tbuckley/cabot-search huggingface dataset:
Characterizing long-term neurocognitive outcomes through diffusion tensor imaging in childhood brain tumor survivors
Authors: Ryan T Oglesby, Chathurangi H Pathiravasan, Elizabeth Olatunji, Leslie Chang, Jill Chotiyanonta, Yuto Uchida, Junghoon Lee, Kenichi Oishi, Rachel Peterson, Sahaja Acharya
Journal: Neuro-Oncology (2025)

Abstract Background Diffusion tensor imaging (DTI) can probe the longitudinal microstructural integrity and development of the brain. This study characterizes the relationship between long-term neurocognition and changes in fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum and hippocampus in childhood brain tumor survivors. Methods Patients diagnosed with a brain tumor at &amp;lt; 18 years of age with ≥ 2 neurocognitive assessments retrospectively paired with DTI were eligible. Multi-trajectory modeling clustered patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed index and working memory. Linear mixed models were used to determine whether patient clusters were associated with change in MD and FA. Patient clusters were compared to healthy subjects. Results From 2014 to 2022, 68 patients with 464 neurocognitive assessments paired with DTI and 80 healthy subjects were included. Multi-trajectory modeling identified two patient clusters: (1) low-performance, with declining scores below the normative mean, and (2) normal-performance. Compared to the low-performance group, the normal-performance group demonstrated greater increase in FA and greater decrease in MD within the corpus callosum and hippocampus, respectively. This pattern was consistent across multiple white matter tracts, highlighting global differences between the groups. Directional change of FA and MD observed in healthy subjects mirrored that of the normal-performance group, but was opposite to that of the low-performance group. Conclusion Compared to the normal performance group, the low-performance group demonstrated reduced white matter microstructural integrity and higher mean diffusivity in the hippocampus over time, opposite to what is observed in normally developing children. This suggests aberrant neurodevelopment may contribute to late neurocognitive impairment.
Diffusion and contrast-enhancement MRI phenotypes associated with immune checkpoint inhibitor exposure and with immune cell infiltration in brain metastases
Authors: Francesco Sanvito, Gianluca Nocera, Zexi Wang, Eileen Shiuan, Lu Sun, Sonoko Oshima, Asher Kim, Irina Kryukov, Guowen Shao, Nicholas S Cho, Noriko Salamon, Benjamin M Ellingson, Robert Prins, Won Kim, Jingwen Yao
Journal: Neuro-Oncology (2025)

Abstract Background MRI-derived apparent diffusion coefficient (ADC) and contrast-enhancement (CE) may represent non-invasive biomarkers to evaluate microstructural tissue changes and histopathological immune cell infiltration induced by immune checkpoint inhibitors (ICI). Methods 125 lesions across 93 patients were analyzed. ADC (reflecting water diffusivity) and CE T1-subtraction maps (reflecting blood-brain barrier permeability) tumor values were used for bivariate histograms of ADC and CE, and to quantify voxel fractions belonging to highADC-highCE and lowADC-lowCE quadrants. The association between ICI exposure and voxel frequency in ADC-CE quadrants was evaluated with multivariate mixed-effects models accounting for corticosteroid exposure and other variables. In a subset of patients (n=23), the association between immune cell counts (CD45+ cell density) from tissue samples and ADC-CE phenotypes was tested. Results ICI and corticosteroid exposure were associated with distinct ADC-CE phenotypes on bivariate histograms. ICI-exposed lesions showed significantly higher voxel frequency in the highADC-highCE quadrant (p&amp;lt;0.001) and lower voxel frequency in the lowADC-lowCE quadrant (p&amp;lt;0.01), compared to ICI-naïve lesions. Multivariate analyses confirmed that ICI exposure was an independent determinant of higher voxel frequency in the highADC-highCE quadrant (p=0.001) and lower voxel frequency in the lowADC-lowCE quadrant (p=0.01) in absence of corticosteroid treatment. Corticosteroid usage significantly influenced the relationship between ADC-CE phenotypes and ICI exposure. Voxel frequency in ADC-CE quadrants was correlated with CD45+ cell density in histopathology (partial ρ=0.56 p=0.01 for highADC-highCE, partial ρ=–0.64 p&amp;lt;0.01 for lowADC-lowCE). Conclusions ADC-CE phenotypes are associated with ICI exposure and immune cell infiltration in BM, representing potential non-invasive markers to monitor ICI-induced pathophysiological changes.
A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma
Authors: Patrick Y Wen, Andrea Manzanera, Caroline Duault, Edgar Gonzalez-Kozlova, Lenika Lopez, Stuart A Grossman, Xiaobu Ye, Joy Fisher, Ian Lee, Tobias Walbert, James Snyder, Steven Brem, Arati Desai, Stephen J Bagley, Chandana Kakani, Roy Strowd, Stephen Tatter, Adrian Laxton, Glenn Lesser, Nduka Amankulor, Frank Lieberman, Jan Drappatz, Megan Mantica, Dan Triggs, Cara Haymaker, Ignacio I Wistuba, Gheath al-Atrash, Julia Mendoza Perez, Andrew Futreal, Latasha D Little, M D Habibul Islam, Dzifa Duose, Peixin Jiang, Alexandre Reuben, Sean E Lawler, Mina Pichavant, Andrew Gentles, Sean Bendall, Alex Kong, Christine Camacho, Diane Del Valle, Seunghee Kim-Schulze, Sacha Gnjatic, Elad Sharon, M Oskar Nowicki, Pierpaolo Peruzzi, Doug Lane, Estuardo Aguilar-Cordova, Laura K Aguilar, Garrett Nichols, Jessica Dwyer, Paul Peter Tak, Holden Maecker, Francesca Barone, E Antonio Chiocca
Journal: Neuro-Oncology (2025)

