tbuckley/cabot-search huggingface dataset:
NCOG-35. PREDICTORS OF POSTOPERATIVE SEIZURES IN PATIENTS WITH GLIOBLASTOMA MULTIFORME
Authors: Yue Zhang, Alper Dincer, Noah Feld, Matthew Carr, Lily Zhang, Charles Opalak, Andrew Rock, William Broaddus
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Seizures are a major cause of morbidity in patients with GBM, resulting in neurocognitive deficits and reduced QOL. There are limited studies on the predictors of postoperative seizures in these patients. Furthermore, there is no consensus among neurosurgeons on the timing of perioperative use of antiepileptic drugs (AEDs). The objective of this study is to determine patient- and tumor-related factors associated with postoperative seizures in GBM patients who undergo surgical resection. METHODS Our patient data registry was queried for adult patients treated for GBM at VCU from 2005 to 2014. Univariate and multivariable logistic regression analyses were performed to identify patient and tumor factors associated with postoperative seizure within a 12 month period. Cox proportional hazards regression analysis was used to evaluate the overall risk of postoperative seizure. RESULTS 146 patients met the criteria for the study. Of these, 39 patients (27%) experienced a postoperative seizure within 12 months. On univariate analysis, factors significantly associated with postoperative seizure within 12-months included percent (%) of FLAIR volume resected (OR: .81; CI: 0.65-0.99; p=.046), history of AED use (OR: 2.51; CI: 1.20-5.25; p = 0.015), and history of seizure (OR: 2.26, CI: 1.07-4.76; p=0.033). On multivariate analysis, % FLAIR resection maintained significance. (OR of 0.79; CI: .63-.99; p = 0.044). The increased overall risk of postoperative seizure was associated with preoperative seizure &amp;lt; 30 days before surgery. (HR:6.65, CI: 1.02-43.36, p=0.048). DISCUSSION Our study found that the increased extent of resection of FLAIR volume correlates with decreased odds of seizure occurrence in the 12-month postoperative period. Epileptogenesis of GBM seizures within this time period may be due to tumor-related edema or infiltrative tumor cells. Evaluation of FLAIR imaging postoperatively may be a useful clinical tool to guide AED management in high-risk patients.
Targeting MARCO and IL37R on Immunosuppressive Macrophages in Lung Cancer Blocks Regulatory T Cells and Supports Cytotoxic Lymphocyte Function
Authors: Linnéa La Fleur, Johan Botling, Fei He, Catarina Pelicano, Chikai Zhou, Chenfei He, Giorgia Palano, Artur Mezheyeuski, Patrick Micke, Jeffrey V. Ravetch, Mikael C. I. Karlsson, Dhifaf Sarhan
Journal: Cancer Research (2020)

Abstract The progression and metastatic capacity of solid tumors are strongly influenced by immune cells in the tumor microenvironment. In non–small cell lung cancer (NSCLC), accumulation of anti-inflammatory tumor-associated macrophages (TAM) is associated with worse clinical outcome and resistance to therapy. Here we investigated the immune landscape of NSCLC in the presence of protumoral TAMs expressing the macrophage receptor with collagenous structure (MARCO). MARCO-expressing TAM numbers correlated with increased occurrence of regulatory T cells and effector T cells and decreased natural killer (NK) cells in these tumors. Furthermore, transcriptomic data from the tumors uncovered a correlation between MARCO expression and the anti-inflammatory cytokine IL37. In vitro studies subsequently showed that lung cancer cells polarized macrophages to express MARCO and gain an immune-suppressive phenotype through the release of IL37. MARCO-expressing TAMs blocked cytotoxic T-cell and NK-cell activation, inhibiting their proliferation, cytokine production, and tumor killing capacity. Mechanistically, MARCO+ macrophages enhanced regulatory T (Treg) cell proliferation and IL10 production and diminished CD8 T-cell activities. Targeting MARCO or IL37 receptor (IL37R) by antibody or CRISPR knockout of IL37 in lung cancer cell lines repolarized TAMs, resulting in recovered cytolytic activity and antitumoral capacity of NK cells and T cells and downmodulated Treg cell activities. In summary, our data demonstrate a novel immune therapeutic approach targeting human TAMs immune suppression of NK- and T-cell antitumor activities. Significance: This study defines tumor-derived IL37 and the macrophage scavenger receptor MARCO as potential therapeutic targets to remodel the immune-suppressive microenvironment in patients with lung cancer.
DIPG-37. PREDICTING OUTCOME IN CHILDHOOD DIFFUSE MIDLINE GLIOMAS USING MAGNETIC RESONANCE IMAGING BASED TEXTURE ANALYSIS
Authors: Elwira Szychot, Adam Youssef, Balaji Ganeshan, Raymond Endozo, Harpreet Hyare, Jenny Gains, Ananth Shankar, Kshitij Mankad
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Diffuse midline gliomas (DMG) are aggressive brain tumours with 10% overall survival (OS) at 18 months. Predicting OS will help refine treatment strategy in this patient group. MRI based texture analysis (MRTA) is a novel technique that provides objective information about spatial arrangement of MRI signal intensity and has potential as an imaging biomarker. OBJECTIVES: To investigate MRTA in predicting OS in childhood DMG. METHODS Retrospective study of patients diagnosed with DMG, based on radiological features, treated at our institution 2007–2017. MRIs were accomplished at diagnosis and 6 weeks after radiotherapy (54Gy in 30 fractions). MRTA, performed using TexRAD software, on T2W sequence and Apparent Diffusion Coefficient (ADC) maps encapsulated tumour in the largest single axial plane. MRTA comprised filtration-histogram technique using statistical and histogram metrics for quantification of texture. Kaplan-Meier analysis determined association of MRI texture parameters with OS. RESULTS 32 children 2–14 years (median 7 years) were included. MRTA was undertaken on T2W (n=32) and ADC (n=22). MRTA on T2W was better at prognosticating than on ADC maps. Children with homogenous tumour texture, at medium scale on baseline T2W MRI, had worse prognosis (mean p=0.0098, SD p=0.0115, entropy p=0.0422, mean of positive pixels (MPP) p=0.0051, kurtosis p=0.0374). MPP was the most significant texture parameter. Median survival in this group as identified by MRTA (medium texture, MPP) was 7.5 months versus 17.5 months. CONCLUSIONS DMG with more homogeneous texture on diagnostic MRI is associated with worse prognosis. MPP texture parameter is the most predictive of OS in childhood DMG.
The Current Landscape of Antibody-based Therapies in Solid Malignancies
Authors: Ashu Shah, Sanchita Rauth, Abhijit Aithal, Sukhwinder Kaur, Koelina Ganguly, Catherine Orzechowski, Grish C Varshney, Maneesh Jain, Surinder K Batra
Journal: Theranostics (2020)

