首页 > 最新文献

EBioMedicine最新文献

英文 中文
Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis. 肌萎缩性脊髓侧索硬化症疾病进展的临床和生物预后标志物:验证及对临床试验设计和分析的影响。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-12 DOI: 10.1016/j.ebiom.2024.105323
Michael Benatar, Eric A Macklin, Andrea Malaspina, Mary-Louise Rogers, Eran Hornstein, Vittoria Lombardi, Danielle Renfrey, Stephanie Shepheard, Iddo Magen, Yahel Cohen, Volkan Granit, Jeffrey M Statland, Jeannine M Heckmann, Rosa Rademakers, Caroline A McHutchison, Leonard Petrucelli, Corey T McMillan, Joanne Wuu

Background: With increasing recognition of the value of incorporating prognostic markers into amyotrophic lateral sclerosis (ALS) trial design and analysis plans, there is a pressing need to understand which among the prevailing clinical and biochemical markers have real value, and how they can be optimally used.

Methods: A subset of patients with ALS recruited through the multi-center Phenotype-Genotype-Biomarker study (clinicaltrials.gov: NCT02327845) was identified as "trial-like" based on meeting common trial eligibility criteria. Clinical phenotyping was performed by evaluators trained in relevant assessments. Serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH), urinary p75ECD, plasma microRNA-181, and an array of biochemical and clinical measures were evaluated for their prognostic value. Associations with functional progression were estimated by random-slopes mixed models of ALS functional rating scale-revised (ALSFRS-R) score. Associations with survival were estimated by log-rank test and Cox proportional hazards regression. Potential sample size savings from adjusting for given biomarkers in a hypothetical trial were estimated.

Findings: Baseline serum NfL is a powerful prognostic biomarker, predicting survival and ALSFRS-R rate of decline. Serum NfL <40 pg/mL and >100 pg/mL correspond to future ALSFRS-R slopes of ∼0.5 and ∼1.5 points/month, respectively. Serum NfL also adds value to the best available clinical predictors, encapsulated by the European Network to Cure ALS (ENCALS) predictor score. In models of functional decline, the addition of NfL yields ∼25% sample size saving above those achieved by inclusion of either clinical predictors or ENCALS score alone. The prognostic value of serum pNfH, urinary p75ECD, and plasma miR-181ab is more limited.

Interpretation: Among the multitude of biomarkers considered, only blood NfL adds value to the ENCALS prediction model and should be incorporated into analysis plans for all ongoing and future ALS trials. Defined thresholds of NfL might also be used in trial design, for enrichment or stratified randomisation, to improve trial efficiency.

Funding: NIH (U01-NS107027, U54-NS092091). ALSA (16-TACL-242).

