EBioMedicine最新文献

{"title":"Corticostriatal glutamate mechanisms underlying beta synchrony and motor deficits via striatal NMDA receptors in Parkinson's disease.","authors":"Zirui Wang, Xinyu Fan, Yuting Zhao, Wenting Su, Xinxin Jiang, Hao Huang, Tong Xu, Xiaoli Gong, Yubo Zhang, Yin Jiang, Ting Zhang, J J Johannes Hjorth, Alexander Kozlov, Jeanette Hällgren Kotaleski, Jun Jia","doi":"10.1016/j.ebiom.2026.106418","DOIUrl":"10.1016/j.ebiom.2026.106418","url":null,"abstract":"<p><strong>Background: </strong>Beta-band (13-30 Hz) oscillations in the cortico-basal ganglia-thalamic (CBT) network strongly correlate with motor deficits in Parkinson's disease (PD), yet their synaptic origins remain unclear. Given that dopamine (DA) loss is necessary but not sufficient to produce sustained beta rhythms, we hypothesised that corticostriatal glutamatergic overdrive may function as a significant non-dopaminergic amplifier of pathological synchrony.</p><p><strong>Methods: </strong>Using an integrated experimental-computational approach, we combined 6-hydroxydopamine (6-OHDA) male rat models, ex vivo striatal patch-clamp recordings, chemogenetic modulation of corticostriatal projection, and multiscale computational network modelling to examine beta oscillation dynamics in the CBT network.</p><p><strong>Findings: </strong>Early DA denervation caused akinesia without beta elevation, while advanced degeneration triggered robust high-beta (25-40 Hz) oscillations and increased corticostriatal coherence. Ex vivo, medium spiny neurons (MSNs) exhibited heightened presynaptic glutamate release correlated with beta power. Computational modelling showed that excessive corticostriatal input under DA depletion increased MSN synchrony, disrupted striatal decorrelation, and was associated with the emergence of pathological beta rhythms, effects reversed by reducing glutamatergic input. In vivo chemogenetic silencing of corticostriatal projections suppressed beta synchrony and improved motor performance in 6-OHDA rats, whereas activation in DA-intact rats had no effect. Notably, striatal NMDA, not AMPA, receptor blockade reduced beta oscillations and motor deficits. Network simulations implicated the subthalamic → motor cortex feedback loop in the maintenance of this pathological beta state.</p><p><strong>Interpretation: </strong>Corticostriatal glutamatergic overdrive, through NMDA receptor-dependent signalling, is linked to the amplification and propagation of beta synchronisation across the CBT circuit, highlighting it as a potential biomarker and a promising therapeutic target in PD.</p><p><strong>Funding: </strong>This research was supported by the National Natural Science Foundation of China (32271173, 82371256) and the Natural Science Foundation of Beijing Municipality (7242214, 7252213). This study was also supported by the Swedish Research Council (VR-M-2020-01652), the Swedish e-Science Research Centre (SeRC), Science for Life Laboratory, KTH Digital Future, EU/Horizon 2020 No. 945539 (HBP 935 SGA3) and No. 101147319 (EBRAINS 2.0 Project), the European Union's Research and Innovation Program Horizon Europe under grant agreement No. 101137289(the Virtual Brain Twin Project).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106418"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711631","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":"Global, regional and national projections of heatwave-related death burdens under climate change, urbanisation, adaptation and population growth scenarios.","authors":"Jinjian Chen, Qiongyu Zhu, Cui Guo, Shaowei Wu, Weeberb J Requia, Kai Chen, Zhaobin Sun, Mohammad Javad Zare Sakhvidi, Joan Ballester, Siru Yang, Honda Yasushi, Shilu Tong, Xuemei Wang, Jun Yang","doi":"10.1016/j.ebiom.2026.106419","DOIUrl":"10.1016/j.ebiom.2026.106419","url":null,"abstract":"<p><strong>Background: </strong>Intensifying heatwaves driven by climate change pose a severe and disproportionate health burden, particularly for populations undergoing rapid demographic and environmental transitions, yet globally comparable projections of future mortality under varying scenarios remain limited.