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Article ; Online: Commentary on "Dysfunctional dendritic cells limit antigen-specific T cell response in glioma".

Prins, Robert M / Everson, Richard G

2022 Volume 25, Issue 2, Page(s) 277–278

MeSH term(s)	Humans ; T-Lymphocytes ; Glioma ; Brain Neoplasms ; Dendritic Cells
Language	English
Publishing date	2022-12-02
Publishing country	England
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noac256
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Article ; Online: Functional magnetic resonance imaging (fMRI) as adjunct for planning laser interstitial thermal therapy (LITT) near eloquent structures.

Rifi, Ziad / Harary, Maya / Walshaw, Patricia D / Frew, Andrew J / Everson, Richard G / Fallah, Aria / Salamon, Noriko / Kim, Won

Acta neurochirurgica

2024 Volume 166, Issue 1, Page(s) 66

Abstract: LITT is a minimally-invasive laser ablation technique used to treat a wide variety of intracranial lesions. Difficulties performing intraoperative mapping have limited its adoption for lesions in/near eloquent regions. In this institutional case series, ... ...

Abstract	LITT is a minimally-invasive laser ablation technique used to treat a wide variety of intracranial lesions. Difficulties performing intraoperative mapping have limited its adoption for lesions in/near eloquent regions. In this institutional case series, we demonstrate the utility of fMRI-adjunct planning for LITT near language or motor areas. Six out of 7 patients proceeded with LITT after fMRI-based tractography determined adequate safety margins for ablation. All underwent successful ablation without new or worsening postoperative symptoms requiring adjuvant corticosteroids, including those with preexisting deficits. fMRI is an easily accessible adjunct which may potentially reduce chances of complications in LITT near eloquent structures.
MeSH term(s)	Humans ; Magnetic Resonance Imaging/methods ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/surgery ; Brain Neoplasms/pathology ; Neurosurgical Procedures/methods ; Laser Therapy/methods ; Lasers
Language	English
Publishing date	2024-02-05
Publishing country	Austria
Document type	Journal Article
ZDB-ID	80010-7
ISSN	0942-0940 ; 0001-6268
ISSN (online)	0942-0940
ISSN	0001-6268
DOI	10.1007/s00701-024-05970-x
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Article ; Online: Modern surgical management of incidental gliomas.

Pradhan, Anjali / Mozaffari, Khashayar / Ghodrati, Farinaz / Everson, Richard G / Yang, Isaac

Journal of neuro-oncology

2022 Volume 159, Issue 1, Page(s) 81–94

Abstract: Purpose: Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may ... ...

Abstract	Purpose: Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may experience no tumor-related symptoms and be incidentally diagnosed. These incidental low-grade gliomas (iLGG) maintain controversial treatment course despite scientific advancements. Here we highlight the recent advancements in classification, neuroimaging, and surgical management of these tumors. Methods: A review of the literature was performed. The authors created five subtopics of focus: histological criteria, diagnostic imaging, surgical advancements, correlation of surgical resection and survival outcomes, and clinical implications. Conclusions: Alternating studies suggest that these tumors may experience higher mutational rates than their counterparts. Significant progress in management of gliomas, regardless of the grade, has been made through modern neurosurgical treatment modalities, diagnostic neuroimaging, and a better understanding of the genetic composition of these tumors. An optimal treatment approach for patients with newly diagnosed iLGG remains ill-defined despite multiple studies arguing in favor of safe maximal resection. Our review emphasizes the not so benign nature of incidental low grade glioma and further supports the need for future studies to evaluate survival outcomes following surgical resection.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Glioma/diagnostic imaging ; Glioma/pathology ; Glioma/surgery ; Humans ; Neurosurgical Procedures/methods ; Treatment Outcome
Language	English
Publishing date	2022-06-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-022-04045-0
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Article ; Online: Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma.

Patel, Kunal S / Tessema, Kaleab K / Kawaguchi, Riki / Dudley, Lindsey / Alvarado, Alvaro G / Muthukrishnan, Sree Deepthi / Perryman, Travis / Hagiwara, Akifumi / Swarup, Vivek / Liau, Linda M / Wang, Anthony C / Yong, William / Geschwind, Daniel H / Nakano, Ichiro / Goldman, Steven A / Everson, Richard G / Ellingson, Benjamin M / Kornblum, Harley I

Neuro-oncology advances

2024 Volume 6, Issue 1, Page(s) vdae005

Abstract: Background: Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma.: Methods: We leveraged single-nucleus RNA sequencing on ...

