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  1. Article ; Online: The modeling of multicancer early detection (MCED) tests' residual risk and the challenges of MCED evaluation and implementation.

    Kessler, Larry / Le Beau, Michelle M / Smith, Robert A / Walter, Fiona M / Wender, Richard

    Cancer

    2023  Volume 129, Issue 13, Page(s) 1966–1968

    MeSH term(s) Humans ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Early Diagnosis ; Early Detection of Cancer
    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.34745
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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.146: Show issues Location:
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  2. Article: A propos d'une observation de M.J. Le Beau de cingulectomie.

    BARUK, H / LE BEAU, J / BROSSEAU, A

    Annales medico-psychologiques

    1953  Volume 111, Issue 2 2, Page(s) 227–232

    Title translation Discussion on J. Beau's article on cingulectomy.
    MeSH term(s) Humans ; Psychosurgery
    Language Undetermined
    Publishing date 1953-07
    Publishing country France
    Document type Journal Article
    ZDB-ID 210836-7
    ISSN 1769-6631 ; 0003-4487
    ISSN (online) 1769-6631
    ISSN 0003-4487
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    In stock of ZB MED Cologne/Königswinter

    Ui I Zs.20: Show issues Location:
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  3. Article ; Online: EGR1 Haploinsufficiency Confers a Fitness Advantage to Hematopoietic Stem Cells Following Chemotherapy.

    Stoddart, Angela / Fernald, Anthony A / Davis, Elizabeth M / McNerney, Megan E / Le Beau, Michelle M

    Experimental hematology

    2022  Volume 115, Page(s) 54–67

    Abstract: Therapy-related myeloid neoplasms (t-MNs) share many clinical and molecular characteristics with AML de novo in the elderly. One common factor is that they arise in the setting of chronic inflammation, likely because of advanced age or chemotherapy- ... ...

    Abstract Therapy-related myeloid neoplasms (t-MNs) share many clinical and molecular characteristics with AML de novo in the elderly. One common factor is that they arise in the setting of chronic inflammation, likely because of advanced age or chemotherapy-induced senescence. Here, we examined the effect of haploinsufficient loss of the del(5q) tumor suppressor gene, EGR1, commonly deleted in high-risk MNs. In mice, under the exogenous stress of either serial transplant or successive doses of the alkylating agent N-ethyl-nitrosourea (ENU), Egr1-haploinsufficient hematopoietic stem cells (HSCs) exhibit a clonal advantage. Complete loss of EGR1 function is incompatible with transformation; mutations of EGR1 are rare and are not observed in the remaining allele in del(5q) patients, and complete knockout of Egr1 in mice leads to HSC exhaustion. Using chromatin immunoprecipitation sequencing (ChIP-seq), we identified EGR1 binding sites in human CD34
    MeSH term(s) Humans ; Mice ; Animals ; Aged ; Haploinsufficiency ; Hematopoietic Stem Cells/metabolism ; Antigens, CD34/metabolism ; Ethylnitrosourea/metabolism ; Inflammation/metabolism ; Early Growth Response Protein 1/genetics ; Early Growth Response Protein 1/metabolism
    Chemical Substances Antigens, CD34 ; Ethylnitrosourea (P8M1T4190R) ; EGR1 protein, human ; Early Growth Response Protein 1 ; Egr1 protein, mouse
    Language English
    Publishing date 2022-08-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2022.08.003
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 922: Show issues Location:
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  4. Article ; Online: Modeling Temperature-Dependent Electron Thermal Diffuse Scattering via Machine-Learned Interatomic Potentials and Path-Integral Molecular Dynamics.

    Kim, Dennis S / Xu, Michael / LeBeau, James M

    Physical review letters

    2024  Volume 132, Issue 8, Page(s) 86301

    Abstract: Electron thermal diffuse scattering is shown to be sensitive to subtle changes in atomic vibrations and shows promise in assessing lattice dynamics at nanometer resolution. Here, we demonstrate that machine-learned interatomic potentials (MLIPs) and path- ...

