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  1. Book: Synthetic DNA

    Hughes, Randall A.

    methods and protocols

    (Methods in molecular biology ; 1472 ; Springer protocols)

    2017  

    Author's details edited by Randall A. Hughes
    Series title Methods in molecular biology ; 1472
    Springer protocols
    Collection
    Keywords BASIC ; COOL program ; DNA sequences ; chemically synthesized DNA ; oligonucleotide synthesis ; synthetic oligonucleotide sequences
    Language English
    Size xiii, 248 Seiten, Illustrationen, Diagramme, 25.4 cm x 17.8 cm, 0 g
    Publisher Humana Press
    Publishing place New York
    Publishing country United States
    Document type Book
    HBZ-ID HT019126285
    ISBN 978-1-4939-6341-6 ; 1-4939-6341-4 ; 9781493963430 ; 1493963430
    Database Catalogue ZB MED Medicine, Health

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  2. Book: Synthetic DNA

    Hughes, Randall A

    methods and protocols

    (Methods in molecular biology, ; 1472 ; Springer protocols)

    2017  

    Author's details edited by Randall A. Hughes
    Series title Methods in molecular biology, ; 1472
    Springer protocols
    MeSH term(s) Genes, Synthetic/genetics ; DNA/biosynthesis ; Computational Biology/methods
    Language English
    Size xiii, 248 pages :, illustrations (some color) ;, 26 cm.
    Document type Book
    Note "Published In: United States, 28 October 2016 " --Distributor's website.
    ISBN 9781493963416 ; 1493963414 ; 9781493963430 ; 1493963430
    Database Catalogue of the US National Library of Medicine (NLM)

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  3. Article ; Online: Synthetic DNA Synthesis and Assembly: Putting the Synthetic in Synthetic Biology.

    Hughes, Randall A / Ellington, Andrew D

    Cold Spring Harbor perspectives in biology

    2017  Volume 9, Issue 1

    Abstract: The chemical synthesis of DNA oligonucleotides and their assembly into synthons, genes, circuits, and even entire genomes by gene synthesis methods has become an enabling technology for modern molecular biology and enables the design, build, test, learn, ...

    Abstract The chemical synthesis of DNA oligonucleotides and their assembly into synthons, genes, circuits, and even entire genomes by gene synthesis methods has become an enabling technology for modern molecular biology and enables the design, build, test, learn, and repeat cycle underpinning innovations in synthetic biology. In this perspective, we briefly review the techniques and technologies that enable the synthesis of DNA oligonucleotides and their assembly into larger DNA constructs with a focus on recent advancements that have sought to reduce synthesis cost and increase sequence fidelity. The development of lower-cost methods to produce high-quality synthetic DNA will allow for the exploration of larger biological hypotheses by lowering the cost of use and help to close the DNA read-write cost gap.
    MeSH term(s) DNA/chemistry ; DNA Replication ; Oligonucleotide Array Sequence Analysis ; Synthetic Biology
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2017-01-03
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a023812
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Recovery of Information Stored in Modified DNA with an Evolved Polymerase.

    Shroff, Raghav / Ellefson, Jared W / Wang, Siyuan S / Boulgakov, Alexander A / Hughes, Randall A / Ellington, Andrew D

    ACS synthetic biology

    2022  Volume 11, Issue 2, Page(s) 554–561

    Abstract: DNA is increasingly being explored as an alternative medium for digital information storage, but the potential information loss from degradation and associated issues with error during reading challenge its wide-scale implementation. To address this, we ... ...

    Abstract DNA is increasingly being explored as an alternative medium for digital information storage, but the potential information loss from degradation and associated issues with error during reading challenge its wide-scale implementation. To address this, we propose an atomic-scale encoding standard for DNA, where information is encoded in degradation-resistant analogues of natural nucleic acids (xNAs). To better enable this approach, we used directed evolution to create a polymerase capable of transforming 2'-
    MeSH term(s) DNA/genetics ; Nucleic Acids/genetics ; RNA/genetics ; RNA-Directed DNA Polymerase/metabolism
    Chemical Substances Nucleic Acids ; RNA (63231-63-0) ; DNA (9007-49-2) ; RNA-Directed DNA Polymerase (EC 2.7.7.49)
    Language English
    Publishing date 2022-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2161-5063
    ISSN (online) 2161-5063
    DOI 10.1021/acssynbio.1c00575
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Survival and disease progression following solitary locoregional recurrence after head and neck radiotherapy.

    Zhao, Lucian / Day, Andrew T / Moon, Dominic / Avkshtol, Vladimir / Sumer, Baran D / Hughes, Randall / Sher, David J

    Head & neck

    2022  Volume 44, Issue 5, Page(s) 1153–1163

    Abstract: Purpose: The management of solitary locoregional recurrence (sLRR) of head and neck squamous cell carcinoma (HNSCC) previously treated with radiotherapy (RT) is challenging. We aimed to identify characteristics associated with improved outcome.: ... ...

