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  1. Article ; Online: Lamotrigine-Associated Hemophagocytic Lymphohistiocytosis.

    Koning, Marvyn T / Janmaat, Cynthia J / Peltenburg, Henny G / Tiren-Verbeet, Nicolette L

    Journal of clinical psychopharmacology

    2021  Volume 41, Issue 4, Page(s) 498–499

    MeSH term(s) Adult ; Antipsychotic Agents/adverse effects ; Humans ; Lamotrigine/adverse effects ; Lymphohistiocytosis, Hemophagocytic/chemically induced ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/therapy ; Male
    Chemical Substances Antipsychotic Agents ; Lamotrigine (U3H27498KS)
    Language English
    Publishing date 2021-06-01
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 604631-9
    ISSN 1533-712X ; 0271-0749
    ISSN (online) 1533-712X
    ISSN 0271-0749
    DOI 10.1097/JCP.0000000000001431
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL.

    Eken, Janneke A / Koning, Marvyn T / Kupcova, Kristyna / Sepúlveda Yáñez, Julieta H / de Groen, Ruben A L / Quinten, Edwin / Janssen, Jurriaan / van Bergen, Cornelis A M / Vermaat, Joost S P / Cleven, Arjen / Navarrete, Marcelo A / Ylstra, Bauke / de Jong, Daphne / Havranek, Ondrej / Jumaa, Hassan / Veelken, Hendrik

    The Journal of experimental medicine

    2024  Volume 221, Issue 5

    Abstract: Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR ... ...

    Abstract Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking. Autonomous BCR signaling was associated with IgM isotype, dependent on somatic BCR mutations and individual HCDR3 sequences, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological oncogenic driver mechanism in DLBCL originating from individual BCR sequences and adds a new dimension to currently proposed genetics- and transcriptomics-based DLBCL classifications.
    MeSH term(s) Animals ; Mice ; B-Lymphocytes ; Lymphoma, Large B-Cell, Diffuse/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; Receptors, Antigen, B-Cell ; Immunoglobulin M
    Chemical Substances Receptors, Antigen, B-Cell ; Immunoglobulin M
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20230941
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma.

    Vletter, Esther M / Koning, Marvyn T / Scherer, Hans Ulrich / Veelken, Hendrik / Toes, Rene E M

    Frontiers in immunology

    2020  Volume 11, Page(s) 241

    Abstract: N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is ... ...

    Abstract N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is only just being appreciated. Most of the N-linked glycans harbored by immunoglobulin variable domain are of the complex biantennary type and are found as a result of the presence of N-linked glycosylation that most often have been introduced by somatic hypermutation. Furthermore, these glycans are ubiquitously present on autoantibodies observed in some autoimmune diseases as well as certain B-cell lymphomas. For example, variable domain glycans are abundantly found by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) as well as by the B-cell receptors of follicular lymphoma (FL). In FL, variable domain glycans are postulated to convey a selective advantage through interaction with lectins and/or microbiota, whereas the contribution of variable domain glycans on autoantibodies is not known. To aid the understanding how these seemingly comparable phenomena contribute to a variety of deranged B-responses in such different diseases this study summarizes the characteristics of ACPA and other auto-antibodies with FL and healthy donor immunoglobulins, to identify the commonalities and differences between variable domain glycans in autoimmune and malignant settings. Our finding indicate intriguing differences in variable domain glycan distribution, frequency and glycan composition in different conditions. These findings underline that variable domain glycosylation is a heterogeneous process that may lead to a number of pathogenic outcomes. Based on the current body of knowledge, we postulate three disease groups with distinct variable domain glycosylation patterns, which might correspond with distinct underlying pathogenic processes.
    MeSH term(s) Anti-Citrullinated Protein Antibodies/immunology ; Arthritis, Rheumatoid/immunology ; Autoimmune Diseases/immunology ; Glycosylation ; Humans ; Immunoglobulin Variable Region/chemistry ; Immunoglobulin Variable Region/metabolism ; Lectins/chemistry ; Lupus Erythematosus, Systemic/immunology ; Lymphoma/immunology ; Myasthenia Gravis/immunology ; Polysaccharides/analysis ; Polysaccharides/chemistry ; Protein Domains
    Chemical Substances Anti-Citrullinated Protein Antibodies ; Immunoglobulin Variable Region ; Lectins ; Polysaccharides
    Language English
    Publishing date 2020-02-18
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00241
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Acquisition of a glycosylated B-cell receptor drives follicular lymphoma toward a dark zone phenotype.

    van Bergen, Cornelis A M / Kloet, Susan L / Quinten, Edwin / Sepúlveda Yáñez, Julieta H / Menafra, Roberta / Griffioen, Marieke / Jansen, Patty M / Koning, Marvyn T / Knijnenburg, Jeroen / Navarrete, Marcelo A / Kiełbasa, Szymon M / Veelken, Hendrik

    Blood advances

    2023  Volume 7, Issue 19, Page(s) 5812–5816

    Language English
    Publishing date 2023-07-24
    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.2023010725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Autonomous B-cell receptor signaling and genetic aberrations in chronic lymphocytic leukemia-phenotype monoclonal B lymphocytosis in siblings of patients with chronic lymphocytic leukemia.

