tbuckley/cabot-search huggingface dataset:
IMG-12. CHARACTERISATION OF MODELS OF <i>H3F3A</i>_G34R/V MUTANT PAEDIATRIC GLIOBLASTOMA <i>IN VIVO</i> USING MAGNETIC RESONANCE IMAGING
Authors: Jessica Boult, Lynn Bjerke, Mariama Fofana, Maria Vinci, Valeria Molinari, Alan Mackay, Sara Temelso, Gary Box, Suzanne Eccles, Angel Carcaboso, Maria Castro, Angela Waanders, Kristina Cole, Chris Jones, Simon Robinson
Journal: Neuro-Oncology (2020)

Abstract Approximately 15% of paediatric/young adult cerebral hemispheric glioblastomas (pGBM) harbour G34R/V mutations in H3F3A, encoding the histone H3.3 variant. Development of novel therapeutic interventions demands models that accurately recapitulate this subset of disease and sensitive imaging methods with which to study tumours in situ. Three H3F3A_G34R primary-patient-derived cultures, alongside established cell-line KNS42 (H3F3A_G34V), were implanted orthotopically in immunocompromised mice. KNS42 (TP53_R342*) tumours were clearly detectable using T2-weighted (T2w)-MRI, enhanced following contrast agent administration, indicating impaired blood-brain barrier (BBB) integrity, and demonstrated minimal invasion. OPBG_GBM_001 cells (TP53_89-90X,ATRX_II2133-2144X) formed infiltrative tumours that were hyperintense on T2w-MRI and demonstrated contrast-enhancement suggestive of heterogeneous BBB integrity. HSJD_GBM_002 cells (TP53_P278T,ATRX_R666*) spread diffusely throughout the brain with their full extent typically not discernible by T2w-MRI, the BBB also remaining intact. No evidence of CHOP_GBM_001 tumour was detected by MRI 11months post-implantation. Immunocompetent syngeneic models using tumour cells induced by mutations modelling hemispheric pGBM (NRAS/shP53/shATRX±H3.3G34R) are being explored. Fast growing heterogeneous lesions with variable contrast-enhancement were identified; the H3.3G34R mutation conferred longer median survival (2 clones:25/28days, control:14days). These models have the advantage of an intact immune system and short latency for initial efficacy studies. Primary pGBM cells yield tumours that are more representative of the spectrum of clinical disease; variable hyperintensity on T2w-MRI corresponding to cellular density, with diffusely infiltrative disease less clearly definable, a paucity of oedema and a range of contrast-enhancement. Pathological features including giant multinucleated cells, and mitotic figures were also evident.
Abstract 15010: Risk Reduction of Stroke and Early Post-Stroke Mortality in Patients With Non-Valvular Atrial Fibrillation (NVAF): A Comparison of Rivaroxaban vs Warfarin
Authors: Mark Alberts, Jennifer H Lin, Yen-Wen Chen, Deepti Bisht, Emily Kogan, Kathryn Twyman, Dejan Milentijevic
Journal: Circulation (2018)

Background: The ROCKET-AF trial demonstrated lower event rates of disabling stroke and stroke with outcome of death in NVAF patients treated with rivaroxaban compared to warfarin. However, limited ...
NIMG-04. MRI EVALUATION OF THE EFFECT OF WHOLE BRAIN RADIOTHERAPY ON BRAIN METASTASIS
Authors: William Crowe, Dawen Zhao, Zhongwei Zhang, Lulu Wang, John Bourland
Journal: Neuro-Oncology (2020)

Abstract Poor prognosis of breast cancer brain metastasis partially results from the inability of therapeutics to penetrate the Blood-Brain-Barrier (BBB). Whole Brain Radiotherapy (WBRT) is standard-of-care for brain metastasis, however the early effects of fractionated WBRT on brain metastases have not been evaluated. Here, we applied longitudinal MRI to study WBRT’s effect on tumor volume, BBB permeability, and tumor-cell killing using anatomic, Dynamic Contrast Enhanced (DCE), and Diffusion-weighted (DW) MRI, evaluating tumor volume, permeability, and cytotoxic effect, respectively. The BCBM mouse model was established with left ventricle MDA-MB231-Br cell injection. MRI occurred before and 24h after 3 daily fractionated 4Gy WBRT (2.4Gy/min) or sham irradiation. In addition to anatomic MRI, DW MRI measured tissue ADC to study cytotoxic effect, and DCE MRI measured BBB permeability, quantified as the permeability variable Ktrans. Before treatment, T2-weighted images revealed hyperintense multifocal lesions in brains, and many had intact BBB indicated by no T1-w contrast-enhancement. WBRT tumors were smaller than sham irradiated tumors after 3 days (p&amp;lt; 0.05), while no difference in the number of new lesions was observed. DW MRI demonstrated increased ADC in WBRT tumors (p&amp;lt; 0.05), correlating well with elevated Caspase-3 staining of apoptotic cells. T1-w contrast enhanced images of tumors after treatment revealed no differences in the population of contrast-enhanced tumors between the WBRT and sham radiation groups. However, quantitative DCE MRI showed higher Ktrans in WBRT treated tumors relative to sham treated lesions, and an increase in Ktrans of WBRT tumors (p&amp;lt; 0.05), despite high permeability heterogeneity both inter- and intra-tumorally, indicating remaining impermeable BBB. In addition to monitoring tumor volume, longitudinal MRI provided non-invasive assessments of temporal and spatial changes in cellularity and vascular permeability of brain metastasis in response to WBRT, which may prove to be useful for defining an ideal treatment window for potential combination BCBM treatments.
