ACS Nano最新文献

{"title":"NG2 at the core: tackling MLLr B-ALL resistance.","authors":"Duohui Jing","doi":"10.1182/blood.2024026106","DOIUrl":"https://doi.org/10.1182/blood.2024026106","url":null,"abstract":"","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"144 19","pages":"1977-1978"},"PeriodicalIF":21.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Promyelocytic Leukemia: Long-Term Outcomes from the HARMONY Project.","authors":"Maria Teresa Voso, Luca Guarnera, Sören Lehmann, Konstanze Döhner, Hartmut Döhner, Uwe Platzbecker, Nigel H Russell, Richard James Dillon, Ian Thomas, Gert J Ossenkoppele, Torsten Haferlach, Marco Vignetti, Edoardo La Sala, Alfonso Piciocchi, Paola Fazi, Ángela Villaverde Ramiro, Laura Tur Giménez, Carmelo Gurnari, Lars Bullinger, Jesus M Hernandez","doi":"10.1182/blood.2024026186","DOIUrl":"https://doi.org/10.1182/blood.2024026186","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment outcomes for acute promyelocytic leukemia (APL) have improved with the widespread use of targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Our study aimed to validate these data in a large patient cohort, and to redefine prognostic factors.</p><p><strong>Patients and methods: </strong>Leveraging the HARMONY Platform, we analyzed 1438 newly-diagnosed APL patients, diagnosed between 1999 to 2022. Patient data derived from the 2 international multicenter GIMEMA-APL0406 and NCRI-AML17 trials, and 4 European registries (HOVON, AMLSG, Swedish AML Registry and SAL).</p><p><strong>Results: </strong>The study cohort included 721 males and 717 females, with a median age of 50.5 years (range 16-94 years). Of 1309 patients starting therapy, 562 received ATRA-ATO, and 747 AIDA-like chemotherapy. Early death (ED) occurred in 85 of 1438 patients (5.9%) at a median of 9 days after APL diagnosis and was independently associated with increasing age and high Sanz risk score (OR:1.06, 95% C.I: 1.04-1.08, and OR:4.65, 95% C.I.:2.55-8.51, respectively).The median follow-up was 5.5 years (IQR=3.2-7.5). ATRA-ATO regimen was associated with the best outcome, reaching 91% 7-year overall survival (vs 81% for AIDA-like, HR:2.14, 95%C.I.:1.51-3.05), 89% event-free survival (vs 71% for AIDA-like, HR:2.72 95%CI: 2.01-3.69) and 3% relapse (vs 13% for AIDA-like, HR:4.19, 95%CI:2.38-7.39, p<0.001 for all outcomes). The survival advantage of ATRA/ATO was independent of patients' age, Sanz-risk score, and treatment scenario.</p><p><strong>Conclusions: </strong>Our study confirms the superiority of ATRA-ATO over ATRA-chemotherapy in APL patients. ED represents an unmet medical need, in particular in older patients and in high-risk APL.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep RNA sequencing of human dorsal root ganglion neurons reveals somatosensory mechanisms","authors":"","doi":"10.1038/s41593-024-01795-0","DOIUrl":"https://doi.org/10.1038/s41593-024-01795-0","url":null,"abstract":"We used single-soma deep RNA sequencing to generate a high-resolution atlas of human somatosensory dorsal root ganglion neurons. This work revealed human-specific molecular features, pain-sensing neuron types, properties of sensory fibers, and potential therapeutic targets, which inform understanding of human somatosensory mechanisms and could facilitate improved success in translational research.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"18 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping out multiple sclerosis with spatial transcriptomics","authors":"Kellie Horan, Anna C. Williams","doi":"10.1038/s41593-024-01798-x","DOIUrl":"https://doi.org/10.1038/s41593-024-01798-x","url":null,"abstract":"In this issue, Alsema, Wijering, Miedema, Kotah et al. and Lerma-Martin, Badia-i-Mompel et al. demonstrate the ever-growing possibilities of spatial transcriptomics by applying it to the spatially heterogeneous disease multiple sclerosis. They validate the technique by comparison to classic pathology and reveal insights into demyelinated lesion markers, pathological cell types and lesion evolution.