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1.
N Engl J Med ; 391(3): 213-223, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39018531

RESUMO

BACKGROUND: The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown. METHODS: In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab. RESULTS: In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).


Assuntos
Anticorpos Monoclonais , Doença de Crohn , Ustekinumab , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Análise de Intenção de Tratamento , Indução de Remissão , Índice de Gravidade de Doença , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Endoscopia Gastrointestinal
2.
Proc Natl Acad Sci U S A ; 121(5): e2316914121, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38252828

RESUMO

High-performance sodium storage at low temperature is urgent with the increasingly stringent demand for energy storage systems. However, the aggravated capacity loss is induced by the sluggish interfacial kinetics, which originates from the interfacial Na+ desolvation. Herein, all-fluorinated anions with ultrahigh electron donicity, trifluoroacetate (TFA-), are introduced into the diglyme (G2)-based electrolyte for the anion-reinforced solvates in a wide temperature range. The unique solvation structure with TFA- anions and decreased G2 molecules occupying the inner sheath accelerates desolvation of Na+ to exhibit decreased desolvation energy from 4.16 to 3.49 kJ mol-1 and 24.74 to 16.55 kJ mol-1 beyond and below -20 °C, respectively, compared with that in 1.0 M NaPF6-G2. These enable the cell of Na||Na3V2(PO4)3 to deliver 60.2% of its room-temperature capacity and high capacity retention of 99.2% after 100 cycles at -40 °C. This work highlights regulation of solvation chemistry for highly stable sodium-ion batteries at low temperature.

3.
Nature ; 581(7808): 278-282, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433619

RESUMO

Human eyes possess exceptional image-sensing characteristics such as an extremely wide field of view, high resolution and sensitivity with low aberration1. Biomimetic eyes with such characteristics are highly desirable, especially in robotics and visual prostheses. However, the spherical shape and the retina of the biological eye pose an enormous fabrication challenge for biomimetic devices2,3. Here we present an electrochemical eye with a hemispherical retina made of a high-density array of nanowires mimicking the photoreceptors on a human retina. The device design has a high degree of structural similarity to a human eye with the potential to achieve high imaging resolution when individual nanowires are electrically addressed. Additionally, we demonstrate the image-sensing function of our biomimetic device by reconstructing the optical patterns projected onto the device. This work may lead to biomimetic photosensing devices that could find use in a wide spectrum of technological applications.


Assuntos
Materiais Biomiméticos , Biomimética/instrumentação , Compostos de Cálcio , Nanofios , Óxidos , Retina , Titânio , Desenho de Equipamento , Humanos , Robótica/instrumentação , Visão Ocular
4.
Proc Natl Acad Sci U S A ; 120(8): e2216367120, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36791111

RESUMO

Recently, evidence for a conducting surface state (CSS) below 19 K was reported for the correlated d-electron small gap semiconductor FeSi. In the work reported herein, the CSS and the bulk phase of FeSi were probed via electrical resistivity ρ measurements as a function of temperature T, magnetic field B to 60 T, and pressure P to 7.6 GPa, and by means of a magnetic field-modulated microwave spectroscopy (MFMMS) technique. The properties of FeSi were also compared with those of the Kondo insulator SmB6 to address the question of whether FeSi is a d-electron analogue of an f-electron Kondo insulator and, in addition, a "topological Kondo insulator" (TKI). The overall behavior of the magnetoresistance of FeSi at temperatures above and below the onset temperature TS = 19 K of the CSS is similar to that of SmB6. The two energy gaps, inferred from the ρ(T) data in the semiconducting regime, increase with pressure up to about 7 GPa, followed by a drop which coincides with a sharp suppression of TS. Several studies of ρ(T) under pressure on SmB6 reveal behavior similar to that of FeSi in which the two energy gaps vanish at a critical pressure near the pressure at which TS vanishes, although the energy gaps in SmB6 initially decrease with pressure, whereas in FeSi they increase with pressure. The MFMMS measurements showed a sharp feature at TS ≈ 19 K for FeSi, which could be due to ferromagnetic ordering of the CSS. However, no such feature was observed at TS ≈ 4.5 K for SmB6.

