientific advisor or member of Pensieve Health and Renalytix AI. ZAF discloses consulting fees from Alexion, GlaxoSmithKline, and Trained Therapeutix Discovery and research funding from Daiichi Sankyo, Amgen, Bristol Myers Squibb, and Siemens Healthineers. ZAF receives financial compensation as a board member and advisor to Trained Therapeutix Discovery and owns equity in Trained Therapeutix Discovery as a cofounder. The remaining authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Purpose: Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants with a nonpsychotic affective disorder and participants with no history of psychiatric disease; (2) to examine the relationship between hippocampal neurometabolites and baroreflex sensitivities in these three groups. We hypothesized that baroreflex sensitivity would be reduced and correlated with hippocampal neurometabolite levels in participants with psychosis, but not in the control groups., Methods: We assessed baroreflex sensitivity during the Valsalva maneuver separated into vagal and adrenergic components. Metabolite concentrations for cellular processes were quantitated in the entire multivoxel hippocampus using H 1 -MR spectroscopic (MRS) imaging and were compared with baroreflex sensitivities in the three groups., Results: Vagal baroreflex sensitivity (BRS-V) was reduced in a significantly larger proportion of participants with psychosis compared with patients with nonpsychotic affective disorders, whereas participants with psychosis had increased adrenergic baroreflex sensitivity (BRS-A) compared with participants with no history of psychiatric disease. Only in psychotic cases were baroreflex sensitivities associated with hippocampal metabolite concentrations. Specifically, BRS-V was inversely correlated with myo-inositol, a marker of gliosis, and BRS-A was positively correlated with energy dependent dysmyelination (choline, creatine) and excitatory activity (GLX)., Conclusions: Abnormal baroreflex sensitivity is common in participants with psychosis and is associated with MRS markers of hippocampal pathology. Future longitudinal studies are needed to examine causality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Currently, there is no laboratory test that can accurately identify children at risk of developing peanut allergy. Utilizing a subset of children randomized to the peanut avoidance arm of the LEAP trial, we monitored the development of epitope-specific (ses-)IgE and ses-IgG4 from 4-11 months to 5 years of age., Objective: The aim of the study was to evaluate the prognostic ability of epitope-specific antibodies to predict the result of an oral food challenge (OFC) at 5 years., Methods: A Bead-Based Epitope Assay was used to quantitate IgE and IgG4 to 64 sequential (linear) epitopes from Ara h 1-3 proteins at 4-11 months, 1 and 2.5 years of age in 74 subjects (38 of them with a positive OFC at 5 years). Specific IgE (sIgE) to peanut and component proteins was measured using ImmunoCAP. Machine learning methods were used to identify the earliest time point to predict 5-year outcome, developing prognostic algorithms based only on 4-11 month samples, 1-year or 2.5-year, and a combination of them. Data from 74 children were iteratively split 3:1 into training and validation sets, and machine learning models were developed to predict the 5-year outcome. A test set (n = 90) from an independent cohort was used for final evaluation., Results: Elastic-Net algorithm combining ses-IgE and IgE to Ara h 1, 2, 3, and 9 proteins could predict the 5-year peanut allergy status of LEAP participants with an average validation accuracy of 64% at baseline. Samples taken at 1 year accurately predicted a 5-year OFC outcome with 83% accuracy. This performance remained consistent when evaluated on an independent CoFAR2 cohort with an accuracy of 78% for the 1-year model., Conclusion: IgE antibody profiles at 1 year of age are predictive of peanut OFC at 5 years in children avoiding peanuts. If further confirmed, this model may enable early identification of infants who may benefit from early immunotherapeutic interventions., (© 2022 S. Karger AG, Basel.)

