EBioMedicine最新文献

{"title":"Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies.","authors":"Peng Xu, Santiago Estrada, Rika Etteldorf, Dan Liu, Mohammad Shahid, Weiyi Zeng, Deborah Früh, Martin Reuter, Monique M B Breteler, N Ahmad Aziz","doi":"10.1016/j.ebiom.2024.105513","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105513","url":null,"abstract":"<p><strong>Background: </strong>Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking.</p><p><strong>Methods: </strong>We used cross-sectional data from the Rhineland Study (N = 5812, 55.2 ± 13.6 years, 58% women) and the UK Biobank Imaging Study (UKB) (N = 45,076, 64.2 ± 7.7 years, 53% women), two large-scale population-based cohort studies. Volumes of hypothalamic structures were obtained from 3T structural magnetic resonance images through an automatic parcellation procedure (FastSurfer-HypVINN). The standardised cognitive domain scores were derived from extensive neuropsychological test batteries. We employed multivariable linear regression to assess associations of hypothalamic volumes with age, sex and cognitive performance.</p><p><strong>Findings: </strong>In older individuals, volumes of total, anterior and posterior hypothalamus, and mammillary bodies were smaller, while those of medial hypothalamus and tuberal region were larger. Larger medial hypothalamus volume was related to higher cortisol levels in older individuals, providing functional validation. Volumes of all hypothalamic structures were larger in men compared to women. In both sexes, larger volumes of total, anterior and posterior hypothalamus, and mammillary bodies were associated with better domain-specific cognitive performance, whereas larger volumes of medial hypothalamus and tuberal region were associated with worse domain-specific cognitive performance.</p><p><strong>Interpretation: </strong>We found strong age and sex effects on hypothalamic structures, as well as robust associations between these structures and domain-specific cognitive functions. Overall, these findings thus implicate specific hypothalamic subregions as potential therapeutic targets against age-associated cognitive decline.</p><p><strong>Funding: </strong>Institutional funds, Federal Ministry of Education and Research of Germany, Alzheimer's Association.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105513"},"PeriodicalIF":9.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D ultrasound localization microscopy of the nonhuman primate brain.","authors":"Paul Xing, Vincent Perrot, Adan Ulises Dominguez-Vargas, Jonathan Porée, Stephan Quessy, Numa Dancause, Jean Provost","doi":"10.1016/j.ebiom.2024.105457","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105457","url":null,"abstract":"<p><strong>Background: </strong>Haemodynamic changes occur in stroke and neurodegenerative diseases. Developing imaging techniques allowing the in vivo visualisation and quantification of cerebral blood flow would help better understand the underlying mechanism of these cerebrovascular diseases.</p><p><strong>Methods: </strong>3D ultrasound localization microscopy (ULM) is a recently developed technology that can map the microvasculature of the brain at large depth and has been mainly used until now in rodents. In this study, we tested the feasibility of 3D ULM of the nonhuman primate (NHP) brain with a single 256-channel programmable ultrasound scanner.</p><p><strong>Findings: </strong>We achieved a highly resolved vascular map of the macaque brain at large depth (down to 3 cm) in presence of craniotomy and durectomy using an 8-MHz multiplexed matrix probe. We were able to distinguish vessels as small as 26.9 μm. We also demonstrated that transcranial imaging of the macaque brain at similar depth was feasible using a 3-MHz probe and achieved a resolution of 60 μm.</p><p><strong>Interpretation: </strong>This work paves the way to clinical applications of 3D ULM. In particular, transcranial 3D ULM in humans could become a tool for the non-invasive study and monitoring of the brain cerebrovascular changes occurring in neurological diseases.</p><p><strong>Funding: </strong>This work was supported by the New Frontier in Research Fund (NFRFE-2022-00590), by the Canada Foundation for Innovation under grant 38095, by the Natural Sciences and Engineering Research Council of Canada (NSERC) under discovery grant RGPIN-2020-06786, by Brain Canada under grant PSG2019, and by the Canadian Institutes of Health Research (CIHR) under grant PJT-156047 and MPI-452530. Computing support was provided by the Digital Research Alliance of Canada.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105457"},"PeriodicalIF":9.