EBioMedicine最新文献

{"title":"Role of human infection challenge studies (HICs) in drug development for respiratory syncytial virus (RSV): systematic review and meta-analysis.","authors":"Prosenjit Kundu, Mark Quinn, Elaine Thomas, Jared C Christensen, Sima S Toussi, Negar Niki Alami, Anindita Banerjee","doi":"10.1016/j.ebiom.2025.105765","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105765","url":null,"abstract":"<p><strong>Background: </strong>Human infection challenge studies (HICs) are powerful in establishing early proof-of-concept for experimental drugs and understanding disease pathogenesis. A comprehensive assessment of HICs will allow to understand the viral load (VL) dynamics and symptom score kinetics of respiratory syncytial virus (RSV) and facilitate drug development for RSV.</p><p><strong>Methods: </strong>In this study, we conducted a systematic search of double-blind, placebo-controlled RSV HICs using Biosis Previews, Embase, Ovid MEDLINE, PubMed, ClinicalTrials.gov, and EudraCT from 1990 to August 2023. We estimated VL and symptom related measures in placebo and relative mean reduction (RMR) of the measures in the experimental drug compared to placebo. The primary outcomes are RMR of VL area under curve (AUC) and RMR of total symptom score (TSS) AUC, and the secondary outcomes are mean placebo VL AUC, mean placebo VL at peak, time to mean placebo peak VL, mean placebo TSS AUC, and time to mean placebo peak TSS. We used random-effects meta-analysis, except for time to mean peak VL and time to mean peak TSS, where descriptive statistics were summarised.</p><p><strong>Findings: </strong>Number of studies varied across measures, from 4 (144 subjects in total) to 7 (247 subjects in total). Overall, relative mean reductions of 54% (95% CI: 32%-76%, I² = 91%) and 76% (95% CI: 61%-91%, I² = 21%) are observed in VL AUC and TSS AUC, respectively.</p><p><strong>Interpretation: </strong>Assessment based on our primary outcomes showed, on average, a 54% reduction in VL AUC with significant heterogeneity between these studies. In contrast, the TSS AUC showed a greater average reduction of 76%, with much lower heterogeneity indicating more consistent results across studies for this measure. Our findings inform researchers on disease course and VL kinetics, critical data needed for designing RSV treatment studies and understanding implications in clinical practice.</p><p><strong>Funding: </strong>This study was supported by Pfizer Inc.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"117 ","pages":"105765"},"PeriodicalIF":9.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186769","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":"Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron disease.","authors":"Cory J Holdom, Rakesh Pilkar, Christine C Guo, Ruben P A van Eijk, Nadia Sethi, Robert D Henderson, Shyuan T Ngo, Frederik J Steyn","doi":"10.1016/j.ebiom.2025.105779","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105779","url":null,"abstract":"<p><strong>Background: </strong>Motor neuron disease (MND) leads to progressive functional decline, making reliable measures of disease progression critical for patient care and clinical trials. Current clinical outcome measures lack the ability to continuously and objectively track functional decline in daily life of patients with MND. This study assessed and validated wrist-worn accelerometry outcome measures for continuous monitoring in MND, with the potential to refine clinical trial outcomes.</p><p><strong>Methods: </strong>This longitudinal study included 95 patients with MND who wore an ActiGraph GT9X Link device on their non-dominant wrist for 8 days, with follow-up every 3-4 months. Accelerometer data were processed using ActiLife and GGIR. Joint models were used to simultaneously investigate the longitudinal change in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and accelerometer-derived outcomes alongside their relationship with overall survival. Sample size estimates for clinical trials were generated using both accelerometer- and ALSFRS-R-based outcomes, and principal component analysis (PCA) explored outcome relationships.</p><p><strong>Findings: </strong>Accelerometer outcomes showed a slower rate of decline (-0.03 to -0.07 SD/month) compared to ALSFRS-R (-0.10 SD/month) and had stronger correlations with ALSFRS-R motor subdomains (partial r: 0.60-0.73). PCA revealed that longitudinal measures of accelerometry were distinct from the ALSFRS-R, highlighting the complementary nature of these measures. Peak 6-min activity predicted smaller clinical trial sample sizes for studies over 12 months. Accelerometer-derived outcomes were not significantly associated with survival.