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Deep generative models are key-enabling technology to computer vision, text generation, and large language models. Denoising diffusion probabilistic models (DDPMs) have recently gained much attention due to their ability to generate diverse and high-quality samples in many computer vision tasks, as well as to incorporate flexible model architectures and a relatively simple training scheme. Quantum generative models, empowered by entanglement and superposition, have brought new insight to learning classical and quantum data. Inspired by the classical counterpart, we propose the quantum denoising diffusion probabilistic model (QuDDPM) to enable efficiently trainable generative learning of quantum data. QuDDPM adopts sufficient layers of circuits to guarantee expressivity, while it introduces multiple intermediate training tasks as interpolation between the target distribution and noise to avoid barren plateau and guarantee efficient training. We provide bounds on the learning error and demonstrate QuDDPM's capability in learning correlated quantum noise model, quantum many-body phases, and topological structure of quantum data. The results provide a paradigm for versatile and efficient quantum generative learning.
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The Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. Pregnant women infected with ZIKV may also cause microcephaly in newborns. To date, we still lack conventional antiviral drugs to treat ZIKV infections. Marine natural products have novel structures and diverse biological activities. They have been discovered to have antibacterial, antiviral, anticancer, and other therapeutic effects. Therefore, marine products are important resources for compounds for innovative medicines. In this study, we identified a marine natural product, harzianopyridone (HAR), that could inhibit ZIKV replication with EC50 values from 0.46 to 2.63 µM while not showing obvious cytotoxicity in multiple cellular models (CC50 > 45 µM). Further, it also reduced the expression of viral proteins and protected cells from viral infection. More importantly, we found that HAR directly bound to the ZIKV RNA-dependent RNA polymerase (RdRp) and suppressed its polymerase activity. Collectively, our findings provide HAR as an option for the development of anti-ZIKV drugs.
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Produtos Biológicos , Piridonas , Infecção por Zika virus , Zika virus , Animais , Humanos , Feminino , Recém-Nascido , Gravidez , Antivirais/farmacologia , RNA Polimerase Dependente de RNA/metabolismo , Produtos Biológicos/farmacologia , Replicação ViralRESUMO
We propose an all-fiber reflective sensing scheme to simultaneously measure temperature and strain. A length of polarization-maintaining fiber serves as the sensing element, and a piece of hollow-core fiber assists with introducing Vernier effect. Both theoretical deductions and simulative studies have demonstrated the feasibility of the proposed Vernier sensor. Experimental results have shown that the sensor can deliver sensitivities of -88.73 nm/°C and 1.61 nm/µÎµ for temperature and strain, respectively. Further, Both theoretical analyses and experimental results have suggested the capability of simultaneous measurement for such a sensor. Significantly, the proposed Vernier sensor not only presents high sensitivities, but also exhibits a simple structure, compact size and light weight, as well as demonstrates ease of fabrication and hence high repeatability, thus holding great promise for widespread applications in daily life and industry world.
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In this paper, the effects of optical power factors like laser power, the powers of the laser beams in the two arms of the optical system, and the power of the photodetector on laser-linewidth measurements are studied. From the experiments, it can be found that when the average optical input power for the photodetector is about 50% of its linear saturation power, the measured laser line width is a minimum. When the optical powers of the laser beams in the two arms are equal in short-delay self-homodyne system, the measured laser line width is narrowest. In the low output power range of the laser, its line width decreases with the increase in optical power. By comparing experiments, it can also be clear that the conventional measurement method is seriously affected by different noise types, which causes the measured line width to become wider and not change even if the laser linewidth changes. However, based on the short-delay coherent envelope method, the measured coherent envelope changes significantly when the laser line width changes slightly, and its corresponding laser-linewidth values are also clearly visible. It confirms the low noise and high resolution of the short-delay self-homodyne coherent-envelope laser-measurement method. The outcomes of this study can provide helpful information for precision ultra-narrow laser-linewidth measurements.
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Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus Didymella sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4+ T and CD8+ T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)/eukaryotic translation initiation factor (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate.
