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Open research questions in Mast cells and histamine

139 gap statements mined from Mast cells and histamine papers in our 4.5M-paper local library, which holds 723 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Data on sleep disturbances and quality of life in pediatric cutaneous mastocytosis remain limited. The relationship between sleep parameters and dermatology-related quality of life in children with cutaneous mastocytosis is not comprehensively characterized.

    Sleep disturbances and dermatology-related quality of life in children with cutaneous mastocytosis: a patient-centered perspective · 2026 · DOI

  • The paper identifies the need for further investigation to resolve the relationship between the mast-cell proliferation and the FGFR1-rearranged myeloid/lymphoid neoplasm. The authors highlight the limitations of the original report, including the lack of assay-level detail to verify coverage of individual non-D816V KIT variants.

    Commentary: Case Report: Experience of a rare case of primary acute mast cell leukemia with FGFR1 gene rearrangement · 2026 · DOI

  • The mechanisms underlying severe pulmonary injury in patients with SARS-CoV-2 infection are not fully understood. The role of IgE-mediated pathways in acute lung injury and prolonged post-COVID immune dysregulation is not well characterized.

    High Free IgE and Mast Cell Activation in Long COVID: Mechanisms of Persistent Immune Dysregulation · 2025 · DOI

  • While mast cells (MCs) are known to infiltrate tumors, their specific immunomodulatory functions remain incompletely characterized.

    Mast cell-derived MIF Polarizes Th17 cells to drive lung adenocarcinoma progression · 2026 · DOI

  • Antigen stimulation rapidly and temporally induces cofilin dephosphorylation (activation) to depolymerize actin in rat basophilic leukemia (RBL-2H3) cells; however, the roles of SSH and LIMK in mast cell activation remain unclear.

    Slingshot Phosphatase and LIM Kinase Modulate Mast Cell Activation Beyond the Regulation of Actin Dynamics · 2026 · DOI

  • A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking.

    Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal · 2024 · DOI

  • The study does not investigate the in vivo effects of Trifluoperazine on mast cells. The study uses a limited number of cell types to assess the selectivity of Trifluoperazine.

    Trifluoperazine causes mast cell apoptosis through a secretory granule-mediated pathway · 2026 · DOI

  • The lack of advanced immunological tools in foundational literature limits the understanding of brain mast cells.

    Mast Cells in the Brain: Enduring Mysteries, Emerging Roles · 2026 · DOI

  • The function of mast cells in the CNS is not well understood, and their role in CNS physiology and pathology remains speculative. There is a need to clarify what is known and what remains speculative about brain mast cells.

    Mast Cells in the Brain: Enduring Mysteries, Emerging Roles · 2026 · DOI

  • There is a need for targeted drug delivery systems for cutaneous mastocytosis. Current treatments are mainly symptomatic and have limitations such as poor skin penetration and lack of targeted delivery.

    CUTANEOUS MASTOCYTOSIS THERAPEUTIC CHALLENGES AND OPPORTUNITIES IN ADVANCED TARGET NANOCARRIER SYSTEM · 2026 · DOI

  • The diagnostic criteria for mast cell activation syndrome are not clearly defined. The existence of histamine intolerance is controversial. There is a need for further research on the diagnostic criteria for mast cell disorders.

    Only specific combinations of findings indicate mastocytosis, hereditary α-tryptasemia, histamine intolerance, or mast cell activation syndrome · 2026 · DOI

  • Diagnosis is often delayed due to nonspecific symptoms. Treatment options are limited, particularly for advanced systemic mastocytosis. There is a lack of studies confirming the impact of maintenance therapy with a KIT inhibitor on long-term survival.

    Mastocytosis in clinical practice – current standards of care · 2026 · DOI

  • There is a lack of studies confirming the impact of maintenance therapy with a KIT inhibitor on long-term survival. Determining the success of allogeneic haematopoietic stem cell transplantation is challenging due to limited data.

    Mastocytosis in clinical practice – current standards of care · 2026 · DOI

  • Other limitations include the lack of standardized morphological classification criteria, a semi-quantitative mast cell scoring system, and limited external validity due to the ethnic and geographic constraints of the single-center cohort. Larger prospective and molecular studies are warranted to confirm these findings.

    Mast cell burden and immunophenotype of Chinese patients with cutaneous mastocytosis: a 10-year study with focus on the easily neglected pathogenic features · 2026 · DOI

  • The properties of allergens that generate an optimal effector cell response are not well understood. The impact of allergen valency and epitope spatial arrangement on FcεRI aggregate organization is unclear.