5.
Chem Soc Rev ; 53(8): 4230-4301, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38477330

RESUMO

Sodium-ion batteries (SIBs) are experiencing a large-scale renaissance to supplement or replace expensive lithium-ion batteries (LIBs) and low energy density lead-acid batteries in electrical energy storage systems and other applications. In this case, layered oxide materials have become one of the most popular cathode candidates for SIBs because of their low cost and comparatively facile synthesis method. However, the intrinsic shortcomings of layered oxide cathodes, which severely limit their commercialization process, urgently need to be addressed. In this review, inherent challenges associated with layered oxide cathodes for SIBs, such as their irreversible multiphase transition, poor air stability, and low energy density, are systematically summarized and discussed, together with strategies to overcome these dilemmas through bulk phase modulation, surface/interface modification, functional structure manipulation, and cationic and anionic redox optimization. Emphasis is placed on investigating variations in the chemical composition and structural configuration of layered oxide cathodes and how they affect the electrochemical behavior of the cathodes to illustrate how these issues can be addressed. The summary of failure mechanisms and corresponding modification strategies of layered oxide cathodes presented herein provides a valuable reference for scientific and practical issues related to the development of SIBs.

6.
Small ; 20(12): e2307132, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37946700

RESUMO

Large reserves, high capacity, and low cost are the core competitiveness of disordered carbon materials as excellent anode materials for sodium-ion batteries (SIBs). And the existence and improper treatment of a large number of organic solid wastes will aggravate the burden on the environment, therefore, it is significant to transform wastes into carbon-based materials for sustainable energy utilization. Herein, a kind of hard carbon materials are reported with waste biomass-foam as the precursor, which can improve the sodium storage performance through pre-oxidation strategy. The introduction of oxygen-containing groups can promote structural cross-linking, and inhibit the melting and rearrangement of carbon structure during high-temperature carbonization that produces a disordered structure with a suitable degree of graphitization. Moreover, the micropore structure are also regulated during the high-temperature carbonization process, which is conducive to the storage of sodium ions in the low-voltage plateau region. The optimized sample as an electrode material exhibits excellent reversible specific capacity (308.0 mAh g-1) and initial Coulombic efficiency (ICE, 90.1%). In addition, a full cell with the waste foam-derived hard carbon anode and a Na3V2(PO4)3 cathode is constructed with high ICE and energy density. This work provides an effective strategy to conversion the waste to high-value hard carbon anode for sodium-ion batteries.

7.
Small ; 20(11): e2306690, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37926792

RESUMO

Non-aqueous solvents, in particular N,N-dimethylaniline (NMP), are widely applied for electrode fabrication since most sodium layered oxide cathode materials are readily damaged by water molecules. However, the expensive price and poisonousness of NMP unquestionably increase the cost of preparation and post-processing. Therefore, developing an intrinsically stable cathode material that can implement the water-soluble binder to fabricate an electrode is urgent. Herein, a stable nanosheet-like Mn-based cathode material is synthesized as a prototype to verify its practical applicability in sodium-ion batteries (SIBs). The as-prepared material displays excellent electrochemical performance and remarkable water stability, and it still maintains a satisfactory performance of 79.6% capacity retention after 500 cycles even after water treatment. The in situ X-ray diffraction (XRD) demonstrates that the synthesized material shows an absolute solid-solution reaction mechanism and near-zero-strain. Moreover, the electrochemical performance of the electrode fabricated with a water-soluble binder shows excellent long-cycling stability (67.9% capacity retention after 500 cycles). This work may offer new insights into the rational design of marvelous water stability cathode materials for practical SIBs.