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Antineoplásicos , Neoplasias Pulmonares , Melanoma , Camundongos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Morte Celular Imunogênica , eIF-2 Quinase/metabolismo , Estresse do Retículo Endoplasmático , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Mitocôndrias/metabolismo , Fator de Transcrição CHOP/metabolismoRESUMO
As a traditional Tibetan medicine in China, Meconopsis grandis Prain has been used to treat a variety of illnesses by local people for thousands of years. However, the active ingredients contained in Meconopsis grandis Prain and its pharmacodynamic mechanisms have scarcely been reported. We isolated a meroterpenoid named D1399 from Meconopsis grandis Prain endophytic fungi with strong antitumor activity. The structure analysis showed that D1399 is an alkaloid containing a 13-membered macrocyclic structure. The IC50 of D1399 for human lung cancer cells' viability ranged from 0.88 to 2.45 µM. Furthermore, we utilized TUNEL assay and western blotting to investigate the antitumor effectiveness of D1399. The results have shown that D1399 induced the apoptosis of lung cancer cells on the extrinsic and intrinsic pathways by boosting ROS generation and repressing AKT activity. In the mouse xenograft model, the average tumor weight with 30 mg·kg-1 D1399 treatment exhibited 73.19% inhibition compared with the untreated control, without affecting body weight loss. Above all, for the first time, our study provides a possible mechanism for the antitumor activity of D1399 in vitro and in vivo as a natural product from Tibetan medicine with Meconopsis grandis Prain, which may be a potentially promising antitumor drug candidate.
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Antineoplásicos , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Medicina Tradicional Tibetana , Apoptose , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de CélulasRESUMO
Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally approved antiviral drugs for the treatment of ZIKV infection, and symptomatic management remains the primary clinical approach. Consequently, the exploration of safe and effective anti-ZIKV drugs has emerged as a paramount imperative in ZIKV control efforts. In this study, we performed a screening of a compound library consisting of 1789 FDA-approved drugs to identify potential agents with anti-ZIKV activity. We have identified dapoxetine, an orally administered selective serotonin reuptake inhibitor (SSRI) commonly employed for the clinical management of premature ejaculation (PE), as a potential inhibitor of ZIKV RNA-dependent RNA polymerase (RdRp). Consequently, we conducted surface plasmon resonance (SPR) analysis to validate the specific binding of dapoxetine to ZIKV RdRp, and further evaluated its inhibitory effect on ZIKV RdRp synthesis using the ZIKV Gluc reporter gene assay. Furthermore, we substantiated the efficacy of dapoxetine in suppressing intracellular replication of ZIKV, thereby demonstrating a concentration-dependent antiviral effect (EC50 values ranging from 4.20 µM to 12.6 µM) and negligible cytotoxicity (CC50 > 50 µM) across diverse cell lines. Moreover, cell fluorescence staining and Western blotting assays revealed that dapoxetine effectively reduced the expression of ZIKV proteins. Collectively, our findings suggest that dapoxetine exhibits anti-ZIKV effects by inhibiting ZIKV RdRp activity, positioning it as a potential candidate for clinical therapeutic intervention against ZIKV infection.
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Infecção por Zika virus , Zika virus , Masculino , Humanos , Infecção por Zika virus/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , RNA Polimerase Dependente de RNA/metabolismo , Antivirais/uso terapêutico , Replicação ViralRESUMO
BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.
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COVID-19 , Humanos , Feminino , Saúde Mental , SARS-CoV-2 , Depressão/epidemiologia , Ansiedade/psicologia , Surtos de Doenças , Inquéritos e Questionários , China/epidemiologiaRESUMO
Absorptive polarizers are pivotal components for realizing a low ambient reflection in liquid crystal displays (LCDs) and organic light-emitting diodes (OLEDs). Different types of absorptive polarizers have been proposed. Nevertheless, the realization of compact and efficient absorptive polarizers remains challenging. Wire grid polarizers (WGPs) are a promising solution because of their high durability and relatively thin thickness. In this paper, two structures of absorptive-WGPs have been proposed and optimized at the target wavelength of 532 nm: one is based on a patterned F e 2 O 3/A l bi-layer on top of a S i O 2 substrate, and the second one builds on the first one by depositing a S i O 2 layer in the gaps of Al. The optimal solutions exhibit a reflectance less than 5%, a transmittance over 45%, and an extinction ratio over 40 dB. To evaluate the manufacturing feasibility, their sensitivity to the wire's dimensional parameters is investigated. Their great spectral performance and large acceptance angles demonstrate that such polarizers have the potential to significantly promote the development of current display technologies.
