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Interactions between respiratory syncytial virus and Streptococcus pneumoniae in the pathogenesis of childhood respiratory infections: a systematic review. 呼吸道合胞病毒与肺炎链球菌在儿童呼吸道感染发病机制中的相互作用:系统综述。
IF 2.2 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-11-01 Epub Date: 2024-07-08 DOI: 10.1016/S2213-2600(24)00148-6
Sjanna B Besteman, Debby Bogaert, Louis Bont, Asuncion Mejias, Octavio Ramilo, Daniel M Weinberger, Ron Dagan

Lower respiratory tract infections, commonly caused by respiratory syncytial virus (RSV) or Streptococcus pneumoniae (pneumococcus), pose a substantial global health burden, especially in children younger than 5 years of age. A deeper understanding of the relationship between RSV and pneumococcus would aid the development of health-care approaches to disease prevention and management. We completed a systematic review to identify and assess evidence pertaining to the relationship between RSV and pneumococcus in the pathogenesis of childhood respiratory infections. We found mechanistic evidence for direct pathogen-pathogen interactions and for indirect interactions involving host modulation. We found a strong seasonal epidemiological association between these two pathogens, which was recently confirmed by a parallel decrease and a subsequent resurgence of both RSV and pneumococcus-associated disease during the COVID-19 pandemic. Importantly, we found that pneumococcal vaccination was associated with reduced RSV hospitalisations in infants, further supporting the relevance of their interaction in modulating severe disease. Overall evidence supports a broad biological and clinical interaction between pneumococcus and RSV in the pathogenesis of childhood respiratory infections. We hypothesise that the implementation of next-generation pneumococcal and RSV vaccines and monoclonal antibodies targeting RSV will act synergistically to reduce global morbidity and mortality related to childhood respiratory infections.

下呼吸道感染通常由呼吸道合胞病毒(RSV)或肺炎链球菌(pneumococcus)引起,对全球健康造成巨大负担,尤其是对 5 岁以下儿童。深入了解 RSV 和肺炎球菌之间的关系有助于制定疾病预防和管理的医疗保健方法。我们完成了一项系统性综述,以确定和评估与 RSV 和肺炎球菌在儿童呼吸道感染发病机制中的关系有关的证据。我们发现了病原体与病原体直接相互作用以及涉及宿主调节的间接相互作用的机理证据。我们发现这两种病原体在流行病学上有很强的季节性关联,最近在 COVID-19 大流行期间,RSV 和肺炎球菌相关疾病的发病率同时下降,随后又重新上升,这证实了这种关联。重要的是,我们发现肺炎球菌疫苗接种与婴儿 RSV 住院率降低有关,这进一步证明了它们在调节严重疾病方面的相互作用的相关性。总体证据表明,肺炎球菌和 RSV 在儿童呼吸道感染的发病机制中存在广泛的生物和临床相互作用。我们假设,下一代肺炎球菌和 RSV 疫苗以及针对 RSV 的单克隆抗体的应用将发挥协同作用,降低全球与儿童呼吸道感染相关的发病率和死亡率。
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引用次数: 0
Clean energy demand must secure sustainable nickel supply 清洁能源需求必须确保可持续的镍供应
IF 39.8 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-11-01 DOI: 10.1016/j.joule.2024.10.008
R. Basuhi, Karan Bhuwalka, Elizabeth A. Moore, Isabel Diersen, Rameen H. Malik, Eric Young, Romain G. Billy, Robert Stoner, Gerbrand Ceder, Daniel B. Müller, Richard Roth, Elsa A. Olivetti
Unprecedented demand for critical energy transition metals will expand global mineral supply and reshape commodity landscapes. We discuss the opportunity for demand signals to discern the nature of supply development and create incentives for sustainable production in the long term. We focus on global nickel supply and outline the nickel industry’s challenges in aligning economic incentives and socio-ecological impacts as it responds to growing demand. We explore the evolving role of Indonesia in the nickel and battery supply chain and envision how discerning demand structures can influence regional production priorities. We argue that discerning demand signals must be translated into responsible practices with effective standards to support low-impact nickel processing. To this end, coordinated minerals policy, harmonized governance mechanisms, and inclusive decision-making processes will be essential.