Abstract Background For newly diagnosed glioblastoma (GBM), combination of surgical upfront immunotherapy with aglatimagene besadenovec (CAN-2409), followed by chemoradiation and then adjuvant nivolumab has not been tested. The aim of this study was to test the safety of this regimen and determine metrics of immune activation that may correlate with clinical outcomes. Methods 41 patients with suspected newly diagnosed GBM by imaging were enrolled in this multi-institutional, open label, phase 1b clinical trial before surgical resection. Frozen section confirmation of high-grade glioma was required for administration of aglatimagene besadenovec. This was then followed with chemoradiation and adjuvant nivolumab. Tumor and blood were assayed for genetic and immune markers before and during treatment. Results The regimen was well tolerated and generated measurable immune activation. Factors linked to survival were identified, such as baseline mutated gene pairs (e.g. MED15/ HRC), tumor immune cell composition, and changes in systemic cytokine, immune cells, and T cell diversity. The most significant serial systemic immune changes were observed in a long-term survivor subset of patients with gross total resection (GTR)/ methylated methylguanine methyltransferase (MGMT) promoter tumors. Median overall survival (mOS) in these patients was 30.6 months, while it was less for patients with unmethylated or subtotal resections. Conclusions These findings suggest the opportunity for patient stratification and the potential for more durable antitumor immune responses in future clinical trials of this multimodal standard of care and combined immunotherapy regimen. ClinicalTrials.gov identifier: NCT03576612.
Spatial lipidomics reveals sphingolipid metabolism as anti-fibrotic target in the liver
Authors: Aleksandra Gruevska, Jack Leslie, Elena Perpin Án, Hannah Maude, Amy L Collins, Sophia Johnson, Laila Evangelista, Eleanor Sabey, Jeremy French, Steven White, John Moir, Stuart M Robinson, Wasfi Alrawashdeh, Rohan Thakkar, Roberta Forlano, Pinelopi Manousou, Robert Goldin, David Carling, Matthew Hoare, Mark Thursz, Derek A Mann, Inˆes Cebola, Joram M Posma, Niloufar Safinia, Fiona Oakley, Zoe Hall
Journal: Metabolism (2025)
Dissecting the genetic architecture of key agronomic traits in lettuce using a MAGIC population
Authors: Hongyun Chen, Jiongjiong Chen, Ruifang Zhai, Dean Lavelle, Yue Jia, Qiwei Tang, Ting Zhu, Menglu Wang, Zedong Geng, Jianzhong Zhu, Hui Feng, Junru An, Jiansheng Liu, Weibo Li, Shenzhao Deng, Wandi Wang, Weiyi Zhang, Xiaoyan Zhang, Guangbao Luo, Xin Wang, Sunil Kumar Sahu, Huan Liu, Richard Michelmore, Wanneng Yang, Tong Wei, Hanhui Kuang
Journal: Genome biology (2025)