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We propose a precision measurement method of laser linewidth based on short-delay self-homodyne, using the second peak-valley difference (SPVD) feature of the coherent power spectrum to fit laser linewidth. The SPVD model of the self-homodyne coherent envelope spectrum was established. One-to-one correspondence among the values of SPVD, the delay length, and the laser linewidth was determined theoretically and through simulations, while the reliability and stability of the method was verified experimentally. By comparing the detected results, it is found that the fitted laser linewidth obtained by the self-homodyne system is closer to its true value than that obtained by the self-heterodyne system. Hence, the simpler structure of the short-delay self-homodyne coherent envelope laser linewidth measurement method proposed is expected to substitute the previous laser linewidth measurement method, including complex short-delay self-heterodyne coherent envelope laser linewidth measurement method and traditional self-homodyne/heterodyne laser linewidth measurement method, to achieve more precise laser linewidth value.
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PURPOSE: This study aimed to explore the prevalence and distribution of mental disorders in the elderly population 5 years after the Lushan earthquake in Ya'an, China. METHODS: A multi-stage, group-matching random sampling method was adopted with 2579 elderly participants (≥ 60 years old) who were interviewed from January to May 2019. Preliminary screening was conducted using the scale by trained psychiatric nurses, followed by a diagnostic interview during the second stage using Chinese Version of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorder by trained psychiatrists. RESULTS: A total of 2561 participants were included in this study with complete data. The weighted lifetime prevalence of all mental disorders in the elderly was 16.2% (95% CI 15.3-17.1), and the weighted 12-month prevalence was 15.2% (95% CI 13.4-17.0). Depressive disorders, anxiety disorders, substance-related and addictive disorders were the most common mental disorders. The 12-month prevalence of all mental disorders were significantly higher in the elderly living alone, with chronic somatic disease, and being poor (P < 0.05). The 12-month prevalence of posttraumatic stress disorder (PTSD) was significantly higher in the elderly in extremely severely earthquake-affected areas (P < 0.001). CONCLUSION: The results of this study show that mental health status of the elderly in Ya'an area differ by socio-economic development, geographical location, and natural disasters. The social and economic development characteristics, the impact of major natural disasters (e.g., earthquakes), and population characteristics should be combined to formulate strategies and interventions to promote the mental health of the elderly.
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Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , Idoso , Humanos , Pessoa de Meia-Idade , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , China/epidemiologia , Fatores de Risco , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologiaRESUMO
BACKGROUND: Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. METHODS: We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. RESULTS: The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. CONCLUSIONS: In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).
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Antiasmáticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Antiasmáticos/efeitos adversos , Antiasmáticos/farmacologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Asma/classificação , Broncodilatadores/uso terapêutico , Criança , Método Duplo-Cego , Quimioterapia Combinada , Eosinofilia/induzido quimicamente , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Injeções Subcutâneas/efeitos adversos , Análise de Intenção de Tratamento , Interleucina-13 , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-4/antagonistas & inibidores , Adulto JovemRESUMO
Metasurfaces are usually planar structures and do not possess intrinsic chirality and therefore hardly generate optical activity. Here we realized a tunable optical activity in a terahertz wave through a microfluid-based soft metasurface. The meta-atom is a chiral structured microchannel made of soft polydimethylsiloxane and injected with the liquid metal Galinstan. A microfluid pressure system is bonded to the metasurface to reconfigure all meta-atoms simultaneously. By pumping glycerol liquid into the pressure system, the metasurface is deformed from a planar structure to a three dimensional one, which manifests intrinsic chirality for optical activity realization. By controlling the injected glycerol volume, a polarization rotation from 0°to 14° at 0.19 THz is demonstrated. The soft metasurface with tunable optical activity can be flexibly applied in various applications such as polarization microscopy, bio-detection and material analysis, etc.
