EBioMedicine最新文献

{"title":"Foetal cortical expansion is associated with neurodevelopmental outcome at 2-years in congenital heart disease: a longitudinal follow-up study.","authors":"Siân Wilson, Hyuk Jin Yun, Anjali Sadhwani, Henry A Feldman, Seungyoon Jeong, Nicholas Hart, Kaysi Herrera Pujols, Jane W Newburger, P Ellen Grant, Caitlin K Rollins, Kiho Im","doi":"10.1016/j.ebiom.2025.105679","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105679","url":null,"abstract":"<p><strong>Background: </strong>In adolescents and adults with complex congenital heart disease (CHD), abnormal cortical folding is a putative predictor of poor neurodevelopmental outcome. However, it is unknown when this relationship first emerges. We test the hypothesis that it begins in utero, when the brain starts to gyrify and folding patterns first become established.</p><p><strong>Methods: </strong>We carried out a prospective, longitudinal case-control study, acquiring foetal MRIs at two timepoints in utero, (Scan 1 = 20-30 Gestational Weeks (GW) and Scan 2 = 30-39 GW), then followed up participants at two years of age to assess neurodevelopmental outcomes. We used normative modelling to chart growth trajectories of surface features across 60 cortical regions in a control population (n = 157), then quantified the deviance of each foetus with CHD (n = 135) and explored the association with neurodevelopmental outcomes at two years of age.</p><p><strong>Findings: </strong>Differences in cortical development between CHD and Control foetuses only emerged after 30 GW, and lower regional cortical surface area growth was correlated with poorer neurodevelopmental outcomes at two years of age in the CHD group.</p><p><strong>Interpretation: </strong>This work highlights the third trimester specifically as a critical period in brain development for foetuses with CHD, where the reduced surface area expansion in specific cortical regions becomes consequential in later life, and predictive of neurodevelopmental outcome in toddlerhood.</p><p><strong>Funding: </strong>This research was supported by the NINDS (R01NS114087, K23NS101120) and NIBIB (R01EB031170) of the NIH, PHN Scholar Award, AAN Clinical Research Training Fellowship, BBRF Young Investigator Awards, and the Farb Family Fund.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105679"},"PeriodicalIF":9.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751607","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":"A computational DNA methylation method to remove contaminated DNA from spent embryo culture medium for noninvasive preimplantation genetic testing.","authors":"Yidong Chen, Jin Huang, Fuchou Tang, Lu Wen, Jie Qiao","doi":"10.1016/j.ebiom.2025.105669","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105669","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In the last fifty years, assisted reproductive technology (ART) has achieved remarkable breakthroughs, culminating in the birth of 12 million infants. At the heart of ART success is preimplantation genetic testing (PGT), which enables the detection of chromosomal anomalies, single-gene disorders, and structural rearrangements, enhancing embryo selection and mitigating genetic risk. However, current PGT methods, including trophectoderm (TE) biopsy, face limitations such as challenges related to convenience and potential impacts on embryonic health. In this evolving field, noninvasive PGT (niPGT) has emerged as a promising alternative. By analysing cell-free DNA (cfDNA) in spent embryo culture medium (SECM), niPGT offers a less intrusive approach. However, maternal DNA contamination within SECM remains a marked barrier to its clinical application as underscored by our research and other studies. There is an urgent need for innovation and optimisation in niPGT methodologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We developed a computational algorithm to eliminate contaminated nonembryonic DNA from spent embryo culture medium. The rationale is based on the phenomenon that the DNA methylation level of a mammalian preimplantation embryo reaches its minimum at the blastocyst stage during a global DNA demethylation wave. Therefore, selecting hypomethylated reads is expected to enrich blastocyst DNA over nonembryonic DNA. To investigate this, we retrieved single-cell-resolution DNA methylation data from oocytes (n = 33), inner cell masses (ICMs, n = 74), TEs (n = 71) and sperm cells (n = 21), bulk DNA methylation data from cumulus cells, and DNA methylation data from SECM samples (n = 194) from our previously published database, and conducted a comparative analysis of DNA methylation patterns