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The article explores the association between single-nucleotide polymorphisms (SNPs) previously linked to inhaled corticosteroid response and obese-asthma in children. Childhood obesity is a significant risk factor for asthma development and may reduce response to conventional treatment. The study suggests that the SNP rs517762 in the NEGR1 gene, implicated in poor ICS response, is also associated with obesity in children with asthma. The findings highlight potential underlying mechanisms of the pediatric obese-asthma phenotype and call for further validation through prospective and functional studies. [Extracted from the article]

Background: Specific allergy sensitization pattern, using "component‐resolved diagnosis" (CRD), is a central component of allergy and asthma in childhood. Besides this, allergic asthma has been characterized by a Th2‐shifted endotype with elevation of classical Th2 cytokines. Recently, other endotypes with distinct mechanisms focusing on cytokine regulation evolved, yet those pathways are still not well understood. Objective: (a) To define reproducible immunological endotypes using cytokine expression in an asthma cohort and (b) to characterize their sensitization profile and clinical phenotype. Methods: Supernatants from PBMCs of 234 children (median age 10 years) of an asthma cohort were analysed for cytokine expressions. The children were split into a training (n = 49) and validation (n = 185) group. The training group was used to identify immunological endotypes by clustering cytokine expressions, which were then assessed regarding clinical characteristics and specific IgE of recombinant allergen components. Next, our findings were validated in the validation group. Results: We identified novel endotypes based on primarily unstimulated cytokine expression. One endotype showed an IFN‐γ/Interleukin (IL)‐17/IL‐5 predominance, a different sensitization pattern (high in birch/apple; p <.01), and inferior lung function (p <.01). A second endotype grouped young children with food allergy and reduced lung function. Our findings were reproducible in the validation group. Conclusion and clinical relevance: We identified two novel clinical asthma endotypes via cytokine expression pattern with distinct sensitization patterns. These novel findings are critical for clinical guidance and open avenues for identifying underlying mechanisms and more patient‐specific therapies. [ABSTRACT FROM AUTHOR]

Byline: Ratna. Basak, Varsha. Malpani, Khalid. Kakish, Susan. Vargese, Nageshwar. Chauhan, Andreas. Boeck A 2-month-old infant presented to our emergency department with fever, altered consciousness, and focal seizures of acute [...]

Background: Asthma is the most common chronic disease in children. Underlying immunologic mechanisms—in particular of different phenotypes—are still just partly understood. The objective of the study was the identification of distinct cellular pathways in allergic asthmatics (AA) and nonallergic asthmatics (NA) vs healthy controls (HC). Methods: Peripheral blood mononuclear cells (PBMCs) of steroid‐naïve children (n(AA/NA/HC) = 35/13/34)) from the CLARA study (n = 275) were stimulated (anti‐CD3/CD28, LpA) or kept unstimulated. Gene expression was investigated by transcriptomics and quantitative RT‐PCR. Differentially regulated pathways between phenotypes were assessed after adjustment for sex and age (KEGG pathways). Networks based on correlations of gene expression were built using force‐directed graph drawing. Results: Allergic asthmatics vs NA and asthmatics overall vs HC showed significantly different expression of Ca2+ and innate immunity‐associated pathways. PCR analysis confirmed significantly increased Ca2+‐associated gene regulation (ORMDL3 and ATP2A3) in asthmatics vs HC, most prominent in AA. Innate immunity receptors (LY75, TLR7), relevant for virus infection, were also upregulated in AA and NA compared to HC. AA and NA could be differentiated by increased ATP2A3 and FPR2 in AA, decreased CLEC4E in AA, and increased IFIH1 expression in NA following anti‐CD3/28 stimulation vs unstimulated (fold change). Conclusions: Ca2+ regulation and innate immunity response pattern to viruses were activated in PBMCs of asthmatics. Asthma phenotypes were differentially characterized by distinct regulation of ATP2A3 and expression of innate immune receptors (FPR2, CLEC4E, IFIH1). These genes may present promising targets for future in‐depth investigation with the long‐term goal of more phenotype‐specific therapeutic interventions in asthmatics. [ABSTRACT FROM AUTHOR]

