Citations

Abstract Oligodendroglioma is a primary central nervous system tumor classified by the presence of isocitrate dehydrogenase (IDH) mutations and codeletion of 1p/19q. Here we describe the generation of an IDH-mutant 1p/19q-codeleted oligodendroglioma mouse model using in utero electroporation. We identified IDH1 R132H , PIK3CA E545K , Cic KO , Fubp1 KO and Cdkn2a KO as the optimal combination (termed Oligo Cdkn2a ) to drive fully penetrant tumors that histologically resemble human grade II/III IDH-mutant, 1p/19q-codeleted oligodendroglioma. Replacing Cdkn2a with Trp53 loss in this mouse model shifted tumor histology towards high grade astrocytoma. Oligo Cdkn2a tumors displayed metabolic and transcriptional changes associated with IDH and CIC mutations, and single cell sequencing identified a bias towards oligodendrocyte differentiation compared to an IDH wild-type glioblastoma mouse model. Oligo Cdkn2a tumors represent the first mouse model system to recapitulate the genetic, histological and transcriptional features of human IDH-mutant 1p/19q-codeleted oligodendrogliomas, offering a platform to further dissect tumor biology and test new therapeutic strategies.

Abstract Rationale We hypothesize that corticosteroid resistance causes uncontrolled inflammation and severe asthma. The genetic and molecular mechanisms underlying steroid responsiveness in asthma remain poorly understood (PMID28493293). This study aims to characterize transcriptomic profiles distinguishing steroid responders from steroid resistant asthma. Methods Longitudinal bulk RNA-seq of SARP3 sputum samples was analyzed before and after an “induced phenotype” with 40 mg triamcinolone acetonide (TCA) injection (PMID 27967215). Participants were classified as responders or non-responders based on whether their FEV₁ change after TCA exceeded the median. Paired differential gene expression analyses were performed separately for each group using limma and voom, with participant as a factor and adjustment for sputum cell count differentials. Z-scores were calculated to compare gene expression changes after TCA injection between responders and non-responders, and pathway enrichment was assessed using the fgsea package. Results Baseline demographics and clinical characteristics of 696 SARP3 asthma participants receiving TCA are shown in Table 1. The median [IQR] FEV1 change post-TCA was 1.81% [-2.16, 7.17]. Responders had higher baseline FEV1%, FEV1/FVC ratio, blood eosinophil counts, and sputum eosinophil percentages, but lower serum CRP levels. Steroid responsiveness was associated with asthma severity (Table 1). Among 154 participants with paired sputum RNA-seq data, 70 (45%) exhibited >1.81% improvement in FEV₁ and were classified as responders. Following TCA treatment, non-responders showed no significant changes in gene expression. In responders, 18 genes were upregulated and 203 downregulated. Downregulated genes were associated with Th2 immunity (IL13, IL1RL1, CCL17, SIGLEC8), IgE signaling (FCER1A, FCER2), epithelial barrier function and mucus production (MUC2, MUC7, ALOX15, TFF3), tissue remodeling and fibrosis (MMP10, TIMP3), ciliary function (DNAH5, CFAP43, FOXJ1), and airway hyperreactivity (HRH4, RAMP1). Key genes notably downregulated in responders compared to non-responders included IL13, CCL5, PTGDR2, FCER2, and CLEC10A. Pathway analysis revealed enhanced IL-10-mediated anti-inflammatory signaling, suppression of pro-inflammatory pathways (NF-κB, IL-1, Th1/Th2, asthma, arachidonic acid metabolism, chemokine, NOTCH4), and regulation of mitochondrial oxidative phosphorylation. Conclusions Steroid resistance impairs glucocorticoid-mediated suppression of pro-inflammatory pathways, including NF-κB, IL-1, and Th1/Th2 signaling. This persistent airway inflammation limits improvements in lung function and contributes to worse clinical outcomes, including increased airflow obstruction, and symptom burden. Glucocorticoid resistance in asthma may be driven by receptor dysfunction, airway inflammation, epigenetic changes, and environmental exposures resulting in persistent airway inflammation and remodeling. Elucidating the molecular mechanisms underlying steroid resistance is critical for developing personalized targeted therapies in asthma. This abstract is funded by: NIH-NHLBI - R01 HL161674 (PI: Joe Zein)