对关键能源过渡金属前所未有的需求将扩大全球矿产供应,重塑商品格局。我们讨论了需求信号对供应发展性质的影响,以及对长期可持续生产的激励。我们重点关注全球镍供应,并概述了镍行业在应对日益增长的需求时,在协调经济激励和社会生态影响方面所面临的挑战。我们探讨了印度尼西亚在镍和电池供应链中不断演变的角色,并设想了辨别需求结构如何影响地区生产的优先次序。我们认为,明确的需求信号必须转化为负责任的实践,并制定有效的标准,以支持低影响的镍加工。为此,协调的矿产政策、统一的管理机制和包容性的决策过程将至关重要。
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引用次数: 0
The expanded French compassionate programme for elexacaftor-tezacaftor-ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study. 在无 F508del CFTR 变异的囊性纤维化患者中使用 elexacaftor-tezacaftor-ivacaftor 的法国扩大同情计划:一项真实世界研究。
IF 38.7 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-11-01 Epub Date: 2024-08-13 DOI: 10.1016/S2213-2600(24)00208-X
Pierre-Régis Burgel, Isabelle Sermet-Gaudelus, Emmanuelle Girodon, Isabelle Durieu, Véronique Houdouin, Camille Audousset, Julie Macey, Dominique Grenet, Michele Porzio, Marlène Murris-Espin, Philippe Reix, Mélisande Baravalle, Chantal Belleguic, Laurent Mely, Juliette Verhille, Laurence Weiss, Martine Reynaud-Gaubert, Marie Mittaine, Rebecca Hamidfar, Sophie Ramel, Laure Cosson, Benoit Douvry, Isabelle Danner-Boucher, Pierre Foucaud, Charlotte Roy, Espérie Burnet, Caroline Raynal, Marie-Pierre Audrezet, Jennifer Da Silva, Clémence Martin
<p><strong>Background: </strong>Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response.</p><p><strong>Methods: </strong>The French compassionate programme expanded access to elexacaftor-tezacaftor-ivacaftor to people with cystic fibrosis, aged 6 years and older, without a F508del variant, excluding those with two variants previously characterised as non-responsive. Participants at France's 47 cystic fibrosis centres were given a 4-6 week trial of elexacaftor-tezacaftor-ivacaftor and response was determined by a centralised committee based on evolution of clinical data, lung function, and sweat chloride concentration. Responsiveness of individual CFTR variants was derived from observed clinical responses.</p><p><strong>Findings: </strong>The first compassionnate programme was launched on May 19, 2022; by March 8, 2024, 516 people with cystic fibrosis had been identified for inclusion in this real-word study: 37 were not included due to the presence of two variants previously characterised as non-responsive to elexacaftor-tezacaftor-ivacaftor, and 479 (229 females [48%] and 250 males [52%]) received elexacaftor-tezacaftor-ivacaftor for 4-6 weeks. Among 443 participants who received no CFTR modulator before elexacaftor-tezacaftor-ivacaftor, 83 had at least one FDA-approved variant, of whom 81 (98%) were responders and continued elexacaftor-tezacaftor-ivacaftor; in responders, mean absolute change in sweat chloride was -44·5 mmol/L (95% CI -39·1 to -49·8) and percentage of predicted FEV<sub>1</sub> (ppFEV<sub>1</sub>) was 11·1 percentage points (95% CI 8·4 to 13·7; both comparisons p<0·0001). Among 360 participants with no FDA-approved variant and no previous CFTR modulator, 177 (49%) were responders; in responders, mean