    Quinten, Edwin / Sepúlveda-Yáñez, Julieta H / Koning, Marvyn T / Eken, Janneke A / Pfeifer, Dietmar / Nteleah, Valeri / De Groen, Ruben A L / Saravia, Diego Alvarez / Knijnenburg, Jeroen / Stuivenberg-Bleijswijk, Hedwig E / Pantic, Milena / Agathangelidis, Andreas / Keppler-Hafkemeyer, Andrea / Van Bergen, Cornelis A M / Uribe-Paredes, Roberto / Stamatopoulos, Kostas / Vermaat, Joost S P / Zirlik, Katja / Navarrete, Marcelo A /
    Jumaa, Hassan / Veelken, Hendrik

    Haematologica

    2024  Volume 109, Issue 3, Page(s) 824–834

    Abstract: Clonal expansion of CD5-expressing B cells, commonly designated as monoclonal B lymphocytosis (MBL), is a precursor condition for chronic lymphocytic leukemia (CLL). The mechanisms driving subclinical MBL B-cell expansion and progression to CLL, ... ...

    Abstract Clonal expansion of CD5-expressing B cells, commonly designated as monoclonal B lymphocytosis (MBL), is a precursor condition for chronic lymphocytic leukemia (CLL). The mechanisms driving subclinical MBL B-cell expansion and progression to CLL, occurring in approximately 1% of affected individuals, are unknown. An autonomously signaling B-cell receptor (BCR) is essential for the pathogenesis of CLL. The objectives of this study were functional characterization of the BCR of MBL in siblings of CLL patients and a comparison of genetic variants in MBL-CLL sibling pairs. Screening of peripheral blood by flow cytometry detected 0.2-480 clonal CLL-phenotype cells per microliter (median: 37/μL) in 34 of 191 (17.8%) siblings of CLL patients. Clonal BCR isolated from highly purified CLL-phenotype cells induced robust calcium mobilization in BCR-deficient murine pre-B cells in the absence of external antigen and without experimental crosslinking. This autonomous BCR signal was less intense than the signal originating from the CLL BCR of their CLL siblings. According to genotyping by single nucleotide polymorphism array, whole exome, and targeted panel sequencing, CLL risk alleles were found with high and similar prevalence in CLL patients and MBL siblings, respectively. Likewise, the prevalence of recurrent CLL-associated genetic variants was similar between CLL and matched MBL samples. However, copy number variations and small variants were frequently subclonal in MBL cells, suggesting their acquisition during subclinical clonal expansion. These findings support a stepwise model of CLL pathogenesis, in which autonomous BCR signaling leads to a non-malignant (oligo)clonal expansion of CD5+ B cells, followed by malignant progression to CLL after acquisition of pathogenic genetic variants.
    MeSH term(s) Humans ; Animals ; Mice ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Siblings ; DNA Copy Number Variations ; Lymphocytosis/genetics ; Leukemia ; Receptors, Antigen, B-Cell/genetics ; Phenotype
    Chemical Substances Receptors, Antigen, B-Cell
    Language English
    Publishing date 2024-03-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2022.282542
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A case of fulminant Epstein-Barr virus encephalitis in an immune-competent adult.

    Koning, Marvyn T / Brik, Tessa / Hagenbeek, Rogier / van den Wijngaard, Ido

    Journal of neurovirology

    2019  Volume 25, Issue 3, Page(s) 422–425

    Abstract: A 21-year-old female presented with headache, nausea and vomiting, dysarthria, difficulty finding words, vertigo, episodical diplopia and an abnormal gait since 2 days. Additionally, we found marked ataxia and disturbed liver chemistry whilst her ... ...