Abstract Rationale Primary ciliary dyskinesia (PCD) pathogenic gene variants disrupt motile cilia, leading to both PCD and asthma through epithelial dysfunction. Asthma shows sex differences, and progesterone regulates ciliary beat frequency, indicating that genetic defects in ciliary proteins may exert sex-dependent effects. Therefore, we hypothesize that rare, pathogenic variants in PCD genes contribute to asthma risk in a sex-specific manner. Methods We performed a rare-variant aggregation analysis of the DNAH11 gene using UK Biobank OQFE exome dosages, with sex-stratified analyses. Within each sex, genotype dosages were coded as individual-level minor allele counts (0-2) and filtered to include variants with a minor allele frequency (MAF) ≤1% and a minor allele count (MAC) ≥5 across the cohort. Asthma phenotypes were defined from a curated dataset (N = 452,927), excluding COPD and other lung diseases. For each sex, logistic null models adjusted for age were fitted, and gene-level associations for binary outcomes were tested using SKAT, Burden, and SKAT-O. To assess variant-specific influences, we performed leave-one-out (LOO) analyses, sequentially omitting each variant and recalculating p-values. The effect size across the cohort was calculated by fitting a Firth logistic regression comparing carriers to non-carriers, adjusted for age by sex. Finally, sex modification was tested using a Firth model including carrier-by-sex interaction term. Results After filtering, DNAH11 included two rare variants; 7:21564185-G>T and 7:21591370-G>A in each sex (MAF≈1-2x10-5). Among females (N = 245,718; 28,649 with asthma), 16 carriers were observed (MAC≈16). Gene-based tests showed a significant association with asthma (Burden_p=0.004; SKAT-O_p=0.005; SKAT_p=0.013). Firth carrier model OR was 4.58 (95% CI 1.62-11.98, p = 0.0055) (Figure 1A). LOO analyses (Figure 1B) showed both variants contributed to the signal; removing 7:21591370-G>A increased SKAT-O p to 0.075 (Δ-log10p≈+1.15), while removing 7:21564185-G>T increased p to 0.014 (Δ-log10p≈+0.41, with the association remaining significant after removing the latter. Among males (N = 207,209; 20,777 with asthma), 10 carriers were observed (MAC≈10) with no significant association (Burden_p=0.926; SKAT-O_p=0.797; SKAT_p=0.668; Firth_p=0.781). The carrier-by-sex interaction term in the combined Firth model was not significant (p = 0.190), suggesting the female-specific signal could not be detected in the males due to limited power. Conclusions This analysis provides primary evidence that these rare, pathogenic variants in the DNAH11 PCD gene may contribute to asthma susceptibility in a sex-specific manner, with a significant association observed only in females. The signal was predominantly driven by 7:21591370-G>A. This suggests that genetic disruption of ciliary function may interact with female-specific hormonal factors (i.e., progesterone) to influence asthma risk. This abstract is funded by: NIH

Abstract Rationale Asthma and obesity are common comorbidities, both driven by inflammation and oxidative stress. Oxylipins are derivatives of polyunsaturated fatty acids that regulate the onset and resolution of inflammation. Oxylipin profiles are altered in obesity and have been shown to differentiate asthma from non-asthma; however, the association between oxylipins and asthma outcomes and the impact of obesity is not known. This study aims to identify differences in serum oxylipins associated with asthma morbidity and evaluate the effect modification by BMI. Methods We analyzed 150 participants in the Best African American Response to Asthma Drugs (BARD) clinical trial. Ninety oxylipins were quantified using liquid chromatography tandem mass spectroscopy from serum obtained at the time of randomization. Oxylipins found to be above the limit of detection in > 80% of samples were log-transformed and included in the analysis. Asthma severity measures included past 12-month systemic corticosteroid use for asthma exacerbation, spirometry, asthma control and asthma quality of life questionnaires (AQLQ). The associations between oxylipins and asthma outcomes were tested using multivariable regression models adjusted for sex, age, BMI, absolute eosinophil count, percent African ancestry, and child vs adult/adolescent cohort. A false discovery rate (FDR) of < 0.1 is used to determine statistical significance. Results Of the 90 oxylipins measured, 42 (46.7%) were detected in > 80% of all samples and included in the analysis. In multivariable models, the pro-inflammatory