</p><p><strong>Methods: </strong>We constructed a global, grid-based, and three-stage framework covering 176 countries, integrating climate projections from 20 CMIP6 models under four Shared Socioeconomic Pathways (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). Heatwaves were defined as ≥2 consecutive days with grid-specific daily mean temperatures exceeding the 95th percentile. Historical heatwave-mortality associations from 750 locations, together with future population distributions, urbanisation trajectories, and adaptation scenarios, were incorporated to estimate excess heatwave-attributable deaths during the 2030s, 2050s, and 2090s, with uncertainty quantified via Monte Carlo simulations.</p><p><strong>Findings: </strong>Global heatwave-related deaths are projected to increase from 1,018,776 (95% UI: 935,188-1,106,785) in the 2000s to 5,289,925 (95% UI: 2,665,816-8,287,210), 8,814,669 (95% UI: 5,055,306-13,734,514), 13,690,238 (95% UI: 9,902,215-19,250,977), and 16,133,330 (95% UI: 11,559,920-21,300,978) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. Sub-Saharan Africa will suffer from the largest heatwave-related deaths in the 2090s, contributing to the proportion of approximately 20.33%-24.92%. Projected slopes are steeper under low urbanisation level, SSP3 population scenario, and no adaptation scenario.</p><p><strong>Interpretation: </strong>The projected heatwave mortality burden underscores the urgent need for targeted climate adaptation, urban planning, and public health strategies. The findings reveal differential vulnerability across populations and regions, offering guidance for resource allocation to strengthen resilience in a warming world.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (No. 42575195), China Postdoctoral Science Foundation (No. 2025M780707), and Guangdong Provincial General Colleges and Universities Innovation Team Project (Natural Science) (No. 2024KCXTD004).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106419"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723102","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":"Longitudinal progression, metrics, age-dependence, and modifiers of ataxia severity in SCA27B: a multicentre study of 219 patients.","authors":"Andreas Traschütz, Ralf-Dieter Hilgers, Friedrich Erdlenbruch, Christel Depienne, Thomas Wirth, Clarisse Delvallée, Astrid Nümann, Catherine Ashton, David Pellerin, Elisabetta Indelicato, Felix Heindl, Mathilde Renaud, Max Borsche, Marcus Grobe-Einsler, Jennifer Faber, Thomas Klockgether, Ludger Schöls, Bernard Brais, Mathieu Anheim, Dagmar Timmann, Matthis Synofzik","doi":"10.1016/j.ebiom.2026.106437","DOIUrl":"10.1016/j.ebiom.2026.106437","url":null,"abstract":"<p><strong>Background: </strong>Spinocerebellar Ataxia 27B (SCA27B) is a novel, frequent and likely treatable late-onset autosomal-dominant ataxia caused by GAA repeat-expansions in FGF14. For understanding disease evolution and imminent trial planning, metrics of the most widely used clinical outcome assessment (Scale for the Assessment and Rating of Ataxia/SARA), longitudinal progression and modifiers thereof are warranted.</p><p><strong>Methods: </strong>Multicentre intercontinental observational study (2015-2024) of 661 assessments from 219 patients with SCA27B (age: 68 ± 10 years; SARA: 9 ± 6 points) with item-level distribution-based analyses to characterise SARA metrics relative to ageing-related impairment in 390 healthy controls; and linear mixed-effects modelling to determine longitudinal progression and demographic or genetic modifiers.</p><p><strong>Findings: </strong>Ataxia severity in SCA27B as assessed by SARA was primarily attributable to gait, stance, and lower-limb impairment; other ataxia domains scored ≤1 SARA point in 79-94% of patients. Discrimination of SCA27B motor performance from controls decreased with age due to ageing-related motor variability captured by SARA, thus limiting potential metric response windows for symptomatic treatments. Disease progression was faster in the presence of interfering ageing-related comorbidities in 14 (6%) patients. Overall longitudinal progression of SCA27B was 0.54 SARA points/year [95% CI: 0.37-0.71]. Expansions of (GAA)_{> 180} repeats were frequent also on the shorter allele (n = 18 (8%), range: 196-348 repeats), and associated with faster progression (+1.6 SARA points/year, [95% CI: 0.9-2.2]), including also otherwise less affected ataxia domains speech and sitting.