    Abstract A 21-year-old female presented with headache, nausea and vomiting, dysarthria, difficulty finding words, vertigo, episodical diplopia and an abnormal gait since 2 days. Additionally, we found marked ataxia and disturbed liver chemistry whilst her infection parameters were low. Her head CT scan was unremarkable, but her MRI scan showed leptomeningeal enhancement along the cerebellar folia. A lumbar punction revealed mononuclear leucocytosis and increased protein in her cerebrospinal fluid. She was admitted on a working diagnosis of herpes simplex encephalitis. Shortly after admission, she had a generalised seizure. She was tested for a wide range of viruses, bacteria and auto-immune antibodies and treated empirically with aciclovir, ceftriaxone, doxycycline and intravenous immunoglobulins. All tests continued to come back negative until the fifth day of admission, when repeat Epstein-Barr virus (EBV) serology showed evidence of an acute EBV infection, even though negative tests were acquired at admission. EBV encephalitis is a rare complication of EBV infection that is usually restricted to children and immune-compromised individuals. This is only the fifth case describing EBV encephalitis in an immune-competent adult, presenting with unique clinical features including a lack of fever and leptomeningeal enhancement on MRI investigation. Most interestingly, she tested negative for EBV until a few days after admission, underlining the need for repeated investigations in suspected virological encepahlitis. Even though our patient did not receive the often recommended glucocorticosteroids, she made a good neurological recovery.
    MeSH term(s) Encephalitis, Viral/virology ; Epstein-Barr Virus Infections/complications ; Female ; Humans ; Young Adult
    Language English
    Publishing date 2019-01-22
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 1283265-0
    ISSN 1538-2443 ; 1355-0284
    ISSN (online) 1538-2443
    ISSN 1355-0284
    DOI 10.1007/s13365-018-0718-1
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  7. Article ; Online: Tandem Substitutions in Somatic Hypermutation.

    Sepúlveda-Yáñez, Julieta H / Alvarez Saravia, Diego / Pilzecker, Bas / van Schouwenburg, Pauline A / van den Burg, Mirjam / Veelken, Hendrik / Navarrete, Marcelo A / Jacobs, Heinz / Koning, Marvyn T

    Frontiers in immunology

    2022  Volume 12, Page(s) 807015

    Abstract: Upon antigen recognition, activation-induced cytosine deaminase initiates affinity maturation of the B-cell receptor by somatic hypermutation (SHM) through error-prone DNA repair pathways. SHM typically creates single nucleotide substitutions, but tandem ...

    Abstract Upon antigen recognition, activation-induced cytosine deaminase initiates affinity maturation of the B-cell receptor by somatic hypermutation (SHM) through error-prone DNA repair pathways. SHM typically creates single nucleotide substitutions, but tandem substitutions may also occur. We investigated incidence and sequence context of tandem substitutions by massive parallel sequencing of V(D)J repertoires in healthy human donors. Mutation patterns were congruent with SHM-derived single nucleotide mutations, delineating initiation of the tandem substitution by AID. Tandem substitutions comprised 5,7% of AID-induced mutations. The majority of tandem substitutions represents single nucleotide juxtalocations of directly adjacent sequences. These observations were confirmed in an independent cohort of healthy donors. We propose a model where tandem substitutions are predominantly generated by translesion synthesis across an apyramidinic site that is typically created by UNG. During replication, apyrimidinic sites transiently adapt an extruded configuration, causing skipping of the extruded base. Consequent strand decontraction leads to the juxtalocation, after which exonucleases repair the apyramidinic site and any directly adjacent mismatched base pairs. The mismatch repair pathway appears to account for the remainder of tandem substitutions. Tandem substitutions may enhance affinity maturation and expedite the adaptive immune response by overcoming amino acid codon degeneracies or mutating two adjacent amino acid residues simultaneously.
    MeSH term(s) Alleles ; Codon ; DNA Mismatch Repair ; High-Throughput Nucleotide Sequencing ; Humans ; Immunoglobulin Heavy Chains/genetics ; Mutation ; Receptors, Antigen, B-Cell/genetics ; Somatic Hypermutation, Immunoglobulin ; Tandem Repeat Sequences ; V(D)J Recombination
    Chemical Substances Codon ; Immunoglobulin Heavy Chains ; Receptors, Antigen, B-Cell
    Language English
    Publishing date 2022-01-07
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.807015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Two Independent Hematological malignancies in a B-Cell Deficient Good Syndrome Patient.

    Koning, Marvyn T / van Rossum, André P / Tiren-Verbeet, Nicolette L / Burgers, Jacobus A / Karim, A Faiz

    Rheumatology (Oxford, England)

    2020  Volume 60, Issue 4, Page(s) e126–e128

    MeSH term(s) Agammaglobulinemia/complications ; Agammaglobulinemia/pathology ; Aged ; Autoimmune Diseases/complications ; Autoimmune Diseases/pathology ; B-Lymphocytes/pathology ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/pathology ; Humans ; Male
    Language English
    Publishing date 2020-11-10
    Publishing country England
    Document type Case Reports ; Letter
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keaa666
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  9. Article ; Online: Incidence and clinical relevance of cage subsidence in anterior cervical discectomy and fusion: a systematic review.

