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The type, functions, and mechanisms of biological nitrification inhibitors (BNIs) from rice were investigated using a combination of chemical and molecular techniques, bacterial bioassays, and soil microcosm experiments. We report the discovery of an effective nitrification inhibitor, syringic acid, in the root exudates of rice. Nitrification inhibition activity by syringic acid was verified in both weakly acidic and neutral pure cultures of Nitrosomonas europaea, and was superior to the widely used synthetic nitrification inhibitor, dicyandiamide (DCD). Moreover, syringic acid exhibited a dual inhibitory effect on ammonia monooxygenase (AMO), active in ammonium/ammonia oxidation, and on urease, active in urea hydrolysis. Nitrification inhibition by syringic acid was also demonstrated in a paddy soil system, and the abundance of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) was significantly inhibited under all syringic acid treatments. A synergistic effect of syringic acid and another rice BNI, 1,9-decanediol, on nitrification was found in two pure Nitrosomonas cultures and a paddy soil. Together, our results enhance our understanding of BNI production by rice and enable the design of natural inhibitor formulations that regulate soil N transformation in a concerted manner.

ImportanceErythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization.ObjectiveTo assess dupilumab’s efficacy and safety in patients with erythrodermic AD in clinical trials.Design, Setting, and ParticipantsThis post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020.InterventionsDupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS).Main Outcomes and MeasuresEfficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately.ResultsOf 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (−42.0% [7.7%] and −39.9% [6.5%] vs −17.2% [11.0%]; P = .03) and concomitant TCS (−63.2% [6.7%] and −56.1% [9.1%] vs −14.5% [7.3%]; P P = .004 and P = .003, respectively) and concomitant TCS (−78.9% [7.8%] and −70.6% [10.1%] vs 19.3% [8.2%]; P P P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis.Conclusions and RelevanceIn this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials’ overall patient population.Trial RegistrationClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649

BACKGROUND: Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline. OBJECTIVE: We assessed dupilumab's effect on key asthma outcomes in QUEST patients with/without evidence of allergic patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline. OBJECTIVE: We assessed dupilumab's effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE >= 30 IU/mL and >= 1 perennial aeroallergen-specific IgE >= 0.35 kU/L at baseline). METHODS: Severe exacerbation rates and change from baseline in FEV1, asthma control, and markers of type 2 inflammation during the 52-week treatment period were assessed. RESULTS: In the allergic asthma subgroup (n = 1083), dupilumab 200/300 mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (-36.9%/-45.5%; both P < .01), improved FEV1 at week 12 (0.13 L/0.16 L; both P < .001; improvements were evident by the first evaluation at week 2) with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline, and improved asthma control. Dupilumab treatment also resulted in rapid and sustained reductions in type 2 inflammatory biomarkers. Comparable results were observed in patients without evidence of allergic asthma (n = 819). CONCLUSION: Dupilumab reduced severe exacerbation rates, improved FEV1 and asthma control, and suppressed type 2 inflammatory biomarkers in patients with uncontrolled, moderate-to-severe asthma with or without evidence of allergic asthma, highlighting the key role of IL-4 and IL-13 in airway inflammation. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Plant diseases have received common attention, and deep learning has also been applied to plant diseases. Deep neural networks (DNNs) have achieved outstanding results in plant diseases. Furthermore, DNNs are very fragile, and adversarial attacks in image classification deserve much attention. It is important to detect the robustness of DNNs through adversarial attacks. The paper firstly improves the EfficientNet by adding the SimAM attention module. The SimAM-EfficientNet is proposed in this paper. The experimental results show that the accuracy of the improved model on PlantVillage reaches 99.31%. The accuracy of ResNet50 is 98.33%. The accuracy of ResNet18 is 98.31%. The accuracy of DenseNet is 98.90%. In addition, the GP-MI-FGSM adversarial attack algorithm improved by gamma correction and image pyramid in this paper can increase the success rate of attack. The model proposed in this paper has an error rate of 87.6% whenattacked by the GP-MI-FGSM adversarial attack algorithm. The success rate of GP-MI-FGSM proposed in this paper is higher than other adversarial attack algorithms, including FGSM, I-FGSM, and MI-FGSM.