</p><p><strong>Interpretation: </strong>Disease progression in SCA27B is characterised by mild progression, ageing-related motor variabilities and comorbidities, and associated with repeat size on both alleles.</p><p><strong>Funding: </strong>Else-Kröner-Fresenius-Stiftung, EU, DFG, BMBF, CIHR, NAF, Ataxia-UK, CSC.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106437"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758264","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":"Immunodominance hierarchy of influenza A haemagglutinin antigenic sites: an observational cohort study across distinct exposure histories.","authors":"José Luis Martínez-Guevara, Tsoi Ying Lai, Mitali Mishra, Minh Thu Hoang, William Shea, Caroline Katherine Page, Pamela Sinywimaanzi, Edgar Simulundu, Richard Eric Rothman, Andrew Pekosz, Katherine Zela Joan Fenstermacher, Catherine Gayle Sutcliffe, Viviana Simon, Peter Palese, Weina Sun, Irene González-Domínguez","doi":"10.1016/j.ebiom.2026.106412","DOIUrl":"10.1016/j.ebiom.2026.106412","url":null,"abstract":"<p><strong>Background: </strong>Antibody responses to influenza A viruses are strongly focused on immunodominant antigenic sites within the haemagglutinin (HA) head domain. Although immunodominance hierarchies have been described for H1 and H3 subtypes in adults, it remains unclear whether these patterns are shaped by first early-life exposure or by cumulative influenza infections or vaccinations over time.</p><p><strong>Methods: </strong>We evaluated HA antigenic site immunodominance using haemagglutination inhibition (HI) assays with panels of H1 and H3 mutant viruses lacking individual classical antigenic sites. Sera from two human cohorts with different exposure histories were analysed: adults from New York City with mixed exposures through vaccination and infection, as well as children and adults living in rural Zambia exposed only through infection. Analyses of children with presumed first exposure were conducted to assess how initial influenza exposure shapes immunodominance hierarchies.</p><p><strong>Findings: </strong>Across both cohorts, H1-specific antibody responses were consistently dominated by antigenic sites Sb and Ca2, regardless of age, geography, or exposure history. For H3, sites A and B shared immunodominance. The first influenza A infection in children was associated with the establishment of these hierarchies. Importantly, influenza B infection did not alter the immunodominance profiles of influenza A H1 or H3 haemagglutinin.</p><p><strong>Interpretation: </strong>Immunodominance hierarchies of influenza A haemagglutinin antigenic sites are established early in life following first exposure and appear not to be substantially affected by diverse exposure histories.</p><p><strong>Funding: </strong>This project was financially supported by Center for Excellence on Influenza Research and Response, the Center of Excellence for Influenza Research and Surveillance, the Collaborative Influenza Vaccine Innovation Centers programme as well as institutional funds from the Center for Vaccine Research and Pandemic Preparedness, and the National Institute of Allergy and Infectious Diseases.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106412"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683557","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":"NMR metabolomics and glycomics for cancer detection in patients with non-specific symptoms: a prospective observational cohort study.","authors":"Tereza Kacerova, Abi G Yates, James R Larkin, Boris Shulgin, Jack J J J Miller, Philippa L Harris Gleave, Sebastian de Jel, Jack Cheeseman, Georgia Elgood-Hunt, Eric Schiffer, Daniel I R Spencer, Suzie Anthony, Daniel C Anthony","doi":"10.1016/j.ebiom.2026.106434","DOIUrl":"10.1016/j.ebiom.2026.106434","url":null,"abstract":"<p><strong>Background: </strong>Early cancer diagnosis in patients with non-specific symptoms is limited by the lack of discriminatory tests. Within the Oxfordshire Suspected CANcer (SCAN) pathway, exploratory biomarker work showed that serum ¹H NMR-based metabolomics can identify cancer with high accuracy. SCAN2 evaluated whether integrating metabolomics with glycomics provides complementary molecular information and improves discrimination in a clinically complex, real-world population.