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for tumor targeting and mechanisms of therapeutic resistance that is not only caused by the heterogeneity of tumor antigen, but also the resistance imposed by tumor microenvironment (TME), including inefficient delivery to the tumor, alteration of effector functions in the TME, and Fc-gamma receptor expression diversity and polymorphism. Further, this article provides a perspective on potential strategies to overcome these barriers and how diagnostic and prognostic biomarkers are being used in predicting response to mAb-based therapies. Overall, understanding these interdependent parameters can improve the current mAb-based formulations and develop novel mAb-based therapeutics for achieving durable clinical outcomes in a large subset of patients.
PATH-04. THE BLOOD-BRAIN BARRIER IN DIFFUSE MIDLINE GLIOMA AND ITS IMPLICATIONS FOR DRUG DELIVERY
Authors: Rianne Haumann, Fatma El-Khouly, Marjolein Breur, Sophie Veldhuijzen van Zanten, Gertjan Kaspers, Harry Hendrikse, Esther Hulleman, Dannis van Vuurden, Marianna Bugiani
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Chemotherapy has been unsuccessful for pediatric diffuse midline glioma (DMG) most likely due to an intact blood-brain barrier (BBB). However, the BBB has not been characterized in DMG and therefore its implications for drug delivery are unknown. In this study we characterized the BBB in DMG patients and compared this to healthy controls. METHODS End-stage DMG pontine samples (n=5) were obtained from the VUmc diffuse intrinsic pontine glioma (DIPG) autopsy study and age-matched healthy pontine samples (n=22) were obtained from the NIH NeuroBioBank. Tissues were stained for BBB markers claudin-5, zonula occludens-1, laminin, and PDGFRβ. Claudin-5 stains were used to determine vascular density and diameter. RESULTS In DMG, expression of claudin-5 was reduced and dislocated to the abluminal side of endothelial cells. In addition, the expression of zonula occludens-1 was reduced. The basement membrane protein laminin expression was reduced at the glia limitans in both pre-existent vessels and neovascular proliferation. PDGFRβ expression was not observed in DMG but was present in healthy pons. Furthermore, the number of blood vessels in DMG was significantly (P&amp;lt; 0.01) reduced (13.9 ± 11.8/mm2) compared to healthy pons (26.3 ± 14.2/mm2). Markedly, the number of small blood vessels (&amp;lt; 10µm) was significantly lower (P&amp;lt; 0.01) while larger blood vessels (&amp;gt; 10µm) were not significantly different (P= 0.223). The mean vascular diameter was larger for DMG 9.3 ± 9.9µm compared to 7.7 ± 9.0µm for healthy pons (P= 0.016). CONCLUSION Both the BBB and the vasculature are altered at end-stage DMG. The reduced vascular density might have implications for several drug delivery methods such as focused ultrasound and convection enhanced delivery that are being explored for the treatment of DMG. The functional effects of the structurally altered BBB remain unknown and further research is needed to evaluate the BBB integrity at end-stage DMG
Abstract P350: The Link Between Cognitive Function and Cause-specific Mortality in US Adults
Authors: Sanaz Sedaghat, Behnam SABAYAN, Farzaneh A Sorond, Mercedes R Carnethon
Journal: Circulation (2020)

