tbuckley/cabot-search huggingface dataset:
EPID-03. COMPARISON OF SURVIVAL IN ADULT AND PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA: A 2018 SEER BASED ANALYSIS
Authors: Hanna M Moisander-Joyce, Anoushka Sinha, Shannon Fernandez-Ledon, Davon T Lee, Satoki Hatano, Justine Kahn, James H Garvin, Stergios Zacharoulis, Robyn D Gartrell-Corrado
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB) is the most common high-grade primary brain malignancy in children and accounts for 1% of adult brain tumors. Previous studies have compared survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database finding no difference. However, diagnostic subgroup analyses are limited. We examined survival in children (age 0–19) and adults (20–79) coded as MB in the 2018 SEER database (2000–2016), using Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI).). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n=1,728). ICD 9473, supratentorial PNET (sPNET, n=97) is biologically distinct so was analyzed separately. 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n= 488, 79.1%) (HR=0.97, CI: 0.79 – 1.17, p=0.50). Subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n=222, p=0.09), large cell MB (n=73, p=0.46), or MB NOS (n=1330, p=0.10). In contrast, children with sPNET had improved survival (n=65, 72.3%) compared to adults (n=29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p=0.02,). In conclusion, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment. Comparison of adults and children with MB and sPNET will be re-evaluated using the new 2016 World Health Organization classification.
Transgender women of color in the U.S. South: A qualitative study of social determinants of health and healthcare perspectives
Authors: Benjamin D. Smart, Lilli Mann-Jackson, Jorge Alonzo, Amanda E. Tanner, Manuel Garcia, Lucero Refugio Aviles, Scott D. Rhodes
Journal: International Journal of Transgender Health (2020)

Background: Research has shown that transgender and nonbinary people experience health disparities. However, few studies have explored, in-depth, the health-related experiences, perceptions, needs, and priorities of transgender women of color living in the U.S. South, a region that poses unique challenges to achieving health for transgender people. Aims: This study explored the social determinants of health, healthcare experiences, and health-related priorities of transgender women of color living in the U.S. South. Methods: Using a community-based participatory research approach, we conducted iterative in-depth interviews with 15 African American/Black and Latinx transgender women in North Carolina in May-July 2019 for a total of 30 interviews. We analyzed interview data using constant comparison, an approach to grounded theory. Results: Participants' mean age was 34 (range 19-56) years. Twenty themes emerged that were categorized into three domains: (1) social determinants of health (family rejection; bullying, discrimination, and violence; isolation; policy barriers; mistrust in systems; employment obstacles; sex work; high cost of care; transportation barriers; church antagonism; and substance misuse), (2) healthcare experiences (emotional burden of healthcare interactions; name and gender misidentification; staff discomfort and insensitivity; sexual risk assumptions; and use of nonmedical or predatory providers), and (3) health-related priorities (understanding healthcare; respect at all levels of healthcare; inclusive gender-affirming care; and comprehensive resources). Discussion: Transgender women of color living in the U.S. South face profound health barriers compounded throughout the life course and have unmet healthcare needs. Participants faced multilayered minority stressors: racial discrimination from society at large and within the LGTBQ community; gender identity discrimination within their regional context and racial/ethnic communities; and exclusion from existing health equity movements for transgender women of color, which often are found in and focus on larger urban communities. Health interventions mindful of this intersection are needed, including antidiscrimination policies and increasing gender-affirming healthcare access.
MBCL-08. INTEGRATIVE MOLECULAR ANALYSIS OF PATIENT-MATCHED DIAGNOSTIC AND RELAPSED MEDULLOBLASTOMAS
Authors: Rahul Kumar, Maximilian Deng, Kyle Smith, Anthony Liu, Girish Dhall, Laura Kleese, Daniel Bowers, Murali Chintagumpala, Sarah Leary, Javad Nazarian, Brent Orr, Arzu Onar-Thomas, Stefan Pfister, Andrey Korshunov, Giles Robinson, Amar Gajjar, David Jones, Vijay Ramaswamy, Paul Northcott
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The next generation of clinical trials for relapsed medulloblastoma demands a thorough understanding of the clinical behavior of relapsed tumors as well as the molecular relationship to their diagnostic counterparts. METHODS A multi-institutional molecular cohort of patient-matched (n=126 patients) diagnostic MBs and relapses/subsequent malignancies was profiled by DNA methylation array. Entity, subgroup classification, and genome-wide copy-number aberrations were assigned while parallel next-generation (whole-exome or targeted panel) sequencing on the majority of the cohort facilitated inference of somatic driver mutations. RESULTS Comprised of WNT (2%), SHH (41%), Group 3 (18%), Group 4 (39%), primary tumors retained subgroup affiliation at relapse with the notable exception of 10% of cases. The majority (8/13) of discrepant classifications were determined to be secondary glioblastomas. Additionally, rare (n=3) subgroup-switching events of Group 4 primary tumors to Group 3 relapses were identified coincident with MYC/MYCN pathway alterations. Amongst truly relapsing MBs, copy-number analyses suggest somatic clonal divergence between primary MBs and their respective relapses with Group 3 (55% of alterations shared) and Group 4 tumors (63% alterations shared) sharing a larger proportion of cytogenetic alterations compared to SHH tumors (42% alterations shared; Chi-square p-value &amp;lt; 0.001). Subgroup- and gene-specific patterns of conservation and divergence amongst putative driver genes were also observed. CONCLUSION Integrated molecular analysis of relapsed MB discloses potential mechanisms underlying treatment failure and disease recurrence while motivating rational implementation of relapse-specific therapies. The degree of genetic divergence between primary and relapsed MBs varied by subgroup but suggested considerably higher conservation than prior estimates.