Background Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16. Objective The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator’s Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children’s Dermatology Life Quality Index from baseline. Results Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9–53.3]; both p 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5–66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7–48.1]; both p 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration ClinicalTrials.gov; NCT03054428. Video abstract Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4 212916 kb) Electronic supplementary material The online version of this article (10.1007/s40257-019-00478-y) contains supplementary material, which is available to authorized users.

Summary Background Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13] is approved for patients aged ≥ 12 years with inadequately controlled, moderate‐to‐severe atopic dermatitis (AD). Dupilumab trials of up to 52 weeks demonstrated efficacy and a favourable safety profile in patients with moderate‐to‐severe AD inadequately controlled with topical medications. Objectives To further characterize the safety of dupilumab by evaluating clinical laboratory findings from three randomized, double‐blinded, placebo‐controlled phase III trials (LIBERTY AD SOLO 1 & 2 and LIBERTY AD CHRONOS). Methods Patients were randomized 1 : 1 : 1 (SOLO 1 & 2) or 3 : 1 : 3 (CHRONOS) for 16 and 52 weeks, respectively, to dupilumab weekly, every 2 weeks or placebo. CHRONOS patients received a standardized concomitant topical corticosteroid regimen. Laboratory outcomes were summarized descriptively in 1376 patients from SOLO 1 & 2 and 740 from CHRONOS. Results Treatment groups had similar results in baseline laboratory parameters. Platelets and neutrophils showed mild decreases from baseline in dupilumab vs. placebo groups. Some dupilumab‐treated patients had small transient increases in eosinophils. Grade 3 eosinophilia was reported in < 1% of dupilumab‐treated and placebo‐treated patients; no adverse events were associated with eosinophilia. Lactate dehydrogenase levels decreased from baseline during dupilumab treatment in all trials. No clinically meaningful changes were observed between treatment groups in other haematology, chemistry or urinalysis parameters. Conclusions There were no clinically important changes in routine laboratory parameters that could be attributed to dupilumab. This study supports the use of dupilumab as a systemic treatment for moderate‐to‐severe AD that does not require laboratory monitoring. What's already known about this topic? Long‐term treatment of atopic dermatitis (AD) with conventional immunosuppressive agents is limited by the risk of significant side‐effects and a need for repeated tests to monitor haematological and/or organ (e.g. liver, kidney) toxicities.Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13] is approved for the treatment of patients with inadequately controlled, moderate‐to‐severe AD.In 16‐week and 52‐week studies, dupilumab demonstrated a positive risk/benefit profile in moderate‐to‐severe AD. What does this study add? This study is the first comprehensive analysis of dupilumab laboratory safety data of the 16‐week SOLO 1 & 2 (pooled N = 1376) and 52‐week CHRONOS (N = 740) trials, demonstrating an absence of clinically important changes in haematology, serum chemistry and urinalysis parameters in patients with moderate‐to‐severe AD treated with dupilumab.Our data support the use of dupilumab as a systemic treatment for the long‐term management of moderate‐to‐severe AD without routine laboratory monitoring in clinical practice., Respond to this article

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Auxin, primarily indole-3-acetic acid (IAA), is a versatile signal molecule that regulates many aspects of plant growth, development, and stress response. Recently, microRNAs (miRNAs), a type of short non-coding RNA, have emerged as master regulators of the auxin response pathways by affecting auxin homeostasis and perception in plants. The combination of these miRNAs and the autoregulation of the auxin signaling pathways, as well as the interaction with other hormones, creates a regulatory network that controls the level of auxin perception and signal transduction to maintain signaling homeostasis. In this review, we will detail the miRNAs involved in auxin signaling to illustrate its in planta complex regulation.