among them. Then, we constructed a decontamination algorithm based on single read and applied it to remove contamination originating from cumulus cells, polar bodies, and sperm cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;By selecting hypomethylated reads, we successfully enriched blastocyst DNA over DNA originating from cumulus cells, polar bodies and sperm (enrichment factors = 4, 1.2, and 2.5, respectively). By testing simulated SECM samples, the method demonstrated a substantial reduction in the false-negative rate even with up to 75% cumulus cell contamination. In real clinical SECM samples, the method improved aneuploidy detection sensitivity at a cumulus cell contamination ratio of 50%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our study introduces a novel computational strategy for reducing nonembryonic DNA contamination, thereby enhancing aneuploidy detection sensitivity in SECM cfDNA methylation analyses. In combination with DNA methylation methodologies, this approach holds considerable promise for advancing niPGT applications in ART.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This study was supported by grants from the Beijing Natural Science Found","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105669"},"PeriodicalIF":9.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751603","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":"Intratumoural pks⁺Escherichia coli is associated with risk of metachronous colorectal cancer and adenoma development in people with Lynch syndrome.","authors":"Yen Lin Chu, Peter Georgeson, Mark Clendenning, Khalid Mahmood, Romy Walker, Julia Como, Sharelle Joseland, Susan G Preston, Toni Rice, Brigid M Lynch, Roger L Milne, Melissa C Southey, Graham G Giles, Amanda I Phipps, John L Hopper, Aung K Win, Christophe Rosty, Finlay A Macrae, Ingrid Winship, Mark A Jenkins, Daniel D Buchanan, Jihoon E Joo","doi":"10.1016/j.ebiom.2025.105661","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105661","url":null,"abstract":"<p><strong>Background: </strong>The adverse gut microbiome may underlie the variability in risks of colorectal cancer (CRC) and metachronous CRC in people with Lynch syndrome (LS). The role of pks^+/-Escherichia coli (pks^+/-E. coli), Enterotoxigenic Bacteroides fragilis (ETBF), and Fusobacterium nucleatum (Fn) in CRCs and adenomas in people with LS is unknown.</p><p><strong>Methods: </strong>A total of 358 LS cases, including 386 CRCs, 90 adenomas, 195 normal colonic mucosa DNA from the Australasian Colon Cancer Family Registry were tested using multiplex TaqMan qPCR. Logistic regression was used to compare the intratumoural prevalence of each bacteria in Lynch CRCs with 1336 sporadic CRCs. Cox proportional-hazards regression estimated the associations of each bacteria with the risk of metachronous CRC and neoplasia.</p><p><strong>Findings: </strong>Pks⁺ E. coli (odds ratio [95% confidence interval] = 1.60 [1.08-2.35], P = 0.017), pks^-E. coli (3.87 [2.58-5.80], P < 0.001) and Fn (19.47 [13.32-28.87], P < 0.001) were significantly enriched in LS CRCs when compared with sporadic CRCs. Pks⁺ E. coli in the initial CRC was associated with an increased risk of metachronous CRC (hazard ratio [95% confidence interval] = 2.32 [1.29-4.17], P = 0.005) and metachronous colorectal neoplasia (1.51 [1.02-2.23], P = 0.040) when compared with CRCs without pks⁺ E. coli.</p><p><strong>Interpretation: </strong>Pks⁺ E. coli, pks^-E. coli, and Fn are enriched within LS CRCs, suggesting possible roles in CRC development in LS. Having intratumoural pks⁺ E. coli is associated with increased risk of metachronous CRC, suggesting that, if validated, people with LS might benefit from pks⁺ E. coli screening and eradication.</p><p><strong>Funding: </strong>This work was funded by an NHMRC Investigator grant (GNT1194896) and a Cancer Australia/Cancer Council NSW co-funded grant (GNT2012914).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105661"},"PeriodicalIF":9.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751626","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":"Impact of rosuvastatin on the memory potential and functionality of CD8⁺ T cells from people with HIV.","authors":"Federico Perdomo-Celis, Caroline Passaes, Valérie Monceaux, Olivier Lambotte, Dominique Costagliola, Mathieu F Chevalier, Laurence Weiss, Asier Sáez-Cirión","doi":"10.1016/j.ebiom.2025.105672","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105672","url":null,"abstract":"<p><strong>Background: </strong>Virus-specific CD8⁺ T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8⁺ T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities. Considering the implication of the cholesterol pathway in the induction of T cell exhaustion, here we evaluated the impact of rosuvastatin, an inhibitor of cholesterol synthesis, on the functionality and memory profile of HIV-specific CD8⁺ T cells from people on antiretroviral treatment.