Lettuce is a globally important leafy vegetable that exhibits diverse horticultural types and strong population structure, which complicates genetic analyses. To address this challenge, we develop the first multi-parent, advanced generation inter-cross (MAGIC) population for lettuce using 16 diverse founder lines. Whole-genome sequencing of the 16 founder lines and 381 inbred progeny reveal minimal population structure, enabling informative genome-wide association studies (GWAS). GWAS of the lettuce MAGIC population identifies numerous loci associated with key agricultural traits, including 51 for flowering time, 11 for leaf color, and 5 for leaf shape. Notably, loss-of-function mutations in the LsphyB and LsphyC genes, encoding phytochromes B and C, dramatically delay flowering in lettuce, which is in striking contrast to many other plant species. This unexpected finding highlights the unique genetic architecture controlling flowering time in lettuce. The wild-type LsTCP4 gene plays critical roles in leaf flatness and its expression level is negatively correlated with leaf curvature. Additionally, a novel zinc finger protein (ZFP) gene is required for the development of lobed leaves; a point mutation leads to its loss of function and consequently converted lobed leaves to non-lobed leaves, as exhibited by most lettuce cultivars. The MAGIC population's lack of structure and high mapping resolution enables the efficient dissection of complex traits. The identified loci and candidate genes provide significant genetic resources for improving agronomic performance and leaf quality in lettuce.
aurora: a machine learning gwas tool for analyzing microbial habitat adaptation
Authors: Dalimil Bujdoš, Jens Walter, Paul W. O’Toole
Journal: Genome biology (2025)

Abstract A primary goal of microbial genome-wide association studies is identifying genomic variants associated with a particular habitat. Existing tools fail to identify known causal variants if the analyzed trait shaped the phylogeny. Furthermore, due to inclusion of allochthonous strains or metadata errors, the stated sources of strains in public databases are often incorrect, and strains may not be adapted to the habitat from which they were isolated. We describe a new tool, aurora , that identifies autochthonous strains and the genes associated with habitats while acknowledging the potential role of the habitat adaptation trait in shaping phylogeny.
ASPM mediates nuclear entrapment of FOXM1 via liquid-liquid phase separation to promote progression of hepatocarcinoma
Authors: Xunliang Jiang, Jun Liu, Ke Wang, Jianyong Sun, Huilong Yin, Yu Jiang, Yongkang Liu, Ningbo Wang, Xiaochen Ding, Pu Gao, Lin Li, Xiang Zhang, Jipeng Li, Rui Zhang
Journal: Genome biology (2025)

Fork-head box protein M1 (FOXM1) plays critical roles in development and progression of multiple cancers, including hepatocellular carcinoma (HCC). However, the exact regulatory hierarchy of FOXM1 remains unclear. Here, a genome-wide screen is performed to identify intranuclear proteins that promote FOXM1 transcription activity via liquid–liquid phase separation (LLPS). Abnormal spindle-like microcephaly associated (ASPM) is identified to interact with FOXM1 protein via LLPS and enhance its stability by preventing proteasome-mediated degradation. ChIP-sequencing data show ASPM and FOXM1 co-occupy the promoters of multiple genes to promote their transcription, enhancing FOXM1-driven oncogenic progression. In functional experiments, inhibition of ASPM suppresses tumor growth of HCC cells in vivo and in vitro, while overexpression of ASPM has opposite effects. Importantly, reconstitution of FOXM1 partially compensates for the weakened proliferative capacity of HCC cells caused by ASPM silencing. Intriguingly, FOXM1 binds to the promoter region of ASPM and transcriptionally activates ASPM expression in HCC cells. Furthermore, we find that a higher co-expression of ASPM and FOXM1 significantly correlates with poor prognosis in HCC patients. It indicates a double positive feedback loop between ASPM and FOXM1 which coordinately promotes the aggressive progression of HCC. Collectively, we demonstrate that LLPS and transcriptional regulation form an oncogenic double positive feedback loop between ASPM and FOXM1. This provides a rationale strategy to treat HCC by targeting this mechanism.
Current Drug Treatment for Acute and Recurrent Pericarditis
Authors: Aldo Bonaventura, Davide Santagata, Alessandra Vecchié, Antonio Abbate
Journal: Drugs (2025)