Abstract	Background: Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma. Methods: We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas ( Results: Tumor cells in NE regions are enriched in neural progenitor cell-like cellular states, while CE regions are enriched in mesenchymal-like states. NE glioma cells have similar proportions of proliferative and putative glioma stem cells relative to CE regions, without significant differences in % Ki-67 staining. Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Our findings in recurrent GBM paralleled some of the findings in a re-analysis of a dataset from primary GBM. Cell-, gene-, and pathway-level analyses of the tumor microenvironment in the NE region reveal relative downregulation of tumor-mediated neovascularization and cell-mediated immune response, but increased glioma-to-nonpathological cell interactions. Conclusions: This comprehensive analysis illustrates differing tumor and nontumor landscapes of CE and NE regions in high-grade gliomas, highlighting the NE region as an area harboring likely initiators of recurrence in a pro-tumor microenvironment and identifying possible targets for future design of NE-specific adjuvant therapy. These findings also support the aggressive approach to resection of tumor-bearing NE regions.
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdae005
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Article ; Online: Cell-Based Immunotherapy of Gliomas.

Everson, Richard G / Antonios, Joseph P / Liau, Linda M

Progress in neurological surgery

2018 Volume 32, Page(s) 90–100

Abstract: Current cell-based immunotherapeutic strategies attempt to produce and maintain an immune response against glioma cells by artificially stimulating the immune system using passive and/or active approaches. Cellular immunotherapy is taken to mean the ... ...

Abstract	Current cell-based immunotherapeutic strategies attempt to produce and maintain an immune response against glioma cells by artificially stimulating the immune system using passive and/or active approaches. Cellular immunotherapy is taken to mean the administration of live immune cells that either have immune effector capabilities themselves (passive immunotherapy) or engender a downstream antitumor response (active immunotherapy). Passive cellular immunotherapy most often takes the form of the adoptive transfer of a range of cell types, whereby antitumor immune cells from a patient (or allogeneic donor) are created, activated, and/or expanded ex vivo and subsequently administered back to the patient to directly attack the neoplasm. Active cellular immunotherapy approaches for the treatment of malignant gliomas have most often taken the form of dendritic cell (DC)-based vaccines.
MeSH term(s)	Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Cancer Vaccines/immunology ; Cell- and Tissue-Based Therapy/methods ; Dendritic Cells/immunology ; Glioma/immunology ; Glioma/therapy ; Humans ; Immunotherapy, Active/methods ; Immunotherapy, Adoptive/methods
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2018-07-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	1662-3924 ; 0079-6492
ISSN (online)	1662-3924
ISSN	0079-6492
DOI	10.1159/000469683
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Article ; Online: Simultaneous quantification of perfusion, permeability, and leakage effects in brain gliomas using dynamic spin-and-gradient-echo echoplanar imaging MRI.

Sanvito, Francesco / Raymond, Catalina / Cho, Nicholas S / Yao, Jingwen / Hagiwara, Akifumi / Orpilla, Joey / Liau, Linda M / Everson, Richard G / Nghiemphu, Phioanh L / Lai, Albert / Prins, Robert / Salamon, Noriko / Cloughesy, Timothy F / Ellingson, Benjamin M

European radiology

2023

Abstract: Objective: To determine the feasibility and biologic correlations of dynamic susceptibility contrast (DSC), dynamic contrast enhanced (DCE), and quantitative maps derived from contrast leakage effects obtained simultaneously in gliomas using dynamic ... ...

Abstract	Objective: To determine the feasibility and biologic correlations of dynamic susceptibility contrast (DSC), dynamic contrast enhanced (DCE), and quantitative maps derived from contrast leakage effects obtained simultaneously in gliomas using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) during a single contrast injection. Materials and methods: Thirty-eight patients with enhancing brain gliomas were prospectively imaged with dynamic SAGE-EPI, which was processed to compute traditional DSC metrics (normalized relative cerebral blood flow [nrCBV], percentage of signal recovery [PSR]), DCE metrics (volume transfer constant [K Results: In IDH wild-type gliomas (IDH Conclusions: Dynamic SAGE-EPI enables simultaneous quantification of brain tumor perfusion and permeability, as well as mapping of novel metrics related to cytoarchitecture (TRATE) and blood-brain barrier disruption (ΔR Clinical relevance statement: Simultaneous DSC and DCE analysis with dynamic SAGE-EPI reduces scanning time and contrast dose, respectively alleviating concerns about imaging protocol length and gadolinium adverse effects and accumulation, while providing novel leakage effect metrics reflecting blood-brain barrier disruption and tumor tissue cytoarchitecture. Key points: • Traditionally, perfusion and permeability imaging for brain tumors requires two separate contrast injections and acquisitions. • Dynamic spin-and-gradient-echo echoplanar imaging enables simultaneous perfusion and permeability imaging. • Dynamic spin-and-gradient-echo echoplanar imaging provides new image contrasts reflecting blood-brain barrier disruption and cytoarchitecture characteristics.
Language	English
Publishing date	2023-10-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-023-10215-z
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Book ; Online: How Bayesian Should Bayesian Optimisation Be?

