tbuckley/cabot-search huggingface dataset:
EPID-05. EVALUATION OF THE INCIDENCE OF CENTRAL NERVOUS SYSTEM TUMORS IN A CHILDHOOD CANCER TREATMENT CENTER AND THE CREATION OF A SPECIFIC GROUP
Authors: Alessandra Azambuja, Juliana Barreto, Lilian Maria Cristofani, Felipe Sanders, Helena Baraldi, Eduardo Weltman, Leandro Lucato, Vitor Paes, Fernando Frassetto, Carlo Petitto, Sergio Rosemberg, Hamilton Matushita, Vicente Odone
Journal: Neuro-Oncology (2020)

Abstract Central Nervous System Tumors (CNST) are the main solid neoplasm of childhood, representing 20% diagnosis. Based on this information, a search was carried out at a reference treatment center for childhood cancer in the state of Sao Paulo, belonging to University of Sao Paulo- ITACI/HCFMUSP, and at between 2017 and 2019, 352 new patients, 116 of which were neoplasm of CNS (32.9%). Aiming at an incidence of new cases, in 2019, an institutional group was created, with a team composed of Pediatric Oncologists, Neurosurgeons, Radiologists, Radiotherapists and Pathologists. In this first year, 31,8% of the 132 new patients were diagnosed with CNS tumor. According to WHO 2016, 15 patients were classified as a group that includes Diffuse Astrocytomas, Oligodendrioglial Tumors and Other Astrocytic Tumors. Among the other patients, 14.2% were Medulloblastomas, 4.7% Embryonic Tumors and 2.3% ART / RT. Patients diagnosed with diffuse brainstem glioma accounted for 11.9% of the total. The institution had a diagnosis of Angiocentric Glioma, Craniopharyngioma, Plexiform Neurofibroma and Anaplastic Ependymoma. Neuronal-glial tumors accounted for 9.5% of cases. Choroid plexus tumors represents 5%. Among them, 4.72% had metastatic tumors: Neuroblastoma and Ewing’s Sarcoma. Of the total of 42 patients, there were 5 deaths, 4 due to disease progression and one due to clinical complications. With the group, the discussions were carried out, allowing us to analyze that the presence of the Radiotherapy, Neurosurgery and Pathology team from the first moment, optimized the beginning of treatment and increased the patients’ survival.
Петр Савенко — ученый, хирург, знаток минеральних вод
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2020)

В статье освещены жизненный путь и профессиональная деятельность Петра Назаровича Савенко (1795–1843) — ученого, хирурга-уролога, исследователя минеральных вод. Он сделал значительный вклад в развитие науки и клинической хирургический практики, прежде всего в урологии. Ценны его исследования в области лечебных свойств минеральных вод.
PATH-20. METHYLATION ARRAY PROFILING OF PEDIATRIC BRAIN TUMORS; SINGLE CENTRE EXPERIENCE
Authors: Michal Zapotocky, Ales Vicha, Lenka Krskova, Josef Zamecnik, Lucie Stolova, Adela Misove, Katerina Vanova, Miroslav Koblizek, Vijay Ramaswamy, David Jones, David Sumerauer
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Significant heterogeneity of pediatric brain tumors poses major challenge on diagnostics. Therefore, we aimed to evaluate feasibility of methylation array in the diagnostic process. METHODS Methylation array (Infinium MethylationEPIC, Illumina) was performed on DNA extracted from fresh frozen tissue from prospective newly diagnosed and selected retrospective patients. Results from Heidelberg classifier (www.molecularneuropathology.org) were compared to the histological diagnosis and further genetic testing was performed to establish integrated morphological/molecular diagnosis. RESULTS Within years 2018–2019, we performed methylation array profiling of 102 samples consisting mainly of ependymoma, medulloblastoma high-grade and low-grade glioma. High calibrated score (&amp;gt;0.9) was achieved in 62 patients (61%). In 46 cases (74%) with score &amp;gt;0.9, the histological diagnosis matched the methylation class (MC). In the remaining cases (16) that were classified by histopathology mainly as ependymomas, the methylation profiles were classified as novel molecular entities (HGNET_BCOR, HGNET_MN1, etc.) or different tumor type. In 40 cases (39%) with the score &amp;lt;0.9, six were found to have high normal tissue content. Nine cases had no match in the classifier and 25 were assigned MC with score 0.3 to 0.89. In 20 out of 34 cases with low score, the molecular diagnosis could be confirmed based on copy number variants inferred from the methylation array or using additional testing for gene fusions and mutations. CONCLUSIONS Our experience on the first 100+ cases demonstrated that methylation array could be integral part of diagnostic process in order to establish integrated morphological and molecular diagnosis of pediatric brain tumors.
