Biology subjects

Ene, C.

Publications and source records attributed to Ene, C..

3 recordsLinked to original sources

bioRxiv2025

Integrated single cell spatial multi-omics landscape of WHO grades 2-4 diffuse gliomas identifies locoregional metabolomic regulators of glioma growth

Diffuse infiltrating gliomas are aggressive tumors of the central nervous system driven by intra-tumoral heterogeneity and aberrant normal-tumor cell-cell interactions. Grade specific and locoregional metabolic dependencies driving aberrant cell-states linked to treatment resistance, seizures and infiltration of gliomas remain elusive. Here, we applied spatial transcriptomics (stRNAseq), imaging mass cytometry (IMC) and mass spectrometry imaging (MSI; metabolites, peptides and glycans) to the core and edge tumor tissue from patients with World Health Organization (WHO) grades 2-4 diffuse infiltrating gliomas including isocitrate dehydrogenase (IDH) mutant oligodendrogliomas (WHO Grades 2 and 3) and IDH wildtype astrocytomas including anaplastic astrocytoma (prior 2016 WHO histological grade 3) and glioblastoma (GBM, WHO grade 4) stRNAseq identified regions-specific differentially expressed genes with significant overall survival implications particularly in IDH wildtype GBM. Integration of stRNA seq and MSI-derived metabolite expression demonstrated enrichment of L-glutamine in SOX4+ Neural progenitor-like (NPC-like) cells and DL-dopamine in GPNMB+ Mesenchymal-like (MES-like) GBM cells at the tumor edge relative to the core. Our results uncover clinically relevant and locoregional cell state-specific metabolites that may contribute to GBM proliferation, infiltration and seizures. This comprehensive pan-diffuse infiltrating glioma multi-omics study could serve as a resource for uncovering region-specific metabolic vulnerabilities encompassing metabolites, glycans and peptides within transcriptionally defined cell states across WHO 2-4 diffuse glioma.

cancer biology↗

bioRxiv2024

Non-Invasive Brain Mapping Localizes Essential Language Function in Surgical Glioma Patients

IntroductionGlioma patients with tumors near critical language regions present significant clinical challenges. Surgeons often lack the tools to understand how each unique surgical approach may impact linguistic ability, leading to subjective decisions and unpredictable outcomes. ObjectiveWe aim to develop an approach that uses data-driven preoperative brain mapping to quantitatively predict the impact of planned resections on long-term language function. MethodsThis study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (nTMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language evaluations pre and postoperatively. The resection of regions identified by preoperative mapping was correlated with persistent postoperative language deficits (PLDs). ResultsThe resection of TMS points did not predict PLDs. However, a TMS point subgroup defined by white matter connectivity significantly predicted PLDs (OR=8.74, p<.01) and exhibited a canonical group-level anatomical distribution of cortical language sites. TMS-derived tracts recapitulated normative group-level patterns of white matter connectivity defined by the Human Connectome Project (HCP). Subcortical resection of TMS tracts predicted PLDs independently of cortical resection (OR=60, p<.001). The resected TMS tract segments in patients with PLDs co-localized with normative, language-associated subcortical pathways, in contrast to the resected TMS tract segments in non-aphasic patients (p<.05). Accordingly, resecting patient- specific co-localizations between TMS tracts and normative tracts in native space predicted PLDs with an accuracy of 94% (OR=134, p<.001). Co-localization between individualized and normative tracts precisely predicted the linguistic performance of a patient intraoperatively in response to direct electrophysiological stimulation of subcortical brain. ConclusionThis study outlines a data-driven brain mapping approach that provides surgical insight by preoperatively predicting the impact of individual glioma resection on long-term language function. Key PointsO_LIWhite matter connectivity determines the long-term functionality of cortical language sites mapped by TMS. C_LIO_LILong-term deficits in language processing result from resecting individualized subcortical regions within language-associated white matter tracts. C_LIO_LINon-invasive TMS language mapping combined with routine preoperative imaging can predict language outcomes of individual surgical approaches with an accuracy of 94%. C_LI

neuroscience↗

bioRxiv2019

Prediction of multiple drug resistant pulmonary tuberculosis against drug sensitive pulmonary tuberculosis by CT nodular consolidation sign

Multidrug-resistant tuberculosis (mdrtb) refers to TB infection resistant to at least two most powerful anti-TB drugs, isoniazid and rifampincin. It has been estimated that globally 3.5% (which can be much higher in some regions) of newly diagnosed TB patients, and 20.5% of previously treated patients had mdrtb. Extensively drug-resistant TB (xdrtb) has resistance to rifampin and isoniazid, as well as to any member of the quinolone family and at least one of the second line injectable drugs: kanamycin, amikacin and capreomycin. xdrtb accounts for 4-20% of mdrtb. Early detection and targeted treatment are priorities for mdrtb/xdrtb control. The suspicion of mdr/xdr -pulmonary TB (mdrptb or xdrptb) by chest imaging shall suggest intensive diagnostic testing for mdrptb/xdrptb. We hypothesize that multiple nodular consolidation (NC) may serve one of the differentiators for separating dsptb vs mdrptb/xdrptb cases. For this study, mdrptb cases (n=310) and XDR-PTB cases ([xcap]=I58) were from the NIAID TB Portals Program (TBPP) . Drug sensitive pulmonary TB (dsptb) cases were from the TBPP collection (n=112) as well as the Shenzhen Center for Chronic Disease Control (n=111), Shenzhen, China, and we excluded patients with HIV(+) status. Our study shows NC, particularly multiple NCs, is more common in mdrptb than in dsptb, and more common in xdrptb than in mdrptb. For example, 2.24% of dsptb patients, 13.23% of mdrptb patients, and 20.89% of xdrptb patients, respectively, have NCs with diameter >= 10mm equal or more than 2 in number.

pathology↗