Pericarditis is the most frequent pericardial disease and presents with a relatively benign course when treated according to guideline-directed therapies at first presentation. Recurrence is the most frequent complication and may occur more frequently after a first episode, in patients with autoimmune etiology, in patients who received glucocorticoids, or after rapid (i.e., within 1 month) tapering of anti-inflammatory drugs. The therapeutic armamentarium for pericarditis includes high-dose nonsteroidal anti-inflammatory drugs (NSAIDs) that are tapered rapidly once symptoms are controlled. Colchicine is necessary to both relieve symptoms and reduce the rate of recurrences and is continued for at least 3-6 months. Low- to moderate-dose glucocorticoids are reserved for patients with a first recurrence for which NSAIDs and colchicine failed and/or who have an autoimmune disorder, with a slow tapering. Interleukin-1 blockers-anakinra, rilonacept, and goflikicept-are used as a third-line option in patients who cannot come off glucocorticoids or as second-line therapy after NSAIDs and colchicine in patients with contraindications to glucocorticoids or in those with high-risk features (i.e., multiple episodes, markedly elevated inflammatory markers, or extensive abnormalities at pericardial imaging) in whom treatment with glucocorticoids is unlikely to succeed.
Recent applications of EEG-based brain-computer-interface in the medical field
Authors: Xiu-Yun Liu, Wen-Long Wang, Miao Liu, Ming-Yi Chen, Tânia Pereira, Desta Yakob Doda, Yu-Feng Ke, Shou-Yan Wang, Dong Wen, Xiao-Guang Tong, Wei-Guang Li, Yi Yang, Xiao-Di Han, Yu-Lin Sun, Xin Song, Cong-Ying Hao, Zi-Hua Zhang, Xin-Yang Liu, Chun-Yang Li, Rui Peng, Xiao-Xin Song, Abi Yasi, Mei-Jun Pang, Kuo Zhang, Run-Nan He, Le Wu, Shu-Geng Chen, Wen-Jin Chen, Yan-Gong Chao, Cheng-Gong Hu, Heng Zhang, Min Zhou, Kun Wang, Peng-Fei Liu, Chen Chen, Xin-Yi Geng, Yun Qin, Dong-Rui Gao, En-Ming Song, Long-Long Cheng, Xun Chen, Dong Ming
Journal: Military Medical Research (2025)

Abstract Brain-computer interfaces (BCIs) represent an emerging technology that facilitates direct communication between the brain and external devices. In recent years, numerous review articles have explored various aspects of BCIs, including their fundamental principles, technical advancements, and applications in specific domains. However, these reviews often focus on signal processing, hardware development, or limited applications such as motor rehabilitation or communication. This paper aims to offer a comprehensive review of recent electroencephalogram (EEG)-based BCI applications in the medical field across 8 critical areas, encompassing rehabilitation, daily communication, epilepsy, cerebral resuscitation, sleep, neurodegenerative diseases, anesthesiology, and emotion recognition. Moreover, the current challenges and future trends of BCIs were also discussed, including personal privacy and ethical concerns, network security vulnerabilities, safety issues, and biocompatibility.
Use of inhaled corticosteroids in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)
Authors: Jennifer Pollock, Eva Polverino, Raja Dhar, Katerina Dimakou, Letizia Traversi, Apostolos Bossios, Charles Haworth, Michael R Loebinger, Anthony De Soyza, Montserrat Vendrell, Pierre Regis Burgel, Pontus Mertsch, Melissa Jane McDonnell, Sabina Skgrat, Luis Maiz-Carro, Oriol Sibila, Menno van der Eerden, Paula Kauppi, Adam T Hill, Robert Wilson, Branislava Milenkovic, Rosario Menéndez, Marlene Murris, Megan L Crichton, Sermin Borecki, Dusanka Obradovic, Muhammed Irfan, Venera Eshenkulova, Adam Nowinski, Adelina Amorim, Antoni Torres, Natalie Lorent, Tobias Welte, Francesco Blasi, Eva Van Braeckel, Josje Altenburg, Michal Shteinberg, Wim Boersma, Joseph Stuart Elborn, Stefano Aliberti, Felix C Ringshausen, Pieter Goeminne, James D Chalmers
Journal: Thorax (2025)