Background: IgE-epitope profiling can accurately diagnose clinical peanut allergy., Objective: We sought to determine whether sequential (linear) epitope-specific IgE (ses-IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double-blind, placebo-controlled food challenges utilizing PRACTALL dosing., Methods: Sixty four ses-IgE antibodies were quantified in blood samples using a bead-based epitope assay. A pair of ses-IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope-based predictor was validated on 331 subjects from five independent cohorts (ages 4-25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated., Results: In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho = 0.61, p < .05); this correlation was 0.51 (p < .05) in validation. Using the ses-IgE-based predictor, subjects were assigned into "high," "moderate," or "low" dose-reactivity groups. On average, subjects in the "high" group were four times more likely to tolerate a specific dose, compared with the "low" group. For example, predicted probabilities of tolerating 4, 14, 44, and 144 or 444 mg in the "low" group were 92%, 77%, 53%, 29%, and 10% compared with 98%, 95%, 94%, 88%, and 73% in the "high" group., Conclusions: Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study-specific challenge protocols. Despite these limitations, an epitope-based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Molecular studies of hen's egg allergens help define allergic phenotypes, with IgE to sequential (linear) epitopes on the ovomucoid (OVM) protein associated with a persistent disease. Epitope profiles of other egg allergens are largely unknown. The objective of this study was to construct an epitope library spanning across 7 allergens and further evaluate sequential epitope-specific (ses-)IgE and ses-IgG4 among baked-egg reactive or tolerant children., Methods: A Bead-Based Epitope Assay was used to identify informative IgE epitopes from 15-mer overlapping peptides covering the entire OVM and ovalbumin (OVA) proteins in 38 egg allergic children. An amalgamation of 12 B-cell epitope prediction tools was developed using experimentally identified epitopes. This ensemble was used to predict epitopes from ovotransferrin, lysozyme, serum albumin, vitellogenin-II fragment, and vitellogenin-1 precursor. Ses-IgE and ses-IgG4 repertoires of 135 egg allergic children (82 reactive to baked-egg, the remaining 52 tolerant), 46 atopic controls, and 11 healthy subjects were compared., Results: 183 peptides from OVM and OVA were screened and used to create an aggregate algorithm, improving predictions of 12 individual tools. A final library of 65 sequential epitopes from 7 proteins was constructed. Egg allergic children had higher ses-IgE and lower ses-IgG4 to predominantly OVM epitopes than both atopic and healthy controls. Baked-egg reactive children had similar ses-IgG4 but greater ses-IgE than tolerant group. A combination of OVA-sIgE with ses-IgEs to OVM-023 and OVA-028 was the best predictor of reactive phenotype., Conclusion: We have created a comprehensive epitope library and showed that ses-IgE is a potential biomarker of baked-egg reactivity., (© 2021 S. Karger AG, Basel.)

Background: Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts., Methods: The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years., Results: In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%., Conclusions: In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Birch pollen is a prevalent aeroallergen during the springtime allergy season. In field studies, variable allergen exposure and environmental factors can affect data quality while environmental exposure units (EEUs) deliver controlled, standardized, and reproducible allergen exposures., Objective: To inform study design for EEU trials evaluating antiallergic therapies., Methods: In this prospective study, 76 participants with birch allergy experienced 3 exposures to birch pollen: (1) an out-of-season EEU challenge (two 3-hour sessions on consecutive days); (2) a natural seasonal exposure; and (3) an in-season EEU challenge (3-hour exposure for 2 weeks after birch pollen season initiation)., Results: The total nasal symptom score, total ocular symptom score, and total symptom score (TSS = total nasal symptom score plus total ocular symptom score) were assessed every 30 minutes and daily during EEU and natural exposures. A high association between TSSs and day 2 of the out-of-season and in-season EEU challenges was noted, with a good association between the maximum TSS during the natural and in-season EEU challenges, and natural season and day 2 of the out-of-season EEU challenge (P < .001 for all). Participants had higher maximum change from the baseline TSS during day 2 of the out-of-season EEU challenge (12.4) vs the following: (1) first day (9.8); (2) in-season EEU challenge (8.4); and (3) natural seasonal exposure (7.6) (P < .001 for all)., Conclusion: A strong association was seen between the presence of allergy