absolute change in sweat chloride was -20·5 mmol/L (-17·2 to -23·8) and ppFEV<sub>1</sub> was 13·2 percentage points (11·4 to 15·0; both comparisons p<0·0001). Among 36 participants who were receiving ivacaftor before elexacaftor-tezacaftor-ivacaftor, 32 (89%) continued elexacaftor-tezacaftor-ivacaftor. Of 251 individual CFTR variants, 64 (28 FDA-approved) were classified as responsive or possibly responsive to elexacaftor-tezacaftor-ivacaftor, and 123 (two FDA-approved) as non-responsive or possibly non-responsive to elexacaftor-tezacaftor-ivacaftor.</p><p><strong>Interpretation: </strong>In France, over half of the population with cystic fibrosis without a F508del variant responded to elexacaftor-tezacaftor-ivacaftor, with mo
背景:欧洲已批准 Elexacaftor-tezacaftor-ivacaftor 用于治疗至少有一种 F508del CFTR 变异的囊性纤维化患者。此外,美国食品和药物管理局(FDA)也批准该药用于治疗至少有一种 177 个罕见变异体的囊性纤维化患者。本研究旨在描述法国无F508del CFTR变异体的囊性纤维化患者对eexacaftor-tezacaftor-ivacaftor的临床反应,并根据观察到的临床反应确定CFTR变异体对eexacaftor-tezacaftor-ivacaftor的反应:法国同情计划扩大了 elexacaftor-tezacaftor-ivacaftor 的使用范围,年龄在 6 岁及以上、无 F508del 变异的囊性纤维化患者均可使用,但不包括那些先前被认定为无应答的两种变异的患者。法国 47 个囊性纤维化中心的参与者接受了为期 4-6 周的 elexacaftor-tezacaftor-ivacaftor 试验,由一个中央委员会根据临床数据、肺功能和汗液氯化物浓度的变化来确定反应。根据观察到的临床反应推导出单个 CFTR 变体的反应性:第一项同情计划于 2022 年 5 月 19 日启动;截至 2024 年 3 月 8 日,已确定 516 名囊性纤维化患者可纳入这项实词研究:其中 37 人因存在两种变异型而未被纳入,这两种变异型之前被定性为对 elexacaftor-tezacaftor-ivacaftor 无应答;479 人(229 名女性[48%]和 250 名男性[52%])接受了为期 4-6 周的 elexacaftor-tezacaftor-ivacaftor 治疗。在接受依来卡夫托-替扎卡夫托-依瓦卡夫托治疗前未接受过 CFTR 调节剂治疗的 443 名参与者中,83 人至少有一种 FDA 批准的变异体,其中 81 人(98%)为应答者,并继续接受依来卡夫托-替扎卡夫托-依瓦卡夫托治疗;在应答者中,汗液氯化物的平均绝对变化为-44-5 mmol/L(95% CI -39-1至-49-8),预测FEV1(ppFEV1)的百分比为11-1个百分点(95% CI 8-4至13-7;两组比较p1均为13-2个百分点(11-4至15-0;两组比较p1均为13-2):在法国,半数以上无F508del变异体的囊性纤维化患者对依来卡夫托-替扎卡夫托-依瓦卡夫托产生了反应,其中大多数反应者无FDA批准的变异体。治疗时间相对较短,需要进一步研究来描述 elexacaftor-tezacaftor-ivacaftor 在该人群中的长期安全性和有效性:资助机构:法国黏液粘稠性疾病协会(Association Vaincre la Mucoviscidose)、法国黏液粘稠性疾病学会(Société Française de la Mucoviscidose)和MUCO-CFTR罕见疾病基金会(Filière Maladies Rares MUCO-CFTR)。
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引用次数: 0
Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab-ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial. 日本铂类联合化疗加 pembrolizumab 与铂类联合化疗加 nivolumab-ipilimumab 治疗免疫性晚期非小细胞肺癌的比较(JCOG2007):一项开放标签、多中心、随机的 3 期试验。
IF 38.7 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI: 10.1016/S2213-2600(24)00185-1
Yoshimasa Shiraishi, Shogo Nomura, Shunichi Sugawara, Hidehito Horinouchi, Yasuto Yoneshima, Hidetoshi Hayashi, Koichi Azuma, Satoshi Hara, Seiji Niho, Ryo Morita, Masafumi Yamaguchi, Toshihide Yokoyama, Kiyotaka Yoh, Takayasu Kurata, Hiroaki Okamoto, Masaki Okamoto, Takashi Kijima, Kazuo Kasahara, Yutaka Fujiwara, Shuji Murakami, Shintaro Kanda, Hiroaki Akamatsu, Shinnosuke Takemoto, Hiroyasu Kaneda, Toshiyuki Kozuki, Masahiko Ando, Yuta Sekino, Haruhiko Fukuda, Yuichiro Ohe, Isamu Okamoto

Background: The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.