    IgE Occupancy and Antigen Valency Cooperate to Control FcεRI Aggregation Geometry and Signaling Efficiency · 2026 · DOI

  • Due to their in vivo location, MCT are likely central drivers of allergic responses in the airways and digestive tissues, but little is known about the differential sensitivity of each subset to both activation and desensitization.

    Serum factor regulation of mast cell desensitization following combined immunotherapy 2308953 · 2026 · DOI

  • However, the mechanisms through which MCs dialog and influence the intestinal tissue are not completely known.

    Mast cells-intestinal cancer cells crosstalk is mediated by TNF-alpha and sustained by the IL-33/ST2 axis · 2025 · DOI

  • The true prevalence of systemic mastocytosis is likely underreported, highlighting the importance for clinicians to be familiar with the condition, particularly in cases of osteoporosis.

    Management of Bone Health in Adult Mastocytosis · 2025 · DOI

  • One challenge is the limited data on bone mineral density in children with mastocytosis - Another challenge is the potential for occult SM in some patients, which cannot be excluded without systematic bone marrow…

    Low BMD is uncommon in pediatric mastocytosis: a DEXA- based cohort study · 2026 · DOI

  • Further study on the implications of FGFR1 rearrangement in mast-cell disease, - Investigation of non-D816V KIT variants in mast-cell disease, - Research on the role of CD117 in mast-cell…

    Commentary: Case Report: Experience of a rare case of primary acute mast cell leukemia with FGFR1 gene rearrangement · 2026 · DOI

  • Further study of the coexistence of multiple clonal hematologic diseases, - Investigation of the molecular mechanisms underlying the development of these diseases, - Development of more precise diagnostic criteria for plasma-cell…

    Case Report: Coexistence of advanced systemic mastocytosis, chronic myelomonocytic Leukemia, and t(11;14)-positive plasma-cell neoplasm: a rare triple-clonal hematologic case · 2026 · DOI

  • The study does not provide information on long-term effects - The study does not provide information on potential side effects - The study only examined a limited number of cell lines and primary…

    Triterpenoid Exposure and HO-1 Blockade Sensitize Neoplastic Mast Cells Against Midostaurin and Avapritinib · 2026 · DOI

  • Investigation of the effects of bardoxolone methyl and omaveloxolone on other types of cancer cells - Examination of the potential of bardoxolone methyl and omaveloxolone as therapeutic agents in combination with other…

    Triterpenoid Exposure and HO-1 Blockade Sensitize Neoplastic Mast Cells Against Midostaurin and Avapritinib · 2026 · DOI

  • Further investigation of the role of mast cells in the tumor microenvironment. Development of new therapies targeting CTSG and other key regulators of immunotherapy resistance.

    CTSG-expressing mast cells confer resistance to immunotherapy in colorectal cancer · 2026 · DOI

  • Further studies on the properties of allergens that generate an optimal effector cell response, - Investigation of the role of epitope number and spacing in mast cell and basophil activation, - Research on the correlation between FcεRI aggregation on the cell surface and signaling…

    IgE Occupancy and Antigen Valency Cooperate to Control FcεRI Aggregation Geometry and Signaling Efficiency · 2026 · DOI

Most-cited papers in Mast cells and histamine

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Open questions raised by papers listed on this page include: (1) Data on sleep disturbances and quality of life in pediatric cutaneous mastocytosis remain limited (“Sleep disturbances and dermatology-related quality of life in children with…”, 2026); (2) The authors highlight the limitations of the original report, including the lack of assay-level detail to verify coverage of individual non-D816V KIT variants (“Commentary: Case Report: Experience of a rare case of primary acute mast cell…”, 2026); (3) While mast cells (MCs) are known to infiltrate tumors, their specific immunomodulatory functions remain incompletely characterized (“Mast cell-derived MIF Polarizes Th17 cells to drive lung adenocarcinoma…”, 2026); (4) Antigen stimulation rapidly and temporally induces cofilin dephosphorylation (activation) to depolymerize actin in rat basophilic leukemia (RBL-2H3) cells; however, the roles of SSH and LIMK in mast cell activation remain unclear (“Slingshot Phosphatase and LIM Kinase Modulate Mast Cell Activation Beyond the…”, 2026); (5) The lack of advanced immunological tools in foundational literature limits the understanding of brain mast cells (“Mast Cells in the Brain: Enduring Mysteries, Emerging Roles”, 2026). 139 gap statements have been mined from Mast cells and histamine papers in our 4.5M-paper local library, which holds 723 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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