De Ath, George / Everson, Richard / Fieldsend, Jonathan

2021

Abstract: Bayesian optimisation (BO) uses probabilistic surrogate models - usually Gaussian processes (GPs) - for the optimisation of expensive black-box functions. At each BO iteration, the GP hyperparameters are fit to previously-evaluated data by maximising the ...

Abstract	Bayesian optimisation (BO) uses probabilistic surrogate models - usually Gaussian processes (GPs) - for the optimisation of expensive black-box functions. At each BO iteration, the GP hyperparameters are fit to previously-evaluated data by maximising the marginal likelihood. However, this fails to account for uncertainty in the hyperparameters themselves, leading to overconfident model predictions. This uncertainty can be accounted for by taking the Bayesian approach of marginalising out the model hyperparameters. We investigate whether a fully-Bayesian treatment of the Gaussian process hyperparameters in BO (FBBO) leads to improved optimisation performance. Since an analytic approach is intractable, we compare FBBO using three approximate inference schemes to the maximum likelihood approach, using the Expected Improvement (EI) and Upper Confidence Bound (UCB) acquisition functions paired with ARD and isotropic Matern kernels, across 15 well-known benchmark problems for 4 observational noise settings. FBBO using EI with an ARD kernel leads to the best performance in the noise-free setting, with much less difference between combinations of BO components when the noise is increased. FBBO leads to over-exploration with UCB, but is not detrimental with EI. Therefore, we recommend that FBBO using EI with an ARD kernel as the default choice for BO. Comment: To appear in the Proceedings of Genetic and Evolutionary Computation Conference Companion (GECCO 2021), ACM. 10 pages (main paper) + 26 pages (supplement)
Keywords	Computer Science - Machine Learning ; Statistics - Machine Learning
Subject code	310
Publishing date	2021-05-03
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Context-Aware Generative Models for Prediction of Aircraft Ground Tracks

Pepper, Nick / De Ath, George / Thomas, Marc / Everson, Richard / Dodwell, Tim

2023

Abstract: Trajectory prediction (TP) plays an important role in supporting the decision-making of Air Traffic Controllers (ATCOs). Traditional TP methods are deterministic and physics-based, with parameters that are calibrated using aircraft surveillance data ... ...

Abstract	Trajectory prediction (TP) plays an important role in supporting the decision-making of Air Traffic Controllers (ATCOs). Traditional TP methods are deterministic and physics-based, with parameters that are calibrated using aircraft surveillance data harvested across the world. These models are, therefore, agnostic to the intentions of the pilots and ATCOs, which can have a significant effect on the observed trajectory, particularly in the lateral plane. This work proposes a generative method for lateral TP, using probabilistic machine learning to model the effect of the epistemic uncertainty arising from the unknown effect of pilot behaviour and ATCO intentions. The models are trained to be specific to a particular sector, allowing local procedures such as coordinated entry and exit points to be modelled. A dataset comprising a week's worth of aircraft surveillance data, passing through a busy sector of the United Kingdom's upper airspace, was used to train and test the models. Specifically, a piecewise linear model was used as a functional, low-dimensional representation of the ground tracks, with its control points determined by a generative model conditioned on partial context. It was found that, of the investigated models, a Bayesian Neural Network using the Laplace approximation was able to generate the most plausible trajectories in order to emulate the flow of traffic through the sector.
Keywords	Electrical Engineering and Systems Science - Systems and Control ; Computer Science - Machine Learning
Subject code	670
Publishing date	2023-09-26
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Dendritic Cell Vaccination in Conjunction with a TLR Agonist Polarizes Interferon Immune Responses in Malignant Glioma Patients.

Everson, Richard G / Hugo, Willy / Sun, Lu / Antonios, Joseph / Lee, Alexander / Ding, Lizhong / Bu, Melissa / Khattab, Sarah / Chavez, Carolina / Billingslea-Yoon, Emma / Salazar, Andres / Ellingson, Benjamin M / Cloughesy, Timothy F / Liau, Linda M / Prins, Robert M

Research square

2023

Abstract: Autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination is a promising immunotherapy for patients with high grade gliomas, but responses have not been demonstrated in all patients. To determine the most effective combination of autologous ... ...