Abstract P361: Racial/Ethnic and Age Differences in Dietary Sources of Protein, NHANES, 2011 - 2016
Authors: Collin J Popp, Jeannette M Beasley, Melanie J Firestone, Rienna Russo, Stella S Yi
Journal: Circulation (2020)

Background: Dietary protein serves a pivotal role in providing the body with essential amino acids, which are required for the maintenance of body proteins, and the assimilation of structural and functional components required for basic survival. Understanding dietary protein sources can help inform intervention efforts to increase protein intake that will accommodate the growing diversity of the United States. Objective: The purpose of this analysis was to identify the top 10 food category sources of dietary protein by age and race and ethnicity in a nationally representative sample. Methods: Cross-sectional data on adults (18+ years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 with one 24-hour dietary recall were analyzed (n=15,697). Population proportions were calculated for What We Eat In America food categories. Results: The analytic sample (n=15,697) was 15.0% Hispanic (95%CI [12.1, 17.9], 65.0% to non-Hispanic White (95%CI [60.8, 69.3]), 11.5% to non-Hispanic Black (95%CI [9.1, 13.9]), 5.4% to non-Hispanic Asian (95%CI [4.3, 6.6]) and 3.1% other (95%CI [2.5, 3.6]). In all racial and ethnic groups, chicken (whole pieces) was the top-ranked source of dietary protein. In addition to chicken (whole pieces), beef (excludes ground), eggs and omelets, and meat mixed dishes food categories ranked in the top ten sources of protein for every race/ethnicity. Conversely, each race/ethnicity group had at least one food category that uniquely ranked as a top ten source (other Mexican mixed dishes, cheese, burger (single code), rice, stir-fry and soy-based dishes, and nuts and seeds). Older adults consumed the least absolute protein (71 gram per day, 95% CI: [69,73]) and energy (1819 calories, 95%CI[1779, 1860] compared to other age groups (p-value for all &lt;0.0001). Conclusion: The top ten sources of protein accounted for over 40% of dietary protein irrespective of race/ethnicity or age category, having major implications for the sustainability of our nation’s food supply. Public health strategies that encourage incorporating higher amounts of protein in food preparation have the potential to shift the overall population protein intake distribution. Funding Source: R01HL141427
Unraveling Myths of Platelet Function and Genetic Testing: The Road to Making Tailored Antiplatelet Therapy a Reality⁎⁎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: Dominick J. Angiolillo
Journal: Journal of the American College of Cardiology (2011)
RARE-43. FAVORABLE OUTCOME OF A YOUNG GIRL WITH RECURRENT METASTATIC PINEOBLASTOMA ASSOCIATED WITH A DICER1 MUTATION
Authors: Adam Rossi, Gregory Verona, Ann Ritter, Hope Richard, India Sisler, Zhihong Wang
Journal: Neuro-Oncology (2020)

Abstract Pineoblastomas have been thought to portend a poor prognosis, especially in younger children or those with metastases. Long term survivors after relapse, especially for those with metastatic disease are rare. We report a young girl with a DICER1 mutation who survived recurrent metastatic pineoblastoma. She was initially diagnosed at the age of 3 with a localized pineoblastoma, underwent gross total surgical resection, and received high dose chemotherapy with autologous stem cell transplant per COG ACNS0334 without radiation therapy. 16 months after completion of treatment, she relapsed at primary site with widespread spinal metastasis. She then received cranial spinal radiation of 3600Gy with proton beam, with boost to primary to 5580Gy, followed by chemotherapy with Temozolomide, Irinotecan and Avastin per COG ACNS0821. She is now 3 years and 3 months from completion of treatment, is doing well clinically with stable imaging findings. No particular alteration was identified from the tumor molecular testing of her initial pineoblastoma. Of note, she was diagnosed with pleuropulmonary blastoma soon after her initial diagnosis of pineoblastoma, and was found to have a DICER1 mutation (c.2062C&amp;gt;T; pR688*) thought to be a nonsense mutation. While radiation therapy following recurrence is known to improve the outcome, more recent studies suggest that tumors lacking the molecular features of high grade glioma also has a positive impact on prognosis. In addition, we speculate that DICER1 mutations might increase sensitivity of cancer cells to some chemotherapy through modulating gene expression and /or interfering with DNA repair mechanisms, therefore, affecting treatment outcome.