Ethnopharmacological relevance Colorectal cancer (CRC) is one type of worldwide popular and refractory tumors. Compound Kushen Injection (CKI) is a frequently applied traditional Chinese medicine formula as an adjuvant drug for the chemotherapy of CRC. P53 is the most commonly mutated gene in CRC, accounting for the development, malignant and prognosis progression of CRC. However, effect of CKI on the therapeutic efficacy of p53-mutant CRC remains understood. Besides, the combined efficacy of different chemotherapeutics drugs in combination with CKI for CRC treatment is rarely concerned. Aim of study To investigate the combined efficacy of the CKI-derived combination strategies in the p53-mutant CRC. Materials and methods Two CRC cell lines HCT116 and SW480 cells, which respectively harbor wild-type p53 and p53-R273H/P309S mutant, were applied. Cisplatin (Cis) and 5-fluorouracil (5FU) were combined chemotherapeutics drugs of CKI-derived combination strategies in this article. In vitro antitumor activity was detected by sulforhodamine B (SRB) assay and colony formation assay. Combenefit soft was applied to evaluate the synergetic/antagonistic effect of drug combination. Lentivirus-mediated overexpression method was used to generate a set of p53-mutant and wild-type CRC cell lines harboring identical genomes. Transcriptomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were applied to predicate the underlying mechanism of synergetic interaction between drug combination. Western blot was performed to verify predicated pathways contributing to the synergy of drug combination. Results CKI preferentially combined with Cis but not 5FU, to produce a synergistical antitumor efficiency for p53-R273H/P309S mutant, rather than wild-type p53 harboring CRC cells. The combination of CKI and Cis strongly reprogrammed the transcriptional profiles of SW480 cells. Cytokine-cytokine receptor interaction pathway was a key pathway involved in cooperativity between CKI and Cis in SW480 cells. Mechanistically, compared to that Cis individually triggered necroptosis, the co-treatment of CKI and Cis reinforced the cell death of SW480 cells in a possible synergistic manner by inducing extrinsic apoptosis pathway. Conclusion This article provides a novel perspective into the precision clinical application of CKI-derived combination therapy programs of CRC based on genetic variation and the classes of chemotherapeutics drugs.

Summary Background In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient‐Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results At week 16, 278 of 449 dupilumab q2w‐treated patients (median age 36·0 years) and 396 of 443 placebo‐treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P < 0·001). Conclusions In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects., What's already known about this topic? An Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin) is considered the regulatory standard for treatment success in trials of patients with atopic dermatitis in the U.S.A.It is currently unknown whether patients receiving dupilumab treatment for moderate‐to‐severe atopic dermatitis derive clinical and quality‐of‐life benefit even if they have an end‐of‐treatment IGA score > 1. What's does this study add? This post hoc analysis of patients with an end‐of‐treatment IGA score > 1 from two randomized, placebo‐controlled trials showed that after 16 weeks of treatment dupilumab significantly improved their outcome measures compared with placebo, including measures of signs, symptoms and quality of life.These results show that the regulatory IGA ≤ 1 end point used in clinical trials significantly underestimates clinically relevant dupilumab treatment effects, underscoring potential limitations of the IGA scale. Linked Comment: https://doi.org/10.1111/bjd.18037. https://www.bjdonline.com/article/