arachidonic acid (AA) derivative 5,6-DiHETrE was associated with decreased odds of past 12-month systemic corticosteroid use (FDR-adjusted p-value 0.0628). AA derivatives TXB2, PGF2a, and 6-α-prostaglandin were associated with increased FEV1/FVC (FDR-adjusted p-values=0.0925). Thirteen oxylipins were associated with decreased asthma-related quality of life in multivariable models, including AA metabolites 5S-HETE, 5-KETE, 14,15-EET, LTB4, and Lipoxin A4; dihomo-gamma-linoleic acid metabolites 5-HETrE and 15-HETrE; linoleic acid metabolites 3-OxoODE and 9-OxoODE; and eicosapentaenoic acid metabolites 15-HEPE and 17,18-EpETE, all with FDR-adjusted p-values<0.05. Oxylipin-BMI interaction was significant only in the AQLQ models. In all but LTE4, increased concentrations of oxylipins were associated with a decreased quality of life in individuals with higher BMI (Figure). Six of these oxylipins are products of lipoxygenase activity. Conclusions In this study, we find decreased quality of life with increasing concentrations of pro-inflammatory and resolving oxylipins among those with obesity. These oxylipins are primarily produced via lipoxygenases and may represent an important inflammatory pathway in obesity-associated asthma. Quantification of sputum oxylipins and correlation with serum levels will be important in understanding potential mechanisms and is forthcoming. This abstract is funded by: K12TR004412, R01HL123385, U10HL098075, Parker B. Francis Fellowship, 2L30HL159725

Abstract Rationale Asthma exacerbations remain a leading cause of emergency visits and impaired quality of life. The 2025 Global Initiative for Asthma (GINA) report emphasizes early identification of Type 2 inflammation, treatable traits, and comorbidities to prevent attacks. Machine learning (ML) was applied to population level data to uncover complex, nonlinear relationships between biomarkers, lifestyle factors, and exacerbation risk. This study aimed to identify key predictors of asthma exacerbations using explainable ML techniques and to interpret these predictors through the lens of GINA 2025 guidelines. Methods A cross-sectional analysis was performed using the National Health and Nutrition Examination Surveys (NHANES) 2017-2020. Adults aged ≥18 years with available asthma history and laboratory data (n = 7,922) were included. The outcome was self-reported asthma exacerbation within the past 12 months. Univariable logistic regression was used to preselect covariates from 680 demographic, dietary, laboratory, and anthropometric variables using a significance threshold of p < 0.0001. Selected covariates were then entered into an XGBoost classifier. Model discrimination was assessed by the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Feature importance was ranked by the Gain metric, and Shapley Additive Explanations (SHAP) were applied to improve interpretability and align results with GINA 2025 clinical domains. Results The final model included 55 covariates and achieved an AUROC of 0.737, sensitivity of 0.960, and NPV of 0.967 for predicting exacerbations. The most influential features were octanoic acid intake, eosinophil percentage, hip circumference, standing height, and high-sensitivity C-reactive protein (hs-CRP). Individuals reporting exacerbations had higher eosinophil percentages (3.36% vs. 2.76%), larger hip circumference (115.2 cm vs. 107.2 cm), and higher hs-CRP (6.08 vs. 4.00 mg/L). These findings correspond to GINA 2025’s emphasis on eosinophils as biomarkers for anti-inflammatory therapy, systemic inflammation as a treatable trait, and obesity as a modifiable risk factor for symptom control and exacerbation prevention. Conclusion Explainable ML applied to NHANES data accurately identified physiologic and inflammatory predictors of asthma exacerbations that mirror the GINA 2025 framework. Eosinophil levels, systemic inflammation, and adiposity emerged as key treatable traits linked to exacerbation risk. These findings demonstrate the utility of ML in translating population-level data into actionable insights consistent with GINA 2025’s strategy for individualized, inflammation-guided asthma management. This abstract is funded by: None