8.
Phys Rev Lett ; 132(25): 256503, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996236

RESUMO

The recently discovered superconductivity with critical temperature T_{c} up to 80 K in the double-layer Nickelate La_{3}Ni_{2}O_{7-δ} under pressure has drawn great attention. Here, we report the positive muon spin relaxation (µ^{+}SR) study of polycrystalline La_{3}Ni_{2}O_{6.92} under ambient pressure. Zero-field µ^{+}SR experiments reveal the existence of magnetic order in La_{3}Ni_{2}O_{6.92} with T_{N}=154 K. The weak transverse field µ^{+}SR measurements reveal the bulk nature of magnetism. In addition, a small quantity of oxygen deficiencies can greatly broaden the internal magnetic field distribution sensed by muons.

9.
Chemistry ; : e202304106, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083260

RESUMO

Sodium-oxygen batteries have been regarded as promising energy storage devices due to their low overpotential and high energy density. Its applications, however, still face formidable challenges due to the lack of understanding about the influence of electrocatalysts on the discharge products. Here, a phosphorous and nitrogen dual-doped carbon (PNDC) based cathode is synthesized to increase the electrocatalytic activity and to stabilize the NaO2 superoxide nanoparticle discharge products, leading to enhanced cycling stability when compared to the nitrogen-doped carbon (NDC). The PNDC air cathode exhibits a low overpotential (0.36 V) and long cycling stability (120 cycles). The reversible formation/decomposition and stabilization of the NaO2 discharge products are clearly proven by in-situ synchrotron X-ray diffraction and ex-situ X-ray diffraction. Based on the density functional theory calculation, the PNDC has much stronger adsorption energy (-2.85 eV) for NaO2 than that of NDC (-1.80 eV), which could efficiently stabilize the NaO2 discharge products.

10.
Inorg Chem ; 63(25): 11592-11603, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38861349

RESUMO

In order to take advantage of the distinct reversible multielectron transfer properties of polyoxometalates (POMs) and increase the electron density at the active sites during the electrochemical reduction of CO2 (CO2RR), a range of transition metal-doped polyoxometalates (TMSPOMs) was entrapped within the porphyrin-based framework of PCN-224 via an encapsulation method, known as TMSPOMs@PCN-224 (TMSPOMs = [XW11O39MII(H2O)]n-, [XW11O40VIV]n-, M = CoII, MnII; X = Si, n = 6; X = P, n = 5). The central elements (Si, P) and the incorporated transition metals (VIV, CoII, and MnII) both play a role in adjusting the electronic structure and electron transfer during the CO2RR process. Remarkably, the composite material with cobalt substitution displayed significantly improved performance. Through fine-tuning the POM loading, the electrocatalytic activity was optimized, leading to an impressive Faradaic efficiency for CO production (FECO) of 89.9% for SiW11Co@PCN-224, a significant improvement compared to the 12.1% FECO of PCN-224. Furthermore, the electrochemical stability of this catalyst was demonstrated over 20 h. Comparative analyses involving six composite materials indicated a relationship between the negative charge of the polyanions and their ability to facilitate effective electron transfer, ultimately enhancing the catalyst's performance. Meanwhile, these findings were supported by density functional theory (DFT) calculations.

11.
Environ Sci Technol ; 58(26): 11256-11267, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38885093

RESUMO

Short-term exposure to particles with aerodynamic diameters less than 2.5 µm (PM2.5) and ozone (O3) are important risk factors for human health. Despite the awareness of reducing attributable health burden, region-specific and source-specific strategies remain less explored due to the gap between precursor emissions and health effects. In this study, we isolate the health burden of individual sector sources of PM2.5 and O3 precursors, nitrogen oxides (NOx) and volatile organic compounds (VOCs), across the globe. Specifically, we estimate mortalities attributable to short-term exposure using machine-learning-based daily exposure estimates and quantify sectoral impacts using chemical transport model simulations. Globally, short-term exposure to PM2.5 and O3 result in 713.5 (95% Confidence Interval: 598.8-843.3) thousand and 496.3 (371.3-646.1) thousand mortalities in 2019, respectively, of which 12.5% are contributed by fuel-related NOx emissions from transportation, energy, and industry. Sectoral impacts from anthropogenic NOx and VOC emissions on health burden vary significantly among seasons and regions, requiring a target shift from transportation in winter to industry in summer for East Asia, for instance. Emission control and health management are additionally complicated by unregulated natural influences during climatic events. Fire-sourced NOx and VOC emissions, respectively, contribute to 8.5 (95% CI: 6.2-11.7) thousand and 4.8 (3.6-5.9) thousand PM2.5 and O3 mortalities, particularly for tropics with high vulnerability to climate change. Additionally, biogenic VOC emissions during heatwaves contribute to 1.8 (95% CI: 1.5-2.2) thousand O3-introduced mortalities, posing challenges in urban planning for high-income regions, where biogenic contributions to health burden during heatwaves are 13% of anthropogenic contributions annually. Our study provides important implications for temporally dynamic and sector-targeted emission control and health management strategies, which are of urgency under the projection of continuously increasing energy consumption and changing climate.


