{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:51:13Z","timestamp":1791899473770,"version":"4.3.4"},"reference-count":93,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Triple\u2010negative breast cancer (TNBC) has an aggressive nature, a specific set of molecular characteristics, distinct patterns of metastasis, and a lack of targeted treatment. Many types of cancer have Notch pathway dysregulation, which leads to tumor initiation, spreading, and increased therapeutic resistance. In breast cancer, the overexpression of NOTCH1 and NOTCH4 in tumors suggests their role as oncogenes. The Notch signaling pathway is highly active in breast cancer tissues and thus can be considered a possible target. This project is aimed at developing a protein\u2010based vaccine that targets NOTCH1 and NOTCH4 antigens associated with TNBC, using bioinformatic and in silico tools for increased precision, immunogenic potency, and faster therapeutic intervention development. The designed vaccine demonstrated coverage for 99.27%, indicating its potential effectiveness across diverse populations. Epitope\u2010MHC docking simulations demonstrated strong binding affinities, with docking scores ranging from \u2212135.96 to \u2212285.59, suggesting effective immune system activation. The immune modeling analysis suggested that the vaccine can induce a consistent and accurate immune response alongside an increase in immunoglobulins, B cells, memory T cells, and cytotoxic T cells. Physicochemical evaluations confirmed the vaccine\u2032s stability, with an instability index of 39.70, indicating its robustness under physiological conditions. Furthermore, structural modeling of the vaccine indicated high stability and reliability under physiological conditions. Molecular docking demonstrated strong binding affinities with MHC I, MHC II, TLR4, and TLR7 molecules, with the highest docking score of \u2212317.05 for TLR7 and the most favorable\n                    <jats:italic>\u0394<\/jats:italic>\n                    G of \u221215.5\u2009kcal\/mol for TLR4. Molecular dynamics simulations (repeated three times) showed that the vaccine and its complexes with MHC I, MHC II, and TLR4 are stable, with the docked complexes exhibiting dynamic interaction. These findings collectively highlight a targeted approach to combating TNBC, demonstrating the vaccine\u2032s potential as a therapeutic candidate.\n                  <\/jats:p>","DOI":"10.1155\/bmri\/9723304","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:03:01Z","timestamp":1768798981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Designing a Multi\u2010Epitope Vaccine Against NOTCH1 and NOTCH4: A Computational Approach for Triple\u2010Negative Breast Cancer"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5374-7991","authenticated-orcid":false,"given":"Pooriya","family":"Teimoori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9175-8093","authenticated-orcid":false,"given":"Kosar","family":"Khatir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-0561","authenticated-orcid":false,"given":"Mohammadreza","family":"Heidari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2022.08.010"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/BCTT.S348060"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.05.005"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/0118715303261691231107113548"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.692173"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102204"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.07.012"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-023-07107-7"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.154735"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13132175"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-018-0248-x"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-4"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.09.032"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.2174\/1875035400801010022"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4315"},{"key":"e_1_2_13_17_2","first-page":"175","article-title":"A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences","volume":"6","author":"Sonnhammer E. 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