    Abstract Purpose: The management of solitary locoregional recurrence (sLRR) of head and neck squamous cell carcinoma (HNSCC) previously treated with radiotherapy (RT) is challenging. We aimed to identify characteristics associated with improved outcome.
    Methods: We identified patients treated with non-sinus, mucosal HNSCC who initially received IMRT. We characterized overall survival (OS) and locoregional control (LRC). Multivariable analysis (MVA) on survival and patterns-of-failure were performed using Cox and Fine-Gray competing risks analysis.
    Results: We identified 90 patients with available follow-up. In total, 67 (74%) patients received curative-intent salvage, while 23 (26%) received palliative care. On MVA, significantly improved OS and LRC were associated with lower initial N-classification and use of salvage total laryngectomy (TL) or neck dissection (ND).
    Conclusion: A nontrivial number of patients with sLRR cannot undergo salvage. Among patients treated with curative intent, TL or ND were clearly associated with improved OS and LRC.
    MeSH term(s) Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/surgery ; Disease Progression ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/surgery ; Humans ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Squamous Cell Carcinoma of Head and Neck/radiotherapy
    Language English
    Publishing date 2022-02-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645165-2
    ISSN 1097-0347 ; 0148-6403 ; 1043-3074
    ISSN (online) 1097-0347
    ISSN 0148-6403 ; 1043-3074
    DOI 10.1002/hed.27012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Highly variable timing renders immunotherapy efficacy and toxicity impractical biomarkers of one another in clinical practice.

    von Itzstein, Mitchell S / Yang, Yuqiu / Wang, Yiqing / Hsiehchen, David / Sheffield, Thomas Y / Fattah, Farjana / Popat, Vinita / Ahmed, Murtaza / Homsi, Jade / Dowell, Jonathan E / Rashdan, Sawsan / Lohrey, Jay / Hammers, Hans J / Hughes, Randall S / Wang, Tao / Xie, Yang / Gerber, David E

    Frontiers in immunology

    2024  Volume 15, Page(s) 1351739

    Abstract: Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of ... ...

    Abstract Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI.
    Methods: Using two-sided Fisher exact and Cochran-Armitage tests, we determined the relative timing of initial efficacy assessment and irAE occurrence in a cohort of 155 ICI-treated patients (median age 68 years, 40% women).
    Results: Initial efficacy assessment was performed a median of 50 days [interquartile range (IQR) 39-59 days] after ICI initiation; median time to any irAE was 77 days (IQR 28-145 days) after ICI initiation. Median time to first irAE was 42 days (IQR 20-88 days). Overall, 58% of any irAE and 47% of first irAE occurred after initial efficacy assessment. For clinically significant (grade ≥2) irAE, 60% of any and 53% of first occurred after initial efficacy assessment. The likelihood of any future irAE did not differ according to response (45% for complete or partial response vs. 47% for other cases;
    Conclusions: In contrast to that seen with chemotherapy and molecularly targeted therapies, the temporal relationship between ICI efficacy and toxicity is complex and bidirectional. In practice, neither parameter can be routinely relied on as a clinical biomarker to predict the other.
    MeSH term(s) Humans ; Female ; Male ; Aged ; Immune Checkpoint Inhibitors/adverse effects ; Immune Checkpoint Inhibitors/therapeutic use ; Middle Aged ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/therapy ; Biomarkers ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Treatment Outcome ; Time Factors
    Chemical Substances Immune Checkpoint Inhibitors ; Biomarkers
    Language English
    Publishing date 2024-04-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1351739
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: EBNA1 Inhibitors Block Proliferation of Spontaneous Lymphoblastoid Cell Lines From Patients With Multiple Sclerosis and Healthy Controls.

    Monaco, Maria Chiara G / Soldan, Samantha S / Su, Chenhe / Clauze, Annaliese / Cooper, John F / Patel, Rishi J / Lu, Fang / Hughes, Randall J / Messick, Troy E / Andrada, Frances C / Ohayon, Joan / Lieberman, Paul M / Jacobson, Steven

    Neurology(R) neuroimmunology & neuroinflammation

    2023  Volume 10, Issue 5

    Abstract: Background and objectives: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that establishes lifelong latency in memory B cells and has been identified as a major risk factor of multiple sclerosis (MS). B cell depletion therapies have disease- ... ...

    Abstract Background and objectives: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that establishes lifelong latency in memory B cells and has been identified as a major risk factor of multiple sclerosis (MS). B cell depletion therapies have disease-modifying benefit in MS. However, it is unclear whether this benefit is partly attributable to the elimination of EBV
    Methods: In this study, we describe the establishment of spontaneous lymphoblastoid cell lines (SLCLs) generated ex vivo with the endogenous EBV of patients with MS and controls and treated with either an Epstein-Barr virus nuclear antigen 1 (EBNA1) inhibitor (VK-1727) or cladribine, a nucleoside analog that eliminates B cells.
    Results: We showed that a small molecule inhibitor of EBNA1, a critical regulator of the EBV life cycle, blocks the proliferation and metabolic activity of these SLCLs. In contrast to cladribine, a highly cytotoxic B cell depleting therapy currently used in MS, the EBNA1 inhibitor VK-1727 was cytostatic rather than cytotoxic and selective for EBV
    Discussion: This study shows that patient-derived SLCLs provide a useful tool for interrogating the role of EBV
    MeSH term(s) Humans ; Cell Line ; Cell Proliferation ; Cladribine/pharmacology ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/drug therapy ; Epstein-Barr Virus Infections/genetics ; Epstein-Barr Virus Nuclear Antigens ; Herpesvirus 4, Human ; Multiple Sclerosis ; Case-Control Studies
    Chemical Substances Cladribine (47M74X9YT5) ; Epstein-Barr Virus Nuclear Antigens
    Language English
    Publishing date 2023-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2767740-0
    ISSN 2332-7812 ; 2332-7812
    ISSN (online) 2332-7812
    ISSN 2332-7812
    DOI 10.1212/NXI.0000000000200149
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Efficacy and Quality-of-Life Following Involved Nodal Radiotherapy for Head and Neck Squamous Cell Carcinoma: The INRT-AIR Phase II Clinical Trial.