Introduction: Multiple studies demonstrated an independent and inverse association between cognitive function and mortality but little is known about the cause of death. Hypothesis: We hypothesized that lower cognitive function is related to higher mortality risk and this association is stronger for cardiovascular related deaths. Methods: We included 5569 persons (mean[SE] age 71[0.05], 52% women), from the Third National Health and Nutrition Examination Survey (NHANES III) with available cognitive function measurements and mortality follow-up. Cognitive domains include orientation, attention, immediate and delayed memory as well as global cognition. We used weighted Cox proportional regression models adjusted for age, sex, education, systolic and diastolic blood pressure, body mass index, smoking, history of diabetes and cardiovascular disorders. Results: During an average follow-up of 12 years, 1887 participants died from cardiovascular causes and 2675 died from non-cardiovascular causes. Each SD lower global cognitive performance (SD=6) was related to a 1.11 (95% CI: 1.05, 1.17) higher hazard of all-cause mortality. The associations were more prominent with cardiovascular mortality than with non- cardiovascular mortality (Table). Conclusion: Cognitive impairment in the absence of manifest dementia is an important independent predictor of mortality, in particular from cardiovascular causes.
QOL-22. MACHINE-LEARNING INFERENCE MAY PREDICT QUALITY OF LIFE SUBGROUPS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA
Authors: Astrid C Hengartner, Eric Prince, Susan Staulcup, Trinka Vijmasi, Mark Souweidane, Eric M Jackson, James M Johnston, Richard C E Anderson, Robert P Naftel, Gerald Grant, Toba N Niazi, Roy Dudley, David D Limbrick, Kevin Ginn, Amy Smith, Lindsay Kilburn, George Jallo, Greta Wilkening, Todd Hankinson
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Due to disease and/or treatment-related injury, such as hypothalamic, visual, and endocrine damage, quality of life (QoL) scores after childhood-onset Adamantinomatous Craniopharyngioma (ACP) are among the lowest of all pediatric brain tumors. Decision-making regarding management would be aided by more complete understanding of a patients likely QoL trajectory following intervention. METHODS We retrospectively analyzed caregiver and patient-reported QoL-instruments from the first 50 patients (ages 1–17 years at diagnosis) enrolled in the international Advancing Treatment for Pediatric Craniopharyngioma (ATPC) consortium. Surveys included 205 pediatric-relevant questions and were completed at diagnosis, and 1- and 12-months following diagnosis. Using Multiple Correspondence Analysis (MCA), these categorical QoL surveys were interrogated to identify time-dependent patient subgroups. Additionally, custom deep learning classifiers were developed using Google’s TensorFlow framework. RESULTS By representing QoL data in the reduced dimensionality of MCA-space, we identified QoL subgroups that either improved or declined over time. We assessed differential trends in QoL responses to identify variables that were subgroup specific (Kolmogorov-Smirnov p-value &amp;lt; 0.1; n=20). Additionally, our optimized deep learning classifier achieved a mean 5-fold cross-validation area under precision-recall curve score &amp;gt; 0.99 when classifying QoL subgroups at 12 month follow-up, using only baseline data. CONCLUSIONs This work demonstrates the existence of time-dependent QoL-based ACP subgroups that can be inferred at time-of-diagnosis via machine learning analyses of baseline survey responses. The ability to predict an ACP patient’s QoL trajectory affords caregivers valuable information that can be leveraged to maximize that patient’s psychosocial state and therefore improve overall therapy.
49P Discontinuation of immune checkpoint inhibitors in patients with relapsed and refractory classical Hodgkin lymphoma
Authors: L. Fedorova, K. Lepik, P. Kotselyabina, E. Kondakova, M. Popova, E. Borzenkova, I. Moiseev, N. Mikhailova, A. Kulagin
Journal: Annals of Oncology (2020)
A 1 Per 1,000 Mortality Rate After Catheter Ablation of Atrial Fibrillation: An Acceptable Risk?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Bernard Belhassen
Journal: Journal of the American College of Cardiology (2009)
HGG-53. PROJECT HOPE: “PEDIATRIC AND AYA HIGH-GRADE GLIOMA OMICS PROJECT”- A LONGITUDINAL MOLECULAR LANDSCAPE OF HIGH-GRADE GLIOMAS RESOLVED AT SINGLE-CELL LEVEL
Authors: Olivia A Hack, Husam Babikir, Li Jiang, Karin Shamardani, Ilon Liu, McKenzie Shaw, Kennedy Cunliffe-Koehler, Adam Resnick, Michael Prados, Michelle Monje, Aaron Diaz, Mariella G Filbin
Journal: Neuro-Oncology (2020)