Methods: This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing.

Findings: Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group.

Interpretation: The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival.

Funding: The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development.

背景:铂类化疗和PD-1或其配体PD-L1抗体(无论有无CTLA-4抗体)的联合治疗改善了转移性非小细胞肺癌(NSCLC)患者的生存率。然而,还没有随机对照试验评估过在铂类化疗加 PD-1 或 PD-L1 抑制剂的基础上加用 CTLA-4 抑制剂对生存的益处:这项开放标签、随机3期试验在日本48家医院进行。符合条件的患者年龄在20岁或20岁以上,既往未经治疗的晚期NSCLC患者,且东部合作肿瘤学组(Eastern Cooperative Oncology Group)表现状态为0或1。不包括已知驱动癌基因的患者。参与者被随机分配(1:1)接受铂类化疗(四个周期)加pembrolizumab(pembrolizumab组)或铂类化疗(两个周期)加nivolumab-ipilimumab(nivolumab-ipilimumab组)。主要终点是总生存期,在意向治疗的基础上对所有随机分配的患者进行评估。该试验已在日本临床试验注册中心(JRCTs031210013)注册,目前已不再接受新的注册,仍在进行中:研究结果:从2021年4月6日开始招募患者到2023年3月30日终止试验期间,nivolumab-ipilimumab组的148名患者中有11人(7%)发生了治疗相关死亡。由于治疗相关死亡人数较多,因此提前终止了患者招募,结果有295名患者(236名[80%]男性和59名[20%]女性)入组;主要分析是在117例死亡(少于要求的329例死亡)的基础上进行的。截至2023年5月25日(数据截止日),nivolumab-ipilimumab组和pembrolizumab组的总生存期没有显著差异(中位23-7个月[95% CI 17-6无法估计] vs 20-5个月[17-6无法估计],分别为0-98[90% CI 0-72-1-34];P=0-46)。在nivolumab-ipilimumab组的146名患者中,有87人(60%)发生了3级或更严重的非血液学不良事件;在pembrolizumab组的144名患者中,有59人(41%)发生了3级或更严重的非血液学不良事件。与nivolumab-ipilimumab组相比,pembrolizumab组的生活质量往往更高:安全性和有效性数据表明,nivolumab-ipilimumab联合铂类化疗与pembrolizumab联合铂类化疗作为晚期NSCLC患者的一线治疗相比,收益-风险情况并不理想,但最终结论有待对总生存期的最新分析:国家癌症中心研究与发展基金和日本医学研究开发机构。
{"title":"Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab-ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial.","authors":"Yoshimasa Shiraishi, Shogo Nomura, Shunichi Sugawara, Hidehito Horinouchi, Yasuto Yoneshima, Hidetoshi Hayashi, Koichi Azuma, Satoshi Hara, Seiji Niho, Ryo Morita, Masafumi Yamaguchi, Toshihide Yokoyama, Kiyotaka Yoh, Takayasu Kurata, Hiroaki Okamoto, Masaki Okamoto, Takashi Kijima, Kazuo Kasahara, Yutaka Fujiwara, Shuji Murakami, Shintaro Kanda, Hiroaki Akamatsu, Shinnosuke Takemoto, Hiroyasu Kaneda, Toshiyuki Kozuki, Masahiko Ando, Yuta Sekino, Haruhiko Fukuda, Yuichiro Ohe, Isamu Okamoto","doi":"10.1016/S2213-2600(24)00185-1","DOIUrl":"10.1016/S2213-2600(24)00185-1","url":null,"abstract":"<p><strong>Background: </strong>The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.</p><p><strong>Methods: </strong>This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing.</p><p><strong>Findings: </strong>Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group.</p><p><strong>Interpretation: </strong>The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival.</p><p><strong>Funding: </strong>The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development.</p>","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":" ","pages":"877-887"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial. 罗达司他乙酯治疗肺动脉高压的安全性和有效性(ELEVATE-2):一项剂量范围、随机、多中心、2b 期试验。
IF 38.7 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-11-01 Epub Date: 2024-09-19 DOI: 10.1016/S2213-2600(24)00226-1