RADT-22. RE-IRRADIATION FOR RECURRENT GLIOBLASTOMAS (GBM)
Authors: Mario Moro
Journal: Neuro-Oncology (2020)

Abstract AIMS In this report, we describe our experience in dealing with recurrent GBMs in terms of efficacy and toxicity of second RT course (re-RT) with 3DCTR or VMAT protocols. We carefully reviewed our patient’s outcomes and additionally performed a comprehensive and updated meta-analysis of recent recurrent re-RT GBMs literature to compare our results with the ongoing findings of the t studies. METHODS We retrospectively collected data between 2017 and 2020 at our Institution. Also, we used the random-effects model to pool outcomes across studies about re-RT GBMs from the recent literature (prospective studies from 2010 to 2020, ≥ 30 patients, re-RT with 3DCTR or IMRT-VMAT) to have a more homogenous cohort in terms of treatment modalities, thus reducing the selection bias. RESULTS Re-irradiation was performed at a median interval time of 13.5 (range 4 - 192 months) months from the first RT. The median re-RT dose was 18 Gy (range 12–36 Gy), and the median fraction size was 3,45 Gy (range 1,8–6 Gy). The total median equivalent dose (EQD2) was 84 Gy (range 65.7 – 110 Gy). Our cohort median PFS is 12.5 months (range 4 – 192 months), while the median OS was 26 months (range 6 – 213 months). Our results show that OS-6 and OS-12, from time of re-irradiation, to be 69.2% and 30.7% respectively and the PFS-6 and PFS-12 to be 76.9% and 23.0%, respectively. None of our patients experienced acute toxicity. In our literature research, we found 22 eligible studies, including 1065 patients. The results of the pooled outcomes were: OS-12 rate 35% (95% CI: 30–40%), PFS-12 rate 16% (95% CI 13–19%), and Grade 3 + AE rate &amp;lt; 5% (95% CI 0–10%). CONCLUSIONS Our data confirm re-RT is safe and feasible treatment with a limited toxicity for salvage treatment in recurrent GBMs.
HGG-39. CLINICAL CHARACTERISTICS AND OUTCOME OF PATIENTS WITH RADIATION-INDUCED GLIOMA
Authors: Makoto Ohno, Yasuji Miyakita, Masamichi Takahashi, Takaki Ohmura, Natsuko Satomi, Yukie Tamura, Yuko Matsushita, Koichi Ichimura, Yoshitaka Narita
Journal: Neuro-Oncology (2020)

Abstract The development of gliomas subsequent to therapeutic cranial irradiation is a rare but serious complication. The purpose of this study is to understand the clinical characteristics and outcome of patients with radiation-induced glioma (RIG). Between 2001 and 2018, we identified 10 patients with RIG, which satisfied the Cahan’s criteria in our data base. There was no sex predominance (M: 5, F: 5), and the median age of the primary diseased was 13.5 years (range: 1–39). The primary diseases included 2 germinoma, 2 acute lymphoblastic lymphoma, 2 medulloblastoma, 1 diffuse astrocytoma, 1 pilocytic astrocytoma, 1 pituitary adenoma and 1 metastatic tumor from lung cancer. All the patients received cranial radiation (range: 12–60 Gy). The median latency time between primary disease and RIG was 16 years (range: 9–30 years), which was not correlated with age at the time of primary disease (r2= 0.014, p=0.74). Radiation-induced gliomas included 8 glioblastoma and 2 grade III glioma based on histological diagnosis. After surgical removal or biopsy of the RIG, 4 patients underwent chemotherapy alone (nimustine, temozolomide (TMZ), carboplatin and etoposide), and 6 received chemotherapy (nimustine, TMZ, bevacizumab) combined with radiotherapy (range: 40-66Gy). The median progression free survival and survival time from RIG were 10.1 and 27.5 months, respectively. In summary, RIG may occur many years after successful initial treatment using radiotherapy, and the outcome of our patients with RIG supports the use of radiotherapy and/or chemotherapy after surgical resection.
