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  1. Article: Elucidation of bioinformatic-guided high-prospect drug repositioning candidates for DMD via Swanson linking of target-focused latent knowledge from text-mined categorical metadata.

    Ulm, J Wes / Barthélémy, Florian / Nelson, Stanley F

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1226707

    Abstract: Duchenne Muscular Dystrophy (DMD)'s complex multi-system pathophysiology, coupled with the cost-prohibitive logistics of multi-year drug screening and follow-up, has hampered the pursuit of new therapeutic approaches. Here we conducted a systematic ... ...

    Abstract Duchenne Muscular Dystrophy (DMD)'s complex multi-system pathophysiology, coupled with the cost-prohibitive logistics of multi-year drug screening and follow-up, has hampered the pursuit of new therapeutic approaches. Here we conducted a systematic historical and text mining-based pilot feasibility study to explore the potential of established or previously tested drugs as prospective DMD therapeutic agents. Our approach utilized a Swanson linking-inspired method to uncover meaningful yet largely hidden deep semantic connections between pharmacologically significant DMD targets and drugs developed for unrelated diseases. Specifically, we focused on molecular target-based MeSH terms and categories as high-yield bioinformatic proxies, effectively tagging relevant literature with categorical metadata. To identify promising leads, we comprehensively assembled published reports from 2011 and sampling from subsequent years. We then determined the earliest year when distinct MeSH terms or category labels of the relevant cellular target were referenced in conjunction with the drug, as well as when the pertinent target itself was first conclusively identified as holding therapeutic value for DMD. By comparing the earliest year when the drug was identifiable as a DMD treatment candidate with that of the first actual report confirming this, we computed an Index of Delayed Discovery (IDD), which serves as a metric of Swanson-linked latent knowledge. Using these findings, we identified data from previously unlinked articles subsetted via MeSH-derived Swanson linking or from target classes within the DrugBank repository. This enabled us to identify new but untested high-prospect small-molecule candidates that are of particular interest in repurposing for DMD and warrant further investigations.
    Language English
    Publishing date 2023-08-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1226707
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Elucidation of bioinformatic-guided high-prospect drug repositioning candidates for DMD via Swanson linking of target-focused latent knowledge from text-mined categorical metadata

    J. Wes Ulm / Florian Barthélémy / Stanley F. Nelson

    Frontiers in Cell and Developmental Biology, Vol

    2023  Volume 11

    Abstract: Duchenne Muscular Dystrophy (DMD)’s complex multi-system pathophysiology, coupled with the cost-prohibitive logistics of multi-year drug screening and follow-up, has hampered the pursuit of new therapeutic approaches. Here we conducted a systematic ... ...

    Abstract Duchenne Muscular Dystrophy (DMD)’s complex multi-system pathophysiology, coupled with the cost-prohibitive logistics of multi-year drug screening and follow-up, has hampered the pursuit of new therapeutic approaches. Here we conducted a systematic historical and text mining-based pilot feasibility study to explore the potential of established or previously tested drugs as prospective DMD therapeutic agents. Our approach utilized a Swanson linking-inspired method to uncover meaningful yet largely hidden deep semantic connections between pharmacologically significant DMD targets and drugs developed for unrelated diseases. Specifically, we focused on molecular target-based MeSH terms and categories as high-yield bioinformatic proxies, effectively tagging relevant literature with categorical metadata. To identify promising leads, we comprehensively assembled published reports from 2011 and sampling from subsequent years. We then determined the earliest year when distinct MeSH terms or category labels of the relevant cellular target were referenced in conjunction with the drug, as well as when the pertinent target itself was first conclusively identified as holding therapeutic value for DMD. By comparing the earliest year when the drug was identifiable as a DMD treatment candidate with that of the first actual report confirming this, we computed an Index of Delayed Discovery (IDD), which serves as a metric of Swanson-linked latent knowledge. Using these findings, we identified data from previously unlinked articles subsetted via MeSH-derived Swanson linking or from target classes within the DrugBank repository. This enabled us to identify new but untested high-prospect small-molecule candidates that are of particular interest in repurposing for DMD and warrant further investigations.
    Keywords data mining ; drug repositioning ; Swanson linking ; MeSH ; DMD ; drug repurposing ; Biology (General) ; QH301-705.5
    Subject code 006
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: COVID-19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates.