Olivier Sitbon, Andris Skride, Jeremy Feldman, Sandeep Sahay, Oksana A Shlobin, Vallerie McLaughlin, Hossein-Ardeschir Ghofrani, David Langleben, Ed Parsley, Gwyn D'Souza, Tonya Marmon, Watiri Kamau-Kelley, Renee Jones, Ravi Grewal, Steve Wring, Michelle Palacios, Himanshu Naik, Jill Denning, Howard M Lazarus, Marc Humbert
<p><strong>Background: </strong>The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results.</p><p><strong>Methods: </strong>ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America. Eligible participants were aged 18 years or older, had pulmonary arterial hypertension with WHO functional class II or III symptom severity, and had received a stable dose and regimen of one or more pulmonary arterial hypertension treatments for at least 12 weeks. Participants were randomly assigned 1:1:1 to receive two placebo tablets, one placebo and one rodatristat ethyl 300 mg tablet, or two rodatristat ethyl 300 mg tablets twice daily using an interactive response system. Participants, investigators, site personnel, and sponsors were masked to treatment allocation. Participants who completed the 24 week treatment period were invited to continue in an open-label extension. The primary endpoint was percent change in pulmonary vascular resistance (PVR) from baseline to week 24. Primary efficacy analyses were conducted on the intention-to-treat population and analyses of harms were conducted in the safety population, which included all patients who received any amount of the study drug. This trial is registered with ClinicalTrials.gov, NCT04712669, and is now complete.</p><p><strong>Findings: </strong>Between March 18, 2021 and Dec 13, 2022, 108 participants were enrolled and randomly assigned. 36 participants received placebo, 36 received rodatristat ethyl 300 mg, and 36 received rodatristat ethyl 600 mg twice daily. Overall, 85 (79%) of participants were female and 23 (21%) were male. The mean age was 52·8 years (SD 14·7) in the full analysis set. In the open-label extension phase, 62 (82%) of participants were female and 14 (18%) were male, and the mean age was 52·8 years (SD 14·7); this phase was terminated following sponsor review of unmasked main study results. Least-squares mean percent change in PVR from baseline to week 24 favoured placebo and was 5·8% (SE 18·1) for the placebo group, 63·1% (18·5) for the rodatristat ethyl 300 mg group, and 64·2% (18·0) for the rodatristat ethyl 600 mg group. Treatment-emergent adverse events (TEAE) were reported for 29 (81%) patients in the placebo group, 33 (92%) patients in the rodatristat ethyl 300 mg group, and all 36 (100%) patients in the rodatristat ethyl 600 mg group. TEAE leading to study discontinuation were reported for three (8%) patients in the placebo group, four (11%) patients in the rodatristat ethyl 300 mg group, and four (11%) in the rodatristat ethyl 600 mg group. There was one (3%) TEAE leading to death in