</p><p><strong>Interpretation: </strong>Wrist-worn accelerometry offers a practical solution for continuous monitoring in MND, complementing ALSFRS-R. Measures of peak performance, and specifically peak 6-min activity shows promise, potentially reducing sample sizes and improving disease tracking over longer duration studies. Further refinement and validation are needed to adopt actigraphy measures as clinical assessment outcomes.</p><p><strong>Funding: </strong>This study was supported by Wesley Medical Research (2016-32), the Honda Foundation, Motor Neurone Disease Research Australia, and FightMND. CJH received a Higher Degree Research Scholarship from UQ. STN received support from the Scott Sullivan Fellowship (MND and Me Foundation/RBWH Foundation), a FightMND Mid-Career Fellowship, and the AIBN.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"117 ","pages":"105779"},"PeriodicalIF":9.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186768","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":"Long-term outcomes of patients with pre-existing coronary artery disease after SARS-CoV-2 infection.","authors":"Roham Hadidchi, Porsche Lee, Shawn Qiu, Sagar Changela, Sonya Henry, Tim Q Duong","doi":"10.1016/j.ebiom.2025.105778","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105778","url":null,"abstract":"<p><strong>Background: </strong>The long-term outcomes of patients with pre-existing coronary artery disease (CAD) after SARS-CoV-2 infection are unknown.</p><p><strong>Methods: </strong>Patients with pre-existing CAD were classified as COVID+ or COVID- based on the polymerase-chain-reaction test in the Montefiore Health System between March 11, 2020, and January 12, 2024. The final cohorts comprised 1380 hospitalised with COVID-19, 1702 non-hospitalised with COVID-19, 7264 contemporary COVID- controls, and 8492 historical controls (January 1, 2016-December 31, 2019). Primary outcomes were all-cause mortality, new-onset congestive heart failure (CHF), myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE). Cox and Fine-Gray regression models with multivariate adjustment, propensity matching, and inverse probability weighting were applied. Outcomes were also analysed with respect to inflammatory and haematologic biomarkers obtained during acute infection.</p><p><strong>Findings: </strong>Compared to contemporary controls, patients hospitalised with COVID-19, but not patients not hospitalised with COVID-19, had higher future risk of MACE (adjusted HR = 1.58 [1.38, 1.80]), mortality, CHF, MI, and stroke up to four years post-infection (p < 0.05). Analysis using propensity-score matching and inverse probability weighting corroborated the results of multivariate regression. Sensitivity analyses using historical controls and a cohort without excluding early death or loss to follow-up showed consistent results. Among patients hospitalised for COVID-19, elevated neutrophil-to-lymphocyte ratio, ferritin, D-dimer, creatinine, low haemoglobin, and abnormal platelets were associated with increased risk for MACE.</p><p><strong>Interpretation: </strong>Severe COVID-19 is associated with long-term cardiovascular risk in patients with pre-existing CAD. Abnormal biomarkers during acute infection were associated with increased risk for MACE. These findings underscore the need for monitoring for cardiovascular risk in patients with pre-existing CAD.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105778"},"PeriodicalIF":9.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180561","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":"Paroxysmal cortical slowing linked to drug-resistant epilepsy.","authors":"Yonatan Serlin, Hamza Imtiaz, Tamir Avigdor, Anna Minarik, Sina Lash, Timothy Bardouille, Ben Whatley, Kristin M Ikeda, Dan Z Milikovsky, Sara K Inati, Theodor Rüber, Rainer Surges, Attila Rácz, Alon Friedman","doi":"10.1016/j.ebiom.2025.105780","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105780","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal slow wave events (PSWEs), defined as electroencephalography (EEG) segments where the median power frequency falls below 6 Hz for ≥5 s, have been shown to predict epilepsy in patients with a first seizure. We evaluated the prevalence and localisation of PSWEs in large independent EEG datasets, exploring their potential as biomarkers for drug-resistant epilepsy (DRE).</p><p><strong>Methods: </strong>An exploratory analysis used 1064 participants from the Temple University EEG corpus, comparing patients with epilepsy (N = 903) with participants with seizure-mimics and normal EEGs (N = 161). Validation analysis used an independent cohort from Bonn University, comprising drug-responsive (N = 51) and patients with DRE (N = 44).