EPEN-13. PRIMARY EXTRADURAL SACROCOCCYGEAL SUBCUTANEOUS MYXOPAPILAR EPENDYMOMA MISDIAGNOSED AS PILONIDAL CYST IN A 7 YEAR-OLD BOY: A CASE REPORT
Authors: Regina M Navarro-Martin del Campo, Geronimo M Tavares-Macias, Luis Ivan Pozos-Ochoa, Ana L Orozco-Alvarado, Fernando Sanchez-Zubieta, Luis Angel Arredondo-Navarro
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Ependymomas occur in the brain or spinal cord and rarely as an extraspinal variety at the sacrococcygeal region, separated from the spinal cord. This rare presentation is thought to originate from a group of heterotopic ependymal cells called the coccygeal medullary vestige. There are few reports of this occurrence in children. CLINICAL CASE: A 7-year-old male presented with a history of a soft mass arising in the sacrococcygeal area 3 years earlier, diagnosed as pilonidal cyst at primary level and treated with surgery twice, as this mass recurred the boy was sent to our hospital, a 3rd surgery was performed, all tumoral tissue was removed, no attachment with dural space was founded, pathology revealed myxopapilar ependymoma with positivity for PS100, EMA and Vimentin. After surgery a Follow up MRI of cranium and spine showed absence of disease, no radiotherapy neither chemotherapy was implemented. He has been on surveillance from 3 years now without recurrence. CONCLUSION This report highlights the fact that pediatric ependymoma can have an extradural presentation and can be confounded with pilonidal cyst, total resection is needed to control the disease. Potential for recurrence or metastatic disease can continue 20 years from the time of primary tumor, so prolonged surveillance is important.
COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA
Authors: Amanda Immidisetti, Sean Munier, Nitesh Patel
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND High-grade gliomas (HGG) pose therapeutic challenges stemming from blood brain barrier, infiltrative growth, suppressed immune function, and tumor heterogeneity. Oncolytic viruses (OVs) are gaining traction for addressing these challenges. There is evidence that the SARS-CoV-2 glycoprotein spike binds the ACE-2 receptor in nasal epithelium and reaches the brainstem and thalamus via axonal transport through the olfactory pathway, making it an attractive candidate for OV therapy. Prior studies on chimerization of pathogenic virus-derived glycoprotein spikes with non-pathogenic strains exploit neurotropism of a wild-type virus while improving the safety profile of the resulting OV. We review, 1) the engineering of chimeric OVs used in the treatment of HGG; 2) potential for a novel chimeric virotherapy in which the SARS-CoV-2 glycoprotein spike can be used to deliver OV therapy intranasally; and 3) areas which warrant further investigation to develop this approach for clinical use. METHODS We performed an extensive review of chimeric OVs and specific modifications engineered to optimize safety and efficacy. Additionally, we assessed potential to use these principals to engineer the SARS-CoV-2 glycoprotein spike onto a non-pathogenic, replication competent virus to yield a novel chimeric for noninvasive, intranasal delivery. RESULTS Viruses with pathogenic properties in wild-type have been successfully used as components of OVs and have demonstrated potential in both preclinical and clinical trials. Outcomes show that despite wild-type virulence, notable toxicities were not observed in clinical trials, highlighting the potential of viral pseudotyping as a safe therapeutic approach. CONCLUSIONS The proposed method to utilize the SARS-CoV-2 glycoprotein in a novel chimeric poses advantages including 1) potential for non-invasive delivery, 2) therapy without need for maximal or uniform tumor coverage due to replication competence, 3) ability to reach infiltrative glioma cells, 4) potential to reach the brainstem, and 5) stimulation of host immunity through tumor cell lysis and antigen presentation