</p><p><strong>Methods: </strong>Serum from 369 SCAN patients (59 cancers) was analysed using AXINON® System-derived NMR metabolomics and HPLC-MS glycomics. Machine-learning models were trained to predict cancer status, with performance assessed by receiver operating characteristic (ROC) analysis of pooled cross-validated predictions. To place cancer risk in a broader clinical context, a second classifier modelling alternative non-cancer diagnosis was incorporated, and mean predicted probabilities from both models were jointly projected into a two-dimensional space, maintaining strict separation of training and test data.</p><p><strong>Findings: </strong>In the full cohort, integration of glycomics with metabolomics achieved an AUC of 0.814 (95% CI 0.808-0.820). In a refined sub-cohort excluding major comorbidities and selected cancer types (32 cancers, 277 non-cancers), performance improved to an AUC of 0.884 (95% CI 0.879-0.890). Discriminatory features included cancer-associated biantennary fucosylated glycans alongside amino acid metabolites (glutamate, histidine) and lipoprotein-related measures. A classifier distinguishing metastatic from non-metastatic disease (n = 29 vs. 30) achieved an AUC of 0.80. Joint probability analysis in the full cohort preserved cancer-associated signatures across comorbidity burden, with projection-based classification achieving an accuracy of 89.2% (95% CI 85.7-92.6).</p><p><strong>Interpretation: </strong>These findings validate the SCAN1 metabolomic signature in a more clinically complex cohort and indicate that integrating glycomics with metabolomics provides complementary biological information for cancer discrimination. Joint probability analysis provides an interpretable framework for cancer risk stratification within multimorbid diagnostic pathways, supporting the clinical potential of scalable multi-omics blood testing.</p><p><strong>Funding: </strong>EPSRC, EU Horizon 2020, Wellcome/MLSTF, Novo Nordisk Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106434"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757719","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":"Early HHV-6 IgG and IgA responses during acute SARS-CoV-2 infection in relation to long COVID: a multicohort observational study.","authors":"Ananya Choudhury, Michael J Burry, Woo Joo Kwon, Xihui Yin, Alysa Rallistan, Sonia Presti, Gabrielle S Ndakwah, Emily Q Cheng, Muge Kalaycioglu, Marlayna Harris, Jennifer Frankovich, Elizabeth W Karlson, Jenna Bollyky, Paul J Utz, Tyler R Prestwood","doi":"10.1016/j.ebiom.2026.106455","DOIUrl":"10.1016/j.ebiom.2026.106455","url":null,"abstract":"<p><strong>Background: </strong>Long COVID is a heterogeneous condition associated with both early immune responses to SARS-CoV-2 and antibody responses to herpesviruses. However, herpesvirus-directed antibody responses during acute SARS-CoV-2 infection and their relationship to subsequent long COVID remain poorly understood.</p><p><strong>Methods: </strong>We developed a multiplex bead-based serologic assay using recurrent, public peptide epitopes spanning all eight human herpesviruses. Antibody responses were profiled in longitudinal samples from acute SARS-CoV-2 infection and in early post-infection samples from participants in the NIH RECOVER observational cohort. IgG, IgA, and IgM responses were analysed using peptide-, virus-, and factor-level approaches.