背景:近几十年来,人们对血清素在肺动脉高压中的作用进行了广泛的研究,临床前数据有力地证明了血清素参与了疾病的发病机制;然而,临床研究的结果却不尽相同:ELEVATE-2是一项2b期剂量范围、随机、双盲、安慰剂对照的多中心试验,研究将罗达司他乙酯作为肺动脉高压患者的治疗药物。该研究在欧洲和北美 16 个国家的 64 个地点进行。符合条件的参与者年龄在18岁或18岁以上,患有肺动脉高压,症状严重程度为WHO功能分级II级或III级,接受过一种或多种肺动脉高压治疗方法的稳定剂量和疗程至少12周。参试者通过交互式应答系统以 1:1:1 的比例随机分配接受两片安慰剂、一片安慰剂和一片 300 毫克罗达司他乙酯片剂,或每天两次接受两片 300 毫克罗达司他乙酯片剂。参与者、研究人员、研究机构人员和赞助商均对治疗分配进行了蒙蔽。完成 24 周治疗的参与者将被邀请继续进行开放标签延长治疗。主要终点是肺血管阻力 (PVR) 从基线到第 24 周的变化百分比。主要疗效分析在意向治疗人群中进行,危害分析在安全人群中进行,安全人群包括接受任何剂量研究药物的所有患者。该试验已在 ClinicalTrials.gov 登记,编号为 NCT04712669,现已完成:在 2021 年 3 月 18 日至 2022 年 12 月 13 日期间,108 名参与者入组并被随机分配。36名参与者接受安慰剂治疗,36名参与者接受乙基棒曲霉素300毫克治疗,36名参与者接受乙基棒曲霉素600毫克治疗,每天两次。总体而言,85 名参与者(79%)为女性,23 名参与者(21%)为男性。整个分析组的平均年龄为 52-8 岁(标准偏差为 14-7)。在开放标签扩展阶段,62 名(82%)参与者为女性,14 名(18%)为男性,平均年龄为 52-8 岁(标准差为 14-7);该阶段在赞助商对未掩盖的主要研究结果进行审查后终止。安慰剂组从基线到第24周的PVR最小二乘法平均百分比变化率为5-8%(SE 18-1),罗达司他乙酯300毫克组为63-1%(18-5),罗达司他乙酯600毫克组为64-2%(18-0)。安慰剂组有29名(81%)患者报告了治疗突发不良事件(TEAE),300毫克罗达司他他乙酯组有33名(92%)患者报告了治疗突发不良事件(TEAE),600毫克罗达司他他乙酯组有36名(100%)患者报告了治疗突发不良事件(TEAE)。安慰剂组有 3 名(8%)患者、300 毫克罗达司他他乙酯组有 4 名(11%)患者、600 毫克罗达司他他乙酯组有 4 名(11%)患者出现导致研究中止的 TEAE。罗达司他丁酯 300 毫克组有 1 例(3%)TEAE 导致死亡:我们的研究结果表明,通过罗达司他他乙酯降低外周血清素浓度会对肺动脉高压患者的肺血流动力学和心脏功能产生负面影响。这一研究结果表明,操纵这一途径可能不是治疗肺动脉高压的合适选择:Enzyvant Therapeutics(现为住友制药美国公司)。
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引用次数: 0
Strengthening intensive care: addressing challenges and embracing opportunities. 加强重症监护:应对挑战,抓住机遇。
IF 38.7 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-11-01 Epub Date: 2024-09-26 DOI: 10.1016/S2213-2600(24)00294-7
Elie Azoulay, Maurizio Cecconi, Jan J De Waele
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引用次数: 0
Electro-biodiesel empowered by co-design of microorganism and electrocatalysis 通过微生物和电催化的共同设计实现电生物柴油
IF 39.8 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-10-31 DOI: 10.1016/j.joule.2024.10.001
Kainan Chen, Peng Zhang, Yayun Chen, Chengcheng Fei, Jiali Yu, Jiahong Zhou, Yuanhao Liang, Weiwei Li, Sisi Xiang, Susie Y. Dai, Joshua S. Yuan
Efficient and sustainable energy production is essential for climate change mitigation, yet current approaches like biofuels or electro-fuels have limitations in efficiency and product profile. We advanced a new electro-biodiesel route via integrating electrocatalysis and bioconversion to produce lipids from CO2 for biodiesel. We first revealed bioenergetic and metabolic limits in C2+ intermediate utilization through simulations and metabolomics, guiding the synthetic biology design to achieve reductant balance, more ATP production, efficient lipid conversion, and higher lipid yield. Furthermore, we discovered specific ratios of ethanol and acetate to achieve co-substrate synergy, empowering bimetallic catalyst design to improve bioconversion efficiency. The microbial and catalyst co-design achieved a solar-energy-to-molecule conversion efficiency of 4.5% for CO2-to-lipid conversion. Electro-biodiesel leverages the high efficiency of electrocatalysis and longer-carbon-chain products from microbial lipid synthesis, overcoming the limitations for both electrocatalysis and bioconversion. Electro-biodiesel achieved 45 times less land usage than soybean biodiesel, competitive economics, and substantial carbon emission reduction.