</p><p><strong>Findings: </strong>In the exploratory analysis, the proportion of time PSWEs were detected was longer in epilepsy compared with participants without epilepsy (P < 0.0001). Analyses of aetiology and EEG localisation revealed that PSWEs were most prolonged in patients with reported focal epilepsy (P = 0.004), particularly with temporal lobe involvement (P = 0.005). Patients with DRE had prolonged time in PSWEs (P = 0.005), corresponding with an increased risk of refractoriness (OR = 1.9; 95% CI 1.2-2.9). Validation analysis confirmed these findings, with prolonged PSWEs in DRE vs. drug-responsive patients (P < 0.0001, AUC = 0.829). Based on the cutoff established in the exploratory cohort, prolonged time in PSWEs in the validation cohort was associated with increased DRE risk (OR = 5.14, 95% CI 2.1-12.3). In patients with poor surgical outcomes (Engel IB-IV, N = 13), pre-surgical EEGs showed prolonged time in PSWEs compared with Engel IA (N = 24, P = 0.038).</p><p><strong>Interpretation: </strong>Analysis of 1159 EEGs from two independent cohorts demonstrated that PSWEs are more prevalent and prolonged in patients with focal epilepsy and may indicate a lack of therapeutic response.</p><p><strong>Funding: </strong>The Canadian Institutes of Health Research (168164, 180636).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105780"},"PeriodicalIF":9.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180644","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":"Radiomic and proteomic signatures of body mass index on brain ageing and Alzheimer's-like patterns of brain atrophy.","authors":"Filippos Anagnostakis, Michail Kokkorakis, Keenan A Walker, Ioanna Skampardoni, Junhao Wen, Guray Erus, Duygu Tosun, Vasiliki Tassopoulou, Yuhan Cui, Sindhuja T Govindarajan, Dhivya Srinivasan, Randa Melhem, Elizabeth Mamourian, Haochang Shou, Ilya M Nasrallah, Christos S Mantzoros, Christos Davatzikos","doi":"10.1016/j.ebiom.2025.105763","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105763","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The impact of high body mass index (BMI) states and associated proteomic factors on brain ageing and Alzheimer's disease (AD) remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We sought to evaluate machine learning (ML)-based neuroimaging markers of brain age and AD-like brain atrophy in participants with obesity or overweight without diagnosed cognitive impairment (WODCI), in a harmonised study of 46,288 participants in 15 studies (the Imaging-Based Coordinate System for Aging and Neurodegenerative Diseases (iSTAGING) consortium). We also assessed the association between cognition, serum proteins, and brain ageing indices. Data were acquired between 1999 and 2020 and analysed from November 2024 onwards.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The study comprised 46,288 participants, including 24,897 females and 21,391 males, with a mean age of 64.33 years (SD = 8.13) and a mean BMI of 26.81 kg/m&lt;sup&gt;2&lt;/sup&gt; (SD = 4.49). The results demonstrate that the impact of obesity on brain ageing, and AD-like brain atrophy is weaker with increasing age and is significantly pronounced in males compared to females. Additionally, in males, obesity was significantly associated with approximately 2 additional years of brain ageing compared to normal weight and 1 additional year compared to the overweight group. Males with overweight also showed higher brain ageing values (8 additional months) than males with normal weight. Regarding AD-like brain atrophy, males with obesity displayed higher AD-like brain atrophy than males with normal weight, but females with normal weight showed higher AD-like brain atrophy than females with overweight. Sex differences within the same BMI categories were observed, with males exhibiting increased brain ageing compared to females, in obesity (1 additional year) and overweight groups (3 additional months). Higher AD-like brain atrophy was observed in males with overweight than in females with overweight. Females with normal weight displayed increased brain ageing (8 additional months) and AD-like brain atrophy relative to males with normal weight. In both retrospective and cross-sectional proteomics studies, five and eight proteins out of 1463 proteins were significantly (positively or negatively) associated with brain ageing and 1-SD BMI change (SD = 4.2 kg/m&lt;sup&gt;2&lt;/sup&gt;), respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The findings demonstrate that higher BMI states are associated with accelerated brain ageing and AD-like atrophy, particularly in males, while females with normal weight demonstrated higher brain ageing and AD-like atrophy than males with normal weight. Moreover, the impact of obesity on brain ageing and AD-like brain atrophy becomes weaker with increasing age. Further research is needed to investigate sex-specific mechanisms by which weight gain influences brain ageing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;National Institute on Aging's Intramural Research Program, National Institute on Ag","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105763"},"PeriodicalIF":9.