tbuckley/cabot-search huggingface dataset:
<i>BJSM</i>leadership: honouring a legacy and a look to the future
Authors: Jonathan A Drezner
Journal: British Journal of Sports Medicine (2020)

BJSM is more than a scientific journal. It is the international home for sports and exercise medicine (SEM) research, education, and scholarship, and strives to support and serve the broad SEM community. The BJSM community embodies SEM clinicians and researchers around the globe who are dedicated to improving patient care, advancing the scientific foundation of our discipline and open to constructive dialogue and exchange. The journal and its multimedia platform have emerged as the premier home for presenting and disseminating the best in SEM research. As the BJSM ‘family’ continues to grow, so does our opportunity and responsibility to impact the patients under our care and the communities in which we live.

It is my great honour and humble privilege to become the next Editor-in-Chief of this prestigious journal and an ambassador for this respected community. Of course, our success sits on the broad shoulders of the leaders that have come before. It is thus with massive appreciation and gratitude we must thank Professor Karim Khan ( BJSM Editor-in-Chief, 2008–2020) whose dedication and vision have both elevated the journal and reshaped how we engage in new science and discovery.

For so many of us, Karim has been both a mentor and a friend. From the first time we met (2001), I was taken by his genuine interest to understand who I was and what my interests were. As we sat for dinner on the streets of …
NCOG-14. PSYCHOSOCIAL OUTCOMES IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 AND PLEXIFORM NEUROFIBROMAS
Authors: Diane Puccetti, Paige Mission, Shawn Damodharan
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE This case series seeks to examine neurocognitive outcomes, social-emotional functioning, and family burden in young children diagnosed with Neurofibromatosis, type 1 (NF1) with early growing plexiform neurofibromas (PNFs). BACKGROUND Neurofibromatosis, type 1 (NF1) is a common predisposing chronic disease arising in early childhood, with an incidence of approximately 1:3000. Though NF1 displays a wide range of phenotypic variability, the primary feature of the disease is peripheral nerve sheath tumors called neurofibromas. Less is well known regarding the broader neurocognitive and social-emotional profile in presentations with more complex tumor growths, namely PNFs, which are present in at least half of the NF1-affected population. METHODS Participants with NF1 and PNFs (n=2) aged 6-7years completed comprehensive neuropsychological evaluations and parents completed measures of quality of life, social-emotional/behavioral functioning of child, parental stress, family adaptability, and family cohesion. RESULTS Outcomes suggest broad neurocognitive dysfunction (e.g., executive functioning deficits, attention problems, visual-motor delays, and poor motor coordination), social-emotional challenges (e.g., symptoms of anxiety and depression, and poor social skills), and familial distress. CONCLUSIONS Findings indicate the value of early and frequent monitoring of children with PNFs in medical systems and multi-disciplinary teams, and the importance of early intervention for both children and families.
LINC-13. THE STATE OF PEDIATRIC NEURO-ONCOLOGY IN ARMENIA
Authors: Samvel Bardakhchyan, Armen Tananyan, Samvel Danielyan, Jemma Arakelyan, Sergo Mkhitaryan, Karen Bedirian, Liana Safaryan, Mikayel Arustamyan, Gevorg Tamamyan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Every year in Armenia we have approximately 80–90 new pediatric cancer cases from which 10–15 are brain tumors (PBT). Here we try to summarize the current state of pediatric neuro-oncology in Armenia. DISCUSSION: In Armenia pediatric neuro-oncology is still in its first steps. Surgical treatment of PBTs is performed only in one medical center – “Sourb Astvatsamayr” Medical Center, with 7 practicing pediatric neurosurgeons. Radiation therapy service with two linear accelerators is located at the “National Oncology Center”, however there are no dedicated pediatric radiation neuro-oncologists, and 2 specialists are treating pediatric tumors. Chemotherapy for all pediatric cancers currently is performed at the Pediatric Cancer and Blood Disorders Center of Armenia, established in February 2019 as a result of merging of all pediatric oncology units in the country. Among the 11 practicing pediatric hematologist/oncologists no one is dedicated specifically to PBTs. Since September 2017 we have started discussing all PBT cases (up to now 18 cases) through the telemedicine with St. Jude Children’s Research Hospital (SJCRH). In Sept 2019 neuro-oncology multidisciplinary team was created with the involvement of local and foreign specialists. On a weekly basis the multidisciplinary team discusses all new and problematic cases. The team also concentrates on adaptation of diagnostic and treatment guidelines for pediatric CNS tumors, creation of educational materials for different stakeholders, and identification of current problems and their possible solutions. CONCLUSION To the best of our knowledge this is the first report summarizing the current state of pediatric neuro-oncology in Armenia.