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PURPOSE: This study aimed to (1) explore the prevalence and relevant influencing factors of different mental disorders 5 years after the Lushan earthquake in Ya'an, China. METHODS: An epidemiological mental health survey was conducted to identify the prevalence of mental disorders in general population in Ya'an. A multi-stage, group-matching random sampling method was adopted. Face-to-face interviews were done with a two-stage design by trained interviewers and psychiatrists. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) was used for the diagnosis. RESULTS: There were 8876 participants who were interviewed in this study. The total 12-month and lifetime prevalence of all mental disorders were 12.5% and 14.7%, respectively. There was a significant difference between males and females in the prevalence patterns of several mental disorders. Han ethnic group had higher prevalence of anxiety disorders (2.7%), and the Tibetan group had higher prevalence of alcohol-related disorders (5.0%). Logistic regression analysis showed that the areas severely affected by the earthquake had significantly higher prevalence of depressive disorders, and the extremely severe affected areas had significantly higher prevalence of trauma- and stressor-related disorders. CONCLUSION: Our findings show that the prevalence of a range of mental disorders 5 years after the earthquake in Ya'an are high, and the prevalence of depressive and trauma- and stressor-related disorders may be influenced differently by the various severity of earthquake impact. This study may be crucial for the health policy-making, cultural-specific mental health services and long-term mental recovery after the earthquake.
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Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , China/epidemiologia , Depressão , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Prevalência , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários , SobreviventesRESUMO
Two dissimilarity indices are introduced to measure the disharmony of a human body system by mimicking the population bioequivalence and the individual bioequivalence concepts. Hypotheses for the treatment effect of a traditional Chinese medicine are formulated based on the two indices and then tested under the proposed designs by reverting an approximate confidence upper bound. The proposed methods can also be used when a drug product has multiple components or a trial has multiple endpoints.
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Medicamentos Biossimilares/uso terapêutico , Medicina Tradicional Chinesa/estatística & dados numéricos , Análise de Componente Principal , Equivalência Terapêutica , Humanos , Medicina Tradicional Chinesa/métodos , Análise de Componente Principal/métodos , Resultado do TratamentoRESUMO
Three test diets containing three different levels (1, 3, and 5â¯gâ¯kg-1) of dietary chitosan oligosaccharides (COs) were formulated and used to test the growth performance, body composition, intestine digestive enzymes, antioxidant responses and resistance to Aeromonas hydrophila of loach Paramisgurnus dabryanus. A basal diet without any COs served as the control. After 60 days of feeding, the growth performance, intestine digestive-enzyme activities, body protein content and total polyunsaturated fatty acids, antioxidant responses, and resistance to A. hydrophila of loach P. dabryanus were higher than those of the control when the loach P. dabryanus was fed with CO-containing diets. The optimum dose of dietary COs required for the maximum growth of loach was 3â¯gâ¯kg-1 of the diet. Results indicated that dietary COs can improve the growth performance, body composition, intestine digestive enzymes, antioxidant responses, and resistance to A. hydrophila of loach P. dabryanus and can thus be used as a diet supplement for them.
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Quitosana/administração & dosagem , Cipriniformes/crescimento & desenvolvimento , Cipriniformes/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata , Intestinos/enzimologia , Aeromonas hydrophila , Ração Animal , Animais , Composição Corporal , Suplementos Nutricionais , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/imunologia , Oligossacarídeos/administração & dosagemRESUMO
BACKGROUND: Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist, irrespective of baseline eosinophil count. METHODS: We did this randomised, double-blind, placebo-controlled, parallel-group, pivotal phase 2b clinical trial at 174 study sites across 16 countries or regions. Adults (aged ≥18 years) with an asthma diagnosis for 12 months or more based on the Global Initiative for Asthma 2009 Guidelines receiving treatment with medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist were eligible for participation. