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  1. Article ; Online: Next-generation microfluidic point-of-care diagnostics.

    Ng, Alphonsus H C / Wheeler, Aaron R

    Clinical chemistry

    2015  Volume 61, Issue 10, Page(s) 1233–1234

    MeSH term(s) Clinical Chemistry Tests/instrumentation ; Equipment Design ; Humans ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques/instrumentation ; Point-of-Care Systems ; Smartphone/instrumentation
    Language English
    Publishing date 2015-05-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 80102-1
    ISSN 1530-8561 ; 0009-9147
    ISSN (online) 1530-8561
    ISSN 0009-9147
    DOI 10.1373/clinchem.2015.240226
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.171: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Large libraries of single-chain trimer peptide-MHCs enable antigen-specific CD8+ T cell discovery and analysis.

    Chour, William / Choi, Jongchan / Xie, Jingyi / Chaffee, Mary E / Schmitt, Thomas M / Finton, Kathryn / DeLucia, Diana C / Xu, Alexander M / Su, Yapeng / Chen, Daniel G / Zhang, Rongyu / Yuan, Dan / Hong, Sunga / Ng, Alphonsus H C / Butler, Jonah Z / Edmark, Rick A / Jones, Lesley C / Murray, Kim M / Peng, Songming /
    Li, Guideng / Strong, Roland K / Lee, John K / Goldman, Jason D / Greenberg, Philip D / Heath, James R

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 528

    Abstract: The discovery and characterization of antigen-specific ... ...

    Abstract The discovery and characterization of antigen-specific CD8
    MeSH term(s) Humans ; CD8-Positive T-Lymphocytes ; COVID-19 ; SARS-CoV-2/genetics ; Antigens ; Epitopes ; Peptides/genetics
    Chemical Substances Antigens ; Epitopes ; Peptides
    Language English
    Publishing date 2023-05-16
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-04899-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Organ-specific immunity: A tissue analysis framework for investigating local immune responses to SARS-CoV-2.

    Ng, Alphonsus H C / Hu, Huiqian / Wang, Kai / Scherler, Kelsey / Warren, Sarah E / Zollinger, Daniel R / McKay-Fleisch, Jill / Sorg, Kristina / Beechem, Joseph M / Ragaglia, Emily / Lacy, J Matthew / Smith, Kelly D / Marshall, Desiree A / Bundesmann, Michael M / López de Castilla, Diego / Corwin, David / Yarid, Nicole / Knudsen, Beatrice S / Lu, Yue /
    Goldman, Jason D / Heath, James R

    Cell reports

    2023  Volume 42, Issue 10, Page(s) 113212

    Abstract: Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, ...

    Abstract Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; Post-Acute COVID-19 Syndrome ; Inflammation ; Immunity
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113212
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1

    Yue Lu / Alphonsus H. C. Ng / Frances E. Chow / Richard G. Everson / Beth A. Helmink / Michael T. Tetzlaff / Rohit Thakur / Jennifer A. Wargo / Timothy F. Cloughesy / Robert M. Prins / James R. Heath

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: The response to neoadjuvant immune checkpoint blockade (ICB) in patients with recurrent gliolastoma multiforme (GBM) has been challenging to interpret. Here the authors develop a tumor analysis framework that reveals molecular similarities between GBM ... ...

    Abstract The response to neoadjuvant immune checkpoint blockade (ICB) in patients with recurrent gliolastoma multiforme (GBM) has been challenging to interpret. Here the authors develop a tumor analysis framework that reveals molecular similarities between GBM and melanoma and unique patterns of immunosuppression in GBM indicating potential co-targets for neoadjuvant ICB.
    Keywords Science ; Q
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells

    Jiajun Du / Yapeng Su / Chenxi Qian / Dan Yuan / Kun Miao / Dongkwan Lee / Alphonsus H. C. Ng / Reto S. Wijker / Antoni Ribas / Raphael D. Levine / James R. Heath / Lu Wei

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 16

    Abstract: Single-cell metabolomics can offer deep insights into the metabolic reprogramming that accompanies disease states. Here, the authors use Raman spectro-microscopy for non-invasive metabolite analysis and identification of druggable metabolic ... ...