    Ulm, J Wes / Nelson, Stanley F

    Transboundary and emerging diseases

    2020  Volume 68, Issue 2, Page(s) 313–317

    Abstract: Repurposing of existing anti-viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A ... ...

    Abstract Repurposing of existing anti-viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule anti-virals had previously demonstrated remarkable in vitro specificity for SARS-CoV or MERS-CoV, with high selectivity indices, EC
    MeSH term(s) Animals ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Clinical Trials as Topic ; Drug Repositioning ; Humans ; Pandemics ; SARS-CoV-2
    Chemical Substances Antiviral Agents
    Keywords covid19
    Language English
    Publishing date 2020-07-20
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2414822-2
    ISSN 1865-1682 ; 1865-1674
    ISSN (online) 1865-1682
    ISSN 1865-1674
    DOI 10.1111/tbed.13710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: COVID‐19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates

    Ulm, J. Wes / Nelson, Stanley F

    Transboundary and emerging diseases. 2021 Mar., v. 68, no. 2

    2021  

    Abstract: Repurposing of existing anti‐viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID‐19 pandemic. A ... ...

    Abstract Repurposing of existing anti‐viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID‐19 pandemic. A comprehensive text‐mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule anti‐virals had previously demonstrated remarkable in vitro specificity for SARS‐CoV or MERS‐CoV, with high selectivity indices, EC₅₀ and/or IC₅₀. Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations and thus largely overlooked as treatment prospects in the current COVID‐19 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing‐focused clinical trials, while detailing the most promising untested candidates with prior documented success against the aetiologic agents of SARS and/or MERS.
    Keywords COVID-19 infection ; RNA ; animals ; drugs ; public health ; statistics
    Language English
    Dates of publication 2021-03
    Size p. 313-317.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note NAL-AP-2-clean ; REVIEW
    ZDB-ID 2414822-2
    ISSN 1865-1682 ; 1865-1674
    ISSN (online) 1865-1682
    ISSN 1865-1674
    DOI 10.1111/tbed.13710
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: COVID‐19 drug repurposing

    Ulm, J. Wes / Nelson, Stanley F.

    Transboundary and Emerging Diseases ; ISSN 1865-1674 1865-1682

    Summary statistics on current clinical trials and promising untested candidates

    2020  

    Keywords General Immunology and Microbiology ; General Veterinary ; General Medicine ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    DOI 10.1111/tbed.13710
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: COVID-19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates

    Ulm, J Wes / Nelson, Stanley F

    Transbound. emerg. dis. (Internet)

    Abstract: Repurposing of existing anti-viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A ... ...

    Abstract Repurposing of existing anti-viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule anti-virals had previously demonstrated remarkable in vitro specificity for SARS-CoV or MERS-CoV, with high selectivity indices, EC50 and/or IC50 . Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations and thus largely overlooked as treatment prospects in the current COVID-19 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing-focused clinical trials, while detailing the most promising untested candidates with prior documented success against the aetiologic agents of SARS and/or MERS.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #623197
    Database COVID19

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  7. Article: Acinetobacter bacteremia following a hamster bite in a child with history of kidney transplant

    Azaran, Benjamin / Puliyanda, Dechu / Ulm, J. Wes / Equils, Ozlem

    Journal of Pediatric Infectious Diseases

    2010  Volume 05, Issue 03, Page(s) 281–284

    Abstract: Acinetobacter is an uncommon cause of serious infection in healthy individuals. Here we describe a case of Acinetobacter bacteremia in a 5-year-old kidney transplant patient following a hamster bite. Although most Acinetobacter infections occur ... ...

    Abstract Acinetobacter is an uncommon cause of serious infection in healthy individuals. Here we describe a case of Acinetobacter bacteremia in a 5-year-old kidney transplant patient following a hamster bite. Although most Acinetobacter infections occur following soil contamination of wounds, the organism is a natural constituent of oral flora in many animals, and can thus pose a risk to immunocompromised pet owners. Systemic Acinetobacter infection should therefore be considered in the differential diagnosis of febrile infections in immunocompromised children who are exposed to pets.
    Keywords hamster ; immune-compromise ; kidney transplant ; animal bite ; infection ; pet ownership and child
    Language English
    Publishing date 2010-09-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2236947-8
    ISSN 1305-7693 ; 1305-7707 ; 1871-0336
    ISSN (online) 1305-7693
    ISSN 1305-7707 ; 1871-0336
    DOI 10.3233/JPI-2010-0252
    Database Thieme publisher's database

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  8. Article ; Online: Online self-report data for duchenne muscular dystrophy confirms natural history and can be used to assess for therapeutic benefits.