Introduction Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe. Methods Patients with bronchiectasis were enrolled into the European Bronchiectasis Registry from 2015 to 2022. Patients were grouped into ICS users and non-users at baseline and clinical characteristics associated with ICS use were investigated. Patients were followed up for clinical outcomes of exacerbation, hospitalisation and mortality for up to 5 years. We evaluated if elevated blood eosinophil counts (above the laboratory upper limit of normal) modified the effect of ICS on exacerbations. Results 19 324 patients were included for analysis and 10 109 (52.3%) were recorded as being prescribed ICS at baseline. After exclusion of patients with a history of asthma, COPD and/or ABPA, 3174/9715 (32.7%) patients with bronchiectasis were prescribed ICS. Frequency of ICS use varied across countries, ranging from 17% to 85% of included patients. ICS users had more severe disease, with significantly worse lung function, higher Bronchiectasis Severity Index scores and more frequent exacerbations at baseline (p&lt;0.0001). Overall, ICS users did not have a reduced risk of exacerbation or hospitalisation during follow-up, but a significant reduction in exacerbation frequency was observed in the subgroup of ICS users with elevated blood eosinophil counts (relative risk 0.70, 95% CI 0.59 to 0.84, p&lt;0.001). Conclusion ICS use is common in bronchiectasis, including in those not currently recommended ICS according to bronchiectasis guidelines. ICS use may be associated with reduced exacerbation frequency in patients with elevated blood eosinophils.
Functional genomic profiling of O-GlcNAc reveals its context-specific interplay with RNA polymerase II
Authors: Sofia Rucli, Nicolas Descostes, Yulia Ermakova, Urvashi Chitnavis, Jeanne Couturier, Ana Boskovic, Matthieu Boulard
Journal: Genome biology (2025)

Abstract Background How reversible glycosylation of DNA-bound proteins acts on transcription remains scarcely understood. O-linked β-N-acetylglucosamine (O-GlcNAc) is the only known form of glycosylation modifying nuclear proteins, including RNA polymerase II (RNA Pol II) and many transcription factors. Yet, the regulatory function of the O-GlcNAc modification in mammalian chromatin remains unclear. Results Here, we combine genome-wide profiling of O-GlcNAc-modified proteins with perturbations of intracellular glycosylation, RNA Pol II-degron, and super-resolution microscopy. Genomic profiling of O-GlcNAc-modified proteins shows a non-random distribution across the genome, with high densities in heterochromatin regions as well as on actively transcribed gene promoters. Large-scale intersection of the O-GlcNAc signal at promoters with public ChIP-seq datasets identifies a high overlap with RNA Pol II and specific cofactors. Knockdown of O-GlcNAc Transferase ( Ogt ) shows that most direct target genes are downregulated, supporting a global positive role of O-GlcNAc on the transcription of cellular genes. Rapid degradation of RNA Pol II results in the decrease of the O-GlcNAc levels at promoters encoding transcription factors and DNA modifying enzymes. RNA Pol II depletion also unexpectedly causes an increase of O-GlcNAc levels at a set of promoters encoding for the transcription machinery. Conclusions This study provides a deconvoluted genomic profiling of O-GlcNAc-modified proteins in murine and human cells. Perturbations of O-GlcNAc or RNA Pol II uncover a context-specific reciprocal functional interplay between the transcription machinery and the O-GlcNAc modification.
Light‐Activated Pharmacological Tools for Exploring the Cholinergic System
Authors: Alessio Colleoni, Giulia Galli, Clelia Dallanoce, Marco De Amici, Pau Gorostiza, Carlo Matera
Journal: Medicinal Research Reviews (2025)

ABSTRACT Cholinergic transmission plays a critical role in both the central and peripheral nervous systems, affecting processes such as learning, memory, and inflammation. Conventional cholinergic drugs generally suffer from poor selectivity and temporal precision, leading to undesired effects and limited therapeutic efficacy. Photopharmacology aims to overcome the limitations of traditional drugs using photocleavable or photoswitchable ligands and spatiotemporal patterns of illumination. Spanning from muscarinic and nicotinic modulators to cholinesterase inhibitors, this review explores the development and application of light‐activated compounds as tools for unraveling the role of cholinergic signaling in both physiological and pathological contexts, while also paving the way for innovative phototherapeutic approaches.