Abstract Rationale Asthma, a chronic inflammatory airway disease, can be influenced by hormonal fluctuations that affect immune function and airway responsiveness. During in-vitro fertilization (IVF), women undergo sequential hormonal treatments—including gonadotropin administration to stimulate follicle development and induce ovulation, and progesterone and estrogen to support implantation and early pregnancy. These precisely timed hormonal changes may affect asthma symptoms and increase the risk of exacerbations. This study evaluates the hypothesis that undergoing IVF increases the risk of asthma exacerbations prior to, but not during or after pregnancy. Methods Data were extracted from the Mayo Clinic electronic health records. Women were included if their pregnancy was recorded in the Mayo Clinic obstetric delivery dataset. Asthma was defined as the presence of an ICD code J45.xx in combination with a prescription for any asthma medication. For women with multiple pregnancies, only the first pregnancy was analyzed. An asthma exacerbation was defined as a course of oral corticosteroids lasting ≤28 days or a corticosteroid injection. Multivariable logistic regression was used to assess exacerbation risk, adjusting for age, body mass index (BMI), and prior history of diabetes mellitus. Results Among 3,623 pregnant women, 112 underwent IVF treatment. Compared with non-IVF patients, women undergoing IVF were older (mean ± SD: 34.16 ± 5.24 vs. 29.11 ± 5.55, p < 0.001), had lower parity (1.44 ± 0.79 vs. 1.83 ± 1.20, p = 0.001), and fewer full-term deliveries (1.31 ± 0.79 vs. 1.68 ± 1.11, p = 0.001) (Table 1). There were no differences in pre-pregnancy BMI, racial distribution, ethnicity, or prior history of diabetes mellitus. Adjusted analysis indicated that IVF was associated with an increased risk of asthma exacerbation in the year before pregnancy (adjusted OR [95% CI]: 1.097 [1.025-1.173]), but not during (adjusted OR [95% CI]: 1.044 [0.973-1.121]) or after pregnancy (adjusted OR [95% CI]: 1.026 [0.963-1.094]). Conclusion These findings suggest that the preconception hormonal changes associated with IVF may temporarily worsen asthma control. Further studies are warranted to replicate these results, clarify the underlying mechanisms, and guide asthma management in women undergoing fertility treatment. This abstract is funded by: NIH

Abstract Rationale Asthma is a chronic inflammatory airway disorder influenced by pulmonary and systemic factors. Epidemiologic and experimental data suggest associations between asthma, anemia, and reduced iron stores. Sex may modify this relationship: females, with lower baseline iron reserves, menstrual blood loss, and hormone-mediated immune effects, may exhibit greater susceptibility, whereas males, with higher iron stores and androgen-related anti-inflammatory influences, appear less affected. This study tested the hypothesis that diminished iron stores, rather than anemia itself, are associated with asthma, and that this relationship differs by sex. Methods Data were analyzed from nine consecutive NHANES 2-year cycles (1999-2018), a nationally representative U.S. dataset. Lifetime asthma was defined as a prior physician diagnosis and active asthma as “Do you still have asthma?”. Anemia was defined by WHO criteria (hemoglobin <12 g/dL in females and <13 g/dL in males), and iron deficiency as ferritin <30 ng/mL. Accordingly, iron status was categorized as normal, iron deficiency anemia (IDA), iron deficiency without anemia (IDWA), and anemia without iron deficiency (AWID). Analyses followed NHANES guidelines and were conducted with the SURVEY package in R. Results Female participants were older and had lower eosinophil counts, ferritin, and hemoglobin levels, with a higher prevalence of anemia, lifetime asthma, and current asthma. Similar trends were observed among participants with available ferritin data (Table 1). In unadjusted analyses, ferritin levels were inversely associated with lifetime (β = -0.19; p <0.001) and active asthma (β = -0.35; p <0.001), but these associations were not significant after adjustment for sex, age, BMI, race, and log10-transformed eosinophil count (lifetime: β = 0.03; p = 0.61; active: β = -0.08; p = 0.40). In contrast, anemia was associated with increased odds of lifetime (adjusted OR [95% CI], 1.52 [1.21-1.92]) and active (1.50 [1.13-1.99]) asthma in males, but not in females (0.98 [0.86-1.12] and 0.98 [0.83-1.15], respectively). Among males, AWID was associated with active asthma (2.07 [1.08-3.96]), whereas IDA and IDWA were not. No associations were observed among females. Conclusion The relationship between anemia and asthma may be primarily driven by inflammation related to asthma rather than true iron deficiency. After adjustment, ferritin was not independently associated with asthma, whereas anemia—particularly AWID—remained associated among males. These findings suggest that asthma-associated systemic inflammation contributes to anemia of chronic disease, underscoring the need to distinguish inflammatory anemia from nutritional iron deficiency in research and clinical management. This abstract is funded by: NIH