Household Transmission of SARS-CoV-2
Authors: Zachary J. Madewell, Yang Yang, Ira M. Longini, M. Elizabeth Halloran, Natalie E. Dean
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Crowded indoor environments, such as households, are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). <h3>Objectives</h3> To examine evidence for household transmission of SARS-CoV-2, disaggregated by several covariates, and to compare it with other coronaviruses. <h3>Data Source</h3> PubMed, searched through October 19, 2020. Search terms included<i>SARS-CoV-2</i>or<i>COVID-19</i>with<i>secondary attack rate</i>,<i>household</i>,<i>close contacts</i>,<i>contact transmission</i>,<i>contact attack rate</i>, or<i>family transmission</i>. <h3>Study Selection</h3> All articles with original data for estimating household secondary attack rate were included. Case reports focusing on individual households and studies of close contacts that did not report secondary attack rates for household members were excluded. <h3>Data Extraction and Synthesis</h3> Meta-analyses were done using a restricted maximum-likelihood estimator model to yield a point estimate and 95% CI for secondary attack rate for each subgroup analyzed, with a random effect for each study. To make comparisons across exposure types, study was treated as a random effect, and exposure type was a fixed moderator. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. <h3>Main Outcomes and Measures</h3> Secondary attack rate for SARS-CoV-2, disaggregated by covariates (ie, household or family contact, index case symptom status, adult or child contacts, contact sex, relationship to index case, adult or child index cases, index case sex, number of contacts in household) and for other coronaviruses. <h3>Results</h3> A total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI, 4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95% CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) than in households with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%). <h3>Conclusions and Relevance</h3> The findings of this study suggest that given that individuals with suspected or confirmed infections are being referred to isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.
IMMU-30. DISSECTING THE DYNAMIC RESPONSES OF GLIOBLASTOMA TO CAR T CELL THERAPY USING PATIENT-DERIVED TUMOR ORGANOIDS AND SINGLE-CELL MULTI-OMICS ANALYSES
Authors: Daniel Zhang, Ryan Salinas, Donald O’Rourke, Guo-Li Ming, Hongjun Song
Journal: Neuro-Oncology (2020)

Abstract Immunotherapy, including chimeric antigen receptor (CAR) T cell therapy, has yielded major advancements for a number of hard-to-treat cancers; however, its transformative potential has yet to be realized in glioblastoma (GBM). Clinical studies of EGFRvIII targeted CAR T cell therapy have indicated that tumor heterogeneity, immune microenvironment, and adaptive responses to treatment may play important roles in limiting overall efficacy. We sought to examine comprehensively the dynamic molecular landscape of CAR T cell therapy in GBM using patient-derived GBM organoids (GBOs), a newly established laboratory model of inter- and intra- tumoral heterogeneity. Especially advantageous in these studies, GBOs preserve the intrinsic composition of somatic mutations, transcriptomic states, and non-neoplastic cells that contribute to the tumor microenvironment. Complementing the complexity of this biological system, we constructed an integrated single-cell multi-omics platform to interrogate gene expression, cell surface protein expression, somatic variants, and TCR sequences all from the same cell. Co-culture of GBOs and EGFRvIII targeted CAR T cells led to rapid T cell activation with concomitant upregulation of cytokine response gene programs in both antigen-positive and antigen-negative tumor cells. The adaptive tumor response also included expression of immune checkpoint receptor (ICR) ligands, such as PD-L1. At later time points, T cells transitioned into a dysfunctional or exhausted state, as characterized by increased cell surface expression of inhibitory receptors, such as PD-1, and decreased markers of effector activity despite the presence of antigen. Interestingly, CAR T cell therapy not only led to changes in immune-related pathways and tumor microenvironment, but it also induced shifts in tumor cell states with the depletion of an oligodendrocyte precursor cell-like state and corresponding enrichment in an astrocyte-like state. This finding suggests that EGFRvIII targeted CAR T cell therapy may leverage intrinsic cellular plasticity to induce differentiation-like effects in the surviving tumor cells.