Abstract: Background: Allergic and non‐allergic childhood asthma has been characterized by distinct immune mechanisms. While interferon regulating factor 1 (IRF‐1) polymorphisms (SNPs) influence atopy risk, the effect of SNPs on asthma phenotype‐specific immune mechanisms is unclear. We assessed whether IRF‐1 SNPs modify distinct immune‐regulatory pathways in allergic and non‐allergic childhood asthma (AA/NA). Methods: In the CLARA study, asthma was characterized by doctor's diagnosis and AA vs NA by positive or negative specific IgE. Children were genotyped for four tagging SNPs within IRF‐1 (n = 172). mRNA expression was measured with qRT‐PCR. Gene expression was analyzed depending on genetic variants within IRF‐1 and phenotype including haplotype estimation and an allelic risk score. Results: Carrying the risk alleles of IRF‐1 in rs10035166, rs2706384, or rs2070721 was associated with increased risk for AA. Carrying the non‐risk allele in rs17622656 was associated with lower risk for AA but not NA. In AA carrying the risk alleles, an increased pro‐inflammatory expression of ICAM3, IRF‐8, XBP‐1, IFN‐γ, RGS13, RORC, and TSC2 was observed. NOD2 expression was decreased in AA with risk alleles in rs2706384 and rs10035166 and with risk haplotype. Further, AA with risk haplotype showed increased IL‐13 secretion. NA with risk allele in rs2070721 compared to non‐risk allele in rs17622656 showed significantly upregulated calcium, innate, mTOR, neutrophil, and inflammatory‐associated genes. Conclusion: IRF‐1 polymorphisms influence the risk for childhood allergic asthma being associated with increased pro‐inflammatory gene regulation. Thus, it is critical to implement IRF‐1 genetics in immune assessment for childhood asthma phenotypes. [ABSTRACT FROM AUTHOR]

This paper describes the development of an automated ac quantum voltmeter toward a turnkey system, which can be used for calibration of common dc and ac voltage standards. The setup was tested in an accredited commercial calibration laboratory to characterize Fluke 5700A calibrators and voltage standards. The measured voltage in dependence on various parameters is presented in the range of dc to 2 kHz with amplitudes up to 10 V. The uncertainty components are discussed, and the system relevant Type B uncertainty for ac voltage calibrations is 0.15 \mu \textV /V. The contribution of the leakage current is investigated in detail and found to be notable for frequencies above 1 kHz due to parasitic capacitances. The combined measurement uncertainty for calibration ac voltages is less than 0.62 \mu \textV /V ( $k=1$ and 40 Hz–1 kHz) and is limited by the noise of the calibrator. Comparison measurements at Physikalisch-Technische Bundesanstalt have been done and confirm the system reproducibility. [ABSTRACT FROM PUBLISHER]

Individual tree mortality prediction is a key component of single tree-based stand simulators. However, accurate modeling of long-term research plot data is hampered by rare events, variable lengths of observation, and multiple sources of heterogeneity. This study makes use of a result from medicine that demonstrates the equivalence of logistic and Cox proportional hazards regression for modeling survival data in the case of large sample sizes, rare events, and variable interval periods of observation. Pooled logistic regression models are used to model tree mortality across multiple observation periods with random effects to account for heterogeneity due to plots and calendar year. The models are applied to data from 21,051 observation periods (each approximately 5 years) from 9,292 beech trees in a Bavarian long-term forest research plot network. Among the observation periods studied, 604 (2.9%) resulted in a mortality. Indices measuring competition from light, trees of the same species, conifer trees, and shading are significantly associated with mortality, whereas other variables, including dbh, fail to add additional predictive value. Analytic equations for predicting mortality in new trees are provided and yield an area underneath the receiver operating characteristic curve of 91.5%. [ABSTRACT FROM AUTHOR]