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173152","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":"Automatic identification of Parkinsonism using clinical multi-contrast brain MRI: a large self-supervised vision foundation model strategy.","authors":"Xueling Suo, Mengyao Chen, Li Chen, Chunyan Luo, Graham J Kemp, Su Lui, Huaiqiang Sun","doi":"10.1016/j.ebiom.2025.105773","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105773","url":null,"abstract":"<p><strong>Background: </strong>Valid non-invasive biomarkers for Parkinson's disease (PD) and Parkinson-plus syndrome (PPS) are urgently needed. Based on our recent self-supervised vision foundation model the Shift Window UNET TRansformer (Swin UNETR), which uses clinical multi-contrast whole brain MRI, we aimed to develop an efficient and practical model ('SwinClassifier') for the discrimination of PD vs PPS using routine clinical MRI scans.</p><p><strong>Methods: </strong>We used 75,861 clinical head MRI scans including T1-weighted, T2-weighted and fluid attenuated inversion recovery imaging as a pre-training dataset to develop a foundation model, using self-supervised learning with a cross-contrast context recovery task. Then clinical head MRI scans from n = 1992 participants with PD and n = 1989 participants with PPS were used as a downstream PD vs PPS classification dataset. We then assessed SwinClassifier's performance in confusion matrices compared to a comparative self-supervised vanilla Vision Transformer (ViT) autoencoder ('ViTClassifier'), and to two convolutional neural networks (DenseNet121 and ResNet50) trained from scratch.</p><p><strong>Findings: </strong>SwinClassifier showed very good performance (F1 score 0.83, 95% confidence interval [CI] [0.79-0.87], AUC 0.89) in PD vs PPS discrimination in independent test datasets (n = 173 participants with PD and n = 165 participants with PPS). This self-supervised classifier with pretrained weights outperformed the ViTClassifier and convolutional classifiers trained from scratch (F1 score 0.77-0.82, AUC 0.83-0.85). Occlusion sensitivity mapping in the correctly-classified cases (n = 160 PD and n = 114 PPS) highlighted the brain regions guiding discrimination mainly in sensorimotor and midline structures including cerebellum, brain stem, ventricle and basal ganglia.</p><p><strong>Interpretation: </strong>Our self-supervised digital model based on routine clinical head MRI discriminated PD vs PPS with good accuracy and sensitivity. With incremental improvements the approach may be diagnostically useful in early disease.</p><p><strong>Funding: </strong>National Key Research and Development Program of China.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105773"},"PeriodicalIF":9.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173129","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":"Induction of haemodynamic travelling waves by glial-related vasomotion in a rat model of neuroinflammation: implications for functional neuroimaging.","authors":"Mickaël Pereira, Marine Droguerre, Marco Valdebenito, Louis Vidal, Guillaume Marcy, Sarah Benkeder, Paul Marchal, Jean-Christophe Comte, Olivier Pascual, Luc Zimmer, Benjamin Vidal","doi":"10.1016/j.ebiom.2025.105777","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105777","url":null,"abstract":"<p><strong>Background: </strong>Cerebral haemodynamics are crucial for brain homoeostasis and serve as a key proxy for brain activity. Although this process involves coordinated interaction between vessels, neurons, and glial cells, its dysregulation in neuroinflammation is not well understood.</p><p><strong>Methods: </strong>We used in vivo mesoscopic functional ultrasound imaging to monitor cerebral blood volume changes during neuroinflammation in male rats injected with lipopolysaccharide (LPS) in the visual cortex, under resting-state or visual stimulation, combined to advanced ex vivo techniques for glial cell reactivity analysis.</p><p><strong>Findings: </strong>Cortical neuroinflammation induced large oscillatory haemodynamic travelling waves in the frequency band of vasomotion (∼0.1 Hz) in both anaesthetized and awake rats. Vasomotor waves travelled through large distances between adjacent penetrating vessels, spanning the entire cortex thickness, and even extending to subcortical areas. Moreover, vasomotion amplitude correlated with microglial morphology changes and was significantly reduced by astrocytic toxins, suggesting that both microglia and astrocytes are involved in the enhancement of vasomotion during neuroinflammation. Notably, functional connectivity was increased under this oscillatory state and functional hyperaemia was exacerbated.