symptoms and exposure to birch pollen in the EEU (maximum change in symptom scores during day 2) and in the field. A hybrid trial design may be useful to demonstrate the clinical efficacy of novel antiallergic therapies requiring fewer participants and shorter timelines and expediting treatment availability., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the LEAP (Learning Early About Peanut Allergy) trial, early consumption of peanut in high-risk infants was found to decrease the rate of peanut allergy at 5 years of age. Sequential epitope-specific (ses-)IgE is a promising biomarker of clinical peanut reactivity., Objective: We sought to compare the evolution of ses-IgE and ses-IgG 4 in children who developed (or not) peanut allergy and to evaluate the immunomodulatory effects of early peanut consumption on these antibodies., Methods: Sera from 341 children (LEAP cohort) were assayed at baseline, 1, 2.5, and 5 years of age, with allergy status determined by oral food challenge at 5 years. A bead-based epitope assay was used to quantitate ses-IgE and ses-IgG 4 to 64 sequential epitopes from Ara h 1 to Ara h 3 and was analyzed using linear mixed-effect models., Results: In children avoiding peanut who became peanut allergic, the bulk of peanut ses-IgE did not develop until after 2.5 years. Minimal increases of ses-IgE occurred after 1 year in consumers, but not to the same epitopes as those in children developing peanut allergy. No major changes in ses-IgE were seen in nonallergic or sensitized children. IgE in sensitized consumers was detected against peanut proteins. ses-IgG 4 increased over time in most children regardless of consumption or allergy status., Conclusions: Early peanut consumption in infants at high risk of developing peanut allergy appears to divert the immunologic response to a presumably "protective" effect. In general, consumers tend to generate ses-IgG 4 earlier and in greater quantities than nonconsumers do, whereas only avoiders tend to generate significant quantities of ses-IgE., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Summary: Analysis of epitope-specific antibody repertoires has provided novel insights into the pathogenesis of inflammatory disorders, especially allergies. A novel multiplex immunoassay, termed Bead-Based Epitope Assay (BBEA), was developed to quantify levels of epitope-specific immunoglobulins, including IgE, IgG, IgA and IgD isotypes. bbeaR is an open-source R package, developed for the BBEA, provides a framework to import, process and normalize .csv data files exported from the Luminex reader, evaluate various quality control metrics, analyze differential epitope-binding antibodies with linear modeling, visualize results and map epitopes' amino acid sequences to their respective primary protein structures. bbeaR enables streamlined and reproducible analysis of epitope-specific antibody profiles., Availability and Implementation: bbeaR is open-source and freely available from GitHub as an R package: https://github.com/msuprun/bbeaR; vignettes included., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes., Methods: Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment., Results: A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD., Conclusions: These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease-2019 (COVID-19), a pandemic that brought the whole world to a standstill, has led to financial and health care burden. We aimed to evaluate epidemiological characteristics, needs of resources, outcomes, and global burden of the disease., Methods: Systematic review was performed searching PubMed from December 1, 2019, to March 25, 2020, for full-text observational studies that described epidemiological characteristics, following MOOSE protocol. Global data were collected from the JHU-Corona Virus Resource Center, WHO-COVID-2019 situation reports, KFF.org, and Worldometers.info until March 31, 2020. The prevalence percentages were calculated. The global data were plotted in excel to calculate case fatality rate (CFR), predicted CFR, COVID-19 specific mortality rate, and doubling time for cases and deaths. CFR was predicted using Pearson correlation, regression models, and coefficient of determination., Results: From 21 studies of 2747 patients, 8.4% of patients died, 20.4% recovered, 15.4% were admitted to ICU and 14.9% required ventilation. COVID-19 was more prevalent in patients with hypertension (19.3%), smoking (11.3%), diabetes mellitus (10%), and cardiovascular diseases (7.4%). Common complications were pneumonia (82%), cardiac complications (26.4%), acute respiratory distress syndrome (15.7%), secondary infection (11.2%), and septic shock (4.3%). Though CFR and COVID-19 specific death rates are dynamic, they were consistently high for Italy, Spain, and Iran. Polynomial growth models were best fit for all countries for predicting CFR. Though many interventions have been implemented, stern measures like nationwide lockdown and school closure occurred