EBioMedicine最新文献

{"title":"Menopausal timing and senescent-immune coupling in age-related lobular involution of the human breast: a longitudinal cohort study.","authors":"Jaida C Lue, Melody Stallings-Mann, Tanya Hoskin, Bryan M McCauley, Robert A Vierkant, Laura Pacheco-Spann, Jessica L Fischer, Denice L Gehling, Lisa R Seymour, Darren J Baker, Amy C Degnim, Stacey J Winham, Mark E Sherman, Derek C Radisky","doi":"10.1016/j.ebiom.2026.106463","DOIUrl":"10.1016/j.ebiom.2026.106463","url":null,"abstract":"<p><strong>Background: </strong>Incomplete postmenopausal breast involution leaves persistent epithelial-rich lobules and elevated breast density in about 40% of women and is associated with higher breast cancer risk, but why remodelling stalls remains unclear.</p><p><strong>Methods: </strong>We studied a longitudinal cohort of 81 women with paired benign breast biopsies (baseline age 45-55 years; follow-up 2-10 years), all with baseline NanoString transcriptomics and two-timepoint digital morphometry, and with multiplex immunofluorescence in spatial-imaging subsets (baseline n = 14-16 depending on panel; follow-up n = 14). A separate postmenopausal endpoint cohort (12 women: eight noninvoluted, four completely involuted), profiled by genome-wide expression array and multiplex immunofluorescence, defined the persistent-lobule phenotype.</p><p><strong>Findings: </strong>Noninvoluted postmenopausal tissue retained a proliferation-competent, tumour-associated epithelial state and showed immune accumulation at lobular boundaries with reduced access to p16⁺ (senescence-associated) epithelial foci. The same SASP and innate immune programmes that predicted slower involution across the menopausal transition predicted faster involution after menopause. Follow-up boundary CD45→p16 engagement was directionally consistent with this reversal in Pre→Post and Post→Post women. Spatial imaging resolved this reversal into a perimenopausal stall architecture and a postmenopausal clearance-associated architecture marked by direct CD16⁺ innate-effector engagement of p16⁺ epithelium; macrophage targeting provided convergent support (two-sided exact permutation interaction p = 0.0077).</p><p><strong>Interpretation: </strong>Menopausal timing conditions whether senescent-immune programmes couple to productive clearance or to spatially uncoupled surveillance and persistent risk-associated tissue. Biomarker interpretation should therefore be anchored to menopausal timing.</p><p><strong>Funding: </strong>Casey DeSantis Cancer Fund and US National Cancer Institute.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106463"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound localisation microscopy predicts neoadjuvant chemotherapy response in patients with breast cancer.","authors":"Céline Porte, Matthias Kohlen, Thomas Lisson, Stefanie Dencks, Saskia von Stillfried, Zuzanna A Magnuska, Brigitte S Winkler, Anne Rix, Patrick Koczera, Peter Boor, Steven R Talbot, Georg Schmitz, Elmar Stickeler, Fabian Kiessling","doi":"10.1016/j.ebiom.2026.106442","DOIUrl":"10.1016/j.ebiom.2026.106442","url":null,"abstract":"<p><strong>Background: </strong>Patients with breast cancer undergoing neoadjuvant chemotherapy mostly show insufficient therapy response and would highly benefit from an early prediction of pathological complete response (pCR). As vessels play a major role in drug delivery, ultrasound localisation microscopy (ULM) holds great promise as predictive tool by visualising vascular networks in high detail, at a resolution beyond the acoustic diffraction limit.</p><p><strong>Methods: </strong>In this prospective pilot study (NCT05445050), we examined patients with breast cancer undergoing neoadjuvant chemotherapy using a ULM algorithm designed for conventional clinical ultrasound systems. To generate a vascular fingerprint, we performed the most detailed radiomics ULM analysis to date, based on longitudinal data from 20 patients. Features were used to classify therapy response using logistic regression and the performance of ULM was compared to clinically available imaging methods.</p><p><strong>Findings: </strong>Compared to patients with non-pCR (n = 12), patients with pCR (n = 8) showed a more pronounced vascular network before therapy. Furthermore, their vessel coverage strongly changed following the first chemotherapy administration (26.97 [20.23-36.24] % vs. 6.00 [2.73-10.49] %), representing a promising biomarker for therapy prediction (p < 0.01, effect size: 2.21). ULM features allowed to correctly predict up to 85% (AUC: 0.85) of patient responses and already 75% (AUC: 0.73) before the start of therapy, thus outperforming tumour size measurements (accuracy up to 60%, AUC up to 0.53), B-mode images (accuracy up to 75%, AUC up to 0.76), maximum intensity projections of contrast-enhanced ultrasound (accuracy up to 75%; AUC up to 0.79), and histological CD31 staining (accuracy: 75%; AUC: 0.83).