ETMR-06. DISSECTING THE MOLECULAR AND DEVELOPMENTAL BASIS OF PINEOBLASTOMA THROUGH GENOMICS
Authors: Brian Gudenas, Bernhard Englinger, Anthony P Y Liu, Yiai Tong, David Meredith, Elke Pfaff, Tong Lin, Brent A Orr, Paul Klimo, Laure Bihannic, Leena Paul, Rahul Kumar, Eric Bouffet, Sridharan Gururangan, John R Crawford, Stewart J Kellie, Murali Chintagumpala, Michael J Fisher, Daniel C Bowers, Tim Hassall, Daniel J Indelicato, David W Ellison, Frederick A Boop, Thomas E Merchant, Jason Chiang, Giles W Robinson, Amar Gajjar, Sanda Alexandrescu, David T W Jones, Mariella G Filbin, Paul A Northcott
Journal: Neuro-Oncology (2020)

Abstract Pineoblastoma (PB) is an aggressive embryonal brain tumor comprising 1% of pediatric CNS tumors. The clinico-molecular heterogeneity and developmental origins underlying PB are poorly understood; therefore, we have assembled a molecular cohort of histologically defined PBs (n=43) with corresponding outcome data. Methylation profiling revealed four molecularly and clinically distinct PB subgroups, including two novel entities. Mutational and transcriptional analysis identified characteristic molecular features of each subgroup, such as mutations in the miRNA processing pathway or FOXR2 proto-oncogene overexpression. Furthermore, subgroups exhibited differences in propensity for metastasis, cytogenetics, and clinical outcomes. To dissect PB developmental origins and resolve PB subgroup biology, we have employed a combination of single-cell genomics and genetically engineered mouse modeling. We created a single-cell transcriptional atlas of the developing murine pineal gland across 11 timepoints and are currently integrating these data with single nuclei RNA-seq data of human PB (n=25). Single-cell analysis of the developing pineal gland revealed three distinct populations of pinealocytes, referred to as early, mid and late pinealocytes, which segregate by developmental stage yet lie along a single developmental trajectory. Preliminary results implicate significant associations between PBs and the early pinealocyte population as well as subgroup-specific differences in intratumoral heterogeneity. Furthermore, this knowledge has informed the downstream generation of biologically faithful disease models, including a transgenic mouse model of the PB-RB subgroup. Remarkably, this model shows up-regulation of key markers of PB such as Crx, Asmt and Otx2 and substantiates early pinealocytes as the probable cell-of-origin for this PB subgroup.
LGG-45. A REPORT OF IDH-MUTANT BRAINSTEM ASTROCYTOMAS IN YOUNG ADULTS
Authors: Ellen Chang, Benita Tamrazi, Jennifer Cotter, Ashley Margol
Journal: Neuro-Oncology (2020)

Abstract IDH-mutant astrocytomas are well-recognized in the adult population and while increasingly identified, are rare in children and young adults. These tumors typically arise in cortical locations, however cases of these tumors occurring in the brainstem have been reported in the adult literature. Here we present two cases of young adults with IDH-mutant astrocytomas of the brainstem. Patient 1 was initially diagnosed with an infiltrative low grade glioma (LGG) of the brainstem at 19 years of age based on conventional magnetic resonance imaging and magnetic resonance spectroscopy characteristics. She was treated with LGG therapy and had stable disease for over three years. At the time of disease progression she underwent biopsy and pathology was consistent with an anaplastic astrocytoma, IDH1 R132S mutant. Despite treatment she experienced rapid disease progression and died six months later. Patient 2 is a 17-year-old male who underwent up-front biopsy of an infiltrating brainstem lesion; pathology was consistent with diffuse astrocytoma, IDH1 R132H mutant. He was treated with focal irradiation and chemotherapy and continues to have stable disease 26 months post diagnosis. To our knowledge, this is the first report of IDH-mutant astrocytomas occurring the brainstem in young adult patients. Both patients’ tumors harbored accompanying TP53 mutations, but not ATRX mutations. These two cases reveal the importance of obtaining biopsies for brainstem tumors to perform molecular characterization and appropriate prognostication.