NIMG-27. THRESHOLD VALUES OF EARLY METABOLIC CHANGES IN 1H MRSI METABOLIC METRICS PREDICTIVE FOR SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA
Authors: Samir Patel, Michael Wang, Keith Wachowicz, Atiyah Yahya, Albert Murtha, John Amanie, Harvey Quon, Jonathan Chainey, Sunita Ghosh, Wilson Roa
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy. METHODS Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRS scans were performed at baseline, week 4 of radiation therapy (RT), and two months post-RT to measure tumor choline, creatine, and N-acetylaspartate (NAA) normalized to contralateral normal brain. Serial changes in metabolites were assessed using the Wilcoxon signed-rank test. Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival. RESULTS Median follow-up time was 13.4 years, and vital status was available for 95.1% of patients. Mean normalized choline, creatine and choline/creatine decreased significantly after baseline to post-RT in the overall group of patients (all P &amp;lt; 05). Overall survival (OS) was longer in patients with ≤ 20% increase (vs. &amp;gt; 20%) in normalized choline (P = .024) or choline/NAA (P = .024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in with patients ≤ 40% increase (vs. &amp;gt; 40%) in normalized choline (P = .013). From mid-RT to post-RT, ≤ 40% decrease (vs. &amp;gt; 40%) in normalized choline/NAA (P &amp;lt; .001) or choline/creatine (P = .014), or ≤ 40% increase (vs. &amp;gt; 40%) in NAA/creatine (P = .030) were associated with reduced median OS. CONCLUSIONS Threshold values for serial changes in choline metrics on MRSI associated with OS and PFS were identified. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response, and could enable risk-adapted therapy in clinical trial development and clinical practice.
The 2020 race towards SARS-CoV-2 specific vaccines
Authors: Tomasz M. Karpiński, Marcin Ożarowski, Agnieszka Seremak-Mrozikiewicz, Hubert Wolski, Donald Wlodkowic
Journal: Theranostics (2020)

The global outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a requirement for two pronged clinical interventions such as development of effective vaccines and acute therapeutic options for medium-to-severe stages of "coronavirus disease 2019" (COVID-19). Effective vaccines, if successfully developed, have been emphasized to become the most effective strategy in the global fight against the COVID-19 pandemic. Basic research advances in biotechnology and genetic engineering have already provided excellent progress and groundbreaking new discoveries in the field of the coronavirus biology and its epidemiology. In particular, for the vaccine development the advances in characterization of a capsid structure and identification of its antigens that can become targets for new vaccines. The development of the experimental vaccines requires a plethora of molecular techniques as well as strict compliance with safety procedures. The research and clinical data integrity, cross-validation of the results, and appropriated studies from the perspective of efficacy and potently side effects have recently become a hotly discussed topic. In this review, we present an update on latest advances and progress in an ongoing race to develop 52 different vaccines against SARS-CoV-2. Our analysis is focused on registered clinical trials (current as of November 04, 2020) that fulfill the international safety and efficacy criteria in the vaccine development. The requirements as well as benefits and risks of diverse types of SARS-CoV-2 vaccines are discussed including those containing whole-virus and live-attenuated vaccines, subunit vaccines, mRNA vaccines, DNA vaccines, live vector vaccines, and also plant-based vaccine formulation containing coronavirus-like particle (VLP). The challenges associated with the vaccine development as well as its distribution, safety and long-term effectiveness have also been highlighted and discussed.