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks or every 4 weeks, or placebo, over a 24-week period. The primary endpoint was change from baseline at week 12 in forced expiratory volume in 1 s (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per µL assessed in the intention-to-treat population. Safety outcomes were assessed in all patients that received at least one dose or part of a dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT01854047, and with the EU Clinical Trials Register, EudraCT number 2013-000856-16. FINDINGS: 769 patients (158 in the placebo group and 611 in the dupilumab groups) received at least one dose of study drug. In the subgroup with at least 300 eosinophils per µL, the greatest increases (200 mg every 2 weeks, p=0·0008; 300 mg every 2 weeks, p=0·0063) in FEV1 compared with placebo were observed at week 12 with doses every 2 weeks in the 300 mg group (mean change 0·39 L [SE 0·05]; mean difference 0·21 [95% CI 0·06-0·36; p=0·0063]) and in the 200 mg group (mean change 0·43 L [SE 0·05]; mean difference 0·26 [0·11-0·40; p=0·0008]) compared with placebo (0·18 L [SE 0·05]). Similar significant increases were observed in the overall population and in the fewer than 300 eosinophils per µL subgroup (overall population: 200 mg every 2 weeks, p<0·0001; 300 mg every 2 weeks, p<0·0001; <300 eosinophils per µL: 200 mg every 2 weeks, p=0·0034; 300 mg every 2 weeks, p=0·0086), and were maintained to week 24. Likewise, dupilumab every 2 weeks produced the greatest reductions in annualised rates of exacerbation in the overall population (70-70·5%), the subgroup with at least 300 eosinophils per µL (71·2-80·7%), and the subgroup with fewer than 300 eosinophils per µL (59·9-67·6%). The most common adverse events with dupilumab compared with placebo were upper respiratory tract infections (33-41% vs 35%) and injection-site reactions (13-26% vs 13%). INTERPRETATION: Dupilumab increased lung function and reduced severe exacerbations in patients with uncontrolled persistent asthma irrespective of baseline eosinophil count and had a favourable safety profile, and hence in addition to inhaled corticosteroids plus long-acting ß2-agonist therapy could improve the lives of patients with uncontrolled persistent asthma compared with standard therapy alone. FUNDING: Sanofi-Genzyme and Regeneron Pharmaceuticals.
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Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Asma/tratamento farmacológico , Administração por Inalação , Adulto , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados , Asma/fisiopatologia , Testes Respiratórios , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Combinação Fluticasona-Salmeterol/uso terapêutico , Volume Expiratório Forçado , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Combinação Furoato de Mometasona e Fumarato de Formoterol/uso terapêutico , Óxido Nítrico/análise , Resultado do TratamentoRESUMO
The kurtosis-based indexes are usually used to identify the optimal resonant frequency band. However, kurtosis can only describe the strength of transient impulses, which cannot differentiate impulse noises and repetitive transient impulses cyclically generated in bearing vibration signals. As a result, it may lead to inaccurate results in identifying resonant frequency bands, in demodulating fault features and hence in fault diagnosis. In view of those drawbacks, this manuscript redefines the correlated kurtosis based on kurtosis and auto-correlative function, puts forward an improved correlated kurtosis based on squared envelope spectrum of bearing vibration signals. Meanwhile, this manuscript proposes an optimal resonant band demodulation method, which can adaptively determine the optimal resonant frequency band and accurately demodulate transient fault features of rolling bearings, by combining the complex Morlet wavelet filter and the Particle Swarm Optimization algorithm. Analysis of both simulation data and experimental data reveal that the improved correlated kurtosis can effectively remedy the drawbacks of kurtosis-based indexes and the proposed optimal resonant band demodulation is more accurate in identifying the optimal central frequencies and bandwidth of resonant bands. Improved fault diagnosis results in experiment verified the validity and advantage of the proposed method over the traditional kurtosis-based indexes.
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Kurtograms have been verified to be an efficient tool in bearing fault detection and diagnosis because of their superiority in extracting transient features. However, the short-time Fourier Transform is insufficient in time-frequency analysis and kurtosis is deficient in detecting cyclic transients. Those factors weaken the performance of the original kurtogram in extracting weak fault features. Correlated Kurtosis (CK) is then designed, as a more effective solution, in detecting cyclic transients. Redundant Second Generation Wavelet Packet Transform (RSGWPT) is deemed to be effective in capturing more detailed local time-frequency description of the signal, and restricting the frequency aliasing components of the analysis results. The authors in this manuscript, combining the CK with the RSGWPT, propose an improved kurtogram to extract weak fault features from bearing vibration signals. The analysis of simulation signals and real application cases demonstrate that the proposed method is relatively more accurate and effective in extracting weak fault features.
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We investigate the formation of polarized vortex solitons in nonlocal media with Bessel optical lattices and show the various dynamics of these solitons. Particularly, the stable high-order polarized vortex solitons, which are not found in local media with Bessel optical lattices, are found in nonlocal media. It is found that the nonlocal nonlinearity plays an important role in the stability of these solitons which is similar to that of phase vortex solitons. However, we show that the dynamics of these polarized vortex solitons are quite different from the phase vortex solitons.