</p><p><strong>Interpretation: </strong>Our findings emphasise the importance of vascular assessment in predicting pCR in patients with breast cancer and promote the translation of ULM as powerful clinical tool with the potential to optimise neoadjuvant treatment schedules.</p><p><strong>Funding: </strong>This work was supported by the German Research Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106442"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG signatures of psychotropic medications: opportunities and challenges for translational psychiatry.","authors":"Louisa Krile, Khadijeh Raeisi, Andrea B Protzner","doi":"10.1016/j.ebiom.2026.106431","DOIUrl":"10.1016/j.ebiom.2026.106431","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106431"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain pro-resolving-to-pro-inflammatory lipids and cPLA₂ activation associations with late-life cognitive trajectories.","authors":"Anat Yaskolka Meir, Xinhui Wang, Boyang Li, Robert S Wilson, David A Bennett, Stan G Louie, Hussein N Yassine, Zoe Arvanitakis","doi":"10.1016/j.ebiom.2026.106421","DOIUrl":"10.1016/j.ebiom.2026.106421","url":null,"abstract":"<p><strong>Background: </strong>Lipidome alterations are linked to neurodegenerative disorders, but the association between calcium-dependent phospholipase A2 (cPLA₂)-related lipid ratios, which reflect pro-resolving and pro-inflammatory lipid biology, and age-related cognitive decline remains unclear.</p><p><strong>Methods: </strong>In postmortem dorsolateral prefrontal cortex samples from participants in the Religious Orders Study and the Rush Memory and Aging Project (lipidomics n = 191; transcriptomics n = 411), we quantified three ratios of cPLA₂-released fatty acid precursors (primary exposures), three indices of arachidonic acid (AA) metabolism, and two AA transcriptomic activation scores (secondary exposures). Global cognition (primary outcome) and five cognitive domains were derived from annual neuropsychological testing.</p><p><strong>Findings: </strong>In mixed-effect change point models (death-age, sex, education, and apolipoprotein E ε4 (APOEε4)-adjusted), higher brain eicosapentaenoic acid/AA was associated with better global cognition proximate-to-death (β = 0.254, 95% CI [0.064-0.455]) and a slower rate of cognitive decline (β = 0.045, 95%CI [0.005-0.081]). Separate models including an APOEε4 × cPLA₂ lipid-ratio interaction showed that the association between lipoxin A4/AA and global cognition proximate-to-death differed significantly between APOEε4 carriers and non-carriers (β = 0.396, 95% CI [0.015-0.776]). A secondary analysis, repeating these models with three indices of AA metabolism-to-AA ratios and examining the association between the six cPLA₂ lipid ratios and five cognition domains, yielded similar results. Higher AA transcriptomic activation scores, indicating greater cPLA₂ activation, were associated with lower global cognition at death (β = -0.148, 95% CI [-0.266 to -0.028]) and with multiple cognitive domains.</p><p><strong>Interpretation: </strong>Modulation of brain lipid ratios warrants further investigation as a potential target related to cognitive decline.</p><p><strong>Funding: </strong>National Institute of Health, the Council for Higher Education-Zuckerman support program for outstanding postdoctoral female researchers.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106421"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of plasmacytoid dendritic cells in humoural and CD8⁺ T-cell memory responses following BNT162b2 mRNA vaccination: a preclinical mouse study.","authors":"Chiara Pizzichetti, Irene Latino, Tommaso Virgilio, Arianna Capucetti, Kamil Chahine, Luciano Cascione, Simone G Moro, Giorgia Bilato, Melanie Brügger, Nedim Kozarac, Alain Pulfer, Louis Renner, Roshan S Thakur, Charaf Benarafa, Daniel F Legler, Santiago F González","doi":"10.1016/j.ebiom.2026.106432","DOIUrl":"10.1016/j.ebiom.2026.106432","url":null,"abstract":"<p><strong>Background: </strong>The Pfizer-BioNTech coronavirus vaccine (BNT162b2) was among the first nanoparticle-based vaccines approved by the World Health Organisation (WHO) and demonstrated 95% efficacy against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Despite its success, the precise immune mechanism behind its effectiveness remains poorly understood. This study investigated the early immune responses occurring in the draining lymph node (dLN) following vaccination.</p><p><strong>Methods: </strong>A well-established murine vaccination model was used to investigate the distribution and immunological effects of BNT162b2 in vivo. Vaccine trafficking to the dLN, cellular uptake, and spike protein expression were assessed following immunisation. Single-cell transcriptomic analyses and functional in vivo experiments were performed to identify the immune cell populations involved in orchestrating vaccine-induced responses and to characterise their interactions with adaptive immune cells.