The respiratory microbiota during and following mechanical ventilation for respiratory infections in children
Authors: Emma M. de Koff, Wing Ho Man, Marlies A. van Houten, Nicolaas J.G. Jansen, Kayleigh Arp, Raiza Hasrat, Elisabeth A.M. Sanders, Debby Bogaert
Journal: European Respiratory Journal (2020)

<b>During mechanical ventilation for an LRTI in children, the respiratory microbiota shifted from <i>Haemophilus-</i> and <i>Moraxella</i>-dominated profiles to profiles dominated by antibiotic-resistant <i>Enterobacteriaceae,</i> and <i>Staphylococcus</i> and <i>Streptococcus</i> species.</b>https://bit.ly/3pGfvhQ
Acute Decompensated Heart Failure: The Quest to Live Longer and Feel Better: Can We Have it All?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: J. Malcolm O. Arnold, Liane Porepa
Journal: Journal of the American College of Cardiology (2012)
GCT-58. BRAZILIAN CENTRAL NERVOUS SYSTEM GERM CELL TUMOR CONSORTIUM PROTOCOL
Authors: Andréa M Cappellano, Nasjla S Silva, Bruna Mançano, Daniela B Almeida, Sergio Cavalheiro, Patricia A Dastoli, Frederico A Silva, Sidnei Epelman, Simone S Aguiar, Jonathan L Finlay
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Primary central nervous system (CNS) germ cell tumors (GCT) account for 2–3% brain tumors children/adolescents in Western hemisphere. The report aim is to present the results of a Brazilian CNSGCT consortium protocol. METHODS Since 2013, 45 patients with histologic and/or tumor marker (TM) diagnosis of germinoma with/without HCGβ levels≤200mIU/ml (n=33), four between 100-200mIU/ml and NGGCT (n=12), received carboplatin/etoposide/cyclophosphamide (4–6 cycles), followed by 18Gy ventricular field irradiation and primary site(s) boost. Autologous bone marrow transplant (ABMT) was conducted for NGGCT low responders. RESULTS Mean age 12.9 years (4.7-20y), 34 males. Diagnosis was made by TM (n=9), surgery (n=19), both (n=15). Two bifocal cases, (-)TM were treated as germinoma. Primary tumor location was pineal (n=20), suprasellar (n=13), bifocal (n=11) and basal ganglia/thalamus (n=1). Fourteen had ventricular/spinal spread. Second-look surgery occurred in 5 patients. For the germinoma group, 26 achieved complete response (CR) after chemotherapy, seven showed residual teratoma/scar. For the NGGCT after 2/4 cycles, four patients showed CR, 2 failure/progression and 6 partial response (4 (-)TM). Two were submitted to ABMT. Radiotherapy was performed as described, except in three. One recurrence to date. Two patients died (endocrinologic complications/progression). Toxicity was mostly grade ¾ neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 38 months, OS was 100% for Germinoma and 85% NGGCT. CONCLUSION The treatment is tolerable and VFI dose reduction to 18Gy seems to preserve efficacy. Further follow-up is warranted to assess the NG group and the slow-responder patients.
Paclitaxel Versus Sirolimus: The Battle Is Still Ongoing⁎⁎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: Christodoulos Stefanadis, Konstantinos Toutouzas
Journal: Journal of the American College of Cardiology (2009)
Left Ventricular Hypertrophy and Excess Cardiovascular Mortality: Is Late Gadolinium Enhancement the Imaging Link?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Michael L. Chuang, Warren J. Manning
Journal: Journal of the American College of Cardiology (2009)
DIPG-39. NOVEL PROTEOMIC ANALYSIS REVEALS EPIGENETIC THERAPEUTIC TARGETS IN PEDIATRIC GLIOMA
Authors: Daphne Li, Tina Huang, Jeannie Camarillo, Andrea Piunti, Jin Qi, Shejuan An, Javad Nazarian, Paul Thomas, Amanda Saratsis
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Diffuse midline glioma is a highly morbid pediatric cancer. Up to 80% harbor Histone H3K27M mutation, which alters Histone H3 post-translational modifications (PTMs) and genomic enrichment patterns, affecting chromatin structure and transcription. We previously identified tumorigenic patterns of H3K27Ac/bromodomain co-enrichment and pre-clinical efficacy of bromodomain inhibition (JQ1) in DMG. Here, we employ a novel proteomics approach developed at our institution to further elucidate the impact of H3K27M mutation on glioma epigenetic signatures and treatment response. METHODS Epiproteomic analysis was performed on pediatric glioma cells (H3K27 WT n=2, H3K27M n=2) to characterize 95 distinct Histone H3 N-terminal tail modification states. Cells were treated with JQ1 or DMSO, and collected at 0h, 24h, 48h, Histones extracted from isolated nuclei and immunopurified, then analyzed by LC-MS/MS. Results were integrated with RNA-Seq and ChIP Seq (H3.3K27M, H3.3, H3K27Ac, H3K27me3, H3K4me1, H3K4me3) from the same cell lines. Pediatric glioma tissues (H3K27M WT n=3, H3K27M n= 9) were similarly analyzed to validate cell line results. RESULTS Cell PTM profiles cluster by H3 mutation status on unsupervised analysis. Significant differential PTM abundance and genomic enrichment H3K27M, H3.3 WT, H3K27Me3 and H3K27Ac was observed between mutant and wild type cell lines with epigenetic-targeted therapy, correlating with cell transcriptomes. CONCLUSIONS Histone H3 tail analysis reveals the effects of H3K27M mutation and bromodomain inhibition on the tumor epigenetic landscape, providing insight into mechanisms of tumorigenesis and therapy response. Further investigation of the utility of these signatures as biomarkers for diagnosis and monitoring treatment response are therefore underway.