</p><p><strong>Methods: </strong>We analysed samples from 10 individuals with HIV-1 on ART who participated in the IMEA 043-CESAR trial and received rosuvastatin for 12 weeks. We explored whether rosuvastatin treatment was accompanied by changes in the memory potential of CD8⁺ T cells. We evaluated the phenotype and functionality of total and HIV-specific CD8⁺ T cells before, during, and after treatment with rosuvastatin. A mixed effects model was used for repeated measures and corrected for multiple comparisons.</p><p><strong>Findings: </strong>Total and HIV-specific CD8⁺ T cell survival and functionality were enhanced in individuals who received a 12-week course of rosuvastatin, with a consistent increase in polyfunctional IFN-γ⁺ TNF-α⁺ cells. The superior CD8⁺ T cell functionality after rosuvastatin treatment was associated with intrinsic metabolic changes, including the decrease of fatty acid uptake, as well as a reduction in effector/exhaustion markers. Changes in the characteristics of CD8⁺ T cells coincided with the duration of rosuvastatin administration, and most effects waned after the cessation of the treatment.</p><p><strong>Interpretation: </strong>CD8⁺ T cell metabolic reprogramming by targeting the cholesterol pathway, combined with other available immunotherapies, might represent a promising strategy in the search for the cure of HIV or other chronic viral infections.</p><p><strong>Funding: </strong>The CESAR trial was sponsored by IMEA. This work was supported by the NIH (grants UM1AI164562 and R01DK131476).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105672"},"PeriodicalIF":9.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751610","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":"Examining the link between 179 lipid species and 7 diseases using genetic predictors.","authors":"Linda Ottensmann, Rubina Tabassum, Sanni E Ruotsalainen, Mathias J Gerl, Christian Klose, Daniel L McCartney, Elisabeth Widén, Kai Simons, Samuli Ripatti, Veronique Vitart, Caroline Hayward, Matti Pirinen","doi":"10.1016/j.ebiom.2025.105671","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105671","url":null,"abstract":"<p><strong>Background: </strong>Genome-wide association studies of lipid species have identified several loci shared with various diseases, however, the relationship between lipid species and disease risk remains poorly understood. Here we investigated whether the plasma levels of lipid species are causally linked to disease risk.</p><p><strong>Methods: </strong>We built genetic predictors of 179 lipid species, measured in 7174 Finnish individuals, by utilising either 11 high-impact genomic loci or genome-wide polygenic scores (PGS). We assessed the impact of the lipid species on seven diseases by performing disease association across FinnGen (n = 500,348), UK Biobank (n = 420,531), and Generation Scotland (n = 20,032). We performed univariable Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to examine whether lipid species impact disease risk independently of standard lipids.</p><p><strong>Findings: </strong>PGS explained >4% of the variance for 34 lipid species but variants outside the high-impact loci had only a marginal contribution. Variants within the high-impact loci showed association with all seven diseases. MVMR supported a causal role of ApoB in ischaemic heart disease after accounting for lipid species. Phosphatidylethanolamine-increasing LIPC variants seemed to lower age-related macular degeneration risk independently of HDL-cholesterol. MVMR suggested a protective effect of four lipid species containing arachidonic acid on cholelithiasis risk independently of Total Cholesterol.</p><p><strong>Interpretation: </strong>Our study demonstrates how genetic predictors of lipid species can be utilised to gain insights into disease risk. We report potential links between lipid species and age-related macular degeneration and cholelithiasis risk, which can be explored for their utility in disease risk prediction and therapy.</p><p><strong>Funding: </strong>The funders had no role in the study design, data analyses, interpretation, or writing of this article.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105671"},"PeriodicalIF":9.