    Sher, David J / Moon, Dominic H / Vo, Dat / Wang, Jing / Chen, Liyuan / Dohopolski, Michael / Hughes, Randall / Sumer, Baran D / Ahn, Chul / Avkshtol, Vladimir

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2023  Volume 29, Issue 17, Page(s) 3284–3291

    Abstract: Purpose: Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy, but it is associated with significant dose to normal organs-at-risk (OAR). In this ... ...

    Abstract Purpose: Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy, but it is associated with significant dose to normal organs-at-risk (OAR). In this prospective phase II study, we investigated the efficacy and tolerability of eliminating ENI and strictly treating involved and suspicious lymph nodes (LN) with intensity-modulated radiotherapy.
    Patients and methods: Patients with newly diagnosed HNSCC of the oropharynx, larynx, and hypopharynx were eligible for enrollment. Each LN was characterized as involved or suspicious based on radiologic criteria and an in-house artificial intelligence (AI)-based classification model. Gross disease received 70 Gray (Gy) in 35 fractions and suspicious LNs were treated with 66.5 Gy, without ENI. The primary endpoint was solitary elective volume recurrence, with secondary endpoints including patterns-of-failure and patient-reported outcomes.
    Results: Sixty-seven patients were enrolled, with 18 larynx/hypopharynx and 49 oropharynx cancer. With a median follow-up of 33.4 months, the 2-year risk of solitary elective nodal recurrence was 0%. Gastrostomy tubes were placed in 14 (21%), with median removal after 2.9 months for disease-free patients; no disease-free patient is chronically dependent. Grade I/II dermatitis was seen in 90%/10%. There was no significant decline in composite MD Anderson Dysphagia Index scores after treatment, with means of 89.1 and 92.6 at 12 and 24 months, respectively.
    Conclusions: These results suggest that eliminating ENI is oncologically sound for HNSCC, with highly favorable quality-of-life outcomes. Additional prospective studies are needed to support this promising paradigm before implementation in any nontrial setting.
    MeSH term(s) Humans ; Artificial Intelligence ; Head and Neck Neoplasms/radiotherapy ; Prospective Studies ; Quality of Life ; Radiotherapy, Intensity-Modulated/adverse effects ; Squamous Cell Carcinoma of Head and Neck/radiotherapy
    Language English
    Publishing date 2023-09-06
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-0334
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Viral Immune signatures from cerebrospinal fluid extracellular vesicles and particles in HAM and other chronic neurological diseases.

    Pleet, Michelle L / Welsh, Joshua A / Stack, Emily H / Cook, Sean / Johnson, Dove-Anna / Killingsworth, Bryce / Traynor, Tim / Clauze, Annaliese / Hughes, Randall / Monaco, Maria Chiara / Ngouth, Nyater / Ohayon, Joan / Enose-Akahata, Yoshimi / Nath, Avindra / Cortese, Irene / Reich, Daniel S / Jones, Jennifer C / Jacobson, Steven

    Frontiers in immunology

    2023  Volume 14, Page(s) 1235791

    Abstract: Background and objectives: Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role ... ...

    Abstract Background and objectives: Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease.
    Methods: We analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease.
    Results: Significant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups (
    Discussion: These data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals.
    MeSH term(s) Humans ; Paraparesis, Tropical Spastic ; Central Nervous System ; Extracellular Vesicles ; Nervous System Diseases ; CD40 Antigens ; Chronic Disease
    Chemical Substances CD40 Antigens
    Language English
    Publishing date 2023-08-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1235791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Limited effects of source population identity and number on seagrass transplant performance.

    Novak, Alyssa B / Plaisted, Holly K / Hays, Cynthia G / Hughes, Randall A

    PeerJ

    2017  Volume 5, Page(s) e2972

    Abstract: Global declines in coastal foundation species highlight the importance of effective restoration. In this study, we examined the effects of source population identity and diversity (one vs. three sources per plot) on seagrass ( ...

    Abstract Global declines in coastal foundation species highlight the importance of effective restoration. In this study, we examined the effects of source population identity and diversity (one vs. three sources per plot) on seagrass (
    Language English
    Publishing date 2017-02-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.2972
    Database MEDical Literature Analysis and Retrieval System OnLINE

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