</p><p><strong>Findings: </strong>BNT162b2 was rapidly transported to the dLN, where it was predominantly captured by leukocytes that subsequently expressed the SARS-CoV-2 spike protein. Among these cells, plasmacytoid dendritic cells (pDCs) emerged as regulators involved in both inflammatory and humoural immune responses. Single-cell transcriptomic profiling revealed active interactions between pDCs and CD8⁺ T cells. Functional in vivo studies further demonstrated that pDCs promoted CD8⁺ T-cell activation and expansion, indicating an involvement in shaping adaptive immunity following vaccination.</p><p><strong>Interpretation: </strong>These findings identify pDCs as antigen-presenting cells involved in coordinating the immune response to BNT162b2. By regulating both innate and adaptive immune pathways and facilitating CD8⁺ T-cell activation, pDCs appear to play a functional role in the efficacy of this mRNA vaccine. This study provides additional insights into the immunological processes underlying mRNA vaccine-induced protection and may inform the future design and optimisation of mRNA-based immunotherapies and vaccines.</p><p><strong>Funding: </strong>Swiss National Science Foundation, Leonardo Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106432"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial diabetes mellitus: real world insights from the GENOMIT registry-a multinational, longitudinal cohort study.","authors":"Luisa Semmler, Boriana Büchner, Cornelia Kornblum, Marcus Deschauer, Saskia Wortmann, Chiara La Morgia, Serenella Servidei, Peter Freisinger, Alexander Mensch, Markus Schuelke, Holger Prokisch, Michelangelo Mancuso, Costanza Lamperti, Thomas Klopstock","doi":"10.1016/j.ebiom.2026.106458","DOIUrl":"10.1016/j.ebiom.2026.106458","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is a common but incompletely characterised manifestation of mitochondrial diseases (MD). Data on risk factors, clinical course, and treatment recommendations are lacking.</p><p><strong>Methods: </strong>In this multinational cohort study, we analysed longitudinal data of patients with a genetically confirmed MD from the GENOMIT registry included at German, Austrian, and Italian sites between 07/2009-01/2025. Our objectives were to (1) expand the genetic spectrum of mitochondrial diabetes mellitus (mDM), (2) identify risk factors, (3) delineate the clinical course, and (4) characterise real-world use of antidiabetic therapies.</p><p><strong>Findings: </strong>Of 2399 patients, 1225 (51%) were female, and 281 (12%; 172 female) had mDM. Diabetes occurred across 31 genotypes and exhibited marked genotype dependence, with the highest prevalence in m.3243A>G carriers (177/360 [49%]). Only the m.3243A>G variant was associated with a significantly increased risk of mDM (HR = 10.3; 95% CI 5.2-20.4, p < 0.0001), whereas single mtDNA deletions, multiple mtDNA deletions, and primary LHON variants, as well as sex, BMI, ethnicity, smoking, hypertension and dyslipidaemia did not show a significant association. Median diabetes onset in patients with the m.3243A>G variant was at 47.7 years (SD 45.2-52.0). Among patients with mDM, 140/281 (50%) used insulin, and 111/281 (40%) received non-insulin antidiabetic drugs, most commonly metformin, which was discontinued in 8/50 users. Literature review revealed neurological events temporally linked to metformin application in m.3243A>G carriers, though long-term use without adverse events was likewise reported.</p><p><strong>Interpretation: </strong>mDM is frequent in patients with MD, and the individual risk is strongly genotype dependent. While caution is warranted, our data do not justify universal avoidance of metformin; prospective, genotype-informed studies are needed to guide management.</p><p><strong>Funding: </strong>German Ministry of Research, Technology and Space; Italian Ministry of Health; European Union.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106458"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human microbiota, an emerging player in chronic obstructive pulmonary disease.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2026.106479","DOIUrl":"10.1016/j.ebiom.2026.106479","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106479"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of A(H5N8) stockpiled vaccine against a virus genetically identical to a human isolate of bovine A(H5N1) influenza virus.","authors":"Ryuta Uraki, Maki Kiso, Kiyoko Iwatsuki-Horimoto, Mutsumi Ito, Seiya Yamayoshi, Masaki Imai, Yoshihiro Kawaoka","doi":"10.1016/j.ebiom.2026.106430","DOIUrl":"10.1016/j.ebiom.2026.106430","url":null,"abstract":"<p><strong>Background: </strong>Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo.</p><p><strong>Methods: </strong>In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated.</p><p><strong>Findings: </strong>Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses.</p><p><strong>Interpretation: </strong>An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic.</p><p><strong>Funding: </strong>This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the Japan Agency for Medical Research and Development.