Deaths From COVID-19
Authors: Howard K. Koh, Alan C. Geller, Tyler J. VanderWeele
Journal: JAMA (2020)

In any year, keeping track of new health trends can be difficult.But this year, the dynamic nature of coronavirus disease 2019 (COVID-19) has made clarity almost impossible.Declines in mortality, after daily COVID-19-related deaths peaked last spring, initially fueled hope that the worst was over.But following a summer increase in deaths, trends have accelerated even faster.This fall, a million new cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which previously had increased monthly, began appearing weekly; as of December 13, cumulative infections totaled more than 16 million in the United States. 1 Meanwhile, the media regularly report a flood of statistics that can be difficult to contextualize.In this issue of JAMA, the simple, yet powerful, analysis by Woolf et al 2 puts these numbers into perspective.Ranking the once unfamiliar threat of COVID-19 against more familiar illnesses, they compare US mortality from COVID-19 (March-October 2020) to leading causes of death 2 years prior to the pandemic (March-October 2018).The analysis, 2 combined with their prior research on death and life expectancy trends, 2-4 suggest 4 major conclusions.First, COVID-19 ranks as a leading cause of death; at certain times, it is the leading cause of death.Compared with leading causes of death from the same period in 2018, novel COVID-19 was the third leading cause of death for children and adults (697.5 deaths/million), ranking only behind heart disease (1287.7 deaths/million) and cancer (1219.8deaths/million). 2 No age group has been spared, although COVID-19 was not the leading cause of death for the younger age groups.These figures probably underestimate true excess mortality by at least 20%, due, in part, to the indirect effects of the pandemic on non-COVID-19 deaths 2 including the death risk that lethal communicable diseases pose to others.Woolf et al note that the rapidly rising death rates this fall will exceed spring death rates when COVID-19 was the leading cause of death.Between November 1, 2020, and December 8, 2020, the 7-day average for daily COVID-19 deaths nearly tripled-826 to 2226 deaths per day. 2 Daily deaths in the first 13 days of December averaged 2381 per day, 1 already well exceeding the 1900 average daily deaths during the initial peak from April 15 to May 15. 1 On December 9, 2020, deaths reached a record high of 3411, 1 more than 2 per minute and roughly 400 more than the September 11, 2001, attack. 2 Such numbers elevate COVID-19 as a cause of death higher than heart disease and cancer, which, for decades, accounted for 1700 and 1600 deaths per day, respectively. 2umulative COVID-19 deaths in the United States just surpassed 300 000 on December 14. 1 The United States, which
CSIG-22. CANCER-ASSOCIATED MISSENSE SINGLE NUCLEOTIDE VARIANTS REGULATE THE STABILITY AND SUBCELLULAR LOCALIZATION OF NF2/MERLIN
Authors: Charlotte Eaton, Paola Bisignano, David Raleigh
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Alterations in the NF2 tumor suppressor gene lead to meningiomas and schwannomas, but the tumor suppressor functions of the NF2 gene product, Merlin, are incompletely understood. To address this problem, we performed a structure-function analysis of Merlin by expressing cancer-associated missense single-nucleotide variants (mSNVs) in primary cancer cells for biochemical and cell biology experiments. METHODS All NF2 mSNVs were assembled from cBioPortal and COSMIC, and modelled on the FERM, a-helical, and C-terminal domains of Merlin (PDB 4ZRJ) using comparative structure prediction on the Robetta server and visually inspected using Pymol. mSNV hotspots were defined from sliding windows with at least 10 mutations within 5 residues in either direction. mSNVs from hotspots in meningiomas, schwannomas, or both, were selected for in vitro mechanistic analyses using immunofluorescence and immunoblotting of whole cell, plasma membrane, cytoskeletal, cytoplasmic, nuclear, and chromatin subcellular fractions from M10G meningioma cells and HEI-193 schwannoma cells. RESULTS We identified the following cancer-associated hotspot mSNVs in NF2, which were over-expressed for mechanistic studies: L46R, S156N, W191R, A211D, V219M, R418C and R462K. Endogenous Merlin was detected in all subcellular compartments, but was enriched in the nucleus. L46R and A211D mapped to hydrophobic pockets in the FERM domain, destabilized Merlin, and excluded Merlin from all subcellular compartments except the cytoskeleton. S156N, W191R and V219M also mapped to the FERM domain, but did not affect Merlin stability, and V219M attenuated chromatin localization, suggesting this motif may be involved in binding events that regulate subcellular localization. R418C and R463K mapped to the a-helical domain, but only R418C destabilized Merlin. CONCLUSION Our results suggest that cancer-associated mSNVs inactive the tumor suppressor functions of NF2 by altering the stability, subcellular localization, or binding partners of Merlin. Further work is required to identify and understand the impact of binding partners and subcellular localization on Merlin function.