IMMU-44. PRE-DIAGNOSTIC EOSINOPHIL LEVEL AND GLIOBLASTOMA DEVELOPMENT IN PATIENTS WITH AND WITHOUT ATOPIC DISEASE
Authors: Omar Bushara, Alexander Guzner, Kirsten Burdett, Patrick Murday, Matias Pollevick, Denise Scholtens, Priya Kumthekar
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Glioblastoma (GBM) is the most common primary malignant brain tumor and carries a very poor prognosis. Recent data report a negative association between the incidence of GBM and atopic disease. The underlying immunologic mechanisms of protection and the associated potential biomarkers are unclear. The aim of this retrospective study is to assess the relationship of eosinophil count to GBM risk by collecting eosinophil count in GBM patients with and without existing atopic disease. METHODS This is a retrospective study of 790 patients diagnosed with GBM from 2009–2019. Of those patients, 140 had laboratory values at least one year prior to diagnosis. Chart review was used to exclude patients with lymphoma, leukemia, other cancers, myelodysplastic syndromes, and unconfirmed drug, food, and adhesive reactions. 14 patients with chart-confirmed allergic rhinitis, asthma, or eczema and 47 controls were found. Wilcoxon rank sum test was used to compare the two groups. RESULTS The two groups did not differ in pre-diagnostic eosinophil counts (p=0.426). The two groups also did not differ in pre-diagnostic basophil, lymphocyte, neutrophil, or monocyte counts. Pre-diagnostic eosinophil to lymphocyte, monocyte to lymphocyte, and neutrophil to lymphocyte ratios also did not differ between the two groups. There were no other quantitative differences that would suggest a difference in immune cell profile. CONCLUSIONS In our study, the subset of GBM patients with atopic disease did not significantly differ in eosinophil count or other white blood cell subtypes when compared to GBM patients without atopic disease. Given that atopic disease is a known protective factor, and our atopic patients with GBM had normal eosinophil counts, we conclude that underlying immunologic factors such as eosinophilia may be protective from GBM as opposed to simply the presence of atopic disease. Prospective analysis to best understand eosinophil count as a surrogate for GBM risk is warranted.
Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223–enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis
Authors: Yong He, Robim M. Rodrigues, Xiaolin Wang, Wonhyo Seo, Jing Ma, Seonghwan Hwang, Yaojie Fu, Eszter Trojnár, Csaba Mátyás, Suxian Zhao, Ruixue Ren, Dechun Feng, Pal Pacher, George Kunos, Bin Gao
Journal: Journal of Clinical Investigation (2020)

Neutrophil infiltration around lipotoxic hepatocytes is a hallmark of nonalcoholic steatohepatitis (NASH); however, how these 2 types of cells communicate remains obscure. We have previously demonstrated that neutrophil-specific microRNA-223 (miR-223) is elevated in hepatocytes to limit NASH progression in obese mice. Here, we demonstrated that this elevation of miR-223 in hepatocytes was due to preferential uptake of miR-223–enriched extracellular vesicles (EVs) derived from neutrophils as well other types of cells, albeit to a lesser extent. This selective uptake was dependent on the expression of low-density lipoprotein receptor (LDLR) on hepatocytes and apolipoprotein E (APOE) on neutrophil-derived EVs, which was enhanced by free fatty acids. Once internalized by hepatocytes, the EV-derived miR-223 acted to inhibit hepatic inflammatory and fibrogenic gene expression. In the absence of this LDLR- and APOE-dependent uptake of miR-223–enriched EVs, the progression of steatosis to NASH was accelerated. In contrast, augmentation of this transfer by treatment with an inhibitor of proprotein convertase subtilisin/kexin type 9, a drug used to lower blood cholesterol by upregulating LDLR, ameliorated NASH in mice. This specific role of LDLR and APOE in the selective control of miR-223–enriched EV transfer from neutrophils to hepatocytes may serve as a potential therapeutic target for NASH.
INNV-11. GLIOBLASTOMA IN THE OLDER PERSON – HOW DO WE DECIDE ON TREATMENT?