Assuntos
Poluentes Atmosféricos , Ozônio , Material Particulado , Humanos , Exposição Ambiental , Compostos Orgânicos Voláteis , Óxidos de Nitrogênio
12.
Environ Sci Technol ; 58(18): 7891-7903, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38602183

RESUMO

Tropospheric nitrogen dioxide (NO2) poses a serious threat to the environmental quality and public health. Satellite NO2 observations have been continuously used to monitor NO2 variations and improve model performances. However, the accuracy of satellite NO2 retrieval depends on the knowledge of aerosol optical properties, in particular for urban agglomerations accompanied by significant changes in aerosol characteristics. In this study, we investigate the impacts of aerosol composition on tropospheric NO2 retrieval for an 18 year global data set from Global Ozone Monitoring Experiment (GOME)-series satellite sensors. With a focus on cloud-free scenes dominated by the presence of aerosols, individual aerosol composition affects the uncertainties of tropospheric NO2 columns through impacts on the aerosol loading amount, relative vertical distribution of aerosol and NO2, aerosol absorption properties, and surface albedo determination. Among aerosol compositions, secondary inorganic aerosol mostly dominates the NO2 uncertainty by up to 43.5% in urban agglomerations, while organic aerosols contribute significantly to the NO2 uncertainty by -8.9 to 37.3% during biomass burning seasons. The possible contrary influences from different aerosol species highlight the importance and complexity of aerosol correction on tropospheric NO2 retrieval and indicate the need for a full picture of aerosol properties. This is of particular importance for interpreting seasonal variations or long-term trends of tropospheric NO2 columns as well as for mitigating ozone and fine particulate matter pollution.


Assuntos
Aerossóis , Poluentes Atmosféricos , Monitoramento Ambiental , Dióxido de Nitrogênio , Estações do Ano , Dióxido de Nitrogênio/análise , Poluentes Atmosféricos/análise , Ozônio/análise
13.
Int J Colorectal Dis ; 39(1): 143, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289199

RESUMO

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.


Assuntos
Colonoscopia , Polietilenoglicóis , Humanos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Constipação Intestinal , Adulto , Relação Dose-Resposta a Droga , Idoso , Defecação/efeitos dos fármacos , Resultado do Tratamento , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/diagnóstico
14.
Neurosurg Rev ; 47(1): 560, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39242449