Abstract Introduction Inhaled corticosteroid/fast-acting beta2-agonist combinations are recommended over albuterol-alone as rescue in asthma due to superior exacerbation reduction. In adults with asthma, BATURA and MANDALA demonstrated as-needed albuterol-budesonide 180/160 μg reduced the risk of severe exacerbation by 46% in mild and 28% in moderate-to-severe asthma for patients aged ≥18 years versus albuterol 180 μg. However, albuterol is the long-held rescue therapy standard for treatment of bronchoconstriction. In the ALbuterol-budesonide Treatment in Acute Airway Obstruction (ALTA) (NCT05555290) study, repetitive albuterol-budesonide 180/160 ug versus albuterol 180 ug treatment resulted in equally rapid improvement in lung function over 60 minutes and provided enhanced bronchodilation at 480 minutes post-mannitol challenge: least squares mean/LSM(standard error/SE) [95%CI] difference in ΔFEV1=91.2 (27.4) [36.7-145.7] mL. This post-hoc analysis of ALTA evaluated whether baseline lung function affects treatment response. Methods ALTA was a Phase 3b, multicenter, randomized, double-blind, 2-period, crossover study evaluating efficacy of repetitive albuterol-budesonide 180/160 μg vs albuterol 180 μg in adults with mild asthma experiencing ≥15% fall in FEV1 with cumulative mannitol exposure ≤635 mg. Inclusion criteria included use of short-acting beta2-agonist as the only pre-enrollment therapy for ≥4 weeks and pre-challenge FEV1 ≥1.500 L and 60%-<90% of predicted. Participants received albuterol-budesonide or albuterol at end-mannitol challenge (time 0) and 20, 40, and 60 minutes thereafter. FEV1 was assessed starting pre-mannitol challenge (-30 minutes) and over 480 minutes post-challenge. For participants with baseline FEV1 60%-<80% and 80%-<90% predicted, LSM(SE) [95%CI] difference between treatment arms in ΔFEV1 from time 0 min at 480 minutes was analyzed using a linear mixed effects model. Results 88 randomized participants receiving ≥1 dose of study drug were included: mean(SD) age=44.5(13.7) years; 56.8% female; mean(SD) FEV1=2.462(0.540) L (76.7[7.7]% predicted). 56 participants had baseline FEV1 ≥60%-<80% predicted; 32 had baseline FEV1 80%-<90% predicted. Percent fall in FEV1 post-challenge was similar between lung function subgroups. Improvement in FEV1 post-mannitol (time 0 min) at 480 min was greater with albuterol-budesonide vs albuterol treatment for both FEV1 subgroups: LSM(SE) [95%CI] difference 71.0(29.8) [11.0-131.0] mL, p = 0.021 in the lower and 114.0(55.1) [1.0-227.0] mL, p = 0.048 in the higher baseline FEV1 participants (Figure). There was no significant difference in the treatment by subgroup interaction, suggesting consistent treatment efficacy between subgroups. Conclusions Albuterol-budesonide relieves acute obstruction better than albuterol over time in mild asthma whether or not baseline lung function falls within a normal range. This abstract is funded by: AstraZeneca

Abstract Rationale Lung fibroblasts (FBs) play a pivotal role in airway remodeling in asthma. During profibrotic and inflammatory conditions, FB undergoes myofibroblast differentiation, which contributes to airway wall thickening, stiffness, and airflow obstruction. Myofibroblast differentiation is a process in which fibroblasts transform into highly contractile fibers in response to profibrotic mediators such as transforming growth factor-beta 1 (TGF-β1). This transition is characterized by increased production of alpha-smooth muscle actin (α-SMA), and the formation of actin stress fibers, which are crucial for contractile machinery. Our previous findings identified the important role of Kisspeptin/KISS1R (Kp/KISS1R) in airway smooth muscle remodeling. However, there is no information about the expression and function of Kp/KISS1R in the lung FB. This study investigates the expression of Kp/KISS1R in lung FB and their role in myofibroblast transition. Methods Primary human lung FBs were isolated from surgical lung resections (Mayo IRB-approved) and cultured