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The feasibility of conducting a fully remote, interventional, phase II decentralized clinical trial (DCT) was investigated in major depressive disorder (MDD). Key learnings were collated to improve future DCTs. A double‐blind, placebo‐controlled, parallel‐group, DCT enrolled adult MDD patients with inadequate response to first‐line antidepressant monotherapy (ongoing ≥8 weeks) and a Montgomery‐Åsberg Depression Rating Scale total score (MADRS) ≥22 at screening. Patients were randomized 1:1 to BI 1358894 125 mg or placebo daily for 6 weeks remotely. Safety parameters, primary end point (change from baseline in MADRS at Week 6), and patient experience were assessed. The DCT was considered feasible if the trial protocol could be successfully executed. Overall, DCT procedures were successfully executed per protocol. However, despite achieving a vast patient outreach, the trial was terminated early due to deficient enrollment. Of the 136 patients who consented for enrollment and underwent screening, 45 were randomized and 43 received treatment (BI 1358894, n = 20; placebo, n = 23); 97.7% of patients completed the trial. Patients had a mean (SD) age of 42.2 (13.1) years and most (83.7%) were female. Adverse events were reported by 86.0% of patients (BI 1358894, 90.0%; placebo, 82.6%). Most patients (88%) reported a positive experience with the DCT. Key learnings related to the impact of stringent eligibility criteria, recruitment optimization strategies, plus the benefits and limitations of digital technologies. A fully remote, interventional DCT was feasible in MDD, and was well perceived by trial participants. Learnings related to recruitment optimization and trial design should be considered for future interventional DCTs. [ABSTRACT FROM AUTHOR]

An isocratic reversed-phase high-performance liquid chromatography method with UV detection is developed and validated for the simultaneous determination of ketamine, xylazine, and midazolam in canine plasma. Analytes are extracted from alkalinized samples into diethyl ether–methylene chloride (7:3, v:v) using single-step liquid–liquid extraction. Chromatographic separation is performed on a C18 column using a mobile phase containing an acetonitrile–methanol–10 mM sodium heptanesulfonate buffer adjusted to pH 3, with glacial acetic acid (44:10:46, v:v) at a detection wavelength of 210 nm, with a total runtime of 10 min. The calibration is linear over the range of 78.125–5000 ng/mL for ketamine and 15.625–1000 ng/mL for xylazine and midazolam. The limits of detection are 17.8, 10.3, and 15.1 ng/mL for ketamine, xylazine, and midazolam, respectively. The extraction recoveries are 76.1% for ketamine, 91.0% for midazolam, and 78.2% for xylazine. The method is successfully used for clinical and pharmacokinetic studies of the three-drug fixed dose combination formulations. [ABSTRACT FROM PUBLISHER]

The chemical and physical interaction mechanisms of the water mist with diffusion flame of liquid fuels are investigated. The difference of the thermograms and the thermal field isograms between ethanol flame and kerosene flame with the water mist application is explained. With the water mist application, the differences between ethanol and kerosene in heat release rate, O[sub 2] and CO concentrations of their combustion products, and the temperature of their smoke are analyzed. At the same time, the interaction mechanism of the water mist with diffusion flame is presented and their relationship to the fuel species and to the concentration of water mist is described. [ABSTRACT FROM AUTHOR]

Rationale: While exposure to air pollution is a known risk factor for adverse pulmonary outcomes, its impact in individuals with idiopathic pulmonary fibrosis (IPF) is less well understood., Objective: To investigate the effects of long-term exposure to air pollution on disease severity and progression in patients with IPF and to determine whether genomic factors, such as MUC5B promoter polymorphism or telomere length, modify these associations., Methods: We performed analyses at enrollment and after one year of follow-up in the IPF-PRO Registry, a prospective observational registry that enrolled individuals with IPF at 46 US sites from June 2014 to October 2018. Five-year average pollution exposures (PM 2.5 , NO 2 , O 3 ) prior to enrollment date were estimated at participants' residential addresses with validated national spatio-temporal models. Multivariable regression models estimated associations between pollution exposure and physiologic measurements (FVC, DL CO , supplemental oxygen use at rest) and quality of life measurements (St. George's Respiratory Questionnaire [SGRQ], EuroQoL, Cough and Sputum Assessment Questionnaire) at enrollment. Cox proportional hazard models estimated associations between pollutants and a composite outcome of death, lung transplant, or >10% absolute decline in FVC % predicted in the year after enrollment. Models were adjusted for individual-level and spatial confounders, including proxies for disease onset. Gene-environment interactions with MUC5B and telomere length were assessed., Results: Of 835 participants, 94% were non-Hispanic Whites, 76% were male, mean (SD) age was 70 (7.7) years. In fully adjusted analyses, higher PM 2.5 exposure was associated with worse quality of life per SGRQ activity score (3.48 [95% confidence interval (CI) 0.64, 6.32] per 2µg/m 3 PM 2.5 ) and EuroQoL scores (-0.04 [95%CI -0.06, -0.01] per 2µg/m 3 PM 2.5 ), and lower FVC % predicted and lower DL CO % predicted at enrollment. Each 3 parts per billion difference in O 3 exposure was associated with a 1.57% [95% CI 0.15, 2.98] higher FVC % predicted at enrollment, although this effect was attenuated in multi-pollutant models. There was no association between NO 2 and enrollment measures, between pollution exposure and one-year outcomes, or evidence for gene-environment interactions., Conclusion: In the IPF-PRO Registry, long-term exposure to PM 2.5 was associated with worse quality of life and lung function at enrollment, but not with short-term disease progression or mortality. There was no evidence of effect modification by interaction of genomic factors with pollution. The reason for the unexpected relationship between O 3 exposure and higher FVC is unclear.

Background: The brown planthopper (BPH), Nilaparvata lugens (Stål), is a very destructive pest that poses a major threat to rice plants worldwide. BPH and rice have developed complex feeding and defense strategies in the long-term co-evolution., Methods: To explore the molecular mechanism of BPH's adaptation to resistant rice varieties, the lncRNA expression profiles of two virulent BPH populations were analyzed. The RNA-seq method was used to obtain the lncRNA expression data in TN1 and YHY15., Results: In total, 3,112 highly reliable lncRNAs in TN1 and YHY15 were identified. Compared to the expression profiles between TN1 and YHY15, 157 differentially expressed lncRNAs, and 675 differentially expressed mRNAs were identified. Further analysis of the possible regulation relationships between differentially expressed lncRNAs and differentially expressed mRNAs, identified three pair antisense targets, nine pair cis -regulation targets, and 3,972 pair co-expressed targets. Function enriched found arginine and proline metabolism, glutathione metabolism, and carbon metabolism categories may significantly affect the adaptability in BPH when it is exposed to susceptible and resistant rice varieties. Altogether, it provided scientific data for the study of lncRNA regulation of brown planthopper resistance to rice. These results are helpful in the development of new control strategies for host defense against BPH and breeding rice for high yield., Competing Interests: The authors declare that they have no competing interests., (© 2022 Zha et al.)