RESUMO

The role of a low-profile visualized intraluminal support stent (LVIS) and Enterprise in the treatment of unruptured intracranial aneurysms is well established. Although previous studies have investigated one single type of stent for the treatment of ruptured intracranial aneurysms (RIA), the safety and efficacy between the two types of stents has not been fully explored. Herein we conducted a study to compare the outcomes of the two stents for treatment of RIA. This is a prospective registry database of aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to a single institution between 2018 and 2021. We collected patient baseline information, secondary complications, follow-up angiographic data, long-term prognostic outcomes, and conducted propensity score matching (PSM) analysis with 1:1 ratio and a multivariable logistic regression to compare the outcomes of the two types of stents. A total of 231 patients with RIAs were included in this study, with 108 treated using the LVIS device and 123 treated using the Enterprise device. Before PSM analysis, only the incidence of poor prognosis after 12 months was higher in the Enterprise group comparing to the LVIS group (20% vs. 10%, P = 0.049). After PSM analysis, there was a higher occurrence of delayed cerebral ischemia (DCI) in the Enterprise group compared to the LVIS group (odds ratio [OR] 3.95, 95% confidence interval [CI] [1.20-13.01], P = 0.024). However, no significant difference in prognosis was observed after PSM adjustment. Furthermore, subgroup analysis revealed that patients with female (P = 0.019), hypertension (P = 0.048), and anterior circulation aneurysms (P = 0.019) receiving the Enterprise device had a higher risk of DCI. The overall efficacy of LVIS and Enterprise in the treatment of RIA is comparable, while the incidence of DCI in the LVIS group is lower than that in the Enterprise group after PSM analysis. Registration number: NCT05738083 ( https://clinicaltrials.gov/ ).


Assuntos
Aneurisma Roto , Embolização Terapêutica , Aneurisma Intracraniano , Pontuação de Propensão , Stents , Humanos , Aneurisma Intracraniano/terapia , Feminino , Masculino , Aneurisma Roto/terapia , Pessoa de Meia-Idade , Embolização Terapêutica/métodos , Embolização Terapêutica/instrumentação , Idoso , Adulto , Resultado do Tratamento , Estudos de Coortes , Procedimentos Endovasculares/métodos , Hemorragia Subaracnóidea/terapia
15.
COPD ; 21(1): 2369541, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39087240

RESUMO

To investigate the clinical effects and application value of self-made disseminating and descending breathing exercises on home rehabilitation of patients with stable chronic obstructive pulmonary disease (COPD). Seeking to generate concepts for creating novel, convenient, and efficient COPD prognosis rehabilitation exercises aimed at enhancing the well-being and rehabilitation confidence of both COPD patients and their families. A total of 70 COPD patients admitted to our outpatient department from July 2019 to September 2021 were randomly divided into the exercise group (n = 35) and the control group (n = 35). The control group received routine breathing training, while the exercise group was treated with self-made disseminating and descending breathing exercises. The respiratory function, including pulmonary function (FVC, FEV1, FEV1/FVC) and respiratory muscle strength (MIP, MEP), exercise tolerance (6-min walking distance, 6MWT), Modified Medical Research Council Dyspnea Scale (mMRC, Borg), COPD quality of life score (CAT, SGRQ), anxiety and depression scores (HAMA, HAMD) were compared between the two groups after 12-week exercise. After 12-week training, the FEV1, MIP, and MEP in the exercise group were significantly higher than those in the control group (p < 0.001), and the 6MWT was significantly increased in the exercise group compared to the control group (p < 0.001); while the mMRC, Borg score, the scores of CAT, SGRQ, HAMA, and HAMD were found significantly lower than those in the control group (p < 0.001). The self-made disseminating and descending breathing exercises can improve respiratory function and reduce symptoms of dyspnea in COPD patients, while enhancing exercise tolerance and relieving anxiety and depression, and are worthy of clinical application.


Assuntos
Exercícios Respiratórios , Tolerância ao Exercício , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Exercícios Respiratórios/métodos , Idoso , Pessoa de Meia-Idade , Dispneia/etiologia , Dispneia/reabilitação , Força Muscular , Depressão , Ansiedade/etiologia , Músculos Respiratórios/fisiopatologia , Teste de Caminhada , Volume Expiratório Forçado
16.
JAMA ; 332(11): 881-897, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39037800

RESUMO

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.


