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Background Dual bronchodilation combining a long-acting β 2 -agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials. Methods The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments. Results The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV 1 ; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV 1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies. Conclusions IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments. Trial registration ClinicalTrials.gov number: NCT01985334 .

COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function. Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy. This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting β -agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID. CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings. Three definitions of CID (D1-D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV ), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD). In D1 and D2, either TDI or CCQ was evaluated along with FEV and AECOPD, whereas in D3, all 4 parameters were included. ClinicalTrials.gov number: NCT01985334. Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments. The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30-0.55]; D2: OR 0.41 [95% CI: 0.31-0.55]; D3: OR 0.39 [95% CI: 0.29-0.52]). Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56-1.02]; D2: OR 0.75 [95% CI: 0.56-1.00]; D3: OR 0.67 [95% CI: 0.51-0.89]). In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice.

The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction. Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery-Åsberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Efficacy and tolerability were assessed by pre-switch SSRI therapy where possible, and by participant characteristics. Greater improvements in TESD were seen in the vortioxetine compared with escitalopram groups based on: participant demographics (≤45 years, women; P = 0.045), prior SSRI treatment (P = 0.044), number of prior major depressive episodes (MDEs) (1-3; P = 0.001), and duration of prior SSRI therapy (>1 year; P = 0.001). Prior SSRI treatment did not appear to influence the incidence or severity of TEAEs, except for nausea. Regardless of prior SSRI, both treatments maintained antidepressant efficacy after 8 weeks. Results suggest that vortioxetine is a safe and effective switch therapy for treating SSRI-induced sexual dysfunction in adults with well-treated MDD. Also, improvement in sexual dysfunction with vortioxetine or escitalopram may be influenced by prior SSRI usage, sex, age, and history of MDEs.

Macrophages (Mϕs) critically contribute to wound healing by coordinating inflammatory, proliferative, and angiogenic processes. A proper switch from proinflammatory M1 to anti‐inflammatory M2 dominant Mϕs accelerates the wound healing processes leading to favorable wound‐care outcomes. Herein, an exosome‐guided cell reprogramming technique is proposed to directly convert M1 to M2 Mϕs for effective wound management. The M2 Mϕ‐derived exosomes (M2‐Exo) induce a complete conversion of M1 to M2 Mϕs in vitro. The reprogrammed M2 Mϕs turn Arginase (M2‐marker) and iNOS (M1‐marker) on and off, respectively, and exhibit distinct phenotypic and functional features of M2 Mϕs. M2‐Exo has not only Mϕ reprogramming factors but also various cytokines and growth factors promoting wound repair. After subcutaneous administration of M2‐Exo into the wound edge, the local populations of M1 and M2 Mϕs are markedly decreased and increased, respectively, showing a successful exosome‐guided switch to M2 Mϕ polarization. The direct conversion of M1 to M2 Mϕs at the wound site accelerates wound healing by enhancing angiogenesis, re‐epithelialization, and collagen deposition. The Mϕ phenotype switching induced by exosomes possessing the excellent cell reprogramming capability and innate biocompatibility can be a promising therapeutic approach for various inflammation‐associated disorders by regulating the balance between pro‐ versus anti‐inflammatory Mϕs. An exosome‐guided cell reprogramming technique to directly convert M1 to M2 macrophages in situ is introduced as a promising therapeutic strategy for effective and rapid wound healing. With excellent cell reprogramming capabilities and biocompatibility, the exosome‐guided macrophage reprogramming technique can be applied not only to wound healing but also to various inflammation related diseases.

Responsive soft materials capable of exhibiting various three-dimensional (3D) shapes under the same stimulus are desirable for promising applications including adaptive and reconfigurable soft robots. Here, we report a laser rewritable magnetic composite film, whose responsive shape-morphing behaviors induced by a magnetic field can be digitally and repeatedly reprogrammed by a facile method of direct laser writing. The composite film is made from an elastomer and magnetic particles encapsulated by a phase change polymer. Once the phase change polymer is temporarily melted by transient laser heating, the orientation of the magnetic particles can be re-aligned upon change of a programming magnetic field. By the digital laser writing on selective areas, magnetic anisotropies can be encoded in the composite film and then reprogrammed by repeating the same procedure, thus leading to multimodal 3D shaping under the same actuation magnetic field. Furthermore, we demonstrated their functional applications in assembling multistate 3D structures driven by the magnetic force-induced buckling, fabricating multistate electrical switches for electronics, and constructing reconfigurable magnetic soft robots with locomotion modes of peristalsis, crawling, and rolling. Responsive soft materials which can exhibit various three-dimensional (3D) shapes under the same stimulus are desirable for applications in adaptive and reconfigurable soft robots. Here, the authors report a laser rewritable magnetic composite film, whose responsive shape-morphing behaviors induced by a magnetic field can be digitally and repeatedly reprogrammed by a facile method of direct laser writing.