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742649","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":"Efflux pump modulation by Montelukast and its roles in restoring antibiotic susceptibility in multidrug-resistant Staphylococcus aureus.","authors":"Suvendu Ojha, Simran Sinsinwar, Puja Chatterjee, Sarmistha Biswal, Pinkilata Pradhan, Tushar Kant Beuria","doi":"10.1016/j.ebiom.2025.105658","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105658","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus and its drug-resistant mutants are mentioned among the WHO's high-priority list of pathogens. Antibiotics like fluoroquinolones and cephalosporins are used to treat multidrug-resistant S. aureus infections. However, a higher expression of efflux pumps (NorA, NorB, and AbcA) induces multidrug resistance. The master regulator, MgrA, regulates the expression of most of these efflux pumps in S. aureus. The phosphorylation status of MgrA is determined by the cellular PknB/RsbU ratio, where PknB, a serine-threonine kinase, and RsbU, a serine-threonine phosphatase, are critical for MgrA functioning.</p><p><strong>Methods: </strong>An FDA-approved drug library was screened using an EtBr-accumulation assay to identify efflux pump inhibitors (EPIs). The synergy of EPIs with antibiotics was studied in vitro and in vivo in the murine skin infection model of female BALB/c mice. The effect of EPIs on mgrA, norB, pknB, and rsbU gene expression, interaction with MgrA, and effects on MgrA phosphorylation were studied.</p><p><strong>Findings: </strong>We identified Montelukast as an effective EPI, which showed synergy with moxifloxacin, a substrate of the NorB efflux pump, both in vitro and in the murine skin infection model. Further, Montelukast decreased norB expression and increased the pknB/rsbU expression ratio. Our in vitro results demonstrated that Montelukast strongly interacted with MgrA, facilitated MgrA phosphorylation, and enhanced its affinity for the norB promoter.</p><p><strong>Interpretation: </strong>Our study showed that Montelukast repressed MgrA expression and promoted MgrA phosphorylation to suppress norB expression and efflux pump activity, leading to the restoration of antibiotic susceptibility in multidrug-resistant S. aureus.</p><p><strong>Funding: </strong>The study was supported by SERB-DST, India (CRG/2021/005069), and the BRIC-ILS core.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105658"},"PeriodicalIF":9.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742648","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":"Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trials.","authors":"Christopher L Cooper, Gavin Morrow, Maoli Yuan, Thomas S Postler, Maxwell L Neal, Robert W Cross, Courtney Woolsey, Krystle N Agans, Viktoriya Borisevich, Ryan P McNamara, Caroline Atyeo, Vicky Roy, Daritza Germosen, Fuxiang Hou, Shui L Li, Lucia Reiserova, Yesle Choi, Aaron Wilson, Denise Wagner, Olivia Wallace-Selman, Alexei Carpov, Fuqiang Geng, Deborah J Frederick, Joanne DeStefano, Anne M Ercolini, Adrian S Enriquez, Kathryn M Hastie, Suzane Ramos da Silva, Eddy Sayeed, John W Coleman, Andrew Kilianski, Galit Alter, Erica Ollmann Saphire, John D Aitchison, Thomas W Geisbert, Swati B Gupta, Mark B Feinberg, Christopher L Parks","doi":"10.1016/j.ebiom.2025.105647","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105647","url":null,"abstract":"<p><strong>Background: </strong>Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its geographic range is expected to expand due to influences like climate change and land usage, and this will place larger parts of Africa at risk. We conducted preclinical development on a promising experimental vaccine that allowed its advancement into human trials.</p><p><strong>Methods: </strong>The LF vaccine is based on a vesicular stomatitis virus (VSV) vector in which the VSV glycoprotein (G) was replaced with the LASV glycoprotein complex (GPC). Earlier studies showed that this vaccine (VSVΔG-LASV-GPC) was efficacious in macaques, thus we regenerated VSVΔG-LASV-GPC using laboratory and documentation practices required to support vaccine manufacturing and human trials. The efficacy of the clinical vaccine candidate was assessed in cynomolgus macaques and more extensive immunologic analysis was performed than previously to investigate immune responses associated with protection.</p><p><strong>Findings: </strong>A single VSVΔG-LASV-GPC vaccination elicited innate, humoural and cellular immune responses, prevented development of substantial LASV viraemia, and protected animals from disease. Vaccinated macaques developed polyfunctional antibodies and serum was shown to neutralize virus expressing GPCs representative of geographically diverse LASV lineages.