背景:随着越来越多的人认识到将预后标志物纳入肌萎缩侧索硬化症(ALS)试验设计和分析计划的价值,人们迫切需要了解目前流行的临床和生化标志物中哪些具有真正的价值,以及如何优化使用这些标志物:通过多中心表型-基因型-生物标记物研究(clinicaltrials.gov: NCT02327845)招募的 ALS 患者子集被确定为 "类似试验",其依据是符合共同的试验资格标准。临床表型由接受过相关评估培训的评估人员进行。血清神经丝轻型(NfL)和磷酸化神经丝重型(pNfH)、尿p75ECD、血浆microRNA-181以及一系列生化和临床指标的预后价值得到了评估。通过ALS功能评分量表-修订版(ALSFRS-R)评分的随机斜率混合模型估计了与功能进展的关系。通过对数秩检验和 Cox 比例危险度回归估算了与存活率的关系。对假设试验中调整特定生物标志物可能节省的样本量进行了估算:基线血清 NfL 是一种强有力的预后生物标志物,可预测存活率和 ALSFRS-R 下降率。血清 NfL 100 pg/mL 与未来 ALSFRS-R 斜率分别为 0.5 和 1.5 分/月相对应。血清 NfL 还能增加现有最佳临床预测指标的价值,欧洲 ALS(肌萎缩性脊髓侧索硬化症)治愈网络(ENCALS)的预测指标评分囊括了这些指标。在功能衰退模型中,加入 NfL 比仅加入临床预测因子或 ENCALS 评分节省了 25% 的样本量。血清 pNfH、尿液 p75ECD 和血浆 miR-181ab 的预后价值较为有限:在考虑的多种生物标志物中,只有血液NfL能为ENCALS预测模型增加价值,应将其纳入所有正在进行的和未来的ALS试验的分析计划中。定义的NfL阈值也可用于试验设计,进行富集或分层随机化,以提高试验效率:国家卫生研究院(U01-NS107027、U54-NS092091)。ALSA(16-TACL-242)。
{"title":"Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis.","authors":"Michael Benatar, Eric A Macklin, Andrea Malaspina, Mary-Louise Rogers, Eran Hornstein, Vittoria Lombardi, Danielle Renfrey, Stephanie Shepheard, Iddo Magen, Yahel Cohen, Volkan Granit, Jeffrey M Statland, Jeannine M Heckmann, Rosa Rademakers, Caroline A McHutchison, Leonard Petrucelli, Corey T McMillan, Joanne Wuu","doi":"10.1016/j.ebiom.2024.105323","DOIUrl":"10.1016/j.ebiom.2024.105323","url":null,"abstract":"<p><strong>Background: </strong>With increasing recognition of the value of incorporating prognostic markers into amyotrophic lateral sclerosis (ALS) trial design and analysis plans, there is a pressing need to understand which among the prevailing clinical and biochemical markers have real value, and how they can be optimally used.</p><p><strong>Methods: </strong>A subset of patients with ALS recruited through the multi-center Phenotype-Genotype-Biomarker study (clinicaltrials.gov: NCT02327845) was identified as \"trial-like\" based on meeting common trial eligibility criteria. Clinical phenotyping was performed by evaluators trained in relevant assessments. Serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH), urinary p75<sup>ECD</sup>, plasma microRNA-181, and an array of biochemical and clinical measures were evaluated for their prognostic value. Associations with functional progression were estimated by random-slopes mixed models of ALS functional rating scale-revised (ALSFRS-R) score. Associations with survival were estimated by log-rank test and Cox proportional hazards regression. Potential sample size savings from adjusting for given biomarkers in a hypothetical trial were estimated.</p><p><strong>Findings: </strong>Baseline serum NfL is a powerful prognostic biomarker, predicting survival and ALSFRS-R rate of decline. Serum NfL <40 pg/mL and >100 pg/mL correspond to future ALSFRS-R slopes of ∼0.5 and ∼1.5 points/month, respectively. Serum NfL also adds value to the best available clinical predictors, encapsulated by the European Network to Cure ALS (ENCALS) predictor score. In models of functional decline, the addition of NfL yields ∼25% sample size saving above those achieved by inclusion of either clinical predictors or ENCALS score alone. The prognostic value of serum pNfH, urinary p75<sup>ECD</sup>, and plasma miR-181ab is more limited.</p><p><strong>Interpretation: </strong>Among the multitude of biomarkers considered, only blood NfL adds value to the ENCALS prediction model and should be incorporated into analysis plans for all ongoing and future ALS trials. Defined thresholds of NfL might also be used in trial design, for enrichment or stratified randomisation, to improve trial efficiency.</p><p><strong>Funding: </strong>NIH (U01-NS107027, U54-NS092091). ALSA (16-TACL-242).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to "The significance of recurrent de novo amino acid substitutions that emerged during chronic SARS-CoV-2 infection: an observational study" [eBioMedicine, 2024;107:105273]. 慢性 SARS-CoV-2 感染期间反复出现的新氨基酸置换的意义:一项观察性研究》[eBioMedicine,2024;107:105273]的更正。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-24 DOI: 10.1016/j.ebiom.2024.105371
Jonathan Daniel Ip, Wing-Ming Chu, Wan-Mui Chan, Allen Wing-Ho Chu, Rhoda Cheuk-Ying Leung, Qi Peng, Anthony Raymond Tam, Brian Pui-Chun Chan, Jian-Piao Cai, Kwok-Yung Yuen, Kin-Hang Kok, Yi Shi, Ivan Fan-Ngai Hung, Kelvin Kai-Wang To
{"title":"Corrigendum to \"The significance of recurrent de novo amino acid substitutions that emerged during chronic SARS-CoV-2 infection: an observational study\" [eBioMedicine, 2024;107:105273].","authors":"Jonathan Daniel Ip, Wing-Ming Chu, Wan-Mui Chan, Allen Wing-Ho Chu, Rhoda Cheuk-Ying Leung, Qi Peng, Anthony Raymond Tam, Brian Pui-Chun Chan, Jian-Piao Cai, Kwok-Yung Yuen, Kin-Hang Kok, Yi Shi, Ivan Fan-Ngai Hung, Kelvin Kai-Wang To","doi":"10.1016/j.ebiom.2024.105371","DOIUrl":"10.1016/j.ebiom.2024.105371","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Profiling steroid hormone landscape of bladder cancer reveals depletion of intratumoural androgens to castration levels: a cross-sectional study. 一项横断面研究显示,膀胱癌的类固醇激素分布情况表明,瘤内雄激素消耗到了阉割水平。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-28 DOI: 10.1016/j.ebiom.2024.105359
Kimmo Kettunen, Julia Mathlin, Tarja Lamminen, Asta Laiho, Merja R Häkkinen, Seppo Auriola, Laura L Elo, Peter J Boström, Matti Poutanen, Pekka Taimen

