The Journal of Physical Chemistry 最新文献

{"title":"Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations.","authors":"Sebastian Moguilner, Sandra Baez, Hernan Hernandez, Joaquín Migeot, Agustina Legaz, Raul Gonzalez-Gomez, Francesca R Farina, Pavel Prado, Jhosmary Cuadros, Enzo Tagliazucchi, Florencia Altschuler, Marcelo Adrián Maito, María E Godoy, Josephine Cruzat, Pedro A Valdes-Sosa, Francisco Lopera, John Fredy Ochoa-Gómez, Alfredis Gonzalez Hernandez, Jasmin Bonilla-Santos, Rodrigo A Gonzalez-Montealegre, Renato Anghinah, Luís E d'Almeida Manfrinati, Sol Fittipaldi, Vicente Medel, Daniela Olivares, Görsev G Yener, Javier Escudero, Claudio Babiloni, Robert Whelan, Bahar Güntekin, Harun Yırıkoğulları, Hernando Santamaria-Garcia, Alberto Fernández Lucas, David Huepe, Gaetano Di Caterina, Marcio Soto-Añari, Agustina Birba, Agustin Sainz-Ballesteros, Carlos Coronel-Oliveros, Amanuel Yigezu, Eduar Herrera, Daniel Abasolo, Kerry Kilborn, Nicolás Rubido, Ruaridh A Clark, Ruben Herzog, Deniz Yerlikaya, Kun Hu, Mario A Parra, Pablo Reyes, Adolfo M García, Diana L Matallana, José Alberto Avila-Funes, Andrea Slachevsky, María I Behrens, Nilton Custodio, Juan F Cardona, Pablo Barttfeld, Ignacio L Brusco, Martín A Bruno, Ana L Sosa Ortiz, Stefanie D Pina-Escudero, Leonel T Takada, Elisa Resende, Katherine L Possin, Maira Okada de Oliveira, Alejandro Lopez-Valdes, Brian Lawlor, Ian H Robertson, Kenneth S Kosik, Claudia Duran-Aniotz, Victor Valcour, Jennifer S Yokoyama, Bruce Miller, Agustin Ibanez","doi":"10.1038/s41591-024-03294-y","DOIUrl":"https://doi.org/10.1038/s41591-024-03294-y","url":null,"abstract":"","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":" ","pages":""},"PeriodicalIF":58.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Not all AI health tools with regulatory authorization are clinically validated","authors":"Sammy Chouffani El Fassi, Adonis Abdullah, Ying Fang, Sarabesh Natarajan, Awab Bin Masroor, Naya Kayali, Simran Prakash, Gail E. Henderson","doi":"10.1038/s41591-024-03293-z","DOIUrl":"10.1038/s41591-024-03293-z","url":null,"abstract":"","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"30 11","pages":"3381-3381"},"PeriodicalIF":58.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03293-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial","authors":"Rebecca A. Shatsky, Meghna S. Trivedi, Christina Yau, Rita Nanda, Hope S. Rugo, Marie Davidian, Butch Tsiatis, Anne M. Wallace, A. Jo Chien, Erica Stringer-Reasor, Judy C. Boughey, Coral Omene, Mariya Rozenblit, Kevin Kalinsky, Anthony D. Elias, Christos Vaklavas, Heather Beckwith, Nicole Williams, Mili Arora, Chaitali Nangia, Evanthia T. Roussos Torres, Brittani Thomas, Kathy S. Albain, Amy S. Clark, Carla Falkson, Dawn L. Hershman, Claudine Isaacs, Alexandra Thomas, Jennifer Tseng, Amy Sanford, Kay Yeung, Sarah Boles, Yunni Yi Chen, Laura Huppert, Nusrat Jahan, Catherine Parker, Karthik Giridhar, Frederick M. Howard, M. Michele Blackwood, Tara Sanft, Wen Li, Natsuko Onishi, Adam L. Asare, Philip Beineke, Peter Norwood, Lamorna Brown-Swigart, Gillian L. Hirst, Jeffrey B. Matthews, Brian Moore, W. Fraser Symmans, Elissa Price, Diane Heditsian, Barbara LeStage, Jane Perlmutter, Paula Pohlmann, Angela DeMichele, Douglas Yee, Laura J. van ’t Veer, Nola M. Hylton, Laura J. Esserman","doi":"10.1038/s41591-024-03267-1","DOIUrl":"https://doi.org/10.1038/s41591-024-03267-1","url":null,"abstract":"<p>Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody–drug conjugate, datopotamab–deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin–cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin–cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.</p><p>ClinicalTrials.gov registration: NCT01042379.</p>","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"3 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial","authors":"Katia Khoury, Jane L. Meisel, Christina Yau, Hope S. Rugo, Rita Nanda, Marie Davidian, Butch Tsiatis, A. Jo Chien, Anne M. Wallace, Mili Arora, Mariya Rozenblit, Dawn L. Hershman, Alexandra Zimmer, Amy S. Clark, Heather Beckwith, Anthony D. Elias, Erica Stringer-Reasor, Judy C. Boughey, Chaitali Nangia, Christos Vaklavas, Coral Omene, Kathy S. Albain, Kevin M. Kalinsky, Claudine Isaacs, Jennifer Tseng, Evanthia T. Roussos Torres, Brittani Thomas, Alexandra Thomas, Amy Sanford, Ronald Balassanian, Cheryl Ewing, Kay Yeung, Candice Sauder, Tara Sanft, Lajos Pusztai, Meghna S. Trivedi, Ashton Outhaythip, Wen Li, Natsuko Onishi, Adam L. Asare, Philip Beineke, Peter Norwood, Lamorna Brown-Swigart, Gillian L. Hirst, Jeffrey B. Matthews, Brian Moore, W. Fraser Symmans, Elissa Price, Carolyn Beedle, Jane Perlmutter, Paula Pohlmann, Rebecca A. Shatsky, Angela DeMichele, Douglas Yee, Laura J. van ‘t Veer, Nola M. Hylton, Laura J. Esserman","doi":"10.1038/s41591-024-03266-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03266-2","url":null,"abstract":"<p>Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab–deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin–cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2⁻Immune⁻DNA repair deficiency⁻ subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2⁻Immune⁻DNA repair deficiency⁻ signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379.