{
  "abstract": "Introduction: Sickle cell leg ulcers (SCLUs) are disabling complications of sickle cell disease (SCD), but the circulating lipid alterations associated with recurrent ulcer status remain poorly characterized. Aim: This study aimed to characterize the plasma lipidomic landscape associated with recurrent SCLUs and identify candidate lipid signatures related to ulcer recurrence. Methodology: We performed an exploratory untargeted plasma lipidomics study in 129 participants from the multicenter REDS-III Brazil SCD cohort, including 72 individuals with recurrent SCLUs and 57 SCD controls without documented ulcer history or follow-up ulcer episodes. Plasma samples were analyzed by LC–MS in negative ion mode using data-independent acquisition. Exploratory feature selection was performed within the training set using nominal unadjusted testing, and supervised classification was evaluated as a secondary, hypothesis-generating analysis using an internal hold-out test split. Results: After quality filtering, 2,419 molecular features were retained. Training-set exploratory screening identified 181 candidate features, of which 44 were structurally annotated and carried forward for biological interpretation. Most annotated candidates were lipids, including glycerophospholipids, fatty acyls, sphingolipids, one steroid, and one glycerolipid. Recurrent SCLUs were characterized by higher lysophospholipids and oxygenated fatty acids/oxylipin-related metabolites, whereas controls showed higher FAHFAs, sphingolipids, and cholesterol sulfate. Discussion: These patterns support candidate lipid axes related to inflammatory lipid remodeling, oxidative lipid modification, and membrane-endothelial homeostasis. In secondary classification analysis, Random Forest showed the highest apparent discrimination in the internal hold-out test split (AUC=0.85), but performance estimates were interpreted cautiously because of the modest test-set size and exploratory feature selection strategy. Conclusion: Untargeted plasma lipidomics identified candidate lipid remodeling patterns associated with recurrent SCLU status in SCD. These findings should not be interpreted as validated biomarkers or causal mediators, but they nominate lipid classes and representative species for targeted quantification, covariate-aware validation, external replication, and longitudinal studies with detailed ulcer phenotyping.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade Municipal de São Caetano do Sul, São Caetano do Sul, SP, Brazil",
    "Fundação Centro de Hematologia e Hemoterapia do Estado de Minas Gerais (Hemominas), Belo Horizonte, MG, Brazil",
    "Vitalant Research Institute, United States",
    "Fundação Pró-Sangue, Immunohematology Division, São Paulo, SP, Brazil",
    "Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (Hemorio), Rio de Janeiro, RJ, Brazil",
    "Department of Medicine, Weill Cornell Medicine, United States",
    "Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil",
    "Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope), Recife, PE, Brazil",
    "University of California San Francisco, United States"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sheila De Oliveira Garcia MATEOS"
    },
    {
      "affs": [
        0
      ],
      "name": "Marcos Eduardo Souza ABREU"
    },
    {
      "affs": [
        0
      ],
      "name": "Fábio Eudes LEAL"
    },
    {
      "affs": [
        0
      ],
      "name": "Felipe Custódio Carvalho DOS SANTOS"
    },
    {
      "affs": [
        1
      ],
      "name": "André Rolim BELISÁRIO"
    },
    {
      "affs": [
        2
      ],
      "name": "Brian Scott CUSTER"
    },
    {
      "affs": [
        3
      ],
      "name": "Carla Luana DINARDO"
    },
    {
      "affs": [
        4
      ],
      "name": "Luiz De Melo Amorim FILHO"
    },
    {
      "affs": [
        5
      ],
      "name": "Scott BOWLER"
    },
    {
      "affs": [
        5
      ],
      "name": "Lishomwa NDHLOVU"
    },
    {
      "affs": [
        6
      ],
      "name": "Paula Fraiman Blatyta CASELLI"
    },
    {
      "affs": [
        7
      ],
      "name": "Dahra TELES"
    },
    {
      "affs": [
        8
      ],
      "name": "Shannon KELLY"
    },
    {
      "affs": [
        0
      ],
      "name": "Álex Aparecido Rosini SILVA"
    },
    {
      "affs": [
        0
      ],
      "name": "Ester Cerdeira SABINO"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aqfmvwkentksp.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.106691",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926004384",
  "id": "aqfmvwkentksp",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.106691",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2716|Hemoglobinopathies and Related Disorders"
    ]
  ],
  "openalex": "W7223099924",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926004384/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/aqfmvwkentksp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:35Z",
      "native_id": "94286bdcaca04f8985a2007ac39fd63b",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.106691"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Hemoglobinopathies and Related Disorders",
      "subfield": "human-genetics"
    }
  ],
  "title": "PLASMA LIPIDOMIC REMODELING ASSOCIATED WITH RECURRENT SICKLE CELL LEG ULCERS",
  "title_text": "PLASMA LIPIDOMIC REMODELING ASSOCIATED WITH RECURRENT SICKLE CELL LEG ULCERS",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:35Z",
  "url": "https://research.draconitic.com/paper/aqfmvwkentksp",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}