Background: Bladder cancer is a highly over-represented disease in males. The involvement of sex steroids in bladder carcinogenesis and the utilisation of steroid hormone action as a therapeutic target have been frequently proposed. However, the intratumoural steroid milieu remains unclear.

Methods: We used mass spectrometry and transcriptomic profiling to determine the levels of 23 steroid hormones and the expression of steroidogenic enzymes in primary tumours from patients who underwent transurethral resection (n = 24), and tumours and adjacent morphologically benign bladder tissues from treatment-naïve patients, who underwent radical cystectomy (n = 20). The corresponding steroids were determined from the patients' sera.

Findings: Our results show that both bladder tumours and non-tumour tissues are androgen-poor, with DHT being virtually unquantifiable and testosterone at castration levels. Intratumoural enzymes that inactivate potent androgens (e.g., HSD17B2) exhibited similar tumour aggressiveness-linked downregulation, as reported in advanced forms of classical steroid-dependent cancers, whereas there was little change in the corresponding activating enzymes. Finally, our results suggest cancer aggressiveness-linked dissimilarities in steroid profiles; the patients with overall low circulating steroid levels and those with an association between androgen receptor expression and intratumoural testosterone levels in place had fewer recurrences than the rest.

Interpretation: By revealing the steroid landscape of bladder cancer, our study not only underscores the androgen-poor nature of the malignancy but also identifies potential alterations in steroid profiles that are linked to disease aggressiveness.

Funding: The Cancer Foundation Finland, the Finnish State Research Funding (VTR).