    Noordhoek, Iris / Koning, Marvyn T / Jacobs, Wilco C H / Vleggeert-Lankamp, Carmen L A

    Acta neurochirurgica

    2018  Volume 160, Issue 4, Page(s) 873–880

    Abstract: Background: The placement of intervertebral cages in anterior cervical discectomy (ACDF) supposedly maintains foraminal height. The most commonly reported cage-related complication is subsidence, although it is unknown whether a correlation between ... ...

    Abstract Background: The placement of intervertebral cages in anterior cervical discectomy (ACDF) supposedly maintains foraminal height. The most commonly reported cage-related complication is subsidence, although it is unknown whether a correlation between subsidence and clinical outcome exists.
    Aim: To assess the incidence and relevance of subsidence.
    Methods: Literature searches were performed in PubMed, MEDLINE, Embase, Web of Science, COCHRANE, and CENTRAL. The inclusion criteria were as follows: ≥ 20 patients, ADCF with cage, subsidence assessed, and primary data. Risk of bias was assessed using adjusted Cochrane checklists.
    Results: Seventy-one studies, comprising 4784 patients, were included. Subsidence was generally defined as ≥ 3-mm loss of height comparing postoperative intervertebral heights with heights at last follow-up. Mean incidence of subsidence was 21% (range 0-83%). Of all patients, 46% of patients received polyether-ether-ketone (PEEK) cages, 31% received titanium cages, 18% received cage-screw-combinations, and 5% received polymethyl-methacrylate (PMMA) cages. Patients treated with cage-screw-combinations had significantly less subsidence than patients treated with PEEK, titanium, or PMMA cages (15.1% vs. 23.5% vs. 24.9% vs. 30.2%; p < 0.001). Thirteen studies assessed clinical outcome in relation to subsidence; the majority did not find a significant correlation. Only four studies correlated subsidence to cage size and/or height; no correlation was established.
    Conclusions: Subsidence in ACDF with cages occurs in 21% of patients. The risk for subsidence seems lower using PEEK or titanium cages or adding screws. Whether subsidence affects clinical outcome is not satisfactorily evaluated in the available literature. Future studies on this correlation are warranted in order to establish the additional value of the interposition of a cage in ACDF.
    MeSH term(s) Bone Screws/adverse effects ; Cervical Vertebrae/surgery ; Diskectomy/adverse effects ; Diskectomy/methods ; Humans ; Incidence ; Ketones/adverse effects ; Polymethyl Methacrylate/adverse effects ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Spinal Fusion/adverse effects ; Spinal Fusion/methods ; Titanium/adverse effects
    Chemical Substances Ketones ; Polymethyl Methacrylate (9011-14-7) ; Titanium (D1JT611TNE)
    Language English
    Publishing date 2018-02-21
    Publishing country Austria
    Document type Journal Article ; Systematic Review
    ZDB-ID 80010-7
    ISSN 0942-0940 ; 0001-6268
    ISSN (online) 0942-0940
    ISSN 0001-6268
    DOI 10.1007/s00701-018-3490-3
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  10. Article ; Online: Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.

    Koning, Marvyn T / Trollmann, Ignis J M / van Bergen, Cornelis A M / Alvarez Saravia, Diego / Navarrete, Marcelo A / Kiełbasa, Szymon M / Veelken, Hendrik

    Frontiers in immunology

    2019  Volume 10, Page(s) 1543

    Abstract: IgE-mediated allergic disease represents an increasing health problem. Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire. IgM, IgG, IgA, and IgE transcripts from ... ...

    Abstract IgE-mediated allergic disease represents an increasing health problem. Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire. IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR. Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform. Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs. IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes. IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA. Many IgE sequences contained N-linked glycosylation motifs. IgE sequences had no clonal relationship with the other isotypes. The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA. The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens. These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE. This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
    MeSH term(s) Adult ; Antibody Affinity/genetics ; B-Lymphocytes/immunology ; Female ; Glycosylation ; Humans ; Immunoglobulin A/genetics ; Immunoglobulin A/immunology ; Immunoglobulin E/genetics ; Immunoglobulin E/immunology ; Immunoglobulin G/genetics ; Immunoglobulin G/immunology ; Immunoglobulin M/genetics ; Immunoglobulin M/immunology ; Male ; Middle Aged ; Mutation
    Chemical Substances Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2019-07-03
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2019.01543
    Database MEDical Literature Analysis and Retrieval System OnLINE

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