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"7 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis","authors":"Astrid M. Alsema, Marion H. C. Wijering, Anneke Miedema, Janssen M. Kotah, Mirjam Koster, Merel Rijnsburger, Hilmar R. J. van Weering, Helga E. de Vries, Wia Baron, Susanne M. Kooistra, Bart J. L. Eggen","doi":"10.1038/s41593-024-01765-6","DOIUrl":"https://doi.org/10.1038/s41593-024-01765-6","url":null,"abstract":"<p>Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions. Expression changes in astrocyte-specific, oligodendrocyte-specific and microglia-specific gene sets characterize the active lesion rims. Furthermore, we identify three WM lesion progression trajectories, predicting how normal-appearing WM can develop into WM active or mixed active–inactive lesions. Our data shed light on the dynamic progression of MS lesions.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"67 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions","authors":"Celia Lerma-Martin, Pau Badia-i-Mompel, Ricardo O. Ramirez Flores, Patricia Sekol, Philipp S. L. Schäfer, Christian J. Riedl, Annika Hofmann, Thomas Thäwel, Florian Wünnemann, Miguel A. Ibarra-Arellano, Tim Trobisch, Philipp Eisele, Denis Schapiro, Maximilian Haeussler, Simon Hametner, Julio Saez-Rodriguez, Lucas Schirmer","doi":"10.1038/s41593-024-01796-z","DOIUrl":"https://doi.org/10.1038/s41593-024-01796-z","url":null,"abstract":"<p>Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood. We used single-nucleus and spatial transcriptomics from subcortical MS and corresponding control tissues to map cell types and associated pathways to lesion and nonlesion areas. We identified niches such as perivascular spaces, the inflamed lesion rim or the lesion core that are associated with the glial scar and a cilia-forming astrocyte subtype. Focusing on the inflamed rim of chronic active lesions, we uncovered cell–cell communication events between myeloid, endothelial and glial cell types. Our results provide insight into the cellular composition, multicellular programs and intercellular communication in tissue niches along the conversion from a homeostatic to a dysfunctional state underlying lesion progression in MS.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"111 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial biases in polygraphs and their legal implications","authors":"Freya Whittaker, Angelica DeFalco, Steven M. Sanders, Emily R. Perkins, Keanan J. Joyner, Daniel E. Bradford","doi":"10.1038/s41562-024-02025-0","DOIUrl":"https://doi.org/10.1038/s41562-024-02025-0","url":null,"abstract":"<p>Widely used in research since the 1800s, SCR (also known as the galvanic skin response or electrodermal activity) measures changes in the electrical conductivity of the skin due to sweat gland activity. SCR has historically been considered a ‘gold standard’ for the objective biological measurement of fear and anxiety. However, myriad emotional, cognitive and physical factors can influence sweating and thereby SCR magnitude, which demonstrates it indexes general arousal. Individuals may exhibit increased SCR when stressed (for example, being deceptive or simply attempting to understand a difficult question) or for reasons unrelated to stress (for example, positive emotions such as happiness or non-emotional processes such as focusing attention⁴). As such, SCR has inherently poor specificity and discriminant validity as a measure of anxiety⁵.</p><p>Since the 1920s, SCR has been a major component of polygraph testing, which has entrenched it in the criminal legal system⁴. Currently, polygraph examinations remain controversial owing to concerns about reliability and validity. Although judges have substantial discretion over whether polygraph results can be presented to the jury⁶, about half of US states still allow polygraph evidence with stipulated agreement by both the defence and prosecution before administering the test. Furthermore, polygraph examinations are also widely accepted as evidence in criminal cases across Europe, in civil cases in China and for all cases in Colombia⁶. Polygraphs are also used at earlier stages of law enforcement to verify witness statements and to justify further interrogation of suspects⁶, and at later stages to track progress under court supervision (for example, monitoring of individuals convicted of a sexual offence).</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"126 1","pages":""},"PeriodicalIF":29.