The application of biological nitrification inhibitors (BNIs) is considered an important new strategy to mitigate nitrogen losses from agricultural soils. 1,9-decanediol was recently identified as a new BNI in rice root exudates and was shown to inhibit nitrification in bioassays using Nitrosomonas. However, the effect of this compound on nitrification and ammonia oxidizers in soils remained unknown. In this study, three typical agriculture soils were collected to investigate the impact of 1,9-decanediol on nitrification and ammonia oxidizers in a 14-day microcosm incubation. High doses of 1,9-decanediol showed strong soil nitrification inhibition in all three agricultural soils, with the highest inhibition of 58.1% achieved in the acidic red soil, 37.0% in the alkaline fluvo-aquic soil, and 35.7% in the neutral paddy soil following 14 days of incubation. Moreover, the inhibition of 1,9-decanediol was superior to the widely used synthetic nitrification inhibitor, dicyandiamide (DCD) and two other BNIs, methyl 3-(4-hydroxyphenyl) propionate (MHPP) and α-linolenic acid (LN), in all three soils. The abundance of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) was significantly inhibited by 1,9-decanediol addition across the three soils. All AOB sequences fell within the Nitrosospira group, and the dominant AOA sequences belonged to the Nitrososphaera cluster in all three soils. Changes in the community composition of AOB were more pronounced than AOA after the application of 1,9-decanediol. The AOB community structure shifted from Nitrosospira cluster 2 and cluster 3a toward Nitrosospira clusters 8a and 8b. As for AOA, no significant impact on the proportion of the dominant Nitrososphaera cluster was observed in the fluvo-aquic soil and paddy soil while only the Nitrosopumilus cluster decreased in the red soil. 1,9-decanediol could also significantly reduce soil N2O emissions, especially in acidic red soil. Our results provide evidence that 1,9-decanediol is capable of suppressing nitrification in agricultural soils through impeding both AOA and AOB rather than affecting soil NH4+ availability. 1,9-decanediol holds promise as an effective biological nitrification inhibitor for soil ammonia-oxidizing bacteria and archaea.

Root exudates of rice (Oryza sativa L.) can inhibit nitrification in Nitrosomonas bioassays, and 1,9-decanediol was recently identified as an important new biological nitrification inhibitor (BNI) from rice. However, the release characteristics of 1,9-decanediol have not been studied. The present study was designed to identify the major factors influencing the release of 1,9-decanediol from rice roots. Rice plants were hydroponically grown in controlled environment chambers for 6 weeks, and root exudates were collected. Responses of exudate release to nitrogen form and concentration, pH, aeration, and bacterial inoculation were explored. The pH of root exudates, collected under different nitrogen-provision regimes, was determined, and 1,9-decanediol levels in exudates were monitored. Ammonium (NH4+) and low pH in the root environment stimulated the release of 1,9-decanediol from rice roots. When only a part of the root system was exposed to NH4+, the secretion of 1,9-decanediol was triggered in the whole root system. Aeration of the root environment significantly enhanced 1,9-decanediol release. The presence of two major nitrifiers (Nitrosomonas europaea and Nitrosomonas stercoris) in the root medium stimulated release of 1,9-decanediol, whereas denitrifiers had no effect. Our results demonstrate that the release of 1,9-decanediol is enhanced by low to moderate concentrations of NH4+ (≤1.0 mM), low pH, and aeration of the rhizosphere. Our study provides the first evidence of significant 1,9-decanediol secretion induced by nitrifying bacteria.

Dupilumab is approved for uncontrolled moderate-to-severe atopic dermatitis (AD); cyclosporine is approved for severe AD for ≤ 1 year. The efficacy/effectiveness of these treat-ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index (EASI) EASI-50/EASI-75 at weeks 12-16 and 24-30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center). Models were adjusted for sex, baseline EASI, and thymus and activation-regulated chemokine level. A total of 106 patients received dupilumab (+ topical cortico-steroids; + TCS), and 57 received cyclosporine (+ TCS). Among University Medical Center patients, estimated EASI-50 responders were, dupilumab vs. cyclosporine, 91% vs. 77% (p = 0.038; weeks 12-16), and 96% vs. 67% (p < 0.0001; weeks 24-30); EASI-75 responders were 78% vs. 56% (p = 0.016; weeks 12-16) and 80% vs. 47% (p