背景:膀胱癌是一种男性高发疾病。性类固醇参与了膀胱癌的发生,利用类固醇激素的作用作为治疗靶点也是经常被提出的。然而,肿瘤内的类固醇环境仍不清楚:我们使用质谱分析和转录组分析方法测定了接受经尿道切除术患者(24 人)的原发性肿瘤中 23 种类固醇激素的水平和类固醇生成酶的表达,以及接受根治性膀胱切除术的未接受治疗患者(20 人)的肿瘤和邻近形态良性膀胱组织中 23 种类固醇激素的水平和类固醇生成酶的表达。相应的类固醇是从患者血清中提取的:我们的研究结果表明,膀胱肿瘤和非肿瘤组织均缺乏雄激素,其中 DHT 几乎无法量化,而睾酮则处于阉割水平。瘤内能使强效雄激素失活的酶(如 HSD17B2)表现出与肿瘤侵袭性相关的类似下调,这在晚期典型的类固醇依赖性癌症中已有报道,而相应的活化酶几乎没有变化。最后,我们的研究结果表明,与癌症侵袭性相关的类固醇谱存在差异;循环类固醇水平总体较低的患者以及雄激素受体表达与肿瘤内睾酮水平之间存在关联的患者的复发率低于其他患者:通过揭示膀胱癌的类固醇情况,我们的研究不仅强调了这种恶性肿瘤缺乏雄激素的特性,还发现了类固醇情况的潜在变化与疾病的侵袭性有关:芬兰癌症基金会、芬兰国家研究基金(VTR)。
{"title":"Profiling steroid hormone landscape of bladder cancer reveals depletion of intratumoural androgens to castration levels: a cross-sectional study.","authors":"Kimmo Kettunen, Julia Mathlin, Tarja Lamminen, Asta Laiho, Merja R Häkkinen, Seppo Auriola, Laura L Elo, Peter J Boström, Matti Poutanen, Pekka Taimen","doi":"10.1016/j.ebiom.2024.105359","DOIUrl":"10.1016/j.ebiom.2024.105359","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer is a highly over-represented disease in males. The involvement of sex steroids in bladder carcinogenesis and the utilisation of steroid hormone action as a therapeutic target have been frequently proposed. However, the intratumoural steroid milieu remains unclear.</p><p><strong>Methods: </strong>We used mass spectrometry and transcriptomic profiling to determine the levels of 23 steroid hormones and the expression of steroidogenic enzymes in primary tumours from patients who underwent transurethral resection (n = 24), and tumours and adjacent morphologically benign bladder tissues from treatment-naïve patients, who underwent radical cystectomy (n = 20). The corresponding steroids were determined from the patients' sera.</p><p><strong>Findings: </strong>Our results show that both bladder tumours and non-tumour tissues are androgen-poor, with DHT being virtually unquantifiable and testosterone at castration levels. Intratumoural enzymes that inactivate potent androgens (e.g., HSD17B2) exhibited similar tumour aggressiveness-linked downregulation, as reported in advanced forms of classical steroid-dependent cancers, whereas there was little change in the corresponding activating enzymes. Finally, our results suggest cancer aggressiveness-linked dissimilarities in steroid profiles; the patients with overall low circulating steroid levels and those with an association between androgen receptor expression and intratumoural testosterone levels in place had fewer recurrences than the rest.</p><p><strong>Interpretation: </strong>By revealing the steroid landscape of bladder cancer, our study not only underscores the androgen-poor nature of the malignancy but also identifies potential alterations in steroid profiles that are linked to disease aggressiveness.</p><p><strong>Funding: </strong>The Cancer Foundation Finland, the Finnish State Research Funding (VTR).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Convergence of SARS-CoV-2 spike antibody levels to a population immune setpoint. SARS-CoV-2尖峰抗体水平向群体免疫设定点靠拢。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-03 DOI: 10.1016/j.ebiom.2024.105319
Eric J Nilles, Kathryn Roberts, Michael de St Aubin, Helen Mayfield, Angela Cadavid Restrepo, Salome Garnier, Gabriela Abdalla, Marie Caroline Etienne, William Duke, Devan Dumas, Petr Jarolim, Timothy Oasan, Farah Peña, Beatriz Lopez, Lucia de la Cruz, Isaac Miguel Sanchez, Kristy Murray, Margaret Baldwin, Ronald Skewes-Ramm, Cecilia Then Paulino, Colleen L Lau, Adam Kucharski

Background: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications.

Methods: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes.

Findings: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile.

Interpretation: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens.

Funding: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).