Abstract	Autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination is a promising immunotherapy for patients with high grade gliomas, but responses have not been demonstrated in all patients. To determine the most effective combination of autologous tumor lysate-pulsed DC vaccination, with or without the adjuvant toll-like receptor (TLR) agonists poly-ICLC or resiquimod, we conducted a Phase 2 clinical trial in 23 patients with newly diagnosed or recurrent WHO Grade III-IV malignant gliomas. We then performed deep, high-dimensional immune profiling of these patients to better understand how TLR agonists may influence the systemic immune responses induced by ATL-DC vaccination. Bulk RNAseq data demonstrated highly significant upregulation of type 1 and type 2 interferon gene expression selectively in patients who received adjuvant a TLR agonist together with ATL-DC. CyTOF analysis of patient peripheral blood mononuclear cells (PBMCs) showed increased expression of PD-1 on CD4+ T-cells, decreases in CD38 and CD39 on CD8+ T cells and elevated proportion of monocytes after ATL-DC + TLR agonist administration. In addition, scRNA-seq demonstrated a higher expression fold change of IFN-induced genes with poly-ICLC treatment in both peripheral blood monocytes and T lymphocytes. Patients who had higher expression of interferon response genes lived significantly longer and had longer time to progression compared to those with lower expression. The results suggest that ATL-DC in conjunction with adjuvant poly-ICLC induces a polarized interferon response in circulating monocytes and specific activation of a CD8+ T cell population, which may represent an important blood biomarker for immunotherapy in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01204684.
Language	English
Publishing date	2023-09-12
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3287211/v1
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Article ; Online: Small pretreatment lesion size and high sphericity as favorable prognostic factors after laser interstitial thermal therapy in brain metastases.

Sanvito, Francesco / Telesca, Donatello / Cho, Nicholas S / Sayari, Jessica T / Nagaraj, Raksha / Raymond, Catalina / Rana, Shivam / Patel, Kunal / Mozaffari, Khashayar / Unterberger, Ansley A / Khanlou, Negar / Magaki, Shino / Pouratian, Nader / Everson, Richard G / Yang, Isaac / Kim, Won / Ellingson, Benjamin M

Journal of neurosurgery

2023 Volume 140, Issue 2, Page(s) 338–349

Abstract: Objective: The objective of this study was to identify baseline clinical and radiological characteristics of brain metastases (BMs) associated with a higher probability of lesion-specific progression-free survival (PFS-L) after laser interstitial ... ...

Abstract	Objective: The objective of this study was to identify baseline clinical and radiological characteristics of brain metastases (BMs) associated with a higher probability of lesion-specific progression-free survival (PFS-L) after laser interstitial thermal therapy (LITT). Methods: A total of 47 lesions in 42 patients with BMs treated with LITT were retrospectively examined, including newly diagnosed BM, suspected recurrent BM, and suspected radiation necrosis. The association of baseline clinical and radiological features with PFS-L was assessed using survival analyses. Radiological features included lesion size measurements, diffusion and perfusion metrics, and sphericity, which is a radiomic feature ranging from 1 (perfect sphere) to 0. Results: The probability of PFS-L for the entire cohort was 88.0% at 3 months, 70.6% at 6 months, 67.4% at 1 and 2 years, and 62.2% at 3 years. For lesions progressing after LITT (n = 13), the median time to progression was 3.9 months, and most lesions (n = 11) progressed within 6 months after LITT. In lesions showing response to LITT (n = 17), the median time to response was 12.1 months. All 3 newly diagnosed BMs showed a long-term response. The mean (± SD) follow-up duration for all censored lesions (n = 34) was 20.7 ± 19.4 months (range 12 days to 6.1 years). The mean pretreatment enhancing volume was 2.68 cm3 and the mean sphericity was 0.70. Pretreatment small enhancing volume (p = 0.003) and high sphericity (p = 0.024) computed from lesion segmentation predicted a longer PFS-L after LITT. Lesions meeting optimal cutoffs of either enhancing volume < 2.5 cm3 (adjusted p = 0.004) or sphericity ≥ 0.705 (adjusted p = 0.019) had longer PFS-L, and their probability of PFS-L was 86.8% at 3 years. Lesions meeting both cutoffs showed a cumulative benefit (p < 0.0001), with a 100% probability of PFS-L at 3 years, which was unchanged at the end of follow-up (4.1 years). Manually computed estimates of lesion size (maximal axial diameter, p = 0.011) and sphericity (p = 0.043) were also predictors of PFS-L. Optimal cutoffs of diameter < 2 cm (adjusted p = 0.035) or manual sphericity ≥ 0.91 (adjusted p = 0.092) identified lesions with longer PFS-L, and lesions meeting both cutoffs showed a cumulative benefit (p = 0.0023). Baseline diffusion imaging did not predict PFS-L. A subset of lesions (n = 7) with highly perfused hotspots had worse PFS-L (adjusted p = 0.010), but perfusion signal contamination from vessels and cortex and underlying size differences were possible confounders. Conclusions: Small size and high sphericity are ideal baseline features for lesions considered for LITT treatment, with a cumulative PFS-L benefit when both features are present, that could aid patient selection.
MeSH term(s)	Humans ; Laser Therapy/methods ; Retrospective Studies ; Prognosis ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/therapy ; Brain Neoplasms/pathology ; Lasers
Language	English
Publishing date	2023-08-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2023.5.JNS23285
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