    Abstract Single-cell metabolomics can offer deep insights into the metabolic reprogramming that accompanies disease states. Here, the authors use Raman spectro-microscopy for non-invasive metabolite analysis and identification of druggable metabolic susceptibilities in single live melanoma cells.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells

    Jiajun Du / Yapeng Su / Chenxi Qian / Dan Yuan / Kun Miao / Dongkwan Lee / Alphonsus H. C. Ng / Reto S. Wijker / Antoni Ribas / Raphael D. Levine / James R. Heath / Lu Wei

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 16

    Abstract: Single-cell metabolomics can offer deep insights into the metabolic reprogramming that accompanies disease states. Here, the authors use Raman spectro-microscopy for non-invasive metabolite analysis and identification of druggable metabolic ... ...

    Abstract Single-cell metabolomics can offer deep insights into the metabolic reprogramming that accompanies disease states. Here, the authors use Raman spectro-microscopy for non-invasive metabolite analysis and identification of druggable metabolic susceptibilities in single live melanoma cells.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1.

    Lu, Yue / Ng, Alphonsus H C / Chow, Frances E / Everson, Richard G / Helmink, Beth A / Tetzlaff, Michael T / Thakur, Rohit / Wargo, Jennifer A / Cloughesy, Timothy F / Prins, Robert M / Heath, James R

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 4031

    Abstract: The response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues ... ...

    Abstract The response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues collected from patients with recurrent glioblastoma and high-risk melanoma, both treated with neoadjuvant checkpoint blockade. We develop a framework that uses multiplex spatial protein profiling, machine learning-based image analysis, and data-driven computational models to investigate the pathophysiological and molecular factors within the tumor microenvironment that influence treatment response. Using melanoma to guide the interpretation of glioblastoma analyses, we interrogate the protein expression in microscopic compartments of tumors, and determine the correlates of cytotoxic CD8+ T cells, tumor growth, treatment response, and immune cell-cell interaction. This work reveals similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade.
    MeSH term(s) Adult ; Aged ; Antineoplastic Agents, Immunological/therapeutic use ; Biomarkers, Tumor/analysis ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; CD8-Positive T-Lymphocytes/immunology ; CTLA-4 Antigen/antagonists & inhibitors ; Female ; Glioblastoma/drug therapy ; Glioblastoma/pathology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Ipilimumab/therapeutic use ; Male ; Melanoma/drug therapy ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; Nivolumab/therapeutic use ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Treatment Outcome ; Tumor Microenvironment/immunology
    Chemical Substances Antineoplastic Agents, Immunological ; Biomarkers, Tumor ; CTLA-4 Antigen ; CTLA4 protein, human ; Immune Checkpoint Inhibitors ; Ipilimumab ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Nivolumab (31YO63LBSN)
    Language English
    Publishing date 2021-06-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-24293-4
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  8. Article ; Online: Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance.

    Su, Yapeng / Bintz, Marcus / Yang, Yezi / Robert, Lidia / Ng, Alphonsus H C / Liu, Victoria / Ribas, Antoni / Heath, James R / Wei, Wei

    PLoS computational biology

    2019  Volume 15, Issue 6, Page(s) e1007034

    Abstract: Phenotypic plasticity is associated with non-genetic drug tolerance in several cancers. Such plasticity can arise from chromatin remodeling, transcriptomic reprogramming, and/or protein signaling rewiring, and is characterized as a cell state transition ... ...