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expediting pathogen genomics adoption for enhanced foodborne disease surveillance in Africa.","authors":"Aquillah M Kanzi, Stella I Smith, Chisomo Msefula, John Mwaba, Abraham Ajayi, Geoffrey Kwenda, Collins K Tanui, Anthony M Smith, Linda A Bester, Firehiwot A Derra, Kaunda Yamba, Daniel L Banda, John B Kalule, Happiness H Kumburu, Yasmina J Fakim, Nyasha Sithole, Patrick M K Njage, Francis F Chikuse, Pascale Ondoa, Sofonias K Tessema, Ebenezer Foster-Nyarko","doi":"10.1016/j.ebiom.2024.105500","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105500","url":null,"abstract":"<p><p>The role of genomics in public health surveillance has been accentuated by its crucial contributions during the COVID-19 pandemic, demonstrating its potential in addressing global disease outbreaks. While Africa has made strides in expanding multi-pathogen genomic surveillance, the integration into foodborne disease (FBD) surveillance remains nascent. Here we highlight the critical components to strengthen and scale-up the integration of whole genome sequencing (WGS) in foodborne disease surveillance across the continent. We discuss priority use-cases for FBD, and strategies for the implementation. We also highlight the major challenges such as data management, policy and regulatory frameworks, stakeholder engagement, the need for multidisciplinary collaborations and the importance of robust monitoring and evaluation, aiming to bolster Africa's preparedness and response to future health threats.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105500"},"PeriodicalIF":9.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Cross talk between the liver microbiome and epigenome in patients with metabolic dysfunction-associated steatotic liver disease\".","authors":"Carlos Jose Pirola, Adrian Salatino, Tomas Fernández Gianotti, Gustavo Osvaldo Castaño, Martin Garaycoechea, Silvia Sookoian","doi":"10.1016/j.ebiom.2024.105525","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105525","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105525"},"PeriodicalIF":9.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positron emission tomography an imaging biomarker in pulmonary fibrosis: from therapeutic mechanism to treatment monitoring.","authors":"Sang-Geon Cho, Erica L Herzog, Stephanie L Thorn, Albert J Sinusas","doi":"10.1016/j.ebiom.2024.105519","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105519","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105519"},"PeriodicalIF":9.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted metabolome atlas for sleep-related phenotypes in the Hispanic community health study/study of Latinos.","authors":"Ying Zhang, Brian W Spitzer, Yu Zhang, Danielle A Wallace, Bing Yu, Qibin Qi, Maria Argos, M Larissa Avilés-Santa, Eric Boerwinkle, Martha L Daviglus, Robert Kaplan, Jianwen Cai, Susan Redline, Tamar Sofer","doi":"10.1016/j.ebiom.2024.105507","DOIUrl":"10.1016/j.ebiom.2024.105507","url":null,"abstract":"<p><strong>Background: </strong>Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep-related phenotypes and blood metabolites.</p><p><strong>Methods: </strong>Utilising data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep-related phenotypes, grouped in several domains (sleep disordered breathing (SDB), sleep duration, sleep timing, self-reported insomnia symptoms, excessive daytime sleepiness (EDS), and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling. Network analysis was employed to visualise and interpret the associations between sleep phenotypes and metabolites.</p><p><strong>Findings: </strong>The patterns of statistically significant associations between sleep phenotypes and metabolites differed by superpathways, and highlighted subpathways of interest for future studies. For example, primary bile acid metabolism showed the highest cumulative percentage of statistically significant associations across all sleep phenotype domains except for SDB and EDS phenotypes. Several metabolites were associated with multiple sleep phenotypes, from a few domains. Glycochenodeoxycholate, vanillyl mandelate (VMA) and 1-stearoyl-2-oleoyl-GPE (18:0/18:1) were associated with the highest number of sleep phenotypes, while pregnenolone sulfate was associated with all sleep phenotype domains except for sleep duration. N-lactoyl amino acids such as N-lactoyl phenylalanine (lac-Phe), were associated with sleep duration, SDB, sleep timing and heart rate during sleep.</p><p><strong>Interpretation: </strong>This atlas of sleep-metabolite associations will facilitate hypothesis generation and further study of the metabolic underpinnings of sleep health.</p><p><strong>Funding: </strong>R01HL161012, R35HL135818, R01AG80598.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105507"},"PeriodicalIF":9.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics.","authors":"Marina Bluma, Konstantinos Chiotis, Marco Bucci, Irina Savitcheva, Anna Matton, Miia Kivipelto, Andreas Jeromin, Giovanni De Santis, Guglielmo Di Molfetta, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg, Agneta Nordberg","doi":"10.1016/j.ebiom.2024.105504","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105504","url":null,"abstract":"<p><strong>Background: </strong>Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness. Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD. This study aims to investigate the specific relationship between the AD biomarkers currently used in clinical practice and the plasma biomarkers.