after very high infection rates (>10cases per 100 000population) prevailed. Given the trend of government measures and decline of new cases in China and South Korea, most countries will reach the peak between April 1-20, if interventions are followed., Conclusions: A collective approach undertaken by a responsible government, wise strategy implementation and a receptive population may help contain the spread of COVID-19 outbreak. Close monitoring of predictive models of such indicators in the highly affected countries would help to evaluate the potential fatality if the second wave of pandemic occurs. The future studies should be focused on identifying accurate indicators to mitigate the effect of underestimation or overestimation of COVID-19 burden., Competing Interests: Conflicts of interest: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

Background: Peanut allergy is characterized by the development of IgE against peanut antigen., Objective: We sought to evaluate the evolution of epitope-specific (es)IgE and esIgG 4 in a prospective cohort of high-risk infants to determine whether antibody profiles can predict peanut allergy after age 4 years., Methods: The end point was allergy status at age 4 + years; samples from 293 children were collected at age 3 to 15 months and 2 to 3 and 4 + years. Levels of specific (s)IgE and sIgG 4 to peanut and component proteins, and 50 esIgE and esIgG 4 were quantified. Changes were analyzed with mixed-effects models. Machine learning algorithms were developed to identify a combination of antigen- and epitope-specific antibodies that using 3- to 15-month or 2- to 3-year samples can predict allergy status at age 4 + years., Results: At age 4 + years, 38% of children were Tolerant or 14% had Possible, 8% Convincing, 24% Serologic, and 16% Confirmed allergy. At age 3 to 15 months, esIgE profiles were similar among groups, whereas marked increases were evident at age 2 and 4 + years only in Confirmed and Serologic groups. In contrast, peanut sIgE level was significantly lower in the Tolerant group at age 3 to 15 months, increased in Confirmed and Serologic groups but decreased in Convincing and Possibly Allergic groups over time. An algorithm combining esIgEs with peanut sIgE outperformed different clinically relevant IgE cutoffs, predicting allergy status on an "unseen" set of patients with area under the curves of 0.84 at age 3 to 15 months and 0.87 at age 2 to 3 years., Conclusions: Early epitope-specific plus peanut-specific IgE is predictive of allergy status at age 4 + years., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG 1 , IgG 4 , IgA, and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied., Methods: Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG 1 , and esIgG 4 antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities., Results: BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE-binding epitopes. Egg-allergic children had lower esIgA 1 (P = .010) and esIgG 1 (P = .016) and higher esIgE (P < .001) and esIgD (P = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P = .038). Network analysis identified most associations between esIgE with either esIgG 4 or esIgD; indicating that IgE-secreting plasma cells could originate from either sequential isotype switch from antigen-experienced intermediate isotypes or directly from the IgD + B cells., Conclusions: Collectively, these data point toward a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The IL-23/T helper type 17 cell axis is a target for psoriasis. The TYK2/Janus kinase 1 inhibitor PF-06700841 will directly suppress TYK2-dependent IL-12 and IL-23 signaling and Janus kinase 1-dependent signaling in cells expressing these signaling molecules, including T cells and keratinocytes. This clinical study sought to define the inflammatory gene and cellular pathways through which PF-06700841 improves the clinical manifestations of psoriasis. Patients (n = 30) with moderate-to-severe psoriasis were randomized to once-daily 30 mg (n = 14) or 100 mg (n = 7) PF-06700841 or placebo (n = 9) for 28 days. Biopsies were taken from nonlesional and lesional skin at baseline and weeks 2 and 4. Changes in the psoriasis transcriptome and genes induced by IL-17 in keratinocytes were evaluated with microarray profiling and reverse transcriptase-PCR. Reductions in IL-17A, IL-17F, and IL-12B mRNA were observed as early as 2 weeks and approximately 70% normalization of lesional gene expression after 4 weeks. Immunohistochemistry showed significant decreases in markers of keratinocyte activation, epidermal thickness, KRT16 and Ki-67 expression, and immune cell infiltrates CD3 + /CD8 + (T cells) and CD11c (dendritic cells) after 2 weeks of treatment, corresponding with improvement in histologic score. PF-06700841 improves clinical symptoms of chronic plaque psoriasis by inhibition of proinflammatory cytokines that require TYK2 and Janus kinase 1 for signal transduction., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)