    Abstract Phenotypic plasticity is associated with non-genetic drug tolerance in several cancers. Such plasticity can arise from chromatin remodeling, transcriptomic reprogramming, and/or protein signaling rewiring, and is characterized as a cell state transition in response to molecular or physical perturbations. This, in turn, can confound interpretations of drug responses and resistance development. Using BRAF-mutant melanoma cell lines as the prototype, we report on a joint theoretical and experimental investigation of the cell-state transition dynamics associated with BRAF inhibitor drug tolerance. Thermodynamically motivated surprisal analysis of transcriptome data was used to treat the cell population as an entropy maximizing system under the influence of time-dependent constraints. This permits the extraction of an epigenetic potential landscape for drug-induced phenotypic evolution. Single-cell flow cytometry data of the same system were modeled with a modified Fokker-Planck-type kinetic model. The two approaches yield a consistent picture that accounts for the phenotypic heterogeneity observed over the course of drug tolerance development. The results reveal that, in certain plastic cancers, the population heterogeneity and evolution of cell phenotypes may be understood by accounting for the competing interactions of the epigenetic potential landscape and state-dependent cell proliferation. Accounting for such competition permits accurate, experimentally verifiable predictions that can potentially guide the design of effective treatment strategies.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Proliferation/genetics ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Evolution, Molecular ; Humans ; Melanoma/genetics ; Melanoma/physiopathology ; Models, Biological ; Phenotype ; Transcriptome/drug effects ; Transcriptome/genetics
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2019-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1007034
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  9. Article ; Online: Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells.

    Du, Jiajun / Su, Yapeng / Qian, Chenxi / Yuan, Dan / Miao, Kun / Lee, Dongkwan / Ng, Alphonsus H C / Wijker, Reto S / Ribas, Antoni / Levine, Raphael D / Heath, James R / Wei, Lu

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 4830

    Abstract: Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic ... ...

    Abstract Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.
    MeSH term(s) Apoptosis ; Cell Line, Tumor ; Fatty Acids/metabolism ; Humans ; Lipid Droplets ; Lipid Metabolism ; Lipidomics ; Lipids ; Melanoma/metabolism ; Metabolomics/methods ; Microscopy/methods ; Oleic Acid ; Spectrum Analysis, Raman/methods ; Stearoyl-CoA Desaturase/metabolism ; Transcriptome
    Chemical Substances Fatty Acids ; Lipids ; Oleic Acid (2UMI9U37CP) ; SCD1 protein, human (EC 1.14.19.1) ; Stearoyl-CoA Desaturase (EC 1.14.19.1)
    Language English
    Publishing date 2020-09-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-18376-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: An inkjet printed, roll-coated digital microfluidic device for inexpensive, miniaturized diagnostic assays.

    Dixon, Christopher / Ng, Alphonsus H C / Fobel, Ryan / Miltenburg, Mark B / Wheeler, Aaron R

    Lab on a chip

    2016  Volume 16, Issue 23, Page(s) 4560–4568

    Abstract: The diagnosis of infectious disease is typically carried out at the point-of-care (POC) using the lateral flow assay (LFA). While cost-effective and portable, LFAs often lack the clinical sensitivity and specificity required for accurate diagnoses. In ... ...

    Abstract The diagnosis of infectious disease is typically carried out at the point-of-care (POC) using the lateral flow assay (LFA). While cost-effective and portable, LFAs often lack the clinical sensitivity and specificity required for accurate diagnoses. In response to this challenge, we introduce a new digital microfluidic (DMF) platform fabricated using a custom inkjet printing and roll-coating process that is scalable to mass production. The performance of the new devices is on par with that of traditional DMF devices fabricated in a cleanroom, with a materials cost for the new devices of only US $0.63 per device. To evaluate the usefulness of the new platform, we performed a 13-step rubella virus (RV) IgG immunoassay on the inkjet printed, roll-coated devices, which yielded a limit of detection of 0.02 IU mL
    Language English
    Publishing date 2016-11-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2056646-3
    ISSN 1473-0189 ; 1473-0197
    ISSN (online) 1473-0189
    ISSN 1473-0197
    DOI 10.1039/c6lc01064d
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