</p><p><strong>Interpretation: </strong>The VSVΔG-LASV-GPC clinical candidate elicited immunity that protected 10 of 10 vaccinated macaques from disease supporting its use in a clinical development program, which recently progressed to phase 2 clinical trials. Moreover, immunologic analysis showed that virus-neutralizing serum antibodies likely played a role in preventing LASV disease in vaccinated macaques.</p><p><strong>Funding: </strong>This work was supported by the Coalition for Epidemic Preparedness Innovations (CEPI), The National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), The Bill and Melinda Gates Global Vaccine Accelerator Program, the Burroughs Wellcome Fund, and financial gifts and support by Nancy Zimmerman, Mark and Lisa Schwartz, and Terry and Susan Ragon.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105647"},"PeriodicalIF":9.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741865","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":"Exploring the neuromagnetic signatures of cognitive decline from mild cognitive impairment to Alzheimer's disease dementia.","authors":"Sinead Gaubert, Pilar Garces, Jörg Hipp, Ricardo Bruña, Maria Eugenia Lopéz, Fernando Maestu, Delshad Vaghari, Richard Henson, Claire Paquet, Denis-Alexander Engemann","doi":"10.1016/j.ebiom.2025.105659","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105659","url":null,"abstract":"<p><strong>Background: </strong>Developing non-invasive and affordable biomarkers to detect Alzheimer's disease (AD) at a prodromal stage is essential, particularly in the context of new disease-modifying therapies. Mild cognitive impairment (MCI) is a critical stage preceding dementia, but not all patients with MCI will progress to AD. This study explores the potential of magnetoencephalography (MEG) to predict cognitive decline from MCI to AD dementia.</p><p><strong>Methods: </strong>We analysed resting-state MEG data from the BioFIND dataset including 117 patients with MCI among whom 64 developed AD dementia (AD progression), while 53 remained cognitively stable (stable MCI), using spectral analysis. Logistic regression models estimated the additive explanation of selected clinical, MEG, and MRI variables for AD progression risk. We then built a high-dimensional classification model to combine all modalities and variables of interest.</p><p><strong>Findings: </strong>MEG 16-38Hz spectral power, particularly over parieto-occipital magnetometers, was significantly reduced in the AD progression group. In logistic regression models, decreased MEG 16-38Hz spectral power and reduced hippocampal volume/total grey matter ratio on MRI were independently linked to higher AD progression risk. The data-driven classification model confirmed, among other factors, the complementary information of MEG covariance (AUC = 0.74, SD = 0.13) and MRI cortical volumes (AUC = 0.77, SD = 0.14) to predict AD progression. Combining all inputs led to markedly improved classification scores (AUC = 0.81, SD = 0.12).</p><p><strong>Interpretation: </strong>These findings highlight the potential of spectral power and covariance as robust non-invasive electrophysiological biomarkers to predict AD progression, complementing other diagnostic measures, including cognitive scores and MRI.</p><p><strong>Funding: </strong>This work was supported by: Fondation pour la Recherche Médicale (grant FDM202106013579).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105659"},"PeriodicalIF":9.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741816","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":"Insights into maternal sleep: a large-scale longitudinal analysis of real-world wearable device data before, during, and after pregnancy.","authors":"Nichole Young-Lin, Conor Heneghan, Yun Liu, Logan Schneider, Logan Niehaus, Ariel Haney, Mercy Asiedu, Karla Gleichauf, Jacqueline Baras Shreibati, Belen Lafon","doi":"10.1016/j.ebiom.2025.105640","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105640","url":null,"abstract":"<p><strong>Background: </strong>Current understanding of pregnancy and postpartum sleep is driven by limited lab or self-reported data. Our goal is to use consumer wearable devices through an observational study to reveal longitudinal, real-world sleep patterns in this population.</p><p><strong>Methods: </strong>We analysed retrospective, de-identified Fitbit device data from 2540 users in the United States and Canada who met strict wear-time requirements (≥80% daily usage for ≥80% of the time periods of interest [12 weeks prepregnancy, throughout pregnancy, and 20 weeks immediately postpartum]). We tracked sleep time and stages using Fitbit devices.