背景:对SARS-CoV-2的个体免疫反应进行了深入研究,但对这些反应对群体免疫动态的综合影响仍知之甚少。鉴于群体免疫在病原体传播中的关键作用,确定推动群体免疫演变的因素对公共卫生具有重要意义:我们在多米尼加共和国西北部和东南部采用多阶段群组调查法选取了 5 岁及以上的人群。在大流行中期(2021 年 8 月)和大流行后期(2022 年 11 月)采集了配对血样。我们测定了血清中针对 SARS-CoV-2 尖峰蛋白的泛免疫球蛋白抗体。我们使用了广义加性模型(GAMs)和随机森林模型来分析抗体水平变化与各种预测变量之间的关系。主成分分析和偏倚图进一步探讨了预测变量与抗体变化之间的关系:我们发现抗体水平的分布从不规则分布转变为归一化的单峰高斯分布,这种转变是由滴度依赖性增强驱动的。无论基线滴度和疫苗接种情况如何,这都会导致抗体水平趋同于一个共同的免疫设定点:我们的研究结果表明,广泛传播驱动的滴度依赖性动力学以一致的方式指导着群体免疫力的演变。这些发现对有针对性的疫苗接种策略和改进未来传播的建模具有重要意义,为了解人群免疫动态提供了初步蓝图,可以指导针对 SARS-CoV-2 和其他潜在病原体的公共卫生和疫苗政策:本研究主要由美国疾病控制和预防中心(Centers for Disease Control and Prevention)的 U01GH002238 (EN) 基金资助。威康信托基金206250/Z/17/Z(AK)和澳大利亚国家健康与医学研究委员会研究员基金APP1158469(CLL)提供了薪金支持。
{"title":"Convergence of SARS-CoV-2 spike antibody levels to a population immune setpoint.","authors":"Eric J Nilles, Kathryn Roberts, Michael de St Aubin, Helen Mayfield, Angela Cadavid Restrepo, Salome Garnier, Gabriela Abdalla, Marie Caroline Etienne, William Duke, Devan Dumas, Petr Jarolim, Timothy Oasan, Farah Peña, Beatriz Lopez, Lucia de la Cruz, Isaac Miguel Sanchez, Kristy Murray, Margaret Baldwin, Ronald Skewes-Ramm, Cecilia Then Paulino, Colleen L Lau, Adam Kucharski","doi":"10.1016/j.ebiom.2024.105319","DOIUrl":"10.1016/j.ebiom.2024.105319","url":null,"abstract":"<p><strong>Background: </strong>Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications.</p><p><strong>Methods: </strong>We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes.</p><p><strong>Findings: </strong>We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile.</p><p><strong>Interpretation: </strong>Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens.</p><p><strong>Funding: </strong>The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
What defines hypervirulent Klebsiella pneumoniae? 如何定义高病毒性肺炎克雷伯氏菌?
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-10 DOI: 10.1016/j.ebiom.2024.105331
Thomas D Stanton, Kelly L Wyres
{"title":"What defines hypervirulent Klebsiella pneumoniae?","authors":"Thomas D Stanton, Kelly L Wyres","doi":"10.1016/j.ebiom.2024.105331","DOIUrl":"10.1016/j.ebiom.2024.105331","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer's disease and Down syndrome. 体液生物标志物在常染色体显性阿尔茨海默病和唐氏综合征中的临床和研究应用。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-10-03 DOI: 10.1016/j.ebiom.2024.105327
María Carmona-Iragui, Antoinette O'Connor, Jorge Llibre-Guerra, Patrick Lao, Nicholas J Ashton, Juan Fortea, Raquel Sánchez-Valle

Autosomal dominant Alzheimer's disease (ADAD) and Down syndrome (DS) constitute genetic forms of Alzheimer's disease (AD). The study of these forms has been crucial in understanding the biomarker changes and disease progression, notably in advancing our knowledge of the natural history of AD. However, some specific characteristics of biomarkers in genetically determined forms and, most importantly, the near full penetrance and predictability of disease onset lead to a very different context of use for biomarkers in these populations. This article delves into the similarities and differences in biomarker profiles between genetically determined AD and sporadic cases, discussing the implications for research and clinical practice. It also emphasizes the need to account for factors that may affect biomarker reliability differently in genetically determined AD. Enhancing our understanding of the disease will pave the way for more personalized therapeutic approaches for affected individuals.