高效和可持续的能源生产对减缓气候变化至关重要,但目前的生物燃料或电燃料等方法在效率和产品特性方面存在局限性。我们通过整合电催化和生物转化技术,推进了一条新的电生物柴油路线,利用二氧化碳生产生物柴油所需的脂质。我们首先通过模拟和代谢组学揭示了 C2+ 中间体利用过程中的生物能和代谢限制,从而指导合成生物学设计实现还原剂平衡、更多 ATP 生成、高效脂质转化和更高的脂质产量。此外,我们还发现了乙醇和醋酸的特定比例,以实现共底物协同作用,从而提高双金属催化剂的设计能力,提高生物转化效率。微生物和催化剂的协同设计使二氧化碳到脂质的太阳能分子转换效率达到 4.5%。电生物柴油利用了电催化的高效率和微生物脂质合成的长碳链产品,克服了电催化和生物转化的局限性。与大豆生物柴油相比,电生物柴油的土地使用量减少了 45 倍,经济效益极具竞争力,并大幅减少了碳排放。
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引用次数: 0
Universal control of four singlet–triplet qubits 对四个单三重子量子比特的通用控制
IF 38.3 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-10-31 DOI: 10.1038/s41565-024-01817-9
Xin Zhang, Elizaveta Morozova, Maximilian Rimbach-Russ, Daniel Jirovec, Tzu-Kan Hsiao, Pablo Cova Fariña, Chien-An Wang, Stefan D. Oosterhout, Amir Sammak, Giordano Scappucci, Menno Veldhorst, Lieven M. K. Vandersypen

The coherent control of interacting spins in semiconductor quantum dots is of strong interest for quantum information processing and for studying quantum magnetism from the bottom up. Here we present a 2 × 4 germanium quantum dot array with full and controllable interactions between nearest-neighbour spins. As a demonstration of the level of control, we define four singlet–triplet qubits in this system and show two-axis single-qubit control of each qubit and SWAP-style two-qubit gates between all neighbouring qubit pairs, yielding average single-qubit gate fidelities of 99.49(8)–99.84(1)% and Bell state fidelities of 73(1)–90(1)%. Combining these operations, we experimentally implement a circuit designed to generate and distribute entanglement across the array. A remote Bell state with a fidelity of 75(2)% and concurrence of 22(4)% is achieved. These results highlight the potential of singlet–triplet qubits as a competing platform for quantum computing and indicate that scaling up the control of quantum dot spins in extended bilinear arrays can be feasible.

对半导体量子点中相互作用的自旋进行相干控制,对于量子信息处理和自下而上地研究量子磁性具有重大意义。在这里,我们展示了一个 2 × 4 锗量子点阵列,其近邻自旋之间的相互作用是完全可控的。作为控制水平的演示,我们在该系统中定义了四个单三重量子比特,并展示了对每个量子比特的双轴单量子比特控制以及所有相邻量子比特对之间的 SWAP 式双量子比特门,其平均单量子比特门保真度为 99.49(8)-99.84(1)% ,贝尔态保真度为 73(1)-90(1)% 。结合这些操作,我们在实验中实现了一种电路,旨在生成和分配整个阵列的纠缠。远程贝尔态的保真度达到 75(2)%,一致性达到 22(4)%。这些结果凸显了单三元量子比特作为量子计算竞争平台的潜力,并表明在扩展的双线性阵列中扩大量子点自旋的控制是可行的。
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引用次数: 0
Green rust for green chemistry 绿色化学的绿色铁锈
IF 36.3 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-10-31 DOI: 10.1038/s41570-024-00669-0
John Dickenson
A new study explores the catalytic potential of green rust for selectively converting carbon monoxide (CO) to acetone without an applied potential. Its unique electronic properties suggest promising applications in CO remediation and future catalyst design.
一项新的研究探索了绿锈的催化潜力,它可以在不施加电位的情况下将一氧化碳(CO)选择性地转化为丙酮。其独特的电子特性表明,它在一氧化碳修复和未来催化剂设计方面具有广阔的应用前景。
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引用次数: 0
Health promotion in the management of respiratory diseases: an Indian perspective 呼吸系统疾病管理中的健康促进:印度视角
IF 76.2 4区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Pub Date : 2024-10-30 DOI: 10.1016/s2213-2600(24)00332-1
Arundhati Garud, Debabani Biswas, Saibal Moitra, Subhabrata Moitra
No Abstract
无摘要
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引用次数: 0
期刊
European Journal of Inorganic Chemistry
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