Pub Date : 2024-11-01Epub Date: 2024-07-08DOI: 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.
{"title":"Interactions between respiratory syncytial virus and Streptococcus pneumoniae in the pathogenesis of childhood respiratory infections: a systematic review.","authors":"Sjanna B Besteman, Debby Bogaert, Louis Bont, Asuncion Mejias, Octavio Ramilo, Daniel M Weinberger, Ron Dagan","doi":"10.1016/S2213-2600(24)00148-6","DOIUrl":"10.1016/S2213-2600(24)00148-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":" ","pages":"915-932"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592088","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}
Pub Date : 2024-11-01DOI: 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.
{"title":"Clean energy demand must secure sustainable nickel supply","authors":"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","doi":"10.1016/j.joule.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.joule.2024.10.008","url":null,"abstract":"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.","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":"4 1","pages":""},"PeriodicalIF":39.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562095","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}
Pub Date : 2024-11-01Epub Date: 2024-08-13DOI: 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
{"title":"The expanded French compassionate programme for elexacaftor-tezacaftor-ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study.","authors":"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","doi":"10.1016/S2213-2600(24)00208-X","DOIUrl":"10.1016/S2213-2600(24)00208-X","url":null,"abstract":"<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","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":" ","pages":"888-900"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996918","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}
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}
Pub Date : 2024-11-01Epub Date: 2024-09-19DOI: 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
{"title":"Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial.","authors":"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","doi":"10.1016/S2213-2600(24)00226-1","DOIUrl":"10.1016/S2213-2600(24)00226-1","url":null,"abstract":"<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","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":" ","pages":"865-876"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300405","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}
Pub Date : 2024-10-31DOI: 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。
{"title":"Electro-biodiesel empowered by co-design of microorganism and electrocatalysis","authors":"Kainan Chen, Peng Zhang, Yayun Chen, Chengcheng Fei, Jiali Yu, Jiahong Zhou, Yuanhao Liang, Weiwei Li, Sisi Xiang, Susie Y. Dai, Joshua S. Yuan","doi":"10.1016/j.joule.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.joule.2024.10.001","url":null,"abstract":"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 CO<sub>2</sub> 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 CO<sub>2</sub>-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.","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":"126 1","pages":""},"PeriodicalIF":39.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556158","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}
Pub Date : 2024-10-31DOI: 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.
{"title":"Universal control of four singlet–triplet qubits","authors":"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","doi":"10.1038/s41565-024-01817-9","DOIUrl":"https://doi.org/10.1038/s41565-024-01817-9","url":null,"abstract":"<p>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.</p>","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":"239 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556261","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}
Pub Date : 2024-10-31DOI: 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.
{"title":"Green rust for green chemistry","authors":"John Dickenson","doi":"10.1038/s41570-024-00669-0","DOIUrl":"https://doi.org/10.1038/s41570-024-00669-0","url":null,"abstract":"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.","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":"240 1","pages":""},"PeriodicalIF":36.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556363","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}
{"title":"Health promotion in the management of respiratory diseases: an Indian perspective","authors":"Arundhati Garud, Debabani Biswas, Saibal Moitra, Subhabrata Moitra","doi":"10.1016/s2213-2600(24)00332-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00332-1","url":null,"abstract":"No Abstract","PeriodicalId":38,"journal":{"name":"European Journal of Inorganic Chemistry","volume":"60 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542070","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}