常染色体显性阿尔茨海默病(ADAD)和唐氏综合征(DS)是阿尔茨海默病(AD)的遗传形式。对这些遗传形式的研究对于了解生物标志物的变化和疾病的进展至关重要,尤其是有助于增进我们对阿尔茨海默病自然史的了解。然而,基因决定型AD的生物标志物具有一些特定的特征,最重要的是,其近乎完全的渗透性和疾病发病的可预测性使得生物标志物在这些人群中的使用环境大相径庭。本文深入探讨了基因决定型 AD 与散发性病例之间生物标志物特征的异同,讨论了其对研究和临床实践的影响。文章还强调了考虑基因决定性 AD 中可能对生物标志物可靠性产生不同影响的因素的必要性。加强我们对该疾病的了解将为受影响的个体采用更个性化的治疗方法铺平道路。
{"title":"Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer's disease and Down syndrome.","authors":"María Carmona-Iragui, Antoinette O'Connor, Jorge Llibre-Guerra, Patrick Lao, Nicholas J Ashton, Juan Fortea, Raquel Sánchez-Valle","doi":"10.1016/j.ebiom.2024.105327","DOIUrl":"10.1016/j.ebiom.2024.105327","url":null,"abstract":"<p><p>Autosomal dominant Alzheimer's disease (ADAD) and Down syndrome (DS) constitute genetic forms of Alzheimer's disease (AD). The study of these forms has been crucial in understanding the biomarker changes and disease progression, notably in advancing our knowledge of the natural history of AD. However, some specific characteristics of biomarkers in genetically determined forms and, most importantly, the near full penetrance and predictability of disease onset lead to a very different context of use for biomarkers in these populations. This article delves into the similarities and differences in biomarker profiles between genetically determined AD and sporadic cases, discussing the implications for research and clinical practice. It also emphasizes the need to account for factors that may affect biomarker reliability differently in genetically determined AD. Enhancing our understanding of the disease will pave the way for more personalized therapeutic approaches for affected individuals.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insights into the use of biomarkers in clinical trials in Alzheimer's disease. 在阿尔茨海默病临床试验中使用生物标记物的启示。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-10-03 DOI: 10.1016/j.ebiom.2024.105322
Tharick A Pascoal, Cristiano S Aguzzoli, Firoza Z Lussier, Lucía Crivelli, Claudia K Suemoto, Juan Fortea, Pedro Rosa-Neto, Eduardo R Zimmer, Pamela C L Ferreira, Bruna Bellaver

Biomarkers have been instrumental in population selection and disease monitoring in clinical trials of recently FDA-approved drugs targeting amyloid-β to slow the progression of Alzheimer's disease (AD). As new therapeutic strategies and biomarker techniques emerge, the importance of biomarkers in drug development is growing exponentially. In this emerging landscape, biomarkers are expected to serve a wide range of contexts of use in clinical trials focusing on AD and related dementias. The joint FDA-NIH BEST (Biomarkers, EndpointS, and other Tools) framework provides standardised terminology to facilitate communication among stakeholders in this increasingly complex field. This review explores various applications of biomarkers relevant to AD clinical trials, using the BEST resource as a reference. For simplicity, we predominantly provide contextual characterizations of biomarkers use from the perspective of drugs targeting amyloid-β and tau proteins. However, general definitions and concepts can be extrapolated to other targets.