</p><p><strong>Interpretation: </strong>These findings further reveal the spatiotemporal properties of cerebral vasomotion and suggest this is a major component of brain haemodynamics in pathological states. Moreover, reactive microglia and astrocytes are participating to increase vasomotion during neuroinflammation. For the field of functional neuroimaging, our results advocate for considering 0.1 Hz haemodynamic oscillations as an important complement to traditional measurements, particularly in neuroinflammatory conditions. Indeed, brain haemodynamics may provide insights not only into neuronal activity but also glial reactivity.</p><p><strong>Funding: </strong>Supported by ANR (\"LabCom-NI2D\", \"Labex Cortex\") and Auvergne-Rhône-Alpes Region (\"BI2D\").</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105777"},"PeriodicalIF":9.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173132","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":"Quantifying Flavin mononucleotide: an internationally validated methodological approach for enhanced decision making in organ transplantation.","authors":"Keyue Sun, Chunbao Jiao, Rebecca Panconesi, Sangeeta Satish, Omer F Karakaya, Femke H C De Goeij, Tobias Diwan, Khaled Ali, Lorenzo A Cadinu, Beatrice Cazzaniga, Qiang Liu, Yuki Miyazaki, Alejandro Pita, Mazhar Khalil, JaeKeun Kim, Ahmed Hussein, Philipp C Müller, Federico Aucejo, David H C Kwon, Eduardo Fernandes, Jamak Modaresi Esfeh, Jacek Cywinski, Masato Fujiki, Lidong Sun, Antonio Pinna, Philipp Dutkowski, Chase J Wehrle, Robert L Fairchild, David Meierhofer, Jeroen De Jonge, Charles Miller, Koji Hashimoto, Andrea Schlegel","doi":"10.1016/j.ebiom.2025.105761","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105761","url":null,"abstract":"<p><strong>Background: </strong>Increasing donor risk, particularly in liver transplantation, where organs are often marginal, has made dynamic organ preservation techniques and viability assessment essential to safely improve organ quality and increase utilisation. However, existing viability parameters are based on routine clinical assessment in patients with acute liver failure, trauma, or liver resections. These parameters often do not correlate with clinically relevant post-transplant outcomes.</p><p><strong>Methods: </strong>This article presents a detailed protocol for the spectrophotometric quantification of Flavin mononucleotide (FMN), a marker of mitochondrial injury. FMN release from mitochondrial complex I was described many decades ago as the initial sign of ischaemia-reperfusion injury, i.e. when oxygen is reintroduced in ischaemic tissues during organ transplantation or machine perfusion. This study describes the detailed FMN quantification in donor plasma and various fluids obtained during machine perfusion, and discusses confounders, challenges, and the role of individual test components.</p><p><strong>Findings: </strong>FMN quantification was identified as an immediate organ assessment tool, demonstrating a strong correlation with graft survival and other relevant complications after human liver transplantation.</p><p><strong>Interpretation: </strong>The results highlight FMN quantification as a reliable and standardized method for assessing organ viability, offering significant potential for improving organ selection and better utilisation. This method could provide better a predictive value for transplant outcomes compared to existing parameters currently in use.</p><p><strong>Funding: </strong>This research received no external funding but was supported by the Catalyst grant No. CCG0280 at Cleveland Clinic Ohio, U.S. dedicated to A.S.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105761"},"PeriodicalIF":9.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173136","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":"Long-term in vivo monitoring of transplanted mesenchymal stromal cells in colitis mice with magnetic particle imaging.","authors":"Tuo Shao, Zelin Gu, Yuzhu Liu, Xiaoyi Wang, Chao Tang, Nannan Chen, Mengqi Wang, Xueqin Liu, Huanhuan Song, Siye Chen, Weihua Li, Hui Hui, Xiaohua Jia, Hui Mao, Raymond T Chung, Steven Liang, Sidong Xiong, Jie Tian","doi":"10.1016/j.ebiom.2025.105775","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105775","url":null,"abstract":"<p><strong>Background: </strong>The successful development of mesenchymal stromal cells (MSCs)-based therapeutic strategies in inflammatory bowel disease (IBD) hinges on the ability to assess the influence of the administration route, while also tracking the cells' in vivo location, distribution, and long-term viability. Moreover, understanding the biological fate of these cells-particularly their activation, differentiation, and interaction within the host environment-is crucial to optimising their therapeutic potential.