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106430"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hallmarks of acute kidney injury: molecular endotypes, precision phenotyping, and phase-adapted therapy.","authors":"Hongtu Hu, Zikang Liu, Rui Ji, Yinghui Huang","doi":"10.1016/j.ebiom.2026.106436","DOIUrl":"10.1016/j.ebiom.2026.106436","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a heterogeneous syndrome for which creatinine and urine output incompletely represent underlying biology and temporal evolution. We organise AKI pathophysiology into four interconnected dimensions: initiation and effector injury; cell fate and immune microenvironment; repair and outcome determination; and systemic integration. These dimensions encompass microvascular and metabolic failure, oxidative injury, regulated cell death, inflammation, adaptive and maladaptive repair, senescence, fibrosis, and organ crosstalk. We translate these hallmarks into measurable phenotypes using biomarkers, imaging, and functional tests, and propose an aetiological trigger-hallmarks-phase (E-H-P) framework linking cause, dominant biology, and disease phase. Practical examples illustrate how E-H-P phenotyping can complement conventional staging and support trial enrichment. We distinguish established supportive care from investigational mechanism-directed therapies and identify priorities for biomarker validation, phase-specific intervention, and prevention of AKI-to-CKD transition.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106436"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infradian rhythms of human heart rate reveal distinct multiday cycle periods in healthy adults.","authors":"Rochelle I De Silva, Rachel E Stirling, Jodie Naim-Feil, Shivam Puri, Elizabeth Paratz, Philippa J Karoly","doi":"10.1016/j.ebiom.2026.106444","DOIUrl":"10.1016/j.ebiom.2026.106444","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronobiology research has historically focused on circadian rhythms; however, longer infradian rhythms are prevalent in human physiology and may have important implications for health and wellbeing. Previous studies have identified widespread infradian rhythms across human physiology, often in the context of hormonal regulation and disease. Despite growing evidence of their ubiquity, the mechanisms, significance, and clinical relevance of these rhythms remain poorly understood, largely reflecting a lack of longitudinal datasets and robust detection methods. The emergence of new wearable technologies enables rich, continuous data capture within individuals, allowing physiological rhythms to be studied at scale.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective, observational cohort study analysed young adults (n = 623), with up to four years of wearable and questionnaire data collected through the University of Notre Dame's (USA) NetHealth project. Participants who recorded at least three months of continuous (&gt;80% data completeness) heart rate data were included and significant infradian rhythms were identified using wavelet analysis. Unsupervised non-negative matrix factorisation was performed to cluster similar wavelet power spectrum distributions. Individuals' heart rate rhythms were compared to known environmental cycles (day-of-week, lunar, seasonal) and considering demographics and social networks. A second, smaller cohort (n = 70) with heart rate and menstrual timing was included to analyse the interplay of hormonal regulation on monthly cycles. Multinomial logistic regression and the Kruskal-Wallis test were applied to quantify the effects of environmental, behavioural and demographic factors on heart rate rhythms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Significant infradian rhythms of heart rate were detected in 70% (369/525) of the cohort and 36% (187/525) had two or more rhythms. Annual, biannual and 10-week rhythms were the most common. Within the 4-45-day band, individuals clustered into three multiday chronotypes based on dominant periodicities in their wavelet power spectra: weekly (∼7 days), monthly (∼25-35 days), and multi-month (&gt;35 days). Heart rate rhythms were influenced by environmental cycles (day-of-week and seasonality) and were synchronised to the menstrual cycle in most menstruating females, although monthly rhythms were also observed in males and menopausal women.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The prevalence of infradian, or multiday heart rate rhythms in healthy young people motivates further scientific investigation to understand the mechanisms of these rhythms and their potential association with autonomic function, and risk of disease or disease-specific symptoms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This study was funded by an Australian Research Council Grant (DP240102899). This study also received funding from the Australian National Health and Medical Research Council Medical Res","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106444"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}