EPEN-38. EZH2 INHIBITORY PROTEIN (EZHIP/Cxorf67) EXPRESSION IS HIGHLY CONCORDANT WITH H3K27me3 LOSS AND IS A PROMISING SURROGATE MARKER FOR POSTERIOR FOSSA TYPE A EPENDYMOMAS
Authors: Aruna Nambirajan, Madhu Rajeshwari, Meher Boorgula, Ramesh Doddamani, Manmohan Singh, Ajay Garg, Vaishali Suri, Chitra Sarkar, Mehar Sharma
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Gene expression and DNA methylation have identified 2 distinct clinicopathological subgroups among the WHO Grade II/III posterior fossa (PF) ependymomas (EPN), of which the PF-A molecular subgroup associates with poor outcome. OBJECTIVE To analyse the utility of immunohistochemistry for H3K27me3, Tenascin C, EZHIP (Cxorf67), EZH2 and fluorescence-in-situ-hybridisation for chromosome 1q21 locus gain in the prognostic stratification of PF-EPNs. METHODS All PF Grade II/III tumors were retrieved (2009–2019). Immunohistochemistry for H3K27me3, H3K27M-mutation-specific antibody, EZH2, EZHIP, Tenascin-C and fluorescence in-situ hybridisation for 1q21 locus was performed and compared with outcome. RESULTS 71 PF-EPNs were included. H3K27me3 loss (PF-A) was seen in 65% (46/71) of cases, of which majority were positive for EZHIP (73%, 24/33) and Tenascin C (65%, 28/43). Minority showed chromosome 1q gain (19%, 8/42). An EZHIP negative PF-A tumor was immunopositive for H3K27M-mutant staining, while all others were negative. PF-A EPNs occurred at a median age of 4.5 years (range 1–53), were predominantly grade III (Grade III:II – 1.6:1), and 50% (10/20) of patients on follow-up experienced tumor progression. EPNs with retained H3K27me3 (PF-B) did not show EZHIP expression (0/20) or 1q gain; however, tenascin C expression was seen in 47% (8/25) of them. They occurred predominantly in adults, showed Grade II preponderance and only 2/11 patients on follow-up experienced progression. EZH2 expression did not correlate with H3K27me3 loss but positively correlated with EZHIP expression (p=0.015). CONCLUSION H3K27me3 is a reliable surrogate for prognostic classification of PF-EPNs. EZHIP expression is highly concordant with H3K27me3 loss and is a valuable adjunct.
Race Based Medicine, Colorblind Disease: How Racism in Medicine Harms Us All
Authors: Ruqaiijah Yearby
Journal: The American Journal of Bioethics (2020)

The genome between socially constructed racial groups is 99.5%–99.9% identical; the 0.1%–0.5% variation between any two unrelated individuals is greatest between individuals in the same racial group; and there are no identifiable racial genomic clusters. Nevertheless, race continues to be used as a biological reality in health disparities research, medical guidelines, and standards of care reinforcing the notion that racial and ethnic minorities are inferior, while ignoring the health problems of Whites. This article discusses how the continued misuse of race in medicine and the identification of Whites as the control group, which reinforces this racial hierarchy, are examples of racism in medicine that harm all us. To address this problem, race should only be used as a factor in medicine when explicitly connected to racism or to fulfill diversity and inclusion efforts.
Declining Life Expectancy in the United States: Missing the Trees for the Forest
Authors: Sam Harper, Corinne A. Riddell, Nicholas B. King
Journal: Annual Review of Public Health (2020)

In recent years, life expectancy in the United States has stagnated, followed by three consecutive years of decline. The decline is small in absolute terms but is unprecedented and has generated considerable research interest and theorizing about potential causes. Recent trends show that the decline has affected nearly all race/ethnic and gender groups, and the proximate causes of the decline are increases in opioid overdose deaths, suicide, homicide, and Alzheimer's disease. A slowdown in the long-term decline in mortality from cardiovascular diseases has also prevented life expectancy from improving further. Although a popular explanation for the decline is the cumulative decline in living standards across generations, recent trends suggest that distinct mechanisms for specific causes of death are more plausible explanations. Interventions to stem the increase in overdose deaths, reduce access to mechanisms that contribute to violent deaths, and decrease cardiovascular risk over the life course are urgently needed to improve mortality in the United States.