</p><p><strong>Methods: </strong>In a memory clinic cohort, we analysed plasma pTau181, pTau217, pTau231, respectively, GFAP, NfL, CSF pTau181, Aβ-PET scans, and MRI/CT visual read of atrophy. We utilized methods based on multiple linear regression to evaluate the specific associations between clinically used and recently developed plasma biomarkers, while also considering demographic variables such as age and sex.</p><p><strong>Findings: </strong>Although plasma pTau181, pTau217, pTau231, and GFAP were significantly associated with both Aβ-PET and CSF pTau181, Aβ-PET explained more variance in the levels of these biomarkers. The effect of CSF pTau181 on plasma GFAP and pTau181 was completely attenuated by Aβ-PET, whereas pTau231 and pTau217 were affected by both Aβ-PET and CSF pTau181 levels. Unlike these biomarkers, increased NfL was rather indicative of brain atrophy and older age. Based on the effect sizes, plasma pTau217 emerged as highly effective in distinguishing between A+ and A-, and T+ and T- individuals, with 60% of variance in plasma pTau217 explained by clinical AD biomarkers.</p><p><strong>Interpretation: </strong>Amyloid burden primarily drives the changes in plasma pTau181, pTau217, pTau231, and GFAP. In contrast to plasma pTau217, a significant portion of variance in plasma pTau181, pTau231, GFAP, NfL remains unexplained by clinical AD biomarkers.</p><p><strong>Funding: </strong>This research is supported by the Swedish Research Council VR: 2017-06086, 2020-4-3018, 2024-2027; Swedish Brain Foundation, Swedish Alzhzeimer Foundation, CIMED Region Stockholm/Karolinska Institutet; the Region Stockholm - Karolinska Institutet regional agreement on medical training and clinical research (ALF), Fondation Recherche sur Alzheimer (France).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105504"},"PeriodicalIF":9.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nature or nurture: genetic and environmental predictors of adiposity gain in adults.","authors":"Laia Peruchet-Noray, Niki Dimou, Reynalda Cordova, Emma Fontvieille, Anna Jansana, Quan Gan, Marie Breeur, Hansjörg Baurecht, Patricia Bohmann, Julian Konzok, Michael J Stein, Christina C Dahm, Nuno R Zilhão, Lene Mellemkjær, Anne Tjønneland, Rudolf Kaaks, Verena Katzke, Elif Inan-Eroglu, Matthias B Schulze, Giovanna Masala, Sabina Sieri, Vittorio Simeon, Giuseppe Matullo, Esther Molina-Montes, Pilar Amiano, María-Dolores Chirlaque, Alba Gasque, Joshua Atkins, Karl Smith-Byrne, Pietro Ferrari, Vivian Viallon, Antonio Agudo, Marc J Gunter, Catalina Bonet, Heinz Freisling, Robert Carreras-Torres","doi":"10.1016/j.ebiom.2024.105510","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105510","url":null,"abstract":"<p><strong>Background: </strong>Previous prediction models for adiposity gain have not yet achieved sufficient predictive ability for clinical relevance. We investigated whether traditional and genetic factors accurately predict adiposity gain.</p><p><strong>Methods: </strong>A 5-year gain of ≥5% in body mass index (BMI) and waist-to-hip ratio (WHR) from baseline were predicted in mid-late adulthood individuals (median of 55 years old at baseline). Proportional hazards models were fitted in 245,699 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to identify robust environmental predictors. Polygenic risk scores (PRS) of 5 proxies of adiposity [BMI, WHR, and three body shape phenotypes (PCs)] were computed using genetic weights from an independent cohort (UK Biobank). Environmental and genetic models were validated in 29,953 EPIC participants.</p><p><strong>Findings: </strong>Environmental models presented a remarkable predictive ability (AUC_BMI: 0.69, 95% CI: 0.68-0.70; AUC_WHR: 0.75, 95% CI: 0.74-0.77). The genetic geographic distribution for WHR and PC1 (overall adiposity) showed higher predisposition in North than South Europe. Predictive ability of PRSs was null (AUC: ∼0.52) and did not improve when combined with environmental models. However, PRSs of BMI and PC1 showed some prediction ability for BMI gain from self-reported BMI at 20 years old to baseline observation (early adulthood) (AUC: 0.60-0.62).</p><p><strong>Interpretation: </strong>Our study indicates that environmental models to discriminate European individuals at higher risk of adiposity gain can be integrated in standard prevention protocols. PRSs may play a robust role in predicting adiposity gain at early rather than mid-late adulthood suggesting a more important role of genetic factors in this life period.</p><p><strong>Funding: </strong>French National Cancer Institute (INCA_N°2019-176) 1220, German Research Foundation (BA 5459/2-1), Instituto de Salud Carlos III (Miguel Servet Program CP21/00058).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105510"},"PeriodicalIF":9.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality-associated plasma proteome dynamics in a prospective multicentre sepsis cohort.","authors":"Lars Palmowski, Maike Weber, Malte Bayer, Yuxin Mi, Karin Schork, Martin Eisenacher, Hartmuth Nowak, Tim Rahmel, Lars Bergmann, Andrea Witowski, Björn Koos, Katharina Rump, Dominik Ziehe, Ulrich Limper, Dietrich Henzler, Stefan Felix Ehrentraut, Alexander Zarbock, Roman Fischer, Julian C Knight, Michael Adamzik, Barbara Sitek, Thilo Bracht","doi":"10.1016/j.ebiom.2024.105508","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105508","url":null,"abstract":"<p><strong>Background: </strong>Sepsis remains a leading cause of mortality in intensive care units. Understanding the dynamics of the plasma proteome of patients with sepsis is critical for improving prognostic and therapeutic strategies.