David Price,1,2 Andrew Menzies-Gow,3 Claus Bachert,4 Giorgio Walter Canonica,5 Janwillem Kocks,1 Asif H Khan,6 Fen Ye,7 Paul J Rowe,7 Yufang Lu,8 Siddhesh Kamat,8 Victoria Carter,1 Jaco Voorham1,9 1Observational and Pragmatic Research Institute (OPRI), Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland; 3Royal Brompton Hospital, London, England; 4Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; 5Personalized Medicine Asthma and Allergy Center, Humanitas University and Research Hospital, IRCCS, Milan, Italy; 6Sanofi, Chilly-Mazarin, Paris, France; 7Sanofi, Bridgewater, NJ, USA; 8Regeneron Pharmaceuticals Inc., Westchester County, NY, USA; 9Data to Insights Research Solutions, Lisbon, PortugalCorrespondence: David PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, ScotlandTel +65 6802 9724Email dprice@opri.sgBackground: Although prevalence of co-existing type 2 inflammatory diseases (cT2) in asthma patients has been reported, limited data exist regarding their impact on asthma outcomes.Objective: To assess the impact of cT2 burden on asthma outcomes and to evaluate patterns of clustering of cT2 in a real-world setting.Methods: From medical records of 4.5 million enrollees in 650 primary care practices in the UK (January 2010–December 2017), patients with ≥ 1 diagnosis code for asthma at any time pre-index date (date of most recent asthma-related medical encounter) and ≥ 2 asthma-related prescriptions during the year before index date were categorized into the Global Initiative of Asthma (GINA) guideline severity steps. A cT2 burden score (range 0– 9) was assigned based on the total number of co-existing conditions (allergic conjunctivitis, allergic rhinitis, anaphylaxis, eczema/atopic dermatitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, nasal polyps, or urticaria) for which patients received a medical diagnosis. Multivariate regression models evaluated associations between cT2 burden score and asthma exacerbations and asthma control. Factor analysis was performed to assess which cT2 comorbidities were correlated and exhibited patterns of clustering.Results: Overall, 245,893 patients with asthma were included (mean [SD] age 44.8 [22.1] years; 43.8% male). Between 55% (GINA step 1) and 60% (GINA step 5) of asthma patients had a medical diagnosis for ≥ 1 other type2dx. Patients with increased cT2 burden were significantly more likely to experience asthma exacerbations and less likely to achieve asthma control.Conclusion: Asthma patients with a higher cumulative cT2 burden score were more likely to experience worse asthma outcomes than those without any cT2 (burden score of 0).Keywords: type 2 inflammation, asthma, exacerbations, control, comorbidities, burden

BACKGROUND In multiple phase 3 trials, dupilumab improved signs, symptoms (including pruritus), and quality-of-life (QoL) in adults with moderate-to-severe atopic dermatitis (AD). In Italy, dupilumab received innovation status but is currently only reimbursed by the National Health Service for adults with Eczema Area Severity Index (EASI) scores ≥24. This analysis assesses disease burden and dupilumab efficacy in adults with EASI scores above and below this threshold. METHODS This post-hoc analysis included 299 adults pooled from two, randomized, placebocontrolled, phase 3 trials, LIBERTY AD CAFE (NCT02755649) and LIBERTY AD CHRONOS (NCT02260986), who received the approved dupilumab regimen (300mg every 2 weeks) or placebo, with concomitant topical corticosteroids. EASI, Peak Pruritus Numerical Rating Scale (PP-NRS), and Dermatology Life Quality Index (DLQI) were assessed in patients with EASI scores ≥20 to

Rhizospheric microorganisms such as denitrifying bacteria are able to affect 'rhizobioaugmention' in aquatic plants and can help boost wastewater purification by benefiting plant growth, but little is known about their effects on the production of plant root exudates, and how such exudates may affect microorganismal nitrogen removal. Here, we assess the effects of the rhizospheric Pseudomonas inoculant strain RWX31 on the root exudate profile of the duckweed Spirodela polyrrhiza, using gas chromatography/mass spectrometry. Compared to untreated plants, inoculation with RWX31 specifically induced the exudation of two sterols, stigmasterol and β-sitosterol. An authentic standard assay revealed that stigmasterol significantly promoted nitrogen removal and biofilm formation by the denitrifying bacterial strain RWX31, whereas β-sitosterol had no effect. Assays for denitrifying enzyme activity were conducted to show that stigmasterol stimulated nitrogen removal by targeting nitrite reductase in bacteria. Enhanced N removal from water by stigmasterol, and a synergistic stimulatory effect with RWX31, was observed in open duckweed cultivation systems. We suggest that this is linked to a modulation of community composition of nirS- and nirK-type denitrifying bacteria in the rhizosphere, with a higher abundance of Bosea, Rhizobium, and Brucella, and a lower abundance of Rubrivivax. Our findings provide important new insights into the interaction of duckweed with the rhizospheric bacterial strain RWX31 and their involvement in the aquatic N cycle and offer a new path toward more effective bio-formulations for the purification of N-polluted waters.