</p>","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing ASO therapies from development to implementation","authors":"Rebecca Schuele,&nbsp;Matthis Synofzik,&nbsp;Holm Graessner,&nbsp;Annemieke Aartsma-Rus","doi":"10.1038/s41591-024-03217-x","DOIUrl":"10.1038/s41591-024-03217-x","url":null,"abstract":"A novel application of antisense oligonucleotide (ASO) technology, developed to treat a single patient, adds to the growing number of ‘personalized’ therapies for rare diseases; but pathways to implementation and access are urgently needed.","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"30 10","pages":"2725-2726"},"PeriodicalIF":58.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial","authors":"Nadia Harbeck, Eva Ciruelos, Guy Jerusalem, Volkmar Müller, Naoki Niikura, Giuseppe Viale, Rupert Bartsch, Christian Kurzeder, Michaela J. Higgins, Roisin M. Connolly, Sally Baron-Hay, María Gión, Valentina Guarneri, Giampaolo Bianchini, Hans Wildiers, Santiago Escrivá-de-Romaní, Manoj Prahladan, Helen Bridge, Nataliya Kuptsova-Clarkson, Nana Scotto, Sunil Verma, Nancy U. Lin","doi":"10.1038/s41591-024-03261-7","DOIUrl":"https://doi.org/10.1038/s41591-024-03261-7","url":null,"abstract":"<p>Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2–positive (HER2⁺) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2⁺ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (<i>n</i> = 263) and no BMs (<i>n</i> = 241)) treated with one or more prior anti-HER2–based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9–67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9–65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5–68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2⁺ mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761.</p>","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial","authors":"Boris Julg, Victoria E. K. Walker-Sperling, Kshitij Wagh, Malika Aid, Kathryn E. Stephenson, Rebecca Zash, Jinyan Liu, Joseph P. Nkolola, Amelia Hoyt, Mike Castro, Leonid Serebryannyy, Katherine Yanosick, Tessa Speidel, Erica N. Borducchi, Tetyana Murzda, Lori Maxfield, Roberto Arduino, Adrian B. McDermott, Lucio Gama, Elena E. Giorgi, Richard A. Koup, Michael S. Seaman, Charlotte-Paige Rolle, Edwin DeJesus, Wenjun Li, Bette Korber, Dan H. Barouch","doi":"10.1038/s41591-024-03247-5","DOIUrl":"https://doi.org/10.1038/s41591-024-03247-5","url":null,"abstract":"<p>Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies^1,2,3,4. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound^5,6,7. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4⁺ T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38–44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and PGDM1400, whereas long-term virologic control in five individuals correlated with reduced immune activation, T cell exhaustion and proinflammatory signaling following bNAb therapy. Our data show the potential of a triple bNAb cocktail to suppress HIV-1 in the absence of ART. ClinicalTrials.gov registration: NCT03721510.</p>","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"149 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initiating second-trimester medical abortions at home","authors":"","doi":"10.1038/d41591-024-00069-3","DOIUrl":"https://doi.org/10.1038/d41591-024-00069-3","url":null,"abstract":"In people undergoing medical abortion after 12 weeks of pregnancy, those who took the first dose of misoprostol at home were less likely to require overnight hospitalization.","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"07 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal exposure to famine affects lifelong health","authors":"","doi":"10.1038/d41591-024-00068-4","DOIUrl":"https://doi.org/10.1038/d41591-024-00068-4","url":null,"abstract":"Analysis of data related to the Ukraine famine of 1932–1933 shows that in utero exposure to famine increases the risk of adult type 2 diabetes by more than twofold.","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"102 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Guyton, J. R. & Boden, W. E.; Schreiber, S. et al.","authors":"W. H. Wilson Tang,&nbsp;Joseph A. DiDonato,&nbsp;Hooman Allayee,&nbsp;Stanley L. Hazen","doi":"10.1038/s41591-024-03222-0","DOIUrl":"10.1038/s41591-024-03222-0","url":null,"abstract":"","PeriodicalId":58,"journal":{"name":"The Journal of Physical Chemistry ","volume":"30 9","pages":"2448-2449"},"PeriodicalIF":58.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}