</p><p><strong>Methods: </strong>This prospective, multicentre observational cohort study included 363 patients with sepsis recruited from five university hospitals in Germany between March 2018 and April 2023. Plasma samples were collected on days 1 and 4 after sepsis diagnosis, and proteome analysis was performed using mass spectrometry. Classical statistical methods and machine learning (random forest) were employed to identify proteins associated with 30-day survival outcomes.</p><p><strong>Findings: </strong>Out of 363 patients, 224 (62%) survived, and 139 (38%) did not survive the 30-day period. Proteomic analysis revealed significant differences in 87 proteins on day 1 and 95 proteins on day 4 between survivors and non-survivors. Additionally, 63 proteins were differentially regulated between day 1 and day 4 in the two groups. The identified protein networks were primarily related to blood coagulation, immune response, and complement activation. The random forest classifier achieved an area under the receiver operating characteristic curve of 0.75 for predicting 30-day survival. The results were compared and partially validated with an external sepsis cohort.</p><p><strong>Interpretation: </strong>This study describes temporal changes in the plasma proteome associated with mortality in sepsis. These findings offer new insights into sepsis pathophysiology, emphasizing the innate immune system as an underexplored network, and may inform the development of targeted therapeutic strategies.</p><p><strong>Funding: </strong>European Regional Development Fund of the European Union. The State of North Rhine-Westphalia, Germany.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105508"},"PeriodicalIF":9.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and safety of autologous cord blood derived cell administration in extremely preterm infants: a single-centre, open-label, single-arm, phase I trial (CORD-SaFe study).","authors":"Lindsay Zhou, Courtney A McDonald, Tamara Yawno, Abdul Razak, Kristyn Connelly, Iona Novak, Suzanne L Miller, Graham Jenkin, Atul Malhotra","doi":"10.1016/j.ebiom.2024.105492","DOIUrl":"10.1016/j.ebiom.2024.105492","url":null,"abstract":"<p><strong>Background: </strong>Evidence from preclinical studies in small and large animal models has shown neuroprotective effects of intravenous administration of umbilical cord blood derived cells (UCBCs). This study aimed to evaluate the feasibility of umbilical cord blood (UCB) collection, extraction of UCBCs, and subsequent safety of intravenous autologous administration of UCBCs in extremely preterm infants (born <28 weeks gestation).</p><p><strong>Methods: </strong>A single-centre, open-label, single-arm, safety and feasibility clinical intervention trial was conducted at Monash Medical Centre and Monash Children's Hospital, Melbourne, Australia. Participants were extremely preterm infants born at less than 28 weeks completed gestation, and exclusions included major congenital malformation, maternal blood-borne virus infection, and severe brain injury on postnatal cranial ultrasound. UCB was collected at birth, and UCBCs were characterised (total nucleated cell count (TNC), mononuclear cell count (MNC), CD34+ cell count) and cryopreserved. Infants were reinfused with autologous UCBCs (25-50 million MNCs/kg) intravenously in the second postnatal week. Primary outcomes included feasibility: sufficient UCB volume (>7 mL) and UCBC numbers following processing (>25 × 10⁶ TNCs/kg); and safety: absence of adverse events directly related to UCBC administration.</p><p><strong>Findings: </strong>Forty-four UCB collections were attempted and sufficient UCB volume/UCBC extraction was demonstrated in 37 (84.1%) infants. Good Manufacturing Practice (GMP) grade cells were obtained in 31/44 (70.4%) of infants. Median (IQR) TNCs and MNCs collected were 130 (67-207) x 10⁶/kg and 60 (39-105) x 10⁶/kg, respectively. 23 infants with median (IQR) gestation of 26 (24-27) weeks and birth weight of 761 (650-946) grams were administered cells at a median (IQR) dose of 42.3 (31.1-62.3) x 10⁶ MNCs/kg). No serious adverse events were noted, and the infusions were well-tolerated.</p><p><strong>Interpretation: </strong>This phase-1 clinical trial has shown UCBC collection and reinfusion was feasible in approximately 70% of extremely preterm infants and was well tolerated without any serious adverse events.</p><p><strong>Funding: </strong>Funding to support this study was obtained from National Health and Medical Research Council of Australia, Cerebral Palsy Alliance, National Stem Cell Foundation of Australia, and Lions Cord Blood Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105492"},"PeriodicalIF":9.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}