    Abstract Electron thermal diffuse scattering is shown to be sensitive to subtle changes in atomic vibrations and shows promise in assessing lattice dynamics at nanometer resolution. Here, we demonstrate that machine-learned interatomic potentials (MLIPs) and path-integral molecular dynamics can accurately capture the potential energy landscape and lattice dynamics needed to describe electron thermal diffuse scattering. Using SrTiO_{3} as a test bed at cryogenic and room temperatures, we compare electron thermal diffuse scattering simulations using different approximations to incorporate thermal motion. Only when the simulations are based on quantum mechanically accurate MLIPs in combination with path-integral molecular dynamics that include nuclear quantum effects is there excellent agreement with experiments.
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.132.086301
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    In stock of ZB MED Bonn / Germany

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  5. Article ; Online: Progress in Cancer Research, Prevention, and Care.

    Schilsky, Richard L / Nass, Sharyl / Le Beau, Michelle M / Benz, Edward J

    The New England journal of medicine

    2020  Volume 383, Issue 10, Page(s) 897–900

    MeSH term(s) Biomedical Research ; Health Policy ; History, 20th Century ; History, 21st Century ; Humans ; Medical Oncology/history ; Medical Oncology/legislation & jurisprudence ; Medical Oncology/trends ; Neoplasms/diagnosis ; Neoplasms/prevention & control ; Neoplasms/therapy
    Language English
    Publishing date 2020-09-02
    Publishing country United States
    Document type Historical Article ; Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMp2007839
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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.34: Show issues Location:
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  6. Article ; Online: The Harmful Consequences of Increased Fitness in Hematopoietic Stem Cells.

    McNerney, Megan E / Le Beau, Michelle M

    Cell stem cell

    2018  Volume 23, Issue 5, Page(s) 634–635

    Abstract: Clonal hematopoiesis of indeterminate potential (CHIP) describes clonal selection of a hematopoietic stem cell with a somatic mutation that confers increased fitness, influenced by a selective environment such as aging, inflammation, or therapeutic ... ...

    Abstract Clonal hematopoiesis of indeterminate potential (CHIP) describes clonal selection of a hematopoietic stem cell with a somatic mutation that confers increased fitness, influenced by a selective environment such as aging, inflammation, or therapeutic exposure. In this issue of Cell Stem Cell, Hsu et al. (2018) explore the role of cytotoxic therapy in disease-relevant CHIP.
    MeSH term(s) Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Inflammation ; Mutation ; Protein Phosphatase 2C
    Chemical Substances PPM1D protein, human (EC 3.1.3.16) ; Protein Phosphatase 2C (EC 3.1.3.16)
    Language English
    Publishing date 2018-11-02
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2018.10.003
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    Zs.A 6589: Show issues Location:
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  7. Article ; Online: Characterization of Quantum Emitters and Extended Defects in ZnSe via Multislice Electron Ptychography.

    Chen, Xi / Gilgenbach, Colin / LeBeau, James M

    Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada

    2023  Volume 29, Issue Supplement_1, Page(s) 342–343

    Language English
    Publishing date 2023-08-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1385710-1
    ISSN 1435-8115 ; 1431-9276
    ISSN (online) 1435-8115
    ISSN 1431-9276
    DOI 10.1093/micmic/ozad067.159
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  8. Article ; Online: Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in

    Carr, Tiffany / McGregor, Stephanie / Dias, Sheila / Verykokakis, Mihalis / Le Beau, Michelle M / Xue, Hai-Hui / Sigvardsson, Mikael / Bartom, Elizabeth T / Kee, Barbara L

    Frontiers in immunology

    2022  Volume 13, Page(s) 845488

    Abstract: T lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in ... ...