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929.","authors":"Nagla Abdel Karim, Jieling Miao, Karen L Reckamp, Carl M Gay, Lauren A Byers, Ying-Qi Zhao, Mary W Redman, Daniel R Carrizosa, Wei-Lien Wang, William J Petty, Kathan Mehta, Bryan A Faller, Edem S Agamah, Samer S Kasbari, Rajini K Malisetti, Atul Kumar, John Schallenkamp, Krishna C Alluri, Jhanelle E Gray, Karen Kelly","doi":"10.1016/j.jtho.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.10.021","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC).</p><p><strong>Methods: </strong>Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients.</p><p><strong>Results: </strong>From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001).</p><p><strong>Conclusion: </strong>Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation","authors":"Huasheng Yu, Saad S. Nagi, Dmitry Usoskin, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Hanying Yan, Suna Li Cranfill, Mayank Gautam, Yijing Su, You Lu, James Wymer, Max Glanz, Phillip Albrecht, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Andrew Marshall, Frank L. Rice, Mingyao Li, Håkan Olausson, Patrik Ernfors, Wenqin Luo","doi":"10.1038/s41593-024-01794-1","DOIUrl":"https://doi.org/10.1038/s41593-024-01794-1","url":null,"abstract":"<p>The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human (h)DRG neurons—critical information to decipher their functions—are lacking due to technical difficulties. In this study, we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect, on average, over 9,000 unique genes per neuron, and we identified 16 neuronal types. These results were corroborated and validated by spatial transcriptomics and RNAscope in situ hybridization. Cross-species analyses revealed divergence among potential pain-sensing neurons and the likely existence of human-specific neuronal types. Molecular-profile-informed microneurography recordings revealed temperature-sensing properties across human sensory afferent types. In summary, by employing single-soma deep RNA-seq and spatial transcriptomics, we generated an hDRG neuron atlas, which provides insights into human somatosensory physiology and serves as a foundation for translational work.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"1 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Guide to Implementation Science for Phase 3 Clinical Trialists","authors":"Harriette G.C. Van Spall MD ,&nbsp;Laura Desveaux PhD ,&nbsp;Tracy Finch PhD ,&nbsp;Cara C. Lewis PhD ,&nbsp;George A. Mensah MD ,&nbsp;Yves Rosenberg MD ,&nbsp;Kavita Singh PhD ,&nbsp;Francois Venter PhD ,&nbsp;Bryan J. Weiner PhD ,&nbsp;Faiez Zannad MD","doi":"10.1016/j.jacc.2024.08.068","DOIUrl":"10.1016/j.jacc.2024.08.068","url":null,"abstract":"<div><div>The delayed and modest uptake of evidence-based treatments following cardiovascular clinical trials highlights the need for greater attention to implementation early in the development and testing of treatments. However, implementation science is not well understood and is often an afterthought following phase 3 trials. In this review, we describe the goals, frameworks, and methods of implementation science, along with common multilevel barriers and facilitators of implementation. We propose that some of the approaches used for implementation well after a trial has ended can be incorporated into the design of phase 3 trials to foster early post-trial implementation. Approaches include, but are not limited to, engaging broad stakeholders including patients, clinicians, and decision-makers in trial advisory boards; using less restrictive eligibility criteria that ensure both internal validity and generalizability; having trial protocols reviewed by regulators; integrating trial execution with the health care system; evaluating and addressing barriers and facilitators to deployment of the intervention; and undertaking cost-effectiveness and cost utility analyses across jurisdictions. We provide case examples to highlight concepts and to guide end-of-trial implementation.</div></div>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"84 20","pages":"Pages 2063-2072"},"PeriodicalIF":21.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}