</p><p><strong>Findings: </strong>During acute SARS-CoV-2 infection, a subset of individuals exhibited increased herpesvirus-directed IgA responses, particularly against beta-herpesviruses, without corresponding increases in IgG or IgM. In RECOVER participants, subsequent long COVID was associated with herpesvirus- and isotype-specific enrichment of high responders, most prominently HHV-6 IgA and HHV-1/HHV-2 IgG. Unsupervised factorisation identified distinct HHV-6 IgG- and IgA-dominant antibody programs with differing clinical and demographic associations. HHV-6 IgG responses were associated with lower symptom burden and relative enrichment among participants without long COVID, whereas HHV-6 IgA responses were associated with greater symptom burden. HHV-6 IgG responses also declined with increasing age, with the association more readily detected among females.</p><p><strong>Interpretation: </strong>Early herpesvirus-directed antibody responses following SARS-CoV-2 infection exhibit distinct virus- and isotype-specific patterns associated with long COVID. These findings suggest that heterogeneity in long COVID may be linked to differential herpesvirus-directed humoural immune responses that emerge early after infection.</p><p><strong>Funding: </strong>This study was funded by Stanford Post-Acute Recovery Cohort; NIH and RECOVER grants; the Henry Gustav Floren Family Trust; the Stanford Department of Medicine Team Science Program; Stanford Institutes of Medicine Summer Research Program (SIMR); the Doris Duke Charitable Foundation; the SPARK Program; Nucleate Dojo; the Jessica Lynn Saal Memorial Award; the William and Marissa Rastetter Research Scholar Fund through the Robinson Life Sciences, Business, and Entrepreneurship Program; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health Award.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106455"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839665","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":"Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases.","authors":"Ajay Konuri, Gonzalo Castro Leal, Niloufar Zebarjadi, Annegret Habich, Nicolás Castellanos-Perilla, María Camila Gonzalez, John-Paul Taylor, Michael Firbank, Daniel Alcolea, Alexandre Bejanin, Kurt Segers, Florence Benoit, Ahmet Turan Isik, Bedia Samanci, Consuelo Cháfer-Pericás, Richard Wade-Martins, Michele T M Hu, Rohan Bhome, Ivelina Dobreva, Zuzana Walker, Dag Aarsland, Eric Westman, Daniel Ferreira, Glenda Halliday, Simon J G Lewis, Rimona S Weil, Ramon Landin-Romero, Christian Lambert, Neil P Oxtoby, Elie Matar","doi":"10.1016/j.ebiom.2026.106400","DOIUrl":"10.1016/j.ebiom.2026.106400","url":null,"abstract":"<p><strong>Background: </strong>Lewy body diseases (LBD) collectively share α-synuclein Lewy pathology, yet present wide clinical heterogeneity, with overlapping motor and non-motor features and progression patterns that challenge traditional diagnostic boundaries.</p><p><strong>Methods: </strong>To resolve this spatiotemporal heterogeneity at the biological level, we applied a data-driven atrophy progression framework to MRI data from 833 individuals across Parkinson's disease, dementia with Lewy bodies, and prodromal isolated REM sleep behaviour disorder using the Subtype and Stage Inference algorithm.</p><p><strong>Findings: </strong>Four transdiagnostic subtypes (A: Early cortico-limbic/late basal ganglia, B: Early basal ganglia/late limbic, C: Early temporo-limbic/late basal ganglia, and D: Early basal ganglia-cingulate/late cortex) emerged, each defined by a distinct spatiotemporal progression of atrophy that explained cognitive, motor, and psychiatric variability. An early cortico-limbic/late basal ganglia subtype represented a dementia-prone subtype across clinical diagnoses, with limbic involvement associating with the emergence of visual hallucinations.</p><p><strong>Interpretation: </strong>These biologically relevant spatiotemporal atrophy subtypes provide an interpretable stratification of patients with LBD, with the potential to refine prognosis, improve clinical trial stratification, and guide precision therapeutic approaches.</p><p><strong>Funding: </strong>This work was made possible by an Ignition grant from the University of Sydney and University College London (Global Engagement Fund).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106400"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677377","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":"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}