EPEN-04. ONCOGENIC 3D TUMOR GENOME ORGANIZATION IDENTIFIES NEW THERAPEUTIC TARGETS IN EPENDYMOMA
Authors: Konstantin Okonechnikov, Jens-Martin Hübner, Owen Chapman, Abhijit Chakraborty, Meghana Pagadala, Rosalind Bump, Sahaana Chandran, Katerina Kraft, Rocio Acuna Hidalgo, Stefan Mundlos, Robert Wechsler-Reya, Edwin F Juarez, Nicole Coufal, Michael Levy, John Crawford, Kristian Pajtler, Derek Reid, Anthony Schmitt, Hannah Carter, Ferhat Ay, Jesse Dixon, Jill Mesirov, Stefan M Pfister, Marcel Kool, Lukas Chavez
Journal: Neuro-Oncology (2020)

Abstract By profiling enhancers in primary ependymoma tumors, we have recently identified putative oncogenes, molecular targets, and functional pathways. Inhibition of selected targets diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymoma. While enhancers frequently regulate the nearest gene, identification of enhancer target genes remains to be a challenge in the absence of chromosome conformation information. Consequently, we have now used HiC to map the 3-dimensional organization of tumor chromatin in the two most common and aggressive ependymoma subgroups: posterior fossa group A (PF-EPN-A) and supratentorial ependymomas with gene fusions involving the NF-κB subunit gene RELA (ST-EPN-RELA). By an integrative analysis of enhancer and gene expression in the context of the newly derived HiC data, we find that a large number of the predicted enhancer target genes are enriched for strong physical interactions. Importantly, we also identify many new putative tumor-dependency genes activated by long-range promoter-enhancer interactions and complex tumor-specific chromatin clusters of regulatory elements. Complementary to the analysis of gene-enhancer interactions, we have also leveraged the HiC data for resolving structural rearrangements underlying copy number alterations. Copy number gains of the 1q arm of chromosome 1 are especially associated with poor survival. Our preliminary results in PFA relapse samples show complex structural variants underlying 1q gain that lead to inter-chromosomal rearrangements and affect several genes that potentially contribute to poor survival. In ongoing work we are testing the relevance of the novel candidate genes for tumor cell growth and proliferation in-patient derived ependymoma models.
NCOG-41. FUNCTIONAL OUTCOME FOLLOWING NON-DOMINANT HEMISPHERIC GLIOMA SURGERY FROM THE ASPECT OF INDEPENDENCE LEVEL, COGNITIVE FUNCTION AND RETURN TO SOCIAL LIVES
Authors: Riho Nakajima, Masashi Kinoshita, Hirokazu Okita, Mitsutoshi Nakada
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Functional outcome has been paid much attention in surgery for eloquent area or dominant hemisphere. Little is known about functional outcome following surgery for non-dominant hemispheric gliomas, although some resent reports revealed the importance of right cerebral hemisphere on glioma surgery. Here, we investigated functional outcome of right cerebral hemispheric gliomas from the aspect of independence level, cognitive function, and return to social lives. METHODS Totally 82 patients with right cerebral hemispheric gliomas who underwent surgery for resection in Kanazawa university hospital were studied. Patients were divided into two groups, WHO grade II/III and IV. Karnofsky Performance Status (KPS), Mini-mental state examination (MMSE), and whether or not to return to work at pre-operation and chronic phase were evaluated. To reveal responsible region for decline of each index, the voxel-based lesion symptom (VLSM) analyses were performed. RESULTS MMSE; no difference was found through postoperative course in grade II/III, whereas postoperative score of grade IV was declined significantly compared with pre-operation (25.1 and 21.9 point; p=0.048). KPS; preoperative independence level was maintained until chronic phase in grade II/III (94.7 and 89.5). While, in grade IV, postoperative KPS was declined significantly than that of pre-operation (82.0 and 70.0, p=0.007). Results of the VLSM analysis revealed that patients who resected temporo-parietal junction in grade IV showed significantly low KPS score. Return to social lives; Reintegration ratio of working population was 71% and 35% for grade II/III and IV, respectively. Of these, as for grade II/III gliomas, the cingulate cortex and medial orbito-frontal cortex relate to return to social lives. CONCLUSIONS Functional outcome following surgery depends on tumor grade and resected region in right cerebral hemispheric gliomas.