Atopic dermatitis (also known as AD or eczema) is a common skin disease that can cause intense and persistent itching and rashes. Skin creams or ointments are not suitable or effective for some patients with moderate-to-severe AD. In these patients, oral (taken by mouth) or injected medications may be required. Some of those oral or injected treatments could be toxic and often have unwanted side effects, especially when used for a longer period of time, so patients must be regularly tested to see whether those treatments are harming their blood or organs. Dupilumab is a newer injectable drug for treating moderate-to-severe AD. Dupilumab specifically targets key molecules in the body that cause AD. Dupilumab has been tested for up to one year in more than 2000 patients enroled in placebo-controlled clinical trials. During those trials, patients provided blood and urine samples for laboratory testing while they were being treated with dupilumab or placebo (dummy drug). In this paper, the authors from Germany and the U.S.A, analysed how blood cells, blood chemistry, and urine chemistry changed during treatment, to check whether dupilumab is safe to use without the need for regular laboratory tests. After performing many routine laboratory tests on patients' blood and urine, they found that there were no clinically important changes in test results that could be linked to dupilumab. They concluded that patients using dupilumab for moderate-to-severe AD do not need routine laboratory testing. This is a summary of the study: Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS).

Summary The characterization and detection of lithium metal plating during standard operation of commercial Li-ion batteries has been a long-term challenge; the nature of lithium metal plating is unpredictable and highly dependent on operating temperature and charge rate. In operando detection of lithium plating is critical for ongoing and future developments of conventional Li-ion batteries, including fast charging capabilities, extreme temperature applications, and lithium metal secondary batteries. In this study, we describe the use of acoustic ultrasound to detect lithium metal plating on commercial graphite anodes within a standard form factor. Extending from previous work on ultrasound as a battery diagnostic tool, this proof-of-concept study delineates statistically significant linear relationships between ultrasonic time-of-flight and graphite staging, and acoustic time-of-flight and post mortem electrochemical measurements to characterize the extent of lithium metal plating.

Background: Comorbid perennial allergic rhinitis (PAR) or year-round aeroallergen sensitivity substantially contributes to disease burden in patients with asthma. Dupilumab blocks the shared receptor for interleukin (IL) 4 and IL-13, key drivers of type 2 inflammation that play important roles in asthma and PAR. In the LIBERTY ASTHMA QUEST trial (NCT02414854), dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline (blood eosinophils and fractional exhaled nitric oxide). Objective: To assess dupilumab efficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR. Methods: Severe asthma exacerbation rates, FEV1, asthma control (5-item Asthma Control Questionnaire), rhinoconjunctivitis-specific health-related quality of life (Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores), and type 2 inflammatory biomarkers during the 52-week treatment period were assessed. Results: A total of 814 of the 1902 patients (42.8%) had comorbid PAR (defined as an allergic rhinitis history and >= 1 perennial aeroallergen specific immunoglobulin E (IgE) level >= 0.35 kU/L at baseline). Dupilumab, 200 and 300 mg every 2 weeks, vs placebo reduced severe exacerbations rates by 32.2% and 34.6% (P = 300 cells/mL) and fractional exhaled nitric oxide. Dupilumab treatment also numerically improved the 5-item Asthma Control Questionnaire and Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores and suppressed type 2 inflammatory biomarkers. Conclusion: Dupilumab improved key asthma-related outcomes, asthma control, and rhinoconjunctivitisspecific health-related quality of life while suppressing type 2 inflammatory biomarkers and perennial allergen-specific IgE in patients with moderate-to-severe asthma and comorbid PAR, highlighting its dual inhibitory effects on IL-4 and IL-13 and its role in managing asthma and PAR. (C) 2020 American College of Allergy, Asthma & Immunology.