This paper proposes a simple and efficient resonant DC link inverter topology with low current stress on main switches. The inverter has a straightforward structure and is readily controllable, avoids the auxiliary resonant current passing through the main switches of the inverter, and the current passing through the main switches remains consistently equivalent to the load current, thus reducing the current stress and the switching loss of the main switches, thereby the inverter’s efficiency is increased. The proposed inverter’s operating principle is examined and contrasted with the inverter described in the literature. Ultimately, the validity of the resonant DC link inverter is demonstrated through simulation.

In this study, a novel buck–boost DC/DC converter is presented. The circuit structure of the proposed converter consists of a single power switch, two diodes and some energy storage elements. Employing only a single power switch reduces the implementation cost and switching power losses. The proposed converter has higher voltage gain in step-up mode in comparison with conventional buck–boost and Cuk converter. In addition, this converter expands the continuous conduction mode (CCM) operational region. The presented converter has three operation modes in CCM. The second mode reduces the voltage stresses across the capacitors. Therefore the current stresses on diodes are also reduced. To verify the operation of the proposed converter, the experimental results are provided using a hardware prototype.

The article presents a new generation of ultra-fast hybrid switching systems (USH) for reliable, ultra-fast protection of various medium and low voltage DC systems (MVDC and LVDC). The DC switch-off takes place in a vacuum chamber (VC) cooperating with a semiconductor module using current commutation of natural or forced type. Against the background of the current state of science and technology, the paper depicts the basic scopes of USH applications and their particular suitability for operation in high magnetic energy DC circuits. In the case of DC system failures, this magnetic energy should be dissipated outside the system as soon as possible. Usually, magnetic blow-out switches (MBOS) with relatively low operating speed are used for this purpose. The article describes the theoretical basis and principles of construction of two types of novel USH systems: a direct current switching system (DCSS) and a direct current ultra-fast hybrid modular switch (DCU-HM). The DCSS family is designed for quench protection of superconducting electromagnets’ coils in all areas of application. The DCU-HM family is designed for the protection of all systems or vehicles of DC electrical traction and for related industrial applications. The conducted comparative analysis of the effectiveness of USH with respect to MBOS shows clear technical advantages of the new generation switching systems over MBOS. List of abbreviations used in the article is provided at the end.

To develop high‐voltage‐pulsed power switches with better performances, a multi‐gap laser‐triggered vacuum switch is proposed in this study. Based on established test prototype for double‐gap laser‐triggered vacuum switch, closing processes of double‐gap laser‐triggered vacuum switch are discussed combined with laser‐produced plasma. Closing performances of double‐gap laser‐triggered vacuum switch under different gap polarity configurations, operating voltages, laser energies and laser split ratios are investigated. Closing time delay characteristics of double‐gap laser‐triggered vacuum switch and single‐gap laser‐triggered vacuum switch are compared later. The test results prove that, affected by the imbalanced developed initial plasma between gaps, double‐gap laser‐triggered vacuum switch with two positive gaps and 1:1 laser split ratio presents best closing performances than other switches. With the rise of laser energy, closing delay time and jitter time of double‐gap laser‐triggered vacuum switch both decrease, while the influences from increasing voltages are weak. Closing delay time of P–P type double‐gap laser‐triggered vacuum switch can be controlled within 103 ± 1.5 ns under 90 mJ laser energy, and it is about 10 ns longer than single‐gap laser‐triggered vacuum switch. For some direct current applications with changing voltage directions, P–N type double‐gap laser‐triggered vacuum switch with 1:1 laser split ratio shows more stable closing performances. In addition, closing performances of double‐gap laser‐triggered vacuum switch can be further improved by optimizing the developments of initial plasma in series gaps.

Rectenna is the key component in radio-frequency circuits for receiving and converting electromagnetic waves into direct current. However, it is very challenging for the conventional semiconductor diode switches to rectify high-frequency signals for 6G telecommunication (>100 GHz), medical detection (>THz), and rectenna solar cells (optical frequencies). Such a major challenge can be resolved by replacing the conventional semiconductor diodes with tunneling diodes as the rectenna switches. In this work, metal–insulator–metal (MIM) tunneling diodes based on 2D insulating materials were designed, and their performance was evaluated using a comprehensive simulation approach which includes a density-function theory simulation of 2D insulator materials, the modeling of the electrical characteristics of tunneling diodes, and circuit simulation for rectifiers. It is found that novel 2D insulators such as monolayer TiO2 can be obtained by oxidizing sulfur-metal layered materials. The MIM diodes based on such insulators exhibit fast tunneling and excellent current rectifying properties. Such tunneling diodes effectively convert the received high-frequency electromagnetic waves into direct current.