in DMEM-high glucose medium with 10% fetal bovine serum and 1% antibiotic/antimycotic. Upon reaching ∼90% confluence, cells were serum-deprived and treated with kisspeptin-10 (Kp-10, 1 µM) in the presence or absence of TGF-β1 (10 ng/mL). Expression of Kisspeptin, KISS1R and α-SMA in FB cells were assessed by western blotting and confocal microscopy. FB filamentous (F)-actin formation was analyzed by staining with phalloidin. In addition, collagen gel contraction assays were performed to study fibroblast contractility. Results We found the ubiquitous expression of kisspeptin and KISS1R in human FB. Notably, we observed that KISS1R expression was significantly reduced in asthmatic FB compared to non-asthmatic FB cells. Consistent with this observation, exposure of profibrotic mediator TGF-β1 effectively reduced the expression of KISS1R in non-asthmatic FB. Furthermore, TGF-β1 exposure significantly increased the α-SMA expression in human FB cells, a myofibroblast marker. Treatment with Kp-10 significantly reduced TGF-β1-induced α-SMA expression in FB cells. TGF-β1 stimulation in human FB increased the F-actin formation. Kp-10 significantly attenuated TGF-β1-induced F-actin formation in FB cells. Additionally, chronic TGF-β1 exposure enhanced collagen gel contraction by FBs, while Kp-10 treatment effectively reduced this contraction. Conclusion This study demonstrates that activation of Kp/KISS1R signaling attenuates TGF-β1-induced myofibroblast differentiation in lung FB, suggesting KISS1R as a potential therapeutic target against airway remodeling. This abstract is funded by: NIH grant R01-HL146705 (Venkatachalem)

Abstract Rationale Bronchial airways are exposed to continual mechanical forces such as normal breathing, sighs, and clinically applied pressures such as CPAP that influence airway smooth muscle mechanics. Asthmatic airways experience exaggerated mechanical stress due to bronchoconstriction and airway wall thickening (remodeling) which contributes to lung injury. Mechanical stress is known to alter redox balance and ion channel signaling, yet its impact on iron homeostasis in asthmatic human airway smooth muscle cells (hASMs) remain unclear. Ferroptosis and iron dysregulation have emerged as significant factors in epithelial damage and airway inflammation in asthmatic models. In addition, recently discovered mechanosensitive Piezo (PZ) channels play a critical role in calcium influx upon mechanical stimulation and have been shown to contribute to iron dysregulation. In this study, we used hASMs to test the hypothesis that asthmatic patients experience iron dysregulation in the presence of mechanical stimulation. Methods hASMs and lung tissues from adult male and female patients with/without asthma were used (approved by Mayo IRB). Cells were pretreated with either PZ inhibitor GsMTx4 [1 µM] or PZ1 agonist Yoda1 [10 µM] 45 minutes before stretch. Cells were exposed to normal breathing stretch conditions on a FlexCell System at a 5% cyclic strain (15 cycles/minute) or 10% static stretch superimposed onto normal breathing for 24 hours. Cell lysates were examined for iron accumulation and antioxidant and lipid peroxidation markers (FTH1, TfR1, GPX4, and SLC7A11). Levels of intracellular ferrous iron (Fe2+) were determined using the fluorescent dye FerroOrange in non-stretched samples. Results In healthy airways PZ inhibition decreased iron uptake while activation increased intracellular iron uptake. In healthy airways, mechanical stretch upregulated SLC7A11 expression in a PZ1 independent manner, while mechanical stretch in asthmatic patients displayed no increase in the cysteine transporter. Transferrin levels remained unchanged under mechanical stimulation but displayed upregulation in asthmatic cells. In healthy cells, ferritin showed no changes in response to stretch, however, asthmatic cells showed lower baseline expression and increased its expression in response to stretch in a PZ1 independent manner. GPX4 showed no changes in expression between healthy and asthmatic groups or in response to stretch. Conclusions Our findings suggest that PZ and mechanical stretch play a role in iron regulation in hASMs. Additionally, iron regulation is impaired in asthmatic populations, suggesting a resultant increased iron import, decreased capacity to sequester iron, and decreased defensive cysteine import. This abstract is funded by: NIH R01HL171915 (CMP), R01HL056470 (YSP) 24POST1241979 (NAB)