</p><p><strong>Methods: </strong>This study explores the use of magnetic particle imaging (MPI) with superparamagnetic iron oxide nanoparticles (SPIONs) to track MSCs in colitis mice. SPION-labelled MSCs were administered through intravenous (IV), intraperitoneal (IP), and intrarectal (IR) routes. MPI was employed to track MSCs.</p><p><strong>Findings: </strong>MPI provided dynamic tracking of MSC distribution, viability, and homing, revealing that IP injections led to more targeted and sustained delivery to inflamed colon tissues, with higher cell survival and efficacy in modulating inflammation. Other administration routes also demonstrated specific distribution patterns, but with shorter retention times. The prolonged survival of MSCs following IP injection may be attributed to the immune environment in the peritoneal cavity, which significantly impacts MSCs, influencing their survival and migration. Further analyses showed that MSCs exposed to inflammatory peritoneal fluid exhibited enhanced homing capabilities, and IFN-γ pretreatment significantly improved MSC retention in the inflamed colon, as detected by MPI/CT imaging.</p><p><strong>Interpretation: </strong>Our findings, observed through MPI, highlight the potential of IP injection as a preferred method for MSC-based therapies, offering strategies to improve treatment outcomes specifically in IBD and potentially in other inflammatory conditions.</p><p><strong>Funding: </strong>The National Natural Science Foundation of China (62027901, 82372144), the Natural Science Foundation of Jiangsu Province (BK20230491), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105775"},"PeriodicalIF":9.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173134","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":"Integrating genetics and transcriptomics to decipher susceptibility genes for risk stratification of gastric cancer and effect modification of Helicobacter pylori treatment.","authors":"Zhou-Yi Yin, Heng-Min Xu, Meng-Yuan Wang, Xin-Ling Wang, Zong-Chao Liu, Yu Jin, Yang Zhang, Jing-Ying Zhang, Tong Zhou, Wei-Cheng You, Kai-Feng Pan, Wen-Qing Li","doi":"10.1016/j.ebiom.2025.105767","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105767","url":null,"abstract":"<p><strong>Background: </strong>In a transcriptome-wide association study, we deciphered susceptibility genes that may predict gastric cancer (GC) risk and modify the effects of Helicobacter pylori (H. pylori) treatment.</p><p><strong>Methods: </strong>Genetically predicted expression models of 4518 genes were developed based on the GTEx and applied to a nested case-control study (935 GCs and 1869 controls) of the Mass Intervention Trial in Linqu, Shandong Province (MITS), with genes associated with GC risk further validated in BioBank Japan (7921 GCs and 159,201 controls). Transcriptome risk scores (TRSs) integrating key genes were constructed, utilizing imputed transcriptomes from the Shandong Intervention Trial (SIT) and UK Biobank, and observed transcriptomes from the National Upper Gastrointestinal Cancer Early Detection (UGCED) program. We also examined whether TRS may modify the association of H. pylori infection and anti-H. pylori treatment with GC risk.</p><p><strong>Findings: </strong>Integrating 11 independent GC-associated genes identified based on the MITS (FDR-q < 0.05) and BioBank Japan (P < 0.05), the TRS demonstrated a dose-dependent association with an elevated risk of incident GC in both the SIT (P-trend = 0.003) and UK Biobank (P-trend = 0.008), and exhibited an upward trend as gastric lesions progressed based on the UGCED program (P-trend = 5.01 × 10^-4). In the SIT, the increased risk of GC associated with H. pylori infection (P-interaction = 0.03) and beneficial effect of successful H. pylori eradication (P-interaction = 0.05) were significant for individuals with high TRSs.</p><p><strong>Interpretation: </strong>We identified a gene panel which may predict GC risk across populations of multiple ancestries, which offers important insights into GC risk stratification and presents a precision approach to primary prevention.</p><p><strong>Funding: </strong>Funders are listed in the Acknowledgement.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"116 ","pages":"105767"},"PeriodicalIF":9.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155935","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}