Authors: Cressida Lorimer, Anthony Chalmers, Margaret Johnson, Juliet Brock
Journal: Neuro-Oncology (2020)

Abstract The incidence of glioblastoma (GBM) peaks in the 7th and 8th decades of life. Multiple treatment options exist for older patients with GBM however, the assessment of older patients prior to treatment decisions is poorly researched and lacks standardization. In order to address this issue we performed a cross-sectional electronic survey distributed to all full members of the Society for Neuro-Oncology. There were 116 respondents from a total of 1515 recipients (8% response rate). The survey was distributed during the peak of COVID-19 which undoubtedly affected response rates. 97% of respondents were clinicians with 86% academic. 72% had been in practice &amp;gt; 10 years and the majority saw 5–10 new GBM cases per month. 95% of respondents were from the USA, with involvement from Japan, Australia, Canada and Italy. 37% of respondents routinely perform a cognitive or frailty screening test. Of these, MMSE and MoCA were the most commonly used. Of those who performed a screening test, the majority reported that the results changed their treatment decision in approximately 50% of cases. 50% of respondents have access to a multidisciplinary team during their clinic, with physical therapy being the most available. When making treatment decisions, participants ranked performance status as the most important clinical factor. Considering the heterogeneity of this patient population, we argue that performance status is a crude measure of vulnerability within this cohort. In the first survey of this kind, we have shown a disparity in assessment techniques across the international neuro-oncology field and the impact performing a cognitive screen has on decision making. Older patients with GBM represent a unique clinical scenario because of the complexity of distinguishing neuro- oncology related symptoms from general frailty. There is a need for specific geriatric assessment models tailored to the older neuro-oncology population in order to facilitate treatment decisions.
Outcomes of Cord Blood Transplantation for Adult Patients with Hodgkin Lymphoma, a Eurocord and EBMT Lymphoma Working Party Study
Authors: Annalisa Paviglianiti, Karina Tozatto-Maio, Vanderson Rocha, Eve Gehlkopf, Noel Milpied, Albert Esquirol, Patrice Chevallier, Didier Blaise, Gandhi Damaj, Stephanie Nguyen-Quoc, Jean Yves Cahn, Manuel Abecasis, Tsila Zuckerman, Harry C. Schouten, Gunhan Gurman, Marie Therese Rubio, Yves Beguin, Lucia Lopez Corral, Arnon Nagler, John A Snowden, Koc Yener, Nicola Mordini, Francesca Bonifazi, Renato Fanin, Fernanda Volt, Chantal Kenzey, Stephen Robinson, Silvia Montoto, Eliane Gluckman, Annalisa Ruggeri
Journal: Blood (2017)
IMG-22. A DEEP LEARNING MODEL FOR AUTOMATIC POSTERIOR FOSSA PEDIATRIC BRAIN TUMOR SEGMENTATION: A MULTI-INSTITUTIONAL STUDY
Authors: Lydia Tam, Edward Lee, Michelle Han, Jason Wright, Leo Chen, Jenn Quon, Robert Lober, Tina Poussaint, Gerald Grant, Michael Taylor, Vijay Ramaswamy, Chang Ho, Samuel Cheshier, Mourad Said, Nick Vitanza, Michael Edwards, Kristen Yeom
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Brain tumors are the most common solid malignancies in childhood, many of which develop in the posterior fossa (PF). Manual tumor measurements are frequently required to optimize registration into surgical navigation systems or for surveillance of nonresectable tumors after therapy. With recent advances in artificial intelligence (AI), automated MRI-based tumor segmentation is now feasible without requiring manual measurements. Our goal was to create a deep learning model for automated PF tumor segmentation that can register into navigation systems and provide volume output. METHODS 720 pre-surgical MRI scans from five pediatric centers were divided into training, validation, and testing datasets. The study cohort comprised of four PF tumor types: medulloblastoma, diffuse midline glioma, ependymoma, and brainstem or cerebellar pilocytic astrocytoma. Manual segmentation of the tumors by an attending neuroradiologist served as “ground truth” labels for model training and evaluation. We used 2D Unet, an encoder-decoder convolutional neural network architecture, with a pre-trained ResNet50 encoder. We assessed ventricle segmentation accuracy on a held-out test set using Dice similarity coefficient (0–1) and compared ventricular volume calculation between manual and model-derived segmentations using linear regression. RESULTS Compared to the ground truth expert human segmentation, overall Dice score for model performance accuracy was 0.83 for automatic delineation of the 4 tumor types. CONCLUSIONS In this multi-institutional study, we present a deep learning algorithm that automatically delineates PF tumors and outputs volumetric information. Our results demonstrate applied AI that is clinically applicable, potentially augmenting radiologists, neuro-oncologists, and neurosurgeons for tumor evaluation, surveillance, and surgical planning.
Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis
Authors: Kelly Bruton, Paul Spill, Shabana Vohra, Owen Baribeau, Saba Manzoor, Siyon Gadkar, Malcolm Davidson, Tina D. Walker, Joshua F.E. Koenig, Yosef Ellenbogen, Alexandra Florescu, Jianping Wen, Derek K. Chu, Susan Waserman, Rodrigo Jiménez-Saiz, Slava Epelman, Clinton Robbins, Manel Jordana
Journal: Journal of Allergy and Clinical Immunology (2020)