Abstract High-grade gliomas (HGG) are among the most prevalent and fatal cancers in pediatric, adolescent, and young adult (AYA) patients. Especially understudied are older children and young adults, aged 16–39 years. Previously, we profiled primary pediatric HGGs through single-cell transcriptomics and identified the genetic, epigenetic and developmental programs that drive their malignant progression. However, the questions of how these programs compare to those in older HGG patients, what the mechanisms are by which these tumors ultimately evolve to drive recurrence and treatment resistance, and how distinct tumor cell subpopulations bidirectionally communicate with their microenvironment remain to be elucidated. Here, we use single-nucleus RNA sequencing to compare 11 paired, matched high-grade gliomas at diagnosis and recurrence and 15 additional H3K27M primary and recurrent DMG samples in pediatric and AYA patients. In all tumors, we find both undifferentiated and differentiated tumor cells recapitulating distinct glial lineages, as well as diverse microenvironmental cell populations. When longitudinally comparing this tumor architecture within matched pairs, we find substantial differences in transcriptional program expressions. Diagnostic samples include more differentiated, astrocyte-like tumor cells, while cells from recurrent samples more highly express ribosomal and heat-shock protein genes, suggesting tumor progression- and treatment-related shifts. Ongoing sequencing and analysis will allow for unprecedented insight into the evolutionary dynamics of pediatric and AYA high-grade gliomas as well as delineate differences in the biology of DMGs occurring in different age groups. This multi-institutional project was funded by the National Institute of Health.
Effects of prenatal photobiomodulation treatment on neonatal hypoxic ischemia in rat offspring
Authors: Luodan Yang, Yan Dong, Chongyun Wu, Hannah Youngblood, Yong Li, Xuemei Zong, Lei Li, Tongda Xu, Quanguang Zhang
Journal: Theranostics (2020)

Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.
IMG-14. DEVELOPING A PREDICTIVE GRADING MODEL FOR CHILDREN WITH GLIOMAS BASED ON DIFFUSION KURTOSIS IMAGING METRICS: ACCURACY AND CLINICAL CORRELATIONS WITH SURVIVAL
Authors: Ioan Paul Voicu, Antonio Napolitano, Alessia Carboni, Lorenzo Lattavo, Andrea Carai, Maria Vinci, Francesca Diomedi-Camassei, Antonella Cacchione, Giada Del Baldo, Paolo Tomà, Angela Mastronuzzi, Giovanna Stefania Colafati
Journal: Neuro-Oncology (2020)

Abstract PURPOSE To develop a predictive grading model based on diffusion kurtosis imaging (DKI) metrics in children affected by gliomas, and to investigate the clinical impact of the model via correlations with overall survival and progression-free survival. MATERIALS AND METHODS We retrospectively studied 59 children (33M, 26F, median age 7.2 years) affected by gliomas on a 3T magnet. Patients with tumor locations other than infratentorial midline were included. Conventional and DKI sequences were obtained. Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were obtained. Whole tumor volumes (VOIs) were segmented semiautomatically. Mean DKI values were calculated for each metric. The quantitative values from DKI-derived metrics were used to develop a predictive grading model with penalized logistic regression (glmnet package, R). Elasticnet regularization was used to avoid model overfitting. Fitted model coefficients from each metric were used to develop a probability prediction of a high-grade glioma (HGG). Grading accuracy of the resulting probabilities was tested with ROC analysis. Finally, model predictions were correlated to progression-free survival (PFS) with a Kaplan-Meier analysis. RESULTS The cohort included 46 patients with low-grade gliomas (LGG) and 13 patients with HGG. The developed model predictions yielded an AUC of 0.946 (95%CI: 0.890–1). Model predictions were significantly correlated with PFS (23.1 months for HGG vs 34.7 months for LGG, p&amp;lt;0.004). CONCLUSION In our cohort, a DKI-based predictive model was highly accurate for pediatric glioma grading. DKI-based model predictions were significantly correlated with progression-free survival.
Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR
Authors: Hailing Liu, Tian Lan, Hui Li, Lin Xu, Xing Chen, Haotian Liao, Xiangzheng Chen, Jinpeng Du, Yunshi Cai, Jinju Wang, Xuefeng Li, Jiwei Huang, Kefei Yuan, Yong Zeng
Journal: Theranostics (2020)

circular RNAs (circRNAs) have been demonstrated to play a crucial role in cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. The aim of present study is to investigate the role of circular RNAs in KIAA1429-mediated HCC progression.