在最近获得美国食品与药物管理局批准的针对淀粉样蛋白-β的药物临床试验中,生物标志物在人群选择和疾病监测方面发挥了重要作用,以减缓阿尔茨海默病(AD)的进展。随着新的治疗策略和生物标志物技术的出现,生物标志物在药物开发中的重要性正呈指数级增长。在这一新兴领域,生物标志物有望在以阿兹海默病和相关痴呆症为重点的临床试验中广泛应用。FDA-NIH BEST(生物标记物、终点和其他工具)联合框架提供了标准化术语,以促进这一日益复杂领域的利益相关者之间的交流。本综述以 BEST 资源为参考,探讨了与 AD 临床试验相关的生物标记物的各种应用。为简便起见,我们主要从靶向淀粉样蛋白-β和tau蛋白的药物角度提供生物标记物使用的背景特征。不过,一般的定义和概念也可以推广到其他靶点。
{"title":"Insights into the use of biomarkers in clinical trials in Alzheimer's disease.","authors":"Tharick A Pascoal, Cristiano S Aguzzoli, Firoza Z Lussier, Lucía Crivelli, Claudia K Suemoto, Juan Fortea, Pedro Rosa-Neto, Eduardo R Zimmer, Pamela C L Ferreira, Bruna Bellaver","doi":"10.1016/j.ebiom.2024.105322","DOIUrl":"10.1016/j.ebiom.2024.105322","url":null,"abstract":"<p><p>Biomarkers have been instrumental in population selection and disease monitoring in clinical trials of recently FDA-approved drugs targeting amyloid-β to slow the progression of Alzheimer's disease (AD). As new therapeutic strategies and biomarker techniques emerge, the importance of biomarkers in drug development is growing exponentially. In this emerging landscape, biomarkers are expected to serve a wide range of contexts of use in clinical trials focusing on AD and related dementias. The joint FDA-NIH BEST (Biomarkers, EndpointS, and other Tools) framework provides standardised terminology to facilitate communication among stakeholders in this increasingly complex field. This review explores various applications of biomarkers relevant to AD clinical trials, using the BEST resource as a reference. For simplicity, we predominantly provide contextual characterizations of biomarkers use from the perspective of drugs targeting amyloid-β and tau proteins. However, general definitions and concepts can be extrapolated to other targets.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical phenotypes of DCM and their implications in post-surgery recovery. DCM 的临床表型及其对术后恢复的影响。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-19 DOI: 10.1016/j.ebiom.2024.105357
Fauziyya Muhammad, Zachary A Smith
{"title":"Clinical phenotypes of DCM and their implications in post-surgery recovery.","authors":"Fauziyya Muhammad, Zachary A Smith","doi":"10.1016/j.ebiom.2024.105357","DOIUrl":"10.1016/j.ebiom.2024.105357","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study. 对南部非洲出生时性别为女性的人群进行的 Imbokodo(HVTN 705/HPX2008)HIV-1 马赛克疫苗疗效试验的免疫相关性分析:一项两阶段病例对照研究。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-04 DOI: 10.1016/j.ebiom.2024.105320
Avi Kenny, Janine van Duijn, One Dintwe, Jack Heptinstall, Randy Burnham, Sheetal Sawant, Lu Zhang, Dieter Mielke, Sharon Khuzwayo, Faatima Laher Omar, Sherry Stanfield-Oakley, Taylor Keyes, Brooke Dunn, Derrick Goodman, Youyi Fong, David Benkeser, Rodger Zou, John Hural, Ollivier Hyrien, Michal Juraska, Alex Luedtke, Lars van der Laan, Elena E Giorgi, Craig Magaret, Lindsay N Carpp, Laura Pattacini, Tom van de Kerkhof, Bette Korber, Wouter Willems, Leigh H Fisher, Hanneke Schuitemaker, Edith Swann, James G Kublin, Maria G Pau, Susan Buchbinder, Frank Tomaka, Steven Nijs, Ludo Lavreys, Huub C Gelderblom, Lawrence Corey, Kathryn Mngadi, Glenda E Gray, Erica Borducchi, Jenny Hendriks, Kelly E Seaton, Susan Zolla-Pazner, Dan H Barouch, Guido Ferrari, Stephen C De Rosa, M Juliana McElrath, Erica Andersen-Nissen, Daniel J Stieh, Georgia D Tomaras, Peter B Gilbert

Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models.

Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions.

Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker.

Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen.

Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

背景:HVTN 705 Imbokodo 试验在南部非洲进行,共有 2636 名未感染 HIV 且出生时性别为女性的人参加,该试验评估了一种异源 HIV-1 疫苗方案:在第 0、3、6、12 个月接种基于镶嵌腺病毒 26 的疫苗 (Ad26.Mos4.HIV),在第 6、12 个月接种明矾佐剂 C 支系 gp140。从 7 个月到 24 个月期间,按协议接种疫苗对 HIV-1 诊断的有效率(VE)为 14.1%(95% CI:-22.0% 至 39.5%)。方法:在突破性病例对照队列(n = 52 例病例,246 例非病例)中,对第 7 个月时的体液和细胞免疫反应标记物进行评估,作为风险和保护的免疫相关因素。主要指标包括与疫苗株 gp140 结合的 IgG、与不同 Env 抗原结合的 IgG3(IgG3 Env 广度)、与不同 V1V2 抗原结合的 IgG3(IgG3 V1V2 广度)、针对疫苗株 gp140 的抗体依赖性吞噬作用、Env 特异性 CD4+ 和 CD8+ T 细胞反应以及多表位功能:没有任何免疫标记物与风险有显著的统计学相关性。IgG3 V1V2广度呈反相关趋势:每增加10倍,危险比为0.70(95% CI:0.36至1.35;P = 0.29);在包含所有主要标记物的Cox模型中,危险比为0.51(95% CI:0.21至1.24;P = 0.14)。在所有 IgG3 V1V2 广度值低于 667 加权几何平均净 MFI 时,VE 估计值为 11.8%(95% CI:-17.9% 至 34.0%);略高于此值时,VE 估计值急剧增加到 62.6%(95% CI:-17.9% 至 89.6%),在 1471 MFI(标记物分布的第 95 百分位数)时,VE 估计值进一步增加到 80.9%(95% CI:-17.9% 至 99.5%)。通过中介分析,疫苗对该标记物的影响产生了 35.7% 的 VE(95% CI:15.0% 至 51.3%):IgG3 V1V2抗体广度越大,感染HIV的可能性越低,这一趋势与其他三项HIV疫苗疗效试验中发现的V1V2抗体免疫相关性是一致的,这表明应更加重视将HIV-1包膜中的这一区域作为疫苗免疫原进行研究:国家过敏与传染病研究所和杨森疫苗与预防公司。
{"title":"Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.","authors":"Avi Kenny, Janine van Duijn, One Dintwe, Jack Heptinstall, Randy Burnham, Sheetal Sawant, Lu Zhang, Dieter Mielke, Sharon Khuzwayo, Faatima Laher Omar, Sherry Stanfield-Oakley, Taylor Keyes, Brooke Dunn, Derrick Goodman, Youyi Fong, David Benkeser, Rodger Zou, John Hural, Ollivier Hyrien, Michal Juraska, Alex Luedtke, Lars van der Laan, Elena E Giorgi, Craig Magaret, Lindsay N Carpp, Laura Pattacini, Tom van de Kerkhof, Bette Korber, Wouter Willems, Leigh H Fisher, Hanneke Schuitemaker, Edith Swann, James G Kublin, Maria G Pau, Susan Buchbinder, Frank Tomaka, Steven Nijs, Ludo Lavreys, Huub C Gelderblom, Lawrence Corey, Kathryn Mngadi, Glenda E Gray, Erica Borducchi, Jenny Hendriks, Kelly E Seaton, Susan Zolla-Pazner, Dan H Barouch, Guido Ferrari, Stephen C De Rosa, M Juliana McElrath, Erica Andersen-Nissen, Daniel J Stieh, Georgia D Tomaras, Peter B Gilbert","doi":"10.1016/j.ebiom.2024.105320","DOIUrl":"10.1016/j.ebiom.2024.105320","url":null,"abstract":"<p><strong>Background: </strong>The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models.</p><p><strong>Methods: </strong>Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions.</p><p><strong>Findings: </strong>No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker.</p><p><strong>Interpretation: </strong>The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen.</p><p><strong>Funding: </strong>National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A synergistic unsupervised-supervised learning approach for data-driven and clinically applicable patient phenotyping. 一种无监督-监督协同学习方法,用于数据驱动和临床适用的患者表型分析。
IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-09-20 DOI: 10.1016/j.ebiom.2024.105358
Mert Karabacak, Konstantinos Margetis
{"title":"A synergistic unsupervised-supervised learning approach for data-driven and clinically applicable patient phenotyping.","authors":"Mert Karabacak, Konstantinos Margetis","doi":"10.1016/j.ebiom.2024.105358","DOIUrl":"10.1016/j.ebiom.2024.105358","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
EBioMedicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1