COVD-22. COVID-19+ GLIOMA PATIENT CARE: LESSONS FROM A 5-PATIENT CASE SERIES
Authors: Ahmad Daher
Journal: Neuro-Oncology (2020)

Abstract Glioma patients, like other cancer patients, are at an increased risk of COVID-19 infections, but there are no specific guidelines on how their care should be modified during this pandemic. The challenge to develop such guidelines is largely related to the limited number of reported cases and lack of studies on this particular patient population. We present a 5-patient case series of glioma, detailing their baseline characteristics, treatment courses, lab abnormalities, and the changes made to their care after they developed COVID-19. The median age of the patient population was 66 years. All patients had IDH-wild type glioma (3 Grade IV, 1 Grade III, and 1 Grade II) and all of whom had received temozolomide chemotherapy shortly before COVID-19 diagnosis (median = 22 days). Three patients presented with mild non-respiratory symptoms requiring hospitalization to two of them, and adjuvant Temozolomide chemotherapy was held in all. One patient developed severe symptoms of shortness of breath requiring ICU-stay and expired eight days later. One patient was asymptomatic, tested positive during a routine pre-chemotherapy screening, and initiation of temozolomide was delayed by two weeks after a negative repeat test. All four symptomatic patients were rehabilitation facility residents. The most common lab abnormality was lymphopenia seen in 4/5 patients. Other abnormalities seen included elevated ferretin/total bilirubin/CRP/LDH/procalcitonin/D-dimer, thrombocytopenia/leukopenia, and low sodium/vitamin D. Chest x-ray findings were normal in 3/5 patients and showed ground glass opacities in 1 patient. COVID-19 screening during different phases of glioma therapy is recommended. Therapy interruptions or shortening duration of treatment particularly of temozolomide given its risk on lymphopenia may be needed. lymphopenia thresholds, MGMT promoter methylation status, and residence in rehabilitation facilities may help stratify glioma patient COVID-19 risks further. Patients and their family will need to be involved in therapies’ risk:benefit discussions during this pandemic.
STEM-05. SINGLE CELL SEQUENCING CHARACTERIZES SPATIAL AND TEMPORAL RELATIONSHIPS OF ENHANCING AND NON-ENHANCING REGIONS IN HIGH-GRADE GLIOMA
Authors: Kunal Patel, Riki Kawaguchi, Alvaro Alvarado, Deepthi Muthukrishnan, Richard Everson, Linda Liau, Daniel Geschwind, Benjamin Ellingson, Harley Kornblum
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Treatments of high grade glioma focus on the contrast enhancing (CE) portion of the tumor. However, given the invasive nature of glioma, residual tumor cells responsible for recurrence likely exist in the non-enhancing (NE) region. METHODS In 3 patients undergoing surgery for malignant glioma, we used pre-operative magnetic resonance images to prospectively identify biopsy targets in the CE region and locations 0.5-2.0cm beyond the CE edge. We carried out single cell sequencing on image guided biopsy specimens to generate 12,528 RNA profiles. RESULTS In all samples, tumor cells clustered into three predominant groups: tumor cells with astrocyte markers (ASC-like), tumor cells with oligodendrocyte markers (ODC-like), and tumor cells with neither marker. This last group consisted of a small proportion of tumor cells and expressed putative stem cell markers (PROM1, NES, SLC1A3, A2B5, ID1). A trajectory analysis consistently positioned this group as branching off into either ASC-like or ODC-like cells. CE regions had different cellular compositions than NE regions, with higher proportions of tumor, endothelial cells, T-cells, and NK cells. Using location and cell density data, we modeled expected tumor burden, predicting tumor cells up to 1.5cm beyond the CE region of the tumor. There were significant differences in gene expression between CE and NE tumor cells, with increased inflammation and hypoxia in the CE region versus increased proliferative markers in the NE region. Tumor cells in the NE region were characterized by increased proliferation, markers of invasion, and markers of self-renewal. CONCLUSIONS Single cell sequencing illustrates multiple glioma cell types and suggests a hierarchical relationship between tumor cell types. CE and NE regions exhibit different tumor and non-tumor cell populations as well as different gene expression profiles within individual cell types. There remains a significant tumor cell burden in the NE portion of tumor, including actively proliferating cells.