Assuntos
Anticorpos Monoclonais , Colite Ulcerativa , Quimioterapia de Indução , Quimioterapia de Manutenção , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Método Duplo-Cego , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Índice de Gravidade de Doença , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colonoscopia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos
17.
Entropy (Basel) ; 26(7)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39056917

RESUMO

This paper proposes a novel censored autoregressive conditional Fréchet (CAcF) model with a flexible evolution scheme for the time-varying parameters, which allows deciphering tail risk dynamics constrained by price limits from the viewpoints of different risk preferences. The proposed model can well accommodate many important empirical characteristics of financial data, such as heavy-tailedness, volatility clustering, extreme event clustering, and price limits. We then investigate tail risk dynamics via the CAcF model in the price-limited stock markets, taking entropic value at risk (EVaR) as a risk measurement. Our findings suggest that tail risk will be seriously underestimated in price-limited stock markets when the censored property of limit prices is ignored. Additionally, the evidence from the Chinese Taiwan stock market shows that widening price limits would lead to a decrease in the incidence of extreme events (hitting limit-down) but a significant increase in tail risk. Moreover, we find that investors with different risk preferences may make opposing decisions about an extreme event. In summary, the empirical results reveal the effectiveness of our model in interpreting and predicting time-varying tail behaviors in price-limited stock markets, providing a new tool for financial risk management.

18.
Angew Chem Int Ed Engl ; 63(21): e202402342, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38491787

RESUMO

Zn deposition with a surface-preferred (002) crystal plane has attracted extensive attention due to its inhibited dendrite growth and side reactions. However, the nucleation and growth of the Zn(002) crystal plane are closely related to the interfacial properties. Herein, oriented growth of Zn(002) crystal plane is realized on Ag-modified surface that is directly visualized by in situ atomic force microscopy. A solid solution HCP-Zn (~1.10 at. % solubility of Ag, 30 °C) is formed on the Ag coated Zn foil (Zn@Ag) and possesses the same crystal structure as Zn to reduce its nucleation barrier caused by their lattice mismatch. It merits oriented Zn deposition and corrosion-resistant surface, and presents long cycling stability in symmetric cells and full cells coupled with V2O5 cathode. This work provides insights into interfacial regulation of Zn anodes for high-performance aqueous zinc metal batteries.

19.
Angew Chem Int Ed Engl ; 63(3): e202313142, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37917045

RESUMO

Sodium dual-ion batteries (Na-DIBs) have attracted increasing attention due to their high operative voltages and low-cost raw materials. However, the practical applications of Na-DIBs are still hindered by the issues, such as low capacity and poor Coulombic efficiency, which is highly correlated with the compatibility between electrode and electrolyte but rarely investigated. Herein, fluoroethylene carbonate (FEC) is introduced into the electrolyte to regulate cation/anion solvation structure and the stability of cathode/anode-electrolyte interphase of Na-DIBs. The FEC modulates the environment of PF6 - solvation sheath and facilitates the interaction of PF6 - on graphite. In addition, the NaF-rich interphase caused by the preferential decomposition of FEC effectively inhibits side reactions and pulverization of anodes with the electrolyte. Consequently, Sb||graphite full cells in FEC-containing electrolyte achieve an improved capacity, cycling stability and Coulombic efficiency. This work elucidates the underlying mechanism of bifunctional FEC and provides an alternative strategy of building high-performance dual ion batteries.

20.
Angew Chem Int Ed Engl ; : e202410494, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007424

RESUMO

Anion-reinforced solvation structure favors the formation of inorganic-rich robust electrode-electrolyte interface, which endows fast ion transport and high strength modulus to enable improved electrochemical performance. However, such a unique solvation structure inevitably injures the ionic conductivity of electrolytes and limits the fast-charging performance. Herein, a trade-off in tuning anion-reinforced solvation structure and high ionic conductivity is realized by the entropy-assisted hybrid ester-ether electrolyte. Anion-reinforced solvation sheath with more anions occupying the inner Na+ shell is constructed by introducing the weakly coordinated ether tetrahydrofuran into the commonly used ester-based electrolyte, which merits the accelerated desolvation energy and gradient inorganic-rich electrode-electrolyte interface. The improved ionic conductivity is attributed to the weakly diverse solvation structures induced by entropy effect. These enable the enhanced rate performance and cycling stability of Prussian blue||hard carbon full cells with high electrode mass loading. More importantly, the practical application of the designed electrolyte was further demonstrated by industry-level 18650 cylindrical cells.

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