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We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (∼777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.

In this study, novel polyethylene glycol @ Si 3 N 4 nanowires as phase-change materials (PCMs) were developed by using ultrasonic cell disruptor. The results obtained herein indicate that these nanowires can be a potential carrier for preparing PCMs. The results show that PEG is composited in a fluffy nano-network structure of Si 3 N 4 nanowires, which could not be easily leaked from this structure for the solid–liquid phase transition. X-ray diffraction and Fourier transform infrared spectroscopy were employed for investigating the structures of PCMs; the results show that a chemical reaction does not occur between PEG and Si 3 N 4 nanowires. Differential scanning calorimetry analysis results indicated that PCMs exhibit appropriate phase-change temperature and excellent high-phase change enthalpy. From the TGA results, PCMs exhibit perfect thermal stability. The PCMs could perfectly maintain their phase transition after 100 melting–freezing cycles. The thermal conductivity of PCMs-1 was 0.362 W/(mK), which was enhanced by 88.54% in comparison with that to pure PEG. The heat storage or release rate of PCMs is significantly more rapid than that of pure PEG for practical applications. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long-term safety and efficacy of filgotinib (FIL) for Japanese patients with rheumatoid arthritis (RA) and limited/no prior methotrexate (MTX) exposure. We present a Japanese population subanalysis of a global randomised-controlled trial at Week 52 and interim long-term extension (LTE) to Week 48 through June 2020., Methods: Patients were randomised to FIL 200 mg plus MTX, FIL 100 mg plus MTX, FIL 200 mg, or MTX for 52 weeks. At completion, eligible patients could enrol in the LTE. Those receiving FIL continued; those receiving MTX were rerandomised (blinded) to FIL 200 or 100 mg upon discontinuation of MTX. After a 4-week washout period, MTX could be re-added., Results: Adverse event rates at Week 52 and in the LTE to Week 48 were comparable across treatment groups. Week 52 American College of Rheumatology 20% improvement (ACR20) rates were 83% (19/23), 82% (9/11), 75% (9/12), and 76% (19/25) for FIL 200 mg plus MTX, FIL 100 mg plus MTX, FIL 200 mg, and MTX, respectively. Through LTE Week 48, ACR20 rates were maintained., Conclusions: In the 56 Japanese patients treated with FIL, efficacy was maintained through Week 52 and beyond, with no increases in the incidence of adverse events., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure., Methods: Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24., Results: Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP <2.6 at Weeks 12 and 24. Adverse event rates were comparable across treatments and between the Japanese and overall populations., Conclusions: While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure., Methods: This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24., Results: The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments., Conclusions: FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX., Competing Interests: Competing interests: RW reports grant/research support from and serving as a consultant for Celltrion, Galapagos, and Gilead Sciences. WFCR reports serving as a consultant for Gilead Sciences. DvdH reports serving as a consultant for AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi Sankyo, Eisai, Eli Lilly and Co., Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma; and is director of Imaging Rheumatology BV. DWTC reports receiving grants from AbbVie, Gilead Sciences, Pfizer, and Sanofi; and serving as a consultant for AbbVie and Pfizer. WS reports receiving consulting fees from Janssen Research and Development, and research support from GlaxoSmithKline. JK reports research grants paid to his institution from AbbVie, Genentech, Gilead Sciences, Pfizer, and UCB; and has received personal fees from AbbVie, Alvotech,Suisse AG, Amgen, Boehringer Ingelheim GmbH, Celltrion Healthcare Co., Janssen Biotech, Merck Sharp & Dohme Corp., Mylan, Novartis AG, Pfizer, Samsung Bioepis, Sandoz, and UCB. AC reports no conflicts of interest. BB, FM, ZY, and YG are shareholders and employees of Gilead Sciences. CT is a shareholder and employee of Galapagos NV. JSS is a shareholder and former employee of Gilead Sciences; and current employee and shareholder of Pandion Therapeutics. NM is a shareholder and former employee of Gilead Sciences, and current employee of Ichnos Sciences. AJ is a shareholder and former employee of Gilead Sciences. ODM reports serving on a speaker’s bureau for Americas Health Foundation, Amgen, and Pfizer. RBML reports serving as a consultant for AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Novartis, Pfizer and UCB. TA reports grant/research support from AbbVie, Alexion, Astellas, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Daiichi Sankyo Co., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., and Pfizer; and has served as a consultant for AbbVie, Chugai, Daiichi Sankyo Co., Eli Lilly Japan K.K., Gilead Sciences, Pfizer, and UCB Japan Co.; and has served on a speakers bureau for AbbVie, Astellas, Bristol-Myers Squibb Co., Chugai Pharmaceutical Co., Daiichi Sankyo Co., Eisai Co., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Pfizer, Takeda Pharmaceutical Co., and UCB Japan Co. GRB reports serving as a consultant and on a speaker’s bureau for AbbVie, Eli Lilly and Co., Pfizer, and Gilead Sciences., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)