NFB-04. EXAMINING DIFFUSION, ARTERIAL SPIN-LABELED PERFUSION, AND VOLUMETRIC CHANGES IN THE NEUROFIBROMATOSIS TYPE 1 BRAIN USING AN ATLAS-BASED, MULTI-PARAMETRIC APPROACH
Authors: Lydia Tam, Nathan Ng, Peter Moon, Jimmy Zheng, Emily McKenna, Nils Forkert, Cynthia Campen, Kristen Yeom
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Neurofibromatosis Type 1 (NF1) is a multisystem disorder with wide ranging clinical implications. Patients may present with macrocephaly, stroke, and cognitive deficits, all of which may impede normal neural development. We applied atlas-based, multi-parametric MRI analysis of regional brain to evaluate diffusion, arterial spin-labeled (ASL) perfusion, and volumetric changes in children with NF1. METHODS Children evaluated for NF1 from 2009 to 2018 at Stanford University (n=78) were retrospectively reviewed and compared to healthy controls (n=100). All patients underwent diffusion-weighted (DWI) magnetic resonance imaging at 3T, and children with brain tumors were excluded. Using atlas-based DWI analyses, we assessed volume, median apparent diffusion coefficient (ADC), and cerebral blood flow in the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. We also measured volume of the lateral ventricles. Multivariate analysis of covariance was used to test for differences between controls and NF1 patients, controlling for gender and age at time of imaging. RESULTS Comparing NF1 to controls, we detected increased volume and decreased ASL cerebral blood flow in white matter and all subcortical and cortical structures except for brainstem volume. Median ADC was also increased in the thalamus, pallidum, hippocampus, and brainstem. CONCLUSIONS Using a multi-parametric approach, we demonstrate quantitative measures of microstructural and physiologic changes of the NF1 brain. Atlas-based, quantitative MRI brain signatures may serve as biomarkers of neural development and further provide insight into associated cognitive dysfunction or risks for vasculopathy-related strokes in children with NF1.
CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS
Authors: Macarena De La Fuente, Tulay Koru-Sengul, Deborah Heros, Feng Miao, Alain Fernandez Marrero, Dalissa Tejera, Michelle Liendo, Aisha Khan, Nagi Ayad, Michael Ivan, Ricardo Komotar
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.
A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer
Authors: Neil K. Jairath, Alan Dal Pra, Randy Vince, Robert T. Dess, William C. Jackson, Jeffrey J. Tosoian, Sean M. McBride, Shuang G. Zhao, Alejandro Berlin, Brandon A. Mahal, Amar U. Kishan, Robert B. Den, Stephen J. Freedland, Simpa S. Salami, Samuel D. Kaffenberger, Alan Pollack, Phuoc Tran, Rohit Mehra, Todd M. Morgan, Adam B. Weiner, Osama Mohamad, Peter R. Carroll, Matthew R. Cooperberg, R. Jeffrey Karnes, Paul L. Nguyen, Jeff M. Michalski, Jonathan D. Tward, Felix Y. Feng, Edward M. Schaeffer, Daniel E. Spratt
Journal: European Urology (2020)
RONC-25. A CASE OF PEDIATRIC PONTINE GLIOMA TREATED WITH GAMMA KNIFE SURGERY
Authors: Satoshi Kaneko, Juri Kiyokawa, Shin Hirota, Yasuhiro Murota, Mariko Ishikawa, Hiroto Yamaoka, Masataka Yoshimura, Masaaki Yamamoto, Shinji Yamamoto
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric brainstem gliomas rarely occur and are a heterogeneous group of diseases, which increases the difficulty of treatment strategy. Here, we present a case of pediatric pontine glioma treated with Gamma Knife surgery (GKS) after open biopsy. CASE DESCRIPTION: An 11-year-old boy presented with diplopia due to the left MLF syndrome. MRI showed a well-circumscribed, protruding tumor with partial gadolinium enhancement in the dorsal pons. An open biopsy was performed via the suprafacial triangle following midline suboccipital approach. Histological examinations revealed high cellularity and mild atypia. Immunohistochemistry demonstrated positive stain for GFAP and Olig2 antibodies, and negative for p53 protein. The Ki67-labeling index was 6.8%. Pyrosequence analysis indicated IDH1/2 wild type (wt), BRAF V600 wt, H3F3A K27 wt, FGFR1 wt, and TERT wt. The final diagnosis was pediatric diffuse astrocytoma, WHO grade II, pons. GKS was performed one month after the biopsy. After transient worsening of the symptom, it disappeared gradually. The tumor is stable for three years with mild shrinkage of the size. DISCUSSION: Gross total resection (GTR) of pediatric low-grade, brainstem gliomas may result in a good prognosis. However, unlike pilocytic astrocytoma, diffuse astrocytoma is not easy to perform GTR without any complications. There are some reports regarding GKS for brainstem gliomas, which prove an increase in progression free survival rate. No marked tumor regression is achieved in our case, but tumor growth is well-controlled so far. CONCLUSION GKS after biopsy can be a useful treatment option for pediatric low-grade brainstem gliomas.
RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION
Authors: Ingo Mellinghoff, Martin van den Bent, Jennifer Clarke, Elizabeth Maher, Katherine Peters, Mehdi Touat, John de Groot, Macarena De La Fuente, Isabel Arrillaga-Romany, Wolfgang Wick, Benjamin Ellingson, Steven Schoenfeld, Hua Liu, Kha Le, Min Lu, Lori Steelman, Islam Hassan, Shuchi Pandya, Patrick Wen, Timothy Cloughesy
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).