</p><p><strong>Findings: </strong>Pregnant participants experienced a peak in total sleep time (TST) at 10 weeks (447.6 ± 47.6 min), exceeding their prepregnancy average (425.3 ± 43.5 min) before declining throughout pregnancy. This initial TST increase, mirrored by time in bed (TIB), was driven by more light sleep. Deep and rapid-eye movement sleep decreased significantly throughout pregnancy, with maximum reductions of 19.2 ± 13.8 min and 9.0 ± 19.2 min respectively by pregnancy end (two-sided t-test, p < 0.001 for both). Sleep efficiency also slightly declined during pregnancy (median drop: 88.3%-86.8%). Postpartum, TIB remained below prepregnancy levels by 14.7 ± 45.7 min one year after birth and 15.2 ± 47.7 min at 1.5 years after birth.</p><p><strong>Interpretation: </strong>This study revealed a previously unquantified initial increase in sleep followed by decreases in both quantity and quality as pregnancy progresses. Sleep deficits persist for at least 1.5 years postpartum. These quantified trends can assist clinicians and patients in understanding what to expect through their pregnancy and postpartum journey.</p><p><strong>Funding: </strong>Google, LLC.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105640"},"PeriodicalIF":9.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728844","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":"Cerebrospinal fluid metabolomics in autistic regression reveals dysregulation of sphingolipids and decreased β-hydroxybutyrate.","authors":"Jingya Yan, Velda X Han, Hannah F Jones, Timothy A Couttas, Beverly Jieu, F Markus Leweke, Jennifer Lee, Catherine Loi, Richard Webster, Kavitha Kothur, Manoj P Menezes, Jayne Antony, Tejaswi Kandula, Michael Cardamone, Shrujna Patel, Sushil Bandodkar, Russell C Dale","doi":"10.1016/j.ebiom.2025.105664","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105664","url":null,"abstract":"<p><strong>Background: </strong>Autism is highly heritable, however actionable genetic findings are only found in a minority of patients. Many people with autism suffer loss of neurodevelopmental skills, known as autistic regression. The cause of regression is poorly understood, and the diagnostic and therapeutic pathways are lacking.</p><p><strong>Methods: </strong>We used untargeted metabolomics using a UPLC-Q-Exactive-HFx Mass Spectrometry to examine cerebrospinal fluid (CSF) from twenty-two patients with autistic regression compared to sixteen controls with neurodevelopmental disorders (but not autistic regression) and thirty-four controls with other neurological disease (headache, encephalitis, epilepsy). The twenty-two patients with autistic regression consisted of two groups: early (infantile) autistic regression <2 years of age (n = 8), and later regression of skills >4 years of age, often in the context of pre-existing developmental concerns (n = 14). Metabolites of interest were then quantified and validated using targeted assays.</p><p><strong>Findings: </strong>Untargeted case-control studies revealed good separation of patients from controls using multivariate analysis. β-hydroxybutyrate was significantly decreased in the CSF of patients with autistic regression, and the findings were validated using a targeted β-hydroxybutyrate assay. The sphingolipid, sphingosine-1-phosphate was significantly elevated in the discovery case-control studies, and sphingolipid metabolism pathways were also significantly dysregulated. We therefore developed a targeted metabolite assay of forty sphingolipids. After FDR correction, 21 of the 40 sphingolipids were significantly dysregulated (p_FDR < 0.05) (Benjamini-Hochberg correction) in autistic regression compared to the neurodevelopmental controls, and 26 of the 40 sphingolipids were significantly dysregulated in autistic regression compared to other neurological controls, with elevated ceramides, hexosylceramides, sphingosines (including sphingosine-1-phosphate), and sulfatides. By contrast, sphingomyelin levels were generally decreased in autistic regression.</p><p><strong>Interpretation: </strong>Our data shows the potential utility of CSF metabolomics in the context of autistic regression, a clinical syndrome which has historically lacked pathophysiological biomarkers and disease modifying therapies.</p><p><strong>Funding: </strong>Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, Petre Foundation, Cerebral Palsy Alliance, and Ainsworth and SCHF Neuroscience grant scheme.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105664"},"PeriodicalIF":9.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728762","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}