    Abstract T lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in a subset of T-ALL cases but elevated LEF1 expression and activating mutations have also been identified in this disease. Here we show, in a murine model of T-ALL arising due to
    MeSH term(s) Animals ; Lymphoid Enhancer-Binding Factor 1/metabolism ; Mice ; Oncogenes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; TCF Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Lef1 protein, mouse ; Lymphoid Enhancer-Binding Factor 1 ; TCF Transcription Factors ; Transcription Factors
    Language English
    Publishing date 2022-03-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.845488
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  9. Article ; Online: Therapy-related myeloid neoplasms in 109 patients after radiation monotherapy.

    Patel, Anand Ashwin / Rojek, Alexandra E / Drazer, Michael W / Weiner, Howard / Godley, Lucy A / Le Beau, Michelle M / Larson, Richard A

    Blood advances

    2021  Volume 5, Issue 20, Page(s) 4140–4148

    Abstract: Therapy-related myeloid neoplasms (t-MNs) are a late complication of cytotoxic therapy and are defined as a distinct entity by the World Health Organization. Although the link between chemotherapy exposure and risk of subsequent t-MN is well described, ... ...

    Abstract Therapy-related myeloid neoplasms (t-MNs) are a late complication of cytotoxic therapy and are defined as a distinct entity by the World Health Organization. Although the link between chemotherapy exposure and risk of subsequent t-MN is well described, the association between radiation monotherapy (RT) and t-MN risk is less definitive. We analyzed 109 consecutive patients who developed t-MNs after RT and describe latencies, cytogenetic profile, mutation analyses, and clinical outcomes. The most common cytogenetic abnormality was a clonal abnormality in chromosome 5 and/or 7, which was present in 45% of patients. The median latency from RT to t-MN diagnosis was 6.5 years, with the shortest latency in patients with balanced translocations. One-year overall survival (OS) was 52% and 5-year OS was 22% for the entire cohort. Patients with chromosome 5 and/or 7 abnormalities experienced worse 1-year OS (37%) and 5-year OS (2%) compared with other cytogenetic groups (P < .0001). Sixteen patients underwent net-generation sequencing; ASXL1 and TET2 were the most commonly mutated genes (n = 4). In addition, 17 patients underwent germline variant testing and 3 carried pathogenic or likely pathogenic germline variants. In conclusion, patients with t-MN after RT monotherapy have increased frequencies of chromosome 5 and/or 7 abnormalities, which are associated with poor OS. In addition, pathogenic germline variants may be common in patients with t-MN after RT monotherapy.
    MeSH term(s) Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Cytogenetics ; Humans ; Neoplasms, Second Primary/genetics ; Translocation, Genetic
    Language English
    Publishing date 2021-09-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2021004964
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  10. Article: Unlocking Precision Gene Therapy: Harnessing AAV Tropism with Nanobody Swapping at Capsid Hotspots.

    Hoffmann, Mareike D / Gallant, Joseph P / LeBeau, Aaron M / Schmidt, Daniel

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Adeno-associated virus has been remarkably successful in the clinic, but its broad tropism is a practical limitation of precision gene therapy. A promising path to engineer AAV tropism is the addition of binding domains to the AAV capsid that recognize ... ...

    Abstract Adeno-associated virus has been remarkably successful in the clinic, but its broad tropism is a practical limitation of precision gene therapy. A promising path to engineer AAV tropism is the addition of binding domains to the AAV capsid that recognize cell surface markers present on a targeted cell type. We have recently identified two previously unexplored capsid regions near the 2-fold valley and 5-fold pore of the AAV capsid that are amenable to insertion of larger protein domains including nanobodies. Here, we demonstrate that these hotspots facilitate AAV tropism switching through simple nanobody replacement without extensive optimization in both VP1 and VP2. We demonstrate highly specific targeting of human cancer cells expressing fibroblast activating protein (FAP). Our data suggest that engineering VP2 is the preferred path for maintaining both virus production yield and infectivity. Our study shows that nanobody swapping at multiple capsid location is a viable strategy for nanobody-directed cell-specific AAV targeting.
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.27.587049
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