    Wang, Richard T / Silverstein Fadlon, Cheri A / Ulm, J Wes / Jankovic, Ivana / Eskin, Ascia / Lu, Ake / Rangel Miller, Vanessa / Cantor, Rita M / Li, Ning / Elashoff, Robert / Martin, Anne S / Peay, Holly L / Halnon, Nancy / Nelson, Stanley F

    PLoS currents

    2014  Volume 6

    Abstract: To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from ... ...

    Abstract To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from DuchenneConnect, an online registry. Data collected were compared to prior natural history data in regard to age at diagnosis, mutation spectrum, and age at loss of ambulation. Because registrants reported differences in steroid and other medication usage, as well as age and ambulation status, we could explore these data for correlations with age at loss of ambulation. Using multivariate analysis, current steroid usage was the most significant and largest independent predictor of improved wheelchair-free survival. Thus, these online self-report data were sufficient to retrospectively observe that current steroid use by patients with DMD is associated with a delay in loss of ambulation. Comparing commonly used steroid drugs, deflazacort prolonged ambulation longer than prednisone (median 14 years and 13 years, respectively). Further, use of Vitamin D and Coenzyme Q10, insurance status, and age at diagnosis after 4 years were also significant, but smaller, independent predictors of longer wheelchair-free survival. Nine other common supplements were also individually tested but had lower study power. This study demonstrates the utility of DuchenneConnect data to observe therapeutic differences, and highlights needs for improvement in quality and quantity of patient-report data, which may allow exploration of drug/therapeutic practice combinations impractical to study in clinical trial settings. Further, with the low barrier to participation, we anticipate substantial growth in the dataset in the coming years.
    Language English
    Publishing date 2014-10-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2583641-9
    ISSN 2157-3999 ; 2157-3999
    ISSN (online) 2157-3999
    ISSN 2157-3999
    DOI 10.1371/currents.md.e1e8f2be7c949f9ffe81ec6fca1cce6a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells.

    Perron, Michel J / Stremlau, Matthew / Song, Byeongwoon / Ulm, Wes / Mulligan, Richard C / Sodroski, Joseph

    Proceedings of the National Academy of Sciences of the United States of America

    2004  Volume 101, Issue 32, Page(s) 11827–11832

    Abstract: Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including ...

    Abstract Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon after virus entry into the cell has been achieved. A similar block to HIV-1 in rhesus monkey cells is mediated by TRIM5alpha. Here we show that human TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells. Rhesus monkey TRIM5alpha, which potently blocks HIV-1 infection, exhibited only modest inhibition of N-MLV infection. B-MLV was resistant to the antiviral effects of both human and rhesus monkey TRIM5alpha; susceptibility to TRIM5alpha-mediated restriction was conferred by alteration of residue 110 of the B-MLV capsid protein to the amino acid found in the N-MLV capsid. Our results demonstrate that species-specific variation in TRIM5alpha governs its ability to block infection by diverse retroviruses.
    MeSH term(s) Amino Acid Substitution ; Animals ; Antiviral Restriction Factors ; Carrier Proteins/genetics ; Carrier Proteins/pharmacology ; Carrier Proteins/physiology ; Cell Line ; Cyclophilin A/metabolism ; Dose-Response Relationship, Drug ; HIV/drug effects ; HIV/genetics ; HIV/physiology ; Humans ; Infection Control ; Macaca mulatta ; Mice ; Moloney murine leukemia virus/drug effects ; Moloney murine leukemia virus/physiology ; Retroviridae/drug effects ; Retroviridae/physiology ; Species Specificity ; Transfection ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases
    Chemical Substances Antiviral Restriction Factors ; Carrier Proteins ; Tripartite Motif Proteins ; TRIM5 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Cyclophilin A (EC 5.2.1.-)
    Language English
    Publishing date 2004-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0403364101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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